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Sequential Exposure (sequential + exposure)
Selected AbstractsSchedule-dependent Interactions between Raltitrexed and Cisplatin in Human Carcinoma Cell Lines in vitroCANCER SCIENCE, Issue 4 2000Yasuhiko Kano Raltitrexed (,Tomudex") is a new anticancer agent which inhibits thymidylate synthase. To provide a rational basis for clinical trial design of the combination of raltitrexed and cisplatin, we studied the cytotoxic effects of this combination using various schedules in vitro and four human colon cancer cell lines, Colo201, Colo320, LoVo, and WiDr. Cell growth inhibition after 5 days was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of drug combinations at the concentration producing 80% cell growth inhibition (IC80) level were analyzed by the isobologram method. Simultaneous exposure to raltitrexed and cisplatin for 24 h, and sequential exposure to raltitrexed followed by cisplatin produced additive effects in the Colo201, Colo320, and LoVo cells, and additive and synergistic effects in WiDr cells. Sequential exposure to cisplatin followed by raltitrexed produced additive effects in the Colo201 cells and antagonistic effects in other three cell lines. Simultaneous and continuous exposure to both agents for 5 days produced additive effects in all four cell lines. These findings suggest that the simultaneous administration of raltitrexed and cisplatin, or the sequential administration of raltitrexed followed by cisplatin, generally produce the expected cytotoxicity at the cellular level and are optimal schedules, while the sequential administration of cisplatin followed by raltitrexed produces antagonistic effects and is inappropriate for this combination. Further in vivo and clinical studies will be necessary to determine the toxicity and antitumor effects of this schedule. [source] Plasma-Assisted Atomic Layer Deposition of Al2O3 at Room TemperaturePLASMA PROCESSES AND POLYMERS, Issue S1 2009Tommi O. Kääriäinen Abstract A new design of plasma source has been used for the plasma-assisted atomic layer deposition (PA-ALD) of Al2O3 films at room temperature. In this PA-ALD reactor the plasma is generated by capacitive coupling directly in the deposition chamber adjacent to the substrate but can be separated from it by a grid to reduce the ion bombardment while maintaining the flow of radicals directly to the substrate surface. During the ALD cycle a mixture of nitrogen and argon was introduced into the reactor to act as a purge gas between precursor pulses and to facilitate the generation of a plasma during the plasma cycle. Sequential exposures of TMA and excited O2 precursors were used to deposit Al2O3 films on Si(100) substrates. A plasma discharge was activated during the oxygen gas pulse to form radicals in the reactor space. The experiments showed that the growth rate of the film increased with increasing plasma power and with increasing O2 pulse length before saturating at higher power and longer O2 pulse length. The growth rate saturated at the level of 1.78 Å·cycle,1. EDS analysis showed that the films were oxygen rich and had carbon as an impurity. This can be explained by the presence of bonds between hydrocarbons from the unreacted TMA precursor and excess oxygen in the film. ATR-FTIR spectroscopy measurements indicated a change in growth mechanism when the distance between the location of the radical generation and the substrate was varied. A similar effect was observed with the use of different plasma power levels. [source] Immunotoxicity of acute acephate exposure in control or IL-1-challenged rats: correlation between the immune cell composition and corticosteroid concentration in bloodJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2002Ashok K. Singh Abstract Corticosterone concentration and the immune cell composition were measured in rats exposed by intraperitoneal (i.p.) injection to different doses (10,500 mg kg,1) of acephate (Ace) and 250 µg kg,1 of interleukin 1 (IL-1), either alone or in combination. Two different combination protocols were used: IL-1 and Ace were administered simultaneously; and IL-1 was injected 60 min after Ace administration (sequential exposure). Ace, in a dose- and time-dependent manner, inhibited blood and brain acetylcholinesterase (AChE) activities, increased blood corticosterone concentrations, suppressed blood CD4, CD8, B cell and monocyte contents and increased blood neutrophil counts. The Ace-induced changes lasted for up to 24 h after Ace exposure. Interleukin 1 increased blood corticosterone concentrations without affecting blood or brain AChE activities. The IL-1-induced corticosterone concentration returned to the basal level within 3,10 h after IL-1 exposure. The CD4, CD8, B cell and monocyte counts increased significantly at 10 min after IL-1 exposure. The cell counts decreased gradually thereafter and returned to the basal level within 30 min after IL-1 exposure. Simultaneous exposure of rats to Ace and IL-1 partially suppressed the IL-1-induced increase in the immune cell counts and decreased the immune cell numbers below the basal values. Sequential injection of Ace and IL-1 blocked the IL-1-induced increase in the immune cell numbers. Thus, Ace exposure would impair the normal distribution of immune cells and deregulate the IL-1 response in rats. This study therefore suggests that Ace would suppress the immune cell numbers in blood, thus decreasing an organism's immunity. Ace exposure occurring concurrent with injury would augment the acute-phase response, which would augment the toxic effects of IL-1 and other cytokines, and Ace exposure occurring prior to the injury would suppress or abolish the initial stimulatory effects of IL-1, which would decrease an organism's ability to combat infection or injury. Copyright © 2002 John Wiley & Sons, Ltd. [source] Effects of sequential exposure to lipopolysaccharide and heat stress on dental pulp cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2006Chiaki Kitamura Abstract In the present study, we examined the effects of sequential exposure to bacterial lipopolysaccharide (LPS) and heat stress on dental pulp cells. LPS induced the proliferation of pulp cells through the activation of p38 MAPK. HSP27 was expressed in cells with or without LPS during the entire period of heat stress, while transiently phosphorylated by short-term heat stress. In LPS-treated cells, short-term heat stress also induced the phosphorylation of HSF1. The immediate phosphorylation of HSF1 and HSP27 in LPS-treated cells by short-term heat stress occurred dependent on the activation of p38 MAPK. However, with long-term heat stress, the activation of HSF1 and induction of HSP27 occurred independent of p38 MAPK. Further, full activation of Akt in LPS-treated cells was immediately induced by short-term heat stress and lasted during the entire period of heat stress. I,B, was induced and phosphorylated throughout sequential exposure to LPS and heat stress. These results suggest that LPS has the unique effects on the cytoprotection and the cell death of pulp cells during heat stress through the modification and the activation of heat stress responsive molecules, HSF1 and HSP27, and cell survival molecules, Akt and NF-,B/I,B,. J. Cell. Biochem. 99: 797,806, 2006. © 2006 Wiley-Liss, Inc. [source] Enhanced cartilage tissue engineering by sequential exposure of chondrocytes to FGF-2 during 2D expansion and BMP-2 during 3D cultivationJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2001Ivan Martin Abstract Bovine calf articular chondrocytes, either primary or expanded in monolayers (2D) with or without 5 ng/ml fibroblast growth factor-2 (FGF-2), were cultured on three-dimensional (3D) biodegradable polyglycolic acid (PGA) scaffolds with or without 10 ng/ml bone morphogenetic protein-2 (BMP-2). Chondrocytes expanded without FGF-2 exhibited high intensity immunostaining for smooth muscle ,-actin (SMA) and collagen type I and induced shrinkage of the PGA scaffold, thus resembling contractile fibroblasts. Chondrocytes expanded in the presence of FGF-2 and cultured 6 weeks on PGA scaffolds yielded engineered cartilage with 3.7-fold higher cell number, 4.2-fold higher wet weight, and 2.8-fold higher wet weight glycosaminoglycan (GAG) fraction than chondrocytes expanded without FGF-2. Chondrocytes expanded with FGF-2 and cultured on PGA scaffolds in the presence of BMP-2 for 6 weeks yielded engineered cartilage with similar cellularity and size, 1.5-fold higher wet weight GAG fraction, and more homogenous GAG distribution than the corresponding engineered cartilage cultured without BMP-2. The presence of BMP-2 during 3D culture had no apparent effect on primary chondrocytes or those expanded without FGF-2. In summary, the presence of FGF-2 during 2D expansion reduced chondrocyte expression of fibroblastic molecules and induced responsiveness to BMP-2 during 3D cultivation on PGA scaffolds. © 2001 Wiley-Liss, Inc. [source] Biodiversity effects on ecosystem functioning: emerging issues and their experimental test in aquatic environmentsOIKOS, Issue 3 2004Paul S. Giller Recent experiments, mainly in terrestrial environments, have provided evidence of the functional importance of biodiversity to ecosystem processes and properties. Compared to terrestrial systems, aquatic ecosystems are characterised by greater propagule and material exchange, often steeper physical and chemical gradients, more rapid biological processes and, in marine systems, higher metazoan phylogenetic diversity. These characteristics limit the potential to transfer conclusions derived from terrestrial experiments to aquatic ecosystems whilst at the same time provide opportunities for testing the general validity of hypotheses about effects of biodiversity on ecosystem functioning. Here, we focus on a number of unique features of aquatic experimental systems, propose an expansion to the scope of diversity facets to be considered when assessing the functional consequences of changes in biodiversity and outline a hierarchical classification scheme of ecosystem functions and their corresponding response variables. We then briefly highlight some recent controversial and newly emerging issues relating to biodiversity-ecosystem functioning relationships. Based on lessons learnt from previous experimental and theoretical work, we finally present four novel experimental designs to address largely unresolved questions about biodiversity-ecosystem functioning relationships. These include (1) investigating the effects of non-random species loss through the manipulation of the order and magnitude of such loss using dilution experiments; (2) combining factorial manipulation of diversity in interconnected habitat patches to test the additivity of ecosystem functioning between habitats; (3) disentangling the impact of local processes from the effect of ecosystem openness via factorial manipulation of the rate of recruitment and biodiversity within patches and within an available propagule pool; and (4) addressing how non-random species extinction following sequential exposure to different stressors may affect ecosystem functioning. Implementing these kinds of experimental designs in a variety of systems will, we believe, shift the focus of investigations from a species richness-centred approach to a broader consideration of the multifarious aspects of biodiversity that may well be critical to understanding effects of biodiversity changes on overall ecosystem functioning and to identifying some of the potential underlying mechanisms involved. [source] Sperm binding to the human zona pellucida and calcium influx in response to GnRH and progesteroneANDROLOGIA, Issue 5 2002P. Morales Summary. In this study the effect of the sequential exposure of spermatozoa to progesterone and gonadotrophin-releasing hormone (GnRH) upon zona binding and the intracellular free Ca2+ concentration was evaluated. Sperm aliquots were treated as follows: (a) 0.7 ,mol 1,1 progesterone or 0.1% DMSO (progesterone solvent) followed by 50 nmol 1,1 of GnRH; (b) 50 nmol 1,1 of GnRH or distilled water (GnRH solvent) followed by 0.7 ,mol 1,1 of progesterone. Additional aliquots were incubated with DMSO or distilled water (controls) and with 0.7 ,mol 1,1 of progesterone or 50 nmol 1,1 of GnRH. All treatments were for 5 min. Motile spermatozoa were incubated in modified Tyrode's medium, at 37 °, 5% CO2, 10times106 spermatozoa ml,1, for 4.5 h. Intracellular Ca2+ concentration and sperm-zona binding was evaluated using fura 2 and the hemizona assay, respectively. GnRH and progesterone increased sperm-zona binding and the Ca2+ concentration. Regarding zona binding, the effect of GnRH was significantly greater when the spermatozoa had been previously treated with progesterone (progesterone , GnRH = 185 ± 116 zona-bound spermatozoa versus DMSO , GnRH = 99 ± 15, P <0.001). On the other hand, previous treatment with GnRH did not modify their subsequent response to progesterone (GnRH , progesterone = 114 ±19 zona-bound spermatozoa versus distilled water , progesterone = 108 ± 22, NS). The results regarding intracellular Ca2+ showed a similar pattern. These findings suggest a priming effect of progesterone upon a GnRH-induced increase in sperm-zona binding and intracellular Ca2+. [source] Schedule-dependent Interactions between Raltitrexed and Cisplatin in Human Carcinoma Cell Lines in vitroCANCER SCIENCE, Issue 4 2000Yasuhiko Kano Raltitrexed (,Tomudex") is a new anticancer agent which inhibits thymidylate synthase. To provide a rational basis for clinical trial design of the combination of raltitrexed and cisplatin, we studied the cytotoxic effects of this combination using various schedules in vitro and four human colon cancer cell lines, Colo201, Colo320, LoVo, and WiDr. Cell growth inhibition after 5 days was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of drug combinations at the concentration producing 80% cell growth inhibition (IC80) level were analyzed by the isobologram method. Simultaneous exposure to raltitrexed and cisplatin for 24 h, and sequential exposure to raltitrexed followed by cisplatin produced additive effects in the Colo201, Colo320, and LoVo cells, and additive and synergistic effects in WiDr cells. Sequential exposure to cisplatin followed by raltitrexed produced additive effects in the Colo201 cells and antagonistic effects in other three cell lines. Simultaneous and continuous exposure to both agents for 5 days produced additive effects in all four cell lines. These findings suggest that the simultaneous administration of raltitrexed and cisplatin, or the sequential administration of raltitrexed followed by cisplatin, generally produce the expected cytotoxicity at the cellular level and are optimal schedules, while the sequential administration of cisplatin followed by raltitrexed produces antagonistic effects and is inappropriate for this combination. Further in vivo and clinical studies will be necessary to determine the toxicity and antitumor effects of this schedule. [source] | |||||||||||||