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Simultaneous Exposure (simultaneous + exposure)

Distribution by Scientific Domains

Medical Sciences	66%
Life Sciences	25%

Selected Abstracts

Immunotoxicity of acute acephate exposure in control or IL-1-challenged rats: correlation between the immune cell composition and corticosteroid concentration in blood

JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2002
Ashok 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]

Cooperative inhibitory effect of ZD1839 (Iressa) in combination with 17-AAG on glioma cell growth,

MOLECULAR CARCINOGENESIS, Issue 5 2006
Daniel R. Premkumar
Abstract ZD1839 ("Iressa") is an orally active, selective epidermal growth factor (EGF) receptor-tyrosine kinase inhibitor. We evaluated the antitumor activity of ZD1839 in combination with HSP90 antagonist, 17-AAG in malignant human glioma cell lines. ZD1839 independently produced a dose-dependent inhibition of cellular proliferation in glioma cells grown in culture with time- and dose-dependent accumulation of cells in G1 phase of the cell cycle on flow cytometric analysis, although the concentrations required for optimal efficacy were at or above the limits of clinically achievable levels. Because the heat shock protein (HSP) is involved in the conformational maturation of a number of signaling proteins critical to the proliferation of malignant glioma cells, we hypothesized that the HSP90 inhibitor 17-AAG would potentiate ZD 1839-mediated glioma cytotoxicity by decreasing the activation status of EGF receptor, as well as downregulating the levels of other relevant signaling effectors. We, therefore, examined the effects of ZD1839 and 17-AAG, alone and in combination, on signal transduction and apoptosis in a series of malignant glioma cell lines. Simultaneous exposure to these inhibitors significantly induced cell death and quantitative analysis revealed that interaction between ZD1839 and 17-AAG-induced cytotoxicity was synergistic, leading to a pronounced increase in active caspase-3 and PARP cleavage. No significant growth inhibition or caspase activation was seen in control cells. The enhanced cytotoxicity of this combination was associated with diminished Akt activation and a significant downregulation of EGFR receptor, Raf-1 and mitogen activated protein kinase (MAPK). Cells exposed to 17-AAG and ZD1839 displayed a significant reduction in cell cycle regulatory proteins, such as CDK4 and CDK6. Taken together, these findings suggest that ZD1839, an EGF receptor tyrosine kinase inhibitor, plays a critical role in regulating the apoptotic response to 17-AAG and that multi-site targeting of growth signaling and cell survival pathways could provide a potent strategy to treat patients with malignant gliomas. © 2006 Wiley-Liss, Inc. [source]

Simultaneous exposure to low concentrations of dichlorodiphenyltrichloroethane, deltamethrin, nonylphenol and phytoestrogens has negative effects on the reproductive parameters in male Spraque-Dawley rats

ANDROLOGIA, Issue 4 2007
E. Kilian
Summary Many reports suggest that male reproductive health has deteriorated over the last decades, possibly due to environmental contaminants that act as endocrine disruptors. This hypothesis was tested in Sprague-Dawley rats using a modified Organization for Economic Cooperation and Development 415 one-generation test. Group A received cottonseed oil as control, and Groups B, C and D received deltamethrin (DM); DM and dichlorodiphenyltrichloroethane (DDT); and DM, DDT, phytoestrogens and p -nonylphenol, respectively. Rats were exposed in utero and then received the substances for 10 weeks. The seminal vesicle mass (Group B; P = 0.046) and sperm count [Groups C (P = 0.013) and D (P = 0.003)] were lower and the anogenital distance [Group B (P = 0.047) C (P = 0.045) and D (P = 0.002)] shorter compared with the control group. The seminiferous tubule diameter [Groups B (P = <0.001), C (P = <0.001) and D (P = <0.001)] and epithelium thickness [Groups B (P = 0.030), C (P = <0.001) and D (P = <0.001)] were smaller compared with the control. The histology of the testes showed signs of apical sloughing and vacuolisation. Liver weights [Groups C (P = 0.013) and D (P = 0.005)] and liver enzymes [Group D (P = 0.013)] were also affected. These findings may indicate that simultaneous exposure to endocrine disrupting compounds contributes to the deterioration observed in male reproductive health. [source]

Schedule-dependent Interactions between Raltitrexed and Cisplatin in Human Carcinoma Cell Lines in vitro

CANCER SCIENCE, Issue 4 2000
Yasuhiko 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]

Rhinovirus infection and house dust mite exposure synergize in inducing bronchial epithelial cell interleukin-8 release

CLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2008
A. Bossios
Summary Background Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved. Objective To investigate their interaction on the induction of airway epithelial inflammatory responses in vitro. Methods BEAS-2B cells were exposed to activated HDM Dermatophagoides pteronyssinus major allergen I (Der p I), HRVs (HRV1b or HRV16) or both in different sequences. IL-8/CXCL8 release, intercellular adhesion molecule (ICAM)-1 surface expression and nuclear factor ,B (NF-,B) translocation were evaluated. Complementary, primary human bronchial epithelial cells (HBECs) exposed to both Der p I and RVs and IL-8, IL-6, IFN-,-induced protein (IP)-10/CXCL10, IFN-,1/IL-29, regulated upon activation normal T lymphocyte expressed and secreted (RANTES)/CCL5 release were measured. Results RV and Der p I up-regulated IL-8 release, ICAM-1 expression and NF-,B translocation in BEAS-2B cells. Simultaneous exposure to both factors, as well as when cells were initially exposed to HRV and then to Der p I, resulted in further induction of IL-8 in a synergistic manner. Synergism was not observed when cells were initially exposed to Der p I and then to HRV. This was the pattern in ICAM-1 induction although the phenomenon was not synergistic. Concurrent exposure induced an early synergistic NF-,B translocation induction, differentiating with time, partly explaining the above observation. In HBECs, both HRV and Der p I induced IL-8, IL-6, IL-29 and IP-10, while RANTES was induced only by HRV. Synergistic induction was observed only in IL-8. Conclusion HRV and enzymatically active Der p I can act synergistically in the induction of bronchial epithelial IL-8 release, when HRV infection precedes or is concurrent with Der p I exposure. Such a synergy may represent an important mechanism in virus-induced asthma exacerbations. [source]

A CIITA-independent pathway that promotes expression of endogenous rather than exogenous peptides in immune-privileged sites

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2004
Carolina
Abstract A CIITA-independent pathway of MHC class II expression has been found in the eye and the brain, both immune-privileged sites. Although corneal endothelial cells were unable to express MHC class,II in response to IFN-, alone, these cells readily expressed MHC class,II molecules via a CIITA-independent pathway when triggered by simultaneous exposure to IFN-, and TNF-,. CIITA-independent expression of MHCclass,II molecules enabled corneal endothelial cells to present cytosolic, but not endosomal, ovalbumin (OVA) to OVA-primed T,cells. To determine whether CIITA-independentexpression of MHC class,II is relevant in vivo, minor,H-only-incompatible corneal allografts prepared from CIITA knockout (KO) mice, MHC class,II KO mice or wild-type donors were placed ineyes of normal mice. Cornea allografts from wild-type and CIITA KO mice suffered similar rejection fates, whereas far fewer class,II-deficient corneas were rejected. In addition, MHC class,II-bearing macrophages were observed in cuprizone-induced inflammatory and demyelinating brain lesions of CIITA KO mice. We conclude that class,II expression via the CIITA-independent pathway enhances the vulnerability to rejection of corneal grafts expressing minor antigens. The potential relevance of CIITA-independent MHC class,II expression at immune-privileged sites is discussed in relation to tolerance to strong autoantigens. [source]

Homeostasis of neuroactive amino acids in cultured cerebellar and neocortical neurons is influenced by environmental cues

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 1-2 2005
Helle Waagepetersen
Abstract Neuronal function is highly influenced by the extracellular environment. To study the effect of the milieu on neurons from cerebellum and neocortex, cells from these brain areas were cultured under different conditions. Two sets of cultures, one neocortical and one cerebellar neurons, were maintained in media containing [U- 13C]glucose for 8 days at initial concentrations of 12 and 28 mM glucose, respectively. Other sets of cultures (8 days in vitro) maintained in a medium containing initially 12 mM glucose were incubated subsequently for 4 hr either by addition of [U- 13C]glucose to the culture medium (final concentration 3 mM) or by changing to fresh medium containing [U- 13C]glucose (3 mM) but without glutamine and fetal calf serum. 13C Nuclear magnetic resonance (NMR) spectra revealed extensive ,-aminobutyric acid (GABA) synthesis in both cultured neocortical and cerebellar neurons after maintenance in medium containing [U- 13C]glucose for 8 days, whereas no aspartate labeling was observed in these spectra. Mass spectrometry analysis, however, revealed high labeling intensity of aspartate, which was equal in the two types of neurons. Addition of [U- 13C]glucose (4 hr) on Day 8 in culture led to a similar extent of labeling of GABA in neocortical and in cerebellar cultures, but the cellular content of GABA was considerably higher in the neocortical neurons. The cellular content of alanine was similar regardless of culture type. Comparing the amount of labeling, however, cerebellar neurons exhibited a higher capacity for alanine synthesis. This is compatible with the fact that cerebellar neurons could ameliorate a low alanine content after culturing in low glucose (12 mM) by a 4-hr incubation in medium containing 3 mM glucose. A low glucose concentration during the culture period and a subsequent medium change were associated with decreases in glutathione and taurine contents. Moreover, glutamate and GABA contents were reduced in cerebellar cultures under either of these conditions. In neocortical neurons, the GABA content was decreased by simultaneous exposure to low glucose and change of medium. These conditions also led to an increase in the aspartate content in both types of cultures, although most pronounced in the neocortical neurons. Further experiments are needed to elucidate these phenomena that underline the impact of extracellular environment on amino acid homeostasis. © 2004 Wiley-Liss, Inc. [source]

Varying ratios of wavelengths in dual wavelength LED photomodulation alters gene expression profiles in human skin fibroblasts

LASERS IN SURGERY AND MEDICINE, Issue 6 2010
D.H. McDaniel MD
Abstract Background and Objective LED photomodulation has been shown to profoundly influence cellular behavior. A variety of parameters with LED photomodulation can alter cellular response in vitro. The effects of one visible and one infrared wavelength were evaluated to determine the optimal ratio to produce a net increase in dermal collagen by altering the ratio of total energy output of each wavelength. The ratio between the two wavelengths (590 and 870,nm) was shifted in 25% increments. Study Design/Materials and Methods Human skin fibroblasts in culture were exposed to a 590/870,nm LED array with total combined energy density fixed at 4.0,mW/cm.. The ratio of 590/870,nm tested parameters were: 100/0%, 75/25%, 50/50%, 25/75%, and 0/100%. These ratios were delivered using pulsed duty cycle of exposure (250,milliseconds "on" time/100,milliseconds "off" time/100,pulses) for a total energy fluence of 0.1,J/cm.. Gene expression was examined using commercially available extra cellular matrix and adhesion molecule RT PCR Arrays (SA Biosciences, Fredrick, MD) at 24,hours post-exposure. Results Different expression profiles were noticed for each of the ratios studied. Overall, there was an average (in an 80 gene array) of 6% expression difference in up or downregulation between the arrays. The greatest increase in collagen I and decrease in collagenase (MMP-1) was observed with 75/25% ratio of 590/870,nm. The addition of increasing proportions of IR wavelengths causes alteration in gene expression profile. The ratios of the wavelengths caused variation in magnitude of expression. Conclusions Cell metabolism and gene expression can be altered by simultaneous exposure to multiple wavelengths of low energy light. Varying the ratios of specific wavelength intensity in both visible and near infrared light therapy can strongly influence resulting fibroblast gene expression patterns. Lasers Surg. Med. 42:540,545, 2010. © 2010 Wiley,Liss, Inc. [source]

Seed removal in two coexisting oak species: ecological consequences of seed size, plant cover and seed-drop timing

OIKOS, Issue 9 2008
Ignacio M. Pérez-Ramos
Seed predation and dispersal can critically influence plant community structure and dynamics. Inter-specific differences arising at these early stages play a crucial role on tree recruitment patterns, which in turn could influence forest dynamics and species segregation in heterogeneous environments such as Mediterranean forests. We investigated removal rates from acorns set onto the ground in two coexisting Mediterranean oak species ,Quercus canariensis and Q. suber, in southern Spain. We developed maximum likelihood estimators to investigate the main factors controlling probabilities of seed removal and to describe species-specific functional responses. To account for inter-specific differences in seed-drop timing, two experiments were established: a simultaneous exposure of acorns of the two species (synchronous experiments) and a seed exposure following their natural seed-drop phenology (diachronic experiments). A total of 1536 acorns were experimentally distributed along a wide and natural gradient of plant cover, and removal was periodically monitored for three months at two consecutive years (with contrasting differences in seed production and thus seed availability on the ground). The probability of seed removal increased with plant cover (leaf area index, LAI) for the two oak species. Inter-specific differences in acorn removal were higher in open areas and disappeared in closed microhabitats, especially during a non-mast year. Despite later seed-drop, Q. suber acorns were removed faster and at a higher proportion than those of Q. canariensis. The higher probability of seed removal for this species could be attributed to its larger seed size compared to Q. canariensis, as inter-specific differences were less pronounced when similar sized acorns were exposed. Inter-specific differences in seed removal, arising from seed size variability and microsite heterogeneity, could be of paramount importance in oak species niche separation, driving stand dynamics and composition along environmental gradients. [source]

Simultaneous exposure to low concentrations of dichlorodiphenyltrichloroethane, deltamethrin, nonylphenol and phytoestrogens has negative effects on the reproductive parameters in male Spraque-Dawley rats

2132: Celastrol regulates innate immunity response via NF-kB and HSP70 in ARPE-19 cells

ACTA OPHTHALMOLOGICA, Issue 2010
T PAIMELA
Purpose Chronic inflammation participates in the pathology of age-related macular degeneration (AMD). Recent studies indicate that celastrol, a novel triterpene compound, modulates inflammatory responses, but its effect on the human retinal pigment epithelial cells is poorly understood. In this study, we investigated the potential anti-inflammatory role of celastrol and its effect on nuclear factor kappa B (NF-kB) activity in human retinal pigment epithelial cells (ARPE-19). Methods ARPE-19 cells were exposed to lipopolysaccharide (LPS; TLR 4 agonist) with simultaneous exposure to various concentrations of celastrol and the secretion of IL-6 cytokine was analyzed by ELISA. The effect of celastrol exposure on heat shock protein 70 (HSP70) expression was analyzed by western blotting. In response to celastrol and modulated HSP70 levels NF-kB activity was examined by ELISA. Results Celastrol suppressed the LPS-induced IL-6 expression levels via NF-kB transcription factor in ARPE-19 cells. Celastrol evoked elevated HSP70 levels without cytotoxicity. Interestingly, celastrols capability to inhibit NF-kB activity was diminished when HSP70 response was suppressed by siRNA. This reveals that celastrol has potent anti-inflammatory capacity in ARPE-19 cells, and its effect is modulated through NF-kB and HSP70. Conclusion Our findings reveal that celastrol is a novel compound to suppress innate immunity response in human retinal pigment epithelial cells. [source]

Plasma sex steroid concentrations and gonadal aromatase activities in African clawed frogs (Xenopus laevis) from South Africa

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2004
Markus Hecker
Abstract Adult African clawed frogs (Xenopus laevis) were collected from a corn-growing region (CGR) and a non-corn-growing region (NCGR) with different exposure profiles for atrazine and related triazines. Physical, chemical, and biological parameters from the catchment areas were also measured. Frogs were surveyed for possible effects of exposure to triazine herbicides on plasma testosterone (T) and estradiol (E2) titers, gonadal aromatase activity, and gonad growth (GSI). Concentrations of both T and E2 varied among locations and were correlated to some accessory factors, such as pH, several ions, and metals. Greatest median plasma T concentrations (males: 19 ng/ml; females: 16 ng/ml) occurred in frogs inhabiting NCGR as compared to those from the CGR (males: 4 ng/ml; females: 1 ng/ml). Median E2 concentrations were also greater in frogs collected from the NCGR (males: 3 ng/ml; females: 28 ng/ml) than those in frogs from the CGR (males: 2 ng/ml; females: 5 ng/ml). Because some exposure to agricultural chemicals at both regions occurred, as did simultaneous exposures to multiple chemicals, a regression analysis was employed. Negative correlations were observed between plasma T concentrations and concentrations of atrazine, deisopropylatrazine, deethylatrazine, and tertbuthylazine in females and between T and diaminochlorotriazine in males. Estradiol in females exhibited a significant negative correlation with atrazine and deethylatrazine. No correlations were observed between gonadal aromatase activity or GSI and any of the agricultural chemicals measured. Median aromatase activities in ovaries varied among sampling sites ranging from 7 to >3,000 times greater than those in males when measurable. Testicular aromatase activity was below the detection limit of the assay in male frogs at most of the sites. Although exposure to agricultural inputs did not affect aromatase activities, effects of atrazine or coapplied pesticides on sex steroid homeostasis cannot be excluded at this point. [source]