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Differential Effects (differential + effects)
Selected AbstractsEPISTASIS AND DOMINANCE: EVIDENCE FOR DIFFERENTIAL EFFECTS IN LIFE-HISTORY VERSUS MORPHOLOGICAL TRAITSEVOLUTION, Issue 10 2006Derek A. Roff Abstract Dominance and epistatic effects are predicted to be larger in life-history than in morphological traits. We test these predictions using published results from line cross analyses. We find that dominance is found in more than 95% of traits, regardless of the type of trait, but that the magnitude of the effect in relation to the additive effect is much greater in life-history than in morphological traits. Epistatic effects were detected more often in life-history than in morphological traits (79% and 67%, respectively). We also test for a difference in the magnitude of the effects by comparing the ratio of the nonadditive components separately to the additive component. For both dominance and epistatic components, the ratio of the nonadditive component to additive effects in life-history traits is approximately twice as large as that for morphological traits. [source] Differential Effects of Cold Exposure on Muscle Fibre Composition and Capillary Supply in Hibernator and Non-Hibernator RodentsEXPERIMENTAL PHYSIOLOGY, Issue 5 2001S. Egginton Changes in the composition of fibre types and the capillary supply of skeletal muscle (tibialis anterior) were quantified in rats and hamsters subjected to 8-10 weeks of cold exposure and reduced photoperiod (10 °C, 1 h light-23 h dark). Muscle mass decreased in both species (by 12% and 17%, respectively). Following acclimation to cold there were no specific changes in fibre cross-sectional area (FCSA) in rats, whereas in hamsters there was a substantial atrophy of Type II, but not Type I fibres. In rat muscle there was little difference between the two groups in average capillary to fibre ratio (C:F) (1.76 ± 0.15, normothermia, N; 1.69 ± 0.05, hypothermia, H) and average capillary density (CD) (188 ± 14 mm,2, N; 201 ± 12 mm -2, H). Similarly, the average C:F was unaltered in hamsters (2.75 ± 0.11, N; 2.72 ± 0.15, H), although the 30% smaller fibre size observed with hypothermia resulted in a corresponding increase in average CD, to 1539 ± 80 mm,2 (P < 0.01). However, there was a coordinated regional adaptation to cold exposure in hamsters resulting in capillary rarefaction in the glycolytic cortex and angiogenesis in the oxidative core. Following acclimation of rats to cold there was a reduction in the supply area of individual vessels (capillary domain), particularly in the cortex (9310, N; 8938 ,m2, H; P < 0.05). In contrast, hypothermic hamsters showed only a small decrease in mean domain area in the cortex (948 ,m2, N; 846 ,m2, H; n.s.) but a marked reduction in the core (871 ,m2, N; 604 ,m2, H; P < 0.01). Rats showed little or no change in local capillary supply (LCFR) to fast fibres on acclimation to cold, while in hamsters the LCFR of Type IIb fibres showed a decrease in the cortex (2.7, N; 2.3, H) and an increase in the core (3.0, N; 3.3, H) during acclimation to cold. These data suggest that during a simulated onset of winter rats maintain FCSA and capillary supply as part of an avoidance strategy, whereas hamsters increase muscle capillarity in part as a consequence of disuse atrophy. [source] A Comparative Study of Arm-Restraint Methodology: Differential Effects of Mother and Stranger Restrainers on Infants' Distress Reactivity at 6 and 9 Months of AgeINFANCY, Issue 3 2009Christin L. Porter This study examined both differential patterns and the stability of infants' (N = 70) distress reactivity across mother and stranger arm-restraint conditions when infants were 6 and 9 months of age. Reactivity measures included observational variables for the rise, intensity, and duration of infant distress as well as motor activities associated with escape behaviors. Correlation analyses revealed that infant behaviors during arm restraint were modestly stable across conditions and over time; however, mean comparisons also showed that infants' distress responses appear to be sensitive to protocol parameters (whether restrainer is mother or stranger). At 6 months of age, infants cried more during maternal restraint than with strangers and exhibited escape behaviors more frequently with mothers. Findings further indicate that infants' distress reactivity undergoes developmental alterations from 6 to 9 months of age, with infants crying more quickly, reaching peak intensity of distress faster, and displaying more distress at 9 months compared to 6 months. These changes in infants' reactivity were particularly accentuated during maternal compared to stranger restraint conditions at 9 months of age. [source] Differential Effects of Vitamin D Analogs on Vascular Calcification,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007Anna Cardús Abstract We tested the effects of calcitriol and its analog paricalcitol on VSMC calcification in vitro and in vivo. For that reason, cells and animals with five-sixths nephrectomy were treated with both compounds. Calcitriol, but not paricalcitol, increased VSMC calcification in vitro and in vivo independently of calcium and phosphate levels. This increase in calcification was parallel to an increase in the RANKL/OPG ratio. Introduction: Vascular calcification is a common finding in patients with endstage renal disease. Furthermore, those patients often present secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Thus, one of the main therapeutic options is to treat those patients with calcitriol or analogs. However, this treatment presents unwanted side effects, such as increases in vascular calcification. Materials and Methods: We tested the effect on vascular smooth muscle cell (VSMC) calcification of calcitriol and one of its analogs, paricalcitol, in vitro and in vivo in animals with endstage renal disease. Results: Calcitriol increased calcification of VSMCs cultured in calcification media. This effect was not present when cells were incubated with paricalcitol. Furthermore, only cells incubated with calcitriol showed an increased RANKL/ osteoprotegerin (OPG) expression. Animals with renal failure treated with hypercalcemic doses of calcitriol and paricalcitol showed an increase in systolic blood pressure. However, diastolic blood pressure only raised significantly in those animals treated with paricalcitol. This effect led to a significant increase in pulse pressure in animals treated with calcitriol. The increase in pulse pressure was likely caused by the extensive calcification observed in arteries of animals treated with calcitriol. This increase in calcification was not seen in arteries of animals treated with paricalcitol, despite having similar levels of serum calcium and phosphorus as animals treated with calcitriol. Furthermore, the decreases in serum PTH levels were similar in both treatments. Conclusions: We conclude that paricalcitol has a different effect than calcitriol in VSMC calcification and that this could explain part of the differences observed in the clinical settings. [source] Differential Effects of Teriparatide and Alendronate on Bone Remodeling in Postmenopausal Women Assessed by Histomorphometric Parameters,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005Monique Arlot MD Abstract An 18-month randomized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 ,g with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42 patients. Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment. Introduction: Alendronate and teriparatide increased BMD, assessed by DXA, by different mechanisms of action, supported by changes in biochemical markers of bone turnover. The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment. Materials and Methods: Patients were a cohort from a randomized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 ,g and alendronate 10 mg in postmenopausal women with osteoporosis. Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months (n = 23) or 18 months (n = 14); 5 additional patients were biopsied from contralateral sides at 6 and 18 months. Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months (teriparatide, n = 8; alendronate, n = 9) and 15 patients at 18 months (teriparatide, n = 8; alendronate, n = 7). Data were analyzed by two-sample tests. Results: Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months, whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months. Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group, returning to levels comparable with untreated postmenopausal women. In the teriparatide group, the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen, a biochemical marker of bone formation. The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups. Conclusions: These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide. [source] Differential Effects of Different Peers: Further Evidence of the Peer Proximity Thesis in Perceived Peer Influence on College Students' SmokingJOURNAL OF COMMUNICATION, Issue 3 2009Hye-Jin Paek First page of article [source] Differential Effects of Restricted Versus Unlimited High-Fat Feeding in Rats on Fat Mass, Plasma Hormones and Brain Appetite RegulatorsJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2009T. Shiraev The rapid rise in obesity has been linked to altered food consumption patterns. There is increasing evidence that, in addition to total energy intake, the macronutrient composition of the diet may influence the development of obesity. The present study aimed to examine the impact of high dietary fat content, under both isocaloric and hypercaloric conditions, compared with a low fat diet, on adiposity, glucose and lipid metabolism, and brain appetite regulators in rats. Male Sprague,Dawley rats were exposed to one of three diets: control (14% fat), ad lib high-fat palatable (HFD, 35% fat) or high-fat palatable restricted (HFD-R, matched to the energy intake of control) and were killed in the fasting state 11 weeks later. Body weight was increased by 28% in unrestricted HFD fed rats, with an almost tripling of caloric intake and fat mass (P < 0.001) and double the plasma triglycerides of controls. Glucose intolerance and increased insulin levels were observed. HFD-R animals calorie matched to control had double their fat mass, plasma insulin and triglycerides (P < 0.05). Only ad lib consumption of the HFD increased the hypothalamic mRNA expression of the appetite-regulating peptides, neuropeptide Y and pro-opiomelanocortin. Although restricted consumption of palatable HFD had no significant impact on hypothalamic appetite regulators or body weight, it increased adiposity and circulating triglycerides, suggesting that the proportion of dietary fat, independent of caloric intake, affects fat deposition and the metabolic profile. [source] Differential Effects of Stress on Adult Hippocampal Cell Proliferation in Low and High Aggressive MiceJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2007A. H. Veenema Male wild house mice selected for a long (LAL) or a short (SAL) latency to attack a male intruder generally show opposing behavioural coping responses to environmental challenges. LAL mice, unlike SAL mice, adapt to novel challenges with a highly reactive hypothalamic-pituitary-adrenal axis and show an enhanced expression of markers for hippocampal plasticity. The present study aimed to test the hypothesis that these features of the more reactive LAL mice are reflected in parameters of hippocampal cell proliferation. The data show that basal cell proliferation in the subgranular zone (SGZ) of the dentate gyrus, assessed by the endogenous proliferation marker Ki-67, is lower in LAL than in SAL mice. Furthermore, application of bromodeoxyuridine (BrdU) over 3 days showed an almost two-fold lower cell proliferation rate in the SGZ in LAL versus SAL mice. Exposure to forced swimming resulted, 24 h later, in a significant reduction in BrdU + cell numbers in LAL mice, whereas cell proliferation was unaffected by this stressor in SAL mice. Plasma corticosterone and dentate gyrus glucocorticoid receptor levels were higher in LAL than in SAL mice. However, no differences between the SAL and LAL lines were found for hippocampal NMDA receptor binding. In conclusion, the data suggest a relationship between coping responses and hippocampal cell proliferation, in which corticosterone may be one of the determinants of line differences in cell proliferation responses to environmental challenges. [source] Differential Effects of Placental Restriction on IGF-II, ACTH Receptor and Steroidogenic Enzyme mRNA Levels in the Foetal Sheep AdrenalJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2000Ross We have investigated the effects of restriction of placental growth on foetal adrenal growth and adrenal expression of mRNAs for Insulin-like Growth Factor II (IGF-II), the IGF binding protein IGFBP-2, Steroidogenic Factor 1 (SF-1) and adrenocorticotrophic hormone (ACTH) receptor (ACTH-R) and the steroidogenic cytochrome P-450 enzymes: cholesterol side chain cleavage (CYP11A1), 17, -hydroxylase (CYP17) and 21-hydroxylase (CYP21A1); and 3, -hydroxysteroid dehydrogenase/,5,4 isomerase (3,HSD). Endometrial caruncles were removed from non-pregnant ewes before mating (placental restriction group; PR). The total adrenal: foetal weight ratio was higher in PR (n=6 foetuses) than in control foetuses (n=6 foetuses). There was no difference in plasma ACTH concentrations between the PR and control foetuses between 130 and 140 days gestation. Adrenal IGF-II mRNA levels were lower (P<0.05) in the PR group, however, adrenal IGFBP-2 mRNA levels were not different between the PR and control groups. Adrenal ACTH-R mRNA levels were also lower whilst CYP11A1 mRNA levels were increased (P<0.005) in the PR group. We conclude that foetal adrenal growth and steroidogenesis are stimulated as a consequence of foetal growth restriction and that factors other than ACTH are important in foetal adrenal activation during chronic, sustained hypoxaemia. [source] Differential Effects of Acute and Chronic Ethanol Exposure on Orexin Expression in the Perifornical Lateral HypothalamusALCOHOLISM, Issue 5 2010Irene Morganstern Background:, Recent reports support the involvement of hypothalamic orexigenic peptides in stimulating ethanol intake. Our previous studies have examined the effects of ethanol on hypothalamic peptide systems of the paraventricular nucleus (PVN) and identified a positive feedback loop in which PVN peptides, such as enkephalin and galanin, stimulate ethanol intake and ethanol, in turn, stimulates the expression of these peptides. Recently, orexin (OX), a peptide produced mainly by cells in the perifornical lateral hypothalamus (PFLH), has been shown to play an important role in mediating the rewarding aspects of ethanol intake. However, there is little evidence showing the effects that ethanol itself may have on the OX peptide system. In order to understand the feedback relationship between ethanol and the OX system, the current investigation was designed to measure OX gene expression in the PFLH following acute as well as chronic ethanol intake. Methods:, In the first experiment, Sprague,Dawley rats were trained to voluntarily consume a 2 or 9% concentration of ethanol, and the expression of OX mRNA in the PFLH was measured using quantitative real-time polymerase chain reaction (qRT-PCR). The second set of experiments tested the impact of acute oral gavage of 0.75 and 2.5 g/kg ethanol solution on OX expression in the PFLH using qRT-PCR, as well as radiolabeled in situ hybridization. Further tests using digoxigenin-labeled in situ hybridization and immunofluorescence histochemistry allowed us to more clearly distinguish the effects of acute ethanol on OX cells in the lateral hypothalamic (LH) versus perifornical (PF) regions. Results:, The results showed chronic consumption of ethanol versus water to dose-dependently reduce OX mRNA in the PFLH, with a larger effect observed in rats consuming 2.5 g/kg/d (,70%) or 1.0 g/kg/d (,50%) compared to animals consuming 0.75 g/kg/d (,40%). In contrast to chronic intake, acute oral ethanol compared to water significantly enhanced OX expression in the PFLH, and this effect occurred at the lower (0.75 g/kg) but not higher (2.5 g/kg) dose of ethanol. Additional analyses of the OX cells in the LH versus PF regions identified the former as the primary site of ethanol's stimulatory effect on the OX system. In the LH but not the PF, acute ethanol increased the density of OX-expressing and OX-immunoreactive neurons. The increase in gene expression was detected only at the lower dose of ethanol (0.75 g/kg), whereas the increase in OX peptide was seen only at the higher dose of ethanol (2.5 g/kg). Conclusion:, These results lead us to propose that OX neurons, while responsive to negative feedback signals from chronic ethanol consumption, are stimulated by acute ethanol administration, most potently in the LH where OX may trigger central reward mechanisms that promote further ethanol consumption. [source] Differential Effects of Ethanol on Serum GABAergic 3,,5,/3,,5, Neuroactive Steroids in Mice, Rats, Cynomolgus Monkeys, and HumansALCOHOLISM, Issue 3 2010Patrizia Porcu Background:, Acute ethanol administration increases plasma and brain levels of progesterone and deoxycorticosterone-derived neuroactive steroids (3,,5,)-3-hydroxypregnan-20-one (3,,5,-THP) and (3,,5,)-3,21-dihydroxypregnan-20-one (3,,5,-THDOC) in rats. However, little is known about ethanol effects on GABAergic neuroactive steroids in mice, nonhuman primates, or humans. We investigated the effects of ethanol on plasma levels of 3,,5,- and 3,,5,-reduced GABAergic neuroactive steroids derived from progesterone, deoxycorticosterone, dehydroepiandrosterone, and testosterone using gas chromatography-mass spectrometry. Methods:, Serum levels of GABAergic neuroactive steroids and pregnenolone were measured in male rats, C57BL/6J and DBA/2J mice, cynomolgus monkeys, and humans following ethanol administration. Rats and mice were injected with ethanol (0.8 to 2.0 g/kg), cynomolgus monkeys received ethanol (1.5 g/kg) intragastrically, and healthy men consumed a beverage containing 0.8 g/kg ethanol. Steroids were measured after 60 minutes in all species and also after 120 minutes in monkeys and humans. Results:, Ethanol administration to rats increased levels of 3,,5,-THP, 3,,5,-THDOC, and pregnenolone at the doses of 1.5 g/kg (+228, +134, and +860%, respectively, p < 0.001) and 2.0 g/kg (+399, +174, and +1125%, respectively, p < 0.001), but not at the dose of 0.8 g/kg. Ethanol did not alter levels of the other neuroactive steroids. In contrast, C57BL/6J mice exhibited a 27% decrease in serum 3,,5,-THP levels (p < 0.01), while DBA/2J mice showed no significant effect of ethanol, although both mouse strains exhibited substantial increases in precursor steroids. Ethanol did not alter any of the neuroactive steroids in cynomolgus monkeys at doses comparable to those studied in rats. Finally, no effect of ethanol (0.8 g/kg) was observed in men. Conclusions:, These studies show clear species differences among rats, mice, and cynomolgus monkeys in the effects of ethanol administration on circulating neuroactive steroids. Rats are unique in their pronounced elevation of GABAergic neuroactive steroids, while this effect was not observed in mice or cynomolgus monkeys at comparable ethanol doses. [source] Differential Effects of Chronic Ethanol Consumption and Withdrawal on Homer/Glutamate Receptor Expression in Subregions of the Accumbens and Amygdala of P RatsALCOHOLISM, Issue 11 2009Ilona Obara Background:, Homer proteins are constituents of scaffolding complexes that regulate the trafficking and function of central Group1 metabotropic glutamate receptors (mGluRs) and N -methyl- d -aspartate (NMDA) receptors. Research supports the involvement of these proteins in ethanol-induced neuroplasticity in mouse. In this study, we examined the effects of short versus long-term withdrawal from chronic ethanol consumption on Homer and glutamate receptor protein expression within striatal and amygdala subregions of selectively bred, alcohol-preferring P rats. Methods:, For 6 months, male P rats had concurrent access to 15% and 30% ethanol solutions under intermittent (IA: 4 d/wk) or continuous (CA: 7 d/wk) access conditions in their home cage. Rats were killed 24 hours (short withdrawal: SW) or 4 weeks (long withdrawal: LW) after termination of ethanol access, subregions of interest were micropunched and tissue processed for detection of Group1 mGluRs, NR2 subunits of the NMDA receptor and Homer protein expression. Results:, Within the nucleus accumbens (NAC), limited changes in NR2a and NR2b expression were detected in the shell (NACsh), whereas substantial changes were observed for Homer2a/b, mGluRs as well as NR2a and NR2b subunits in the core (NACc). Within the amygdala, no changes were detected in the basolateral subregion, whereas substantial changes, many paralleling those observed in the NACc, were detected in the central nucleus (CeA) subregion. In addition, most of the changes observed in the CeA, but not NACc, were present in both SW and LW rats. Conclusions:, Overall, these subregion specific, ethanol-induced increases in mGluR/Homer2/NR2 expression within the NAC and amygdala suggest changes in glutamatergic plasticity had taken place. This may be a result of learning and subsequent memory formation of ethanol's rewarding effects in these brain structures, which may, in part, mediate the chronic relapsing nature of alcohol abuse. [source] Orexigenic Peptides and Alcohol Intake: Differential Effects of Orexin, Galanin, and GhrelinALCOHOLISM, Issue 11 2007Eve R. Schneider Background:, The question is which hypothalamic systems for food intake might play a role in ethanol intake and contribute to alcohol abuse. The peptide orexin was found to exhibit similar properties to galanin in its relation to dietary fat and may therefore be similar to galanin in having a stimulatory effect on alcohol intake. Methods:, Rats were trained to drink 10% ethanol, implanted with brain cannulas, and then injected in the paraventricular nucleus (PVN), lateral hypothalamus (LH), or nucleus accumbens (NAc) with galanin, orexin-A, and for comparison, ghrelin. Ethanol, food, and water intake were measured at 1, 2, and 4 hours postinjection. Results:, In the PVN, both orexin and galanin significantly increased ethanol intake, whereas ghrelin increased food intake. In the LH, orexin again induced ethanol intake, while ghrelin increased eating. In the NAc, orexin failed to influence ethanol intake but did stimulate food intake. Conclusions:, In ethanol-drinking rats, injection of orexin or galanin into the appropriate locus in the hypothalamus induced significant ethanol intake instead of food intake. Ghrelin, as a positive control, failed to influence ethanol intake at the same hypothalamic sites. In the NAc, as an anatomical control, orexin augmented eating but not ethanol intake. Thus orexin and galanin in the hypothalamus selectively stimulated ethanol intake at sites where other studies have shown that both ethanol and fat increase expression of the endogenous peptides. Thus, a neural circuit that evolved with the capability to augment food intake is apparently co-opted by ethanol and may serve as a potential positive feedback circuit for alcohol abuse. [source] Differential Effects of Ethanol on Insulin-Like Growth Factor-I Receptor SignalingALCOHOLISM, Issue 2 2000Andrea E.M. Seiler Background: Activation of the insulin-like growth factor I receptor (IGF-IR) by its ligands IGF-I and IGF-II induces cell proliferation and protects against apoptosis. Ethanol inhibits IGF-IR tyrosine autophosphorylation, which subsequently interferes with the activation of key downstream signaling mediators including insulin-receptor substrate-1, phosphatidylinositol 3-kinase, and mitogen-activated protein (MAP) kinase. The ethanol-induced inhibition of IGF-IR signaling reduces mitogenesis and enhances apoptosis. In the current study, we demonstrate that the antiproliferative action of ethanol can be modulated by differential sensitivity of the autophosphorylation of the IGF-IR to ethanol. Methods: A series of subclones was generated from 3T3 cells that express the human IGF-IR. Results: There was considerable variability in the ability of ethanol to inhibit IGF-I-dependent IGF-IR tyrosine autophosphorylation and MAP kinase activation, despite equivalent IGF-IR expression. The IGF-IR was completely resistant to a high concentration of ethanol (150 mM) in several subclones. The sensitivity of IGF-IR autophosphorylation to ethanol correlated directly with the inhibition of IGF-I-mediated MAP kinase activation and cell proliferation. Resistant subclones exhibited features of the transformed phenotype including high MAP kinase activity, partial loss of contact inhibition, and the development of foci at confluency. The IGF-IR isolated from ethanol-resistant cells was similarly resistant to ethanol in autophosphorylation reactions in vitro, whereas ethanol inhibited the autophosphorylation of IGF-IR obtained from sensitive cells. Conclusions: Our findings are the first to demonstrate the modulation of ethanol sensitivity of a tyrosine kinase receptor, and they provide a molecular basis for differential effects of ethanol on cell proliferation. [source] Differential Effects of Ethanol on Signal TransductionALCOHOLISM, Issue 1 2000Gail H. Levine Background: PC12 pheochromocytoma cells were used as a model to study the effect of long-term ethanol exposure on signal transduction systems. In PC12 cells, the agonist bradykinin stimulates a phospholipase C specific for inositol-containing phospholipids and a phospholipase D specific for phosphatidylcholine. Methods: PC12 cells were grown in monolayer and cultured in the presence and absence of 1% ethanol for 5 days. After this period, bradykinin-stimulated phospholipase C and D were measured. The effect of long-term ethanol on the bradykinin-mediated activation of mitogen-activated protein (MAP) kinase was also measured. Results: In cells exposed to 1% ethanol for 5 days, bradykinin-stimulated phospholipase D was greatly attenuated, whereas bradykinin-stimulated phospholipase C was not altered. The tyrosine kinase inhibitor, genistein, blocked the bradykinin-mediated activation of phospholipase D but did not affect the stimulation of phospholipase C. However, long-term ethanol treatment did not attenuate the ability of bradykinin to activate MAP kinase, which suggests that ethanol did not have a general effect on all tyrosine kinase pathways. Conclusions: Ethanol has a differential effect on signal transduction in PC12 cells. Activation of phospholipase D may be mediated by a kinase, whereas the activation of phospholipase C is probably mediated by the guanine nucleotide binding protein, Gq. Because of these differences in activation mechanism, the pathways may adapt differently to long-term exposure to ethanol. [source] Differential Effects of Oxidative Stress on Hepatic Endothelial and Kupffer Cell Eicosanoid Release in Response to Endothelin-1MICROCIRCULATION, Issue 6 2006AMEL KARAA ABSTRACT Objective: The vasoconstrictor endothelin-1 can induce vasomodulators release like nitric oxide in the liver. Here the authors explored whether endothelin-1 can stimulate endothelial and Kupffer cells release of other vasomodulators under normal and stress conditions. Methods: Cells were cultured for 24 h and treated with H2O2 (25 ,M) for 6 h and subsequently with endothelin-1 (10 nM) for 10 min. Eicosanoid release was assessed in the media by enzyme immunoassay. Results: Endothelin-1 mediated cPLA2 phosphorylation and increased prostaglandin (PG) I2, PGE2 and thromboxane A2 (TXA2) release in endothelial cells while it only increased TXA2 in Kupffer cells. H2O2 significantly increased PGI2, PGE2 and TXA2 in endothelial cells through an upregulation of cyclooxygenase-2, thromboxane synthase A2, and phosphorylation of cPLA2. Endothelin-1-induced PGI2, PGE2, and TXA2 release in endothelial cells were inhibited by H2O2 correlating with the absence of further cPLA2 phosphorylation. In Kupffer cells, H2O2 only increased TXA2 synthesis and further endothelin-1 stimulation of TXA2 was possible through a higher increase in cPLA2. Conclusion: These results indicate that under normal conditions endothelial cells play a pivotal role in liver microcirculation regulation. Oxidative stress not only disrupts the basal balance of vasomodulators in the liver but also affects endothelin-1-induced effects in both Kupffer cells and endothelial cells. [source] Rapamycin and MPA, But Not CsA, Impair Human NK Cell Cytotoxicity Due to Differential Effects on NK Cell PhenotypeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010D. N. Eissens Cyclosporin A (CsA), rapamycin (Rapa) and mycophenolic acid (MPA) are frequently used for GVHD prophylaxis and treatment after allogeneic stem cell transplantation (SCT). As NK cells have received great interest for immunotherapeutic applications in SCT, we analyzed the effects of these drugs on human cytokine-stimulated NK cells in vitro. Growth-kinetics of CsA-treated cultures were marginally affected, whereas MPA and Rapa severely prevented the outgrowth of CD56bright NK cells. Single-cell analysis of NK cell receptors using 10-color flow cytometry, revealed that CsA-treated NK cells gained a similar expression profile as cytokine-stimulated control NK cells, mostly representing NKG2A+KIR,NCR+ cells. In contrast, MPA and Rapa inhibited the acquisition of NKG2A and NCR expression and NK cells maintained an overall NKG2A,KIR+NCR+/, phenotype. This was reflected in the cytolytic activity, as MPA- and Rapa-treated NK cells, in contrast to CsA-treated NK cells, lost their cytotoxicity against K562 target cells. Upon target encounter, IFN-, production was not only impaired by MPA and Rapa, but also by CsA. Overall, these results demonstrate that CsA, MPA and Rapa each have distinct effects on NK cell phenotype and function, which may have important implications for NK cell function in vivo after transplantation. [source] Differential Effects of Partial Hepatectomy and Carbon Tetrachloride Administration on Induction of Liver Cell Foci in a Model for Detection of Initiation ActivityCANCER SCIENCE, Issue 10 2001Hiroki Sakai Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CC14) administration on induction of glutathione S-transferase placental form (GST-P)-positive foci were investigated in a model for detection of initiation activity. Firstly, we surveyed cell proliferation kinetics and fluctuation in cytochrome P450 (CYP) mRNA levels by means of relative-quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and CYP 2E1 apoprotein amount by immuno-blotting (experiment I) after PH or CC14 administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CC14 administration and induction of liver cell foci, the non-hepatocarcinogen, 1,2-dimethylhydrazine (DMH) was administered to 7-week-old male F344 rats and initiated populations were selected using the resistant hepatocyte model (experiment II). In experiment I, the values of all CYP isozyme mRNAs after PH or CC14 administration were drastically decreased at the 12-h tune point. From 72 h, mRNAs for all CYP isozymes began increasing, with complete recovery after 7 days. The CYP 2E1 apoprotein content in the PH group fluctuated weakly, whereas in the CC14 group it had decreased rapidly after 12 h and was still low at the 48 h point. In experiment II, induction of GST-P-positive foci was related to cell kinetics in the PH group, with about a 6-h time lag between tune for carcinogen administration giving greatest induction of GST-P-positive foci and peaks in bromodeoxyuridine (BrdU) labeling, presumably due to the necessity for bioactivation of DMH. With CC14 administration, induction of foci appeared dependent on the recovery of CYP 2E1. In conclusion, PH was able to induce cell proliferation with maintenance of CYP 2E1, therefore being advantageous for induction of liver cell foci in models to detect initiation activity. [source] Differential Effects of Maternal Sensitivity to Infant Distress and Nondistress on Social-Emotional FunctioningCHILD DEVELOPMENT, Issue 3 2009Esther M. Leerkes Associations between maternal sensitivity to infant distress and nondistress and infant social-emotional adjustment were examined in a subset of dyads from the NICHD Study of Early Child Care (N = 376). Mothers reported on infant temperament at 1 and 6 months postpartum, and maternal sensitivity to distress and nondistress were observed at 6 months. Child behavior problems, social competence, and affect dysregulation were measured at 24 and 36 months. Maternal sensitivity to distress but not to nondistress was related to fewer behavioral problems and higher social competence. In addition, for temperamentally reactive infants, maternal sensitivity to distress was associated with less affect dysregulation. Sensitivity to nondistress only prevented affect dysregulation if sensitivity to distress was also high. [source] Free radical generation and oxidative stress with ageing and exercise: Differential effects in the myocardium and liverACTA PHYSIOLOGICA, Issue 4 2000Bejma Reactive oxygen species and other oxidants are implicated in the mechanisms of biological ageing and exercise-induced tissue damage. The present study examined the effects of ageing and an acute bout of exercise on intracellular oxidant generation, lipid peroxidation, protein oxidation and glutathione (GSH) status in the heart and liver of young adult (8 month, N=24) and old (24 month, N=24) male Fischer 344 rats. Young rats ran on treadmill at 25 m min,1, 5% grade until exhaustion (55.4 ± 2.7 min), whereas old rats ran at 15 m min,1, 5% until exhaustion (58.0 ± 2.7 min). Rate of dichlorofluorescin (DCFH) oxidation, an indication of intracellular oxidant production, was significantly higher in the homogenates of aged heart and liver compared with their young counterparts. In the isolated heart and liver mitochondria, ageing increased oxidant production by 29 and 32% (P < 0.05), respectively. Acute exercise increased oxidant production in the aged heart but not in the liver. When nicodinamide dinucleotide phosphate (reduced), adenosine diphosphate and Fe3+ were included in the assay, DCFH oxidation rate was 47 and 34% higher (P < 0.05) in the aged heart and liver homogenates, respectively, than the young ones. The age differences in the induced state reached 83 and 140% (P < 0.01) in isolated heart and liver mitochondria, respectively. Lipid peroxidation was increased in the aged liver and exercised aged heart, whereas protein carbonyl content was elevated only in the aged heart (P < 0.05). Although our data using DCFH method probably underestimated cellular oxidant production because of time delay and antioxidant competition, it is clear that oxidative stress was enhanced in both heart and liver with old age. Furthermore, aged myocardium showed greater susceptibility to oxidative stress after heavy exercise. [source] Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brainDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2007David Rotllant Abstract Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Morning cortisol Levels in preschool-aged foster children: Differential effects of maltreatment type,DEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2009Jacqueline Bruce Abstract Maltreated foster children are subjected to a range of early adverse experiences, including neglect, abuse, and multiple caregiver disruptions. Research suggests that such disturbances alter the development and subsequent functioning of the hypothalamic-pituitary-adrenocortical system. The current study was designed to investigate morning cortisol levels in 117 foster children and 60 low-income, nonmaltreated children. Maltreatment and foster care placement experiences were coded from official records. Analyses revealed that the foster children were significantly more likely than the nonmaltreated children to have low morning cortisol levels. Additionally, specific maltreatment experiences were significantly associated with the foster children's morning cortisol levels. Foster children with low morning cortisol levels experienced more severe physical neglect than the other foster children. In contrast, foster children with high morning cortisol levels experienced more severe emotional maltreatment. These results suggest that specific early adverse experiences have differential effects on the functioning of the hypothalamic-pituitary-adrenocortical system. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 51: 14,23, 2009 [source] Differential effects of short and long duration insulinotropic agents on meal-related glucose excursionsDIABETES OBESITY & METABOLISM, Issue 2 2001C. J. De Souza SUMMARY Aim Abnormal ,-cell function, characterized as the inability of the ,-cell to mount a rapid secretory response to glucose, is a well-established pathology of type 2 diabetes mellitus. These studies were designed to demonstrate the importance of early insulin release on the control of meal-induced glucose excursions by capitalizing on the significant pharmacodynamic differences between several oral insulin secreting agents. Methods Male Sprague Dawley fitted with indwelling jugular cannulas were used to compare the pharmacodynamic profiles of nateglinide (Nateg), glipizide (Glip) and repaglinide (Repag) through frequent blood samples following the administration of these compounds via oral gavage. In similar animals which were pretrained to consume their daily food intake in two discrete 45-min meals, the effects of compound induced changes in pre-meal, meal and post-meal insulin profiles on glycaemic control were assessed through frequent blood sampling following the administration of these compounds 10 min prior to a 30-min meal. Results There were significant pharmacodynamics differences between the three oral agents tested and the time to elicit peak insulin secretory responses increased from Nateg (4 min) to Repag (10 min) to Glip (45 min). During the meal tolerance test, glibenclamide did not increase pre-meal insulin levels and glucose excursions paralleled those in the control. Conversely, the other three agents, at doses that produced hypoglycaemic responses of similar magnitude, all increased early insulin release (,AUC(-15 to 3 min) = 0.5 ± 0.01, 1.6 ± 0.4, 3.6 ± 0.0, 1.2 ± 0.1 and 1.73 ± 0.4 nmol/min, for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively) and curbed glucose excursions during the meal at varying rates and degrees (,AUC(0,30 min) = 39 ± 6, 8 ± 7, 5 ± 7, ,,1 ± 8 and ,,3 ± 8 mmol/min for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively). However, unlike Nateg, the longer duration of action of Repag and Glip elicited sustained post-meal relative hypoglycaemia. Conclusion These data support the impact of early and rapid insulin release in the control of prandial and post-meal glycaemia and demonstrate that a short anticipatory burst of insulin, restricted to the beginning of a meal, provides a clear metabolic advantage and prevents post-meal hypoglycaemic episodes when compared to a greater but reactive insulin exposure that follows a meal-induced increase in glucose excursion. [source] Differential effects of temporal pole resection with amygdalohippocampectomy versus selective amygdalohippocampectomy on material-specific memory in patients with mesial temporal lobe epilepsyEPILEPSIA, Issue 1 2008Christoph Helmstaedter Summary Purpose: In the surgical treatment of mesial temporal lobe epilepsy, there is converging evidence that individually tailored or selective approaches have a favorable cognitive outcome compared to standard resections. There is, however, also evidence that due to collateral damage, selective surgery can be less selective than suggested. As part of a prospective transregional research project the present study evaluated the outcome in memory and nonmemory functions, following two selective approaches: a combined temporal pole resection with amygdalohippocampectomy (TPR+) and transsylvian selective amygdalohippocampectomy (SAH). Methods: One year after surgery, cognitive outcomes of postoperatively seizure-free patients with mesial TLE and hippocampal sclerosis, who underwent either TPR+ (N = 35) or SAH (N = 62) in two German epilepsy centers (Bonn/Berlin), were compared. Results: Repeated measurement MANOVA and separate post hoc testing indicated a double dissociation of verbal/figural memory outcome as dependent on side and type of surgery. Verbal memory outcome was worse after left-sided operation, but especially for SAH, whereas figural memory outcome was worse after right-sided operation, preferentially for TPR+. Attention improved independent of side or type of surgery, and language functions showed some improvement after right-sided surgeries. Discussion: The results indicate a differential effect of left/right SAH versus TPR+ on material-specific memory insofar as transsylvian SAH appears to be favorable in right and TPR+ in left MTLE. The different outcomes are discussed in terms of a different surgical affection of the temporal pole and stem, and different roles of these structures for verbal and figural memory. [source] Differential effects of US2, US6 and US11 human cytomegalovirus proteins on HLA class,Ia and HLA-E expression: impact on target susceptibility to NK cell subsetsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2003Manuel Llano Abstract We compared in an inducible expression system the individual effect of US2, US6 and US11 human cytomegalovirus (HCMV) proteins on HLA-E and HLA class,Ia surface expression, assessing in parallel their influence on target susceptibility to NK cell clones. To this end, the RPMI,8866 B,lymphoma cell line (HLA-A2, HLA-A3, HLA-B7, HLA-Cw7, HLA-ER, HLA-EG) was stably cotransfected with the ecdysone receptor, together with the US sequences under the control of an ecdysone-inducible promoter. Biosynthesis of viral proteins was turned on by incubating transfectants with Ponasterone,A. US6 down-regulated expression of all class,I molecules, hampering target resistance to NK cell clones controlled by the CD94/NKG2A, KIR2DL2 and/or CD85j (ILT2 or LIR-1) inhibitory receptors. By contrast, US11 reduced the surface levels of class,Ia molecules but preserved HLA-E; this rendered US11+ cells sensitive to NK clones under the control of KIR2DL2 and/or CD85j, while their resistance to CD94/NKG2A+KIR2DL2, effector cells was maintained. US2 preserved as well HLA-E expression but selectively targeted class,Ia molecules; in fact, HLA-A and HLA-C allotypes were down-modulated whereas HLA-B7 remained unaltered. US2+ targets became sensitive to KIR2DL2+ cells but remained resistant to CD94/NKG2A+CD85j+ NK clones. The differential effects of US proteins on HLA class,Ia and HLA-E likely reflect the evolutionary adaptation of HCMV to counteract NK-mediated surveillance. [source] CLINICAL STUDY: Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicatorsADDICTION BIOLOGY, Issue 3 2009Wendy Ooteman ABSTRACT Acamprosate and naltrexone are effective medications in the treatment of alcoholism. However, effect sizes are modest. Pharmacogenomics may improve patient-treatment-matching and effect sizes. It is hypothesized that naltrexone exerts its effect through genetic characteristics associated with the dopaminergic/opioidergic positive reinforcement system, whereas acamprosate works through the glutamatergic/GABAergic negative reinforcement system. Alcohol-dependent subjects were randomly assigned to either acamprosate or naltrexone. Subjects participated in a cue-exposure experiment at the day before and at the last day of medication. Reductions in cue-induced craving and physiological cue reactivity were measured. Differential effects of naltrexone and acamprosate on these outcomes were tested for different polymorphisms of the opioid, dopamine, glutamate and GABA-receptors. Significant matching effects were found for polymorphisms at the DRD2, GABRA6 and GABRB2 gene. In addition, a trend was found for the OPRM1 polymorphism. This provides evidence for the matching potential of genotypes. It is expected that more effective treatments can be offered when genetic information is used in patient-treatment-matching. [source] Differential effects of NT-4, NGF and BDNF on development of neurochemical architecture and cell size regulation in rat visual cortex during the critical periodEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007Maren Engelhardt Abstract Development of inhibition is a crucial determinant of the time course of visual cortical plasticity. BDNF strongly affects interneuron development and the onset and closure of the critical period for ocular dominance plasticity. Less is known on the effects of NT-4 despite a clear involvement in ocular dominance plasticity. We have investigated the effects of NT-4 on interneuron development by supplying NT-4 with osmotic minipumps during two time windows overlapping the onset (P12,20) and the peak (P20,28) of the critical period. We assessed the expression of interneuronal markers and soma size maturation either after the end of the infusion periods or at the end of the critical period (P45). We found that NT-4 was very effective in regulating interneuron development. NPY, SOM and PARV neuron somata grew faster during both infusion periods whereas CR neurons only responded during the early infusion period. The effects of soma size elicited during the earlier infusion period were still present at P45. In PARV neurons, NT-4 caused a long-lasting stabilization of CB and NPY expression. Furthermore, NT-4 accelerated the expression of GAD-65 mRNA in a subset of non-PARV neurons of layer V, which normally up-regulate GAD-65 towards the end of the critical period. Most of these effects were shared by NT-4 and BDNF. Some were unexpectedly also shared by NGF, which promoted growth of layer V PARV neurons, stabilized the CB expression and accelerated the GAD-65 expression. The results suggest that neurotrophins act on critical period plasticity by strengthening inhibition. [source] Differential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2006Anne Kirchner Abstract In vivo, severe hypoglycemia is frequently associated with seizures. The hippocampus is a structure prone to develop seizures and seizure-induced damage. Patients with repeated hypoglycemic episodes have frequent memory problems, suggesting impaired hippocampal function. Here we studied the effects of moderate hypoglycemia on primarily generalized flurothyl-induced seizures in vivo and, using EEG recordings, we determined involvement of the hippocampus in hypoglycemic seizures. Moderate systemic hypoglycemia had proconvulsant effects on flurothyl-induced clonic (forebrain) seizures. During hypoglycemic seizures, seizure discharges were recorded in the hippocampus. Thus, we continued the studies in combined entorhinal cortex,hippocampus slices in vitro. However, in vitro, decreases in extracellular glucose from baseline 10 mm to 2 or 1 mm did not induce any epileptiform discharges. In fact, low glucose (2 and 1 mm) attenuated preexisting low-Mg2+ -induced epileptiform activity in the entorhinal cortex and hippocampal CA1 region. Osmolarity compensation in low-glucose solution using mannitol impaired slice recovery. Additionally, using paired-pulse stimuli we determined that there was no impairment of GABAA inhibition in the dentate gyrus during glucopenia. The data strongly indicate that, although forebrain susceptibility to seizures is increased during moderate in vivo hypoglycemia and the hippocampus is involved during hypoglycemic seizures, glucose depletion in vitro contributes to an arrest of epileptiform activity in the system of the entorhinal cortex,hippocampus network and there is no impairment of net GABAA inhibition during glucopenia. [source] Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarrayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2002Raffaella Molteni Abstract Studies were performed to determine the effects of acute and chronic voluntary periods of exercise on the expression of hippocampal genes. RNAs from rodents exposed to a running wheel for 3, 7 and 28 days were examined using a microarray with 1176 cDNAs expressed primarily in the brain. The expression of selected genes was quantified by Taqman RT-PCR or RNase protection assay. The largest up-regulation was observed in genes involved with synaptic trafficking (synapsin I, synaptotagmin and syntaxin); signal transduction pathways (Ca2+/calmodulin-dependent protein kinase II, CaM-KII; mitogen-activated/extracellular signal-regulated protein kinase, MAP-K/ERK I and II; protein kinase C, PKC-,) or transcription regulators (cyclic AMP response element binding protein, CREB). Genes associated with the glutamatergic system were up-regulated (N -methyl- d -aspartate receptor, NMDAR-2A and NMDAR-2B and excitatory amino acid carrier 1, EAAC1), while genes related to the gamma-aminobutyric acid (GABA) system were down-regulated (GABAA receptor, glutamate decarboxylase GAD65). Brain-derived neurotrophic factor (BDNF) was the only trophic factor whose gene was consistently up-regulated at all timepoints. These results, together with the fact that most of the genes up-regulated have a recognized interaction with BDNF, suggest a central role for BDNF on the effects of exercise on brain plasticity. The temporal profile of gene expression seems to delineate a mechanism by which specific molecular pathways are activated after exercise performance. For example, the CaM-K signal system seems to be active during acute and chronic periods of exercise, while the MAP-K/ERK system seems more important during long-term exercise. [source] Differential effects of Mxi1-SR, and Mxi1-SR, in Myc antagonismFEBS JOURNAL, Issue 17 2007Claire Dugast-Darzacq Mxi1 belongs to the Myc-Max-Mad transcription factor network. Two Mxi1 protein isoforms, Mxi1-SR, and Mxi1-SR,, have been described as sharing many biological properties. Here, we assign differential functions to these isoforms with respect to two distinct levels of Myc antagonism. Unlike Mxi1-SR,, Mxi1-SR, is not a potent suppressor of the cellular transformation activity of Myc. Furthermore, although Mxi1-SR, exhibits a repressive effect on the MYC promoter in transient expression assays, Mxi1-SR, activates this promoter. A specific domain of Mxi1-SR, contributes to these differences. Moreover, glyceraldehyde-3-phosphate dehydrogenase interacts with Mxi1-SR, and enhances its ability to activate the Myc promoter. Our findings suggest that Mxi1 gains functional complexity by encoding isoforms with shared and distinct activities. [source] | ||||||||||||||||||||||||||||||||||||||||||||||