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Age-related Differences (age-related + difference)
Selected AbstractsAge-Related Differences in the Motivation of Learning English as a Foreign Language: Attitudes, Selves, and Motivated Learning BehaviorLANGUAGE LEARNING, Issue 2 2008Judit Kormos Our study describes the motivation for learning English as a foreign language in three distinct learner populations: secondary school pupils, university students, and adult language learners. Questionnaire data were collected from 623 Hungarian students. The main factors affecting students' second language (L2) motivation were language learning attitudes and the Ideal L2 self, which provides empirical support for the main construct of the theory of the L2 Motivational Self-System (Dörnyei, 2005). Models of motivated behavior varied across the three investigated learner groups. For the secondary school pupils, it was interest in English-language cultural products that affected their motivated behavior, whereas international posture as an important predictive variable was only present in the two older age groups. [source] Age-related differences in neural correlates of face recognition during the toddler and preschool yearsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2003Leslie J. Carver Abstract Research on the development of face recognition in infancy has shown that infants respond to faces as if they are special and recognize familiar faces early in development. Infants also show recognition and differential attachment to familiar people very early in development. We tested the hypothesis that infants' responses to familiar and unfamiliar faces differ at different ages. Specifically, we present data showing age-related changes in infants' brain responses to mother's face versus a stranger's face in children between 18 and 54 months of age. We propose that these changes are based on age-related differences in the perceived salience of the face of the primary caregiver versus strangers. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 42: 148,159, 2003 [source] Age-related differences in susceptibility to cisplatin-induced renal toxicity,,JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2010P. Espandiari Abstract Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague,Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6,mg,kg,1 i.p.). Urine samples were collected prior and up to 72,h after treatment in animals that were , 25 days old. Several serum, urinary and ,omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 , 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers. Published in 2009 by John Wiley & Sons, Ltd. [source] Developmental insights into experience-based decision makingJOURNAL OF BEHAVIORAL DECISION MAKING, Issue 1 2010Tim Rakow Abstract In three experiments involving children and adults (N,=,324), option payoffs for sure versus risky choices were either described or experienced via observation of 20 outcomes. Choices revealed a description-experience gap for payoffs with rare events, implying greater impact of small probabilities (,.2) for described than for experienced choices. The size of this effect was independent of participant age. Therefore, the role of cognitive limitations in the description-experience distinction remains unclear, as the age groups would have differed in cognitive capacity. Age-related differences in ,sampling style' in decisions from experience were observed. Pre-choice data acquisition changed markedly with age: From frequent alternation between options towards separate systematic exploration of options with increasing age. A fourth experiment, that manipulated sampling style, failed to demonstrate its link to other age-related features of choice (e.g. risk preferences). Our studies illustrate the value of developmental research for testing theoretical claims and revealing novel phenomena in decision research. Copyright © 2009 John Wiley & Sons, Ltd. [source] Age-related differences in insulin-like growth factor-1 receptor signaling regulates Akt/FOXO3a and ERK/Fos pathways in vascular smooth muscle cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2008Muyao Li Advanced age is a major risk factor for atherosclerosis, but how aging per se influences pathogenesis is not clear. Insulin-like growth factor-1 receptor (IGF-1R) promotes aortic vascular smooth muscle cell (VSMC) growth, migration, and extracellular matrix formation, but how IGF-1R signaling changes with age in VSMC is not known. We previously found age-related differences in the activation of Akt/FOXO3a and ERK1/2 pathways in VSMC, but the upstream signaling remains unclear. Using explanted VSMC from Fischer 344/Brown Norway F1 hybrid rats shown to display age-related vascular pathology similar to humans, we compared IGF-1R expression in early passages of VSMC and found a constitutive activation of IGF-1R in VSMC from old compared to young rats, including IGF-1R expression and its tyrosine kinase activity. The link between IGF-1R activation and the Akt/FOXO3a and ERK pathways was confirmed through the induction of IGF-1R with IGF-1 in young cells and attenuation of IGF-1R with an inhibitor in old cells. The effects of three kinase inhibitors: AG1024, LY294002, and TCN, were compared in VSMC from old rats to differentiate IGF-1R from other upstream signaling that could also regulate the Akt/FOXO and ERK pathways. Genes for p27kip-1, catalase and MnSOD, which play important roles in the control of cell cycle arrest and stress resistance, were found to be FOXO3a-targets based on FOXO3a-siRNA treatment. Furthermore, IGF-1R signaling modulated these genes through activation of the Akt/FOXO3a pathway. Therefore, activation of IGF-1R signaling influences VSMC function in old rats and may contribute to the increased risk for atherosclerosis. J. Cell. Physiol. 217: 377,387, 2008. © 2008 Wiley-Liss, Inc. [source] Age-related differences in MAP kinase activity in VSMC in response to glucose or TNF-,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2003Muyao Li Aortic vascular smooth muscle cells (VSMC) were used to study the effect of age on responses to high glucose concentrations or the cytokine, tumor necrosis factor-alpha (TNF-,). Activator protein-1 (AP-1) binding to DNA increased more in VSMC from old versus young rats (P,<,0.02) and was related to increased expression of its components, c-Fos, Fra-1, and JunD. The relationship to upstream signals, i.e., activities of mitogen-activated protein kinases (MAPK), was studied using antibodies to total and phosphorylated forms of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK) and p38. High glucose and TNF-, increased ERK phosphorylation more in old (P,<,0.05); whereas only TNF-, induced JNK activation in young (P,<,0.04). PD98059, a MEK inhibitor, attenuated AP-1 activation, lowered c-Fos and Fra-1 protein levels and reduced cell number and cells positive for proliferating cell nuclear antigen in old. We concluded that age differentially influenced activation of signaling pathways in VSMC exposed to high glucose or TNF-,. This may contribute to the increased risk for vascular disease associated with aging and diabetes mellitus (DM). J. Cell. Physiol. 197: 418,425, 2003© 2003 Wiley-Liss, Inc. [source] Age and gender differences in body composition, energy expenditure, and glucoregulation of adult rhesus monkeysJOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2000Jon J. Ramsey The purpose of this study was to examine the relationship of age to body composition, glucoregulation, activity, and energy expenditure in male and female rhesus monkeys. The animals were studied in three groups, young adults (YA, 7,9 years), middle-aged adults (MA, 13,17 years), and older adults (OA,>23 years) adults. OA had a lower ( P<0.05) lean body mass than the YA and MA. OA also had the lowest values (P<0.06) for energy expenditure (kJ/minute). Age-related differences (P<0.05) were observed in time spent resting and moving. The OA spent the most time resting and the least time in vertical movement. There was a trend towards an age-related decrease in acute insulin response to glucose, while other glucoregulatory parameters were not changed with age. These results are similar to findings in humans, providing further evidence that the rhesus monkey is an appropriate model of human aging. [source] Aging alters regional multichemical profile of the human brain: an in vivo1H-MRS study of young versus middle-aged subjectsJOURNAL OF NEUROCHEMISTRY, Issue 2 2001Igor D. Grachev Age-related differences in the multichemical proton magnetic resonance spectroscopy (1H-MRS) profile of the human brain have been reported for several age groups, and most consistently for ages from neonates to 16-year-olds. Our recent 1H-MRS study demonstrated a significant age-related increase of total chemical concentration (relative to creatine) in the prefrontal and sensorimotor cortices within young adulthood (19,31-year-olds). In the present study we test the hypothesis that the level of brain chemicals in the same cortices, which show increased chemical levels during normal development, are reduced with normal aging after young adulthood. The multichemical 1H-MRS profile of the brain was compared between 19 young and 16 middle-aged normal subjects across multiple brain regions for all chemicals of 1H-MRS spectra. Chemical concentrations were measured relative to creatine. Over all age groups the total relative chemical concentration was highest in the prefrontal cortex. Middle-aged subjects demonstrated a significant decrease of total relative chemical concentration in the dorsolateral prefrontal (F = 54.8, p < 10,7, anova), orbital frontal (F = 3.7, p < 0.05) and sensorimotor (F = 15.1, p < 0.0001) cortices, as compared with younger age. Other brain regions showed no age-dependent differences. The results indicate that normal aging alters multichemical 1H-MRS profile of the human brain and that these changes are region-specific, with the largest changes occuring in the dorsolateral prefrontal cortex. These findings provide evidence that the processes of neuronal maturation of the human brain, and neurotransmitters and other chemical changes as the marker of these neuronal changes are almost finished by young adulthood and then reduced during normal aging toward middle age period of life. The present data also support the notion of heterochronic regressive changes of the aging human brain, where the multichemical brain regional profile seems to inversely recapitulate cortical chemical maturation within normal development. [source] Age-specific functions of Stone Handling, a solitary-object play behavior, in Japanese Macaques (Macaca fuscata)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 3 2007Charmalie A.D. Nahallage Abstract Stone handling (SH) in Japanese macaques, a form of solitary-object play, is newly acquired only by young individuals, and is the first example of a directly nonadaptive behavior that is maintained as a behavioral tradition within free-ranging provisioned social troops. We report here the first systematic investigation of this behavior in a stable captive social troop, the Takahama troop, which is housed in an outdoor enclosure of the Primate Research Institute (PRI), Kyoto University, Japan. This study was conducted to evaluate relevant competing hypotheses regarding the function of object play (e.g., misdirected foraging behavior and motor training) to explain the proximal causes and ultimate function(s) of SH. The "misdirected foraging behavior" hypothesis can be ruled out because of the lack of a clear temporal relationship between feeding and the occurrence of SH in any age class. Age-related differences in SH performance and behavioral patterns were observed, suggesting possible differences in the immediate cause and ultimate function between young and adults. Young individuals engaged in frequent bouts of short duration, involving locomotion and vigorous body actions throughout the day, which is typical for play by young in general. This pattern of behavior is consistent with the motor training hypothesis, which states that play occurs during the development of motor and perceptual skills and is thus potentially critical for neural and cognitive development. This practice is continued by those who acquire it at an early age, with adults engaging in significantly fewer but longer bouts that involve more stationary, complex manipulative patterns, almost exclusively in the late afternoon. We propose that for adults, at the proximate level SH is psychologically relaxing, but ultimately functions to maintain and regenerate neural pathways, and potentially helps to slow down the deterioration of cognitive function associated with advanced age in long-lived provisioned and captive macaques. Am. J. Primatol. 69:1,15, 2007.© 2006 Wiley-Liss, Inc. [source] Remembering when we last remembered our childhood experiences: Effects of age and context on retrospective metamemory judgmentsAPPLIED COGNITIVE PSYCHOLOGY, Issue 5 2009Rachel Abenavoli People sometimes exhibit a ,forgot-it-all-along bias' in which they claim that they have gone for months or years without thinking about certain childhood experiences despite recently recalling those memories. The present study examines memory for memories of childhood experiences, expanding on prior work by using manipulations that require greater reflection when thinking about remembered experiences and when making retrospective metamemory judgments. Age-related differences in memory-for-memory accuracy were also examined. Young (18,20) and older adults (63,89) recalled various events while focusing on emotional or perceptual details for some, and several weeks later were asked to indicate the last time they had remembered various events. Results showed that young adults were more accurate than older adults overall, though both age groups still exhibited a forgot-it-all-along bias that was reduced but not eliminated when a contextual reminder was provided. Copyright © 2008 John Wiley & Sons, Ltd. [source] Effectiveness of participation as a defendant: the attorney,juvenile client relationship,BEHAVIORAL SCIENCES & THE LAW, Issue 2 2003Melinda G. Schmidt M.A. Recent changes in the processing of juveniles in the justice system place greater significance on children's capacities to participate in legal contexts. Effective participation as a defendant encompasses abilities beyond those legally required for adjudicative competence, which may nevertheless influence the quality and nature of a defendant's participation in the trial process. Based in developmental judgment theory, the current study compares 203 juveniles and 110 adults detained pre-trial using a hypothetical attorney,client vignette to examine how psychosocial factors are reflected in decision-making processes and link to decision outcomes and effective participation within the attorney,client relationship. Age-related differences in legally relevant decision-making processes and outcomes are identified, and implications for policy are made. Copyright © 2003 John Wiley & Sons, Ltd. [source] Age-related differences in the pharmacokinetics of stavudine in 272 children from birth to 16 years: a population analysisBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2007V. Jullien Aims To develop a population pharmacokinetic model for stavudine in children and to investigate the consistency of the currently recommended dose based on adult target concentrations. Methods The pharmacokinetics of stavudine were investigated using a population approach. Individual estimates of CL/F were used to calculate the stavudine dose required to achieve the area under the concentration-time curve reported in adults given recommended doses. Results Stavudine pharmacokinetics were well described by a one-compartment model with zero-order absorption. Typical population estimates (% interindividual variability) of the apparent distribution volume (V/F) and plasma clearance (CL/F) were 40.9 l (32%) and 16.5 l h,1 (38%), respectively. Stavudine V/F and CL/F were similarly related to age. Mean calculated doses (0.61 mg kg,1 for children less than 2 weeks, 1.23 mg kg,1 for children more than 2 weeks with bodyweight less than 30 kg, and 31.5 mg for children with a bodyweight between 30 and 60 kg) were in agreement with the current paediatric doses (0.5 mg kg,1, 1 mg kg,1, and 30 mg, respectively). Conclusions Our findings support the current recommended paediatric dosage regimens for stavudine, as they result in the same exposure to the drug as in adults. [source] Creutzfeldt,Jakob disease risk and PRNP codon 129 polymorphism: necessity to revalue current dataEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2005E. Mitrová The polymorphism at codon 129 (M129V) of the prion protein gene (PRNP) is a recognized genetic marker for susceptibility to Creutzfeldt,Jakob disease (CJD) in the Caucasians. The distribution of this polymorphism in healthy individuals provides an important starting point for the evaluation of CJD risk in the general population. Early studies of reference population cohorts demonstrated that methionine/valine heterozygosity was the most frequent genotype. These studies were performed in relatively small numbers of control subjects and do not correspond with the findings of more recent investigations. In this study, we present an analysis of the codon M129V distribution in 613 corneal donors, representing one of the largest control groups examined to date. Methionine homozygotes represented 48.1%, valine homozygotes 8.7% and methionine/valine heterozygotes 43.2%. While age-related difference was not significant, differentiation according to the gender showed significant difference. The observed highest proportion of methionine homozygotes and statistically significant difference between genders as well as comparison with results obtained in other countries underline the need to re-evaluate the generally used reference data on M129V, including consideration of the gender, age and geographical distribution. [source] SERCA function declines with age in adrenergic nerves from the superior cervical ganglionAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 5-6 2000W. J. Pottorf 1 Intracellular calcium is a universal second messenger integrating numerous cellular pathways. An age-related breakdown in the mechanisms controlling [Ca2+]i homeostasis could contribute to neuronal degeneration. One component of neuronal calcium regulation believed to decline with age is the function of sarco/endoplasmic reticulum calcium ATPase (SERCA) pumps. 2 Therefore we investigated the impact of age on the capacity of SERCA pumps to control high (68 m M) [K+]-evoked [Ca2+]i -transients in acutely dissociated superior cervical ganglion (SCG) cells from 6- and 20-month-old Fisher-344 rats. Calcium transients were measured by fura-2 microfluorometry in the presence of vanadate (0.1 ,M) to selectively block plasma membrane calcium ATPase (PMCA) pumps, dinitrophenol (100 ,M) to block mitochondrial calcium uptake and extracellular sodium replaced with tetraethylammonium to block Na+/Ca2+ -exchanger, thus forcing the neuronal cells to rely on SERCA uptake to control [Ca2+]i homeostasis. 3 In the presence of these calcium buffering blockers, the rate of recovery of [Ca2+]i was significantly slower and time to recover to approximately 90% of resting [Ca2+]i was significantly greater in SCG cells from old (20 months) compared with young (6 months) animals. 4 This age-related change in the recovery phase of [K+]-evoked [Ca2+]i -transients could not be explained by differences in the sensitivity of SCG cells to the calcium buffering blockers, as no age-related difference in basal [Ca2+]i was observed. 5 These studies illustrate that when rat SCG cells are forced to rely on SERCAs to buffer [K+]-evoked [Ca2+]i -transients, an age-related decline in SERCA function is revealed. Such age-related declines in calcium regulation coupled with neuronal sensitivity to calcium overload underscore the importance of understanding the components of [Ca2+]i homeostasis and the functional compensation that may occur with advancing age. [source] Differential age-related changes in motor unit properties between elbow flexors and extensorsACTA PHYSIOLOGICA, Issue 1 2010B. H. Dalton Abstract Aim:, Healthy adult ageing of the human neuromuscular system is comprised of changes that include atrophy, weakness and slowed movements with reduced spinal motor neurone output expressed by lower motor unit discharge rates (MUDRs). The latter observation has been obtained mostly from hand and lower limb muscles. The purpose was to determine the extent to which elbow flexor and extensor contractile properties, and MUDRs in six old (83 ± 4 years) and six young (24 ± 1 years) men were affected by age, and whether any adaptations were similar for both muscle groups. Methods:, Maximal isometric voluntary contraction (MVC), voluntary activation, twitch contractile properties, force,frequency relationship and MUDRs from sub-maximal to maximal intensities were assessed in the elbow flexors and extensors. Results:, Both flexor and extensor MVCs were significantly (P < 0.05) less (,42% and ,46% respectively) in the old than in the young. Contractile speeds and the force,frequency relationship did not show any age-related differences (P > 0.05). For the elbow flexors contraction duration was ,139 ms and for the extensors it was ,127 ms for both age groups (P > 0.05). The mean MUDRs from 25% MVC to maximum were lower (,10% to ,36%) in the old than in the young (P < 0.01). These age-related differences were larger for biceps (Cohen's d = 8.25) than triceps (Cohen's d = 4.79) brachii. Conclusion:, Thus, at least for proximal upper limb muscles, mean maximal MUDR reductions with healthy adult ageing are muscle specific and not strongly related to contractile speed. [source] Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI studyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2002Elizabeth R Sowell PhD The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High-resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age-related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray-matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white-matter proportion was significantly greater than the change in total cerebral gray-matter proportion over this age range, suggesting that the relative gray-matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age-related differences in gray and white matter in normally developing children and adolescents. [source] Developmental changes in baseline cortisol activity in early childhood: Relations with napping and effortful controlDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2004Sarah E. Watamura Abstract Development of the hypothalamic,pituitary,adrenocortical (HPA) axis was examined using salivary cortisol levels assessed at wake-up, midmorning, midafternoon, and bedtime in 77 children aged 12, 18, 24, 30, and 36 months, in a cross-sectional design. Hierarchical linear modeling (HLM) analyses were used to characterize cortisol production across the day and to examine age-related differences. Using area(s) under the curve (AUC), cortisol levels were higher among the 12-, 18-, and 24-month children than among the 30- and 36-month children. For all five age groups, cortisol levels were highest at wake-up and lowest at bedtime. Significant decreases were noted between wake-up and midmorning, and between midafternoon and bedtime. Unlike adults, midafternoon cortisol levels were not significantly lower than midmorning levels. Over this age period, children napped less and scored increasingly higher on parent reports of effortful control. Among the 30- and 36-month children, shorter naps were associated with more adultlike decreases in cortisol levels from midmorning to midafternoon. Considering all of the age groups together, effortful control correlated negatively with cortisol levels after controlling for age. These results suggest that circadian regulation of the HPA axis continues to mature into the third year in humans, and that its maturation corresponds to aspects of behavioral development. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 45: 125-133, 2004. [source] Age-related differences in neural correlates of face recognition during the toddler and preschool yearsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2003Leslie J. Carver Abstract Research on the development of face recognition in infancy has shown that infants respond to faces as if they are special and recognize familiar faces early in development. Infants also show recognition and differential attachment to familiar people very early in development. We tested the hypothesis that infants' responses to familiar and unfamiliar faces differ at different ages. Specifically, we present data showing age-related changes in infants' brain responses to mother's face versus a stranger's face in children between 18 and 54 months of age. We propose that these changes are based on age-related differences in the perceived salience of the face of the primary caregiver versus strangers. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 42: 148,159, 2003 [source] Age-dependent reproductive costs and the role of breeding skills in the Collared flycatcherACTA ZOOLOGICA, Issue 2 2007Joanna Sendecka Abstract This study addressed whether there are any age-related differences in reproductive costs. Of especial interest was whether young individuals increased their reproductive effort, and thereby their reproductive cost, as much as older birds when brood size was enlarged. To address these questions, a brood-size manipulation experiment with reciprocal cross-fostering of nestlings of young and middle-aged female Collared flycatchers, Ficedula albicollis, was performed on the Swedish island of Gotland. Nestlings' body mass, tarsus length and survival were recorded to estimate the parental ability and parental effort of the experimental female birds. Female survival and clutch size were recorded in the following years to estimate reproductive costs. We found that middle-aged female flycatchers coped better with enlarged broods than younger females or invested more in reproduction. In the following year, young female birds that had raised enlarged broods laid smaller clutches than the females from all the other experimental groups. This result shows that the young female birds pay higher reproductive costs than the middle-aged females. Both young and middle-aged female flycatchers seemed to increase their reproductive effort when brood size was increased. However, such an increase resulted in higher reproductive costs for the young females. The difference in reproductive costs between birds of different ages is most likely a result of insufficient breeding skills of the young individuals. [source] Transplacental mutagenicity of N -ethyl- N -nitrosourea at the hprt locus in T-lymphocytes of exposed B6C3F1 miceENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2001Hillary E. Sussman Abstract Previous studies have compared age-related differences in total mutagenic burden in mice of differing age (preweanling, weanling, or young adult) after single intraperitoneal (i.p.) injections of ethylnitrosourea (ENU). The purpose of the present investigation was to determine the effects of time elapsed since treatment on the frequency of hprt mutant T-cells (Mf) from mice treated transplacentally with single acute vs. multiple split doses of ENU. To this end, pregnant C57BL/6 mice (n = 13,16/group), which had been bred to C3H males, were given i.p. injections of 40 mg ENU/kg bw in a single dose on day 18 of gestation, in a split dose of 6 mg ENU/kg bw on days 12 through 18 of gestation, or DMSO vehicle alone. Groups of pups were necropsied on days 10, 13, 15 (single dose only), 17, 20, 40, and 70 postpartum for T-cell isolations and hprt Mf measurements using the T-cell cloning assay. The time required to reach maximum Mfs in T-cells isolated from thymus of transplacentally treated animals was 2 weeks, the same time span as previously observed after ENU treatment of adult, weanling, and preweanling mice. Mfs in T-cells isolated from spleens of control animals averaged 2.1 ± 0.3 (SE) × 10,6. In spleens of mice treated transplacentally with ENU in a single dose, Mfs reached a maximum at 15 days postpartum [84.7 ± 15.8 (SE) × 10,6] and decreased to lower but still elevated levels at 40 days postpartum. In spleens of mice treated transplacentally with ENU in a split dose, Mfs reached a maximum at 13 days postpartum [74.0 ± 16.3 (SE) × 10,6] and decreased to background levels at 40 days postpartum. The areas under the curves describing the change in hprt Mfs over time for ENU-treated vs. control mice estimate the mutagenic potency for transplacental single- and split-dose exposures to be 1.9 and 0.8 × 103, respectively. Comparison of the mutagenic potency estimates for mice exposed to ENU in utero to 4-week-old mice given a similar dose of the same lot number of ENU indicates that the mouse is more susceptible to ENU-induced mutagenesis during fetal life. Environ. Mol. Mutagen. 38:30,37, 2001 © 2001 Wiley-Liss, Inc. [source] Rufinamide: Clinical pharmacokinetics and concentration,response relationships in patients with epilepsyEPILEPSIA, Issue 7 2008Emilio Perucca Summary Rufinamide is a new, orally active antiepileptic drug (AED), which has been found to be effective in the treatment of partial seizures and drop attacks associated with the Lennox-Gastaut syndrome. When taken with food, rufinamide is relatively well absorbed in the lower dose range, with approximately dose-proportional plasma concentrations up to 1,600 mg/day, but less than dose-proportional plasma concentrations at higher doses due to reduced oral bioavailability. Rufinamide is not extensively bound to plasma proteins. During repeated dosing, steady state is reached within 2 days, consistent with its elimination half-life of 6,10 h. The apparent volume of distribution (Vd/F) and apparent oral clearance (CL/F) are related to body size, the best predictor being body surface area. Rufinamide is not a substrate of cytochrome P450 (CYP450) enzymes and is extensively metabolized via hydrolysis by carboxylesterases to a pharmacologically inactive carboxylic acid derivative, which is excreted in the urine. Rufinamide pharmacokinetics are not affected by impaired renal function. Potential differences in rufinamide pharmacokinetics between children and adults have not been investigated systematically in formal studies. Although population pharmacokinetic modeling suggests that in the absence of interacting comedication rufinamide CL/F may be higher in children than in adults, a meaningful comparison of data across age groups is complicated by age-related differences in doses and in proportion of patients receiving drugs known to increase or to decrease rufinamide CL/F. A study investigating the effect of rufinamide on the pharmacokinetics of the CYP3A4 substrate triazolam and an oral contraceptive interaction study showed that rufinamide has some enzyme-inducing potential in man. Findings from population pharmacokinetic modeling indicate that rufinamide does not modify the CL/F of topiramate or valproic acid, but may slightly increase the CL/F of carbamazepine and lamotrigine and slightly decrease the CL/F of phenobarbital and phenytoin (all predicted changes were <20%). These changes in the pharmacokinetics of associated AEDs are unlikely to make it necessary to change the dosages of these AEDs given concomitantly with rufinamide, with the exception that consideration should be given to reducing the dose of phenytoin. Based on population pharmacokinetic modeling, lamotrigine, topiramate, or benzodiazepines do not affect the pharmacokinetics of rufinamide, but valproic acid may increase plasma rufinamide concentrations, especially in children in whom plasma rufinamide concentrations could be increased substantially. Conversely, comedication with carbamazepine, vigabatrin, phenytoin, phenobarbital, and primidone was associated with a slight-to-moderate decrease in plasma rufinamide concentrations, ranging from a minimum of ,13.7% in female children comedicated with vigabatrin to a maximum of ,46.3% in female adults comedicated with phenytoin, phenobarbital, or primidone. In population modeling using data from placebo-controlled trials, a positive correlation has been identified between reduction in seizure frequency and steady-state plasma rufinamide concentrations. The probability of adverse effects also appears to be concentration-related. [source] A Detailed Analysis of Symptomatic Posterior Cortex Seizure Semiology in Children Younger Than Seven YearsEPILEPSIA, Issue 1 2003András Fogarasi Summary: ,Purpose: To analyze the semiology of seizure onset and evolution in young children with posterior cortex epilepsy (PCE), compare this with adult reports, and assess age-related differences. Methods: We videotaped and analyzed 110 seizures from 18 patients with PCE, aged 3,81 months. All had a good prognosis after posterior epileptogenic zone removal. Ictal events were categorized by behavioral, consciousness, autonomic, and sensory features, as well as motor patterns, which included myoclonic, tonic, clonic, unclassified motor seizures, and epileptic spasm. A time-scaled data sheet was developed to record each epileptic event as onset, very early, early, or late manifestation. Results: Patients had a high seizure frequency with ,100 attacks/day; one third of them showed a cluster tendency. The mean duration of seizures was 67 s. The most common seizure components were motor manifestations (with myoclonic and tonic seizures), but psychomotor (automotor), hypomotor attacks, and isolated auras also were frequently observed. Clinical seizure spread was frequent; auras and visual sensory signs were difficult to record in this age. Typical phenomena during seizures included behavioral changes, ictal vocalization, smile, flush, head nod, oculomotor features, and late-appearing oral automatisms, whereas hypermotor and secondarily generalized tonic,clonic seizures were not seen. Conclusions: Our results suggest that PCE in infants and young children is very heterogeneous but shows important age-related features. Compared with adults, children with PCE have shorter but more frequent seizures; they rarely report aura or visual sensory signs, only sporadically develop hypermotor and secondarily generalized tonic,clonic seizures, whereas ictal smile, flush, head nod, and behavioral change are typical features at this age. Because of frequent subtle ictal phenomena, long-term video-EEG monitoring is a useful diagnostic tool with infants and young children with PCE. [source] Cognitive, Linguistic and Adaptive Functioning in Williams Syndrome: Trajectories from Early to Middle AdulthoodJOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES, Issue 4 2010Patricia Howlin Background, Little is known about trajectories of cognitive functioning as individuals with Williams syndrome (WS) move though adulthood. Method, The present study investigated cognitive, linguistic and adaptive functioning in adults with WS aged 19,55 years, using both cross-sectional and longitudinal approaches. Results, Data from the cross-sectional study (n = 92; mean age = 32 years) indicated that IQ was comparable across age groups (Full-Scale IQ mean = 56,57) with Verbal IQ being slightly higher than Performance IQ. Daily Living Skills (as measured by the Vineland Adaptive Behavior Scales) were significantly higher in older individuals. Language abilities showed no consistent age-related differences. On formal tests of language, comprehension scores were higher than expressive language scores for almost all individuals, although this pattern was not replicated on the Vineland. In the longitudinal study, a follow-up of 47 individuals (mean age = 37 years) first assessed 12 years previously, similar trajectories were found. IQ remained very stable (FSIQ = 61,62 at both time points); there were significant improvements on the Social and Daily Living domains of the Vineland and significant decreases in Maladaptive scores. There were no improvements in language over time. Conclusions, The data indicate that adults with WS (at least up to the age of 50 years) show no evidence of deterioration in cognitive skills. Adaptive abilities continue to develop although language shows relatively little improvement with time. [source] Age-related differences in insulin-like growth factor-1 receptor signaling regulates Akt/FOXO3a and ERK/Fos pathways in vascular smooth muscle cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2008Muyao Li Advanced age is a major risk factor for atherosclerosis, but how aging per se influences pathogenesis is not clear. Insulin-like growth factor-1 receptor (IGF-1R) promotes aortic vascular smooth muscle cell (VSMC) growth, migration, and extracellular matrix formation, but how IGF-1R signaling changes with age in VSMC is not known. We previously found age-related differences in the activation of Akt/FOXO3a and ERK1/2 pathways in VSMC, but the upstream signaling remains unclear. Using explanted VSMC from Fischer 344/Brown Norway F1 hybrid rats shown to display age-related vascular pathology similar to humans, we compared IGF-1R expression in early passages of VSMC and found a constitutive activation of IGF-1R in VSMC from old compared to young rats, including IGF-1R expression and its tyrosine kinase activity. The link between IGF-1R activation and the Akt/FOXO3a and ERK pathways was confirmed through the induction of IGF-1R with IGF-1 in young cells and attenuation of IGF-1R with an inhibitor in old cells. The effects of three kinase inhibitors: AG1024, LY294002, and TCN, were compared in VSMC from old rats to differentiate IGF-1R from other upstream signaling that could also regulate the Akt/FOXO and ERK pathways. Genes for p27kip-1, catalase and MnSOD, which play important roles in the control of cell cycle arrest and stress resistance, were found to be FOXO3a-targets based on FOXO3a-siRNA treatment. Furthermore, IGF-1R signaling modulated these genes through activation of the Akt/FOXO3a pathway. Therefore, activation of IGF-1R signaling influences VSMC function in old rats and may contribute to the increased risk for atherosclerosis. J. Cell. Physiol. 217: 377,387, 2008. © 2008 Wiley-Liss, Inc. [source] Adolescent C57BL/6J (but not DBA/2J) Mice Consume Greater Amounts of Limited-Access Ethanol Compared to Adults and Display Continued Elevated Ethanol Intake into AdulthoodALCOHOLISM, Issue 4 2010Eileen M. Moore Background:, Alcohol use is common during the adolescent period, a time at which a number of crucial neurobiological, hormonal, and behavioral changes occur (Spear, 2000). In order to more fully understand the complex interaction between alcohol use and these age-typical neurobiological changes, animal models must be utilized. Rodents experience a developmental period similar to that of adolescence. Although rat models have shown striking adolescent-specific differences in sensitivity to ethanol, little work has been done in mice despite the fact that the C57BL/6J (B6) and DBA2/J (D2) mice have been shown to markedly differ in ethanol preference drinking and exhibit widely different sensitivities to ethanol. Methods:, The current study examined ethanol intake in adolescent and adult B6 and D2 mice using a limited access alcohol exposure paradigm called Drinking in the Dark (DID). Additionally, the effect of adolescent (or adult) ethanol exposure on subsequent adult ethanol intake was examined by re-exposing the mice to the same paradigm once the adolescents reached adulthood. We hypothesized that adolescent (P25,45) mice would exhibit greater binge-like alcohol intake compared to adults (P60,80), and that B6 mice would exhibit greater binge-like alcohol intake compared to D2 mice. Moreover, we predicted that relative difference in binge-like alcohol intake between adolescents and adults would be greater in D2 mice. Results:, Adolescent B6 mice consumed more ethanol than adults in the DID model. There was no difference between adolescent and adult D2 mice. Conclusions:, This work adds to the literature suggesting that adolescents will consume more ethanol than adults and that this exposure can result in altered adult intake. However, this effect seems largely dependent upon genotype. Future work will continue to examine age-related differences in ethanol intake, preference, and sensitivity in inbred mouse strains. [source] Decreased Sensitivity to Ethanol Reward in Adolescent Mice as Measured by Conditioned Place PreferenceALCOHOLISM, Issue 7 2009Shelly D. Dickinson Background:, Many preclinical studies have demonstrated age-related differential sensitivity to various effects of ethanol between adolescent and adult animals. However, published data addressing possible differences in ethanol's motivational effects are sparse, particularly in mice. The present study examined age-related differences in the conditioned rewarding effects of ethanol in DBA/2J mice. Methods:, In the first experiment an unbiased place conditioning procedure was used to determine the rewarding effects of 2 g/kg ethanol in adult and adolescent DBA/2J mice. In a subsequent place conditioning experiment, the effects of 2 and 4 g/kg were assessed in adolescent mice. Results:, Adolescents demonstrated a place preference with the high dose of 4 g/kg but not with a more moderate dose of 2 g/kg. In contrast, 2 g/kg was sufficient to produce place preference in adult mice. Conclusions:, Adolescents are less sensitive than adults to the rewarding effects of ethanol but can experience reward with high doses. These results extend the current literature on ethanol's effects in adolescent animals. [source] Time Course of Elevated Ethanol Intake in Adolescent Relative to Adult Rats Under Continuous, Voluntary-Access ConditionsALCOHOLISM, Issue 7 2007Courtney S. Vetter Background: Adolescence is a period of elevated alcohol consumption in humans as well as in animal models. Previous studies in our laboratory have shown that adolescent Sprague,Dawley rats consume approximately 2 times more ethanol on a gram per kilogram basis than adult animals in a 2-bottle choice free-access situation. The purpose of the present study was to examine the time course and pattern of elevated ethanol intake during adolescence and the adolescent-to-adult transition, contrast this intake with ontogenetic patterns of food and water intake, and determine whether adolescent access to ethanol elevates voluntary consumption of ethanol in adulthood. Methods: Adolescent [postnatal day (P)27,28] and adult (P69,70) male Sprague,Dawley rats were singly housed with continuous access to both water and 1 of 3 experimental solutions in ball-bearing,containing sipper tubes: unsweetened ethanol (10% v/v), sweetened ethanol (10% v/v+0.1% w/v saccharin), and saccharin alone (0.1% w/v). Results: Ethanol consumption plateaued at approximately 7.5 g/kg/d during the first 2 weeks of measurement (i.e., P28,39) in early adolescence, before declining sharply at approximately P40 to levels that were only modestly elevated compared with adult-typical consumption patterns that were reached by approximately P70. In contrast, intake of food and total calories showed a more gradual decline into adulthood with no distinguishable plateaus in early adolescence. When adolescent-initiated and adult-initiated animals were tested at the same chronological age in adulthood, animals drank similar amounts regardless of the age at which they were first given voluntary access to ethanol. Conclusions: Taken together, these data suggest that the elevated ethanol intake characteristic of early-to-mid adolescence is not simply a function of adolescent-typical hyperphagia or hyperdipsia, but instead may reflect age-related differences in neural substrates contributing to the rewarding or aversive effects of ethanol, as well as possible modulatory influences of ontogenetic differences in sensitivity to novelty or in ethanol pharmacokinetics. Voluntary home cage consumption of ethanol during adolescence, however, was not found to subsequently elevate ethanol drinking in adulthood. [source] Therapeutic range for unfractionated heparin therapy: age-related differences in response in childrenJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2006V. IGNJATOVIC [source] Diabetic autoimmunity in infants and pre-schoolers with type 1 diabetesPEDIATRIC DIABETES, Issue 3 2000Eba H Hathout The incidence of type 1 diabetes is increasing most rapidly in children under 5 yrs of age, a group where the disease appears to be more accelerated than traditional type 1 diabetes. Little is known about demographics, and markers of diabetes autoimmunity, in infants and pre-schoolers with type 1 diabetes. We report an analysis of 47 children diagnosed with type 1 diabetes prior to 5 yrs of age compared with a representative cohort (n=49) diagnosed after 5 yrs of age, and all were followed at Loma Linda University (LLU) Children's Hospital. Ethnic, familial, seasonal, and autoimmune marker characteristics are outlined. To determine the prevalence of diabetes autoimmune markers, ICA512, GAD65 and insulin autoantibodies (IAA) antibodies were measured. Children with early-onset diabetes had a significantly higher incidence of viral illness symptoms (p=0.005) and diabetic ketoacidosis (DKA; p=0.017) at the time of diagnosis. However, hemoglobin A1C (HbA1c) levels at diagnosis were significantly higher in the later-onset group (p=0.001). A honeymoon period was reported in 14.8% of children diagnosed before 5 yrs of age compared with 42.1% in those diagnosed over 5 yrs of age (p=0.038). Islet-cell antibodies (ICAs) and glutamic acid decarboxylase (GAD) antibody titers were significantly different between early- and later-onset groups. ICA titers were positive in 35.29%, and GAD in 41.38% of the early-onset group versus 70.83 and 71.74% in children with later-onset disease, (p=0.001 and 0.009, respectively). IAA titers, drawn after instituting insulin therapy, were not significantly different between the two groups. GAD and ICA512 antibody results suggest a relative lack of diabetes immune markers in infants and toddlers with new-onset diabetes. This finding, and the apparent shorter pre-clinical phase reflected in the lower HbA1c values, may indicate age-related differences in type 1 diabetes autoimmunity or the existence of non-autoimmune diabetogenic mechanisms in younger children. [source] Skin Responses to Ultraviolet Radiation: Effects of Constitutive Pigmentation, Sex, and AncestryPIGMENT CELL & MELANOMA RESEARCH, Issue 5 2002Jennifer K. Wagner Constitutive skin pigmentation and skin responses to ultraviolet radiation were measured on a sample of volunteers (n=250) living in State College, PA, USA. The sample was composed of individuals of European American (n=190), Hispanic (n=45), and East Asian ancestry (n=15). Constitutive pigmentation was measured using the Adjusted Melanin Index (AMI), Erythemal Dose Response (EDR) was measured using the slope of a* at 24 h (,a*), and Melanogenic Dose,Response (MDR) was measured using ,AM, the slope of AMI at 7 d. The relationships between constitutive skin pigmentation, EDR, MDR, sex, age, and ancestry were investigated. European Americans showed a lower constitutive pigmentation, had a significantly higher burn response (EDR), and had a significantly lower tanning response (MDR) than Hispanics and East Asians. No significant difference is seen between Hispanics and East Asians for either constitutive pigmentation or EDR. Constitutive pigmentation in females was slightly lower than in males in all three samples, but the difference was not significant. While no differences were observed in MDR between sexes, males had a stronger EDR than females regardless of population or constitutive pigmentation level, and this difference was significant in European Americans and Hispanics. We observed no age-related differences in any of the populations or measures investigated. We evaluated the relationship between constitutive pigmentation, EDR and MDR. There was a strong inverse correlation between constitutive pigmentation and EDR in the three samples (European Americans, R2=0.176, P < 0.001; Hispanics, R2=0.204, P=0.009; East Asians, R2=0.223, P=0.098) and a strong direct correlation between constitutive pigmentation and MDR in European Americans and Hispanics (European Americans, R2=0.094, P < 0.001; Hispanics, R2=0.164, P=0.012). In other words, persons with lower constitutive pigmentation both burn more and tan less than persons with higher pigmentation. However, after controlling for constitutive pigmentation, EDR and MDR were significantly correlated in European Americans (R2=0.041 P=0.006). Thus, the general observation that persons who burn more tan less is probable because of the common link that these two phenotypes have with constitutive skin pigmentation and, in fact, once pigmentation has been adjusted for, there is a positive correlation between tanning response and burning response in European Americans. [source] | ||||||||||||||||||||||||||||||||||