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Age Dependent (age + dependent)
Selected AbstractsBRAF V599E Mutation is Not Age Dependent: It is Present in Common Melanocytic Nevi in Both Children and AdultsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005J. Cohen BRAF encodes a serine-threonine kinase, which acts in the RAS/RAF/MAPK pathway transducing regulatory signals from RAS to MEK1/2. Somatic mutations in BRAF have been identified in 53,80% of primary melanomas and 70,90% of common melanocytic nevi. More than 90% of these mutations consist of a valine to glutamate substitution at codon 599 (V599E) of exon 15. While a high prevalence of BRAF mutations in common melanocytic nevi has been reported in adults, nevi in children have not been studied. Of interest, we have previously shown that Spitz nevi in children do not harbor mutations in BRAF. To investigate the association of BRAF mutations with patient age, we studied common melanocytic nevi in children for the V599E activating mutation. Tumor cells were microdissected from 6 common melanocytic nevi in children 10 years of age or younger, and analyzed for the V599E mutation in BRAF by allele-specific PCR and gel electrophoresis. In 6 of 6 (100%) nevi, the V599E mutant allele was observed. Our data suggest that similar genetic pathways are involved in the development of common melanocytic nevi in children and adults. The absence of BRAF mutations in Spitz nevi in children is therefore associated with tumor type, not patient age. [source] Maternal size and age affect offspring sex ratio in the solitary egg parasitoid Anaphes nitensENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2007Serena Santolamazza-Carbone Abstract In this study, the effects of maternal age, diet, and size on offspring sex ratio were investigated for the solitary egg parasitoid, Anaphes nitens Girault (Hymenoptera: Mymaridae), both outdoors, during the winter, and inside a climatic chamber under favourable constant conditions. During the winter of 2005,2006, each of seven groups containing 40 1-day-old females was mated and randomly distributed among two treatments: (treatment 1) a droplet of undiluted honey ad libitum + one fresh egg capsule of the snout beetle Gonipterus scutellatus Gyllenhal (Coleoptera: Curculionidae) as host; (treatment 2) drops of water + one fresh egg capsule of G. scutellatus. We recorded the lifetime fecundity, the daily sex allocation, and the lifetime offspring sex ratio to study the existence of a relationship with maternal characteristics. Moreover, we assessed the effect of location (outdoors vs. indoors) and group (groups are representative of early, mid, and late winter) on sex ratio. The most important factor that biased the sex ratio was maternal body size: larger females of both treatments produced more female offspring. As females of A. nitens could gain more advantage than males from body size, larger mothers have a higher fitness return if they produce more daughters. The effect of the treatment was significant: starved females produced more females. Location and group were not significant. Fecundity and sex ratio were age dependent. Old mothers that received honey (treatment 1) had fewer offspring and a more male-biased offspring sex ratio, probably due to reproductive senescence and sperm depletion. Starved females (treatment 2) experienced reproductive decline earlier, perhaps because they invested more energy in maintenance rather than in reproduction. [source] Role of Nitric Oxide in Pentylenetetrazol-Induced Seizures: Age-Dependent Effects in the Immature RatEPILEPSIA, Issue 4 2000Anne Pereira de Vasconcelos Summary: Purpose: Seizure susceptibility and consequences are highly age dependent. To understand the pathophysiologic mechanisms involved in seizures and their consequences during development, we investigated the role of nitric oxide (NO) in severe pentylenetetrazol (PTZ)-induced seizures in immature rats. Methods: Four cortical electrodes were implanted in 10-day-old (P10) and 21-day-old (P21) rats, and seizures were induced on the following day by repetitive injections of subconvulsive doses of PTZ. The effects of NG -nitro- l -arginine methyl ester (l -NAME; 10 mg/kg) and 7-nitroindazole (7NI; 40 mg/kg), two NO synthase (NOS) inhibitors, and l -arginine (l -arg; 300 mg/kg), the NOS substrate, were evaluated regarding the mean PTZ dose, seizure type and duration, and mortality rate. Results: At P10, the postseizure mortality rate increased from 18,29% for the rats receiving PTZ only to 100% and 89% for the rats receiving l -NAME and 7NI, respectively; whereas l -arg had no effect. Conversely, at P21, NOS inhibitors did not affect the 82,89% mortality rate induced by PTZ alone, whereas l -arg decreased the mortality rate to 29%. In addition, all NO-related drugs increased the duration of ictal activity at P10, whereas at P21, L -arg and L -NAME affected the first seizure type, producing clonic seizures with L -arg and tonic seizures with L -NAME. Conclusions: The relative natural protection of very immature rats (P10) against PTZ-induced deaths could be linked to a high availability of L -arg and, hence, endogenous NO. At P21, the modulation of seizure type by NO-related compounds may be related to the maturation of the brain circuitry, in particular the forebrain, which is involved in the expression of clonic seizures. [source] Egg Colour Covaries with Female Expression of a Male Ornament in the Spotless Starling (Sturnus unicolor)ETHOLOGY, Issue 10 2007Isabel López-Rull The sexually selected egg colour hypothesis (SSECH) proposes that egg colouration is as a post-mating sexually selected signal of female phenotypic quality, maintained by a higher allocation of paternal care. Similarly, some female traits can reflect genetic quality or condition and males could use this information in mate choice or in modulating parental investment. In our study, we examined the correlation of individual variation in egg colouration with female expression of a male ornament and how male feeding covaried with these two female traits in the spotless starling, in which egg colour varies widely between clutches and where both sexes possess showy throat feathers that are age dependent and that may signal individual quality. According to the SSECH, high-quality females (females with longer throat feathers) are expected to lay more colourful eggs than low-quality females and males should modify their feeding behaviour accordingly. By means of a principal component analysis, we found that most of the variation in egg colouration was due to brightness differences, and in a lower proportion to chromatic variation. Chromatic variation reflected a ultraviolet (UV) vs. greenness trade-off and was positively associated with throat feather length: females with larger throat feathers laid eggs with higher UV and lower green reflectance. However, egg brightness was not related to female feather length, as the SSECH would predict. Male feedings were positively related to female throat feather length and negatively related to chromatic variation, meaning that males contributed more to nests of females with long throat feathers who laid eggs with higher UV and lower green reflectance. In conclusion, our data provide mixed support for the SSECH: although egg chromatic variation was related to female expression of a male ornament and male parental care, we found no evidence that egg brightness was involved in these processes. [source] Age-dependent effect of prenatal stress on hippocampal cell proliferation in female ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2009Muriel Koehl Abstract Stressors occurring during pregnancy can alter the developmental trajectory of offspring and lead to, among other deleterious effects, cognitive deficits and hyperactivity of the hypothalamo-pituitary-adrenal axis. A recent feature of the prenatal stress (PS) model is its reported influence on structural plasticity in hippocampal formation, which sustains both cognitive functions and stress responsiveness. Indeed, we and others have previously reported that males exposed to stress in utero are characterized by a decrease in hippocampal cell proliferation, and consequently neurogenesis, from adolescence to senescence. Recent studies in females submitted to PS have reported conflicting results, ranging from no effect to a decrease in cell proliferation. We hypothesized that changes in cell proliferation in PS female rats are age dependent. To address this issue, we examined the impact of PS on hippocampal cell proliferation in juvenile, young, middle-aged and old females. As hypothesized, we found an age-dependent effect of PS in female rats as cell proliferation was significantly decreased only when animals reached senescence, a time when adrenal gland weight also increased. These data suggest that the deleterious effects of PS on hippocampal cell proliferation in females are either specific to senescence or masked during adulthood by protective factors. [source] Cellular and molecular studies of B cells exhibiting reverse somatic mutation throughout lifeGENES TO CELLS, Issue 11 2004Takao Kodera Somatic mutation of immunoglobulin (Ig) genes plays an important role in generating antibody diversity. The frequency of somatic mutation appears to vary throughout life. However, this process has been difficult to study in vivo because the DNA in and around rearranged V genes undergoes random mutation, causing silent or replacement mutations. Therefore, we have developed a transgenic mouse model for studying the frequency of B cells exhibiting mutation in young and old mice. The system is based on a reporter transgene (HuG-X) that encodes a chimeric Ig heavy chain composed of a murine VDJ segment and a human IgG1 constant region. The VDJ has been mutated to contain a TAG stop codon in the D segment. Therefore, the transgene is transcribed but not translated. Point mutation of the stop codon results in expression of the chimeric H chain, which is readily detected as human IgG1 expression. In vivo, we found that the transgene undergoes spontaneous reverse somatic mutation at a low frequency. Treatment of HuG-X mice with anti-IgD greatly increases the frequency of somatic mutation. The observed mutation frequency in anti-IgD-treated mice increases with age until adulthood, then plateaux and finally declines in aged mice. The mutations in the stop codon were associated with increased double-stranded DNA breaks (DSB) within and around the TAG site. Our results demonstrate that the rate of frequency of spontaneous reverse mutation is very low in vivo, yet it is significantly increased after stimulation with anti-IgD antibodies. The frequency of point mutation is age dependent and correlates with increased DSB. [source] A randomised comparison of oral desmopressin lyophilisate (MELT) and tablet formulations in children and adolescents with primary nocturnal enuresisINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2007H. Lottmann Summary Aims:, Desmopressin is a useful treatment for primary nocturnal enuresis (PNE), a common childhood condition that can persist into adolescence. This open-label, randomised, cross-over study evaluated the preference of children and adolescents with PNE for sublingual desmopressin oral lyophilisate (MELT) vs. tablet treatment, and the efficacy, safety, compliance and ease of use associated with each formulation. In total, 221 patients aged 5,15 years who were already receiving desmopressin tablets were randomised 1 : 1 to receive desmopressin treatment in the order MELT/tablet (n = 110) or tablet/MELT (n = 111) for 3 weeks each. Each formulation was administered in bioequivalent doses (0.2/0.4 mg tablets , 120/240 ,g MELT). Following treatment, patients were questioned regarding treatment preference. Diary card data and 100 mm Visual Analogue Scale scores were also recorded. Results:, Overall, patients preferred the MELT formulation to the tablet (56% vs. 44%; p = 0.112). This preference was age dependent (p = 0.006); patients aged < 12 years had a statistically significant preference for desmopressin MELT (p = 0.0089). Efficacy was similar for both formulations (MELT: 1.88 ± 1.94 bedwetting episodes/week; tablet: 1.90 ± 1.85 episodes/week). Ease of use of both formulations was high. Compliance (, 80%) was 94.5% for MELT patients vs. 88.9% for the tablet (p = 0.059). No serious/severe adverse events were reported. Conclusions:, There was an overall preference for the MELT, and a statistically significant preference for desmopressin MELT in children aged 5,11 years. Desmopressin MELT had similar levels of efficacy and safety at lower dosing levels than the tablet, and therefore facilitates early initiation of PNE treatment in children aged 5,6 years. [source] Influence of composition on the biochemical and sensory characteristics of commercial Cheddar cheese of variable quality and fat contentINTERNATIONAL JOURNAL OF DAIRY TECHNOLOGY, Issue 2 2007K N KILCAWLEY Ten commercial Cheddar cheeses of variable quality differing in fat content and age were subjected to compositional, proteolytic, lipolytic and sensory analyses. The compositional parameters of the full-fat cheeses were predominantly outside those typically associated with good-quality cheese. Sensory analysis discriminated the full-fat cheeses predominantly by age, with the longer ripened cheeses associated with more negative attributes, some which appeared to be due to excessive lipolysis and/or ,-casein breakdown. Both proteolysis and lipolysis appear to be age dependent. The two reduced-fat cheeses were clearly discriminated from the eight full-fat cheeses by sensory analysis that appeared to be due to differences in composition and the extent of lipolysis. [source] Autonomic Blockade Unmasks Maturational Differences in Rate-Dependent Atrioventricular Nodal Conduction and Facilitation in the MouseJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2003SAMIR SABA M.D. Maturational Differences in Murine AVN Conduction. Introduction: In large animals, rate-dependent AV nodal (AVN) properties of conduction are modulated by autonomic inputs. In this study, we investigated whether the properties of AVN conduction and facilitation are altered by autonomic blockade in the mouse and whether this effect is age dependent. Methods and Results: Young (age 4,6 weeks; n = 11) and adult (age 8,9 months; n = 11) female mice underwent in vivo electrophysiologic testing, before and after autonomic blockade. After autonomic blockade, the adult mice had significantly longer AVN effective refractory period (AVNERP; 67 ± 14 msec vs 56 ± 4 msec, P = 0.05) and functional refractory period (AVNFRP; 81 ± 10 msec vs 72 ± 4 msec, P = 0.05). With autonomic blockade, the increase from baseline of AVN Wenckebach cycle length (,AVW; 1.8 ± 8.1 msec vs 8.8 ± 3.3 msec, P = 0.04), as well as of AVNERP (,AVNERP; 3.5 ± 3.5 msec vs 21.4 ± 12.6 msec, P = 0.002) and AVNFRP (,AVNFRP; 2.3 ± 3.2 msec vs 12.8 ± 9.0 msec, P = 0.008), was significantly larger in adult than in young mice. Compared with young mice, adult mice were less likely to exhibit AVN facilitation (44% vs 90%, P = 0.03) and had smaller maximal shortening of AVN conduction times after the "test beat" for any coupling of the "facilitating beat" (4 ± 4 msec vs 7 ± 3 msec, P = 0.05). Conclusion: Complete autonomic blockade significantly increases AVN conduction times and refractory periods in adult but not in young mice. Adult mice also exhibit less AVN facilitation. Our results confirm that, like in larger animals, rate-dependent murine AVN properties of conduction are under autonomic regulation. Adult mice have higher sympathetic AVN inputs at baseline, leading to slower conduction after autonomic blockade. (J Cardiovasc Electrophysiol, Vol. 14, pp. 191-195, February 2003) [source] Digit ratio (2D:4D), sex differences, allometry, and finger length of 12,30-year olds: Evidence from the British Broadcasting Corporation (BBC) internet studyAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2010John T. Manning Many studies have reported digit ratio (2D:4D) to be sexually dimorphic, (males lower 2D:4D than females). However, Kratochvíl and Flegr ([ 2009]: Biol Lett 5:643-646) have suggested that 2D regressed on 4D has an allometric regression line with nonzero Y -intercept that is shared by males and females. Thus, 2D is shorter than expected when 4D is long, and males have lower 2D:4D than females because they have longer fingers. In this study, it is shown that this suggestion may be incorrect because sex differences in slope were not considered. Participants were recruited in an Internet study and had an age range of 12,30 years. The expected sex difference in 2D:4D was found, and the regression of 2D on 4D showed a significant sex difference in slope (males lower than females). A comparison of 10 age groups (12 years, 13 years,, 21,30 years) showed that sexual dimorphism for fingers was age dependent, varying from monomorphic to very dimorphic. Changes in sexual dimorphism of 2D:4D were much less marked, but there was a significant reduction in mean 2D:4D with age. The tendency for slopes of 2D regressed on 4D to be lower in males compared with females was significant in eight age groups. Sex difference in 2D:4D varied across the age groups and was positively related to the magnitude of the difference in female and male slopes. In contrast to the report of Kratochvíl and Flegr, it was found that the regression of 2D on 4D showed sex differences in slope, and such differences gave rise to the sexual dimorphism in 2D:4D. Am. J. Hum. Biol. 22:604,608, 2010. © 2010 Wiley-Liss, Inc. [source] Epidemiology of holoprosencephaly: Prevalence and risk factors,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Ięda M. Orioli Abstract The wide variation in cerebral and facial phenotypes and the recognized etiologic heterogeneity of holoprosencephaly (HPE) contribute to the observed inter-study heterogeneity. High lethality during the early stages of embryonic and fetal development makes HPE detection age dependent. By reviewing 21 HPE epidemiologic articles, the observed prevalence rate differences can be largely explained by the pregnancy outcome status of the studied cohort: livebirth, stillbirth, and terminations of pregnancy (TOPs): lower than 1 per 10,000 when live and still births were included, higher when TOPs were included, and between 40 and 50 per 10,000 in two classical Japanese studies on aborted embryos. The increasing secular trend observed in some studies probably resulted from an increasing use of prenatal sonography. Ethnic variations in birth prevalence rates (BPRs) could occur in HPE, but the available data are not very convincing. Higher BPRs were generally observed in the less favored minorities (Blacks, Hispanics, Pakistanis), suggesting a bias caused by a lower prenatal detection rate of HPE, and consequently less TOPs. Severe ear defects, as well as microstomia, were part of the spectrum of HPE. Non-craniofacial anomalies, more frequently associated with HPE than expected, were genital anomalies (24%), postaxial polydactyly (8%), vertebral defects (5%), limb reduction defects (4%), and transposition of great arteries (4%). The variable female predominance, found in different HPE studies, could also depend on the proportion of early conceptions in each study sample, as males are more likely to be lost through spontaneous abortions. © 2010 Wiley-Liss, Inc. [source] Post-natal Changes in Testicular Concentrations of Interleukin-1 Alpha and Beta and Interleukin-6 during Sexual Maturation in BullsREPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2010ET Bagu Contents Based on observations in laboratory animals interleukins could be regulators of testicular development. The objects of this study were to see if interleukins (IL-1 and IL-6) are present in the developing bull testis and to establish the temporal patterns of concentrations of IL-1 and IL-6 in the bovine testis during development. Separate groups of six bull calves were castrated every 4 weeks from 5 to 33 weeks of age, and at 56 weeks of age. Mean testicular IL-1 alpha concentrations decreased (p < 0.01) from 5 to 9 weeks of age and 13 to 21 weeks of age. Mean testicular IL-1 beta concentrations decreased (p < 0.01) from 13 to 17 weeks of age and from 29 to 33 weeks of age. Mean IL-1 bioactivity increased from 13 to 17 weeks of age, decreased to 21 weeks, increased to 25 weeks, decreased to 29 weeks and decreased from 33 to 56 weeks of age (p < 0.05). Mean testicular IL-6 concentrations decreased (p < 0.05) from 9 to 13 weeks of age, increased (p < 0.05) to 21 weeks, decreased (p < 0.05) to 25 weeks, increased (p < 0.05) to 29 weeks and decreased (p < 0.01) to 56 weeks of age. In conclusion, testicular IL-1 alpha, IL-1 beta and IL-6 were found in the bovine testis and concentrations were age dependent. Testicular IL-1 alpha and IL-1 beta concentrations were highest in the early post-natal period; however, IL-1 bioactivity and IL-6 concentrations were greatest in the immediate pre-pubertal period. These findings suggest a functional role for interleukins in testicular development in the bull. [source] Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 6 2010R. K. Saurenmann Objective Uveitis is the most common extraarticular manifestation of juvenile idiopathic arthritis (JIA) and is associated with considerable morbidity. The aim of this study was to examine the risk factors associated with uveitis in JIA. Methods We conducted a chart review of 1,047 patients with JIA from a single tertiary care pediatric rheumatology center for factors associated with the development of uveitis. Special emphasis was put on the following known risk factors: oligoarthritis, antinuclear antibody (ANA) status, sex, and age at the time of onset of JIA. Results The risk of uveitis developing was age dependent in girls but not in boys. Among girls, the risk was maximal (47%) in those who were ANA positive and were ages 1,2 years at the time of the onset of JIA; this risk decreased to <10% in those in whom the age at onset was >7 years. Only girls had an age-dependent and ANA-associated increased risk of uveitis. The time interval from the diagnosis of JIA to the diagnosis of uveitis was statistically significantly longer in patients in whom the onset of JIA occurred at a younger age (P = 0.04). This effect was even more pronounced in ANA-positive patients (P = 0.004). The JIA subtype did not influence a patient's risk of the development of uveitis. Conclusion An age-associated risk of uveitis was observed only in girls who were younger than 7 years of age at the time of the onset of JIA. The duration of time between the diagnosis of JIA and the onset of uveitis was longer in patients in whom JIA was diagnosed at a younger age, especially in those who were ANA positive. We suggest that our findings have implications for uveitis screening in patients with JIA. [source] Preterm premature rupture of membranes: diagnosis, evaluation and management strategiesBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2005Hyagriv N. Simhan Preterm premature rupture of the membranes (PPROM) is responsible for one-third of all preterm births and affects 120,000 pregnancies in the United States each year. Effective treatment relies on accurate diagnosis and is gestational age dependent. The diagnosis of PPROM is made by a combination of clinical suspicion, patient history and some simple tests. PPROM is associated with significant maternal and neonatal morbidity and mortality from infection, umbilical cord compression, placental abruption and preterm birth. Subclinical intrauterine infection has been implicated as a major aetiological factor in the pathogenesis and subsequent maternal and neonatal morbidity associated with PPROM. The frequency of positive cultures obtained by transabdominal amniocentesis at the time of presentation with PPROM in the absence of labour is 25,40%. The majority of amniotic fluid infection in the setting of PPROM does not produce the signs and symptoms traditionally used as diagnostic criteria for clinical chorioamnionitis. Any evidence of infection by amniocentesis should be considered carefully as an indication for delivery. Documentation of amniotic fluid infection in women who present with PPROM enables us to triage our therapeutic decision making rationally. In PPROM, the optimal interval for delivery occurs when the risks of immaturity are outweighed by the risks of pregnancy prolongation (infection, abruption and cord accident). Lung maturity assessment may be a useful guide when planning delivery in the 32- to 34-week interval. A gestational age approach to therapy is important and should be adjusted for each hospital's neonatal intensive care unit. Antenatal antibiotics and corticosteroid therapies have clear benefits and should be offered to all women without contraindications. During conservative management, women should be monitored closely for placental abruption, infection, labour and a non-reassuring fetal status. Women with PPROM after 32 weeks of gestation should be considered for delivery, and after 34 weeks the benefits of delivery clearly outweigh the risks. [source] Increased mammography use and its impact on earlier breast cancer detection in Vermont, 1975,1999CANCER, Issue 8 2002Pamela M. Vacek Ph.D. Abstract BACKGROUND A trend toward earlier breast carcinoma detection in the United States has been attributed to screening mammography, although direct evidence linking this trend to the increased use of mammography in a general population is lacking. This study examined the effects of mammography on tumor size and axillary lymph node metastasis in Vermont over 25 years. METHODS Pathology and mammography data from 3499 Vermont women who were diagnosed with invasive breast carcinoma during 1975,1984, 1989,1990, and 1995,1999 were compared. Logistic regression analysis was used to estimate the effects of age, mammography use, and period on the odds of a tumor , 2 cm and the odds of negative lymph nodes. RESULTS The proportion of breast tumors that were detected by screening mammography increased from 2% during 1974,1984 to 36% during 1995,1999 (P < 0.001), and these tumors were more likely to measure , 2 cm than tumors that were detected by other methods. Among women age > 50 years, the odds ratio (OR) was 4.5, with a 95% confidence interval (95% CI) of 3.5,6.4. The effect was smaller in younger women (OR, 1.8; 95% CI, 1.1,3.0). Mammographic detection increased the odds of negative lymph nodes by a similar amount in both age groups, although women age > 50 years were more likely to have negative lymph nodes than younger women (OR, 1.3; 95% CI, 1.1,1.6). Tumor size and lymph node metastasis also were related to the number of mammograms and to the mammographic interval. CONCLUSIONS Most of the trend toward earlier detection in Vermont was due to mammography. Mammography had a lesser effect on tumor size among younger women, which may be related to less frequent screening, although its effect on lymph node metastasis was not age dependent. Women age < 50 years were more likely to have positive lymph nodes, independent of the method of detection or the frequency of mammography. Cancer 2002;94:2160,8. © 2002 American Cancer Society. DOI 10.1002/cncr.10459 [source] Age dependence of cataract induced by ultraviolet radiation-B in miceACTA OPHTHALMOLOGICA, Issue 2007Y ZHANG Purpose: To investigate for the C57BL/6 mouse if there is an age dependence of the dose-response function for in vivo UVR-300 nm induced forward light scattering in the lens. Methods: Each of four age groups of 25 mice aged 3, 6, 12, or 24 weeks were randomly distributed on five age group specific UVR-B dose levels. The dose levels selected for each age group were derived from the expected maximum tolerable dose (MTD). Expected MTDs were set to 1.9, 3.2, 4.8, and 6.0 kJ/m^2 for the 3, 12, and 24 weeks mice, respectively, based on published data for the albino Sprague Dawley rat. Each animal was unilaterally exposed to UVR-B to the pre-determined dose, delivered during 15 minutes. All mice were sacrificed two days after exposure and both lenses were extracted for; macroscopic imaging in incident illumination against a grid and in dark-field illumination, and measurement of intensity of forward light scattering. The difference of intensity of forward light scattering between the exposed and the contralateral not exposed lens was fitted against dose received using regression based on a second order polynomial model. Results: Two days after exposure, subcapsular opacities were observed in the exposed lenses from all dose groups except at 0 kJ/m^2. In all age groups, the difference of intensity of forward light scattering increased with increasing UVR-B dose. The increase was age dependent. Conclusions: In the pigmented C57BL/6 mouse, an increasing in vivo dose of UVR-300 nm induces an increasing intensity of forward light scattering that is age dependent in the age interval 3-24 weeks. This finding should be considered in future design of experiments on UVR-effects to the mouse lens. [source] Allergic sensitization is enhanced in early life through toll-like receptor 7 activationCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2009S. Phipps Summary Background Prospective cohort studies suggest that children hospitalized in early life with severe infections are significantly more likely to develop recurrent wheezing and asthma. Objective Using an inhalational mouse model of allergic airways inflammation, we sought to determine the effect of viral and bacterial-associated molecular patterns on the magnitude of the allergic inflammatory response and whether this effect was age dependent. Methods BALB/c mice were sensitized by intranasal administration of endotoxinlow ovalbumin (OVA) in the absence or presence of viral single-stranded (ss)RNA, lipoteichoic acid or flagellin as neonates (within the first 24 h of life) or as weanlings (4 weeks of age). Mice were challenged four times with OVA at 6 weeks of age and end-points (bronchoalveolar lavage cytology, histology, antigen-specific T and B cell responses) determined at 7 weeks of age. Results Inhalational sensitization (<24 h or 4 weeks of age) and challenge with OVA induced a mild allergic inflammatory response in the airways as indicated by increased numbers of eosinophils and mucus cells, elevated serum OVA-specific IgG1, and production of T helper 2 (Th2) cytokines. Mice sensitized to endotoxinlow OVA at birth in the presence of ssRNA or lipoteichoic acid, but not flagellin, showed an increase in the numbers of airway and tissue eosinophils, mucus producing cells and antigen-specific production of IL-13 as compared with mice exposed only to endotoxinlow OVA. By contrast, all three TLR ligands failed to increase the magnitude of OVA-induced allergic inflammation in mice sensitized as weanlings. Conclusions Recognition of distinct microbial-associated patterns in early life may preferentially promote the de novo differentiation of bystander, antigen-specific CD4+ T cells toward a Th2 phenotype, and promote an asthma-like phenotype upon cognate antigen exposure in later life. [source] AGE-RELATED SYNAPTIC CHANGES IN THE CA1 STRATUM RADIATUM AND SPATIAL LEARNING IMPAIRMENT IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2009Li-Hong Long SUMMARY 1Age-related impairments in hippocampus-dependent spatial learning and memory are not associated with a loss of neurons, but may be related to synaptic changes. In the present study, we analysed the behavioural performance of adult, middle-aged and old Wistar rats using the Morris water maze, as well as the structure of synapses and the expression of autophosphorylated Ca2+/calmodulin-dependent protein kinase II at threonine 286 (pThr286-,CaMKII), a key post-synaptic protein in the CA1 stratum radiatum, in the same rats. 2Old Wistar rats showed significant cognitive deficits. Synaptic density, the area of post-synaptic densities and the total number of synapses in the CA1 stratum radiatum of old rats were significantly decreased compared with adult rats. The decrease in autophosphorylated pThr286-,CaMKII was age dependent. 3These findings reveal that age-related impairments in learning and memory are associated with synaptic atrophy. The decreased expression of pThr286-CaMKII may result in reduced synaptic function with ageing. [source] Ghrelin does not regulate the GH response to insulin-induced hypoglycaemia in children but could be involved in the regulation of cortisol secretionCLINICAL ENDOCRINOLOGY, Issue 1 2007J. Huber Summary Objective, Ghrelin activates the growth hormone secretagogue receptor GHS-R. It strongly stimulates GH secretion and has a role in energy homeostasis. The relationship between plasma ghrelin and cortisol levels during insulin-induced hypoglycaemia in prepubertal and pubertal children has not yet been investigated. The aim of the present study was to establish whether insulin-induced hypoglycaemia stimulates ghrelin secretion and whether changes in ghrelin concentrations are related to changes in GH and cortisol in children. Design and patients, We studied a group of 20 children and adolescents (five girls, 15 boys, mean age 10·8 ± 3·7 years) undergoing insulin tolerance tests (ITTs) for clinical investigation of GH deficiency. Measurements, Stimulation tests were performed to investigate the relationship between ghrelin, GH, cortisol and glucose levels according to age and pubertal stage by determining the ghrelin profiles during insulin-induced hypoglycaemia (at 0, 60 and 120 min). Results, Ghrelin was significantly and inversely related to body weight, height, body mass index (BMI) and age of children (P < 0·05). Significant changes in ghrelin levels (P = 0·00013) were found after the insulin bolus, with a decline at 60 min and an increase to baseline values at 120 min. Changes in cortisol levels were negatively correlated with changes in ghrelin at 60 min (r = ,0·59, P = 0·004) and at 120 min (r = ,0·605, P = 0·003). Conclusions, This study shows that ghrelin might not regulate the GH response to insulin-induced hypoglycaemia in prepubertal and pubertal children. A role for ghrelin in the regulation of cortisol secretion can be hypothesized concerning the negative correlation between changes in ghrelin and cortisol. Furthermore, the results imply that ghrelin secretion is age dependent and is a function of growth. [source] |