Early Exposure (early + exposure)

Distribution by Scientific Domains


Selected Abstracts


Altered Mesencephalic Dopaminergic Populations in Adulthood as a Consequence of Brief Perinatal Glucocorticoid Exposure

JOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2005
S. McArthur
Abstract Early exposure to stressors is strongly associated with enduring effects on central nervous system function, but the mechanisms and neural substrates involved in this biological ,programming' are unclear. This study tested the hypothesis that inappropriate exposure to glucocorticoid stress hormones (GCs) during critical periods of development permanently alters the mesencephalic dopaminergic populations in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Using a rat model, the synthetic GC dexamethasone was added to the maternal drinking water during gestational days 16,19 or over the first week of postnatal life. In adulthood, the effects upon tyrosine hydroxylase immunopositive (TH+) cell numbers in the midbrain, and monoamine levels in the forebrain, of the adult offspring were assessed and compared with control offspring whose dams received normal drinking water. In the VTA, both prenatal and postnatal dexamethasone treatment increased TH+ cell numbers by approximately 50% in males and females. Although prenatal dexamethasone treatment also increased TH+ cell numbers in the SNc by 40,50% in males and females, postnatal treatment affected females only by increasing TH+ cell numbers by approximately 30%. In comparison, similar changes were not detected in the monoamine levels of the dorsolateral striatum, nucleus accumbens or infralimbic cortex of either males or females, which is a feature likely to reflect adaptive changes in these pathways. These studies demonstrate that the survival or phenotypic expression of VTA and SNc dopaminergic neurones is profoundly influenced by brief perinatal exposure to GCs at times when endogenous levels are normally low. These findings are the first to demonstrate permanent changes in the cytoarchitecture within midbrain dopamine nuclei after perinatal exposure to stress hormones and implicate altered functionality. Thus, they have significance for the increasing use of GCs in perinatal medicine and indicate potential mechanisms whereby perinatal distress may predispose to the development of a range of psychiatric conditions in later life. [source]


Enhanced levels of cow's milk antibodies in infancy in children who develop type 1 diabetes later in childhood

PEDIATRIC DIABETES, Issue 5 2008
Kristiina Luopajärvi
Background:, Early exposure to cow's milk (CM) proteins have been implicated in the pathogenesis of type 1 diabetes (T1D). Objective:, We analyzed the development of the humoral immune response to dietary CM proteins in early childhood and its relation to later T1D. Subjects and methods:, We studied a subgroup of 94 children randomized to be weaned to a CM-based infant formula in the trial to reduce insulin-dependent diabetes mellitus in the genetically at risk (TRIGR) pilot study. All subjects carried human leukocyte antigen-conferred T1D susceptibility and had an affected first-degree relative. After 7 years of follow-up, 8 subjects had progressed to T1D, 15 had at least one disease-associated autoantibody, and 71 remained autoantibody negative (controls). Immunoglobulin (Ig) G and IgA class antibodies to whole CM formula, beta-lactoglobulin (BLG), bovine serum albumin, and alpha-casein and IgG antibodies to bovine insulin (BI) were measured with enzyme-linked immunosorbent assays from sequential samples. Results:, The children with later T1D showed increased IgG levels to BLG from 3 to 18 months of age (p = 0.028) and enhanced IgA levels to CM formula at the age of 9 months (p = 0.022) compared with controls. In the children with an affected father or sibling, IgG antibodies to BI were higher in autoantibody-positive subjects than in autoantibody-negative subjects at 18 months of age (p = 0.022). Conclusion:, An enhanced humoral immune response to various CM proteins in infancy is seen in a subgroup of those children who later progress to T1D. Accordingly, a dysregulated immune response to oral antigens is an early event in the pathogenesis of T1D. [source]


Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesis

DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2009
Adelaide Fernandes
Abstract Elevated levels of serum unconjugated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy and cell death. Here, we have further analyzed the effect of UCB on nerve cell differentiation and neuronal development, addressing how UCB may affect the viability of undifferentiated neural precursor cells and their fate decisions, as well as the development of hippocampal neurons in terms of dendritic and axonal elongation and branching, the axonal growth cone morphology, and the establishment of dendritic spines and synapses. Our results indicate that UCB reduces the viability of proliferating neural precursors, decreases neurogenesis without affecting astrogliogenesis, and increases cellular dysfunction in differentiating cells. In addition, an early exposure of neurons to UCB decreases the number of dendritic and axonal branches at 3 and 9 days in vitro (DIV), and a higher number of neurons showed a smaller growth cone area. UCB-treated neurons also reveal a decreased density of dendritic spines and synapses at 21 DIV. Such deleterious role of UCB in neuronal differentiation, development, and plasticity may compromise the performance of the brain in later life. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source]


Improving clinical assessment: evaluating students' ability to identify and apply clinical criteria

EUROPEAN JOURNAL OF DENTAL EDUCATION, Issue 3 2010
C. Redwood
Abstract Aim:, There is ongoing concern by health educators over the inability of professionals to accurately self-assess their clinical behaviour and standards, resulting in doubts over a key expectation of effective self-regulation in the health professions. Participation by students in the assessment process has been shown to increase the understanding of assessment criteria in written assessment tasks. How this might transfer to the clinical setting is the focus of this study. This paper is part of an ongoing investigation of the impact on learning of a series of activities that provides students with opportunities to discuss and apply criteria and standards associated with self-assessment in clinical dentistry. Our aim was to evaluate whether participation in these assessment activities improved the ability of first-year dental students to recognise behaviours demonstrated by ,peers' in videos of clinical scenarios and to relate these to the assessment criteria. Materials and methods:, A series of three workshops in conjunction with weekly clinical assessment activities in Semesters 1 and 2 were use to support first-year students' learning of clinical assessment criteria. The design of the workshops was based on the principles of social constructivist theories of learning and the concept of tacit knowledge. Accordingly workshop activities were planned around videos that were specifically constructed to illustrate procedures and behaviours typical of those observed by staff and tutors in the first year of the dental course at The University of Adelaide, Australia. First-year students viewed the videos prior to and after the workshops and recorded observed behaviours that related to the assessment criteria that were used in their clinical practice course. Student learning outcomes were assessed 10,14 weeks after the initial workshop and again up to 42 weeks later. To check whether learning resulted from repeated viewing of the videos without formal discussion, a reference group of third-year students who did not attend the workshops also viewed the videos two times, separated by 12 weeks, and recorded observations in the same way. Results:, There was no consistent evidence that repeat viewing of the videos in isolation resulted in improved recognition of ,peer' behaviours by third-year dental students. Results for the first-year students indicated that the workshops and clinical assessment activities had a significantly positive effect on the ability of students to identify ,peer' behaviours related to the criteria used for clinical assessment. In particular, students' recognition in others of knowledge and professional behaviours improved significantly. This improvement was retained over the year and students were able to recognise these behaviours in other scenarios relevant to their year level. Conclusions:, This early exposure to the process of clinical assessment, coupled with ongoing self-assessment and tutor feedback throughout first year, improved the ability of first-year students to identify and apply some key assessment criteria to observed ,peer' behaviour, and this ability was retained over time. [source]


PRECLINICAL STUDY: Acquisition and reinstatement of MDMA-induced conditioned place preference in mice pre-treated with MDMA or cocaine during adolescence

ADDICTION BIOLOGY, Issue 4 2009
Manuel Daza-Losada
ABSTRACT Those who take ecstasy are more likely to consume other drugs than non-users with cocaine abuse being reported by 75.5% of high school student MDMA (± 3,4-methylenedioxymetamphetamine hydrochloride) users. The aim of this work was to evaluate the effects of exposure during adolescence to MDMA, cocaine or to both drugs on the MDMA-induced conditioned place preference (CPP) in adult mice. Animals received two daily administrations of saline, 10 mg/kg of MDMA, 25 mg/kg of cocaine or 10 mg/kg of MDMA plus 25 mg/kg of cocaine over 3 days (from PD28 to 30). Three weeks after pre-treatment, the MDMA-induced CPP procedure was initiated (PD52). Acquisition of CPP was induced with a sub-threshold dose of MDMA (1.25 mg/kg) only in animals treated during adolescence with MDMA alone. Preference was established in all the groups after conditioning with 10 mg/kg of MDMA, while the time required to achieve extinction was longer in those pre-treated with cocaine or MDMA alone (46 and 28 sessions, respectively). Moreover, preference was reinstated with progressively lower priming doses of MDMA in mice pre-treated with MDMA or cocaine alone. These results demonstrate that early exposure to MDMA or cocaine induces long-lasting changes that last until adulthood and modify the response of animals to MDMA. [source]


Fetal or Infantile Exposure to Ethanol Promotes Ethanol Ingestion in Adolescence and Adulthood: A Theoretical Review

ALCOHOLISM, Issue 6 2005
Norman E. Spear
Background: Despite good evidence that ethanol abuse in adulthood is more likely the earlier human adolescents begin drinking, it is unclear why the early onset of drinking occurs in the first place. A review of experimental studies with animals complemented by clinical, epidemiologic and experimental studies with humans supports the idea that precipitating conditions for ethanol abuse occur well before adolescence, in terms of very early exposure to ethanol as a fetus or infant. Experimental studies with animals indicate, accordingly, that ethanol intake during adolescence or adulthood is potentiated by much earlier exposure to ethanol as a fetus or infant. Methods: Two broad theoretical frameworks are suggested to explain the increase in affinity for ethanol that follows very early exposure to ethanol, one based on effects of mere exposure and the other on associative conditioning. Studied for 50 years or more in several areas of psychology, "effects of mere exposure" refers to enhanced preference expressed for flavors, or just about any stimuli, that are relatively familiar. An alternative framework, in terms of associative conditioning, is guided by this working hypothesis: During ethanol exposure the fetus or infant acquires an association between ethanol's orosensory (odor/taste) and pharmacological consequences, causing the animal subsequently to seek out ethanol's odor and taste. Results and Conclusions: The implication that ethanol has rewarding consequences for the fetus or young infant is supported by recent evidence with perinatal rats. Paradoxically, several studies have shown that such early exposure to ethanol may in some circumstances make the infant treat ethanol-related events as aversive, and yet enhanced intake of ethanol in adolescence is nevertheless a consequence. Alternative interpretations of this paradox are considered among the varied circumstances of early ethanol exposure that lead subsequently to increased affinity for ethanol. [source]


Induction and Maintenance of Ethanol Self-Administration in Cynomolgus Monkeys (Macaca fascicularis): Long-Term Characterization of Sex and Individual Differences

ALCOHOLISM, Issue 8 2001
J. A. Vivian
Background: Investigations of oral ethanol self-administration in nonhuman primates have revealed important parallels with human alcohol use and abuse, yet many fundamental questions concerning the individual risk to, and the biological basis of, excessive ethanol consumption remain unanswered. Moreover, many conditions of access to ethanol in nonhuman primate research are largely unexplored. This set of experiments extends within- and across-session exposure to ethanol to more fully characterize individual differences in oral ethanol self-administration. Methods: Eight male and eight female adult cynomolgus monkeys (Macaca fascicularis) were exposed to daily oral ethanol self-administration sessions for approximately 9 months. During the first 3 months, a fixed-time (FT) schedule of food delivery was used to induce the consumption of an allotted dose of ethanol in 16-hr sessions. Subsequently, the FT schedule was suspended, and ethanol was available ad libitum for 6 months in 16- or 22-hr sessions. Results: Cynomolgus monkeys varied greatly in their propensity to self-administer ethanol, with sex and individual differences apparent within 10 days of ethanol exposure. Over the last 3 months of ethanol access, individual average ethanol intakes ranged from 0.6 to 4.0 g/kg/day, resulting in blood ethanol concentrations from 5 to 235 mg/dl. Males drank approximately 1.5-fold more than females. In addition, heavy-, moderate-, and light-drinking phenotypes were identified by using daily ethanol intake and the percentage of daily calories obtained from ethanol as criteria. Conclusions: Cynomolgus monkeys displayed a wide intersubject range of oral ethanol self-administration with a procedure that used a uniform and prolonged induction that restricted early exposure to ethanol and subsequently allowed unlimited access to ethanol. There were sex and stable individual differences in the propensity of monkeys to consume ethanol, indicating that this species will be important in characterizing risk factors associated with heavy-drinking phenotypes. [source]


Pseudomonas aeruginosa in children with cystic fibrosis diagnosed through newborn screening: Assessment of clinic exposures and microbial genotypes,

PEDIATRIC PULMONOLOGY, Issue 7 2010
Don Hayes Jr MD
Abstract Background Chronic pulmonary infection with Pseudomonas aeruginosa (PA) is responsible for significant morbidity and mortality in cystic fibrosis (CF). Because of the limited studies evaluating early exposure and the progression of genetic variability of PA, our goal was to assess PA in young children with CF followed in two clinic types. Methods A total of 39 infants with CF diagnosed through newborn screening were randomly assigned to either a segregated (PA-free) or mixed (PA-positive) clinic at two different CF centers, one of which replaced an older, mixed clinic where nosocomial acquisition was suspected. Oropharyngeal (OP) swab cultures were examined with subsequent genotyping to characterize the strains of PA isolated. Results We found that 13/21 segregated clinic patients and 14/18 mixed clinic patients showed positive PA, with median acquisition ages of 3.3 and 2.2 years, respectively (P,=,0.57). The median time to PA acquisition, however, was significantly longer in the new clinic with proper hygiene precautions compared to an old site (5.0 years vs. 1.7 years, P,<,0.001). The majority of subjects isolated a single genotype of PA or AP-PCR types during the study period with eight subjects clearing the isolate after only one positive culture. The development of chronic colonization yielded the predominance of a single major genotype or AP-PCR type. Conclusions Segregation of infants and young children with CF in PA-negative or PA-positive clinics did not alter the time to first PA isolation in this randomized assessment of facilities with hygienic precautions. During the early infection period where PA is first isolated in young children with CF, patients cleared different PA strains until a predominant strain established permanent colonization. Pediatr Pulmonol. 2010; 45:708,716. © 2010 Wiley-Liss, Inc. [source]


Childhood asthma epidemiology: Insights from comparative studies of rural and urban populations,

PEDIATRIC PULMONOLOGY, Issue 2 2008
Gary W.K. Wong MD
Abstract Asthma is one of the most common chronic respiratory disorders. Many epidemiology studies have suggested an increasing trend of asthma in many different regions of the world but the exact reasons explaining such trend remain unclear. Nevertheless, changing environmental factors are most likely important in explaining the trend of asthma. Studies in the past decade have clearly shown a mark difference in the prevalence between urban and rural regions. The consistent findings of a markedly lower prevalence of asthma in children and adults who have been brought up in a farming environment clearly indicate the importance of environmental influence of asthma development. Although the exact protective environmental factors in the rural region remain to be defined, there have been many studies suggesting that early exposure to microbes or microbial products may play a role in modulating the immune system so as to reduce the future risk of asthma and allergies. Advances in the understanding of the genetic predisposition and how these genetic factors may interact with specific environment factors are of paramount importance for the future development of primary preventive strategies for asthma. Pediatr Pulmonol. 2008; 43:107,116. © 2007 Wiley-Liss, Inc. [source]


Morphology of Reproductive Organs, Semen Quality and Sexual Behaviour of the Male Rabbit Exposed to a Soy-containing Diet and Soy-derived Isoflavones during Gestation and Lactation

REPRODUCTION IN DOMESTIC ANIMALS, Issue 6 2009
JR Cardoso
Contents Placental and breastfeeding transfer of soy isoflavones are potential routes for animal and human exposure to phytoestrogens, and reproductive dysfunctions have been linked to early exposure to these compounds. So, the aim of this study was to investigate the effects of perinatal (intrauterine and lactational) exposure to soy-containing diet and soy-derived isoflavones on the reproductive parameters of male rabbits. For this purpose, 12 female rabbits were randomly assigned to receive: (1) a soy- and alfalfa-free diet (control diet); (2) a soy- and alfalfa-free diet supplemented with 10 mg/kg body wt/day of soy isoflavones; (3) a soy- and alfalfa-free diet supplemented with 20 mg/kg body wt/day of soy isoflavones; and (4) a diet containing 18% of soy meal, throughout gestation and lactation. Weight and morphology of the reproductive organs of some of the male offspring were evaluated at weaning (between days 29 and 31). The remaining males were placed on the control diet from weaning to adulthood (gestational and lactational exposure only). Sexual behaviour, semen quality and reproductive organs' morphology were evaluated after puberty. There were no significant differences in litter size and gestation duration between control and treatment groups. Perinatal exposure to soy-containing diet and soy isoflavones did not alter testis, epididymides, proprostate and prostate weight and gross morphology. After puberty, sexual behaviour and semen parameters did not differ significantly from the control group. These results indicate that intrauterine and lactational exposure to soy-containing diet and soy-derived isoflavones may not adversely affect reproductive development and function of male rabbits. [source]


Nurturing of surgical careers by the wellington surgical interest club

ANZ JOURNAL OF SURGERY, Issue 4 2009
Sanket Srinivasa
The Royal Australasian College of Surgeons (RACS) has recently introduced the new Surgical Education and Training programme. The purpose of this was, in part, to help address the anticipated shortage of surgeons in the future, by streamlining the surgical training programme. The formation of the Wellington Surgical Interest Club (WSIC), a student-led initiative, had several complementary goals. These included the desire to identify potential candidates for a career in surgery, promote a surgical career to students especially women, help students acquire basic surgical skills early, inform students about surgical careers, promote student involvement in surgical research and to create an effective mentorship model during undergraduate and junior surgical training. The strengths of WSIC are its goals, which are similar to those of the RACS with regard to promoting surgery as a career option; its easy reproducibility at other medical institutions; its ability to focus on issues of relevance to both students and junior doctors; and being a bridging solution at a time when early exposure to surgical specialties is both desired and necessary. [source]


ALTERNATIVE CURRICULAR OPTIONS IN RURAL NETWORKS (ACORNS): IMPACT OF EARLY RURAL CLINICAL EXPOSURE IN THE UNIVERSITY OF WEST AUSTRALIA MEDICAL COURSE

AUSTRALIAN JOURNAL OF RURAL HEALTH, Issue 1 2000
June Talbot
The aim of this study was to assess the impact of a 4-day rural placement in Western Australia on the interest of fourth year medical students in a career in rural general practice. Students undertaking their Alternative Curricular Options in Rural Networks attachment (ACORNS) completed pre- and post-questionnaires examining their expectations, experiences of, and attitudes to rural general practice. Of the 103 students who participated, 81% expressed an interest in a rural career after the placement, whereas prior to this experience only 48% had been interested. The students also recorded a wide range of learning experiences, both clinical and procedural, and expressed positive attitudes to the variety of experiences and the role of the rural GP. The study concluded that early exposure to rural general practice enhances students' interest in a potential rural practice career and provides them with a broad range of experiences. The role of rural practitioners as role models for students needs to be acknowledged and reinforced. [source]


Do immune responses to inhaled skin flakes modulate the expression of allergic disease?

CLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2007
E. R. Tovey
Summary We examine the nature of the immune responses to inhaled skin particles and query whether early exposure could play a role in providing protection against the development of allergic disease. Currently, the main hypothesis used to explain environmental modulation of allergic diseases, the ,hygiene hypothesis', is linked exclusively to microbial exposures acting upon the innate immune system. However, many of the exposures sustaining this hypothesis also involve co-exposure to skin flakes from humans or animals. Such skin flakes contain a complex mixture of antigens, glycolipids and small peptides that may induce immune responses. Should these responses prove relevant to the modulation of allergic diseases, it provides new opportunities to better understand the epidemic of allergic disease and to develop new interventions for its prevention. [source]


Kisspeptin/GPR54 system as potential target for endocrine disruption of reproductive development and function

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010
M. Tena-Sempere
Summary Kisspeptins, the products of Kiss1 gene acting via G protein-coupled receptor 54 (also termed Kiss1R), have recently emerged as essential gatekeepers of puberty onset and fertility. Compelling evidence has now documented that expression and function of hypothalamic Kiss1 system is sensitive not only to the activational effects but also to the organizing actions of sex steroids during critical stages of development. Thus, studies in rodents have demonstrated that early exposures to androgens and oestrogens are crucial for proper sexual differentiation of the patterns of Kiss1 mRNA expression, whereas the actions of oestrogen along puberty are essential for the rise of hypothalamic kisspeptins during this period. This physiological substrate provides the basis for potential endocrine disruption of reproductive maturation and function by xeno-steroids acting on the kisspeptin system. Indeed, inappropriate exposures to synthetic oestrogenic compounds during early critical periods in rodents persistently decreased hypothalamic Kiss1 mRNA levels and kisspeptin fibre density in discrete hypothalamic nuclei, along with altered gonadotropin secretion and/or gonadotropin-releasing hormone neuronal activation. The functional relevance of this phenomenon is stressed by the fact that exogenous kisspeptin was able to rescue defective gonadotropin secretion in oestrogenized animals. Furthermore, early exposures to the environmentally-relevant oestrogen, bisphenol-A, altered the hypothalamic expression of Kiss1/kisspeptin in rats and mice. Likewise, maternal exposure to a complex cocktail of endocrine disruptors has been recently shown to disturb foetal hypothalamic Kiss1 mRNA expression in sheep. As a whole, these data document the sensitivity of Kiss1 system to changes in sex steroid milieu during critical periods of sexual maturation, and strongly suggest that alterations of endogenous kisspeptin tone induced by inappropriate (early) exposures to environmental compounds with sex steroid activity might be mechanistically relevant for disruption of puberty onset and gonadotropin secretion later in life. The potential interaction of xeno-hormones with other environmental modulators (e.g., nutritional state) of the Kiss1 system warrants further investigation. [source]