The immunomodulatory effects of Ipomoea cornea in rats vary depending on life stage

Ipomoea cameo Jacq. ssp. fistulosa (Mart. Ex Choisy; Convolvulaceae; I. cameo) possesses a toxic component: an indolizidine alkaloid swainsonine (SW) that has immunomodulatory effects due to its inhibition of glycoprotein metabolism. It is also known that SW is excreted into both the amniotic fluid and milk of female rats exposed to I. cameo. Thus, the aim of this study was to determine whether SW exposure, either in utero or from the milk of dams treated with I. cornea, modulates offspring immune function into adulthood. In addition, adult (70 days old) and juvenile rats (21 days old) were exposed to I. cameo in order to evaluate several other immune parameters: lymphoid organs relative weight and cellularity, humoral and cellular immune responses. Offspring exposed to I. cornea during lactation developed rheumatoid arthritis (RA) in adulthood after an immunogenic challenge. In addition, both adult and juvenile rats exposed to I. cameo showed discrepancies in several immune parameters, but did not exhibit any decrease in humoral immune response, which was enhanced at both ages. These findings indicate that SW modulates immune function in adult rats exposed to SW during lactation and in juvenile and adult rats exposed to SW as juveniles and adults, respectively.

Amitriptyline and Acute Inflammation: A Study Using Intravital Microscopy and the Carrageenan-Induced Paw Edema Model

Background/Aims: Antidepressants are reported to exhibit antiinflammatory effects. However, mechanisms involved in this action have not been elucidated. Thus, the objectives of the present study were (a) to evaluate the effects of amitriptyline on the acute inflammatory process, and (b) to investigate the participation of alpha(1)-adrenergic receptors and glucocorticoids as possible mechanisms implicated in the amitriptyline action on inflammation. Methods and Results: Single and multiple doses of amitriptyline were administered to rats submitted to the carrageenan-induced paw edema model. The results showed a significant antiedematous reaction to amitriptyline, mainly when administered at each elimination half-life. The next step was to evaluate its effects on leukocyte behavior, using intravital microscopy. Amitriptyline produced a significant effect on leukocyte behavior. To investigate possible mechanisms involved, a glucocorticoid receptor antagonist (RU-486) and an alpha(1)-adrenergic receptor antagonist (prazosin) were used. RU-486 administration lacked the ability to decrease the amitriptyline antiinflammatory effects in the carrageenan-induced paw edema model. Prazosin pretreatment potentiated the amitriptyline antiinflammatory effect without presenting an effect per se. Conclusion:The present study shows the ability of amitriptyline to decrease edema and affect leukocyte behavior in an acute inflammatory process; and, for the first time to our knowledge, we suggest the involvement of alpha(1)-adrenoceptors in the antiinflammatory effects of amitriptyline. Copyright (C) 2010 S. Karger AG, Basel

Early life course determinants of young adults' gambling behaviour. An Australian Longitudinal Study

Problem gambling represents a public concern as both a social and health issue. Available evidence shows problem gambling is associated with a range of psychological disorders, criminality, and disruption to families. While gambling itself may represent a pleasurable pursuit for the majority, for a proportion, gambling-related activities may assume many of the characteristics of an addiction and have the capacity to undermine individuals� mental and physical health, social relationships, financial independence, as well as the financial and psychological wellbeing of their families and/or friends. The objectives of this study are based on the need to increase our understanding of gambling behaviour, its antecedents, as well its influence on the health and wellbeing of gamblers and their families. One of the most important and unresolved issues in gambling research is whether the mental health and social/family correlates of gambling precede or follow gambling behaviour. This report focuses on this issue.

A longitudinal study of quality of life of elderly with mandibular implant-supported fixed prostheses

Objectives: To verify the consequences of implant-supported fixed oral rehabilitation on the quality of life (QL) of elderly individuals. Material and methods: Fifteen patients were studied, being 10 females and five males; all were aged > 60 years, were completely edentulous, wore removable dentures on both arches, and were treated with implant-supported fixed dentures. Three QL questionnaires were applied, two related to the oral conditions (Oral Impact on Daily Performance - OIDP - and Oral Health Impact Profile, short version - OHIP-14) and one dealing with global aspects (World Health Organization Quality of Life - WHOQOL-BREF), before 3, 6, and 18 months after surgical placement of implants. Results: Scores in the OIDP and OHIP-14 questionnaires were better after dental treatment. The WHOQOL-BREF was less sensitive, confirming the higher reliability of specific questionnaires (focal) compared with general questions in such situations. Conclusion: Treatment with implant-supported fixed prostheses improved QL in the elderly; these effects are better detected by specific instruments focused on the subject.

Fatigue life and failure modes of crowns systems with a modified framework design

Objectives: To evaluate the effect of framework design on the fatigue life and failure modes of metal ceramic (MC, Ni-Cr alloy core, VMK 95 porcelain veneer), glass-infiltrated alumina (ICA, In-Ceram Alumina/VM7), and veneered yttria-stabilized tetragonal zirconia polycrystals (Y-TZP, IPSe.max ZirCAD/IPS e.max,) crowns. Methods: Sixty composite resin tooth replicas of a prepared maxillary first molar were produced to receive crowns systems of a standard (MCs, ICAs, and Y-TZPs, n = 10 each) or a modified framework design (MCm, ICAm, and Y-TZPm, n = 10 each). Fatigue loading was delivered with a spherical steel indenter (3.18 mm radius) on the center of the occlusal surface using r-ratio fatigue (30-300 N) until completion of 10(6) cycles or failure. Fatigue was interrupted every 125,000 cycles for damage evaluation. Weibull distribution fits and contour plots were used for examining differences between groups. Failure mode was evaluated by light polarized and SEM microscopy. Results: Weibull analysis showed the highest fatigue life for MC crowns regardless of framework design. No significant difference (confidence bound overlaps) was observed between ICA and Y-TZP with or without framework design modification. Y-TZPm crowns presented fatigue life in the range of MC crowns. No porcelain veneer fracture was observed in the MC groups, whereas ICAs presented bulk fracture and ICAm failed mainly through the veneer. Y-TZP crowns failed through chipping within the veneer, without core fractures. Conclusions: Framework design modification did not improve the fatigue life of the crown systems investigated. Y-TZPm crowns showed comparable fatigue life to MC groups. Failure mode varied according to crown system. (C) 2010 Elsevier Ltd. All rights reserved.

Prevalence of Adverse Life Events, Depression and Suicidal Thoughts and Behaviour among a Community Sample of Young People aged 15-24 Years

Objective: To provide prevalence data on several key mental health indicators for young people aged 15 to 24 years. Methods: A cross-sectional household survey, using telephone recruitment followed by a postal pencil-and-paper questionnaire. The overall response rate was 67.3%. Results: Difficulties with interpersonal relationships are common causes of distress for young people, in particular problems with parents, problems with friends and relationship break-ups. Depressive symptomatology is common among young people with approximately one in eight males and one in four females reporting current depressive symptomatology. One in three young people reported that they had had suicidal thoughts at some time in the past, 1.2% of young people reported that they had made a plan on how to kill themselves in the four-week period prior to completing the survey and 6.9% of young people reported that they had tried to kill themselves at some time during their life time (4.2% of males and 9.0% of females). Conclusions and implications: The prevalence figures for the various mental health indicators presented in this paper represent good baseline information upon which to examine the progress over time of interventions designed to improve the mental health of young people.

Binding and functional studies with the growth hormone receptor antagonist, B2036-PEG (pegvisomant), reveal effects of pegylation and evidence that it binds to a receptor dimers

GH actions are dependent on receptor dimerization. The GH receptor antagonist, B2036-PEG, has been developed for treating acromegaly. B2036 has mutations in site 1 to enhance receptor binding and in site 2 to block receptor dimerization. Pegylation (B2036-PEG) increases half-life and lowers immunogenicity, but high concentrations are required to control insulin-like growth factor-I levels. We examined antagonist structure and function and the impact of pegylation on biological efficacy. Unpegylated B2036 had a 4.5-fold greater affinity for GH binding protein (GHBP) than GH but similar affinity for membrane receptor. Pegylation substantially reduced membrane binding affinity and receptor antagonism, as assessed by a transcription assay, by 39- and 20-fold, respectively. GHBP reduced antagonist activity of unpegylated B2036 but did not effect antagonism by B2036-PEG. B2036 down-regulated receptors, and membrane binding sites doubled in the presence of dimerization-blocking antibodies, suggesting that B2036 binds to a receptor dimer. It is concluded that the high concentration requirement of B2036-PEG for clinical efficacy relates to pegylation, which decreases binding to membrane receptor but has the advantages of reduced clearance, immunogenicity, and interactions with GHBP. Our studies suggest that B2036 binds to a receptor dimer and induces internalization but not signaling.

Natural selection and quantitative genetics of life-history traits in Western women: A twin study

Whether contemporary human populations are still evolving as a result of natural selection has been hotly debated. For natural selection to cause evolutionary change in a trait, variation in the trait must be correlated with fitness and be genetically heritable and there must be no genetic constraints to evolution. These conditions have rarely been tested in human populations. In this study, data from a large twin cohort were used to assess whether selection Will cause a change among women in contemporary Western population for three life-history traits: age at menarche, age at first reproduction, and age at menopause. We control for temporal variation in fecundity (the baby boom phenomenon) and differences between women in educational background and religious affiliation. University-educated women have 35% lower fitness than those with less than seven years education, and Roman Catholic women have about 20% higher fitness than those of other religions. Although these differences were significant, education and religion only accounted for 2% and 1% of variance in fitness, respectively. Using structural equation modeling, we reveal significant genetic influences for all three life-history traits, with heritability estimates of 0.50, 0.23, and 0.45, respectively. However, strong genetic covariation with reproductive fitness could only be demonstrated for age at first reproduction, with much weaker covariation for age at menopause and no significant covariation for age at menarche. Selection may, therefore, lead to the evolution of earlier age at first reproduction in this population. We also estimate substantial heritable variation in fitness itself, with approximately 39% of the variance attributable to additive genetic effects, the remainder consisting of unique environmental effects and small effects from education and religion. We discuss mechanisms that could be maintaining such a high heritability for fitness. Most likely is that selection is now acting on different traits from which it did in pre-industrial human populations.

Conceptualizing quality of life for elderly people with stroke

Purpose : Despite increased interest in quality of life (QOL) as an outcome measure and as a means of identifying client needs in health care, its conceptualisation and the identification of its constituents have been poorly researched for elderly people with stroke in Hong Kong. Method: This article analysed the literature to identify components relevant to the QOL of Chinese elderly people with stroke living in the community in Hong Kong. Results : While common components of QOL for elderly people with and without stroke and regardless of cultural background were identified, a number were specific to an elderly Chinese stroke population. Conclusion : Recommendations for future research have been made with reference to further exploring and validating these components for the target population. A clear understanding of these aspects is essential for the development of sensitive QOL measures to guide and evaluate service delivery to this population.

Being breastfed in infancy and breast cancer incidence in adult life: Results from the two Nurses' Health studies

Events during perinatal and early life may influence the incidence of breast cancer in adult life, and some case-control studies suggest that having been breastfed may reduce breast cancer risk. The authors studied this association among premenopausal and postmenopausal women by using data from the two Nurses' Health Studies, the Nurses' Health Study (using data from 1992 to 1996) and the Nurses' Health Study II (using data from 1991 to 1997). A history of being breastfed was self-reported by the study participants. During a total of 695,655 person-years, 1,073 cases of invasive breast cancer were diagnosed. The authors did not observe any important overall association between having been breastfed and the development of breast cancer later in life among premenopausal women (covariate-adjusted relative risk = 0.97, 95% confidence interval (CI): 0.78, 1.20) or postmenopausal women (covariate-adjusted relative risk = 1.12, 95% CI: 0.92, 1.37). No significant trend was observed with increasing duration of breastfeeding. The authors also used data on breastfeeding retrospectively collected from 2,103 mothers of participants of the two Nurses' Health Studies. With the mothers' reports, the covariate-adjusted odds ratio of breast cancer was 1.11 (95% CI: 0.88, 1.39) for women who were breastfed compared with those who were not. Data from these two large cohorts do not support the hypothesis that being breastfed confers protection against subsequent breast cancer.

Life on the ocean wave: Testing some intergroup hypotheses in a naturalistic setting

A survey (N= 352) was conducted among British passengers of a cross-channel ferry. The survey aimed to test hypotheses drawn from Realistic Group Conflict, Social Identity and Contact theories using mainly a correlational design. However, an intervention by members of the outgroup (French fishermen blockading a port) also allowed a quasi-experimental test of the effects of a direct experience of intergroup conflict. Results supported the hypotheses since conflict and national identification were associated with more negative and with less positive attitudes toward the outgroup, while contact had the reverse effects. In addition, the salience of group membership in the contact relationship weakly moderated the effect of contact.

Targeting of EBNA1 for rapid intracellular degradation overrides the inhibitory effects of the Gly-Ala repeat domain and restores CD8+T cell recognition

Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) includes a unique glycine-alanine repeat domain that inhibits the endogenous presentation of cytotoxic T lymphocyte (CTL) epitopes through the class I pathway by blocking proteasome-dependent degradation of this antigen. This immune evasion mechanism has been implicated in the pathogenesis of EBV-associated diseases. Here, we show that cotranslational ubiquitination combined with N-end rule targeting enhances the intracellular degradation of EBNA1, thus resulting in a dramatic reduction in the half-life of the antigen. Using DNA expression vectors encoding different forms of ubiquitinated EBNA1 for in vivo studies revealed that this rapid degradation, remarkably, leads to induction of a very strong CTL response to an EBNA1-specific CTL epitope. Furthermore, this targeting also restored the endogenous processing of HLA class I-restricted CTL epitopes within EBNA1 for immune recognition by human EBV-specific CTLs. These observations provide, for the first time, evidence that the glycine-alanine repeat-mediated proteasomal block on EBNA1 can be reversed by specifically targeting this antigen for rapid degradation resulting in enhanced CD8+ T cell-mediated recognition in vitro and in vivo.