Remifentanil post-conditioning attenuates cardiac ischemia-reperfusion injury via κ or δ opioid receptor activation

Background: Ischemic pre- or post-conditioning of the heart has been shown to involve opioid receptors. Remifentanil, an ultra-short-acting selective μ opioid receptor agonist in clinical use, pre-conditions the rat heart against ischemia-reperfusion injury. This study investigates whether remifentanil post-conditioning is also cardioprotective. Methods: Remifentanil post-conditioning (5-min infusion at 1, 5, 10 or 20 μg/kg/min) or ischemic post-conditioning (three cycles of a 10 s reperfusion interspersed with a 10 s ischemia) was induced in an open-chest rat heart model of ischemia and reperfusion injury, in the presence or absence of nor-binaltorphimine, naltrindole or CTOP, specific κ, δ and μ opioid receptor antagonists, respectively. The same sequence of experiments was repeated in the isolated heart model using the maximal protective dose of remifentanil from the dose-response studies. Results: Both ischemic and remifentanil post-conditioning reduced the myocardial infarct size relative to the control group in both models. This cardioprotective effect for both post-conditioning regimes was prevented by the prior administration of nor-binaltorphimine and naltrindole but not CTOP. The sole administration of the antagonists had no effect on the size of myocardial infarction. Conclusions: These results indicate that remifentanil post-conditioning protects the heart from ischemia-reperfusion injury to a similar extent as of ischemic post-conditioning. This protection involves κ and δ but not μ opioid receptor activation. This drug has great potential as a clinical post-conditioning modality as it can be given in large doses without prolonged opioid-related side effects. © 2009 The Acta Anaesthesiologica Scandinavica Foundation.postprin

The influence of parents and the home environment on preschoolers' physical activity behaviours: A qualitative investigation of childcare providers' perspectives

<p>Abstract</p> <p>Background</p> <p>Physical activity offers numerous physiological and psychological benefits for young children; however, many preschool-aged children are not engaging in sufficient activity. The home environment, inclusive of parent role modeling, has been identified as influencing preschoolers' physical activity. This study sought to examine childcare providers' perspectives of the importance of parents and the home environment for supporting the physical activity behaviours of preschool-aged children (aged 2.5-5 years) attending childcare.</p> <p>Methods</p> <p>A heterogeneous sample of childcare providers (<it>n </it>= 84; response rate 39%) working at childcare facilities in London, Ontario participated. Thirteen semi-structured focus groups were conducted in London centres between February 2009 and February 2010. Focus groups were audio recorded and transcribed verbatim and inductive content analysis was used to code and classify themes. A number of strategies were used to verify the trustworthiness of the data.</p> <p>Results</p> <p>Childcare providers acknowledged their reliance on parents/guardians to create a home environment that complements the positive physical activity messaging children may receive in childcare. Moreover, childcare staff highlighted the need for positive parent role modeling and parent support to encourage active healthy lifestyles among young children.</p> <p>Conclusion</p> <p>This study's findings highlight the need for increased parent-caregiver partnering in terms of communication and cooperation in service of promoting appropriate amounts of physical activity among London preschoolers.</p

Learned vocal variation is associated with abrupt cryptic genetic change in a parrot species complex

<div><p>Contact zones between subspecies or closely related species offer valuable insights into speciation processes. A typical feature of such zones is the presence of clinal variation in multiple traits. The nature of these traits and the concordance among clines are expected to influence whether and how quickly speciation will proceed. Learned signals, such as vocalizations in species having vocal learning (e.g. humans, many birds, bats and cetaceans), can exhibit rapid change and may accelerate reproductive isolation between populations. Therefore, particularly strong concordance among clines in learned signals and population genetic structure may be expected, even among continuous populations in the early stages of speciation. However, empirical evidence for this pattern is often limited because differences in vocalisations between populations are driven by habitat differences or have evolved in allopatry. We tested for this pattern in a unique system where we may be able to separate effects of habitat and evolutionary history. We studied geographic variation in the vocalizations of the crimson rosella (<em>Platycercus elegans</em>) parrot species complex. Parrots are well known for their life-long vocal learning and cognitive abilities. We analysed contact calls across a <em>ca</em> 1300 km transect encompassing populations that differed in neutral genetic markers and plumage colour. We found steep clinal changes in two acoustic variables (fundamental frequency and peak frequency position). The positions of the two clines in vocal traits were concordant with a steep cline in microsatellite-based genetic variation, but were discordant with the steep clines in mtDNA, plumage and habitat. Our study provides new evidence that vocal variation, in a species with vocal learning, can coincide with areas of restricted gene flow across geographically continuous populations. Our results suggest that traits that evolve culturally can be strongly associated with reduced gene flow between populations, and therefore may promote speciation, even in the absence of other barriers.</p> </div

Program for expectant and new mothers: a population-based study of participation

<p>Abstract</p> <p>Background</p> <p>The Manitoba Healthy Baby Program is aimed at promoting pre- and perinatal health and includes two components: 1) prenatal income supplement; 2) community support programs. The goal of this research was to determine the uptake of these components by target groups.</p> <p>Methods</p> <p>Data on participation in each of the two program components were linked to data on all hospital births in Manitoba between 2004/05 through 2007/08. Descriptive analyses of participation by maternal characteristics were produced. Logistic regression analyses were conducted to identify factors associated with participation in the two programs. Separate regressions were run for two groups of women giving birth during the study period: 1) total population; 2) those receiving provincial income assistance during the prenatal period.</p> <p>Results</p> <p>Almost 30% of women giving birth in Manitoba received the Healthy Baby prenatal income supplement, whereas only 12.6% participated in any community support programs. Over one quarter (26.4%) of pregnant women on income assistance did not apply for and receive the prenatal income supplement, despite all being eligible for it. Furthermore, 77.8% of women on income assistance did not participate in community support programs. Factors associated with both receipt of the prenatal benefit and participation in community support programs included lower SES, receipt of income assistance, obtaining adequate prenatal care, having completed high school and having depressive symptoms. Having more previous births was associated with higher odds of receiving the prenatal benefit, but lower odds of attending community support programs. Being married was associated with lower odds of receiving the prenatal benefit but higher odds of participating in community support programs.</p> <p>Conclusions</p> <p>Although uptake of the Healthy Baby program in Manitoba is greater for women in groups at risk for poorer perinatal outcomes, a substantial number of women eligible for this program are not receiving it; efforts to reach these women should be enhanced.</p

Incretin Receptor Null Mice Reveal Key Role of GLP-1 but Not GIP in Pancreatic Beta Cell Adaptation to Pregnancy

Islet adaptations to pregnancy were explored in C57BL6/J mice lacking functional receptors for glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). Pregnant wild type mice and GIPRKO mice exhibited marked increases in islet and beta cell area, numbers of medium/large sized islets, with positive effects on Ki67/Tunel ratio favouring beta cell growth and enhanced pancreatic insulin content. Alpha cell area and glucagon content were unchanged but prohormone convertases PC2 and PC1/3 together with significant amounts of GLP-1 and GIP were detected in alpha cells. Knockout of GLP-1R abolished these islet adaptations and paradoxically decreased pancreatic insulin, GLP-1 and GIP. This was associated with abolition of normal pregnancy-induced increases in plasma GIP, L-cell numbers, and intestinal GIP and GLP-1 stores. These data indicate that GLP-1 but not GIP is a key mediator of beta cell mass expansion and related adaptations in pregnancy, triggered in part by generation of intra-islet GLP-1

Novel GLP-1 Fusion Chimera as Potent Long Acting GLP-1 Receptor Agonist

GLP-1 has a variety of anti-diabetic effects. However, native GLP-1 is not suitable for therapy of diabetes due to its short half-life (t1/2<2 min). To circumvent this, we developed a long-lasting GLP-1 receptor agonist by the fusion of GLP-1 with human IgG2 Fc (GLP-1/hIgG2). ELISA-based receptor binding assay demonstrated that GLP-1/hIgG2 had high binding affinity to the GLP-1R in INS-1 cells (Kd = 13.90±1.52 nM). Upon binding, GLP-1/hIgG2 was rapidly internalized by INS-1 cells in a dynamin-dependent manner. Insulin RIA showed that GLP-1/IgG2 dose-dependently stimulated insulin secretion from INS-1 cells. Pharmacokinetic studies in CD1 mice showed that with intraperitoneal injection (i.p.), the GLP-1/hIgG2 peaked at 30 minutes in circulation and maintained a plateau for >168 h. Intraperitoneal glucose tolerance test (IPGTT) in mice showed that GLP-1/hIgG2 significantly decreased glucose excursion. Furthermore, IPGTT performed on mice one week after a single drug-injection also displayed significantly reduced glucose excursion, indicating that GLP-1/hIgG2 fusion protein has long-lasting effects on the modulation of glucose homeostasis. GLP-1/hIgG2 was found to be effective in reducing the incidence of diabetes in multiple-low-dose streptozotocin-induced type 1 diabetes in mice. Together, the long-lasting bioactive GLP-1/hIgG2 retains native GLP-1 activities and thus may serve as a potent GLP-1 receptor agonist

Vaccination against GIP for the Treatment of Obesity

BACKGROUND: According to the WHO, more than 1 billion people worldwide are overweight and at risk of developing chronic illnesses, including cardiovascular disease, type 2 diabetes, hypertension and stroke. Current therapies show limited efficacy and are often associated with unpleasant side-effect profiles, hence there is a medical need for new therapeutic interventions in the field of obesity. Gastric inhibitory peptide (GIP, also known as glucose-dependent insulinotropic polypeptide) has recently been postulated to link over-nutrition with obesity. In fact GIP receptor-deficient mice (GIPR(-/-)) were shown to be completely protected from diet-induced obesity. Thus, disrupting GIP signaling represents a promising novel therapeutic strategy for the treatment of obesity. METHODOLOGY/PRINCIPAL FINDINGS: In order to block GIP signaling we chose an active vaccination approach using GIP peptides covalently attached to virus-like particles (VLP-GIP). Vaccination of mice with VLP-GIP induced high titers of specific antibodies and efficiently reduced body weight gain in animals fed a high fat diet. The reduction in body weight gain could be attributed to reduced accumulation of fat. Moreover, increased weight loss was observed in obese mice vaccinated with VLP-GIP. Importantly, despite the incretin action of GIP, VLP-GIP-treated mice did not show signs of glucose intolerance. CONCLUSIONS/SIGNIFICANCE: This study shows that vaccination against GIP was safe and effective. Thus active vaccination may represent a novel, long-lasting treatment for obesity. However further preclinical safety/toxicology studies will be required before the therapeutic concept can be addressed in humans

Patients' age as a determinant of care received following acute stroke: A systematic review

<p>Abstract</p> <p>Background</p> <p>Evidence-based care should improve acute stroke outcomes with the same magnitude of effect for stroke patients of all ages. However, there is evidence to suggest that, in some instances, older stroke patients may receive poorer quality care than younger patients.</p> <p>Our aim was to systematically review evidence of the quality of care provided to patients with acute stroke related to their age. Quality of care was determined by compliance with recommended care processes.</p> <p>Methods</p> <p>We systematically searched MEDLINE, CINAHL, ISI Web of Knowledge, Ageline and the Cochrane Library databases to identify publications (1995-2009) that reported data on acute stroke care process indicators by patient age. Data extracted included patient demographics and process indicator compliance. Included publications were critically appraised by two independent reviewers using the Critical Appraisal Skills Programme tool, and a comparison was made of the risk of bias according to studies' findings. The evidence base for reported process indicators was determined, and meta-analysis was undertaken for studies with sufficient similarity.</p> <p>Results</p> <p>Nine from 163 potential studies met the inclusion criteria. Of the 56 process indicators reported, eleven indicators were evidence-based. Seven of these indicators (64%) showed significantly poorer care for older patients compared to younger ones, while younger patients received comparatively inferior care for only antihypertensive therapy at discharge. Our findings are limited by the variable methodological quality of included studies.</p> <p>Conclusion</p> <p>Patients' age may be a factor in the care they receive after an acute stroke. However, the possible influence of patients' age on clinicians' decision-making must be considered in terms of the many complex issues that surround the provision of optimal care for older patients with acute stroke.</p