Relationship Between Opioid-Receptor Occupancy and Stimulation of Low- K m GTPase in Brain Membranes

Treatment of rat brain membranes with the irreversible opioid ligand cis -3-methylfentanylisothiocyanate (Superfit) was used to reduce gradually the number of available binding sites for the Δ-selective agonist [ 3 H][d-Ser 2 , Leu 5 lenkephalin-Thr 6 ([ 3 H]DSLET). Subsequently, the correlation between ligand binding and low- K m GTPase was investigated. Alkylation with 10 ΜM and 25 ΜM Superfit inactivated 66% and 71% of high-affinity ( K D , 1 n M ) binding sites without decreasing the affinity of the remaining sites and the stimulation of low-. K m GTPase by DSLET. Following exposure of the membranes to 50 ΜM and 75 ΜM Superfit, ligand binding was confined to the low-affinity ( K D , 20 n M ) sites. In these membranes, the Δ-agonists DSLET and [d-Pen 2 ,D-Pen 5 ]enkephalin still stimulated low- K m GTPase, and these effects were blocked by ICI 174864 ( N,N- diallyl-Tyr-AIB-AIB-Phe-Leu-OH; AIB, Α-aminoisobutyric acid), a Δ-selective antagonist. A similar relationship between low-affinity ligand binding and GTPase stimulation was observed following alkylation of the Δ-opioid receptor with the nonselective irreversible antagonist Β-chlomaltrexamine in the presence of protective concentrations of DSLET. The results reveal spare receptor sites in the coupling of the Δ-opioid receptor to low- K m GTPase in brain and identify low-affinity ligand binding as a functional component in the process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65675/1/j.1471-4159.1989.tb01862.x.pd

Intracellular Penetration and Accumulation of Radiographic Contrast Media in the Rat Kidney

Radiographic iodine-containing contrast media (meglumine calcium metrizoate, iohexol and meglumine sodium ioxaglate) were injected intravenously in rats. At various intervals after exposure, in situ cryofixation of kidneys was performed. Thin, freeze-dried cryosections were examined by electron microscopy and X-ray microanalysis. In endothelial cells, erythrocytes and tubular cells high dry weight concentrations of iodine were found. Twenty-four hours after iohexol was injected, no trace of iodine was found in the plasma, microvilli or the nuclei of the tubular cells. Small organelle-like compartments in the cytoplasm of the proximal tubular cells contained high concentrations of iodine, whereas no iodine was found in the surrounding cytoplasm. Since no metabolism of contrast medium has been demonstrated, the iodine signals must be emitted from contrast medium molecules. Other elements were also measured, with the concentrations being always within the ranges found in tubular cells of control animals. The detection of intracellular contrast thus does not seem to be an artifact due to cell injury, but rather represents a physiological event in healthy cells in the rat kidney. Our results are in contradiction to the prevailing opinion that contrast media do not enter healthy cells. However, previous conclusions have been based on the use of conventional preparation methods, and the highly water soluble contrast molecules may have been lost during the different steps of fixation and processing

The blunted effect of glucose-dependent insulinotropic polypeptide in subcutaneous abdominal adipose tissue in obese subjects is partly reversed by weight loss

BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) appears to have impaired effect on subcutaneous abdominal adipose tissue metabolism in obese subjects. The aim of the present study was to examine whether weight loss may reverse the impaired effect of GIP on subcutaneous abdominal adipose tissue in obese subjects. METHODS: Five obese males participated in a 12-week weight loss program, which consisted of caloric restriction (800 Cal day(−)(1)) followed by 4 weeks of weight-maintenance diet. Before and after weight loss, subcutaneous adipose tissue lipid metabolism was studied by conducting regional measurements of arterio-venous plasma concentrations of metabolites and blood flow (adipose tissue blood flow, ATBF) across a segment of the abdominal adipose tissue in the fasting state and during GIP infusion (1.5 pmol kg(−)(1 )min(−)(1)) in combination with a hyperinsulinemic–hyperglycemic clamp. RESULTS: After weight loss (7.5±0.8 kg), glucose tolerance and insulin sensitivity increased significantly as expected. No significant differences were seen in basal ATBF before (1.3±0.4 ml min(−1) 100 g tissue(−1)) and after weight loss (2.1±0.4 ml min(−1) 100 g tissue)(−1); however, a tendency to increase was seen. After weight loss, GIP infusion increased ATBF significantly (3.2±0.1 ml min(−1) 100 g tissue(−1)) whereas there was no increase before weight loss. Triacylglycerol (TAG) uptake did not change after weight loss. Baseline free fatty acid (FFA) and glycerol output increased significantly after weight loss, P<0.001. During the clamp period, FFA and glycerol output declined significantly, P<0.05, with no differences before and after weight loss. Weight loss increased glucose uptake and decreased FFA/glycerol ratio during the clamp period, P<0.05. CONCLUSIONS: In obese subjects, weight loss, induced by calorie restriction, improves the blunted effect of GIP on subcutaneous abdominal adipose tissue metabolism

Designing Videos with and for Adults with ADHD for an Online Intervention: Participatory Design Study and Thematic Analysis of Evaluation

Background: Adults with attention deficit hyperactivity disorder (ADHD) represent a heterogeneous group with both strengths and difficulties associated with the diagnosis. An online intervention attuned to their needs may improve their everyday functioning. When designing online interventions, it is important to adapt the therapeutic content to the values and needs of the target group. Objective: This paper describes and evaluates a participatory process used to produce content for an online intervention for adults with ADHD by producing video vignettes clarifying core training principles grounded in the participants' everyday experiences. Methods: We report on the qualitative data from 2 research phases: the design and evaluation of video vignettes for an online intervention. In the first phase, 12 adults with ADHD, 2 clinicians, and 2 research assistants participated in the production of video vignettes for the online intervention. In the second phase, participants (n=109) gave feedback on the videos as part of a clinical trial of the intervention. A subgroup (n=7) was interviewed in-depth regarding their experiences with the videos. The qualitative data were analyzed using thematic analysis. Results: In the first phase, the participants with ADHD contributed with experiences from challenging everyday situations. In the process, we navigated between therapeutic principles and the participants' experiential perspectives to create content relevant and consistent with the target group's values and experiences. In the second phase, we identified 3 themes related to the participants' experiences and interpretation of the video vignettes: (1) recognition of ADHD-related challenges, (2) connection with the characters and the situations, and (3) video protagonists as companions and role models for change. Conclusions: A participatory design process for designing online mental health interventions can be used to probe and balance between the therapeutic principles defined by clinicians and the participants’ experiences with mental health issues in the production of therapeutic content. In our study, the inclusion of video vignettes in an online intervention enabled a contextualized and relevant presentation of everyday experiences and psychosocial factors in the life of an adult with ADHD.publishedVersio

Do national resources have to be centrally managed? Vested interests and institutional reform in Norwegian fisheries governance

Corporatism -with its privileged access, restricted participation and centralized structures - has a long history in Norwegian fisheries governance. Co-management – understood as a decentralized, bottom-up and more inclusive form of fisheries governance - has not been considered a relevant alternative.. Why does corporatism still prevail in a context where stakeholder status in fisheries governance globally – both in principle and practice - has been awarded environmental organizations, municipal authorities and even consumer advocacy groups? Why then have alternatives to the corporatist system of centralized consultation and state governance never been seriously considered in Norway, in spite of the growing emphasis on fish as a public resource and fisheries management as human intervention in geographically confined and complex ecosystems? We suggest that thismay have to do with the fundamental assumptions behind Norwegian fisheries governance that since fish is a national resource, it must be centrally managed. We argue that this is an assumption that may be contested

Emergency medical service provider decision-making in out of hospital cardiac arrest: An exploratory study

© 2017 The Author(s). Background: There are approximately 60,000 out-of-hospital cardiac arrests (OHCA) in the United Kingdom (UK) each year. Within the UK there are well-established clinical practice guidelines that define when resuscitation should be commenced in OHCA, and when resuscitation should cease. Background literature indicates that decision-making in the commencement and cessation of resuscitation efforts in OHCA is complex, and not comprehensively understood. No relevant research from the UK has been published to date and this research study seeks to explore the influences on UK Emergency Medical Service (EMS) provider decision-making when commencing and ceasing resuscitation attempts in OHCA. The aim of this research to explore the influences on UK Emergency Medical Services provider decision-making when commencing and ceasing resuscitation attempts in OHCA. Methods: Four focus groups were convened with 16 clinically active EMS providers. Four case vignettes were discussed to explore decision-making within the focus groups. Thematic analysis was used to analyse transcripts. Results: This research found that there are three stages in the decision-making process when EMS providers consider whether to commence or cease resuscitation attempts in OHCA. These stages are: the call; arrival on scene; the protocol. Influential factors present at each of the three stages can lead to different decisions and variability in practice. These influences are: factual information available to the EMS provider; structural factors such as protocol, guidance and research; cultural beliefs and values; interpersonal factors; risk factors; personal values and beliefs. Conclusions: An improved understanding of the circumstantial, individual and interpersonal factors that mediate the decision-making process in clinical practice could inform the development of more effective clinical guidelines, education and clinical decision support in OHCA. These changes have the potential to lead to greater consistency. and EMS provider confidence, with the potential for improved patient outcome from OHCA

Jarlmanns saga og Hermanns: A Translation

Agnete Lothʼs edition of the longer version of Jarlmanns saga og Hermanns included an accompanying English paraphrase (by Gillian Fellows Jensen), but there has never been a full translation into English, much less of the shorter version as edited by Hugo Rydberg. We rectify that omission here, providing a normalized text of Rydbergʼs edition with an English translation alongside in the hopes of making this entertaining saga more accessible to a wider audience

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics

Blood Press. 2000;9(2-3):146-51. Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics. Hansson L, Lithell H, Skoog I, Baro F, Bánki CM, Breteler M, Castaigne A, Correia M, Degaute JP, Elmfeldt D, Engedal K, Farsang C, Ferro J, Hachinski V, Hofman A, James OF, Krisin E, Leeman M, de Leeuw PW, Leys D, Lobo A, Nordby G, Olofsson B, Opolski G, Prince M, Reischies FM. University of Uppsala, Department of Public Health, Clinical Hypertension Research, Sweden. Abstract The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment. PMID: 10855739 [PubMed - indexed for MEDLINE

Study on COgnition and Prognosis in the Elderly (SCOPE)

Blood Press. 1999;8(3):177-83. Study on COgnition and Prognosis in the Elderly (SCOPE). Hansson L, Lithell H, Skoog I, Baro F, Bánki CM, Breteler M, Carbonin PU, Castaigne A, Correia M, Degaute JP, Elmfeldt D, Engedal K, Farsang C, Ferro J, Hachinski V, Hofman A, James OF, Krisin E, Leeman M, de Leeuw PW, Leys D, Lobo A, Nordby G, Olofsson B, Zanchetti A, et al. University of Uppsala, Department of Public Health, Sweden. Abstract The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multicentre, prospective, randomized, double-blind, parallel-group study designed to compare the effects of candesartan cilexetil and placebo in elderly patients with mild hypertension. The primary objective of the study is to assess the effect of candesartan cilexetil on major cardiovascular events. The secondary objectives of the study are to assess the effect of candesartan cilexetil on cognitive function and on total mortality, cardiovascular mortality, myocardial infarction, stroke, renal function, hospitalization, quality of life and health economics. Male and female patients aged between 70 and 89 years, with a sitting systolic blood pressure (SBP) of 160-179 mmHg and/or diastolic blood pressure (DBP) of 90-99 mmHg, and a Mini-Mental State Examination (MMSE) score of 24 or above, are eligible for the study. The overall target study population is 4000 patients, at least 1000 of whom are also to be assessed for quality of life and health economics data. After an open run-in period lasting 1-3 months, during which patients are assessed for eligibility and those who are already on antihypertensive therapy at enrolment are switched to hydrochlorothiazide 12.5 mg o.d., patients are randomized to receive either candesartan cilexetil 8 mg once daily (o.d.) or matching placebo o.d. At subsequent study visits, if SBP remains >160 mmHg, or has decreased by 85 mmHg, study treatment is doubled to candesartan cilexetil 16 mg o.d. or two placebo tablets o.d. Recruitment was completed in January 1999. At that time 4964 patients had been randomized. All randomized patients will be followed for an additional 2 years. If the event rate is lower than anticipated, the follow-up will be prolonged. PMID: 10595696 [PubMed - indexed for MEDLINE