Noninvasive assessment of exercise-related intramyocellular acetylcarnitine in euglycemia and hyperglycemia in patients with type 1 diabetes using ¹H magnetic resonance spectroscopy: a randomized single-blind crossover study

OBJECTIVE

Intramyocellular acetylcarnitine (IMAC) is involved in exercise-related fuel metabolism. It is not known whether levels of systemic glucose influence IMAC levels in type 1 diabetes.

RESEARCH DESIGN AND METHODS

Seven male individuals with type 1 diabetes performed 120 min of aerobic exercise at 55–60% of Vo_2max randomly on two occasions (glucose clamped to 5 or 11 mmol/l, identical insulinemia). Before and after exercise, IMAC was detected by ¹H magnetic resonance spectroscopy in musculus vastus intermedius.

RESULTS

Postexercise levels of IMAC were significantly higher than pre-exercise values in euglycemia (4.30 ± 0.54 arbitrary units [a.u.], P < 0.001) and in hyperglycemia (2.44 ± 0.53 a.u., P = 0.01) and differed significantly according to glycemia (P < 0.01). The increase in exercise-related levels of IMAC was significantly higher in euglycemia (3.97 ± 0.45 a.u.) than in hyperglycemia (1.71 ± 0.50 a.u.; P < 0.01).

CONCLUSIONS

The increase in IMAC associated with moderate aerobic exercise in individuals with type 1 diabetes was significantly higher in euglycemia than in hyperglycemia.Intramyocellular acetylcarnitine (IMAC) is involved in the regulation of fat and carbohydrate oxidation in skeletal muscle during moderate aerobic exercise (1). Although carnitine metabolism appears comparable in patients with type 1 diabetes and healthy control subjects (2), it is not known whether IMAC is related to variations in fuel metabolism observed during exercise under differing glycemic levels in type 1 diabetes (3). Given the controversial results from previous studies linking IMAC to increased β-oxidation (4) but also to high glycolytic flux (1), the aim of the present study was to assess exercise-related concentrations of IMAC noninvasively by ¹H magnetic resonance spectroscopy (¹H MRS) (5,6) in patients with type 1 diabetes in euglycemia and hyperglycemia.     

Visual Acuity and Mortality in Older People and Factors on the Pathway

Purpose: To examine vision as a predictor of mortality in older people and the role of mobility, depressed mood, chronic diseases, body mass index, physical activity and injurious accidents in this possible association. Methods: 223 persons aged 75 and 193 persons aged 80 years at the baseline participated in visual acuity measurements. Visual acuity (VA) of < 0.3 in the better eye was defined as visual impairment, VA of ≥ 0.3 but ≤ 0.5 as lowered vision and VA > 0.5 as normal VA. Death dates were received from the official register. Cox regression models were used to determine the relative risks of mortality and to study what factors lie on the pathway from poor vision to mortality. Results: Over the 10-year follow-up, 107 (48%) persons aged 75 years and 138 (72%) aged 80 years at the baseline died. The risk for mortality among the 75-year-olds with lowered vision was 1.98 (95 % CI 1.25–3.13) and with visual impairment 1.90 (95% CI 1.12–3.20) compared to those with normal VA. Lower walking speed, physical inactivity, cardiovascular diseases, injurious accidents, diabetes and depressed mood each attenuated the risk markedly. Nevertheless, lowered vision remained a significant predictor of mortality even after including all these variables in the model. Among the 80-year-olds vision did not correlate with mortality. Conclusions: Lowered vision and severe visual impairment predicted mortality in the 75-year-old but not 80-year-old population. The increased risk was partially explained by lower walking speed, physical inactivity, cardiovascular diseases, depressed mood, diabetes and injurious accidents.     

Effects of corticosterone pellets on baseline and stress-induced corticosterone and corticosteroid-binding-globulin

Exogenous administration of glucocorticoids is a widely used and efficient tool to investigate the effects of elevated concentrations of these hormones in field studies. Because the effects of corticosterone are dose and duration-dependent, the exact course of plasma corticosterone levels after exogenous administration needs to be known. We tested the performance of self-degradable corticosterone pellets (implanted under the skin) in elevating plasma corticosterone levels. We monitored baseline (sampled within 3 min after capture) total corticosterone levels and investigated potential interactions with corticosteroid-binding-globulin (CBG) capacity and the endogenous corticosterone response to handling in Eurasian kestrel Falco tinnunculus and barn owl Tyto alba nestlings. Corticosterone pellets designed for a 7-day-release in rodents elevated circulating baseline total corticosterone during only 2-3 days compared to placebo-nestlings. Highest levels occurred 1-2 days after implantation and levels decreased strongly thereafter. CBG capacity was also increased, resulting in a smaller, but still significant, increase in baseline free corticosterone levels. The release of endogenous corticosterone as a response to handling was strong in placebo-nestlings, but absent 2 and 8 days after corticosterone pellet implantation. This indicates a potential shut-down of the hypothalamo-pituitary-adrenal axis after the 2-3 days of elevated baseline corticosterone levels. 20 days after pellet implantation, the endogenous corticosterone response to handling of nestlings implanted with corticosterone pellets attained similar levels as in placebo-nestlings. Self-degradable pellets proved to be an efficient tool to artificially elevate circulating baseline corticosterone especially in field studies, requiring only one intervention. The resulting peak-like elevation of circulating corticosterone, the concomitant elevation of CBG capacity, and the absence of an endogenous corticosterone response to an acute stressor have to be taken into account.     

FcgammaRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation

These studies investigate how interactions between the BCR and FcgammaRIIB affect B lymphocyte stimulator (BLyS) recep-tor expression and signaling. Previous studies showed that BCR ligation up-regulates BLyS binding capacity in mature B cells, reflecting increased BLyS receptor levels. Here we show that FcgammaRIIB coaggregation dampens BCR-induced BLyS receptor up-regulation. This cross-regulation requires BCR and FcgammaRIIB coligation, and optimal action relies on the Src-homology-2 (SH2)-containing inositol 5 phosphase-1 (SHIP1). Subsequent to FcgammaRIIB/BCR coaggregation, the survival promoting actions of BLyS are attenuated, reflecting reduced BLyS receptor signaling capacity in terms of Pim 2 maintenance, noncanonical NF-kappaB activation, and Bcl-xL levels. These findings link the negative regulatory functions of FcgammaRIIB with BLyS-mediated B-cell survival.     

Effects of alcohol on sleep and the sleep electroencephalogram in healthy young women

BACKGROUND: Although the association between sleep and alcohol has been of interest to scientists for decades, the effects of alcohol on sleep and sleep electroencephalogram (EEG) have not been extensively studied in women. Our specific aim was to determine whether sleep stage variables and/or spectral characteristics of the sleep EEG are altered by alcohol administration in women. METHODS: Changes of sleep and the sleep EEG were investigated after administration of a moderate dose of alcohol (0.49 g/kg) in the hour before bedtime compared with placebo in young healthy women. After approximately 2 weeks at home on a fixed 8.5- or 9-hour stabilization sleep schedule, sleep was continuously recorded by polysomnography for 3 consecutive nights [adaptation, placebo, alcohol (mean breath alcohol concentration 0.043 g/% before bedtime)] in the laboratory in 7 women (ages 22-25, mean=23.5, SD=1 year). Sleep stages were scored according to conventional criteria. Electroencephalogram power spectra of the bipolar derivations Fz/Cz (anterior) and Pz/Oz (posterior) were calculated using a fast Fourier transform routine. RESULTS: Only few changes in sleep and the sleep EEG were observed. Across the entire night rapid eye movement (REM) sleep decreased, while minutes of stage 4 sleep were increased in the first 2-hour interval on alcohol nights compared with placebo nights. Spectral analysis of the EEG showed increased power in the alpha range (9-11 Hz) during all-night non-REM (NREM) sleep in anterior derivations after alcohol compared with placebo. Differences in spectral EEG power were also present in 2-hour intervals of NREM sleep; in particular, EEG power was increased on the alcohol night for frequency bins within the alpha range in anterior derivations and within the delta range (3-4 Hz) in posterior derivations during the initial part of the night. CONCLUSIONS: A moderate dose of alcohol just before bedtime resulted in a short-lived increase in sleep intensity. A limitation of the study, however, was that only a single dose of alcohol was used to examine the effects of alcohol on sleep.     

First insights into community pharmacy based buprenorphine-naloxone dispensing in Finland

BackgroundFinnish community pharmacies have been permitted to dispense buprenorphine-naloxone since February 2008. This study explored the dispensing practices, service experiences, problems encountered and opportunities for future development.MethodsIn August 2011, a questionnaire was mailed to all Finnish community pharmacies dispensing buprenorphine-naloxone (n = 69).ResultsSixty-four pharmacies responded (93%), of which 54 had dispensed buprenorphine-naloxone to 155 clients since 2008. Forty-eight pharmacies had 108 current clients (10% of all buprenorphine-naloxone clients in Finland). Overall satisfaction with buprenorphine-naloxone dispensing was high, with all respondents indicating dispensing had gone ‘well’ or ‘very well’. Fourteen pharmacies (26%) had experienced one or more problems, predominately in relation timing or non-collection of doses. Problems were more common in pharmacies with more than one buprenorphine-naloxone client (odds ratio 1.39, 95% confidence interval 1.05–1.86). Most pharmacies (n = 43, 80%) identified opportunities for improvement, including the need for more education and financial remuneration. Forty-six pharmacies (85%) were willing to dispense buprenorphine-naloxone to more clients; however, 43 pharmacies (80%) perceived that supervision of buprenorphine-naloxone dosing is not a suitable task for pharmacists in Finland.ConclusionProvision of buprenorphine-naloxone in Finnish community pharmacies has remained relatively small-scale. As experiences have been generally positive and problems rare, it may be possible to expand these services.     

Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system

The action of type I interferons in the central nervous system (CNS) during autoimmunity is largely unknown. Here, we demonstrate elevated interferon beta concentrations in the CNS, but not blood, of mice with experimental autoimmune encephalomyelitis (EAE), a model for CNS autoimmunity. Furthermore, mice devoid of the broadly expressed type I IFN receptor (IFNAR) developed exacerbated clinical disease accompanied by a markedly higher inflammation, demyelination, and lethality without shifting the T helper 17 (Th17) or Th1 cell immune response. Whereas adoptive transfer of encephalitogenic T cells led to enhanced disease in Ifnar1(-/-) mice, newly created conditional mice with B or T lymphocyte-specific IFNAR ablation showed normal EAE. The engagement of IFNAR on neuroectodermal CNS cells had no protective effect. In contrast, absence of IFNAR on myeloid cells led to severe disease with an enhanced effector phase and increased lethality, indicating a distinct protective function of type I IFNs during autoimmune inflammation of the CNS.     

Evaluation of an organizational stress management program in a municipal public works organization

The aim of this study was to investigate the effects of employee participation in an organizational stress management program consisting of several interventions aiming to improve psychosocial work environment and well-being. Pre- and postintervention questionnaires were used to measure the outcomes with a 2-year interval. This article describes the background of the program, results of previously published effect studies, and a qualitative evaluation of the program. The authors also tested the effects of level of participation in all interventions among the employees of the service production units by 2 (time) x 3 (group) repeated measures ANOVAs (n = 625). "Active participation" (more than 5.5 days) had a positive effect on feedback from supervisor and flow of information. Work climate remained on a permanent level while it decreased in the categories of moderate and nonparticipation. The level of participation did not improve individual well-being or other aspects of psychosocial work environment as postulated by the work stress models. The qualitative evaluation and practical conclusions drawn by the management of the Organization provided a positive impression of the impact of the program.