Invited review: Milk fat globule membrane-A possible panacea for neurodevelopment, infections, cardiometabolic diseases, and frailty.

Milk is an evolutionary benefit for humans. For infants, it offers optimal nutrients for normal growth, neural development, and protection from harmful microbes. Humans are the only mammals who drink milk throughout their life. Lipids in colostrum originate mostly from milk fat globule membrane (MFGM) droplets extruded from the mammary gland. The MFGM gained much interest as a potential nutraceutical, due to their high phospholipid (PL), ganglioside (GD), and protein contents. In this review, we focused on health effects of MFGM ingredients and dairy food across the life span, especially on neurodevelopment, cardiometabolic health, and frailty in older adults. The MFGM supplements to infants and children reduced gastrointestinal and respiratory tract infections and improved neurodevelopment due to the higher content of protein, PL, and GD in MFGM. The MFGM formulas containing PL and GD improved brain myelination and fastened nerve conduction speed, resulting in improved behavioral developments. Administration of MFGM-rich ingredients improved insulin sensitivity and decreased inflammatory markers, LDL-cholesterol, and triglycerides by lowering intestinal absorption of cholesterol and increasing its fecal excretion. The MFGM supplements, together with exercise, improved ambulatory activities, leg muscle mass, and muscle fiber velocity in older adults. There are great variations in the composition of lipids and proteins in MFGM products, which make comparisons of the different studies impossible. In addition, investigations of the individual MFGM components are required to evaluate their specific effects and molecular mechanisms. Although we are currently only beginning to understand the possible health effects of MFGM products, the current MFGM supplementation trials as presented in this review have shown significant clinical health benefits across the human life span, which are worth further investigation.

Human information behaviour and physiological measurements as a basis to tailor health information. An explorative study in a physical activity intervention among prediabetic individuals in Northern Finland.

OBJECTIVE: To explore through an interdisciplinary approach the potential to tailor health information on the basis of human information behaviour (HIB) on par with the results of basic physiological measurements of individuals' health. METHODS: The data were collected at the baseline of a physical activity and diabetes prevention intervention with 72 prediabetic participants, conducted in Oulu, Finland, by the University of Oulu and Oulu Deaconess Institute in 2010. Body mass index (BMI), fitness classifications and glucose values were obtained from all prediabetic participants. The interest in, the search for and the use of information on nutrition, physical activity and diabetes were examined through a self-report questionnaire with a response rate of 95.8%. The data were analysed with the SPSS statistics 18 software. RESULTS AND CONCLUSIONS: The study shows that information behaviour of prediabetic individuals differs according to their BMI and fitness level. Poor physical fitness classifications and high BMI values were associated with an increased desire to receive tailored information on nutrition and physical activity frequently. These results add knowledge on the types and preferred frequencies of tailored information. Because of the small sample size, the results should be validated further.

[Objective measurement of physical activity in adults]. / Aikuisten terveysliikunnan laadun ja määrän objektiivinen mittaaminen.

Physical inactivity and overweight are important risk factors for several diseases. Brisk walking or jogging recommended currently for physical exercise may be too demanding for subjects having overweight or poor physical condition. The recommendations do not take daily physical activity into account either. Recording of the total amount and intensity of ambulatory physical activity by the accelerometers allows objective assessment of dose-response relations between physical activity and health. By using threshold values of the intensity of physical activity or step counts, more accurate and effective recommendations for physical exercise can be suggested.

Step Detection Accuracy and Energy Expenditure Estimation at Different Speeds by Three Accelerometers in a Controlled Environment in Overweight/Obese Subjects.

Our aim was to compare three research-grade accelerometers for their accuracy in step detection and energy expenditure (EE) estimation in a laboratory setting, at different speeds, especially in overweight/obese participants. Forty-eight overweight/obese subjects participated. Participants performed an exercise routine on a treadmill with six different speeds (1.5, 3, 4.5, 6, 7.5, and 9 km/h) for 4 min each. The exercise was recorded on video and subjects wore three accelerometers during the exercise: Sartorio Xelometer (SX, hip), activPAL (AP, thigh), and ActiGraph GT3X (AG, hip), and energy expenditure (EE) was estimated using indirect calorimetry for comparisons. For step detection, speed-wise mean absolute percentage errors for the SX ranged between 9.73-2.26, 6.39-0.95 for the AP, and 88.69-2.63 for the AG. The activPALs step detection was the most accurate. For EE estimation, the ranges were 21.41-15.15 for the SX, 57.38-12.36 for the AP, and 59.45-28.92 for the AG. All EE estimation errors were due to underestimation. All three devices were accurate in detecting steps when speed exceeded 4 km/h and inaccurate in EE estimation regardless of speed. Our results will guide users to recognize the differences, weaknesses, and strengths of the accelerometer devices and their algorithms.

Acromegaly caused by a GHRH-producing pancreatic neuroendocrine tumor: a rare manifestation of MEN1 syndrome.

SUMMARY: Multiple endocrine neoplasia type 1 NM_001370259.2(MEN1):c.466G>C(p.Gly156Arg) is characterized by tumors of various endocrine organs. We report on a rare, growth hormone-releasing hormone (GHRH)-releasing pancreatic tumor in a MEN1 patient with a long-term follow-up after surgery. A 22-year-old male with MEN1 syndrome, primary hyperparathyroidism and an acromegalic habitus was observed to have a pancreatic tumor on abdominal CT scanning, growth hormone (GH) and insulin-like growth factor 1 (IGF1) were elevated and plasma GHRH was exceptionally high. GHRH and GH were measured before the treatment and were followed during the study. During octreotide treatment, IGF1 normalized and the GH curve was near normal. After surgical treatment of primary hyperparathyroidism, a pancreatic tail tumor was enucleated. The tumor cells were positive for GHRH antibody staining. After the operation, acromegaly was cured as judged by laboratory tests. No reactivation of acromegaly has been seen during a 20-year follow-up. In conclusion, an ectopic GHRH-producing, pancreatic endocrine neoplasia may represent a rare manifestation of MEN1 syndrome. LEARNING POINTS: Clinical suspicion is in a key position in detecting acromegaly. Remember genetic disorders with young individuals having primary hyperparathyroidism. Consider multiple endocrine neoplasia type 1 syndrome when a person has several endocrine neoplasia. Acromegaly may be of ectopic origin with patients showing no abnormalities in radiological imaging of the pituitary gland.

Key roles of endothelin-1 and p38 MAPK in the regulation of atrial stretch response.

Mechanisms regulating stretch response in the left ventricle are investigated in detail but not well understood in atrial myocardium. Hypertrophic growth of atrial myocardium contributes to the pathogenesis of atrial fibrillation. In this study, we sought to elucidate mechanisms of stretch-induced activation of key signaling pathways and hypertrophy-associated genes in rat atria. Stretching of isolated atria induced a rapid increase in phosphorylation of p38 MAPK and ERK and induced a p38 MAPK-dependent increase in DNA binding activity of transcription factors Elk-1 and GATA-4. Inhibition of the ERK pathway had no effect on the cardiac transcription factors studied. Stretch-induced increase in atrial contractile function was substantially enhanced by inhibition of p38 MAPK. p38 MAPK also regulated stretch-induced increase in c-fos, ß-myosin heavy chain, B-type natriuretic peptide mRNA levels, and atrial natriuretic peptide secretion in isolated atria. Various autocrine/paracrine factors are known to mediate the stretch response in the left ventricle. Stretching of isolated atria resulted in a robust increase in endothelin-1 (ET-1) mRNA levels, while apelin and adrenomedullin signaling cascades were downregulated. Administration of mixed ET(A/B) receptor antagonist bosentan attenuated the stretch-induced activation of GATA-4 in isolated atria, whereas ANG II receptor type-1 antagonist CV-11974 had no effect. Moreover, analysis of RNA from intact atrial and ventricular myocardium revealed significantly higher mRNA levels of ET(A) receptor and ET converting enzyme-1 in atrial compared with ventricular myocardium. In conclusion, our findings identify the local ET-1 system and p38 MAPK as key regulators of load-induced hypertrophic response in isolated rat atria.

Step detection and energy expenditure at different speeds by three accelerometers in a controlled environment.

Physical activity (PA) is one of the most efficient ways to prevent obesity and its associated diseases worldwide. In the USA, less than 10% of the adult population were able to meet the PA recommendations when accelerometers were used to assess PA habituation. Accelerometers significantly differ from each other in step recognition and do not reveal raw data. The aim of our study was to compare a novel accelerometer, Sartorio Xelometer, which enables to gather raw data, with existing accelerometers ActiGraph GT3X+ and activPAL in terms of step detection and energy expenditure estimation accuracy. 53 healthy subjects were divided into 2 cohorts (cohort 1 optimization; cohort 2 validation) and wore 3 accelerometers and performed an exercise routine consisting of the following speeds: 1.5, 3, 4.5, 9 and 10.5 km/h (6 km/h for 2nd cohort included). Data from optimization cohort was used to optimize Sartorio step detection algorithm. Actual taken steps were recorded with a video camera and energy expenditure (EE) was measured. To observe the similarity between video and accelerometer step counts, paired samples t test and intraclass correlation were used separately for step counts in different speeds and for total counts as well as EE estimations. In speeds of 1.5, 3, 4.5, 6, 9 and 10.5 km/h mean absolute percentage error (MAPE) % were 8.1, 3.5, 4.3, 4.2, 3.1 and 7.8 for the Xelometer, respectively (after optimization). For ActiGraph GT3X+ the MAPE-% were 96.93 (87.4), 34.69 (23.1), 2.13 (2.3), 1.96 (2.6) and 2.99 (3.8), respectively and for activPAL 6.55 (5.6), 1.59 (0.6), 0.81 (1.1), 10.60 (10.3) and 15.76 (13.8), respectively. Significant intraclass correlations were observed with Xelometer estimates and actual steps in all speeds. Xelometer estimated the EE with a MAPE-% of 30.3, activPAL and ActiGraph GT3X+ with MAPE percentages of 20.5 and 24.3, respectively. The Xelometer is a valid device for assessing step counts at different gait speeds. MAPE is different at different speeds, which is of importance when assessing the PA in obese subjects and elderly. EE estimates of all three devices were found to be inaccurate when compared with indirect calorimetry.

PCSK9 Levels and Metabolic Profiles in Elderly Subjects with Different Glucose Tolerance under Statin Therapy.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades low-density lipoprotein cholesterol (LDL-C) receptors, and thus regulates the LDL-C levels in the circulation. Type 2 diabetics often have elevated LDL-C levels. However, the functions of PCSK9 in patients with alterations of glu-cose metabolism and statin therapy are still unclear. METHOD: we investigated a large cohort of 608 subjects, born in 1945 in Oulu, Finland (Oulu Cohort 1945). We studied the effects of PSCK9 lev-els with different glucose tolerances (normal glucose tolerance (NGT), prediabetes (PreDM) or type 2 diabetes (T2D)) with and without statin medication, and analyzed clinical data, NMR metabolomics and PCSK9 plasma levels. RESULTS: PCSK9 plasma levels did not significantly differ between the three groups. Statin therapy significantly increased the PCSK9 levels in NGT, PreDM and T2D groups compared with subjects with no statins. In the NGT group, negative associations between PCSK9 and LDL-C, intermediate-density lipoprotein cholesterol (IDL-C), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol and LDL and IDL triglycerides were observed under statin medication. In contrast, in the PreDM and T2D groups, these associa-tions were lost. CONCLUSIONS: our data suggest that in subjects with abnormal glucose metabolism and statin therapy, the significant PCSK9-mediated effects on the lipid metabolites are lost com-pared to NGT subjects, but statins reduced the LDL-C and VLDL-C levels.

(Neuro) Peptides, Physical Activity, and Cognition.

Regular physical activity (PA) improves cognitive functions, prevents brain atrophy, and delays the onset of cognitive decline, dementia, and Alzheimer's disease. Presently, there are no specific recommendations for PA producing positive effects on brain health and little is known on its mediators. PA affects production and release of several peptides secreted from peripheral and central tissues, targeting receptors located in the central nervous system (CNS). This review will provide a summary of the current knowledge on the association between PA and cognition with a focus on the role of (neuro)peptides. For the review we define peptides as molecules with less than 100 amino acids and exclude myokines. Tachykinins, somatostatin, and opioid peptides were excluded from this review since they were not affected by PA. There is evidence suggesting that PA increases peripheral insulin growth factor 1 (IGF-1) levels and elevated serum IGF-1 levels are associated with improved cognitive performance. It is therefore likely that IGF-1 plays a role in PA induced improvement of cognition. Other neuropeptides such as neuropeptide Y (NPY), ghrelin, galanin, and vasoactive intestinal peptide (VIP) could mediate the beneficial effects of PA on cognition, but the current literature regarding these (neuro)peptides is limited.

Effects of repeated whole-body cold exposures on serum concentrations of growth hormone, thyrotropin, prolactin and thyroid hormones in healthy women.

Cold therapy is used to relieve pain and inflammatory symptoms. Humoral changes may account for the pain alleviation related to the cold exposures. The aim of the present study was to examine the effects of two types of cold therapy, winter swimming in ice-cold water (WS) and whole body cryotherapy (WBC), on the serum levels of the growth hormone, prolactin, thyrotropin and free fractions of thyroid hormones (fT3, fT4). One group of healthy females (n = 6) was exposed to WS (water 0-2 degrees C) for 20 s and another group (n = 6) to WBC (air 110 degrees C) for 2 min, three times a week for 12 weeks. Blood samples used for the hormone measurements were taken on weeks 1, 4 and 12 before and 35 min after the cold exposures and on the days of the respective weeks, when the cold exposures were not performed. During the WS treatments, serum thyrotropin increased significantly at 35 min on weeks 1 (p < 0.01) and 4 (p < 0.05), but the responses were within the health-related reference interval. During the WS, the serum prolactin measured at 35 min on week 12 was lower than during the control treatment, and no changes in fT3 or fT4 were observed. During the WBC, no changes in the serum levels of the studied hormones were observed during the 12 weeks. In conclusion, repeated WS and WBC treatments for healthy females do not lead to disorders related to altered secretions of the growth hormone, prolactin, thyrotropin, or thyroid hormones.

Time-course of exercise and its association with 12-month bone changes.

BACKGROUND: Exercise has been shown to have positive effects on bone density and strength. However, knowledge of the time-course of exercise and bone changes is scarce due to lack of methods to quantify and qualify daily physical activity in long-term. The aim was to evaluate the association between exercise intensity at 3, 6 and 12 month intervals and 12-month changes in upper femur areal bone mineral density (aBMD) and mid-femur geometry in healthy premenopausal women. METHODS: Physical activity was continuously assessed with a waist-worn accelerometer in 35 healthy women (35-40 years) participating in progressive high-impact training. To describe exercise intensity, individual average daily numbers of impacts were calculated at five acceleration levels (range 0.3-9.2 g) during time intervals of 0-3, 0-6, and 0-12 months. Proximal femur aBMD was measured with dual x-ray absorptiometry and mid-femur geometry was evaluated with quantitative computed tomography at the baseline and after 12 months. Physical activity data were correlated with yearly changes in bone density and geometry, and adjusted for confounding factors and impacts at later months of the trial using multivariate analysis. RESULTS: Femoral neck aBMD changes were significantly correlated with 6 and 12 months' impact activity at high intensity levels (> 3.9 g, r being up to 0.42). Trochanteric aBMD changes were associated even with first three months of exercise exceeding 1.1 g (r = 0.39-0.59, p < 0.05). Similarly, mid-femoral cortical bone geometry changes were related to even first three months' activity (r = 0.38-0.52, p < 0.05). In multivariate analysis, 0-3 months' activity did not correlate with bone change at any site after adjusting for impacts at later months. Instead, 0-6 months' impacts were significant correlates of 12-month changes in femoral neck and trochanter aBMD, mid-femur bone circumference and cortical bone attenuation even after adjustment. No significant correlations were found at the proximal or distal tibia. CONCLUSION: The number of high acceleration impacts during 6 months of training was positively associated with 12-month bone changes at the femoral neck, trochanter and mid-femur. These results can be utilized when designing feasible training programs to prevent bone loss in premenopausal women. TRIAL REGISTRATION: Clinical trials.gov NCT00697957.

Narrow-band ultraviolet B (NB UV-B) exposures improve mood in healthy individuals differently depending on chronotype.

The evening chronotype is associated with psychological symptoms such as depressed mood, while skin exposure to ultraviolet radiation (UVR) may affect mood and behavior through neural and humoral routes. This pilot study aimed to investigate the impact of whole-body narrow-band (NB) UV-B exposure on current mood state and circulating 25-hydroxyvitamin D3 (25(OH)D3), interleukin-6 (IL-6), cortisol and ß-endorphin (ß-END) levels in healthy participants. Here, eleven healthy women received full-body NB UV-B exposures on four afternoons, and the chronotype was assessed with a shortened version of Horne and Östberg's Morningness-Eveningness Questionnaire (MEQ). Perceived mood was evaluated using the Visual Analogue Scale (VAS), and serum 25(OH)D3, IL-6, cortisol and ß-END concentrations were monitored daily. Decreasing VAS values showed mood to improve significantly over the five days after the four suberythematous NB UV-B exposures (p = .038), and the more the circadian preference was inclined toward eveningness, the greater the improvement in the mood dimension of wellbeing (p = .021). Baseline mood state was correlated with baseline 25(OH)D3 (r = -0.54, 95% CI: -0.86 to -0.09) and with baseline cortisol (r = -0.57, 95% CI: -0.87 to -0.04). During the NB UV-B exposures, 25(OH)D3 increased significantly, as expected, and IL-6 declined significantly by -0.35 (95% CI: -0.69 to -0.07) pg/mL from the initial values of 1.12 ± 0.66 pg/mL (p = .025). In conclusion, in our pilot study, NB UV-B exposure improved mood, especially among those with evening preference for their daily activities, as well as circulating 25(OH)D3 levels, whereas circulating IL-6 levels decreased. Abbreviations: UVR: Ultraviolet radiation; NB UV-B: narrow-band UV-B; VAS: Visual Analogue Scales; ß-END: ß-endorphin; IL-6: Interleukin-6.

Effect of Physical Activity on Plasma PCSK9 in Subjects With High Risk for Type 2 Diabetes.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a liver serine protease regulating LDL cholesterol metabolism. PCSK9 binds to LDL receptors and guides them to lysosomes for degradation, thus increasing the amount of circulating LDL cholesterol. The aim of the study was to investigate associations between physical activity and plasma PCSK9 in subjects with high risk for type 2 diabetes (T2D). METHODS: Sixty-eight subjects from both genders with a high risk for T2D were included to a randomized controlled trial with a 3-month physical activity intervention. Physical activity intensities and frequencies were monitored throughout the intervention using a hip worn portable accelerometer. The plasma was collected before and after intervention for analysis of PCSK9 and cardiovascular biomarkers. RESULTS: Plasma PCSK9 did not relate to physical activity although number of steps were 46% higher in the intervention group than in the control group (p < 0.029). Total cholesterol was positively correlated with plasma PCSK9 (R = 0.320, p = 0.008), while maximal oxygen uptake was negatively associated (R = -0.252, p = 0.044). After the physical activity intervention PCSK9 levels were even stronger inversely associated with maximal oxygen uptake (R = -0.410, p = 0.0008) and positively correlated with HDL cholesterol (R = 0.264, p = 0.030). Interestingly, plasma PCSK9 levels were higher in the beginning than at the end of the study. CONCLUSION: The low physical activity that our subjects with high risk for T2D could perform did not influence plasma PCSK9 levels. Intervention with higher physical activities might be more effective in influencing PCSK9 levels.

Association of Physical Activity With Telomere Length Among Elderly Adults - The Oulu Cohort 1945.

Introduction: Physical activity (PA) has been associated with telomere shortening. The association of PA intensity or volume with telomere length (TL) is nonetheless unclear. The aim of our study was to investigate the associations of exercise intensity and volume with TL in elderly adults from Northern Finland (65° latitude North). Methods: Seven hundred elderly subjects born in 1945 in the Oulu region were investigated. PA was measured during a 2-week period with a wrist-worn accelerometer. In addition, a questionnaire was used to assess sedentary time and to achieve a longitudinal PA history and intensity. Relative telomere lengths (RTL) were determined from frozen whole blood samples using a qPCR-based method. Results: Relative telomere lengths were significantly longer in women than men and negatively correlated with age in both genders (men r = -0.210, p = 0.000, women r = -0.174, and p = 0.000). During the 2-week study period, women took more steps than men (p = 0.001), but the association between steps and RTL was only seen in men (p = 0.05). Total steps taken (r = 0.202 and p = 0.04) and sedentary time (r = -0.247 and p = 0.007) significantly correlated with RTLs in 70-year old subjects. Moderate PA was associated with RTL in subjects with the highest quartile of moderate PA compared to the three lower quartiles (p-values: 0.023 between 4th and 1st, 0.04 between 4th and 2nd, and 0.027 between 4th and 3rd) in the 70-year old subjects. Conclusion: Women had longer RTL and a higher step count compared to men. However, exercise volume and RTL correlated positively only in men. Surprisingly, age correlated negatively with RTL already within an age difference of 2 years. This suggests that telomere attrition rate may accelerate in older age. Moderate physical activity at the time of study was associated with RTL.

Seasonal levels of melatonin, thyroid hormones, mood, and cognition near the Arctic Circle.

INTRODUCTION: The associations between melatonin and thyroid hormones and changes in mood and cognitive performance caused by exposure to cold and darkness were examined in 12 circumpolar residents during winter and summer. METHODS: Each participant was exposed to three different experimental conditions in random order: 1) 22 degrees C and bright light; 2) 10 degrees C and bright light; and 3) 10 degrees C and dim light. The duration of each exposure was 24 h. RESULTS: Increased serum melatonin and thyrotropin were associated with decreased rectal temperature (r = -0.446 - -0.580) and increased mean skin temperature (r = 0.204-0.519). Higher serum melatonin was associated with increased vigor (r = 0.330) and decreased accuracy on simple cognitive tasks (r = -0.332 - -0.430). Increased serum free triiodothyronine (fT3) was associated with decreased negative mood scores (r = -0.365 - -0.483), decreased response time (RT) on the simple reaction time (SRT) task (r = -0.606), and decreased accuracy on the addition/subtraction task (r = -0.372). Higher serum free thyroxine was associated with decreased fatigue and anger (r = -0.409 - -0.522). Increased serum thyrotropin was associated with decreased accuracy and RT on the SRT task and decreased RT on the grammatical reasoning task (r = -0.315 - -0.415). CONCLUSIONS: Associations between serum melatonin and thyroid hormones with mood were consistent with the psychological changes associated with the polar triiodothyronine syndrome. Also, serum melatonin and thyrotropin were associated with impaired and fT3 with improved cognitive performance, supporting the decrements in cognitive performance associated with the polar triiodothyronine syndrome.

Autonomic nervous function during whole-body cold exposure before and after cold acclimation.

INTRODUCTION: Cold habituation could affect sympatho-vagal balance, which modulates cold stress responses. The study examined cardiovascular autonomic function at the sinus node level during controlled breathing and while undertaking isometric exercise during whole-body cold exposure before and after cold acclimation. METHODS: There were 10 male subjects who were exposed to control (25 degrees C) and cold (10 degrees C) environments for 2 h on 10 successive days in a laboratory. Time and frequency domain heart rate variability (HRV) in terms of root mean square of successive differences in RR intervals, total, high, and low frequency power were determined from controlled breathing at the beginning and end of cold acclimation. Heart rate and blood pressure during an isometric handgrip test (30% MVC for 3 min) were recorded at the beginning and end of cold acclimation. Catecholamines (NE and E), mean skin (Tsk), and rectal temperatures (Trect) were measured. RESULTS: Acute cold exposure increased total (36%), low (16%), and high frequency power (25%) and RMSSD (34%). Cold acclimation resulted in higher Tsk (0.6 degrees C) and lower NE (24%) response in cold. The cold-induced elevation in high frequency power became significant after cold acclimation, while other HRV parameters remained unchanged. A smaller increase in heart rate and blood pressure occurred at 10 degrees C during the handgrip test after cold acclimation. DISCUSSION: Cold exposure increased sympathetic activity, which was blunted after cold acclimation. Parasympathetic activity showed a minor increase in cold, which was enhanced after cold acclimation. In conclusion, cold habituation lowers sympathetic activation and causes a shift toward increased parasympathetic activity.

Plasma Orexin-A Levels Do Not Undergo Circadian Rhythm in Young Healthy Male Subjects.

Orexin-A (OXA) has been originally isolated from a precursor peptide prepro-orexin from the lateral hypothalamus. The orexin system has been attributed to important functions in sleep, arousal and regulation of energy homeostasis. In addition to its high levels in cerebrospinal fluid, OXA is present in blood. However, reported peptide concentrations in plasma vary significantly depending on the method used. Therefore, a specific and sensitive OXA radioimmunoassay (RIA) with solid phase extraction method was developed to determine whether plasma OXA concentrations is affected by acute feeding and/or wake and sleep in young healthy males. Blood samples were collected for 24 h from nine healthy males (aged 20-24 years; BMI 20.7-26.5) every 2 h starting at 11 a.m. Food was served at 12 p.m, 5:30 p.m, 8 p.m and 8 a.m and the sleep time was between 10 p.m and 7 a.m. Plasma samples were analyzed in addition for cortisol and melatonin levels. Blood pressure was monitored through the experimental period. OXA antibody was raised in rabbits. OXA antiserum had only minor cross-reactivity with prepro-orexin precursor (<0.001%), amino-terminal peptide (<0.001%), carboxy-terminal peptide (0.001%), and orexin-B (0.3%) with high sensitivity (0.15 pg/tube). Plasma OXA levels varied between 0.5 and 16 pg/ml in seven subjects and were undetectable (below 0.5 pg/ml) in two subjects. The OXA concentrations did not correlate to feeding nor wake/sleep, whereas cortisol, melatonin and mean arterial blood pressure presented a clear circadian rhythm in each subject. In conclusion, OXA is present in blood in low amounts and its levels do not follow autonomic nor neuroendocrine circadian rhythms. Thereby, studies examining regulatory mechanisms and influences of OXA from blood samples should interpret results very cautiously.

Effect of physical activity on pulse wave velocity in elderly subjects with normal glucose, prediabetes or Type 2 Diabetes.

Carotid-femoral pulse wave velocity ((cf)PWV) is a measure of arterial stiffness, predicting cardiovascular disease. We hypothesized that the amount of physical activity (PA) is correlated with reduced arterial stiffness in Type 2 diabetic (T2D) subjects. 570 subjects from the 1945 Oulu birth cohort were included in the analysis. (cf)PWV was determined by a non-invasive applanation tonometry. Oral glucose tolerance test was performed and LDL and HDL cholesterol analyzed. PA was registered daily with a wrist-worn acceleration meter for two weeks. (cf)PWV values in subjects with impaired glucose metabolism (IGM) and T2D were higher than in normal glycemic subjects (P < 0.001). PA, fasting and 2 h glucose and HbA1c correlated significantly with (cf)PWV, but HDL or LDL cholesterol did not. The 2 h glucose, heart rate and alcohol consumption in T2D subjects had independent effects on (cf)PWV in multiple regression analysis. T2D and IGM were significantly associated to (cf)PWV. Interestingly, lipids did not have an additional effect on (cf)PWV. Subjects walking more than 10 000 steps/day had 0.2 m/s lower (cf)PWV than those walking less than 6000 steps/day. Presence of T2D, elevated heart rate and alcohol consumption in males were associated with increased aortic stiffening in elderly subjects.

Effect of impact exercise and its intensity on bone geometry at weight-bearing tibia and femur.

INTRODUCTION: Physical activity is known to enhance the mechanical competence of bone. However, information about the optimal type of exercise is limited. The aim of this study was to evaluate the contribution of jumping exercise to changes in bone geometry. METHODS: We carried out a 12-month population-based trial with 120 women (aged 35-40 years), randomly assigned to an exercise group or to a control group. The exercise regimen consisted of supervised, progressive high-impact exercises three times per week and an additional home program. The intensity of impact loading was assessed as the magnitude of acceleration peaks using an accelerometer-based body movement monitor. The activity was analyzed as the daily number of impacts within five acceleration ranges (0.3-1.0g, 1.1-2.4g, 2.5-3.8g, 3.9-5.3g and 5.4-9.2g; g=acceleration of gravity, 9.81 m/s(2)). Bone geometry was assessed with spiral quantitative computed tomography (QCT) scanner at mid-femur, proximal tibia and distal tibia. RESULTS: Thirty-nine women (65%) in the exercise group and 41 women (68%) in the control group completed the study. QCT and physical activity data were available from 65 subjects. The exercise group showed a significant 0.2% (p=0.033) higher gain in bone circumference compared to the control group at mid-femur. Subgroup analyses revealed geometric changes indicating up to a 2.5% increment in bone strength in favor of the most active exercisers (>66 exercise sessions during the 12 months) compared to the least active exercisers (<19 sessions). In pooled groups, the changes in cortical attenuation and cross-sectional moment of inertia correlated positively (p<0.05-p<0.01) with the number of impacts exceeding 1.1g, while changes in cortical thickness (p<0.05) and bone circumference (p<0.05-p<0.01) were positively associated with impacts 3.9g, or more. The number and intensity of impacts during the 12 months were the most significant predictors of changes in bone geometry explaining up to 36% of changes. CONCLUSIONS: Bone geometry adapts to impact exercise and the adaptation is most marked at the mid-femur. The changes in bone geometry are associated with the number and intensity of daily impacts while the redistribution of bone mineral appears to be the main mechanism in the skeletal adaptation to varying intensities of exercise.

Involvement of endogenous ouabain-like compound in the cardiac hypertrophic process in vivo.

The Na(+)/K(+)-ATPase inhibitor ouabain has been shown to trigger hypertrophic growth of cultured cardiomyocytes; however, the significance of endogenous ouabain-like compound (OLC) in the hypertrophic process in vivo is unknown. Here we characterized the involvement of OLC in left ventricular (LV) hypertrophy induced by norepinephrine (NE) and angiotensin II (Ang II) infusions in rats. Administration of NE (300 microg/kg/h) via subcutanously implanted osmotic minipumps for 72 h resulted in a significant increase in left ventricular weight to body weight (LVW/BW) ratio (P<0.001) and a substantial up-regulation of atrial natriuretic peptide (ANP) gene expression (13.2-fold, P<0.001). NE infusion induced a transient increase in plasma OLC levels at 12 h (P<0.05), which returned to control levels by 72 h. Adrenalectomy markedly reduced both basal and NE-induced increase in plasma OLC levels. LVW/BW ratio was not modulated by adrenalectomy; however, ANP gene expression was blunted by 44% (P<0.01) and 47% (P<0.05) at 12 and 72 h, respectively. In agreement, adrenalectomy reduced up-regulation of ANP without affecting LV mass in rats infused with Ang II (33 microg/kg/h). Administration of exogenous ouabain (1 nM to 100 microM) for 24 h had no effect on ANP gene expression in cultured neonatal rat ventricular myocytes. However, the up-regulation of ANP mRNA levels induced by the alpha-adrenergic agonist phenylephrine (1 microM) was markedly enhanced by ouabain (100 microM) (5.6-fold vs. 9.6-fold, P<0.01). These data show that OLC as an adrenal-derived factor may be required for the induction LV ANP gene expression during the hypertrophic process.