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.

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.

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.

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.

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.

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.

Low level activity thresholds for changes in NMR biomarkers and genes in high risk subjects for Type 2 Diabetes.

Our objectives were to determine if there are quantitative associations between amounts and intensities of physical activities (PA) on NMR biomarkers and changes in skeletal muscle gene expressions in subjects with high risk for type 2 diabetes (T2D) performing a 3-month PA intervention. We found that PA was associated with beneficial biomarker changes in a factor containing several VLDL and HDL subclasses and lipids in principal component analysis (P = <0.01). Division of PA into quartiles demonstrated significant changes in NMR biomarkers in the 2nd - 4th quartiles compared to the 1st quartile representing PA of less than 2850 daily steps (P = 0.0036). Mediation analysis of PA-related reductions in lipoproteins showed that the effects of PA was 4-15 times greater than those of body weight or fat mass reductions. In a subset study in highly active subjects' gene expressions of oxidative fiber markers, Apo D, and G0/G1 Switch Gene 2, controlling insulin signaling and glucose metabolism were significantly increased. Slow walking at speeds of 2-3 km/h exceeding 2895 steps/day attenuated several circulating lipoprotein lipids. The effects were mediated rather by PA than body weight or fat loss. Thus, lower thresholds for PA may exist for long term prevention of cardio-metabolic diseases in sedentary overweight subjects.

Urinary thrombomodulin and catecholamine levels are interrelated in healthy volunteers immersed in cold and warm water.

Severe hypothermia has been shown to influence the levels of catecholamines and thrombomodulin, an endothelial protein essentially involved in the regulation of haemostasis and inflammation. A link between thrombomodulin and catecholamines during cold exposure has also been previously suggested. The aim of this study was to assess the influence of short-term cold exposure without hypothermia on catecholamines and the circulating and urinary thrombomodulin levels. Seven healthy male subjects were immersed in cold water (+10°C) for 10 minutes followed by a 20-minute immersion in +28°C water. Warm water immersion was performed separately for each subject (+30°C for 30 minutes). Thrombomodulin and catecholamine concentrations were measured from pre- and post-immersion (up to 23 hours) samples. In urine, the thrombomodulin level correlated strongly with adrenaline (ρ = 0.806) and noradrenaline (ρ = 0.760) levels. There were no significant differences in thrombomodulin levels between immersion temperatures. Post-immersion urinary thrombomodulin levels were significantly lower than the pre-immersion level at both immersion temperatures. Median concentrations of plasma noradrenaline and urinary adrenaline were higher after exposure to +10°C than to +30°C. Thus, further evidence of the association between thrombomodulin and catecholamines was gained in a physiologically relevant setting in humans. Additionally, it is evident that a short-term cold exposure was not able to elicit changes in the thrombomodulin levels in a follow-up period of up to 23 hours. These findings provide further understanding of the physiological responses to cold during immersion, and of the potential influence of stress on haemostatic and inflammatory responses.

The effects of group and single housing and automated animal monitoring on urinary corticosterone levels in male C57BL/6 mice.

Mice are used extensively in physiological research. Automated home-cage systems have been developed to study single-housed animals. Increased stress by different housing conditions might affect greatly the results when investigating metabolic responses. Urinary corticosteroid concentration is considered as a stress marker. The aim of the study was to compare the effects of different housing conditions and an automated home-cage system with indirect calorimetry located in an environmental chamber on corticosterone levels in mice. Male mice were housed in different conditions and in automated home-cage system to evaluate the effects of housing and measuring conditions on urine corticosterone levels. Corticosterone levels in single-housed mice in the laboratory animal center were consistently lower compared with the group-housed mice. Single-housed mice in a separate, small animal unit showed a rise in their corticosterone levels a day after they were separated to their individual cages, which decreased during the following 2 days. The corticosterone levels of group-housed mice in the same unit were increased during the first 7 days and then decreased. On day 7, the corticosterone concentrations of group-housed mice were significantly higher compared with that of single-housed mice, including the metabolic measurement protocol. In conclusion, single housing caused less stress when compared with group-housed mice. In addition, the urine corticosterone levels were decreased in single-housed mice before the metabolic measurement started. Thus, stress does not affect the results when utilizing the automated system for measuring metabolic parameters like food and water intake and calorimetry.

Transcranial bright light exposure via ear canals does not suppress nocturnal melatonin in healthy adults--a single-blind, sham-controlled, crossover trial.

We investigated whether transcranial bright light (TBL) affects nocturnal melatonin and cortisol secretion in sham-controlled crossover trial. Young healthy adults were exposed in random order to 24 minutes of TBL or sham exposure via ear canals at 01:10 h. Saliva and urine samples were collected hourly between 21 h-03 h and 06 h-09 h. There were no significant differences in melatonin or cortisol concentrations between TBL and sham exposures at any sampling point indicating that TBL via ear canals does not suppress nocturnal melatonin secretion. Thus, non-visual effects of TBL are mediated via a pathway not involving melatonin suppression.

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.

Endogenous Na/K ATPase inhibitor ouabain in critically ill children with lung injury.

OBJECTIVES: To measure ouabain, an endogenous adrenocortical Na/K ATPase inhibitor, in critically ill children with acute lung injury and relate it to parameters reflecting epithelial sodium transport. DESIGN: Prospective observational study. SETTING: Paediatric Intensive Care Unit of Royal Liverpool Children's Hospital. SUBJECTS: Consecutive children ventilated on a Paediatric Intensive Care Unit. MEASUREMENTS AND MAIN RESULTS: 27 patients were recruited including 11 children with septicemia, 5 patients with localized infections, and 11 patients ventilated for non-infective causes like elective surgery and head injury. Median age of included patients was 5 years (range 1.1-15.5 years). 17 patients had lung injury with radiological evidence of pulmonary edema and/or a paO(2)/FiO(2) ratio of <300 on admission. Ouabain levels were measured in peripheral blood by radioimmunoassay on admission and correlated with sweat sodium levels and renal sodium excretion, paO(2)/FiO(2) ratio and analysis of a chest X-ray on admission. Ouabain levels in all patients had a mean of 23.6pmol/l (SD 13.3, range 10.2-58.2). Ouabain levels were higher in male patients versus female. Children with radiological evidence of septicemia related pulmonary edema, ventilation requirements indicating lung injury or inotrope requirements did not have significantly different ouabain levels compared to patients without lung injury or not on inotropes. There was no significant correlation between sweat sodium or renal sodium excretion and ouabain levels (p=0.91 and p=0.19 respectively). CONCLUSIONS: Ouabain levels in children ventilated on a Paediatric Intensive Care Unit were not different in patients with lung injury or inotrope requirements. Quabain levels did not relate to parameters reflecting epithelial sodium transport in sweat gland or kidney.

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.

Plasma levels of heat shock protein 72 (HSP72) and beta-endorphin as indicators of stress, pain and prognosis in horses with colic.

A prospective observational study was performed to evaluate whether the plasma concentration of heat shock protein 72 (HSP72) or beta-endorphin is related to clinical signs, blood chemistry, or severity of pain of colic. Seventy-seven horses with colic and 15 clinically healthy controls were studied. The horses were divided into four groups which reflected increasing severity of colic, from normal control horses to horses with mild, moderate and severe colic. Blood samples were collected before any treatment. Packed cell volume (PCV) and plasma HSP72, beta-endorphin, cortisol, adrenocorticotropic hormone (ACTH) and lactate concentrations were measured. Plasma beta-endorphin was related with severity of colic and survival, as well as with plasma cortisol, ACTH and lactate concentrations, heart rate, PCV and pain score. High plasma HSP72 concentration may indicate circulatory deficits, but was not associated with clinical signs of colic. Plasma lactate still seemed to be the most useful single prognostic parameter in horses with colic.