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Biomedical subjects

Juhani Leppäluoto

Publications and source records attributed to Juhani Leppäluoto.

At least 19 recordsLinked to original sources

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.

Adult↗

Urinary melatonin: a noninvasive method to follow human pineal function as studied in three experimental conditions.

The aim of this study was to examine whether urinary melatonin, rather than urinary 6-sulfatoxymelatonin (aMT6s), can be used as an indicator of diurnally and seasonally changing melatonin secretion. The subjects (n=15) spent three separate 24-hr periods in a climatic chamber during winter (n=7) and summer (n=8). Blood and urine samples were obtained during each period at 2- to 5-hr intervals. Serum melatonin and urinary melatonin and aMT6s were assayed by radioimmunoassay. The serum melatonin levels increased nearly 10-fold from low daytime to high nocturnal values. The mean nocturnal increase of urinary melatonin was 1.7-fold and that of urinary aMT6s was 4.6-fold. Both urinary melatonin and aMT6s correlated significantly with area under the curve melatonin in serum during the night, during the day and throughout the entire 24-hr observation period in all cases. The ratio between urinary melatonin and aMT6s excretion showed significant diurnal variation, being ninefold higher at 16:00 hr than at 07:00 or at 09:00 hr. The ninefold decrease in the urinary melatonin/aMT6s excretion ratio between the evening and the morning may reflect increased liver metabolism of melatonin during the night. Both urinary melatonin and aMT6s are good indicators of melatonin secretion, but the variation is significantly smaller for the former molecule.

Adult↗

Biobank research.

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Arctic Regions↗

Effect of repeated exposures to cold on cognitive performance in humans.

The effects of repeated exposure to cold temperature on cognitive performance were examined in 10 male subjects who were exposed to control (25 degrees C) and cold (10 degrees C) conditions on 10 successive days. A cognitive test battery (ANAM-ICE) was administered each day to assess complex and simple cognitive functioning accuracy, efficiency and response time. Rectal (T(rect)) and skin temperatures, thermal sensations, metabolic rate (M) and cardiovascular reactivity were also recorded. With the used cold exposure, inducing cold sensations and discomfort, superficial skin cooling (6-7 degrees C) and a slightly lowered T(rect) (0.4 degrees C) we observed three distinct patterns of cognitive performance: 1) negative, reflected in increased response times and decreased accuracy and efficiency; 2) positive, reflected in decreased response time and increased efficiency; and 3) mixed, reflected in a pattern of increases in both accuracy and response time and decreases in efficiency, and a pattern of decreases in both accuracy and response time. T(rect), thermal sensations, diastolic blood pressure (DBP) and heart rate (HR) were independent predictors of decreased accuracy, but also decreased response time. Cognitive performance efficiency was significantly improved and response times shorter over the 10-d period both under control and cold exposures suggesting a learning effect. However, the changes in cognitive performance over the 10-d period did not differ markedly between control and cold, indicating that the changes in the thermal responses did not improve performance. The results suggest that cold affects cognitive performance negatively through the mechanisms of distraction and both positively and negatively through the mechanism of arousal.

Acclimatization↗

Effect of daily physical activity on proximal femur.

BACKGROUND: The incidence of osteoporotic fractures is increasing and has become one of the major health problems in developed countries. Physical exercise has been found to be effective in the prevention of osteoporosis. However, the optimal amount of exercise is not known. The aim of this study was to examine the association between the intensity of physical activity and bone mineral density at the proximal femur, using long-term quantification of daily physical activity. METHODS: The study subjects were 64 women (age 35-40 years), who carried an accelerometer-based body movement recorder for 12 months for individual quantification of their daily physical activity. The average distribution of daily accelerations was defined using 33 acceleration levels. FINDINGS: A significant relationship between physical activity data and proximal femur bone mineral density was found. Physical activity that induced acceleration levels exceeding 3.6g correlated positively with the bone mineral density change at the proximal femur, the association being strongest at the femoral neck at 5.7 g (r = 0.416, P = 0.001). INTERPRETATION: The association between physical activity and changes in proximal femur bone mineral density was dependent on the acceleration level of exercise. The quantity and quality of exercise can be monitored with the accelerometer-based physical activity monitor, and the method might be used for optimizing exercise for prevention of osteoporosis.

Acceleration↗

The partial female to male sex reversal in Wnt-4-deficient females involves induced expression of testosterone biosynthetic genes and testosterone production, and depends on androgen action.

Wnt-4 signaling has been implicated in female development, because its absence leads to partial female to male sex reversal in the mouse. Instead of Mullerian ducts, Wnt-4-deficient females have Wolffian ducts, suggesting a role for androgens in maintaining this single-sex duct type in females. We demonstrate here that testosterone is produced by the ovary of Wnt-4-deficient female embryos and is also detected in the embryonic plasma. Consistent with this, the expression of several genes encoding enzymes in the pathway leading to the synthesis of testosterone in the mouse is induced in the Wnt-4-deficient ovary, including Cyp11a, Cyp17, Hsd3b1, Hsd17b1, and Hsd17b3. Inhibition of androgen action with an antiandrogen, flutamide, during gestation leads to complete degeneration of the Wolffian ducts in 80% of the mutant females and degeneration of the cortical layer that resembles the tunica albuginea in the masculinized ovary. However, androgen action is not involved in the sexually dimorphic organization of endothelial cells in the Wnt-4 deficient ovary, because flutamide did not change the organization of the coelomic vessel. These data imply that Wnt-4 signaling normally acts to suppress testosterone biosynthesis in the female, and that testosterone is the putative mediator of the masculinization phenotype in Wnt-4-deficient females.

17-Hydroxysteroid Dehydrogenases↗

Gonadotropin-induced adrenocortical neoplasia in NU/J nude mice.

In response to prepubertal gonadectomy certain inbred mouse strains, including DBA/2J, develop sex steroid-producing adrenocortical neoplasms. This phenomenon has been attributed to a lack of gonadal hormones or a compensatory increase in gonadotropins. To assess the relative importance of these mechanisms, we created a new inbred model of adrenocortical neoplasia using female NU/J nude mice. These mice developed adrenocortical neoplasms in response to either gonadectomy or gonadotropin elevation from xenografts of human chorionic gonadotropin (hCG)-secreting Chinese hamster ovary cells. In each instance the adrenal tumors resembled the neoplasms found in gonadectomized DBA/2J mice and were composed of spindle-shaped A cells and lipid-laden B cells. Both cell populations were defined by ectopic expression of GATA-4 and an absence of the adrenocortical markers melanocortin-2-receptor and steroid 21-hydroxylase, but only B cells expressed the gonadal steroidogenic markers inhibin-alpha, LH receptor, P450c17, and P450c19. Expression of sex steroidogenic markers was attenuated in the neoplastic adrenal cortex of hCG-treated vs. gonadectomized mice. Whereas neoplastic adrenals were an obvious source of estradiol in gonadectomized mice, ovaries appeared to be the major source of this hormone in hCG-treated mice. Gonadectomy and hCG treatment elicited comparable increases in serum estradiol, but testosterone levels increased significantly only in hCG-treated mice. We conclude that chronic gonadotropin elevation, caused by either gonadectomy or hCG administration, signals a population of cells in the adrenal subcapsular region of permissive mice to undergo differentiation along a gonadal rather than an adrenal lineage. Thus, NU/J nude mice can be used as a model to study both neoplasia and adrenogonadal lineage specification.

Adrenal Cortex↗

Single assay for amino-terminal fragments of cardiac A- and B-type natriuretic peptides.

BACKGROUND: High circulating concentrations of N-terminal fragments of A- and B-type natriuretic peptides (NT-proANP and NT-proBNP) identify patients with impaired cardiac function. ProANP-derived peptides are particularly sensitive to increased preload of the heart and proBNP-derived peptides to increased afterload; therefore, combining the information from the ANP and BNP systems into a single analyte could produce an assay with increased diagnostic and prognostic power. METHODS: We prepared a hybrid peptide containing peptide sequences from both NT-proBNP and NT-proANP (referred to as NT-proXNP) by recombinant techniques and used it to develop a RIA combining weighed concentrations of NT-proANP and NT-proBNP into a new virtual analyte, NT-proXNP. We used the novel method to measure the circulating concentrations in healthy persons and in patients with cardiac disorders. We also characterized the assay by HPLC analysis of the immunoreactive molecular forms in human plasma and serum. RESULTS: The results from the novel assay correlated well with independent home-made NT-proANP and NT-proBNP assays (r2 = 0.75-0.85) as well with the arithmetic sum of NT-proANP and NT-proBNP (r2 = 0.92). Patients with valvular heart disease (VHD) and coronary artery disease (CAD) had significantly increased NT-proXNP concentrations. The areas under the curve (AUC) of the NT-proXNP assay in detecting VHD and CAD (0.961 and 0.924, respectively) were significantly larger than the AUC of either NT-proANP (0.947 and 0.872) or NT-proBNP (0.913 and 0.782) assays. HPLC analysis showed that the novel NT-proXNP assay detects two major classes of circulating immunoreactivity corresponding to peptides derived from NT-proANP and NT-proBNP. CONCLUSIONS: Our novel immunoassay mimics the physiologic signaling system working in the body by converging the information obtained from the activation of ANP and BNP into a single virtual analyte, NT-proXNP. It appears to have a diagnostic efficiency equal to or slightly better than that of individual NT-proANP or NT-proBNP assays.

Adult↗

The expression of MT1 and MT2 melatonin receptor mRNA in several rat tissues.

The mechanisms that mediate the various effects of melatonin in mammalian tissues are not always known. Therefore, the aim of this study was to investigate whether MT(1) and MT(2) melatonin receptors are expressed in certain tissues of the rat. The expression of MT(1) and MT(2) melatonin receptor mRNA was determined using a real-time quantitative RT-PCR method. In addition, we examined whether mRNA for either subtype of receptor shows any difference in the expression between midnight and noon, similar to the changes in melatonin concentrations in plasma and tissue samples. MT(1) and MT(2) melatonin receptor mRNAs were found in the rat hypothalamus, retina and small intestine. We also showed a low expression of MT(2) mRNA in the rat liver and heart SA node. In the heart apex and the Harderian gland, no appearance of either of the receptor mRNAs was detectable. A significant difference in the expression of MT(1) mRNA between day and night was found in the hypothalamus. In conclusion, our findings suggest that at least some effects of melatonin are mediated through membrane MT(1) and MT(2) receptors in the hypothalamus, the retina and the small intestine. Down-regulation of receptors might be one reason for the difference in the hypothalamic MT(1) melatonin receptor mRNA expression between midnight and noon. In the liver and the heart SA node, the physiological significance of possible MT(2) receptors remains unclear. According to our negative midnight and noon results in the Harderian gland and heart apex melatonin may exert its effect on these tissues by a non-receptor mechanism.

Animals↗

Influence of seasonally adjusted exposure to cold and darkness on cognitive performance in circumpolar residents.

The effects of seasonally adjusted 24-h exposure to cold and darkness on cognitive performance in urban circumpolar residents was assessed in 15 male subjects who spent three 24-h periods in a climatic chamber at 65 degrees latitude during the winter (January-March) and/or summer (August-September). Each subject was exposed to three different environmental conditions in random order: (1) 22 degrees C temperature and 500 lx lighting; (2) 10 degrees C temperature and 500 lx lighting; and (3) 10 degrees C temperature and 0.5-l lx lighting. Accuracy on an addition-subtraction task was significantly greater in the summer than in the winter (p= 0.038), while accuracy on a repeated acquisition task was significantly greater in the winter than in the summer (p < 0.001). Independent of season, exposure to cold and darkness was significantly associated with a decline in response time on five cognitive tests, an improvement in accuracy on three tests measuring complex cognitive tasks, and a decline in accuracy on two tests measuring simple tasks. Increased performance on complex tasks may result from increased arousal in response to the combination of cold temperatures and dim light characteristic of the winter in urban circumpolar settings.

Adult↗

Postural sway during single and repeated cold exposures.

INTRODUCTION: Tissue cooling changes sensory and neuromuscular functions that are also involved in postural control. The purpose of the study was to determine how acute and repeated exposures to cold affect whole body postural control. METHODS: Postural sway was measured from 10 subjects during standing with eyes open (EO) and closed (EC) using an inclinometer-based method. Sway was assessed at at 10 degrees C on 10 consecutive days and at 25 degrees C on days 1, 5, and 10. Sway path length, area, velocity, side-to-side and forward-backward movement were assessed. At the same time, rectal and skin temperatures, muscle tonus/ shivering, thermal sensations, and comfort were recorded. RESULTS: Acute exposure to 10 degrees C caused thermal discomfort, significantly lowered (26.1-26.5 degrees C) mean skin temperatures, slightly lowered rectal temperature (36.7 degrees C) and increased (140-260%) muscle tone, increased sway path length (67-87%, p < 0.05), velocity (63-71%, p < 0.05), total sway area (42-67%, p < 0.05), and forward-backward movement (35-57%, p < 0.05) compared with 25 degrees C. Side-to-side movements were not altered in the cold. Postural sway increased with EC, and further when exposed to cold, but the effect of cold was smaller compared with EO. Repeated exposures over the 10-d period decreased sway 10-40% both at 25 degrees C and at 10 degrees C (p < 0.05-0.01), suggesting motor learning. The difference in sway between 25 degrees C and 10 micro C remained the same throughout the 10-d period, suggesting that the observed cold habituation responses do not affect sway. CONCLUSIONS: The results demonstrate that postural control is impaired in cold, which may affect physical performance in cold environmental conditions.

Adult↗

Thermal sensation and comfort in women exposed repeatedly to whole-body cryotherapy and winter swimming in ice-cold water.

Whole-body cryotherapy (WBC; -110 degrees C) and winter swimming (WS) in ice-cold water are severe ambient cold exposures, which are voluntarily practiced by humans in minimal clothing. The purpose was to examine thermal sensation and thermal comfort associated with WBC and WS. Twenty women similar in body mass index, age, physical activity, and use of hormonal contraception were pairwise randomized either to the WBC group or the WS group. The duration of each WBC exposure was 2 min, which was repeated three times per week for 3 months (13 weeks). Similar exposure frequency was used for the WS group, but each exposure lasted 20 s in outdoor conditions. Thermal sensation and comfort were asked with standard scales. After WBC, 65% of the thermal sensation votes were 'neutral' or 'slightly cool.' After WS, 81% of the thermal sensation votes were 'warm,' 'neutral,' or 'slightly cool.' Majority of comfort votes immediately after exposures in WBC group (98%) and in the WS group (93%) were 'comfortable' or 'slightly uncomfortable.' Thermal sensation and comfort became habituated in both groups at an early stage of trials, but the changes were less conclusive in WS group due to variable conditions outdoors. In the WBC group, cold sensation was less intense already after the second exposure. In conclusion, repeated exposures to WBC and WS in healthy women were mostly well tolerated and comfortable. The results indicate that during repeated severe whole-body cold stress of short duration, thermal sensation and comfort become habituated during the first exposures.

Adult↗

Molecular heterogeneity has a major impact on the measurement of circulating N-terminal fragments of A- and B-type natriuretic peptides.

BACKGROUND: The N-terminal fragments of A- and B-type natriuretic peptides (NT-proANP and NT-proBNP) are powerful markers of cardiac function. The current assays require refinement with regard to standardization with native calibrators and the ability to detect the actual circulating forms. METHODS: The following peptides were prepared with recombinant methods: NT-proANP, NT-proBNP, proBNP1-108, and Tyr0-proBNP77-108. Fifteen peptides of 13-22 amino acids, spanning the sequences of NT-proANP and NT-proBNP, were prepared by solid-phase peptide synthesis. Two immunoassays for NT-proANP and four for NT-proBNP were set up, each with a different epitope specificity. The assays were applied for the measurement of NT-proANP and NT-proBNP in healthy individuals and in patients with acute myocardial infarction. The circulating molecular forms were analyzed by gel-filtration and reversed-phase HPLC. RESULTS: According to the HPLC analyses, circulating NT-proANP consists mainly of the full-length peptide, with some degradation at both ends. In contrast, circulating NT-proBNP is very heterogeneous. Most immunoreactive NT-proBNP is significantly smaller in size than NT-proBNP1-76, with truncation at both termini. The smallest fragments can be detected by assays directed at the central part of NT-proBNP only; assays directed at the ends gave 30-40% lower values. Despite the difference, the various assays correlated reasonably well with each other (r2 = 0.77-0.85). In patients with acute myocardial infarction, NT-proANP and NT-proBNP concentrations were 1.8-2.3 and 4.2-4.5 times higher than in healthy individuals. The development of heart failure further increased the concentrations. CONCLUSIONS: Molecular heterogeneity of the circulating forms causes a serious risk of preanalytical errors in assays for NT-proBNP and, to a lesser extent, NT-proANP. The development of a sandwich assay for NT-proBNP would be especially challenging. The most robust and reliable assays use antibodies directed at the central portions of NT-proANP or NT-proBNP.

Adult↗

Effects of high-impact exercise on bone mineral density: a randomized controlled trial in premenopausal women.

INTRODUCTION: The purpose of this randomized controlled study was to assess the effects of high-impact exercise on the bone mineral density (BMD) of premenopausal women at the population level. MATERIALS AND METHODS: The study population consisted of a random population-based sample of 120 women from a cohort of 5,161 women, aged 35 to 40 years. They were randomly assigned to either an exercise or control group. The exercise regimen consisted of supervised, progressive high-impact exercises three times per week and an additional home program for 12 months. BMD was measured on the lumbar spine (L1-L4), proximal femur, and distal forearm, by dual-energy X-ray absorptiometry at baseline and after 12 months. Calcaneal bone was measured using quantitative ultrasound. RESULTS: Thirty-nine women (65%) in the exercise group and 41 women (68%) in the control group completed the study. The exercise group demonstrated significant change compared with the control group in femoral neck BMD (1.1% vs -0.4%; p=0.003), intertrochanteric BMD (0.8% vs -0.2%; p=0.029), and total femoral BMD (0.1% vs -0.3%; p=0.006). No exercise-induced effects were found in the total lumbar BMD or in the lumbar vertebrae L2-L4. Instead, L1 BMD (2.2% vs -0.4%; p=0.002) increased significantly more in the exercise group than in the control group. Calcaneal broadband ultrasound attenuation showed also a significant change in the exercise group compared with the control group (7.3% vs -0.6%; p=0.015). The changes were also significant within the exercise group, but not within the control group. There were no significant differences between or within the groups in the distal forearm. CONCLUSIONS: This study indicates that high-impact exercise is effective in improving bone mineral density in the lumbar spine and upper femur in premenopausal women, and the results of the study may be generalized at the population level. This type of training may be an efficient, safe, and inexpensive way to prevent osteoporosis later in life.

Adult↗

Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era.

OBJECTIVES: This prospective study tested whether the natriuretic peptides predict cardiac death among patients using beta-blocking therapy after an acute myocardial infarction (AMI). BACKGROUND: Natriuretic peptides have provided prognostic information after AMI, but their predictive value has not been well established in the era of beta-blocker use. METHODS: A series of 521 patients (mean age 61 +/- 10 years) with AMI was included in the study. The end points were total mortality and non-sudden and sudden cardiac death (SCD). Plasma concentrations of atrial natriuretic peptide (ANP), N-terminal atrial natriuretic propeptide (N-ANP), brain natriuretic peptide (BNP), and ejection fraction (EF) were analyzed before hospital discharge. The cardiac medication was optimized (e.g., adherence to beta-blocking therapy was 97% at discharge and 95% at one year after AMI). RESULTS: During a mean follow-up of 43 +/- 13 months, total mortality was 11.5% (60/521), cardiac mortality was 6.3% (33/521), and 3.1% (16/521) experienced SCD. On univariate analysis, high levels of all measured peptides and low EF predicted the occurrence of non-SCD (p < 0.001 for all). Peptides and EF also predicted the occurrence of SCD (p < 0.05), with elevated BNP (>23.0 pmol/l) being the most powerful predictor (hazard ratio [HR] 4.4, 95% confidence interval [CI] 1.4 to 13.8; p = 0.01). After adjusting for clinical variables, only elevated BNP (HR 3.9, 95% CI 1.2 to 12.3, p = 0.02) and low EF (<40%) (p = 0.03) remained as significant predictors of SCD. CONCLUSIONS: Natriuretic peptides retain their prognostic value in the beta-blocking era among survivors of AMI. Elevated BNP provides information on the risk of subsequent SCD, independent of clinical variables and left ventricular EF.

Adrenergic beta-Antagonists↗

Seasonal changes in thermal responses of urban residents to cold exposure.

To determine whether urban circumpolar residents show seasonal acclimatisation to cold, thermoregulatory responses and thermal perception during cold exposure were examined in young men during January-March (n=7) and August-September (n=8). Subjects were exposed for 24 h to 22 and to 10 degrees C. Rectal (T(rect)) and skin temperatures were measured throughout the exposure. Oxygen consumption (VO(2)), finger skin blood flow (Q(f)), shivering and cold (CDT) and warm detection thresholds (WDT) were assessed four times during the exposure. Ratings of thermal sensations, comfort and tolerance were recorded using subjective judgement scales at 1-h intervals. During winter, subjects had a significantly higher mean skin temperature at both 22 and 10 degrees C compared with summer. However, skin temperatures decreased more at 10 degrees C in winter and remained higher only in the trunk. Finger skin temperature was higher at 22 degrees C, but lower at 10 degrees C in the winter suggesting an enhanced cold-induced vasoconstriction. Similarly, Q(f) decreased more in winter. The cold detection threshold of the hand was shifted to a lower level in the cold, and more substantially in the winter, which was related to lower skin temperatures in winter. Thermal sensations showed only slight seasonal variation. The observed seasonal differences in thermal responses suggest increased preservation of heat especially in the peripheral areas in winter. Blunted vasomotor and skin temperature responses, which are typical for habituation to cold, were not observed in winter. Instead, the responses in winter resemble aggravated reactions of non-cold acclimatised subjects.

Adult↗