Chemical versus dual energy x-ray absorptiometry for detecting age-associated body compositional changes in male rats

Aging is associated with increases in body mass and fat mass (FM), whereas fat-free mass (FFM) either decreases or remains unchanged. The purpose of this study was to determine whether dual-energy X-ray absorptiometry (DXA) accurately detects age-associated changes in male Fischer 344 x Brown-Norway rats ages 8, 18, and 28 months. Eviscerated animal carcasses were first examined via the Lunar DPX-IQ DXA (small animal software version 1.0; HiRes (0.6 x 1.2 mm) medium mode). Eviscerated carcasses were then weighed, autoclaved, homogenized, and fat isolated from aliquots of homogenate via methanol/chloroform extraction. In both chemical (CHEM) and DXA analysis, carcass mass (CM), FM, and % fat were significantly higher (P < 0.0001) in the 18 and 28 versus 8-month-old rats. CHEM showed greater FFM in the 18 versus 8 months-old rats but not the 28 months-old animals. DXA was unable to detect the age-associated changes in FFM. Regression analysis showed a strong correlation between CHEM and DXA methods for CM (r = 0.98, P < 0.0001) and FM (r = 0.97, P < 0.0001), but less strong for FFM (r = 0.59, P = 0.0002). In conclusion, compared to CHEM, DXA consistently overestimated CM and FM across the age groups by 9% and 77%, respectively, and underestimated FFM by 5%.     

Age-related changes in the diurnal rhythm of serotonin turnover in microdissected brain areas of estradiol-treated ovariectomized rats

The purpose of this study was to determine whether 1) a diurnal rhythm in serotonin turnover is present in specific hypothalamic nuclei of middle-aged ovariectomized rats and 2) in middle-aged animals exposure to estrogen can induce the pattern of serotonin dynamics which appears necessary for the occurrence of an LH surge in young rats. Young (3-4 month old) and middle-aged (8-10 month old) rats which demonstrated estrous cyclicity were bilaterally ovariectomized. Seven days later half of the young and middle-aged animals received Silastic estradiol capsules. On day 9 post ovariectomy the groups were again divided; half of the rats in each group were killed at 0800, 1200, 1800, and 2400 h. Remaining animals were treated with pargyline (75 mg/kg BW, ip) at these times and were killed 10 min later, and the following brain areas were microdissected and analyzed for serotonin (5HT) and 5-hydroxyindole acetic acid: median eminence (ME), suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), arcuate nucleus (AN), and globus pallidus. In young ovariectomized rats the SCN, MPN, and AN exhibited a diurnal rhythm in 5HT activity which was high during the light hours and low during the dark. The diurnal rhythm could not be detected in any hypothalamic nuclei of ovariectomized middle-aged animals. The loss in the circadian component of 5HT activity is not due to a loss in serotonergic function, since overall turnover rates were not reduced compared to young animals. Estrogen treatment modified the diurnal pattern of 5HT activity in the SCN, MPN, and AN in young rats but had no effect in the middle-aged rats. In young rats, estrogen induced a transitory rise in ME-5HT turnover at 1200 h, just before the expected onset of the LH surge. In middle-aged animals the increase in ME-5HT turnover did not occur until 1800 h and correlates with a delay in the initiation of the estradiol-induced LH surge. We conclude that: 1) there is a loss in the rhythm of 5HT activity in middle-aged rats and 2) the diurnal rhythmicity of 5HT turnover may be necessary for the maintenance of normal cyclic release of LH.     

Absence of ultradian rhythm or diurnal variation in insulin-like growth factor-I in rats

We studied the variation in plasma insulin-like growth factor-I (IGF-I) concentrations in unrestrained, cannulated rats. To detect rapid changes, 6 rats were sampled every 15 min for 6 h. Plasma was assayed for growth hormone (GH), and for IGF-I before and after acid-ethanol (AE) extraction to reduce the masking effect of plasma binding proteins. AE increased the immunoreactivity of freshly collected rat serum and heparinized plasma by 3-fold, but had no effect on serum after 4 weeks of storage at -20 degrees C. In contrast, heparinized plasma maintained its sensitivity to AE for many months after collection. AE-extracted serum was identical in potency to serum that was subjected to acid gel chromatography. GH showed high amplitude, synchronized pulses every 3.3 +/- 0.15 h. Despite variations in IGF-I concentrations that resembled pulsations, when the data from both unextracted and AE-extracted plasma were subjected to 2 computer algorithms designed to detect hormone pulses, no pulses were identified in 8 of the 24 series of analyses. The two programs concurred only 4 times in their identification of a pulse in unextracted plasma, and in only one instance was a pulse identified in both unextracted and AE-extracted plasma from a given sample. Based on repeated measurements of a single serum sample, the program of Santen and Bardin (S&B) had a false-positive rate of 11%, and that of Merriam and Wachter (M&W) less than 10%. There was no positive correlation between summed GH and IGF-I concentrations over the 6 h of sampling, or after a 1- or 2-hour lag period. To detect diurnal variations, a second group of 5 rats was sampled every 2 h for 36 h. These animals showed little fluctuation of IGF-I concentrations and no differences between the light and dark periods. Our studies provide no evidence for episodic release of IGF-I or diurnal variations entrained to light or feeding cycles.     

Altered diurnal rhythm of prolactin in systemic sclerosis

OBJECTIVE: Mild hyperprolactinemia has been reported in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). We investigated whether the elevated serum level of prolactin (Prl) detected in SSc is due to a sustained increase over 24 h and/or a shift in the diurnal rhythm, and whether Prl autoantibodies--originally described in SLE--may interfere in the assay. METHODS: The serum level of Prl was measured by ELISA and compared between 73 patients with SSc and 73 age and sex matched controls (78% women, age 56 +/- 11 years). The diurnal rhythms of Prl and thyrotropin (thyroid stimulating hormone, TSH) were compared between 3 patients with SSc and 10 healthy controls. Blood was taken at 2-3, 6-7, 10-11 a.m., and 2-3, 6-7, 10-11 p.m. The serum level of Prl autoantibodies was measured by ELISA and compared between matched patients with SSc and SLE and controls (n = 42 each). Standard curves of the Prl ELISA were spiked with 10% sera containing high levels of Prl autoantibodies to test interference. RESULTS: Serum levels of Prl measured in the morning (8-10 a.m.) were significantly higher in patients with SSc (17.9 +/- 7.7 ng/ml), compared with controls (9.3 +/- 4.2 ng/ml; p < 0.05). In SSc, 40% of patients had Prl levels > 20 ng/ml, but no correlation was found with Scl-70 or Prl autoantibodies. Younger patients (< 50 years, n = 23/73) showed higher serum levels of Prl than older patients (21.3 +/- 10.3 vs 16.3 +/- 6.2 ng/ml; p < 0.05). The diurnal rhythm of Prl revealed that both a sustained increase over 24 h and some shift occurred in SSc. Peaks of secretion were detected between 6 and 11 a.m., instead of 2-6 a.m. The median levels of TSH over 24 h in patients with SSc ranged within the normal limits. Nevertheless, in SSc, a significant correlation (r = 0.59, p < 0.01) was found between diurnal rhythms of Prl and TSH. The prevalence of Prl autoantibodies in serum was 8% in SSc, 27% in SLE, and < 5% in controls. However, the presence of Prl autoantibodies did not interfere with our assay. CONCLUSION: Our data confirm that mild hyperprolactinemia occurs in a subgroup of patients with SSc, and showed that the elevated serum level of Prl is due to both a sustained increase over 24 h and a shift in the diurnal rhythm. The correlation between diurnal rhythms of Prl and TSH suggests common regulatory mechanisms.     

Structural and physiological age-associated changes in aging lungs

The tissues of the lungs undergo changes with age that lead to an increase in alveolar size without any destruction of alveolar walls. This lowers the alveolar surface tension and so reduces the elastic recoil of the lungs, which in turn causes a reduction in maximum achievable flow in the airways during the breathing cycle. Muscle performance diminishes with age and the chest wall becomes stiffer, which together lead to an increased residual volume and also counter the possible increase in total lung capacity (TLC) from the reduced elastic recoil. Exercise performance falls with age, with a small decrease in arterial oxygenation that stabilizes over the age of 70 years. Predicting lung function for the elderly is not easy, and basing clinical decisions on percent of predicted may lead to age, sex, and height bias. Focusing on what function remains can allow survival predictions to guide decisions on treatment options.     

The effect of ziprasidone on body weight and energy expenditure in female rats

Ziprasidone, a novel antipsychotic agent with a unique receptor-binding profile, has been reported to have lower propensity for weight gain compared with other atypical antipsychotics. Here, we examined the effects of ziprasidone on resting energy expenditure, physical activity, thermogenesis, food intake, and weight gain in female Sprague-Dawley rats. Ziprasidone (20 mg/kg) or vehicle was administered once daily for 7 weeks; and body weight, food intake, resting energy expenditure, locomotor activity, colonic temperature on cold exposure, and abdominal fat were measured. Compared with control animals, ziprasidone-treated rats gained significantly less weight (P = .031), had a lower level of physical activity (P = .016), showed a higher resting energy expenditure (P < .001), and displayed a greater capacity for thermogenesis when subjected to cold (P < .001). In addition, ziprasidone-treated rats had a lower level of abdominal fat than did controls, although the difference was not significant. Ziprasidone had no effect on food intake. Our results indicate that, in female Sprague-Dawley rats, a 7-week treatment regimen of ziprasidone induces a significant decrease in weight gain by increasing resting energy expenditure without decreasing food intake and even with a lower level of physical activity. Further studies are needed to elucidate the precise mechanism of lower propensity of weight gain of ziprasidone.     

Effects of estradiol on the diurnal rhythm of serotonin activity in microdissected brain areas of ovariectomized rats

The purpose of these studies was to determine whether diurnal rhythms in serotonin (5HT) activity are detectable in individual hypothalamic nuclei of ovariectomized rats and whether estradiol induces specific rhythms of 5HT which may be necessary to cyclic release of LH and/or PRL. Young (3- to 4-month old) rats were bilaterally ovariectomized and 7 days later half the animals received Silastic estradiol capsules. Two days later groups were again divided: half the animals in each group were killed at 0800, 1200, 1800, and 2400 h. The remaining animals received pargyline (75 mg/kg body weight, ip) at these times and were killed 10 min later. The median eminence (ME), suprachiasmatic nucleus (SCN), medial preoptic area (MPN), arcuate nucleus (AN), and globus pallidus (GP) were microdissected and assayed for 5HT by HPLC using electrochemical detection. A diurnal rhythm in 5HT turnover was found in the SCN, MPN, and AN of ovariectomized rats. 5HT turnover in these areas was significantly higher during the light hours (0800, 1200, and 1800 h) compared to the dark phase (2400 h). The ME and GP of ovariectomized rats did not exhibit a diurnal rhythm in 5HT activity. Exposure to estrogen altered the pattern of 5HT activity in all hypothalamic areas examined. In the ME, treatment with estradiol increased 5HT turnover at 1200 h, just before the predicted LH and PRL surge, and suppressed activity at all other times. In the SCN, estradiol reversed the 5HT rhythm: turnover was low during the light hours and high during the dark. In the AN and MPN, estradiol treatment increased 5HT activity and abolished the diurnal rhythm. 5HT activity in the GP was not altered by exposure to estrogen. We conclude from these data that specific brain nuclei exhibit diurnal rhythms in 5HT turnover and that the patterns of 5HT activity in specific hypothalamic nuclei exhibit individual and unique responses to the presence of estrogen. These data suggest that the estradiol-induced diurnal pattern of 5HT activity may be necessary for the induction of cyclic release of LH and/or PRL.     

A diurnal melatonin rhythm in primate cerebrospinal fluid.

Melatonin was measured in cerebrospinal fluid (CSF) withdrawn continuously from partially restrained rhesys monkeys. There was a daily rhythm in CSF melatonin with peak night values 2- to greater than 15-fold higher than day values. The increase occurred shortly after lights were turned off, and the decrease occurred soon after lights were turned on. There was substantial variation in the magnitude of the rhythm among animals. However, there was little day to day variation in the rhythm of individual animals studied for 3 or 6 consecutive days. Although the concentration of melatonin in CSF was lower than that in plasma, the changes in CSF melatonin concentrations seemed to reflect large daily changes in plasma melatonin concentrations.     

Skin temperature and energy expenditure

The value of mean skin temperature as an estimate of energy expenditure was verified in a sample of 10 normal-weight adult male subjects. Measurements were carried out with thermometric probes under conditions of rest and environmental thermoneutrality. Total heat losses were then calculated through a computerized complex mathematical formula. The value for mean energy expenditure obtained in this manner (100.2 +/- 7.02 kcal/h) is extremely close to the value for theoretical metabolism derived from the predictive equations in the literature (95.01 +/- 6.14). This verification of the validity of transforming cutaneous temperature data into energy expenditure, in accurately standardized experimental conditions, confirms the importance that the value of mean skin temperature, in the area of variability among individuals, can have in conditioning the energy balance at different levels, for a given caloric intake and with all other parameters being equal (age, sex, physical activity). In this connection, these results suggest that skin temperature may play a role in the pathogenesis of obesity.     

Muscle activity and energy expenditure

Most of increases in energy metabolism are induced by exercise. They are related with power and efficiency. In cycle ergometer exercise efficiency is positively correlated with exercise power and negatively correlated with pedaling rate. Ramp exercises are associated with an apparent increase in efficiency. Movements of daily life activity are too complex to make evaluation of power or efficiency possible. Energy expenditure assessment is based on direct measurement of the energy metabolism increase. The energy cost of movement or economy is calculated. Daily activity recording provides an assessment of the energy metabolism ability of patients. Muscle contractile activity is linked with ATP splitting. The pathways to resynthesize ATP include anaerobic glycogenolysis and the aerobic breakdown of substrates. Type I fibres have a higher oxidative capacity than type II fibres. Type II fibres demonstrate a higher glycolytic capacity, contract faster, and are more fatigable. Information relative to energy expenditure during daily life activity allows clinicians to better assess the clinical implications of the stress tests results.     

Relative changes in resting energy expenditure during weight loss: a systematic review

A more comprehensive understanding of the effects of weight loss on the changes in resting energy expenditure (EE) is relevant. A MEDLINE search was performed to identify studies with information relevant to this systematic review. From this search, the mean rate of resting EE decrease relative to weight loss was calculated from 90 available publications. A decrease of resting EE relative to weight loss of ?15.4 ± 8.7 kcal kg^?1 was observed from 2996 subjects. No sex differences were noted in the overall resting EE decrease relative to weight loss. However, a significant sex differences was seen with pharmacological interventions, which seemed to depress the resting EE relative to weight loss to a greater extent in men than in women (P < 0.05). A greater drop in resting EE relative to weight loss was observed for short interventions (more than 2 but less than 6 weeks) when compared with long interventions (<6 weeks) (–27.7 ± 6.7 vs. ?12.8 ± 7.1 kcal kg^?1) (P < 0.001). Men and women have a similar decrease in resting EE relative to weight loss except in the case of pharmacological interventions. Short interventions also produced greater resting EE losses relative to weight loss.     

The age-associated changes of dopamine-acetylcholine interaction in the striatum

The age-associated decline of dopamine D2 receptor (D2R) densities is one of the notable features of aging in mammalian brains. The concept of a functional dopamine (DA)-acetylcholine (ACh) interaction in the striatum has been strongly supported. However, the effects of this decline of D2R on the striatal DA-ACh interaction still remain to be elucidated. In the current study we examined the effects of different concentrations of a D2R agonist, quinpirole, on the striatal ACh release in three groups of rats at different ages (6-, 15-, 25-months-old) by in vivo microdialysis. The ACh release in the striatum was significantly decreased by quinpirole infusion in all three age groups. The old rats showed a significantly smaller decrease of the ACh release by quinpirole than that of the middle-aged rats at the dose of 0.1 microM and that of the young rats at the dose of 1 microM. The current study suggested that the striatal DA-ACh interaction was affected by the aging process.     

Leisure-time energy expenditure in asthmatics and non-asthmatics

An association between obesity and asthma has been documented previously, but the nature of this relationship remains unknown. This study aimed to determine if asthma is associated with a sedentary lifestyle which may explain this association. The energy expenditure (EE) on leisure activities was examined in 16,813 subjects, of at least 12 years of age, who participated in the Canadian National Population Health Survey 1994-95. Energy expenditure was calculated by multiplying the duration of leisure-time physical activity by its estimated metabolic energy cost. Asthma was considered to be present if an affirmative response was given to the question, 'Do you have asthma diagnosed by a health professional?' The average EE (+/- standard error) in males was 2.47 (+/- 0.11) kcal kg(-1) day(-1) for asthmatics and 1.98 (+/- 0.03) kcal kg(-1) day(-1) for non-asthmatics. The corresponding average EEs in females were 1.77 (+/- 0.08) and 1.54 (+/- 0.02) kcal kg(-1) day(-1) for asthmatics and non-asthmatics, respectively. The mean EE values decreased with increasing age. A significant interaction between asthma and age was noted with respect to EE; asthmatics tended to have higher mean EE values than non-asthmatics among younger subjects, and lower mean EE values in older subjects. This effect was more pronounced in females than in males. It was concluded that asthmatics were not consistently inactive compared with non-asthmatics. Leisure-time physical activity cannot explain the positive association between obesity and asthma.     

原发性高血压患者心肌能量消耗水平变化与左心室舒张功能的关系

目的探讨左心室舒张功能障碍与舒张功能正常的原发性高血压患者心肌能量消耗(MEE)水平的不同及其临床意义。方法选取原发性高血压患者128例,分别用组织多普勒和脉冲多普勒成像技术测量左心室舒张功能指标二尖瓣环舒张早期及舒张晚期运动速度之比(E'/A')、二尖瓣口舒张早期及舒张晚期血流速度之比(E/A)以及F/F';同时测量心脏结构指标、收缩功能指标,计算左心室收缩末周向室壁应力(cESS)、MEE。根据E'/A'将患者分为Gl组(E'/A'≥1)和G2组(E'/A'<1),根据E/A分为G3组(E/A≥1)和G4组(E/A<1),根据E/E'分为G5组(E/E'≥8)和G6组(E/E'<8)。结果 G2组左心房内径、左心室内径、室间隔厚度、左心室后壁(PWTd)、左心室质量指数、cESS及MEE明显高于G1组,LVEF明显低于G1组(P<0.01);G4组年龄、PWTd明显高于G3组;G6组体重指数、短轴缩短率、LVEF明显高于G5组,左心房内径、每搏输出量及左心室射血时间、心率、cESS及MEE明显低于G5组。双变量相关分析显示,E'/A'、E/E'与cESS、MEE等各指标间均有相关关系。结论左心室舒张功能障碍的原发性高血压患者MEE水平明显高于舒张功能正常的原发性高血压患者。     

Origin and age-associated changes in the expression of a physiologic autoantibody

Aging is accompanied by increased prevalence of serum autoantibodies. One commonly detected autoantibody, IgM rheumatoid factor, is also found associated with rheumatoid arthritis and other autoimmune disorders. Much evidence indicates that this autoantibody plays a physiologic role in the immune response. The potential of human subjects to secrete this autoantibody and the age-related changes in its expression by human peripheral blood and bone marrow lymphocytes have been investigated. The size of this self-reactive B cell pool increases with advancing age. The lymphocytes expressing this potential are found predominantly in an early B cell subset in elderly individuals as compared to a more mature B cell subset in individuals with rheumatoid arthritis. Preliminary data show that IgM rheumatoid factors share idiotypes implying a common origin, possible from a single light chain gene or a closely related family of light chain genes.     

Reversal of age-associated memory impairment by rosuvastatin in rats

Increased levels of iron in brain regions have been reported in neurodegenerative disorders as well as in normal brain aging. We have previously demonstrated that neonatal iron loading induces cognitive impairment in adult rats. Here, we evaluate the effects of neonatal iron treatment on cognition in aged rats. We also investigated the effects of a late subchronic rosuvastatin treatment on iron- and age-induced cognitive deficits. Rats received vehicle or 10.0 mg/kg Fe²⁺ orally at postnatal days 12–14. When animals reached the age of 23 months, they received daily intraperitoneal injections of saline or rosuvastatin (0.2 or 2.0 mg/kg) for 21 days. Twenty-four hours after the last injection, they were submitted to novel object recognition training. Retention test sessions were performed 1.5 and 24 h after training, in order to assess short-term and long-term memory, respectively. Results indicated that aged animals that received iron in the neonatal period showed more severe memory deficits than vehicle-treated ones, suggesting that iron potentiates age-associated memory impairments. Rosuvastatin improved recognition memory deficits associated with iron loading and aging, providing evidence that statins may be considered for the treatment of age-associated cognitive decline.