HRT provides no additional beneficial effect on sarcopenia in physically active postmenopausal women: a cross-sectional, observational study

OBJECTIVES: Physical activity can prevent or retard the loss of muscle mass associated with aging. On the other hand, it has been suggested that HRT may also help prevent sarcopenia in postmenopausal women. We thus examined if HRT provides additional beneficial effect in physically active postmenopausal women. METHODS: Forty postmenopausal women aged between 55 and 65 years old (normal weight, healthy and no medication) were recruited. Seventeen women were already taking HRT for at least one year whereas 23 were never submitted to HRT. Body composition was measured by DXA and physical activity metabolism was obtained by the use of accelerometry. Subjects were divided in tertile groups based on their daily physical activity energy expenditure (PAEE). RESULTS: Physical activity groups were similar for age, HRT users distribution, BMI, trunk fat-free mass (FFM), and all fat mass (FM) components. The group of women who were the most physically active significantly displayed greater total FFM, appendicular FFM, and muscle mass index (MMI) compared to the group of less active women (P < 0.05) whereas HRT added no additional effect on any FFM components. CONCLUSIONS: Our results suggest that in active postmenopausal women, HRT does not provide any additional beneficial effect on body composition.     

IL-8-mediated angiogenic responses of endothelial cells to lipid antigen activation of iNKT cells depend on EGFR transactivation

iNKT cells are a unique T cell subset, which is CD1d-restricted and specific for glycolipid antigens. In advanced atherosclerotic plaques, focal collections of inflammatory cells correlate with areas of intraplaque neovascularization. We reported recently that iNKT cells might facilitate intraplaque neovascularization by enhancing EC migration and sprouting in an IL-8-dependent manner. This study investigated the participating effector mechanisms. In ECs, CM, derived from antigen-stimulated human iNKT cells (CM+), induced up-regulation of IL-8R CXCR2 and the phosphorylation of EGFR and of multiple intracellular signaling effectors, including FAK, Src, Erk, Jnk, p38-MAPK, and STAT1 and -3. We found that a cascade of events, which were IL-8-dependent and involved EGFR activation, was responsible for signaling through FAK and Src kinases and necessary for acquisition of angiogenic morphology, migration in a two-dimensional wound assay, and sprout outgrowth in a three-dimensional model of angiogenesis in vitro. The data support that IL-8-dependent activation of angiogenic behavior in ECs, in response to activated iNKT, involves CXCR2, transactivation of EGFR, and subsequent FAK/Src signaling. We found too that activated iNKT increased VEGFR2 expression in ECs. Functional studies confirmed that EGF is the motogenic-enhancing factor in CM+ and is necessary, together with an exogenous source of VEGF, for iNKT-promoted sprout formation. EGFR inhibition may represent a novel therapeutic modality aimed at plaque stabilization through control of neovascularization within developing atherosclerotic plaques.     

脂质过氧化对培养人内皮细胞的损伤作用

Lipid peroxidation (LPO) was initiated and facilitated in cultured human endothelial cells (ECs) by treating the cells with diamidel first. The concentration of lipid peroxide in the cells and medium increased with the increase of diamide concentration. Under SEM and TEM, 0.05 x 10(-4) M diamide might induce ultrastructural changes. The prominent changes were contraction, plasma membrane blebbing, and rounding, swelling and dilatation of mitochondria. Vacuolization appeared in cells at 4.0 x 10(-4) M diamide, A decrease of prostacyclin synthesis in these cells accompanied the morphologic changes. The results showed that ECs are sensitive to LPO, suggesting that LPO may play an important role in atherogenesis.     

Hyperventilation-induced changes of blood cell counts depend on hypocapnia

Voluntary hyperventilation for 20 mm causes haemoconcentration and an increase of white blood cell and thrombocyte numbers. In this study, we investigated whether these changes depend on the changes of blood gases or on the muscle work of breathing. A group of 12 healthy medical students breathed 36 l· min^–1 of air, or air with 5% CO₂ for a period of 20 min. The partial pressure of CO₂ decreased by 21.4 mmHg (2.85 kPa;P < 0.001) with air and by 4.1 mmHg (0.55 kPa;P < 0.005) with CO₂ enriched air. This was accompanied by haemoconcentration of 8.9% with air (P < 0.01) and of 1.6% with CO₂ enriched air (P < 0.05), an increase in the lymphocyte count of 42% with air (P < 0.001) and no change with CO₂ enriched air, and an increase of the platelet number of 8.4% with air (P < 0.01) and no change with CO₂ enriched air. The number of neutrophil granulocytes did not change during the experiments, but 75 min after deep breathing of air, band-formed neutrophils had increased by 82% (P < 0.025), whereas they were unchanged 75 min after the experiment with CO₂ enriched air. Adrenaline and noradrenaline increased by 360% and 151% during the experiment with air, but remained unchanged with CO₂ enriched air. It was concluded that the changes in the white blood cell and platelet counts and of the plasma catecholamine concentrations during and after voluntary hyperventilation for 20 min were consequences of marked hypocapnic alkalosis. It was found that minimal changes of the blood gases, the muscle work of breathing, the chest movements or mechanical influences on the spleen did not contribute to hyperventilation-induced changes of these variables.     

The effect of physical activity on endothelial function in man

Endothelial dysfunction occurs early in the atherosclerosis in response to elevated atherosclerotic risk factors, and endothelial dysfunction itself may exacerbate the atherosclerotic process. Treatments that reduce atherosclerotic risk factors also generally improve endothelial function. The present review seeks to summarize the effect of exercise training on endothelial function in human subjects. Cross-sectional studies comparing healthy physically active and inactive subjects as well as longitudinal exercise training studies of healthy individuals show little effect of exercise training on endothelial function. In contrast, both cross-section and longitudinal studies document improved endothelial function with exercise training in subjects with abnormal baseline endothelial function, including the elderly and patients with heart failure or coronary artery disease. Improvements in endothelial function with physical activity may explain some of the benefits of exercise in subjects with, or at risk for, vascular disease.     

Medroxyprogesterone acetate versus norethisterone: effect on estradiol-induced changes of markers for endothelial function and atherosclerotic plaque characteristics in human female coronary endothelial cell cultures

OBJECTIVE: Progestin addition to estradiol (E(2)) replacement therapy may lead to a deterioration of beneficial effects on the vasculature. The effect of the two clinically most common progestins, medroxyprogesterone acetate (MPA) and norethisterone (NET), during continuous combination with E(2) on the synthesis of markers for coronary endothelial function, atherosclerotic plaque initiation, and plaque formation was investigated in human female vascular cell cultures and compared with that of E(2) alone. DESIGN: Endothelial cell cultures from human female coronary arteries were used to evaluate the effect of progestin addition to E(2) on the production of the following endothelial markers: prostacyclin, endothelin, plasminogen activator inhibitor-1, E-selectin, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 (MCP-1), and the precursor of matrix metalloproteinase-1 (pro-MMP-1). E(2) was tested at 0.1 microM, 1 microM, and 10 microM alone and in equimolar combinations with MPA or NET. The markers were determined by enzyme immunoassays in the cell supernatant. RESULTS: E(2) induced a significant increase of endothelial prostacyclin production and was able to significantly decrease the synthesis of endothelin, plasminogen activator inhibitor-1, E-selectin, and intercellular adhesion molecule-1. Neither MPA nor NET addition negatively interfered with these E(2)-induced benefits. However, MPA antagonized the E(2)-induced significant reduction of MCP-1 synthesis, with the difference between both progestins being significant (p < 0.01). Interestingly, an enhancement of the positive E(2)-effect on pro-MMP-1 production was observed by the addition of both MPA and NET (p < 0.01). CONCLUSION: E(2) can positively influence various markers of endothelial function. Addition of MPA or NET can elicit different effects, which has been demonstrated for the first time in human coronary cell cultures. No impact was found on markers representing primarily vasotonus and thrombogenicity. In terms of MMP-1, which is crucial for atherosclerotic plaque stability, an enhancement of the beneficial E(2) effect was observed. However, regarding MCP-1, contrary effects of progestins cannot be excluded. This indicates that progestins may differ in their effects, particularly in the early stages of atherosclerosis, which has also been supported by other studies.     

Functional endothelial progenitor cells derived from adipose tissue show beneficial effect on cell therapy of traumatic brain injury

Endothelial progenitor cells (EPCs) are responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Adipose tissue (AT) is an abundant source of mesenchymal stem cells (MSCs), which have multipotent differentiation ability. We successfully derived EPCs from AT, which maintained a strong proliferative capacity and demonstrated the characteristic endothelial function of uptaking of acetylated low-density lipoprotein. They formed tube-like structures in vitro. Endothelial nitric oxide synthase (eNOS) gene expression in EPCs was similar to that in mature endothelial cells. Transplantation of EPCs derived from AT after the acute phase was applied in rats with traumatic brain injury (TBI). Transplanted EPCs participated in the neovascularization of injured brain. Improving functional recovery, reducement of deficiency volume of brain, host astrogliosis and inflammation were found. These results suggest that adult AT derived stem cells can be induced to functional EPCs and have beneficial effect on cell therapy.     

Does the impairment of the hypothalamic-pituitary-gonadal axis in anorexia nervosa depend on increased sensitivity to endogenous melatonin?

The authors hypothesize that the impairment of hypothalamic-pituitary-gonadal axis in patients suffering from anorexia nervosa depends (at least in part) on the increased sensitivity to endogenous melatonin. The hypothesis is based mainly on the following facts: (1) melatonin is well known to exert an inhibitory effect on gonadotropin secretion; (2) melatonin binding is increased in brains of fasted rats; (3) undernutrition dramatically increases the inhibitory effect of exogenous melatonin on gonadotropin-releasing hormone-induced gonadotropin secretion in female rats; (4) the administration of propranolol in girls suffering from anorexia nervosa diminishes the nocturnal peak of melatonin and, in parallel, restores the gonadotropin response to gonadotropin-releasing hormone.     

The effect of glucose and mental stress on cutaneous microvascular endothelial function

Glucose and mental stress, independently, have been found to impair arterial endothelial function (an indicator of vascular health). The present study sought to determine whether the combination of glucose and stress would have a greater effect on microvascular endothelial function than each on its own. To assess endothelial function, surges in skin blood flow (reactive hyperemia), following the release of cuff pressure to the upper arm at 200 mmHg for 5 min, were measured with laser Doppler flowmetry in 40 young, healthy females. Endothelial function did not change significantly following a 5-min mathematics stressor or the consumption of 75 g of glucose. However, the combination of glucose and stress impaired endothelium-dependent dilatation 30 min after glucose consumption. These findings suggest that combinations of vascular risk factors may be more threatening to cardiovascular health than singularly occurring factors.     

Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex

The orbitofrontal cortex has been hypothesized to carry information regarding the value of expected rewards. Such information is essential for associative learning, which relies on comparisons between expected and obtained reward for generating instructive error signals. These error signals are thought to be conveyed by dopamine neurons. To test whether orbitofrontal cortex contributes to these error signals, we recorded from dopamine neurons in orbitofrontal-lesioned rats performing a reward learning task. Lesions caused marked changes in dopaminergic error signaling. However, the effect of lesions was not consistent with a simple loss of information regarding expected value. Instead, without orbitofrontal input, dopaminergic error signals failed to reflect internal information about the impending response that distinguished externally similar states leading to differently valued future rewards. These results are consistent with current conceptualizations of orbitofrontal cortex as supporting model-based behavior and suggest an unexpected role for this information in dopaminergic error signaling.     

The effect of acute exercise on endothelial function following a high-fat meal

The transient impairment of endothelial function following a high-fat meal is well established. Brachial artery flow-mediated dilation (FMD) decreases between 2 and 6 h post ingestion. Whether this impairment can be reduced with acute aerobic exercise has not been investigated. The purpose of this study was to investigate if a single sustained aerobic exercise session can counteract the postprandial attenuation in brachial artery FMD associated with the ingestion of a high-fat meal. Eight apparently healthy adults (five men, three women), age 25.5 ± 0.8 years, performed three treatment conditions in a counter-balanced design: (1) low-fat meal alone (LFM), (2) high-fat meal alone (HFM), and (3) one session of aerobic exercise presented 2 h after ingesting a high-fat meal (HFM-EX). The examination of brachial artery FMD was performed at baseline and 4 h following the ingestion of the meal for each treatment condition. A 3 × 2 (treatment × time) repeated measures ANOVA exhibited a significant interaction (P = 0.019). Preprandial FMDs were similar (P = 0.863) among all three treatment conditions. The FMDs following the LFM (7.18 ± 1.31%) and HFM-EX (8.72 ± 0.94%) were significantly higher (P = 0.001) than the FMD following the HFM (4.29 ± 1.64%). FMD was significantly elevated above preprandial values following the HFM-EX (5.61 ± 1.54 to 8.72 ± 0.94%, P = 0.005) but was unchanged following the LFM (6.17 ± 0.94 to 7.18 ± 1.31%, P = 0.317) and the HFM (5.73 ± 1.23 to 4.29 ± 1.64%, P = 0.160). These findings suggest that a single aerobic exercise session cannot only counteract the postprandial endothelial dysfunction induced by the ingestion of a high-fat meal, but also increase brachial artery FMD in apparently healthy adults.     

Differentiation of endothelial cells in avian embryos does not depend on gastrulation.

Unincubated quail eggs were treated with Cytochalasin B. By this means, gastrulation of the blastodiscs was inhibited. Fragments of these blastodiscs were grafted into wings buds of chick embryos, and the differentiation fate of graft-derived cells was studied. Results show that only endothelial cells differentiate from the grafts. They were even found outside the graft site in vessels made up of a chimeric endothelium. It can be concluded that determination, differentiation and migration of endothelial cells does not depend on gastrulation.     

Seasonal changes in membrane lipid transitions and thyroid function in the hedgehog.

Upper (Tf) and lower (Ts) temperature limits of order-disorder transitions in blood cell lipids of hedgehogs, Erinaceus europaeus, were determined over an annual cycle. There was a significant decrease in the temperature of both Tf and Ts from values of 19 and 6 degrees C, respectively, for summer animals to values of 14 and -2.0 degrees C for winter animals. Plasma thyroxine levels decreased from a summer mean of 16.0 nmol/liter to a mean of 2.3 nmol/liter in winter. Basal oxygen consumption also decreased from the summer mean 0.45 ml/g body wt/h to a mean 0.39 ml/g body wt/h in winter. In winter a group of hedgehogs kept indoors at room temperature was compared with a group kept outdoors exposed to natural winter conditions, and there was no significant difference between them in the above parameters. We conclude that the winter membrane lipid and metabolic changes are not a response to low temperature per se but part of a circannual homeostatic adjustment at least partly regulated by thyroid hormone.     

Lack of beneficial effect of levamisole on Marek's disease

Levamisole hydrochloride administered by subcutaneous inoculation at 2.5 mg/kg or 25 mg/kg bodyweight under three dosage regimens to chicks infected by Marek's disease virus had no beneficial influence on the course of the disease.     

缺氧状态下细胞自噬变化及其对心血管疾病的改善

自噬是细胞维持内环境稳态的重要方式之一,它是一种细胞缺血及代谢应激时与缺氧相关联的幸存机制。在某些心血管疾病中,缺血（缺氧）微环境会通过多种途径激活自噬,适当的自噬能够降解自身受损蛋白等来维持细胞生存,但当自噬过度时,则会损伤细胞,甚至使细胞发生II型程序性死亡。目前,治疗这类心血管疾病的方式主要有药物疗法和干细胞移植法,而白噬在这其中扮演着重要角色。对于不同类型和不同程度的心血管疾病,自噬可作为促存活机制,也可作为促死亡机制。因此,如何利用自噬有效改善某些心血管疾病是难点所在。     

Age-related changes in immune function: effect on airway inflammation

Immunosenescence is defined as changes in the innate and adaptive immune response associated with increased age. The clinical consequences of immunosenescence include increased susceptibility to infection, malignancy and autoimmunity, decreased response to vaccination, and impaired wound healing. However, there are several immune alterations that might facilitate persistence of asthma into late adulthood or development of asthma after the age of 50 to 60 years. Asthma in older patients is not uncommon, and this is a growing population as the average lifespan increases. Specific innate changes that might affect severity of asthma in older patients or be involved in the development of late-onset asthma include impaired mucociliary clearance and changes in airway neutrophil, eosinophil, and mast cell numbers and function. Additionally, age-related altered antigen presentation and decreased specific antibody responses might increase the risk of respiratory tract infections. Respiratory tract infections exacerbate asthma in older patients and possibly play a role in the pathogenesis of late-onset asthma. Furthermore, cytokine profiles might be modified with aging, with some investigators suggesting a trend toward T(H)2 cytokine expression. This review examines specific innate and adaptive immune responses affected by aging that might affect the inflammatory response in older adults with asthma.     

Membrane lipid changes and modification of neuronal function homeostasis in aging brain

Three issues are raised which may be relevant to changes in membrane asymmetry, but were not discussed in Schroeder's review: (1) In addition to the contribution of phospholipids and cholesterol in the maintenance of membrane properties and homeostasis, gangliosides also play an important role, particularly in membrane-mediated transfer of information. (2) Increasing evidence implicates a dynamic interaction between neurons and glia in brain function. The functional integrity and homeostasis of this neural/glial interaction could be seriously affected by any number of changes in membrane lipid content and distribution. (3) In addition to the functional implications of lipid asymmetry reviewed by Schroeder, alterations in the asymmetrical distribution of phosphatidylserine may activate certain defense reactions. These reactions may possess their own inherent neural functional consequences, providing certain implications for pharmacological treatment.