The objective of this study was to examine the effects of exercise training in hypoxia on arterial stiffness and flow-mediated vasodilation (FMD) in postmenopausal women. Sixteen postmenopausal women (56±1 years) were assigned to a normoxic exercise group (Normoxic group, n=8) or a hypoxic exercise group (Hypoxic group, n=8). The Hypoxic group performed exercise under hypobaric hypoxic conditions corresponding to 2000 m above sea level, and was exposed to these conditions for 2 h per session. Aquatic exercise was performed at an intensity of around 50% peak oxygen uptake for 30min, 4days per week, for 8 weeks. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV), and FMD was evaluated by peak diameter of the popliteal artery during reactive hyperemia. After the 8 weeks of training, the Normoxic group showed no significant changes. In contrast, baPWV (P < 0.05) was significantly reduced and peak diameter (P<0.05) and %FMD (P<0.01) were significantly increased in the Hypoxic group after training. These results suggest that exercise training under mild intermittent hypoxic conditions could more effectively reduce arterial stiffness in postmenopausal women, compared with exercise training performed at the same relative intensity under normoxic conditions. Our data also indicate that hypoxic exercise training may induce vascular functional adaptation, for example an increase in FMD response. These findings therefore could have important implications for the development of a new effective exercise prescription program.

Liposome-entrapped streptomycin (SM) was compared with free SM for therapeutic efficacy against experimental salmonellosis in mice. All of the mice infected with the virulent strain of Salmonella enteritidis 116-54 died between days 5 and 7, and a dose of 20 mg of free SM per kg administered 24 h after the bacterial inoculation did not prolong the survival. In contrast, the same dose of SM entrapped in liposomes prolonged the survival for all mice to more than 15 days. The therapeutic activity paralleled the dose in the liposomes, and a dose as low as 1. Synthetic phospholipid bilayer vesicles, called liposomes, have attracted considerable interest as potent drug carriers (6). They are nontoxic and biodegradable and can protect the entrapped drugs from enzymatic attack or immune recognition until they reach the target cells. The toxicity of a drug itself can be reduced by this shielding in the liposomes. Upon intravenous injection, liposomes, especially multiplelayer vesicles, are removed rapidly by reticuloendothelial (RE) cells and at least partly localized in lysosomes, where they are slowly degraded (7,13,15). This behavior of liposomes has some advantages for the treatment of diseases caused by intracellular parasites (5).In this study, experimental salmonellosis in mice was adopted as a model system of bacterial infection by intracellular parasites, and the therapeutic effect of streptomycin (SM) entrapped in liposomes was investigated. The results clearly indicated that the administration of liposomeentrapped SM could prolong the survival far more than the injection of free SM. Various applications of this method of selective drug delivery to RE cells were discussed. MATERIALS AND METHODSMice. Male C57BL/6 mice were obtained from the Laboratory of Experimental Animals (Institute of Medical Science, University of Tokyo, Japan). The animals were maintained on laboratory chow and acidified chlorinated water and used when 2 to 4 months old.Lipids. Egg yolk phosphatidylcholine was prepared by chromatography on alumina and silicic acid. Dipalmitoylphosphatidic acid and cholesterol were purchased from Sigma Chemical Co., St. Louis, Mo. Preparation of liposomes containing SM. Liposomes were * Corresponding author. prepared from a lipid mixture of egg yolk phosphatidylcholine (5 p.mol), cholesterol (5 ,umol), and dipalmitoylphosphatidic acid (0.5 ,umol) (negatively charged). The dried lipid film, obtained on rotary evaporation and subsequent vacuum desiccation, was dispersed in 0.5 ml of an SM solution (streptomycin sulfate, Meiji Seika Co. Ltd., Tokyo, Japan) in saline at the following concentrations: 250 mg/ml for an injection of 20 mg/kg, 125 mg/ml for 10 mg/kg, 62.5 mg/ml for 5 mg/kg, 31.2 mg/ml for 2.5 mg/kg, and 15.6 mg/ml for 1.2 mg/kg. Unencapsulated SM was removed by centrifugation at 20,000 x g for 20 min at 4°C, and the final pellet was resuspended in 5 ml of saline. Under these experimental conditions the entrapment of SM in the liposomes was equivalent to about 2 to 4% of the original solution.Measu...

Responses of beta-adrenoceptor (beta-AR) in rat soleus to gravitational unloading and/or changes in the levels of phosphorus compounds by feeding either creatine or its analogue beta-guanidinopropionic acid (beta-GPA) were studied. A decrease in the density of beta-AR (about -35%) was induced by 10 days of hindlimb suspension, but the affinity of the receptor was unaffected. Suspension unloading tended to increase the levels of adenosine triphosphate and phosphocreatine and decrease inorganic phosphate. Even without unloading, the beta-AR density decreased after an oral creatine supplementation (about -20%), which also tended to elevate the high-energy phosphate levels in muscle. However, an elevation of beta-AR density was induced (about +36%) after chronic depletion of high-energy phosphates by feeding beta-GPA (about +125%). Data suggest that the density of beta-AR in muscle is elevated if the high-energy phosphate contents are chronically decreased and vice versa. However, it may not be directly related to the degree of muscle contractile activity.

The effect of daily ambulatory activity on physical fitness has not yet been identified by quantitatively measuring the time spent on the intensity levels of ambulatory activity in elderly women over 75 with different functional capacity levels. The subjects consisted of 147 elderly women over 75 years old (82.8Ϯ4.3 years old) who were all capable of performing basic daily activities by themselves. Physical fitness was measured for 7 items (handgrip strength, knee extensor strength, postural stability, stepping, one-legged standing time with eyes open, 10 m walking, and the Timed Up and Go Test). The subjects wore a triaxial accelerometer for 2 consecutive weeks to measure their daily physical activities. The functional capacity level was assessed by the Tokyo Metropolitan Institute of Gerontology Index of Competence. The subjects were divided into two groups, a group with a score Ն10 points (high functional capacity group, nϭ59) and a score Ͻ10 points (low functional capacity group, nϭ88), and the relationship between physical fitness and physical activity was examined in both groups. In both the high and low functional capacity groups, 10 m walking, the Timed Up and Go Test, and one-legged standing time with eyes open significantly correlated with either the total steps/day or the ambulatory activity intensity. In the high functional capacity group, the knee extensor strength also significantly correlated with the total steps/day and moderate ambulatory activity. It is suggested that very elderly women with a reduced functional capacity should maintain their mobility by simply increasing their daily ambulatory activity.

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