The effects of a 6-week programme of endurance training on soleus muscle capillarity were examined, in terms particularly of the proportions of arteriolar and venular capillaries and their capillary domain area, in young (3-week-old) and middle-aged (54-week-old) Wistar rats. Exercise protocols for the young training group were: 10-22.5 m min-1 60 min day-1 for 6 days a week, with a gradient of 7 degrees during the final 2 weeks; for the middle-aged training group, the protocols were: 10-20 m min-1. 50 min day-1 for 6 days a week. In both young and middle-aged training groups, the density of arteriolar capillaries was significantly increased (P < 0.05), but that of venular and intermediate capillaries was decreased slightly. The proportion of arteriolar capillaries therefore was significantly (P < 0.05) increased, from 63.9 to 73.1% in young rats and from 33.0 to 48.4%, in middle-aged rats after training. The increase in the proportion of arteriolar capillaries is an advantageous adaptation to exercise-induced increases in oxygen demand. In both young and middle-aged rats, capillary domain area and Krogh's tissue cylinder radii in all capillary portions decreased after training. These results suggest that adaptive changes in oxygen transport system, identified as an increase in the arteriolar capillary and a reduction in diffusion distance for oxygen, were observed in middle-aged as well as in young rats. However, capillary angiogenesis induced by exercise appeared to be greater in young than in middle-aged rats.

The effects of 4-week cold exposure on capillary geometry, particularly in terms of the distribution of arteriolar and venular capillaries and their capillary domain areas, were studied for different types of skeletal muscles in male Wistar rats. Morphological data for capillaries and muscles were obtained from muscle cross-sections exposed to a double-staining method that distinguishes arteriolar portions from venular portions of capillaries. In soleus (SOL; type I fibers) and the deep portion of gastrocnemius (GASd; type I and IIa fibers) muscles, total capillary density and density of arteriolar capillary were significantly greater in cold-acclimated (CA) rats than in warm control (WC) rats (p < 0.05). In the superficial portion of the gastrocnemius (GASs; type IIb fibers), however, these changes in capillarity were not observed. After cold acclimation, fiber cross-sectional area was significantly decreased by 21, 28 and 15% in SOL, GASd and GASs (p < 0.05), respectively. In SOL and GASd but not in GASs, capillary domain areas of arteriolar, intermediate and venular portions in CA were significantly smaller than those of the respective portions in WC (p < 0.05). Succinate dehydrogenase activity was significantly increased after cold acclimation, by 31% in SOL and 21% in GASd (p < 0.05). In GASs, however, the activity remained unchanged after cold acclimation. These results suggest that adaptive changes in the oxygen transport system were observed after cold acclimation in the skeletal muscles that are mainly composed of oxidative fibers. These adaptive changes may improve the effective oxygen supply to muscle tissues that contribute to thermogenesis in a cold atmosphere.

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Capillaries are nonuniform thin tubes: The arteriolar and venular capillary portions express alkaline phosphatase (AP) and dipeptidyl peptidase IV (DPPIV), respectively. Differences in enzyme activities between arteriolar and venular capillary portions could be shown by staining sections of cardiac tissues for AP and DPPIV after coronary infusion of microspheres and by staining cultured endothelial cells that had been collected from coronary microvessels. Through use of a double staining method for AP and DPPIV, adaptive changes in the capillary network were studied in rat hearts exposed to cold, exercise, hypertension, chronic coronary occlusion, and transient coronary occlusion followed by reperfusion. Two patterns could be seen in the adaptations of the ventricular capillary network. The increase in the venular capillary portions is accompanied by remarkable increases in capillary density and capillary-to-myocyte ratio. The increase in the arteriolar capillary portion seemed to be accompanied by a decrease or only a limited increase in capillary density in stressed hearts. The increase in the total capillary density improves the capacity for oxygen transport to tissues with a high tissue perfusion and a short diffusion distance for oxygen. The increase in the arteriolar capillaries may also improve oxygen transport by increasing the arterial blood perfusing the tissue. This seems, however, a compensation for the limited angiogenesis: The alleviation of stresses, such as pharmacological treatment of the hypertrophied heart and reperfusion after transient ischemia, increases venular capillary portions and capillary density. These changes are discussed with immunohistochemical observations of rapid and prolonged expressions of angiogenic growth factors.

BackgroundNumerous studies have evaluated protein and amino acid levels in human milk. However, research in this area has been limited by small sample sizes and study populations with little ethnic or racial diversity.ObjectiveEvaluate the protein and amino acid composition of mature (≥30 days) human milk samples collected from a large, multinational study using highly standardized methods for sample collection, storage, and analysis.DesignUsing a single, centralized laboratory, human milk samples from 220 women (30–188 days postpartum) from nine countries were analyzed for amino acid composition using Waters AccQ-Tag high-performance liquid chromatography and total nitrogen content using the LECO FP-528 nitrogen analyzer. Total protein was calculated as total nitrogen×6.25. True protein, which includes protein, free amino acids, and peptides, was calculated from the total amino acids.ResultsMean total protein from individual countries (standard deviation [SD]) ranged from 1,133 (125.5) to 1,366 (341.4) mg/dL; the mean across all countries (SD) was 1,192 (200.9) mg/dL. Total protein, true protein, and amino acid composition were not significantly different across countries except Chile, which had higher total and true protein. Amino acid profiles (percent of total amino acids) did not differ across countries. Total and true protein concentrations and 16 of 18 amino acid concentrations declined with the stage of lactation.ConclusionsTotal protein, true protein, and individual amino acid concentrations in human milk steadily decline from 30 to 151 days of lactation, and are significantly higher in the second month of lactation compared with the following 4 months. There is a high level of consistency in the protein content and amino acid composition of human milk across geographic locations. The size and diversity of the study population and highly standardized procedures for the collection, storage, and analysis of human milk support the validity and broad application of these findings.

Vascular calcification (VC) is a strong predictor of cardiovascular morbidity and mortality, and is linked to ageing, diabetes and chronic kidney diseases (CKD). 1 Growing evidence now suggests that VC is an actively regulated process resembling bone remodelling, including both inductive and inhibitory processes. 2 Abnormal activation of the renin-angiotensin-aldosterone system plays an important role in the development of cardiovascular diseases, among which aldosterone (Aldo) is a major effector. 3 Aldo, a mineralocorticoid hormone, binds to mineralocorticoid receptor (MR) and then activates specific intracellular genomic pathways, thus regulating the homeostasis of the cardiovascular system. Once Aldo is overactivated, it can promote vascular oxidative stress, inflammation and apoptosis, 4 leading to an increased risk of target-organ damage. 5 Previous studies suggested that a MR inhibitor, spironolactone (Spiro) ameliorated CKD-related

We concluded that miR-451 expression is a reliable FFPE tissue biomarker for PTC malignancies and it may have potentials to become a noninvasive, blood-based biomarker for PTC diagnosis and evaluation of LN status.

The predictive value of cumulative blood pressure (BP) on all-cause mortality and cardiovascular and cerebrovascular events (CCE) has hardly been studied. In this prospective cohort study including 52,385 participants from the Kailuan Group who attended three medical examinations and without CCE, the impact of cumulative systolic BP (cumSBP) and cumulative diastolic BP (cumDBP) on all-cause mortality and CCEs was investigated. For the study population, the mean (standard deviation) age was 48.82 (11.77) years of which 40,141 (76.6%) were male. The follow-up for all-cause mortality and CCEs was 3.96 (0.48) and 2.98 (0.41) years, respectively. Multivariate Cox proportional hazards regression analysis showed that for every 10 mm Hg·year increase in cumSBP and 5 mm Hg·year increase in cumDBP, the hazard ratio for all-cause mortality were 1.013 (1.006, 1.021) and 1.012 (1.006, 1.018); for CCEs, 1.018 (1.010, 1.027) and 1.017 (1.010, 1.024); for stroke, 1.021 (1.011, 1.031) and 1.018 (1.010, 1.026); and for MI, 1.013 (0.996, 1.030) and 1.015 (1.000, 1.029). Using natural spline function analysis, cumSBP and cumDBP showed a J-curve relationship with CCEs; and a U-curve relationship with stroke (ischemic stroke and hemorrhagic stroke). Therefore, increases in cumSBP and cumDBP were predictive for allcause mortality, CCEs, and stroke.Hypertension is the most common chronic disease, and the most important risk factor for cardiovascular disease 1 . Stroke and myocardial infarction (MI) are the main complications of hypertension that can lead to death 1-4 . The Framingham Study showed that starting from 115/75 mm Hg, the risk for cardiovascular events increases following the increase in blood pressure (BP) 5 . It takes time for exposure to high BP to become a risk of all-cause mortality and cardiovascular and cerebrovascular events (CCEs); and there are many factors affecting BP, such as age, diet, lifestyle, and use of antihypertensive drugs. Therefore, using a single BP measurement to predict all-cause mortality and the occurrence of CCE is not reliable.Cumulative exposure is calculated as the product of the dose level and the exposure time and has been used to predict the impact of exposures on the target organ. Since Doll and Hill first proposed that high cumulative exposure to smoking is associated with lung cancer 6,7 , it has been suggested that cumulative exposure to high blood sugar level increases the risk of complications of diabetes 8 , cumulative exposure to high cholesterol level increases the risk for coronary heart disease 9 , and cumulative exposure to high BP is associated with kidney damage 10 . However, there is hardly any study on the predictive value of cumulative exposure to elevated BP on all-cause mortality and the occurrence of CCEs. In this study, we used data collected from the Kailuan Study (Trial identification: ChiCTR-TNC-11001489; Trial registration site: http://www.chictr.org.cn/index.aspx; Registration number: 11001489) and analyzed the predictive value of cumulative BP for all-cause mortal...