Context:
Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, ...considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD.
Objectives:
Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD.
Design:
This study used a cross-sectional design.
Setting:
The general community in the United States, United Kingdom, and The Gambia were included in this study.
Participants:
Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included.
Exposures:
Total 25OHD concentration, race, and DBP (GC) genotype exposures were included.
Outcome Measures:
Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures.
Results:
Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80–0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites.
Conclusions:
Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population.
We found no racial or genetic differences in serum vitamin D binding protein. Free 25OHD, directly measured or calculated from DBP (using polyclonal antibodies), was low in Afro-Americans, compared to US whites or blacks from The Gambia.
Adequate sleep timed appropriately during the circadian night is important for numerous biological processes and systems. New evidence suggests that both sleep timing and duration may be important ...for optimal bone health as well. This review examines the diurnal variation of bone turnover markers (BTMs) and the importance of circadian clock genes in regulating bone mass. In addition, this review explores the evidence for a link between shift work (and its associated disturbances in sleep duration/quality and circadian alignment) and alterations in bone metabolism and bone health. Finally, we review how commonly used medications and over-the-counter substances (e.g. caffeine, melatonin) complicate the relationship between sleep and circadian disorders and bone health.
Sleep disruptions and bone health: what do we know so far? Swanson, Christine M
Current opinion in endocrinology, diabetes and obesity./Current opinion in endocrinology, diabetes and obesity,
08/2021, Letnik:
28, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This review briefly summarizes the growing body of literature addressing the skeletal consequences of sleep and circadian disruption.
The most recent data in the field suggest that the diurnal ...variation in bone turnover markers are because of endogenous circadian rhythmicity linked to clock genes in all bone cells; in a small human intervention study, cumulative sleep restriction with concurrent circadian disruption negatively alter bone turnover markers in a way that could explain the lower BMD and increased fracture risk identified in some prior night shift work studies; abnormal sleep duration and obstructive sleep apnea are associated with low BMD and increased fracture risk in some but not all studies.
Normal physiology and some animal and human intervention studies suggest that sleep and circadian disruptions, such as night shift work, abnormal sleep durations and obstructive sleep apnea are detrimental to skeletal health. However, additional research in this area is needed to determine which sleep/circadian disturbances are most detrimental to skeletal health, the reversibility of such impairments, and underlying mechanisms.
JAK-STAT signaling mediates the actions of numerous cytokines and growth factors, and its endogenous brake is the family of SOCS proteins. Consistent with their intracellular roles, SOCS proteins ...have never been identified in the extracellular space. Here we report that alveolar macrophages can secrete SOCS1 and -3 in exosomes and microparticles, respectively, for uptake by alveolar epithelial cells and subsequent inhibition of STAT activation. Secretion is tunable and occurs both in vitro and in vivo. SOCS secretion into lung lining fluid was diminished by cigarette smoking in humans and mice. Secretion and transcellular delivery of vesicular SOCS proteins thus represent a new model for the control of inflammatory signaling, which is subject to dysregulation during states of inflammation.
Background: Collecting a 24-h urine sample is recommended for monitoring the mean population sodium intake, but implementation can be difficult.Objective: The objective was to assess the validity of ...published equations by using spot urinary sodium concentrations to predict 24-h sodium excretion.Design: This was a cross-sectional study, conducted from June to August 2011 in metropolitan Washington, DC, of 407 adults aged 18–39 y, 48% black, who collected each urine void in a separate container for 24 h. Four timed voids (morning, afternoon, evening, and overnight) were selected from each 24-h collection. Published equations were used to predict 24-h sodium excretion with spot urine by specimen timing and race-sex subgroups. We examined mean differences with measured 24-h sodium excretion (bias) and individual differences with the use of Bland-Altman plots.Results: Across equations and specimens, mean bias in predicting 24-h sodium excretion for all participants ranged from −267 to 1300 mg (Kawasaki equation). Bias was least with International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) equations with morning (−165 mg; 95% CI: −295, 36 mg), afternoon (−90 mg; −208, 28 mg), and evening (−120 mg; −230, −11 mg) specimens. With overnight specimens, mean bias was least when the Tanaka (−23 mg; 95% CI: −141, 95 mg) or Mage (−145 mg; −314, 25 mg) equations were used but was statistically significant when using the Tanaka equations among females (216 to 243 mg) and the Mage equations among races other than black (−554 to −372 mg). Significant over- and underprediction occurred across individual sodium excretion concentrations.Conclusions: Using a single spot urine, INTERSALT equations may provide the least biased information about population mean sodium intakes among young US adults. None of the equations evaluated provided unbiased estimates of individual 24-h sodium excretion. This trial was registered at clinicaltrials.gov as NCT01631240.
The choice of a vitamin D–binding protein assay is key in calculating free 25-hydroxyvitamin D levels. The results of this analysis support the use of total 25-hydroxyvitamin D as a marker of vitamin ...D status, regardless of race or GC genotype.
To the Editor:
It is unclear whether circulating free or bioavailable 25-hydroxyvitamin D is a better marker of vitamin D status than is total 25-hydroxyvitamin D, especially in racially diverse populations. Until recently, the only method to compare the levels was to estimate the level of free or bioavailable 25-hydroxyvitamin D from total 25-hydroxyvitamin D, vitamin D–binding protein (also known as gc-globulin, encoded by the
GC
gene), and albumin, with or without the
GC
genotype. Powe et al. reported that levels of vitamin D–binding protein, as measured on a monoclonal enzyme-linked immunosorbent assay (ELISA, R&D Systems), were lower in black . . .
Exercise is recommended for cardiometabolic benefits and to preserve or improve bone health, especially for older adults at increased risk of fracture. However, exercise interventions have modest ...benefits on areal bone mineral density (aBMD), and exercise can lead to bone loss in young athletes under certain conditions. In this narrative review, we discuss evidence for a disruption in calcium homeostasis during exercise that may diminish the skeletal benefits of exercise. Topics include 1) a general overview of the effects of exercise on aBMD; 2) discussion of the exercise-induced disruption in calcium homeostasis; 3) factors that influence the magnitude of the exercise-induced disruption in calcium homeostasis, including age, sex, and exercise mode, intensity, and duration; 4) oral calcium supplementation to minimize the exercise-induced disruption in calcium homeostasis; and 5) potential for exercise-induced increase in parathyroid hormone to be both catabolic and anabolic to bone.
•Exercise can increase bone mass and prevent falls.•There is an acute catabolic response of bone metabolism to exercise.•Not yet known if exercise-induced increase in PTH is anabolic.
Circadian Rhythm of Vascular Function in Midlife Adults Thosar, Saurabh S; Berman, Alec M; Herzig, Maya X ...
Arteriosclerosis, thrombosis, and vascular biology,
2019-June, 2019-06-00, 20190601, Letnik:
39, Številka:
6
Journal Article
Recenzirano
Odprti dostop
OBJECTIVE—Adverse cardiovascular events occur more frequently in the morning than at other times of the day. Vascular endothelial function (VEF)—a robust cardiovascular risk marker—is impaired during ...this morning period. We recently discovered that this morning impairment in VEF is not caused by either overnight sleep or the inactivity that accompanies sleep. We determined whether the endogenous circadian system is responsible for this morning impairment in VEF. We also assessed whether the circadian system affects mechanistic biomarkers, that is, oxidative stress (malondialdehyde adducts), endothelin-1, blood pressure, and heart rate.
APPROACH AND RESULTS—Twenty-one (11 women) middle-aged healthy participants completed a 5-day laboratory protocol in dim light where all behaviors, including sleep and activity, and all physiological measurements were evenly distributed across the 24-hour period. After baseline testing, participants underwent 10 recurring 5-hour 20-minute behavioral cycles of 2-hour 40-minute sleep opportunities and 2 hours and 40 minutes of standardized waking episodes. VEF, blood pressure, and heart rate were measured, and venous blood was sampled immediately after awakening during each wake episode. Independent of behaviors, VEF was significantly attenuated during the subjective night and across the morning (P=0.04). Malondialdehyde adducts and endothelin-1 exhibited circadian rhythms with increases across the morning vulnerable period and peaks around noon (P≤0.01). Both systolic (P=0.005) and diastolic blood pressure (P=0.04) were rhythmic with peaks in the late afternoon.
CONCLUSIONS—The endogenous circadian system impairs VEF and increases malondialdehyde adducts and endothelin-1 in the morning vulnerable hours and may increase the risk of morning adverse cardiovascular events in susceptible individuals.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT02202811.
Adoptive immunotherapy with Tregs is a promising approach for preventing or treating type 1 diabetes. Islet antigen-specific Tregs have more potent therapeutic effects than polyclonal cells, but ...their low frequency is a barrier for clinical application. To generate Tregs that recognize islet antigens, we engineered a chimeric antigen receptor (CAR) derived from a monoclonal antibody with specificity for the insulin B chain 10-23 peptide presented in the context of the IAg7 MHC class II allele present in NOD mice. Peptide specificity of the resulting InsB-g7 CAR was confirmed by tetramer staining and T cell proliferation in response to recombinant or islet-derived peptide. The InsB-g7 CAR redirected NOD Treg specificity such that insulin B 10-23-peptide stimulation enhanced suppressive function, measured via reduction of proliferation and IL-2 production by BDC2.5 T cells and CD80 and CD86 expression on dendritic cells. Cotransfer of InsB-g7 CAR Tregs prevented adoptive transfer diabetes by BDC2.5 T cells in immunodeficient NOD mice. In WT NOD mice, InsB-g7 CAR Tregs prevented spontaneous diabetes. These results show that engineering Treg specificity for islet antigens using a T cell receptor-like CAR is a promising therapeutic approach for the prevention of autoimmune diabetes.
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