Celsus described four of the five cardinal signs of inflammation 2000 years ago, and Eustachio discovered the adrenal glands almost 500 years ago, but not until 1936 did Selye note that in rats exposed to stressors, the adrenal glands were enlarged, and the thymus and lymph nodes shrunken.1–3 Cortisone, the active principle of the adrenal glands, was isolated by Kendall and Reichstein in the late 1940s and shown to suppress immune organs. These scientists, along with Hench, received the Nobel Prize in Physiology and Medicine, after Hench and colleagues showed that cortisone could ameliorate rheumatoid arthritis.4,5 In recent . . .

The Hypothalamic–Pituitary–Adrenal Axis and Immune-Mediated Inflammation

There is a vast literature on the generation and effects of reactive oxygen species in biological systems, both in relation to damage they cause and their involvement in cell regulatory and signaling pathways. The biological chemistry of different oxidants is becoming well understood, but it is often unclear how this translates into cellular mechanisms where redox changes have been demonstrated. This review addresses this gap. It examines how target selectivity and antioxidant effectiveness vary for different oxidants. Kinetic considerations of reactivity are used to assess likely targets in cells and how reactions might be influenced by restricted diffusion and compartmentalization. It also highlights areas where greater understanding is required on the fate of oxidants generated by cellular NADPH oxidases and on the identification of oxidant sensors in cell signaling.

Reconciling the chemistry and biology of reactive oxygen species

Fluorescent Chemosensors Based on Spiroring-Opening of Xanthenes and Related Derivatives Xiaoqiang Chen, Tuhin Pradhan, Fang Wang, Jong Seung Kim,* and Juyoung Yoon* Departments of Chemistry and Nano Science and of Bioinspired Science (WCU), Ewha Womans University, Seoul 120-750, Korea State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemistry and Chemical Engineering, Nanjing University of Technology, Nanjing 210009, China Department of Chemistry, Korea University, Seoul 136-701, Korea

Fluorescent chemosensors based on spiroring-opening of xanthenes and related derivatives.

Objectives  To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design  Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources  Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection  Randomised, double blind, placebo controlled trials of supplementation with vitamin D 3 or vitamin D 2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results  25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity Conclusions  Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration  PROSPERO CRD42014013953.

/pdf/vitamin-d-supplementation-to-prevent-acute-respiratory-tract-2zwmul7x0j.pdf

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses?

https://www.jbc.org/content/281/52/39860.full.pdf

Modeling the Reactions of Superoxide and Myeloperoxidase in the Neutrophil Phagosome: IMPLICATIONS FOR MICROBIAL KILLING*

Effect of anticoagulants and storage temperatures on stability of plasma and serum hormones.

Context: Parenteral iron administration has been associated with hypophosphatemia. Fibroblast growth factor 23 (FGF23) has a physiological role in phosphate homeostasis via suppression of 25-hydroxyvitamin D [25(OH)D] activation and promotion of phosphaturia. We recently reported a case of iron-induced hypophosphatemic osteomalacia associated with marked FGF23 elevation. Objective: Our objective was to prospectively investigate the effect of parenteral iron polymaltose on phosphate homeostasis and to determine whether any observed change was related to alterations in circulating FGF23. Design, Setting, and Participants: Eight medical outpatients prescribed iv iron polymaltose were recruited. Plasma phosphate, 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)2D], PTH, FGF23, and urinary tubular reabsorption of phosphate were measured prior to iron administration and then weekly for a minimum of 3 wk. Results: Plasma phosphate fell from 3.4 ± 0.6 mg/dl at baseline to 1.8 ± 0.6 mg/dl at wk 1 (P < 0.0001) associated...

/pdf/fgf23-elevation-and-hypophosphatemia-after-intravenous-iron-4zm6lqmm5t.pdf

FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study.

Context Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25-OHD) levels and incidence of upper respiratory tract infections (URTIs). However, results of clinical trials of vitamin D supplementation have been inconclusive. Objective To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults. Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch, New Zealand. Intervention Participants were randomly assigned to receive an initial dose of 200 000 IU oral vitamin D 3 , then 200 000 IU 1 month later, then 100 000 IU monthly (n = 161), or placebo administered in an identical dosing regimen (n = 161), for a total of 18 months. Main Outcome Measures The primary end point was number of URTI episodes. Secondary end points were duration of URTI episodes, severity of URTI episodes, and number of days of missed work due to URTI episodes. Results The mean baseline 25-OHD level of participants was 29 (SD, 9) ng/mL. Vitamin D supplementation resulted in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study. There were 593 URTI episodes in the vitamin D group and 611 in the placebo group, with no statistically significant differences in the number of URTIs per participant (mean, 3.7 per person in the vitamin D group and 3.8 per person in the placebo group; risk ratio, 0.97; 95% CI, 0.85-1.11), number of days of missed work as a result of URTIs (mean, 0.76 days in each group; risk ratio, 1.03; 95% CI, 0.81-1.30), duration of symptoms per episode (mean, 12 days in each group; risk ratio, 0.96; 95% CI, 0.73-1.25), or severity of URTI episodes. These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels. Conclusion In this trial, monthly administration of 100 000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults. Trial Registration anzctr.org.au Identifier: ACTRN12609000486224

https://jamanetwork.com/journals/jama/articlepdf/1367547/joc120088_1333_1339.pdf

Effect of Vitamin D3 Supplementation on Upper Respiratory Tract Infections in Healthy Adults: The VIDARIS Randomized Controlled Trial

Repeated acute or chronic exposure to a particular stress results in adaptation whereby the hypothalamopituitary adrenal (HPS) axis becomes less responsive to subsequent or continued exposure to that particular stress. To investigate the adaptive changes that occur in the HPA axis in response to chronic stress in humans, we studied the effect of chronic exercise stress on basal activity of the HPA axis in six highly trained male ultramarathon athletes and six healthy male controls matched for body mass index. After 3-5 of abstention from intense physical activity, the subjects were admitted to a metabolic study ward at 1600 h. Peripheral blood was sampled initially at 0300 h, at 20-min intervals from 0400 to 0900 h, hourly from 0900 to 1200 h, and then every 2 h from 1200 to 1600 h. A 24-h urine collection was completed during the admission. Peripheral blood adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. Plasma and urinary cortisol were measured by enzyme-linked immunoassay. Plasma and injury cortisol were measured by enzyme-linked immunosorbent assay (ELISA). Plasma ACTH and cortisol levels showed the expected diurnal change in athletes and control subjects (P = 0.00001). However, the early morning ACTH and cortisol surge occurred earlier in the athletes than in the controls (P = 0.026). Plasma ACTH levels were significantly higher in the athletes than in the control subjects (P = 0.0026). There was, however, no significant overall difference in plasma cortisol levels between the athletes and the control subjects, and urinary excretion of free cortisol was similar in the two groups. These data show that intense physical training leads to adaptive changes in basal HPA function, including a phase shift and increased pituitary in basal HPA function, including a phase shift and increased pituitary ACTH secretion, but also blunting of the adrenal cortisol response.

John H. Livesey

Papers

Modeling the Reactions of Superoxide and Myeloperoxidase in the Neutrophil Phagosome: IMPLICATIONS FOR MICROBIAL KILLING*

Effect of anticoagulants and storage temperatures on stability of plasma and serum hormones.

FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study.

Effect of Vitamin D3 Supplementation on Upper Respiratory Tract Infections in Healthy Adults: The VIDARIS Randomized Controlled Trial

Adaptation of the hypothalamopituitary adrenal axis to chronic exercise stress in humans