scholarly journals Acute mountain sickness, inflammation, and permeability: new insights from a blood biomarker study

2011 ◽  
Vol 111 (2) ◽  
pp. 392-399 ◽  
Author(s):  
Colleen Glyde Julian ◽  
Andrew W. Subudhi ◽  
Megan J. Wilson ◽  
Andrew C. Dimmen ◽  
Travis Pecha ◽  
...  
Keyword(s):  
Acute Mountain Sickness ◽  
Barometric Pressure ◽  
Hypoxic Exposure ◽  
Hsp 70 ◽  
Double Blind ◽  
Inflammatory Protein ◽  
Chemotactic Protein ◽  
Mountain Sickness ◽  
Anti Inflammatory ◽  
Macrophage Inflammatory Protein

The pathophysiology of acute mountain sickness (AMS) is unknown. One hypothesis is that hypoxia induces biochemical changes that disrupt the blood-brain barrier (BBB) and, subsequently, lead to the development of cerebral edema and the defining symptoms of AMS. This study explores the relationship between AMS and biomarkers thought to protect against or contribute to BBB disruption. Twenty healthy volunteers participated in a series of hypobaric hypoxia trials distinguished by pretreatment with placebo, acetazolamide (250 mg), or dexamethasone (4 mg), administered using a randomized, double-blind, placebo-controlled, crossover design. Each trial included peripheral blood sampling and AMS assessment before (−15 and 0 h) and during (0.5, 4, and 9 h) a 10-h hypoxic exposure (barometric pressure = 425 mmHg). Anti-inflammatory and/or anti-permeability [interleukin (IL)-1 receptor agonist (IL-1RA), heat shock protein (HSP)-70, and adrenomedullin], proinflammatory (IL-6, IL-8, IL-2, IL-1β, and substance P), angiogenic, or chemotactic biomarkers (macrophage inflammatory protein-1β, VEGF, TNF-α, monocyte chemotactic protein-1, and matrix metalloproteinase-9) were assessed. AMS-resistant subjects had higher IL-1RA (4 and 9 h and overall), HSP-70 (0 h and overall), and adrenomedullin (overall) compared with AMS-susceptible subjects. Acetazolamide raised IL-1RA and HSP-70 compared with placebo in AMS-susceptible subjects. Dexamethasone also increased HSP-70 and adrenomedullin in AMS-susceptible subjects. Macrophage inflammatory protein-1β was higher in AMS-susceptible than AMS-resistant subjects after 4 h of hypoxia; dexamethasone minimized this difference. Other biomarkers were unrelated to AMS. Resistance to AMS was accompanied by a marked anti-inflammatory and/or anti-permeability response that may have prevented downstream pathophysiological events leading to AMS. Conversely, AMS susceptibility does not appear to be related to an exaggerated inflammatory response.

scholarly journals Acetazolamide reduces exercise capacity and increases leg fatigue under hypoxic conditions

2003 ◽  
Vol 94 (3) ◽  
pp. 991-996 ◽  
Author(s):  
Luke A. Garske ◽  
Michael G. Brown ◽  
Stephen C. Morrison
Keyword(s):  
Exercise Capacity ◽  
Ventilatory Response ◽  
Acute Mountain Sickness ◽  
Peak Exercise ◽  
Double Blind ◽  
Ventilatory Responses ◽  
Hypoxic Conditions ◽  
Mountain Sickness ◽  
Randomized Crossover Study ◽  
Hypoxic Exercise

Acetazolamide (Acz) is used at altitude to prevent acute mountain sickness, but its effect on exercise capacity under hypoxic conditions is uncertain. Nine healthy men completed this double-blind, randomized, crossover study. All subjects underwent incremental exercise to exhaustion with an inspired O2 fraction of 0.13, hypoxic ventilatory responses, and hypercapnic ventilatory responses after Acz (500 mg twice daily for 5 doses) and placebo. Maximum power of 203 ± 38 (SD) W on Acz was less than the placebo value of 225 ± 40 W ( P < 0.01). At peak exercise, arterialized capillary pH was lower and Po 2 higher on Acz ( P < 0.01). Ventilation was 118.6 ± 20.0 l/min at the maximal power on Acz and 102.4 ± 20.7 l/min at the same power on placebo ( P < 0.02), and Borg score for leg fatigue was increased on Acz ( P < 0.02), with no difference in Borg score for dyspnea. Hypercapnic ventilatory response on Acz was greater ( P < 0.02), whereas hypoxic ventilatory response was unchanged. During hypoxic exercise, Acz reduced exercise capacity associated with increased perception of leg fatigue. Despite increased ventilation, dyspnea was not increased.

scholarly journals Mechanisms Mediating Anti-Inflammatory Effects of Delta-Tocotrienol and Tart Cherry Anthocyanins in 3T3-L1 Adipocytes

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3356
Author(s):  
Lexie Harlan ◽  
London T. Mena ◽  
Latha Ramalingam ◽  
Shasika Jayarathne ◽  
Chwan-Li Shen ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Combined Treatment ◽  
Low Grade ◽  
Tart Cherry ◽  
Metabolic Complications ◽  
Inflammatory Protein ◽  
Anti Inflammatory ◽  
Low Grade Inflammation ◽  
Macrophage Inflammatory Protein

Chronic low-grade inflammation is a primary characteristic of obesity and can lead to other metabolic complications including insulin resistance and type 2 diabetes (T2D). Several anti-inflammatory dietary bioactives decrease inflammation that accompanies metabolic diseases. We are specifically interested in delta-tocotrienol, (DT3) an isomer of vitamin E, and tart cherry anthocyanins (TCA), both of which possess individual anti-inflammatory properties. We have previously demonstrated that DT3 and TCA, individually, reduced systemic and adipose tissue inflammation in rodent models of obesity. However, whether these compounds have combinatorial effects has not been determined yet. Hence, we hypothesize that a combined treatment of DT3 and TCA will have great effects in reducing inflammation in adipocytes, and that these effects are mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), a major inflammatory transcription factor. We used 3T3-L1 adipocytes and treated them with 1–5 µM doses of DT3 along with tart cherry containing 18–36 µg anthocyanin/mL, to assess effects on inflammation. Neither DT3 nor TCA, nor their combinations had toxic effects on adipocytes. Furthermore, pro-inflammatory markers interleukin-6 (IL-6) and p-65 (subunit of NFkB) were reduced at the protein level in media collected from adipocytes with both individual and combined treatments. Additionally, other downstream targets of NFkB including macrophage inflammatory protein 2 (Mip2), and Cyclooxygenase-2 (Cox2) were also significantly downregulated (p ≤ 0.05) when treated with individual and combined doses of DT3 and TCA with no additional combinatorial effects. In summary, DT3 and TCA individually, are beneficial in reducing inflammation with no additional combinatorial effects.

Intermittent altitude exposures reduce acute mountain sickness at 4300 m

2004 ◽  
Vol 106 (3) ◽  
pp. 321-328 ◽  
Author(s):  
Beth A. BEIDLEMAN ◽  
Stephen R. MUZA ◽  
Charles S. FULCO ◽  
Allen CYMERMAN ◽  
Dan DITZLER ◽  
...  
Keyword(s):  
Acute Mountain Sickness ◽  
Urine Volume ◽  
Barometric Pressure ◽  
Self Report ◽  
Altitude Exposure ◽  
Cerebral Symptom ◽  
Cycle Training ◽  
Mountain Sickness ◽  
End Tidal ◽  
Rest And Exercise

Acute mountain sickness (AMS) commonly occurs at altitudes exceeding 2000–2500 m and usually resolves after acclimatization induced by a few days of chronic residence at the same altitude. Increased ventilation and diuresis may contribute to the reduction in AMS with altitude acclimatization. The aim of the present study was to examine the effects of intermittent altitude exposures (IAE), in combination with rest and exercise training, on the incidence and severity of AMS, resting ventilation and 24-h urine volume at 4300 m. Six lowlanders (age, 23±2 years; body weight, 77±6 kg; values are means±S.E.M.) completed an Environmental Symptoms Questionnaire (ESQ) and Lake Louise AMS Scoring System (LLS), a resting end-tidal partial pressure of CO2 (PETCO2) test and a 24-h urine volume collection at sea level (SL) and during a 30 h exposure to 4300 m altitude-equivalent (barometric pressure=446 mmHg) once before (PreIAE) and once after (PostIAE) a 3-week period of IAE (4 h·day-1, 5 days·week-1, 4300 m). The previously validated factor score, AMS cerebral score, was calculated from the ESQ and the self-report score was calculated from the LLS at 24 h of altitude exposure to assess the incidence and severity of AMS. During each IAE, three subjects cycled for 45–60 min·day-1 at 60–70% of maximal O2 uptake (VO2 max) and three subjects rested. Cycle training during each IAE did not affect any of the measured variables, so data from all six subjects were combined. The results showed that the incidence of AMS (%), determined from both the ESQ and LLS, increased (P<0.05) from SL (0±0) to PreIAE (50±22) at 24 h of altitude exposure and decreased (P<0.05) from PreIAE to PostIAE (0±0). The severity of AMS (i.e. AMS cerebral symptom and LLS self-report scores) increased (P<0.05) from SL (0.02±0.02 and 0.17±0.17 respectively) to PreIAE (0.49±0.18 and 4.17±0.94 respectively) at 24 h of altitude exposure, and decreased (P<0.05) from PreIAE to PostIAE (0.03±0.02 and 0.83±0.31 respectively). Resting PETCO2 (mmHg) decreased (i.e. increase in ventilation; P<0.05) from SL (38±1) to PreIAE (32±1) at 24 h of altitude exposure and decreased further (P<0.05) from PreIAE to PostIAE (28±1). In addition, 24-h urine volumes were similar at SL, PreIAE and PostIAE. In conclusion, our findings suggest that 3 weeks of IAE provide an effective alternative to chronic altitude residence for increasing resting ventilation and reducing the incidence and severity of AMS.

scholarly journals Inhibitory Effect of Ferulic Acid and Isoferulic Acid on the Production of Macrophage Inflammatory Protein-2 in Response to Respiratory Syncytial Virus Infection in RAW264.7 Cells

1999 ◽  
Vol 8 (3) ◽  
pp. 173-175 ◽  
Author(s):  
S. Sakai ◽  
H. Kawamata ◽  
T. Kogure ◽  
N. Mantani ◽  
K. Terasawa ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Ferulic Acid ◽  
Dependent Manner ◽  
Inflammatory Drug ◽  
Inflammatory Protein ◽  
Isoferulic Acid ◽  
Infected Cells ◽  
Anti Inflammatory ◽  
Syncytial Virus ◽  
Macrophage Inflammatory Protein

We investigated the effect of ferulic acid (FA) and isoferulic acid (IFA), which are the main active components of the rhizoma ofCimicifuga heracleifolia(CH), an anti-inflammatory drug used frequently in Japanese traditional medicine, on the production of macrophage inflammatory protein-2 (MIR-2) in a murine macrophage cell line, RAW264.7, in response to respiratory syncytial virus (RSV) infection. Following the exposure of cells to RSV for 20 h, the MIP-2 level in condition medium was increased to about 20 ng/ml, although this level in mock-infected cells was negligible. In the presence of either FA or IFA, RSV-infected cells reduced MIP-2 production in a dose-dependent manner. These data suggest that FA and IFA might be responsible, at least in part, for the anti-inflammatory drug effect of CH extract through the inhibition of MIP-2 production.

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