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1.
J Renin Angiotensin Aldosterone Syst ; 17(2): 1470320316653867, 2016.
Article in English | MEDLINE | ID: mdl-27317302

ABSTRACT

INTRODUCTION: Inhaled budesonide is a novel approach to prevent acute mountain sickness (AMS). However, its mechanism is not completely understood. We aimed to investigate the effects of budesonide and dexamethasone on renin-angiotensin-aldosterone system in AMS prevention. MATERIALS AND METHODS: Data were obtained from a randomised controlled trial including 138 participants. The participants were randomly assigned to receive budesonide, dexamethasone or placebo as prophylaxis before they travelled to 3450 m altitude from 400 m by car. Their plasma concentrations of renin, angiotensin-converting enzyme (ACE) and aldosterone were measured at both altitudes. RESULTS: All parameters were comparable among the three groups at 400 m. After high-altitude exposure of 3450, renin in all groups increased significantly; the ACE, aldosterone concentrations, as well as the aldosterone/renin ratio, rose markedly in the dexamethasone and placebo groups but not in the budesonide group. Moreover, the aldosterone/renin ratio correlated closely with ACE concentration. CONCLUSIONS: Upon acute high-altitude exposure, budesonide, but not dexamethasone, blunted the response of aldosterone to renin elevation by suppressing angiotensin converting enzyme.


Subject(s)
Aldosterone/therapeutic use , Altitude Sickness/blood , Altitude Sickness/drug therapy , Budesonide/therapeutic use , Dexamethasone/therapeutic use , Peptidyl-Dipeptidase A/metabolism , Renin/blood , Aldosterone/pharmacology , Altitude , Budesonide/pharmacology , Dexamethasone/pharmacology , Humans , Renin-Angiotensin System/drug effects
3.
J Emerg Med ; 48(2): 197-206, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25294611

ABSTRACT

BACKGROUND: Oral glucocorticoids can prevent acute mountain sickness (AMS). Whether inhaled budesonide (BUD) can prevent AMS remains unknown. OBJECTIVE: Our aim was to investigate the effectiveness of BUD in AMS prevention. METHODS: Eighty subjects were randomly assigned to receive budesonide (BUD, inhaled), procaterol tablet (PT), budesonide/formoterol (BUD/FM, inhaled), or placebo tablet (n = 20 in each group). Subjects were treated for 3 days before ascending from 500 m to 3700 m within 2.5 h by air. Lake Louis AMS questionnaire, blood pressure, heart rate, and oxygen saturation (SpO2) were examined at 20, 72, and 120 h after high-altitude exposure. Pulmonary function was measured at 20 h after exposure. RESULTS: Compared with placebo, BUD significantly reduced the incidence of AMS (70% vs. 25% at 20 h, p < 0.05; both 10% vs. 5% at 72 and 120 h, both p > 0.05) without side effects. The relative risk was 0.357, and the risk difference was 0.45. Mean SpO2 was higher in BUD, BUD/FM, and PT groups than in the placebo group at 20 h (p < 0.05). SpO2 in all 80 subjects dropped after ascent (98.1% to 88.12%, p < 0.01) and increased gradually, but it was still lower at 120 h than at baseline (92.04% vs. 98.1%, p < 0.01). Pulmonary function did not differ among the four groups at 20 h. CONCLUSION: BUD can prevent AMS without side effects. The alleviation of AMS may be related to increased blood oxygen levels rather than pulmonary function.


Subject(s)
Altitude Sickness/prevention & control , Bronchodilator Agents/administration & dosage , Budesonide/administration & dosage , Glucocorticoids/administration & dosage , Acute Disease , Adolescent , Adult , Altitude Sickness/physiopathology , Blood Pressure/physiology , China , Forced Expiratory Volume/physiology , Heart Rate/physiology , Humans , Male , Oxygen Consumption/physiology , Vital Capacity/physiology , Young Adult
4.
Am J Med ; 127(10): 1001-1009.e2, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24784698

ABSTRACT

BACKGROUND: This double-blind, randomized controlled trial aimed to investigate inhaled budesonide and oral dexamethasone compared with placebo for their prophylactic efficacy against acute mountain sickness after acute high-altitude exposure. METHODS: There were 138 healthy young male lowland residents recruited and randomly assigned to receive inhaled budesonide (200 µg, twice a day [bid]), oral dexamethasone (4 mg, bid), or placebo (46 in each group). They traveled to 3900 m altitude from 400 m by car. Medication started 1 day before high-altitude exposure and continued until the third day of exposure. Primary outcome measure was the incidence of acute mountain sickness after exposure. RESULTS: One hundred twenty-four subjects completed the study (42, 39, and 43 in the budesonide, dexamethasone, and placebo groups, respectively). Demographic characteristics were comparable among the 3 groups. After high-altitude exposure, significantly fewer participants in the budesonide (23.81%) and dexamethasone (30.77%) groups developed acute mountain sickness compared with participants receiving placebo (60.46%) (P = .0006 and P = .0071, respectively). Both the budesonide and dexamethasone groups had lower heart rate and higher pulse oxygen saturation (SpO2) than the placebo group at altitude. Only the budesonide group demonstrated less deterioration in forced vital capacity and sleep quality than the placebo group. Four subjects in the dexamethasone group reported adverse reactions. CONCLUSIONS: Both inhaled budesonide (200 µg, bid) and oral dexamethasone (4 mg, bid) were effective for the prevention of acute mountain sickness, especially its severe form, compared with placebo. Budesonide caused fewer adverse reactions than dexamethasone.


Subject(s)
Altitude Sickness/prevention & control , Budesonide/administration & dosage , Dexamethasone/administration & dosage , Acute Disease , Administration, Inhalation , Administration, Oral , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Budesonide/adverse effects , Dexamethasone/adverse effects , Double-Blind Method , Heart Rate/drug effects , Heart Rate/physiology , Humans , Male , Oximetry , Oxygen Consumption/drug effects , Oxygen Consumption/physiology , Prospective Studies , Sleep/drug effects , Sleep/physiology , Spirometry , Young Adult
5.
Neuropharmacology ; 60(6): 921-9, 2011 May.
Article in English | MEDLINE | ID: mdl-21277878

ABSTRACT

Intense noxious stimuli impair GABAergic inhibition in spinal dorsal horn, which has been proposed as a critical contributor to pathological pain. However, how the reduced inhibition exacerbates the transfer of nociceptive information at excitatory glutamatergic synapses is still poorly understood. The present study demonstrated that one of the striking consequences of GABAergic disinhibition was to enhance the function of N-methyl-D-aspartate subtype glutamate receptors (NMDARs), a well-characterized player in central sensitization. We found that intrathecal application of bicuculline, a GABA(A) receptor antagonist, to remove the inhibition readily elicited mechanical allodynia in naive mice, which could be dose-dependently attenuated by NMDARs antagonist D-APV. Biochemical analysis demonstrated that bicuculline did not affect the total expression levels of the obligatory NMDARs subunit NR1 and the regulatory subunit NR2A and NR2B. However, bicuculline promoted NR1 phosphorylation at Serine 897 (NR1-S897) by cAMP-dependent protein kinase (PKA). This PKA-mediated phosphorylation incorporated NR1 along with NR2B into synapses. When PKA inhibitor H-89 was intrathecally applied, it totally eliminated bicuculline-induced NMDARs phosphorylation, synaptic redistribution as well as pain sensitization. Importantly, the reduced inhibition also operated to enhance NMDARs functions after peripheral inflammation, because spinal injection of diazepam to rescue the inhibition in inflamed mice greatly depressed PKA phosphorylation of NR1-S897, reduced the synaptic concentration of NR1/NR2B and meanwhile, alleviated the inflammatory pain. These data suggested that removal of GABAergic inhibition allowed for PKA-mediated NMDARs phosphorylation and synaptic accumulation, thus exaggerating NMDARs-dependent nociceptive transmission and behavioral sensitization.


Subject(s)
Hyperalgesia/physiopathology , Neural Inhibition/physiology , Posterior Horn Cells/physiopathology , Receptors, GABA-A/physiology , Receptors, N-Methyl-D-Aspartate/physiology , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Bicuculline/antagonists & inhibitors , Bicuculline/pharmacology , Diazepam/pharmacology , Drug Interactions , Excitatory Amino Acid Antagonists/pharmacology , GABA-A Receptor Antagonists/pharmacology , Hyperalgesia/chemically induced , Hyperalgesia/metabolism , Isoquinolines/pharmacology , Male , Mice , Mice, Inbred C57BL , Neural Inhibition/drug effects , Phosphorylation/drug effects , Posterior Horn Cells/metabolism , Protein Kinase Inhibitors/pharmacology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolism , Sulfonamides/pharmacology
6.
Molecules ; 13(11): 2859-70, 2008 Nov 17.
Article in English | MEDLINE | ID: mdl-19015625

ABSTRACT

Color is one of the key characteristics used to evaluate the sensory quality of red wine, and anthocyanins are the main contributors to color. Monomeric anthocyanins and CIELAB color values were investigated by HPLC-MS and spectrophotometry during fermentation of Cabernet Sauvignon red wine, and principal component regression (PCR), a statistical tool, was used to establish a linkage between the detected anthocyanins and wine coloring. The results showed that 14 monomeric anthocyanins could be identified in wine samples, and all of these anthocyanins were negatively correlated with the L*, b* and H*ab values, but positively correlated with a* and C*ab values. On an equal concentration basis for each detected anthocyanin, cyanidin-3-O-glucoside (Cy3-glu) had the most influence on CIELAB color value, while malvidin 3-O-glucoside (Mv3-glu) had the least. The color values of various monomeric anthocyanins were influenced by their structures, substituents on the B-ring, acyl groups on the glucoside and the molecular steric structure. This work develops a statistical method for evaluating correlation between wine color and monomeric anthocyanins, and also provides a basis for elucidating the effect of intramolecular copigmentation on wine coloring.


Subject(s)
Anthocyanins/chemistry , Principal Component Analysis/methods , Wine/analysis , Chromatography, High Pressure Liquid/methods , Color , Glucosides/chemistry , Molecular Structure , Reproducibility of Results , Spectrophotometry/methods
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