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- Heredia-Martinez, A., et al.
(author)
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Plasma Nitrate and Nitrite Kinetics after Single Intake of Beetroot Juice in Adult Patients on Chronic Hemodialysis and in Healthy Volunteers : A Randomized, Single-Blind, Placebo-Controlled, Crossover Study
- 2022
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In: Nutrients. - : MDPI. - 2072-6643. ; 14:12
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Journal article (peer-reviewed)abstract
- Nitric oxide (NO) contributes to maintaining normal cardiovascular and renal function. NO is generally formed enzymatically by NO synthase in the vascular endothelium. NO bioactivity can also be attributed to dietary intake of inorganic nitrate, which is abundant in our diet, especially in green leafy vegetables and beets. Ingested nitrate is reduced to nitrite by oral commensal bacteria and further to NO systemically. Previous studies have shown that dialysis, by means of removing nitrate and nitrite from the body, can reduce NO bioactivity. Hence, dietary intervention approaches aimed to boost the nitrate–nitrite–NO pathway may be of benefit in dialysis patients. The purpose of this study was to examine the kinetics of plasma nitrate and nitrite after a single intake of nitrate-rich concentrated beetroot juice (BJ) in adult hemodialysis (HD) patients and in healthy volunteers (HV). Eight HD patients and seven HV participated in this single center, randomized, single-blind, placebo-controlled, crossover study. Each participant received a sequential single administration of active BJ (70 mL 400 mg nitrate) and placebo BJ (70 mL 0 mg nitrate) in a random order separated by a washout period of seven days. For the kinetic analysis, blood samples were collected at different time-points before and up to 44 h after BJ intake. Compared with placebo, active BJ significantly increased plasma nitrate and nitrite levels both in HD patients and HV. The area under the curve and the maximal concentration of plasma nitrate, but not of nitrite, were significantly higher in HD patients as compared with HV. In both groups, active BJ ingestion did not affect blood pressure or plasma potassium levels. Both BJs were well tolerated in all participants with no adverse events reported. Our data provide useful information in planning dietary nitrate supplementation efficacy studies in patients with reduced NO bioactivity. © 2022 by the authors.
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- Kraen, M., et al.
(author)
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Fibroblast growth factor 23 is an independent marker of COPD and is associated with impairment of pulmonary function and diffusing capacity
- 2021
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111. ; 182
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Journal article (peer-reviewed)abstract
- Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that in recent years has been reported to have significant effects on numerous tissues. Chronic obstructive pulmonary disease (COPD) is associated with hypophosphatemia but the evidence for elevated plasma levels of FGF23 in COPD subjects is ambiguous. Recently, FGF23 has even been shown to be involved in the inflammatory pathways activated in COPD, so FGF23 could be a novel biomarker for COPD and impairment of pulmonary function. The purpose was thus to explore the association of FGF23 with COPD and measures of pulmonary function. This was a cross sectional study of 450 subjects who underwent spirometry, body plethysmography, determination of diffusing capacity (DL,CO) and biomarker analysis of FGF23, interleukin (IL)-1 receptor antagonist, IL-6 and IL-8. Forty-four participants were excluded due to missing data or renal impairment (eGFR <45 mL/min/m2). Spirometry identified 123 subjects with COPD. FGF23 levels were elevated in COPD subjects compared to non COPD subjects, and this remained significant after adjustment for age, sex and smoking habits (OR = 1.6, p = 0.02). Linear regression showed significant relationships between FGF23 and FEV1 (β = −0.15, p = 0.003), RV/TLC (β = 0.09, p = 0.05) and DL, CO (β = −0.24, p < 0.001). In conclusion we found that plasma levels of FGF23 are elevated in COPD subjects even when adjusting for traditional risk factors. Furthermore, FGF23 is associated with impairment in lung function as measured by FEV1 and DL,CO. Further studies are needed to establish whether FGF23 could serve as a novel biomarker of COPD and emphysema development.
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| 12. |
- Kraen, M., et al.
(author)
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Matrix Metalloproteinases in COPD and atherosclerosis with emphasis on the effects of smoking
- 2019
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:2
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Journal article (peer-reviewed)abstract
- Background Matrix metalloproteinases (MMP´s) are known biomarkers of atherosclerosis. MMP´s are also involved in the pathophysiological processes underlying chronic obstructive pulmonary disease (COPD). Cigarette smoking plays an important role in both disease states and is also known to affect the concentration and activity of MMP´s systemically. Unfortunately, the epidemiological data concerning the value of MMP´s as biomarkers of COPD and atherosclerosis with special regards to smoking habits are limited. Methods 450 middle-aged subjects with records of smoking habits and tobacco consumption were examined with comprehensive spirometry, carotid ultrasound examination and biomarker analysis of MMP-1, -3, -7, -10 and -12. Due to missing data 33 subjects were excluded. Results The remaining 417 participants were divided into 4 different groups. Group I (n = 157, no plaque and no COPD), group II (n = 136, plaque but no COPD), group III (n = 43, COPD but no plaque) and group IV (n = 81, plaque and COPD). Serum levels of MMP-1,-7,-10-12 were significantly influenced by smoking, and MMP-1, -3, -7 and-12 were elevated in subjects with COPD and carotid plaque. This remained statistically significant for MMP-1 and-12 after adjusting for traditional risk factors. Conclusion COPD and concomitant plaque in the carotid artery were associated with elevated levels of MMP-1 and -MMP-12 even when adjusting for risk factors. Further studies are needed to elucidate if these two MMP´s could be useful as biomarkers in a clinical setting. Smoking was associated with increased serum levels of MMP´s (except for MMP-3) and should be taken into account when interpreting serum MMP results.
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| 13. |
- Kuna, P., et al.
(author)
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Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma
- 2006
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In: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 100:12, s. 2151-2159
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Journal article (peer-reviewed)abstract
- Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-retated morbidity. In this 12-week, randomized, double-blind, double-dummy, parattel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1 s [FEV,] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500pg/day) were randomized to once-daily budesonide/formoterot (80/4.5 tg, 2 inhalations in the evening), twice-daity budesonide/formoterol (80/4.5 pg, 1 inhalation), or a corresponding dose of budesonide once-daily (200pg, 1 inhalation in the evening). AR patients received budesonide (100pg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterot (24.1 l/min), and both were greater than with budesonide (5.5 Unnin; both P < 0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/ formoterol therapy vs. budesonide (P < 0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterot administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma. (c) 2006 Elsevier Ltd. All rights reserved.
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| 14. |
- Lindberg, C A, et al.
(author)
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Total desmosines in plasma and urine correlate with lung function.
- 2011
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936.
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Journal article (peer-reviewed)abstract
- To evaluate the relationship between the matrix degradation biomarkers, desmosine and isodesmosine (desmosines), and lung function.Plasma and creatinine-corrected urinary total desmosines (P- and U-desmosines), lung function and carbon monoxide diffusion capacity (DL,CO) were measured in a cohort of subjects from the Swedish Twin Registry.Concentrations of U- and P-desmosines were measured in 349 and 318 subjects, respectively; approximately one-third of subjects had chronic obstructive pulmonary disease (COPD). Age, female gender, body mass index (BMI) and smoking were significantly associated with U-desmosines in a multiple linear regression analysis. In the overall population, after adjustments for age, gender, height, BMI and smoking, concentrations of U-desmosines were significantly correlated with all lung function measures, and P-desmosines with forced expiratory volume in 1 s and DL,CO (P<0.05). With the exception of residual volume versus P-desmosines, relationships between concentrations of desmosines and lung function measures were markedly stronger in subjects with COPD compared with those without COPD.These cross-sectional data showing associations between desmosines and several lung function variables suggest that desmosines, particularly U-desmosines, could be a useful biomarker of COPD status.
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- Tropea, T, et al.
(author)
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Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction
- 2021
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In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:9
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Journal article (peer-reviewed)abstract
- Nitric oxide (NO) is essential in the control of fetoplacental vascular tone, maintaining a high flow−low resistance circulation that favors oxygen and nutrient delivery to the fetus. Reduced fetoplacental blood flow is associated with pregnancy complications and is one of the major causes of fetal growth restriction (FGR). The reduction of dietary nitrate to nitrite and subsequently NO may provide an alternative source of NO in vivo. We have previously shown that nitrite induces vasorelaxation in placental blood vessels from normal pregnancies, and that this effect is enhanced under conditions of hypoxia. Herein, we aimed to determine whether nitrite could also act as a vasodilator in FGR. Using wire myography, vasorelaxant effects of nitrite were assessed on pre-constricted chorionic plate arteries (CPAs) and veins (CPVs) from normal and FGR pregnancies under normoxic and hypoxic conditions. Responses to the NO donor, sodium nitroprusside (SNP), were assessed in parallel. Nitrate and nitrite concentrations were measured in fetal plasma. Hypoxia significantly enhanced vasorelaxation to nitrite in FGR CPAs (p < 0.001), and in both normal (p < 0.001) and FGR (p < 0.01) CPVs. Vasorelaxation to SNP was also potentiated by hypoxia in both normal (p < 0.0001) and FGR (p < 0.01) CPVs. However, compared to vessels from normal pregnancies, CPVs from FGR pregnancies showed significantly lower reactivity to SNP (p < 0.01). Fetal plasma concentrations of nitrate and nitrite were not different between normal and FGR pregnancies. Together, these data show that nitrite-mediated vasorelaxation is preserved in FGR, suggesting that interventions targeting this pathway have the potential to improve fetoplacental blood flow in FGR pregnancies.
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