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A polyphenol-rich dietary pattern improves intestinal permeability, evaluated as serum zonulin levels, in older subjects: The MaPLE randomised controlled trial.
Del Bo', C, Bernardi, S, Cherubini, A, Porrini, M, Gargari, G, Hidalgo-Liberona, N, González-Domínguez, R, Zamora-Ros, R, Peron, G, Marino, M, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3006-3018
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Abstract
BACKGROUND & AIM: Increased intestinal permeability (IP) can occur in older people and contribute to the activation of the immune system and inflammation. Dietary interventions may represent a potential strategy to reduce IP. In this regard, specific food bioactives such as polyphenols have been proposed as potential IP modulator due to their ability to affect several critical targets and pathways that control IP. The trial aimed to test the hypothesis that a polyphenol-rich dietary pattern can decrease serum zonulin levels, an IP surrogate marker involved in tight junction modulation, and can beneficially alter the intestinal microbiota, and IP-associated biochemical and clinical markers in older subjects. METHODS A randomised, controlled, cross-over intervention trial was performed. Sixty-six subjects (aged ≥ 60 y) with increased IP based on serum zonulin levels, were randomly allocated to one of the two arms of the intervention consisting of a control diet (C-diet) vs. a polyphenol-rich diet (PR-diet). Each intervention was 8-week long and separated by an 8-week wash out period. At the beginning and at the end of each intervention period, serum samples were collected for the quantification of zonulin and other biological markers. Faecal samples were also collected to investigate the intestinal microbial ecosystem. In addition, anthropometrical/physical/biochemical parameters and food intake were evaluated. RESULTS Fifty-one subjects successfully completed the intervention and a high compliance to the dietary protocols was demonstrated. Overall, polyphenol intake significantly increased from a mean of 812 mg/day in the C diet to 1391 mg/day in the PR-diet. Two-way analysis of variance showed a significant effect of treatment (p = 0.008) and treatment × time interaction (p = 0.025) on serum zonulin levels, which decreased after the 8-week PR-diet. In addition, a treatment × time interaction was observed showing a reduction of diastolic blood pressure (p = 0.028) following the PR-diet, which was strongest in those not using antihypertensive drugs. A decrease in both diastolic (p = 0.043) and systolic blood pressure (p = 0.042) was observed in women. Interestingly, a significant increase in fibre-fermenting and butyrate-producing bacteria such as the family Ruminococcaceae and members of the genus Faecalibacterium was observed following the PR intervention. The efficacy of this dietary intervention was greater in subjects with higher serum zonulin at baseline, who showed more pronounced alterations in the markers under study. Furthermore, zonulin reduction was also stronger among subjects with higher body mass index and with insulin resistance at baseline, thus demonstrating the close interplay between IP and metabolic features. CONCLUSIONS These data show, for the first time, that a PR-diet can reduce serum zonulin levels, an indirect marker of IP. In addition, PR-diet reduced blood pressure and increased fibre-fermenting and butyrate-producing bacteria. These findings may represent an initial breakthrough for further intervention studies evaluating possible dietary treatments for the management of IP, inflammation and gut function in different target populations. THIS STUDY WAS REGISTERED AT WWW.ISRCTN. ORG AS ISRCTN10214981.
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Dairy products influence gut hormone secretion and appetite differently: A randomized controlled crossover trial.
Hansson, P, Holven, KB, Øyri, LKL, Brekke, HK, Gjevestad, GO, Rehfeld, JF, Raza, GS, Herzig, KH, Ulven, SM
Journal of dairy science. 2020;(2):1100-1109
Abstract
Little is known about how dairy products with different nutrient contents and food matrices affect appetite sensation and gut hormone secretion. The objective of this study was to investigate how appetite sensation and gut hormone secretion in healthy adults are affected by meals with the same amount of fat but from different dairy products. Forty-seven healthy adults (70% women) were recruited to a randomized controlled crossover study with 4 dairy meals consisting of butter, cheese, whipped cream, or sour cream, corresponding to 45 g (approximately 60 energy percent) of fat. Plasma samples were collected for analysis of cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY), and ghrelin concentrations at 0, 2, 4, and 6 h after the meals and analyzed as the incremental area under the curve (iAUC0-6h) in a mixed model. Hunger, satiety, and appetite sensations were measured with a visual analog scale (VAS) immediately after finishing the meals and at 4 and 6 h postprandially. Intake of cheese induced a higher level of plasma PP-iAUC0-6h compared with butter or whipped cream, and a higher level of plasma CCK-iAUC0-6h compared with whipped cream. Intake of whipped cream increased VAS appetite at 4 h compared with cheese or sour cream, and at 6 h compared with cheese or butter. No significant meal effect was found for hunger, satiety, plasma PYY, or plasma ghrelin concentration. Intake of cheese increased postprandial plasma PP and CCK concentrations and decreased appetite compared with whipped cream but not with sour cream. These findings encourage further investigations of how different dairy products affect gut hormone secretion and appetite sensation.
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Proenkephalin for the early detection of acute kidney injury in hospitalized patients with chronic kidney disease.
Breidthardt, T, Jaeger, C, Christ, A, Klima, T, Mosimann, T, Twerenbold, R, Boeddinghaus, J, Nestelberger, T, Badertscher, P, Struck, J, et al
European journal of clinical investigation. 2018;(10):e12999
Abstract
BACKGROUND The early detection of acute kidney injury (AKI) in patients with chronic kidney disease (CKD) is an unmet clinical need. Proenkephalin (PENK) might improve the early detection of AKI. METHODS One hundred and eleven hospitalized CKD patients undergoing radiographic contrast procedures were enrolled. PENK was measured in a blinded fashion at baseline (before contrast media administration) and on day 1 (after contrast media administration). The potential of PENK levels to predict contrast-induced AKI was the primary endpoint. RESULTS Baseline creatinine and baseline PENK were similar in AKI and no-AKI patients. In AKI patients, day 1 PENK (198 pmol/L vs 121 pmol/L, P < 0.01) was significantly higher compared to no-AKI patients. The area under the curve (AUC) for the prediction of AKI by day 1 PENK was 0.79, 95% CI: 0.70-0.87, similar to serum creatinine: 0.78, 95% CI: 0.61-0.95. Delta PENK was significantly higher in AKI compared to no-AKI patients (53 pmol/L vs 1 pmol/L, P < 0.01). The AUC for the prediction of AKI by delta PENK was high (0.92, 95%CI 0.82-1.00) and remained high for creatinine-blind AKI (0.94, 95% CI: 0.87-0.97). CONCLUSION Delta PENK levels improve the early detection of contrast-induced AKI in CKD patients over serial creatinine sampling. Delta PENK accelerates the detection of creatinine-blind AKI by 24 hours.
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Effect of plasma sodium concentration on blood pressure regulators during hemodialysis: a randomized crossover study.
Ettema, EM, Kuipers, J, van Faassen, M, Groen, H, van Roon, AM, Lefrandt, JD, Westerhuis, R, Kema, IP, van Goor, H, Gansevoort, RT, et al
BMC nephrology. 2018;(1):214
Abstract
BACKGROUND Intradialytic hypotension is a common complication of hemodialysis. The Hemocontrol biofeedback system, improving intradialytic hemodynamic stability, is associated with an initial transient increase in plasma sodium levels. Increases in sodium could affect blood pressure regulators. METHODS We investigated whether Hemocontrol dialysis affects vasopressin and copeptin levels, endothelial function, and sympathetic activity in twenty-nine chronic hemodialysis patients. Each patient underwent one standard hemodialysis and one Hemocontrol hemodialysis. Plasma sodium, osmolality, nitrite and nitrate (NOx), endothelin-1, angiopoietins-1 and 2, and methemoglobin as measures of endothelial function, plasma catecholamines as indices of sympathetic activity and plasma vasopressin and copeptin levels were measured six times during each modality. Blood pressure, heart rate, blood volume, and heart rate variability were repeatedly monitored. Generalized Estimating Equations was used to compare the course of the parameters during the two treatment modalities. RESULTS Plasma sodium and osmolality were significantly higher during the first two hours of Hemocontrol hemodialysis. Overall, mean arterial pressure (MAP) was higher during Hemocontrol dialysis. Neither the measures of endothelial function and sympathetic activity nor copeptin levels differed between the two dialysis modalities. In contrast, plasma vasopressin levels were significantly higher during the first half of Hemocontrol dialysis. The intradialytic course of vasopressin was associated with the course of MAP. CONCLUSIONS A transient intradialytic increase in plasma sodium did not affect indices of endothelial function or sympathetic activity compared with standard hemodialysis, but coincided with higher plasma vasopressin levels. The beneficial effect of higher intradialytic sodium levels on hemodynamic stability might be mediated by vasopressin. TRIAL REGISTRATION ClinicalTrials.gov. Identifier: NCT03578510 . Date of registration: July 5th, 2018. Retrospectively registered.
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Procalcitonin-guided antibiotic therapy in aspiration pneumonia and an assessment of the continuation of oral intake.
Ogasawara, T, Umezawa, H, Naito, Y, Takeuchi, T, Kato, S, Yano, T, Kasamatsu, N, Hashizume, I
Respiratory investigation. 2014;(2):107-13
Abstract
BACKGROUND Procalcitonin-guided antibiotic therapy for community-acquired pneumonia is effective and safe. However, the usefulness of procalcitonin for aspiration pneumonia and its nutrition-related outcomes are unknown. METHODS We conducted a noninferiority randomized controlled study in patients with aspiration pneumonia who were admitted to our hospital between September 2010 and January 2012. We randomly assigned 105 patients to groups with different durations of antibiotic therapy based on the procalcitonin levels upon admission (procalcitonin group) or according to the standard guidelines (control group). The primary endpoints were relapse of aspiration pneumonia and death within 30 days, with a predefined noninferiority boundary of 10%. Secondary endpoints included duration of antibiotic exposure. Furthermore, we conducted a retrospective analysis of the prognostic factors that determined continuation of oral nutritional intake, relapse of pneumonia, and in-hospital death. RESULTS The rate of relapse and death within 30 days were similar in the procalcitonin and control groups (25% versus 37.5%; difference, -12.5%; 95% confidence interval, -30.9% to 5.9%). Procalcitonin-guided antibiotic therapy significantly shortened the median duration of antibiotic exposure (5 versus 8 days; p<0.0001); however, the continuation of oral intake was not increased (56% versus 50%; p=0.54). A multivariable analysis showed a significant association between the continuation of oral nutritional intake and the body mass index upon admission. CONCLUSIONS Procalcitonin-guided antibiotic therapy for aspiration pneumonia can shorten the duration of antibiotic exposure, but it does not increase the continuation of oral intake (UMIN000004800).
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Excluding infection through procalcitonin testing improves outcomes of congestive heart failure patients presenting with acute respiratory symptoms: results from the randomized ProHOSP trial.
Schuetz, P, Kutz, A, Grolimund, E, Haubitz, S, Demann, D, Vögeli, A, Hitz, F, Christ-Crain, M, Thomann, R, Falconnier, C, et al
International journal of cardiology. 2014;(3):464-72
Abstract
BACKGROUND/OBJECTIVES We sought to determine whether exclusion of infection and antibiotic stewardship with the infection biomarker procalcitonin improves outcomes in congestive heart failure (CHF) patients presenting to emergency departments with respiratory symptoms and suspicion of respiratory infection. METHODS We performed a secondary analysis of patients with a past medical history of CHF formerly included in a Swiss multicenter randomized-controlled trial. The trial compared antibiotic stewardship according to a procalcitonin algorithm or state-of-the-art guidelines (controls). The primary endpoint was a 30-day adverse outcome (death, intensive care unit admission); the secondary endpoints included a 30-day antibiotic exposure. RESULTS In the 110/233 analyzed patients (47.2%) with low initial procalcitonin (<0.25 μg/L), suggesting the absence of systemic bacterial infection, those randomized to procalcitonin guidance (n=50) had a significantly lower adverse outcome rate compared to controls (n=60): 4% vs. 20% (absolute difference -16.0%, 95% confidence interval (CI) -28.4% to -3.6%, P=0.01), and significantly reduced antibiotic exposure [days] (mean 3.7 ± 4.0 vs. 6.5 ± 4.4, difference -2.8 [95% CI, -4.4 to -1.2], P<0.01). When initial procalcitonin was ≥0.25 μg/L, procalcitonin-guided patients had significantly reduced antibiotic exposure due to early stop of therapy without any difference in adverse outcomes (25.8% vs. 24.6%, difference [95% CI] 1.2% [-14.5% to 16.9%, P=0.88]). CONCLUSIONS CHF patients presenting to the emergency department with respiratory symptoms and suspicion for respiratory infection had decreased antibiotic exposure and improved outcomes when procalcitonin measurement was used to exclude bacterial infection and guide antibiotic treatment. These data provide further evidence for the potential harmful effects of antibiotic / fluid treatment when used instead of diuretics and heart failure medication in clinically symptomatic CHF patients without underlying infection.
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Midregional proadrenomedullin and its change predicts recurrent major coronary events and heart failure in stable coronary heart disease patients: the LIPID study.
Funke-Kaiser, A, Mann, K, Colquhoun, D, Zeller, T, Hunt, D, Simes, J, Sullivan, D, Sydow, K, West, M, White, H, et al
International journal of cardiology. 2014;(2):411-8
Abstract
BACKGROUND Biomarkers may contribute to risk stratification in coronary heart disease (CHD). We examined whether plasma midregional proadrenomedullin (MR-proADM) concentration at baseline and its change over one year predicts long-term outcomes in stable CHD patients. METHODS The LIPID study randomised patients 3-36 months after an acute coronary syndrome with total cholesterol 4.0-7.0 mmol/L (155-271 mg/dL), to placebo or pravastatin 40 mg. Follow-up was 6.0 years. MR-proADM plasma concentrations at baseline and one year later were determined in 7863 and 6658 patients, respectively. These were categorised into quartiles to perform Cox regression analysis, adjusting for baseline parameters. RESULTS Baseline MR-proADM concentrations predicted major CHD events (non-fatal myocardial infarction or CHD death; hazard ratio (HR) 1.52, 1.26-1.84 for Q4-Q1), CHD death (HR 2.21, 1.67-2.92), heart failure (HR 2.30, 1.78-2.97) and all-cause mortality (HR 1.82, 1.49-2.23). Associations were still significant after adjustment for baseline B-type natriuretic peptide (BNP) concentration. Increase in MR-proADM after one year was associated with increased risk of subsequent CHD events (HR 1.34, 1.08-1.66), non-fatal myocardial infarction (HR 1.50, 1.12-2.03), heart failure (HR 1.78, 1.37-2.30) and all-cause mortality (HR 1.31, 1.04-1.64). Associations with heart failure and all-cause mortality remained significant after adjusting for baseline and change in BNP concentration. Change in MR-proADM moderately improved risk reclassification for major CHD events (net reclassification improvement (NRI) 3.48%) but strongly improved risk reclassification for heart failure (NRI 5.60%). CONCLUSIONS Baseline and change in MR-proADM concentrations over one year are associated with risk of major clinical events, even after adjustment for BNP concentrations.
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Differential effects of vitamin K1 on AFP and DCP levels in patients with unresectable HCC and in HCC cell lines.
Carr, BI, Wang, Z, Wang, M, Wei, G
Digestive diseases and sciences. 2011;(6):1876-83
Abstract
PURPOSE DCP is a useful HCC tumor marker, which reflects a defect in vitamin K metabolism. We tested the hypothesis that vitamin K treatment of HCC patients might suppress this marker and possibly AFP also. EXPERIMENTAL DESIGN HCC patients who had both elevated AFP and DCP were included. A phase I cohort was treated with escalating vitamin K1 intravenous weekly doses and a 27-patient phase II cohort was then treated with a fixed oral daily dose. RESULTS A maximum tolerated dose was not reached up to 100-fold the normal vitamin K1 dose. No toxicities were found up to 1,000 mg/infusion. In the phase II cohort, 93% of patients had tumor marker responses by decreased DCP levels, but only 22% had responses by decreased AFP levels. CT scans showed 11% of patients had PRs, 59% had stable tumors and 29.6% had tumor progression. Mechanism studies showed that vitamin K1 induced phosphorylation of JNK and c-Jun and caspase-mediated apoptosis. CONCLUSIONS Vitamin K1 was non-toxic at high doses, strongly inhibited plasma DCP levels, but weakly suppressed AFP levels. The results provide evidence that the two tumor markers are not directly linked and that DCP levels may not reflect HCC cell growth, as DCP levels were decreased in patients without AFP change, and were suppressed in vitro at 1% of the vitamin K1 concentration needed to inhibit AFP.
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Changes of serum prohepcidin, iron status and zinc-protoporphyrin in a random group of patients with malignant diseases.
Grudeva-Popova, JG, Terzieva, DD, Nenova, IS
Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2011;(2):361-5
Abstract
PURPOSE To investigate the changes in the serum levels of prohepcidin (pHp) and markers of iron homeostasis for gathering more data on the pathogenesis of anemia in malignancies. METHODS In 84 patients with advanced solid malignant tumors, but without iron or vitamin B12 and folate deficiency anemia, we measured serum pHp levels and common markers of iron status, erythropoiesis and inflammation. Two months later the same tests were repeated to determine possible changes in the levels of the measured parameters. RESULTS The first blood sample characterized the group with a moderately low hemoglobin (Hb) and high CRP levels, suggesting anemia in some patients. Two months later higher levels of serum iron (sFe), total iron binding capacity (TIBC), transferrin saturation, ferritin and zinc-protoporphyrine (ZPP) in erythrocytes were found, along with lower pHp and high sensitivity C-reactive protein (hs-CRP). The correlation coefficient (R) between the values of iron-containing substances and pHp were low (R=0.244). Allocations by sex, Hb concentration and pHp showed that the changes in each group were similar, keeping the trend of increased sFe, ferritin and ZPP, decreased hs-CRP and pHp, at a stable hematological state. CONCLUSION Because of low correlation between sFe and pHp, it seems more likely that the positive two-month change of iron-containing substances in the serum of the studied patients is a result of treatment, impaired liver function or malignant intoxication, rather than of decreased pHp.
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Influence of erythropoietin therapy on serum prohepcidin levels in dialysis patients.
Arabul, M, Gullulu, M, Yilmaz, Y, Eren, MA, Baran, B, Gul, CB, Kocamaz, G, Dilek, K
Medical science monitor : international medical journal of experimental and clinical research. 2009;(11):CR583-7
Abstract
BACKGROUND Anemia is a common finding in dialysis patients. Recent evidence has accrued that hepcidin, an iron regulatory peptide, may play a crucial role in the pathophysiology of this condition. This study investigated the effect of erythropoietin (EPO) therapy on serum levels of prohepcidin, the pro-hormone of hepcidin, in patients with end-stage renal disease (ESRD) undergoing chronic dialysis treatment. MATERIAL/METHODS A total of 40 ESRD patients with renal anemia receiving either hemodialysis or peritoneal dialysis were included in this study. The patients were randomly allocated to EPO (subcutaneous 2000 microg three times weekly) plus parenteral iron (n=23) or parental iron only (n=17). Serum prohepcidin levels were measured before and at the end of the study. RESULTS The two groups were comparable in their demographic and laboratory characteristics. No significant differences were found in hemoglobin, hematocrit, iron store indices, or serum levels of prohepcidin at study entry. Significant increases in both hemoglobin and hematocrit as well as a decrease in serum prohepcidin level were evident in the EPO group at the end of the 6-month follow-up in comparison with their values at study entry compared with the control group (P<0.01). CONCLUSIONS It is concluded that EPO therapy, besides enhancing erythropoiesis, modulates serum prohepcidin levels in dialysis patients.