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Administration of mucolytic solution before upper endoscopy - double-blind, monocentric, randomized study.
Stepan, M, Falt, P, Pipek, B, Fojtik, P, Hanousek, M, Hill, M, Urban, O
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2023;(1):69-73
Abstract
AIMS: Sufficient visibility of the mucosa during upper endoscopy is crucial for successful diagnosis, especially for early neoplastic lesions. Data documenting the effect of administration of mucolytic solution prior to gastroscopy in order to improve mucosal visibility are limited in Europe. The aim of the study was to assess the score of mucosal visibility in the upper gastrointestinal tract after administration of the mucolytic solution defined by us. PATIENTS AND METHODS This is a monocentric, double-blind, randomized study involving 134 patients indicated for diagnostic upper endoscopy. Patients were randomly assigned to one of three arms, with mucolytic solution (100 mL water + 400 mg N-acetylcysteine + 20 mg simethicone), without the solution , and with 100 mL pure water. During the examination, 11 photographs were taken in defined areas. The visibility score was given by the sum of the score 0-5 from 5 defined localities evaluated by a blinded endoscopist and subsequently by two blinded endoscopists. Other parameters monitored were examination time and a semiquantitative evaluation of residual gastric fluid. RESULTS The basic characteristics of the group (sex, age, indications for examination) were comparable between arms. The visibility score was similar in all arms - 17.4 ± 1.9 vs. 17.0 ± 2.0 vs. 17.6 ± 1.8 (P=0.32). The examination time and the amount of residual fluid in the stomach were comparable in all arms. CONCLUSIONS Administration of the mucolytic solution in our study did not increase the mucosal visibility score in the esophagus, stomach and duodenum. TRIAL REGISTRATION ClinicalTrials.gov, NCT02967094.
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Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease.
Clarke, R, Von Ende, A, Schmidt, LE, Yin, X, Hill, M, Hughes, AD, Pechlaner, R, Willeit, J, Kiechl, S, Watkins, H, et al
Circulation research. 2023;(4):452-464
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BACKGROUND Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls). METHODS The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use. Apolipoproteins were grouped into 4 lipid-related classes [lipoprotein(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides] and their associations with CHD were adjusted for established CHD risk factors and conventional lipids. Analyses of these apolipoproteins in a subset of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) were used to assess their within-person variability and to estimate a correction for statin use. The findings in the PROCARDIS study were compared with those for incident cardiovascular disease in the Bruneck prospective study (n=688), including new measurements of Apo(a). RESULTS Triglyceride-carrying apolipoproteins (ApoC1, ApoC3, and ApoE) were most strongly associated with the risk of CHD (2- to 3-fold higher odds ratios for top versus bottom quintile) independent of conventional lipid measures. Likewise, ApoB was independently associated with a 2-fold higher odds ratios of CHD. Lipoprotein(a) was measured using peptides from the Apo(a)-kringle repeat and Apo(a)-constant regions, but neither of these associations differed from the association with conventionally measured lipoprotein(a). Among HDL-related apolipoproteins, ApoA4 and ApoM were inversely related to CHD, independent of conventional lipid measures. The disease associations with all apolipoproteins were directionally consistent in the PROCARDIS and Bruneck studies, with the exception of ApoM. CONCLUSIONS Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction.
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Atrial nitroso-redox balance and refractoriness following on-pump cardiac surgery: a randomized trial of atorvastatin.
Jayaram, R, Jones, M, Reilly, S, Crabtree, MJ, Pal, N, Goodfellow, N, Nahar, K, Simon, J, Carnicer, R, DeSilva, R, et al
Cardiovascular research. 2022;(1):184-195
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AIMS: Systemic inflammation and increased activity of atrial NOX2-containing NADPH oxidases have been associated with the new onset of atrial fibrillation (AF) after cardiac surgery. In addition to lowering LDL-cholesterol, statins exert rapid anti-inflammatory and antioxidant effects, the clinical significance of which remains controversial. METHODS AND RESULTS We first assessed the impact of cardiac surgery and cardiopulmonary bypass (CPB) on atrial nitroso-redox balance by measuring NO synthase (NOS) and GTP cyclohydrolase-1 (GCH-1) activity, biopterin content, and superoxide production in paired samples of the right atrial appendage obtained before (PRE) and after CPB and reperfusion (POST) in 116 patients. The effect of perioperative treatment with atorvastatin (80 mg once daily) on these parameters, blood biomarkers, and the post-operative atrial effective refractory period (AERP) was then evaluated in a randomized, double-blind, placebo-controlled study in 80 patients undergoing cardiac surgery on CPB. CPB and reperfusion led to a significant increase in atrial superoxide production (74% CI 71-76%, n = 46 paired samples, P < 0.0001) and a reduction in atrial tetrahydrobiopterin (BH4) (34% CI 33-35%, n = 36 paired samples, P < 0.01), and in GCH-1 (56% CI 55-58%, n = 26 paired samples, P < 0.001) and NOS activity (58% CI 52-67%, n = 20 paired samples, P < 0.001). Perioperative atorvastatin treatment prevented the effect of CPB and reperfusion on all parameters but had no significant effect on the postoperative right AERP, troponin release, or NT-proBNP after cardiac surgery. CONCLUSION Perioperative statin therapy prevents post-reperfusion atrial nitroso-redox imbalance in patients undergoing on-pump cardiac surgery but has no significant impact on postoperative atrial refractoriness, perioperative myocardial injury, or markers of postoperative LV function. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/ct2/show/NCT01780740.
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Pharmacokinetics of Budesonide Oral Suspension in Children and Adolescents With Eosinophilic Esophagitis.
Gupta, SK, Hill, M, Vitanza, JM, Farber, RH, Desai, NK, Williams, J, Song, IH
Journal of pediatric gastroenterology and nutrition. 2022;(2):186-191
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The pharmacokinetic (PK) profile of budesonide oral suspension (BOS) was evaluated during a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in pediatric patients with eosinophilic esophagitis (EoE) (MPI 101-01/NCT00762073). Non-compartmental methods were used to calculate PK parameters in 37 patients after receiving morning doses of BOS, with volume and dose adjusted for age (low dose: 0.35 or 0.5 mg; high dose: 1.4 or 2.0 mg [2-9 or 10-18 years old, respectively]). Relationships between apparent oral clearance and volume of distribution, and bodyweight and body mass index were also evaluated. Budesonide systemic exposure increased with BOS dose. After oral administration, time to maximum plasma budesonide concentration occurred ~1 hour post dose and the half-life of budesonide was 3.3-3.5 hours. PK parameters were similar between age groups for low- and high-dose BOS, indicating that volume and dose adjustments for age were appropriate for pediatric patients with EoE. BOS was well tolerated.
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Yoga Exercise Intervention Improves Balance Control and Prevents Falls in Seniors Aged 65.
Krejčí, M, Hill, M, Kajzar, J, Tichý, M, Hošek, V
Zdravstveno varstvo. 2022;(2):85-92
Abstract
INTRODUCTION Body balance control represents a key factor preventing falls and subsequent injuries in seniors aged 65+. Intervention based on yoga exercises seem to be effective in improving balance. OBJECTIVE The objective is to analyse and compare changes in static, dynamic, and total balance scores, changes in body composition and social indices as effects of yoga-based intervention. METHODS A total of 500 participants (234 men aged 74.5 SD±7.74 and 266 women aged 76.9 SD±7.23) were assessed using the Tinetti Balance Assessment Tool, the InBody 230 bioimpedance body composition analyser, and the SF-36 Health Survey, applied to pre and post-testing. The experimental group (n=262; 122 males; 140 females) underwent a four-week yoga-based intervention, 30 minutes daily, while the control group (n=238; 112 males; 126 females) underwent its usual daily programme at senior homes or centres. The ANOVA model, consisting of the Group, Stage, Subject and Group × Stage interaction factors, was used for data evaluation. RESULTS Intervention led to improvements in the static, dynamic and total balance scores in the experimental group compared to the control group. The results of SF-36 showed positive changes in the psychosocial aspects of health, such as promoting of calmness and happiness in male seniors and reducing fatigue, nervousness and depression in female seniors. The post-intervention decrease in body fat percentage and increase in muscle mass in seniors is discussed. CONCLUSIONS The four-week yoga-based intervention had positive effects on the static, dynamic and total balance scores, body composition and social status.
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A plant-based meal reduces postprandial oxidative and dicarbonyl stress in men with diabetes or obesity compared with an energy- and macronutrient-matched conventional meal in a randomized crossover study.
Malinska, H, Klementová, M, Kudlackova, M, Veleba, J, Hoskova, E, Oliyarnyk, O, Markova, I, Thieme, L, Hill, M, Pelikanova, T, et al
Nutrition & metabolism. 2021;(1):84
Abstract
BACKGROUND Increased oxidative/dicarbonyl stress and chronic inflammation are considered key pathophysiological mediators in the progression of complications in obesity and type 2 diabetes (T2D). Lifestyle and diet composition have a major impact. In this study, we tested the effects of a vegan (V) and a conventional meat containg (M) meal, matched for energy and macronutrients, on postprandial oxidative and dicarbonyl stress, inflammatory markers and appetite hormones. METHODS A randomised crossover design was used to evaluate T2D, obese with normal glucose tolerance and control participants (n = 20 in each group), with serum concentrations of analytes determined at 0, 120 and 180 min. Repeated-measures ANOVA was used for statistical analysis. RESULTS In T2D subjects, we observed decreased postprandial concentrations of oxidised glutathione (p ˂ 0.001) and increased glutathione peroxidase activity (p = 0.045) after the V-meal consumption, compared with the M-meal. In obese participants, V-meal consumption increased postprandial concentrations of reduced glutathione (p = 0.041) and decreased methylglyoxal concentrations (p = 0.023). There were no differences in postprandial secretion of TNFα, MCP-1 or ghrelin in T2D or obese men, but we did observe higher postprandial secretion of leptin after the V-meal in T2D men (p = 0.002) compared with the M-meal. CONCLUSIONS The results show that a plant-based meal is efficient in ameliorating the postprandial oxidative and dicarbonyl stress compared to a conventional energy- and macronutrient-matched meal, indicating the therapeutic potential of plant-based nutrition in improving the progression of complications in T2D and obese patients. Registered under ClinicalTrials.gov Identifier No. NCT02474147.
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Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders.
Smitka, K, Prochazkova, P, Roubalova, R, Dvorak, J, Papezova, H, Hill, M, Pokorny, J, Kittnar, O, Bilej, M, Tlaskalova-Hogenova, H
Frontiers in endocrinology. 2021;:613983
Abstract
The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.
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A plant-based meal affects thalamus perfusion differently than an energy- and macronutrient-matched conventional meal in men with type 2 diabetes, overweight/obese, and healthy men: A three-group randomized crossover study.
Kahleova, H, Tintera, J, Thieme, L, Veleba, J, Klementova, M, Kudlackova, M, Malinska, H, Oliyarnyk, O, Markova, I, Haluzik, M, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1822-1833
Abstract
BACKGROUND & AIMS Reward circuitry in the brain plays a key role in weight regulation. We tested the effects of a plant-based meal on these brain regions. METHODS A randomized crossover design was used to test the effects of two energy- and macronutrient-matched meals: a vegan (V-meal) and a conventional meat (M-meal) on brain activity, gastrointestinal hormones, and satiety in participants with type 2 diabetes (T2D; n = 20), overweight/obese participants (O; n = 20), and healthy controls (H; n = 20). Brain perfusion was measured, using arterial spin labeling functional brain imaging; satiety was assessed using a visual analogue scale; and plasma concentrations of gut hormones were determined at 0 and 180 min. Repeated-measures ANOVA was used for statistical analysis. Bonferroni correction for multiple comparisons was applied. The Hedge's g statistic was used to measure the effect size for means of paired difference between the times (180-0 min) and meal types (M-V meal) for each group. RESULTS Thalamus perfusion was the highest in patients with T2D and the lowest in overweight/obese individuals (p = 0.001). Thalamus perfusion decreased significantly after ingestion of the M-meal in men with T2D (p = 0.04) and overweight/obese men (p = 0.004), and it decreased significantly after ingestion of the V-meal in healthy controls (p < 0.001; Group x Meal x Time: F = 3.4; p = 0.035). The effect size was -0.41 (95% CI, -1.14 to 0.31; p = 0.26) for men with diabetes; -0.72 (95% CI, -1.48 to 0.01; p = 0.05) for overweight/obese men; and 0.82 (95% CI, 0.09 to 1.59; p = 0.03) for healthy men. Postprandial secretion of active GLP-1 increased after the V-meal compared with the M-meal by 42% (95% CI 25-62%; p = 0.003) in men with T2D and by 41% (95% CI 24-61%; p = 0.002) in healthy controls. Changes in thalamus perfusion after ingestion of both test meals correlated with changes in satiety (r = +0.68; p < 0.01), fasting plasma insulin (r = +0.40; p < 0.01), C-peptide (r = +0.48; p < 0.01) and amylin (r = +0.55; p < 0.01), and insulin secretion at 5 mmol/l (r = +0.77; p < 0.05). CONCLUSIONS The higher postprandial GLP-1 secretion after the V-meal in men with T2D, with concomitant greater satiety and changes in thalamus perfusion, suggest a potential use of plant-based meals in addressing the key pathophysiologic mechanisms of food intake regulation. Trial registration ClinicalTrials.gov number, NCT02474147.
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Gluten Degradation, Pharmacokinetics, Safety, and Tolerability of TAK-062, an Engineered Enzyme to Treat Celiac Disease.
Pultz, IS, Hill, M, Vitanza, JM, Wolf, C, Saaby, L, Liu, T, Winkle, P, Leffler, DA
Gastroenterology. 2021;(1):81-93.e3
Abstract
BACKGROUND AND AIMS Celiac disease (CeD) is an immune-mediated disorder triggered by the ingestion of gluten. Despite adhering to a gluten-free diet (the only management option available to patients with CeD), many patients continue to experience symptoms and intestinal injury. Degradation of immunogenic fractions of gluten peptides in the stomach has been proposed as an approach to reduce toxicity of ingested gluten; however, no enzymes evaluated to date have demonstrated sufficient gluten degradation in complex meals. TAK-062 is a novel, computationally designed endopeptidase under development for the treatment of patients with CeD. METHODS Pharmacokinetics, safety, and tolerability of TAK-062 100-900 mg were evaluated in a phase I dose escalation study in healthy participants and patients with CeD. Gluten degradation by TAK-062 was evaluated under simulated gastric conditions in vitro and in healthy participants in the phase I study, with and without pretreatment with a proton pump inhibitor. Residual gluten (collected through gastric aspiration in the phase I study) was quantified using R5 and G12 monoclonal antibody enzyme-linked immunosorbent assays. RESULTS In vitro, TAK-062 degraded more than 99% of gluten (3 g and 9 g) within 10 minutes. In the phase I study, administration of TAK-062 was well tolerated and resulted in a median gluten degradation ranging from 97% to more than 99% in complex meals containing 1-6 g gluten at 20-65 minutes postdose. CONCLUSIONS TAK-062 is well tolerated and rapidly and effectively degrades large amounts of gluten, supporting the development of this novel enzyme as an oral therapeutic for patients with CeD. (ClinicalTrials.gov: NCT03701555, https://clinicaltrials.gov/ct2/show/NCT03701555.).
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Movement as a Positive Modulator of Aging.
Bičíková, M, Máčová, L, Jandová, D, Třískala, Z, Hill, M
International journal of molecular sciences. 2021;(12)
Abstract
The aging of human populations, including those in Europe, is an indisputable fact. The challenge for the future is not simply prolonging human life at any cost or by any means but rather extending self-sufficiency and quality of life. Even in the most advanced societies, the eternal questions remain. Who will take care of the older generations? Will adult children's own circumstances be sufficient to support family members as they age? For a range of complex reasons, including socioeconomic conditions, adult children are often unable or unwilling to assume responsibility for the care of older family members. For this reason, it is imperative that aging adults maintain their independence and self-care for as long as possible. Movement is an important part of self-sufficiency. Moreover, movement has been shown to improve patients' clinical status. At a time when the coronavirus pandemic is disrupting the world, older people are among the most vulnerable. Our paper explores current knowledge and offers insights into the significant benefits of movement for the elderly, including improved immunity. We discuss the biochemical processes of aging and the counteractive effects of exercise and endogenous substances, such as vitamin D.