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Pathophysiology of Gastroparesis Syndromes Includes Anatomic and Physiologic Abnormalities.
Abell, TL, Kedar, A, Stocker, A, Beatty, K, McElmurray, L, Hughes, M, Rashed, H, Kennedy, W, Wendelschafer-Crabb, G, Yang, X, et al
Digestive diseases and sciences. 2021;(4):1127-1141
Abstract
BACKGROUND Factors underlying gastroparesis are not well defined. AIMS We hypothesized that multiple systems may be involved in patients with gastroparesis symptoms and performed a comparative physiologic study. METHODS We studied 43 consecutive eligible patients with gastroparetic symptoms categorized by GI symptoms, metabolic status, illness quantification, and gastric physiology. Patients were evaluated by two methods in each of five core areas: inflammatory, autonomic, enteric, electrophysiologic, and hormonal with abnormalities examined by correlations. RESULTS Patients had similar GI symptoms regardless of baseline gastric emptying or diabetic/idiopathic status, and all patients demonstrated abnormalities in each of the 5 areas studied. Nearly all patients presented with elevated markers of serum TNFα (88%) and serum IL-6 (91%); elevated cutaneous electrogastrogram frequency (95%); and interstitial cells of Cajal count abnormalities (inner: 97%, outer: 100%). Measures of inflammation correlated with a number of autonomic, enteric anatomy, electrophysiologic and hormonal abnormalities. CONCLUSIONS We conclude that patients with the symptoms of gastroparesis have multiple abnormalities, when studied by traditional, as well as newer, diagnostic assessments. Inflammation appears to be a fundamental abnormality that affects other organ systems in symptomatic patients. Future work on gastroparetic syndromes and their treatment may benefit from a focus on the diffuse nature of their illness, diverse pathophysiologic mechanisms involved, especially the possible causes of underlying inflammation and disordered hormonal status. TRAIL REGISTRY This study is registered with Clinicaltrials.gov under study # NCT03178370 https://clinicaltrials.gov/ct2/show/NCT03178370 .
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Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester): Effects Upon High-Sensitivity C-Reactive Protein and Lipid Parameters in Patients With Metabolic Syndrome.
Bays, HE, Ballantyne, CM, Braeckman, RA, Stirtan, WG, Doyle, RT, Philip, S, Soni, PN, Juliano, RA
Metabolic syndrome and related disorders. 2015;(6):239-47
Abstract
BACKGROUND The aim of this analysis was to examine the effects of icosapent ethyl (eicosapentaenoic acid ethyl ester, IPE) on high-sensitivity C-reactive protein (hsCRP) and lipid parameters in patients with metabolic syndrome, with and without stable statin therapy. METHODS This post hoc exploratory analysis evaluated patients with metabolic syndrome treated with IPE 4 grams/day, IPE 2 grams/day, or placebo in phase 3, randomized, placebo-controlled studies entitled: MARINE [triglyceride (TG) levels ≥500 and ≤2000 mg/dL] and ANCHOR [TG levels ≥200 and <500 mg/dL, despite low-density lipoprotein cholesterol (LDL-C) control with stable statin therapy]. RESULTS Compared with placebo in patients with metabolic syndrome in MARINE (n=204) and ANCHOR (n=645), at the approved dose of 4 grams/day, IPE significantly lowered hsCRP levels 40.0% (P=0.0007) in MARINE and 23.0% (P=0.0003) in ANCHOR. Compared with placebo in MARINE, which included patients with and without statin therapy, IPE 4 grams/day significantly reduced hsCRP levels 78.0% in statin-treated patients (P=0.0035, n=16). Compared with placebo in MARINE, IPE 4 grams/day significantly reduced TG levels (35.0%; P<0.0001), non-high-density lipoprotein cholesterol (non-HDL-C; 19.9%; P<0.0001), and apolipoprotein B levels (ApoB) (9.1%; P=0.0015) without raising LDL-C levels. Compared with placebo in ANCHOR, IPE 4 grams/day significantly reduced TG (21.7%; P<0.0001), non-HDL-C (13.5%; P<0.0001), ApoB (8.8%; P<0.0001), LDL-C (5.2%; P=0.0236), and HDL-C levels (4.0%; P=0.0053). CONCLUSIONS Compared with placebo, IPE 4 grams/day significantly lowered hsCRP levels and improved lipids without raising LDL-C levels in patients with metabolic syndrome and high (≥200 and <500 mg/dL) or very high (≥500 and ≤2000 mg/dL) TG levels, with or without stable statin therapy.
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3.
Weight loss improves serum mediators and metabolic syndrome features in android obese subjects.
Chou, CY, Lang, HF, Sheu, WH, Lin, JY
Obesity research & clinical practice. 2013;(1):e81-8
Abstract
Serum anti-/pro-inflammatory molecules such as adiponectin, IL-6, IL-10, and TNF-α, and metabolic syndrome (Met Syn) features in 15 android obese (6 Met Syn and 9 non-Met Syn) subjects were assessed during an 8-week weight control program. The results showed that the body mass index, weight, lean body mass, triglyceride, total cholesterol/high density lipoprotein cholesterol ratio, and TNF-α in Met Syn subjects were significantly (P < 0.05) improved. This study suggests that weight reduction in android obese subjects may be beneficial in reducing cardiovascular diseases via improving serum IL-6 and TNF-α levels, as well as Met Syn features.
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Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study.
Udani, JK, Singh, BB, Barrett, ML, Singh, VJ
Nutrition journal. 2009;:48
Abstract
BACKGROUND The ability to reduce inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes. The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP) levels. METHODS The study was an 8 week randomized, double-blind, placebo-controlled study with a pre-study 2 week washout period. The study included four groups including placebo and three difference doses of the test product, XanGo Juice: 3, 6 or 9 oz twice daily. The primary outcome measure of this study was high-sensitivity (HS)-CRP. Secondary outcome measures included other biochemical indicators of inflammation, anthropomorphic measures and a safety evaluation. RESULTS One hundred twenty two (122) persons were screened for the study, 44 were randomized and 40 completed the study. HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18 oz group when compared to placebo (p = 0.02). Other markers of inflammation (inflammatory cytokines) and a marker for lipid peroxidation (F2 isoprostane) did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups. There were no side effects reported in any of the groups and none of the laboratory or EKG safety assessments indicated clinically significant changes for any subject. CONCLUSION In this pilot, dose-finding study, a proprietary mangosteen juice blend (XanGo Juice) reduced CRP levels (increased change from baseline) compared to placebo for those taking the highest dose of 18 oz per day. Further studies with a larger population are required to confirm and further define the benefits of this juice. The juice was administered safely. TRIAL REGISTRATION ISRCTN9300027.
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Effect of a sequential training programme on inflammatory, prothrombotic and vascular remodelling biomarkers in hypertensive overweight patients with or without metabolic syndrome.
Cicero, AF, Derosa, G, Bove, M, Di Gregori, V, Gaddi, AV, Borghi, C
European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. 2009;(6):698-704
Abstract
BACKGROUND It is not known whether serum level of vascular remodelling parameters, such as matrix metalloproteinases could be modulated by physical activity and whether the eventual change could be influenced by metabolic syndrome (MS) diagnosis. DESIGN Open, intervention study to evaluate the effects of a sequential physical activity training on inflammatory, prothrombotic and vascular remodelling biomarkers in overweight patients with and without MS. METHODS We enrolled 80 overweight patients (mean age: 62.9+/-8.3 years; male : female = 36 : 44) with newly diagnosed hypertension, with or without MS. After 3 months of American Heart Association step 2 diet, they followed a sequential training programme including 56 days of added three metabolic equivalent tasks/week and 56 days of six metabolic equivalent tasks/week. RESULTS All patients experienced a significant decrease in body mass index, waist circumference and blood pressure after both the training phases. High-density lipoprotein-cholesterolemia, triglycerides, and glycaemia significantly improved only after the intensive training phase compared with the baseline in MS patients. Prothrombotic parameters improved irrespectively from the MS diagnosis. High-sensitivity C-reactive protein P level significantly decreased towards baseline and towards the previous phase, after exercise intensification, but only in MS patients. The plasma level of matrix metalloproteinase 2 and 9, and their activated forms improved significantly when compared with the baseline both after the first and the second training period, independently from the MS diagnosis. CONCLUSION Diagnosis of MS is a determinant of changes in metabolic and inflammatory biomarkers, but not of the prothrombotic and vascular remodelling ones in a sample of overweight hypertensive patients.
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Effects of N-3 PUFAs supplementation on insulin resistance and inflammatory biomarkers in hemodialysis patients.
Rasic-Milutinovic, Z, Perunicic, G, Pljesa, S, Gluvic, Z, Sobajic, S, Djuric, I, Ristic, D
Renal failure. 2007;(3):321-9
Abstract
AIMS/HYPOTHESIS It was suggested that polyunsaturated n-3 fatty acids (n-3 PUFAs) could improve insulin sensitivity and have an anti-inflammatory effects in overall population. This study investigates a possible effect of n-3 PUFAs supplementation on the insulin sensitivity and some inflammatory markers; hence, patients with chronic renal failure (CRF) on maintenance hemodialysis (MHD) are presented with insulin resistance. METHODS This study explored the ratio between red blood cells (RBC) phospholipid long chain fatty acids (LC FAs) and components of metabolic syndrome (MeS) in 35 patients (mean age 54.50 +/- 11.99 years) with CRF on MHD. Furthermore, the effects of omega-3 FA eight-week's supplementation (EPA+DHA, 2.4 g/d) on the MeS features and inflammatory markers TNF-alpha, IL 6, and hsCRP were examined. RESULTS Supplementation increased EPA and DHA levels in RBCs (p = 0.009 for EPA and p = 0.002 for DHA). Total n-6 PUFAs: n-3 PUFAs ratio tended to be lower after supplementation (p = 0.31), but not significantly. Data revealed a significant decrease of saturated FAs (SFA) (p = 0.01) as well as total SFA: n-3 PUFAs ratio during the treatment (p = 0.04). The values of serum insulin and calculated IR index-IR HOMA were reduced after supplementation (p = 0.001 for both). There was a significant decrease in the levels of all inflammatory markers (p = 0.01 for TNF alpha, p = 0.001 for IL 6, p = 0.001 for hsCRP, and p = 0.01 for ferritin). In multivariate regression analysis, only the changes in n-6 PUFAs: n-3 PUFAs ratio independently contributed to 40% of the variance in IR HOMA. The impact of changes in PUFAs level in RBCs membrane phospholipid fatty acids on inflammation markers was also registered. The changes in n-6: n-3 PUFAs ratio independently contributed to 18% of the variance in TNF alpha. CONCLUSION It was concluded that the EPA and DHA moderate dose administration in the patients with CRF on MHD had a beneficial effect on insulin resistance decrease. The anti-inflammatory effects of the supplemented PUFAs were also presented.