Higher cerebrospinal fluid to plasma ratio of p-cresol sulfate and indoxyl sulfate in patients with Parkinson’s disease

ConclusionsThe level of pCS and IS in CSF of PD is higher than expected, based on their blood level. It can influence pathogenesis and progression of PD.Graphical abstract
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research

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Abstract Anaerobic choline metabolism by human gut microbiota to produce trimethylamine (TMA) has recently evolved as a potential therapeutic target because of its association with chronic kidney disease and increased cardiovascular risks. Limited examples of choline analogs have been reported as inhibitors of bacterial enzyme choline TMA-lyase (CutC), a key enzyme regulating choline anaerobic metabolism. We utilized a new workflow to discover CutC inhibitors based on focused screening of a diversified library of small molecules for intestinal metabolic stability followed by in vitro CutC inhibitory assay. This wo...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research
In conclusion, sitting for prolonged periods of time without interruption is unfavorably associated with DBP and HDL cholesterol. Exercise Slows Inappropriate Growth of Blood Vessels in a Mouse Model of Macular Degeneration https://www.fightaging.org/archives/2020/07/exercise-slows-inappropriate-growth-of-blood-vessels-in-a-mouse-model-of-macular-degeneration/ Excessive growth of blood vessels beneath the retina is a proximate cause of blindness in conditions such as macular degeneration. Researchers here provide evidence for physical activity to be influential in the pace at which this process of tissue...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
High circulating trimethylamine-N-oxide (TMAO) is associated with an increased risk of cardiovascular disease and mortality in people with chronic kidney disease (CKD). In individuals with CKD, reduced kidney function leads to decreased excretion of TMAO, which results in accumulation in the circulation. Higher circulating TMAO has been linked to higher intake of animal-based foods in omnivorous diets. Thus, plant-based diets have been suggested as an intervention to slow the progression of CKD and reduce cardiovascular risk, perhaps explained in part by reduced TMAO production.
Source: Journal of Renal Nutrition - Category: Urology & Nephrology Authors: Tags: Review Article Source Type: research
In this study, 69 patients undergoing outpatient dialysis were enrolled. Enzyme-linked immunosorbent assay was used to quantitate the baseline plasma TMAO levels in patients. The patients were divided into a high TMAO level group (TMAO ≥ 15 μmol/L) and a low TMAO level group (TMAO
Source: Renal Failure - Category: Urology & Nephrology Tags: Ren Fail Source Type: research
In this study, we validated a method to simultaneously measure urine TMA and TMAO concentrations by liquid chromatography–mass spectrometry (LC/MS). Urine TMA and TMAO can be extracted by hexane/butanol under alkaline pH and transferred to the aqueous phase following acidification for LC/MS quantitation. Importantly, during sample processing, none of the nutrients with a chemical structure containing a TMA moiety were spontaneously cleaved to yield TMA. Moreover, we demonstrated that the acidification of urine prevents an increase of TMA after prolonged storage as was observed in non-acidified urine. Finally, her...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
TRIMETHYLAMINE-N-OXIDE ACUTELY INCREASES CARDIAC MUSCLE CONTRACTILITY. Am J Physiol Heart Circ Physiol. 2020 Apr 03;: Authors: Oakley CI, Vallejo JA, Wang D, Gray MA, Tiede-Lewis LM, Shawgo T, Daon E, Zorn G, Stubbs JR, Wacker MJ Abstract Cardiovascular disease is a major cause of morbidity and mortality among patients with chronic kidney disease (CKD). Trimethylamine-N-oxide (TMAO), a uremic metabolite that is elevated in the setting of CKD, has been implicated as a nontraditional risk factor for cardiovascular disease. While association studies have linked elevated plasma levels of TMAO to adverse c...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research
Abstract Although substantial evidence suggests that an increase in the level of trimethylamine-N-oxide (TMAO) is associated with the risk of cardiovascular diseases, including atherosclerosis, chronic kidney diseases, and hypertension, the direct effect of TMAO on vascular endothelial function remains unclear. Therefore, we investigated the acute effects of TMAO on endothelium-dependent relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries and femoral arteries of rat. In endothelium-intact preparations, it was observed that TMAO (300 µmol/L for 60 min) did not affect AC...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research
CONCLUSIONS: This study for the first time demonstrates that TMAO promotes vascular calcification through activation of NLRP3 inflammasome and NF-κB signals, suggesting the potential link between gut microbial metabolism and vascular calcification. Reducing the levels of TMAO could become a potential treatment strategy for vascular calcification in chronic kidney disease. PMID: 31941382 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research
CONCLUSIONS: The level of pCS and IS in CSF of PD is higher than expected, based on their blood level. It can influence pathogenesis and progression of PD. PMID: 31726035 [PubMed - as supplied by publisher]
Source: International Journal of Clinical Chemistry - Category: Chemistry Authors: Tags: Clin Chim Acta Source Type: research
Chronic kidney disease (CKD) affects 10-15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that required to improve renal function remain unknown. The present study aim to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research
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