scholarly journals Metabolomics of Interstitial Fluid, Plasma and Urine in Patients with Arterial Hypertension: New Insights into the Underlying Mechanisms

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 936
Author(s):  
Angelika Chachaj ◽  
Rafał Matkowski ◽  
Gerhard Gröbner ◽  
Andrzej Szuba ◽  
Ilona Dudka

There is growing evidence that lymphatic system plays a pivotal role in the pathogenesis of hypertension. Here, for the first time, the metabolome of interstitial fluid is analyzed in patients with arterial hypertension. Due to ethical issues to obtain human interstitial fluid samples, this study included only oncological patients after axillary lymph node dissection (ALND). These patients were matched into hypertensive (n = 29) and normotensive (n = 35) groups with similar oncological status. Simultaneous evaluation of interstitial fluid, plasma, and urine was obtained by combining high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy with chemometric analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) provided a clear differentiation between the hypertension and normotensive group, with the discrimination visible in each biofluid. In interstitial fluid nine potential metabolomic biomarkers for hypertension could be identified (creatinine, proline, pyroglutamine, glycine, alanine, 1-methylhistidine, the lysyl group of albumin, threonine, lipids), seven distinct markers in plasma (creatinine, mannose, isobutyrate, glycine, alanine, lactate, acetate, ornithine), and seven respectively in urine (methylmalonate, citrulline, phenylacetylglycine, fumarate, citrate, 1-methylnicotinamide, trans-aconitate). Biomarkers in plasma and urine allowed for the identification of specific biochemical pathways involved in hypertension, as previously suggested. Analysis of the interstitial fluid metabolome provided additional biomarkers compared to plasma or urine. Those biomarkers reflected primarily alterations in the metabolism of lipids and amino acids, and indicated increased levels of oxidative stress/inflammation in patients with hypertension.




2005 ◽  
Vol 107 (2) ◽  
pp. 101-112
Author(s):  
Haiyuan Zhang ◽  
Jinping Wang ◽  
Xin Lu ◽  
Kuiyue Yang ◽  
Chunji Niu


1972 ◽  
Vol 126 (5) ◽  
pp. 492-497 ◽  
Author(s):  
J. S. Tan ◽  
A. Trott ◽  
J. P. Phair ◽  
C. Watanakunakorn


2008 ◽  
Vol 35 (3) ◽  
pp. 423-426 ◽  
Author(s):  
J. Blais ◽  
L. Dubertretf ◽  
F. Gaboriau ◽  
P. Vigny


2021 ◽  
Vol 12 ◽  
Author(s):  
Danial Sharifi Kia ◽  
Kang Kim ◽  
Marc A. Simon

Pulmonary arterial hypertension (PAH) is a disease resulting in increased right ventricular (RV) afterload and RV remodeling. PAH results in altered RV structure and function at different scales from organ-level hemodynamics to tissue-level biomechanical properties, fiber-level architecture, and cardiomyocyte-level contractility. Biomechanical analysis of RV pathophysiology has drawn significant attention over the past years and recent work has found a close link between RV biomechanics and physiological function. Building upon previously developed techniques, biomechanical studies have employed multi-scale analysis frameworks to investigate the underlying mechanisms of RV remodeling in PAH and effects of potential therapeutic interventions on these mechanisms. In this review, we discuss the current understanding of RV structure and function in PAH, highlighting the findings from recent studies on the biomechanics of RV remodeling at organ, tissue, fiber, and cellular levels. Recent progress in understanding the underlying mechanisms of RV remodeling in PAH, and effects of potential therapeutics, will be highlighted from a biomechanical perspective. The clinical relevance of RV biomechanics in PAH will be discussed, followed by addressing the current knowledge gaps and providing suggested directions for future research.



2021 ◽  
Vol 23 (11) ◽  
Author(s):  
Christine Kuehner ◽  
Sibel Nayman

Abstract Purpose of Review In contrast to premenstrual dysphoric disorder (PMDD), premenstrual exacerbations (PMEs) of ongoing mood disorders are understudied. The aim of this review is to describe diagnostic issues, epidemiology, underlying mechanisms, and treatment for PME in unipolar depression and bipolar disorder, and to discuss clinical and research implications. Recent Findings Community-based and clinical studies estimate that in women with mood disorders around 60% report PME, while some women with bipolar disorder also show symptom exacerbations around ovulation. In general, PME predicts a more severe illness course and an increased burden. While heightened sensitivity to fluctuations of sex hormone levels across the menstrual cycle appears to contribute to PME and PMDD, the overlap of their underlying biological mechanisms remains unclear. Beneficial treatments for PMDD show less or no efficacy in PME. Pharmacological treatments for PME in mood disorders predominantly seem to profit from adjustable augmentation of treatment dosages during the luteal phase for the underlying disorder. However, the evidence is sparse and mainly based on earlier small studies and case reports. Summary Previous research is mainly limited by the lack of a clear differentiation between PME and PMDD comorbidity with mood disorders. More systematic research with uniformly defined and prospectively assessed subgroups of PME in larger epidemiological and clinical samples is needed to receive reliable prevalence estimates and information on the clinical impact of PME of mood disorders, and to uncover underlying mechanisms. In addition, larger randomized controlled trials are warranted to identify efficacious pharmacological and psychotherapeutic treatments for affected women.



2003 ◽  
Vol 94 (2) ◽  
pp. 131-140 ◽  
Author(s):  
Haiyuan Zhang ◽  
Xing Lu ◽  
Jinping Wang ◽  
Kuiyue Yang ◽  
Chunji Niu


2020 ◽  
Vol 14 ◽  
Author(s):  
Wei Wu ◽  
Hang Yao ◽  
Ila Dwivedi ◽  
Priscilla D. Negraes ◽  
Helen W. Zhao ◽  
...  

Accumulating evidence has suggested that prenatal exposure to methadone causes multiple adverse effects on human brain development. Methadone not only suppresses fetal neurobehavior and alters neural maturation, but also leads to long-term neurological impairment. Due to logistical and ethical issues of accessing human fetal tissue, the effect of methadone on brain development and its underlying mechanisms have not been investigated adequately and are therefore not fully understood. Here, we use human cortical organoids which resemble fetal brain development to examine the effect of methadone on neuronal function and maturation during early development. During development, cortical organoids that are exposed to clinically relevant concentrations of methadone exhibited suppressed maturation of neuronal function. For example, organoids developed from 12th week till 24th week have an about 7-fold increase in AP firing frequency, but only half and a third of this increase was found in organoids exposed to 1 and 10 μM methadone, respectively. We further demonstrated substantial increases in INa (4.5-fold) and IKD (10.8-fold), and continued shifts of Na+ channel activation and inactivation during normal organoid development. Methadone-induced suppression of neuronal function was attributed to the attenuated increase in the densities of INa and IKD and the reduced shift of Na+ channel gating properties. Since normal neuronal electrophysiology and ion channel function are critical for regulating brain development, we believe that the effect of prolonged methadone exposure contributes to the delayed maturation, development fetal brain and potentially for longer term neurologic deficits.



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