Metabolomic Analysis Identified Reduced Levels of Xenobiotics, Oxidative Stress, and Improved Vitamin Metabolism in Smokers Switched to Vuse Electronic Nicotine Delivery System

Abstract Introduction Switching to noncombustible tobacco products presents an opportunity for cigarette smokers to potentially reduce the health risks associated with smoking. Electronic Nicotine Delivery Systems (ENDS) are one such product because the vapor produced from ENDS contains far fewer toxicants than cigarette smoke. To investigate the biochemical effects of switching from smoking to an ENDS, we assessed global metabolomic profiles of smokers in a 7-day confinement clinical study. Methods In the first 2 days of this clinical study, the subjects used their usual brand of cigarettes and then switched to exclusive ENDS ad libitum use for 5 days. Urine and plasma samples were collected at baseline and 5 days after switching. The samples were analyzed using a mass spectrometry-based metabolomic platform. Results Random forest analyses of urine and plasma metabolomic data revealed excellent predictive accuracy (>97%) of a 30-metabolite signature that can differentiate smokers from 5-day ENDS switchers. In these signatures, most biomarkers are nicotine-derived metabolites or xenobiotics. They were significantly reduced in urine and plasma, suggesting a decreased xenobiotic load on subjects. Our results also show significantly decreased levels of plasma glutathione metabolites after switching, which suggests reduced levels of oxidative stress. In addition, increased urinary and plasma levels of vitamins and antioxidants were identified, suggesting enhanced bioavailability due to discontinuation of cigarette smoking and switching to Vuse ENDS use. Conclusions Our results suggest reduced toxicant exposure, reduced oxidative stress, and potential beneficial changes in vitamin metabolism within 5 days in smokers switching to Vuse ENDS. Implications Switching from smoking to exclusive ENDS use in clinical confinement settings results in significant reduction of nicotine metabolites and other cigarette-related xenobiotics in urine and plasma of subjects. Significantly decreased oxidative stress-related metabolites and increased urinary and plasma levels of vitamin metabolites and antioxidants in 5-day short-term ENDS switchers suggest less toxic physiological environment for consumers of ENDS products and potential health benefits if such changes persist.

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Increased systemic inflammation and oxidative stress in patients with worsening congestive heart failure: improvement after short-term inotropic support

Clinical Science ◽

10.1042/cs20050317 ◽

2006 ◽

Vol 110 (4) ◽

pp. 483-489 ◽

Cited By ~ 69

Author(s):

Michel White ◽

Anique Ducharme ◽

Reda Ibrahim ◽

Lucette Whittom ◽

Joel Lavoie ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Congestive Heart Failure ◽

Systemic Inflammation ◽

Plasma Levels ◽

Inotropic Support ◽

Left Ventricular Ejection ◽

Short Term ◽

Hs Crp ◽

And Oxidative Stress

In the present study, we evaluated circulating pro-inflammatory mediators and markers of oxidative stress in patients with decompensated CHF (congestive heart failure) and assessed whether clinical recompensation by short-term inotropic therapy influences these parameters. Patients with worsening CHF (n=29, aged 61.9±2.7 years), NYHA (New York Heart Association) class III–IV, and left ventricular ejection fraction of 23.7±1.8% were studied. Controls comprised age-matched healthy volunteers (n=15; 54.1±3.2 years). Plasma levels of cytokines [IL (interleukin)-6 and IL-18], chemokines [MCP-1 (monocyte chemotactic protein-1)], adhesion molecules [sICAM (soluble intercellular adhesion molecule), sE-selectin (soluble E-selectin)], systemic markers of oxidation [TBARS (thiobarbituric acid-reactive substances), 8-isoprostaglandin F2α and nitrotyrosine] and hs-CRP (high-sensitivity C-reactive protein) were measured by ELISA and colorimetric assays at admission and 30 days following 72-h milrinone (n=15) or dobutamine (n=14) infusion. Plasma IL-6, IL-18, sICAM, E-selectin, hs-CRP and oxidative markers were significantly higher in patients on admission before inotropic treatment compared with controls (P<0.05). Short-term inotropic support improved clinical status as assessed by NYHA classification and by the 6-min walk test and significantly decreased plasma levels of IL-6, IL-18, sICAM, hs-CRP and markers of oxidation (P<0.05) at 30 days. The effects of milrinone and dobutamine were similar. In conclusion, our results demonstrate that patients with decompensated CHF have marked systemic inflammation and increased production of oxygen free radicals. Short-term inotropic support improves functional status and reduces indices of inflammation and oxidative stress in patients with decompensated CHF.

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Clinical utility of Shabda and Sparsha Pareeksha in evaluation of Prakruta and Vaikruta Garbhavastha

Journal of Ayurveda and Integrated Medical Sciences (JAIMS) ◽

10.21760/jaims.v1i2.3657 ◽

2016 ◽

Vol 1 (2) ◽

Author(s):

Priyanka T K ◽

V.N. K. Usha ◽

Sucheta Kumari M

Keyword(s):

Clinical Study ◽

Clinical Utility ◽

Neonatal Outcome ◽

Predictive Accuracy ◽

Cost Effective ◽

Well Being ◽

Prospective Clinical Study ◽

Clinical Tool ◽

Accuracy Rate ◽

Fetal Pathology

Garbha is a conglomeration of biological mass with different strata including consciousness, needs an innovative clinical tool to evaluate its well being, which proves safe, potent, cost-effective and noninvasive. The idea of taking up this study was to sensitively predict the Prakrutavastha or well being w.r.t Garbha-pushti and ongoing Fetal Pathology, Vaikrutavastha w.s.r Garbhavyapads for a sharp interference to get a possible best neonatal outcome. The objective of this study was to calculate the predictive accuracy of evaluation of Garbhaspandanam on external Shabda and Sparsha Pareeksha. A Prospective Clinical study of Garbhaspandanam (FHS and FM) with external Shabda and Sparsha stimulation on maternal abdomen, from 24th week onwards was conducted in a cohort of 30 Singleton Pregnant women at Dept. of Prasuti Tantra and Stri Roga, S.D.M.C.A. Hospital, Udupi. Among the 9 cases in abnormal category, 2 cases had gone for IUD and one case though placed in abnormal category had responded relatively well to Shabda and Sparsha Pareeksha which may be due to the proper antenatal care and intervention given along with the patient’s Vatakara Nidana Parivarjana. Predictive Accuracy Rate on Shabda and Sparsha Pareeksha showed, FHS 70%, FM 76.7%; FHS 73.3%, FM 66.7% respectively. Shabda and Sparshapareeksha can be utilized as the Garbha - chetana - dyodakalakshana and can be performed as a routine antenatal bedside procedure, which can fairly detect the Prakruta and Vaikrutavastha of Garbha w.r.t Pushti. However larger prospective studies are required.

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Short term effect of atorvastatin on plasma levels of MCP-1, ICAM-1 and C-reactive protein in patients with coronary artery disease

Atherosclerosis ◽

10.1016/s0021-9150(00)80209-9 ◽

2000 ◽

Vol 151 (1) ◽

pp. 46

Author(s):

A Figueredo ◽

L Reinares ◽

A Rueda ◽

A Rodriguez ◽

M Ruiz-Yagüe ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Plasma Levels ◽

Term Effect ◽

C Reactive Protein ◽

Short Term ◽

Short Term Effect ◽

Reactive Protein ◽

Artery Disease

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Maximizing Cochlear Implant Outcomes with Short-Term Aural Rehabilitation

Journal of the American Academy of Audiology ◽

10.1055/s-0041-1722987 ◽

2021 ◽

Author(s):

Claire Marcus Bernstein ◽

Diane Majerus Brewer ◽

Matthew H. Bakke ◽

Anne D. Olson ◽

Elizabeth Jackson Machmer ◽

...

Keyword(s):

Clinical Study ◽

Speech Recognition ◽

Cochlear Implant ◽

Active Control ◽

Analysis Of Variance ◽

Control Group ◽

Active Control Group ◽

Short Term ◽

Aural Rehabilitation ◽

Profound Deafness

Abstract Background Increasing numbers of adults are receiving cochlear implants (CIs) and many achieve high levels of speech perception and improved quality of life. However, a proportion of implant recipients still struggle due to limited speech recognition and/or greater communication demands in their daily lives. For these individuals a program of aural rehabilitation (AR) has the potential to improve outcomes. Purpose The study investigated the effects of a short-term AR intervention on speech recognition, functional communication, and psychosocial outcomes in post lingually deafened adult CI users. Research Design The experimental design was a multisite clinical study with participants randomized to either an AR treatment or active control group. Each group completed 6 weekly 90-minute individual treatment sessions. Assessments were completed pretreatment, 1 week and 2 months post-treatment. Study Sample Twenty-five post lingually deafened adult CI recipients participated. AR group: mean age 66.2 (48–80); nine females, four males; months postactivation 7.7 (3–16); mean years severe to profound deafness 18.4 (2–40). Active control group: mean age 62.8 (47–85); eight females, four males; months postactivation 7.0 (3–13); mean years severe to profound deafness 18.8 (1–55). Intervention The AR protocol consisted of auditory training (words, sentences, speech tracking), and psychosocial counseling (informational and communication strategies). Active control group participants engaged in cognitive stimulation activities (e.g., crosswords, sudoku, etc.). Data Collection and Analysis Repeated measures ANOVA or analysis of variance, MANOVA or multivariate analysis of variance, and planned contrasts were used to compare group performance on the following measures: CasperSent; Hearing Handicap Inventory; Nijmegen Cochlear Implant Questionnaire; Client Oriented Scale of Improvement; Glasgow Benefit Inventory. Results The AR group showed statistically significant improvements on speech recognition performance, psychosocial function, and communication goals with no significant improvement seen in the control group. The two groups were statistically equivalent on all outcome measures at preassessment. The robust improvements for the AR group were maintained at 2 months post-treatment. Conclusion Results of this clinical study provide evidence that a short-term AR intervention protocol can maximize outcomes for adult post lingually deafened CI users. The impact of this brief multidimensional AR intervention to extend CI benefit is compelling, and may serve as a template for best practices with adult CI users.

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A Siamese neural network model for the prioritization of metabolic disorders by integrating real and simulated data

Bioinformatics ◽

10.1093/bioinformatics/btaa841 ◽

2020 ◽

Vol 36 (Supplement_2) ◽

pp. i787-i794

Author(s):

Gian Marco Messa ◽

Francesco Napolitano ◽

Sarah H. Elsea ◽

Diego di Bernardo ◽

Xin Gao

Keyword(s):

Predictive Accuracy ◽

Hybrid Approach ◽

Simulated Data ◽

Original Data ◽

Diagnostic Process ◽

Great Promise ◽

Metabolic Profiles ◽

Inborn Errors ◽

Metabolomic Data ◽

Near Future

Abstract Motivation Untargeted metabolomic approaches hold a great promise as a diagnostic tool for inborn errors of metabolisms (IEMs) in the near future. However, the complexity of the involved data makes its application difficult and time consuming. Computational approaches, such as metabolic network simulations and machine learning, could significantly help to exploit metabolomic data to aid the diagnostic process. While the former suffers from limited predictive accuracy, the latter is normally able to generalize only to IEMs for which sufficient data are available. Here, we propose a hybrid approach that exploits the best of both worlds by building a mapping between simulated and real metabolic data through a novel method based on Siamese neural networks (SNN). Results The proposed SNN model is able to perform disease prioritization for the metabolic profiles of IEM patients even for diseases that it was not trained to identify. To the best of our knowledge, this has not been attempted before. The developed model is able to significantly outperform a baseline model that relies on metabolic simulations only. The prioritization performances demonstrate the feasibility of the method, suggesting that the integration of metabolic models and data could significantly aid the IEM diagnosis process in the near future. Availability and implementation Metabolic datasets used in this study are publicly available from the cited sources. The original data produced in this study, including the trained models and the simulated metabolic profiles, are also publicly available (Messa et al., 2020).

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Oxidative Stress, Glutathione Metabolism, and Liver Regeneration Pathways Are Activated in Hereditary Tyrosinemia Type 1 Mice upon Short-Term Nitisinone Discontinuation

Genes ◽

10.3390/genes12010003 ◽

2020 ◽

Vol 12 (1) ◽

pp. 3

Author(s):

Haaike Colemonts-Vroninks ◽

Jessie Neuckermans ◽

Lionel Marcelis ◽

Paul Claes ◽

Steven Branson ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Liver Regeneration ◽

The Body ◽

Glutathione Metabolism ◽

Short Term ◽

Therapeutic Regime ◽

Tyrosinemia Type 1 ◽

Hereditary Tyrosinemia

Hereditary tyrosinemia type 1 (HT1) is an inherited condition in which the body is unable to break down the amino acid tyrosine due to mutations in the fumarylacetoacetate hydrolase (FAH) gene, coding for the final enzyme of the tyrosine degradation pathway. As a consequence, HT1 patients accumulate toxic tyrosine derivatives causing severe liver damage. Since its introduction, the drug nitisinone (NTBC) has offered a life-saving treatment that inhibits the upstream enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD), thereby preventing production of downstream toxic metabolites. However, HT1 patients under NTBC therapy remain unable to degrade tyrosine. To control the disease and side-effects of the drug, HT1 patients need to take NTBC as an adjunct to a lifelong tyrosine and phenylalanine restricted diet. As a consequence of this strict therapeutic regime, drug compliance issues can arise with significant influence on patient health. In this study, we investigated the molecular impact of short-term NTBC therapy discontinuation on liver tissue of Fah-deficient mice. We found that after seven days of NTBC withdrawal, molecular pathways related to oxidative stress, glutathione metabolism, and liver regeneration were mostly affected. More specifically, NRF2-mediated oxidative stress response and several toxicological gene classes related to reactive oxygen species metabolism were significantly modulated. We observed that the expression of several key glutathione metabolism related genes including Slc7a11 and Ggt1 was highly increased after short-term NTBC therapy deprivation. This stress response was associated with the transcriptional activation of several markers of liver progenitor cells including Atf3, Cyr61, Ddr1, Epcam, Elovl7, and Glis3, indicating a concreted activation of liver regeneration early after NTBC withdrawal.

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Potential Antioxidant and Anti-Inflammatory Effects of Spilanthes acmella and Its Health Beneficial Effects: A Review

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18073532 ◽

2021 ◽

Vol 18 (7) ◽

pp. 3532

Author(s):

Rohanizah Abdul Rahim ◽

Putri Ayu Jayusman ◽

Norliza Muhammad ◽

Norazlina Mohamed ◽

Vuanghao Lim ◽

...

Keyword(s):

Oxidative Stress ◽

Potential Role ◽

Radical Scavenging ◽

Mapk Signaling ◽

Total Phenolic ◽

Thiobarbituric Acid Reactive Substance ◽

Potential Health ◽

Beneficial Effects ◽

Spilanthes Acmella ◽

Anti Inflammatory

Oxidative stress and inflammation are two common risk factors of various life-threatening disease pathogenesis. In recent years, medicinal plants that possess antioxidant and anti-inflammatory activities were extensively studied for their potential role in treating and preventing diseases. Spilanthes acmella (S. acmella), which has been traditionally used to treat toothache in Malaysia, contains various active metabolites responsible for its anti-inflammatory, antiseptic, and anesthetic bioactivities. These bioactivities were attributed to bioactive compounds, such as phenolic, flavonoids, and alkamides. The review focused on the summarization of in vitro and in vivo experimental reports on the antioxidant and anti-inflammatory actions of S. acmella, as well as how they contributed to potential health benefits in lowering the risk of diseases that were related to oxidative stress. The molecular mechanism of S. acmella in reducing oxidative stress and inflammatory targets, such as inducible nitric oxide synthase (iNOS), transcription factors of the nuclear factor-κB family (NF-κB), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) signaling pathways were discussed. Besides, the antioxidant potential of S. acmella was measured by total phenolic content (TPC), total flavonid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and superoxide anion radical scavenging (SOD) and thiobarbituric acid reactive substance (TBARS) assays. This review revealed that S. acmella might have a potential role as a reservoir of bioactive agents contributing to the observed antioxidant, anti-inflammatory, and health beneficial effects.

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