scholarly journals Human hyperpolarized [1-13C] pyruvate CMR and adenosine stress test

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S H Joergensen ◽  
E S S Hansen ◽  
P B Staehr ◽  
C Laustsen ◽  
H Wiggers

Abstract Background Hyperpolarized (HP) [1-13C]pyruvate cardiac magnetic resonance (CMR) imaging can visualize myocardial perfusion and metabolism beyound glucose uptake. Depending on the prevailing metabolic conditions, buid-up of either [1-13C]lactate or 13C-bicarbonate can be measured. The aim of the present study was to assess cardiac metabolism using HP [1-13C]pyruvate rest-stress CMR. Methods Six healthy volunteers underwent cine CMR and HP [1-13C]pyruvate CMR at rest and during an adenosine stress test. Signal from HP [1-13C]pyruvate and its downstream metabolites was measured at the mid-left-ventricle (LV) level. We did semi-quantitative assessment of first-pass myocardial [1-13C]pyruvate perfusion. Pressure-volume loops were assessed non-invasively. Results Myocardial [1-13C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2±2.8 sec to 2.7±1.3 sec, p=0.04. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (kPL) for lactate increased from 0.011±0.009 sec–1 to 0.020±0.010 sec–1, p=0.04. The pyruvate oxidation (kPB) increased from 0.004±0.004 sec–1 to 0.012±0.007 sec–1, p=0.008. This increase in oxidative metabolism was positively correlated with heart rate (R2=0.44, p=0.02). Conclusion We observed a significant increase in carbohydrate oxidation during cardiac stress in the healthy human heart. The present study forms the basis for comparisons in future research in patients with heart failure and coronary artery disease. HP [1-13C]pyruvate CMR could be a possible alternative to PET in the future. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Danish Heart FoundationIndependent Research Fund, Denmark Increased conversion rate of pyruvate Increased metabolite signal in LV

Author(s):  
Chuk Ling Julian Lai ◽  
Daryl Yu Heng Lee ◽  
Monique On Yee Leung

Alteration in cortisol response to acute social stressors has been hypothesized to mediate childhood adversities (CA) and increased morbidity in adulthood. However, the evidence supporting an association between CA and cortisol response to social stressors is inconclusive. The present review addressed this issue by reviewing the literature on CA and cortisol response to acute social stressors, with a focus on studies with adolescents or adults, using the Childhood Trauma Questionnaire (CTQ) to assess CA, and examining salivary cortisol response to the Trier Social Stress Test (TSST). Systematic searches of relevant articles in PsycINFO, PubMed, Web of Science and ScienceDirect in February and March 2020 identified 12 articles including 1196 participants with mean ages ranging from 15.3 to 52.3 yrs. across studies. CTQ scores were significantly associated with cortisol response in 2 studies. In addition, the physical abuse and emotional neglect subscales were associated with cortisol response respectively in 2 separate studies. The lack of association between CA and cortisol response calls for more longitudinal studies, and the use of formal records of maltreatment or informant reports in future research to complement information collected by retrospective measures. In addition, increased attention to biological mechanisms other than that associated with the regulation of cortisol in explaining the connection between CA and psychiatry morbidity is warranted.


Author(s):  
Rodica Baciu ◽  
Brezeanu Petre ◽  
Adrian Simon

This paper intends to apply the Altman Z-score model to all the companies active in the wholesale of motor vehicle parts and accessories (NACE 4531), with extended financial statements. Using the panel data model over the time series for 2008-2016 on the companies of this sector, we conclude that 99% of the Z-score is explained by the independent variables (working capital, capital structure, turnover, earnings before interest and tax), with estimated parameters very close to the models classical values. The sample description of the paper and the corresponding results highlights the Z-score evolution by turnover clusters and principal components, with the largest companies performing the best (the only cluster with Z-score median above 3). We notice a tendency for decreasing high risk companies and increase in the medium risk companies, whereas the low risk companies are relatively stable. This improvement is mostly due to increasing capitalization rate and less external debt, despite the deteriorating working capital and operating margin. We believe that future research to evaluate Z-score sensitivity under stress test scenarios would be very useful to provide an insight of companies’ insolvency risk amid increasing interest rates and different fiscal tax on dividend.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A151-A151
Author(s):  
Joshua Tutek ◽  
Natalie Solomon ◽  
Jessica Dietch ◽  
Norah Simpson ◽  
Rachel Manber

Abstract Introduction Evening chronotype is associated with greater reports of insufficient sleep and sleep-related distress. Little research has examined this relationship within the context of pregnancy. This study investigated whether eveningness predicts insomnia severity, sleep effort, dysfunctional sleep beliefs, and sleep reactivity to stress in pregnant women with insomnia disorder. Methods Pregnant women with insomnia disorder who spoke English or Spanish enrolled in a clinical trial of cognitive behavioral therapy for insomnia (N = 178; M age = 32.6 years). Before beginning treatment, participants completed the Composite Scale of Morningness (CSM), Insomnia Severity Index (ISI), Glasgow Sleep Effort Scale (GSS), Dysfunctional Beliefs and Attitudes about Stress Scale (DBAS), and Ford Insomnia Response to Stress Test (FIRST). Participants were categorized into evening, intermediate, or morning chronotypes (bottom 25%, middle 50%, or top 25% of CSM scores, respectively). MANCOVA examined whether chronotype predicted higher baseline ISI, GSS, DBAS, and FIRST scores after adjusting for age, gestational week of pregnancy, and language. Results Sleep measures collectively differed by chronotype, F(8, 336) = 4.05, p < .001; Wilk’s Λ = .83, partial η-sqd = .09. Follow-up ANOVAs testing individual dependent variables were all significant (partial η-sqd = .04 – .10, p < .05). Pairwise comparisons (Bonferroni-adjusted; p < .05) found that evening types had higher ISI scores than intermediate (M difference = 2.21) and morning types (M difference = 2.30), and higher DBAS scores than morning types (M difference = .95). Morning types had lower FIRST scores than evening (M difference = 5.44) and intermediate types (M difference = 3.89). Conclusion Evening chronotype was associated with greater insomnia severity and maladaptive sleep-related cognition than other chronotypes among pregnant women with insomnia disorder. Future research may examine whether differences in chronotype have implications for insomnia treatment outcome during pregnancy, and whether greater morningness confers protection against sleep challenges during the early postpartum period. Support (if any) NIH R01 NR013662


1975 ◽  
Vol 228 (6) ◽  
pp. 1678-1684 ◽  
Author(s):  
VV Glaviano ◽  
J Goldberg ◽  
MT Pindok

In open-chest dogs anesthized with sodium pentobarbital, acetylcholine (ACh, 5 times 10'-5M) infused into the left circumflex coronary artery caused an increase in coronary flow and a decrease in myocardial O'2 extraction ratio (P less than .01) anduptake (P less than .05). Heart rate and mean arterial pressure were not altered,although left ventricular dP/dt declined from 2,037 plus or minus 205 to 1,873 plus or minus 194 mmHg/s (P less than .02). Intracoronary administration of norepinephrine (NE, 2.4 times 10'-6M) caused an increase in myocardial O'2 uptake (P less than .02); simultaneous infusion of both NE and ACh caused a decline in O'2 extraction ratio (P less than .01) and uptake (P less than 0.5). Myocardial adenylatecyclase activity in response to ACh was not altered significantly from a control levelof 188 plus or minus 22 pmol of '14C-labeled cyclic AMP/mg protein per 10 min. Norepinephrine alone elevated adenylate cyclase activity to 401 plus or minus 45 pmol ['14C]cyclic AMP/mg protein per 10 min (P less than .01). However, with simultaneous infusion of both NE and ACh, adenylate cyclase returned to control levels. Although ACh alone did not alter myocardial hormone-sensitive lipaseactivity, NE elevated lipolytic activity from 8.1 plus or minus .7 to 13.2 plus or minus 1.8 mueq free fatty acid (FTA)/g per 30 min (P less than .05). The administration of both ACh and NE returned lipase activity to nearly control levels. Myocardial uptake of FFA increased significantly during ACh infusion alone (P less than 0.5) and during NE infusion alone (P less than 905). However, when NE and AChwere administered together, a decline in FFA uptake was observed (P less than .02).These data indicate that the effects of ACh on cardiac metabolism are minimal, withthe decline in myocardial O'2 uptake of ACh primarily reflecting the decrease in contractility. On the other hand, antagonism of ACh on NE-stimulated myocardial lipid metabolism appears to involve activity of the adenylate cyclase system.


2020 ◽  
Vol 21 (22) ◽  
pp. 8686
Author(s):  
Meera Adishesh ◽  
Rafah Alnafakh ◽  
Duncan M. Baird ◽  
Rhiannon E. Jones ◽  
Shannon Simon ◽  
...  

Telomeres are transcribed as long non-coding RNAs called TERRAs (Telomeric repeat containing RNA) that participate in a variety of cellular regulatory functions. High telomerase activity (TA) is associated with endometrial cancer (EC). This study aimed to examine the levels of three TERRAs, transcribed at chromosomes 1q-2q-4q-10q-13q-22q, 16p and 20q in healthy (n = 23) and pathological (n = 24) human endometrium and to examine their association with cellular proliferation, TA and telomere lengths. EC samples demonstrated significantly reduced levels of TERRAs for Chromosome 16p (Ch-16p) (p < 0.002) and Chromosome 20q (Ch-20q) (p = 0.0006), when compared with the postmenopausal samples. No significant correlation was found between TERRA levels and TA but both Ch-16p and Ch-20q TERRA levels negatively correlated with the proliferative marker Ki67 (r = −0.35, p = 0.03 and r = −0.42, p = 0.01 respectively). Evaluation of single telomere length analysis (STELA) at XpYp telomeres demonstrated a significant shortening in EC samples when compared with healthy tissues (p = 0.002). We detected TERRAs in healthy human endometrium and observed altered individual TERRA-specific levels in malignant endometrium. The negative correlation of TERRAs with cellular proliferation along with their significant reduction in EC may suggest a role for TERRAs in carcinogenesis and thus future research should explore TERRAs as potential therapeutic targets in EC.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 311-311
Author(s):  
Tessa de Bie ◽  
Michiel Balvers ◽  
Maarten Jongsma ◽  
Renger Witkamp

Abstract Objectives The neurotransmitters γ-aminobutyric acid (GABA) and glutamic acid are present in many common components of our diet like for example tomato. Recent research suggests that oral supplementation of especially GABA can have relevant health effects with regard to diabetes and blood pressure. As of yet it is unclear whether these neurotransmitters are also bioavailable from a food matrix. In this controlled cross-over human intervention study, we aimed to evaluate the relative bioavailability of GABA and glutamic acid from tomato. Methods Eleven healthy men received one liter of water containing 888 mg/L GABA or 3673 mg/L glutamic acid, a liter blended tomato juice or a liter water. Solutions were given one week apart in a random order in a four way crossover design. On every test day 19 blood samples were collected in a period of 24 hours after ingestion of the test product. Plasma GABA and glutamic acid concentrations were determined with ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Results Baseline plasma GABA and glutamic acid concentrations were found to be 16.71 (SD 2.18) ng/mL and 4625.6 (SD 1666.1) ng/mL respectively. GABA baseline levels were constant (5.8 CV%) within individuals over the four consecutive test days while glutamic acid baseline levels varied considerably (23.5 CV%). Interestingly, GABA was determined to be just as bioavailable from tomato juice as from a solution in water; kinetic parameters (AUC, Cmax, Tmax) were not significantly different. For glutamic acid, the tomato food matrix did significantly alter the plasma kinetics, the maximum concentration was lower and the time to the maximum concentration was longer in the tomato condition as compared to glutamic acid dissolved in water. Conclusions These data suggest that GABA is bioavailable from food, and that food products containing GABA could potentially induce health effects similar to what is described for GABA supplements. Future research should focus on determining the bioavailability of GABA from other food products as well as the health effects of a GABA rich diet in humans. Funding Sources This work was supported by a consortium of companies (Agrico Research, Nunhems Netherlands, AVEBE) taking part in a collaborative public-partnership under the “Topsector Agri-Food” programme organised by the Dutch Ministry of Economic Affairs.


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