bluuebunny/crossref_metadata_2025 huggingface dataset:
Mindfulness meditation lowers blood pressure and sympathetic activity in hypertensive patients with chronic kidney disease
Authors: Park Jeanie , Bauer‐Wu Susan
Published: June 2021

Chronic kidney disease (CKD) is characterized by chronic sympathetic nervous system (SNS) overactivation that contributes to hypertension and mortality. Previous reports suggest that mindfulness meditation may have beneficial effects on blood pressure (BP), but the mechanisms are unknown. We hypothesized that mindfulness meditation lowers BP in hypertensive CKD patients by lowering central SNS output. We measured continuous arterial BP and muscle sympathetic nerve activity (MSNA) in 16 male, hypertensive patients with Stage III CKD at baseline, and during 14 minutes of either: a) mindfulness‐based meditation (N=10); or b) health education on hypertension (control intervention, N=6). The meditation group compared to controls had a significantly greater reduction in systolic BP (− 13.2±1.8 vs. −2.3±1.3 mm Hg, p<0.001), diastolic BP (−5.5±1.3 vs. −1.5±0.9, p=0.046), mean arterial pressure (−1.7±0.8 vs. −8.1±1.2 mm Hg, p=0.002), and a trend towards greater reduction in heart rate (−3.3±1.3 vs. +0.2±1.0 beats/min, p=0.071). Concomitantly, there was a significantly greater reduction in MSNA during mindfulness meditation compared to the control intervention (− 6.1±1.3 vs. +1.5±1.3 bursts/min, p=0.002). These findings suggest that mindfulness meditation may lower arterial BP and heart rate by decreasing SNS output in hypertensive patients with CKD. Supported by K grant HL098744.
ALTERNATIVE PATHWAY TO ANGIOTENSIN CONVERTING ENZYME (ACE) FOR ANGIOTENSIN II GENERATION IN MOUSE MESENTERIC ARTERY
Authors: Becari Christiane , Barbosa da Silva Marcondes A. , Salgado Helio C. , Tostes Rita C. A. , Oliveira Eduardo B. , Salgado Maria Cristina O.
Published: June 2021

We investigated the Ang II forming enzymes in the mesenteric artery isolated from C57/BL6 mice. Cumulative concentration curves to Ang I and II were obtained in the absence or presence of losartan (AT1 receptor antagonist; 1 μM), captopril (ACE inhibitor; 10 μM) or chymostatin (serine proteases inhibitor; 100 μM), and association of captopril and chymostatin. Mesenteric arteries mRNA expression for ACE and elastase‐2 was obtained by real time‐PCR. Ang II and I produced a concentration‐dependent vasoconstrictor effect that was abolished by losartan. Ang II responses were not affected by the inhibitors. Chymostatin allowed a small but significant displacement of the curve to Ang I to the right (pPD2=7.3±0.3, p<0.05), while captopril induced greater rightward shift of the curve (pD2=5.4±0.3 vs 7.7±0.2 in controls, p<0.001). Captopril and chymostatin determined a further displacement of the curve to Ang I (pD2=4.4±0.4, p<0.05). mRNA for elastase‐2 and ACE were detected in mesenteric arteries. Ang II formation from Ang I is essentially dependent on ACE, although an alternative chymostatin‐sensitive pathway, probably elastase‐2, is also present in the mouse mesenteric artery. Supported by FAPESP and CNPq.
Systemic CCK increases brown adipose tissue sympathetic nerve activity
Authors: Madden Christopher J
Published: June 2021

The neural circuits responsible for governing sympathetic outflow to brown adipose tissue in response to thermoregulatory and febrile stimuli are very well characterized. In contrast we are only beginning to understand the organization of the metabolic regulation of the sympathetic outflow to brown adipose. The current study determines whether cholecystokine (CCK), a gut hormone released postprandially, activates brown adipose tissue sympathetic nerve activity via the vagus nerve. In urethane/chloralose anesthetized rats (n=3), intravenous administration of cholecystokinin (CCK, 0.5μg/kg) increased brown adipose tissue sympathetic nerve activity (BAT SNA: +141 ± 39% control), brown adipose tissue temperature (+0.5 ± 0.1 oC) and expired CO2 (+0.5 ± 0.1%). The CCK‐evoked increases in BAT SNA, BAT temperature and expired CO2 were sustained for at least 40 minutes. Bilateral cervical vagotomy prevented the CCK‐evoked increases in BAT SNA, BAT temperature and expired CO2 (n=2). These results indicate that peripheral CCK acts via vagal afferents to increase metabolism, energy expenditure and thermogenesis in BAT. The neural circuitry mediating this effect and the physiological significance of this system are under investigation.
Adiponectin receptor mediated weight regulation: an inflammation‐independent mechanism?
Authors: Wintrob Zachary A.P. , Radpasand Hamed , Elmeshad Mohamed H. , Barima Asante , Rabey Jonathan L. , Chmiel Kristina A. , Fayazi Zahra S. , Otvos Lazlo , Surmacz Eva , Faitar Silviu , Ceacareanu Alice C.
Published: June 2021

Adiponectin (ADP), a modulator of insulin actions, recently became an attractive therapeutic tool. We present here the effect of the first‐in‐class ADP receptor agonist (ADP355) on weight gain and biomarker patterns associated with long term high fat diet (HFD).

Adult Sprague‐Dawley (SD) rats (n=23) were fed HFD (60% cal from fat) ad‐libitum for 15 weeks. ADP355 at 0.5mg/kg/dose, or saline was administered intraperitoneally every other day (n=3 each); weight gain, food intake, glucose (Glc) levels and blood biomarkers were assessed weekly. C‐reactive protein, glucagon, IL‐6, TNFα, amylin, insulin and leptin levels were measured by a multiplexed bead‐specific Luminex assay. The assays included 3 randomly selected matched controls. Results were assessed by student t‐test.

After 15 weeks of treatment, the ADP355 group exhibited reduced weight gain (P<0.009), lower Glc levels (P=0.02), n=20, and significantly decreased glucagon (P<0.015) levels relative to control. While leptin levels increased, TNFα and amylin levels decreased significantly in the control group (P<0.002 for all). In the ADP355 group, leptin expression maintained a modestly increasing trend, however, no change was observed in the TNFα or amylin levels. In HFD fed SD rats, stimulation of the ADP receptor might be beneficial for weight gain prevention; however, our data do not support an anti‐inflammatory activity of ADP355 administration.
Omega‐3 fatty acid supplementation improves adaptive coping in a rat model of post‐partum depression
Authors: Gonzales Elisa M , Barrett Douglas W , Gonzalez‐Lima Francisco , Lane Michelle A
Published: June 2021

Omega‐3 fatty acid (O3FA) supplementation may relieve symptoms of post‐partum depression (PPD) and anxiety and aid in learning and memory. Our objective was to determine if O3FA supplementation could decrease anxiety and improve learning and memory in a rat model of PPD. Rats consumed diets prepared with 7% menhaden or sunflower oil (24% vs. 0% O3FA) ad libitum across two cycles of gestation. Open field (OF) and shuttle box escape (SBE) tests began after the second parturition. Data shown are the mean ± SEM, n=10/group. In the OF, both groups showed decreased ambulation from day 1 to 2, indicating habituation; the day 2 decrease was greater in the deficient than supplemented group (5.9 ± 1.6 vs. 1.2 ±1.0 m) using repeated measures ANOVA [F(1,18)=6.022, P=0.025]. In the SBE, the supplemented group had more escapes out of 30 trials [24 ± 1 vs. 18 ± 2; F(1,18)=6.325, P=0.022] and shorter escape latencies [11 ± 1 vs. 15 ± 2 sec; F(1,18)=4.835, P=0.041] than the deficient group. OF results do not indicate reduced anxiety. SBE results indicate that O3FA supplementation may facilitate an adaptive coping mechanism in response to stress. Funded by the Research Enhancement Program, Texas State University.
MEASURING HYDROGEN SULFIDE AT THE CELLULAR AND SUB‐CELLULAR LEVEL WITH FLUORESCENT NANOPARTICLES
Authors: DeLeon Eric R , Galvan Manuel , Bohlson Suzanne S , Olson Kenneth R
Published: June 2021

Despite evidence that hydrogen sulfide (H2S) is an important signaling molecule involved in oxygen sensing, it has been technically difficult to measure H2S production, metabolism or distribution at the cellular and sub‐cellular level in living tissue. Here, we examine the potential for cellular H2S measurement using 150–200 nm diameter silicate nanoparticles (Photonic Explorers for Bioanalysis with Biologically Localized Embedding; PEBBLEs) and demonstrate its applicability. PEBBLES were synthesized with a hydrophilic core containing fluorescein mercuric acetate (FMA), an analyte‐sensitive dye that becomes irreversibly quenched when bound to sulfur moieties, and a hydrophobic shell that is only permeable toH2S. PEBBLES can be delivered into cells via a gene gun, or as in the present experiments, ingested by mouse bone marrow‐derived macrophages (BMDM+P). BMDM+P were exposed to a range of H2S concentrations (10 nM‐10 mM H2S as Na2S) or exposed to hypoxia for 1 h and examined by flow cytometry and confocal microscopy. Increasing H2S concentration dose‐dependently quenched FMA and exposure to 1 nM H2S was readily resolved. Furthermore, hypoxia increased intracellular H2S production. This is the first demonstration of intracellular H2S production in any tissue and clearly shows that during hypoxia intracellular H2S concentration increases. This supports our hypothesis that oxygen sensing is the balance between intrinsic intracellular H2S production and its O2‐dependent metabolism and that this is the key couple in oxygen sensing. It also affirms the validity of this method in H2S research. Support: NSF IOS 1051627
Consequences of a Maternal Vitamin B6 Deficiency on Hypercapnic Response in Rat Pups
Authors: St. Laurent Jessica Lynn , Iceman Kimberly , Harris Michael Bruce
Published: June 2021

Recently, maternal dietary deficiencies have been linked to brainstem neurotransmitter and homeostatic reflex dysfunctions and infant vulnerability to the Sudden Infant Death Syndrome (SIDS). In particular, a gestational and postnatal tryptophan (critical for serotonin, 5HT synthesis) deficiency was shown to induce a serotonergic defect in rat pups, and an attenuated ventilatory response to CO2. We study combined influences of 5HT and the γ‐aminobutyric acid (GABA) mediated chemosensitivity. Vitamin B6 is a coenzyme critical in both 5HT and GABA synthesis. We test the hypothesis that a maternal dietary B6 deficiency (B6d) will alter homeostasis in rat pups. We show multisystem failures with B6d beginning at parturition (P0), reflex disruption when B6d is started at P5, and little effect of B6d started at P10. Data suggest a critical period for B6d sensitivity and the potential that B6d‐induced 5HT and GABAergic deficiencies to produce homeostatic dysfunction that could also influence vulnerability to SIDS. Supported by NIH 2U54NS041069–06A1 and 5P20RR016466.
The development of antiseptic gel from mangosteen shell extract
Authors: Sangcakul Areeporn , Ratananukul Piniti
Published: June 2021

Mangosteen (Garcinia mangostana L.) is widely grown throughout the Southeast Asian countries and well known as the queen of fruits. The mangosteen shell extracts have more potential for antibacterial activity. This study was undertaken to develop an antiseptic hand cleansing gel which increased efficiency for killing potentially pathogenic organisms by effect of xanthones in mangosteen shell extracts and to investigate antibacterial activity of this antiseptic gel. The mangosteen shell was extracted by acetone and the xanthones concentrations were analyzed by using HPLC. The result showed that the extract contained the active xanthones: alpha‐mangostin and gamma‐mangostin 34.12 and 5.63 g%, respectively. The optimum formulation of antiseptic gel contained mangosteen shell extract 0.5% of gel. This antiseptic gel showed good effective to control bacteria; Escherichia coli, MRSA, Micrococcus leteus, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Candida albicans. Consumer acceptance testing with 20 volunteers who were between 18–30 years old showed that 95% of consumers accepted antiseptic gel with mangosteen shell extract and the overall liking was like slightly. Therefore, this antiseptic hand cleansing gel would be possibly for an alternative product for the personal hand hygiene.
Transcription factor BCL11B enforces asymmetric enamel‐secreting cell development in the mouse incisor by bidirectional regulation of gene expression
Authors: Kyrylkova Kateryna , Kyryachenko Sergiy , Kioussi Chrissa , Leid Mark
Published: June 2021

Dental caries is one of the most common diseases, affecting 92% of adults, and is a primary reason for tooth loss. The current state‐of‐the‐art approach to replace a missing tooth is by means of a dental implant, which is, however, prone to mechanical and biological failure. Therefore, the ultimate goal of the therapeutic sciences is to develop dental tissue and whole tooth bioengineering.

Molecular mechanisms of tooth organogenesis and enamel formation can be studied using mouse incisor development. Asymmetric deposition of enamel only on the outer side of the tooth makes mouse incisor an attractive model system.

We show that the transcription factor BCL11B strongly enforces asymmetric localization of enamel‐secreting cells (ameloblasts) in the mouse incisor. BCL11B does so by promoting development and differentiation of the epithelial stem cells into the ameloblasts on the outer side while suppressing these processes on the inner side of the tooth. Underlying these spatio‐specific functions of BCL11B is the bidirectional regulation of a large gene network, comprised of genes encoding members of the FGF, TGFβ, and Sonic hedgehog signaling.

These studies are of significance because they will contribute to a broader understanding of how the activities of transcription and growth factors are regulated during tooth organogenesis and how they can be modulated as an approach to therapy and tooth bioengineering.
Identification of regulatory RNA binding proteins that mediate alternative polyadenylation in cardiac myocytes
Authors: Smith Leah , McGuinness Michael , Paulding Waltke , Roessler Anne , Gabanic Andrew , Kelley Melissa , Haar Lauren , Tranter Michael
Published: June 2021

Introduction

Cardiovascular disease is the leading cause of death in the US with coronary heart disease (ischemia/reperfusion; I/R injury) accounting for approximately half of these deaths. Recent data from our lab suggests that alternative polyadenylation (APA) plays a role in cardiac gene expression following I/R via modulation of mRNA 3′UTR length, leading to the inclusion or exclusion of regulatory sequence elements. The goal of this work is to identify specific RNA binding proteins (RBPs) that are likely to mediate APA in the myocardium.

Methods

The 3′UTR of the heat shock protein 70.3 (Hsp70.3) mRNA was randomly biotinylated throughout and incubated with cardiac protein extract associated with differential APA of the Hsp70.3 3′UTR. Biotinylated RNA and RBPs were co‐precipitated and bound RBPs were identified using mass spectrometry.

Results

We identified a total of 45 known RBPs interacting with the Hsp70.3 3′UTR. Of these, 9 unique RBPs were found to bind only under conditions associated with a long 3′UTR, whereas 10 unique RBPs were found to bind only in association with APA truncation of the 3′UTR. Our results identified RBPs previously indicated to play a role in APA and/or mRNA degradation as well as RBPs whose function remains unknown. Work is ongoing to determine the functional role of these RBPs in alternative polyadenylation and cardiac I/R injury.

This work was partially funded by a UC CCTST Grant (MT).
Coronary arterial function is not impaired in patients following continuous‐flow left ventricular assist device implantation
Authors: Johnson Elizabeth , Diakos Nikos , Selzman Craig , Reid Bruce , Stehlik Josef , Kfoury Abdallah , Saidi Abdulfatah , Wever‐Pinzon Omar , Verma Divya R , Yen Chi‐Gang , Li Dean , Drakos Stavros , Symons J David
Published: June 2021

Continuous‐flow left ventricular assist devices (LVADs) are used in advanced heart failure patients either to bridge them to transplantation or as a permanent‐destination therapy. We sought to determine whether chronic exposure to non‐pulsatile blood flow and acute increases in coronary perfusion pressure associated with LVAD implantation attenuate arterial function. A transmural biopsy of the left‐ventricle was obtained from seven male patients (52±6 years old) at the time of LVAD implant (pre) and 142±12 days later (post) upon LVAD explant. Arteries were dissected free and function was assessed using isometric tension techniques. First, Lmax tension was determined on each vessel. Next, contraction‐response curves to potassium chloride (KCl, 10–100 mM) were performed. To determine endothelium‐dependent and – independent vasorelaxation, respectively, concentration‐response curves to bradykinin (BK, 10−6 to 10−10 M) and sodium nitroprusside (SNP, 10−4 to 10−9 M) were completed on vessels precontracted to ~65% of maximal tension development. Maximal KCl‐evoked contraction (0.99±0.22 and 0.69±0.14 mg tension development/μm vessel length), maximal BK‐evoked vasorelaxation (64±13% and 80±7%), and maximal SNP‐evoked vasorelaxation (92±3% and 92±4%), was similar in arteries obtained from pre (n=13 arteries, 206±40 μm i.d.) and post (n=14 arteries, 288±24 μm i.d.) transmural biopsy samples, respectively. These preliminary data indicate that coronary vascular function is not attenuated by LVAD implantation.
Effects of Race on Dynamic Cerebral Autoregulation in Elderly People
Authors: Serrador Jorge M , Lipsitz Lewis A , Deegan Brian , Laighin Gearóid Ó , Sorond Farzaneh
Published: June 2021

Race is known to affect cardiovascular dynamics, but no research has examined cerebrovascular dynamics. Therefore, we retrospectively examined measures of cerebral autoregulation in a group of elderly individuals recruited into the population‐based MOBILIZE Boston Study.

Of 765 community‐dwelling volunteers that were recruited for the MOBILIZE Boston study, cerebral flow velocity measures were obtained on 451 individuals (78±5 yrs) of which self reported race was African American ‐ AA (43), White (385) and Other (23). Cerebral flow velocity (TCD), beat‐by‐beat blood pressure (Finapres) and end‐tidal CO2 (capnography) were measured during a sit to stand maneuver and while seated.

Race was associated with significant differences in Phase in both the 0.04–0.07 Hz range (AA: 28±41°, White: 46±34°, Other: 55±28°, p<0.05) and 0.07–0.15 Hz range (AA: 7±57°, White: 39±42°, Other: 33±33°, p<0.01). In contrast there was no difference in Gain or Coherence values. Autoregulatory Index was similar across groups (AA: 5.3±2.8, White: 4.8±2.5, Other: 5.0±2.2) as was CO2 Vasoreactivity (AA: 3.0±0.8, White: 3.0±0.7, Other: 3.0±0.7 %/mmHg). We controlled for age, diabetes, hypertension and prescription drugs.

Our preliminary data suggest that race may be an important factor to consider in understanding cerebral autoregulation. The finding that AA had reduced phase suggests impaired autoregulation and may partially explain the increased risk of cerebrovascular events in AA. However, future work is necessary using larger numbers to validate our findings.
Loss of parenchymal arteriolar dilation to K+ contributes to impaired neurovascular coupling in chronic angiotensin II hypertension
Authors: Dunn Kathryn M , Koide Masayo , Nelson Mark T
Published: June 2021

Hypertension has catastrophic effects on the brain. Hypertension induced by angiotensin II (Ang II) impairs neurovascular coupling (NVC), the process by which vasodilation accompanies increases in neuronal activity, but the mechanisms of this dysfunction are not clear. A rise in Ca2+ concentration in perivascular astrocytic processes (“endfeet”) that surround brain parenchymal arterioles (PAs) is a critical step in NVC by stimulating vasodilator release. One key mediator released by endfeet during NVC is K+, which activates inward rectifier K+ channels (Kir) on smooth muscle cells (SMCs) producing vasodilation. We investigated endfoot Ca2+ dynamics and K+‐mediated vasodilation in chronic Ang II hypertension. Using multiphoton microscopy, we found that endfoot Ca2+ dynamics were not altered in brain slices from Ang II hypertensive mice, yet the vasodilation to neuronal depolarization was reduced by 54%. Correspondingly, dilation to K+ was essentially absent in pressurized PAs from hypertensive mice. Further, Kir current in hypertensive pial artery SMCs was reduced from 7 pA/pF to <1 pA/pF. Our results indicate that chronic Ang II‐dependent hypertension profoundly impairs Kir function in brain arterial SMCs, resulting in loss of K+‐mediated dilation and dysfunctional NVC. This study was supported by NIH grants P01 HL095488, R01 HL44455, R01 HL098243, T32 HL07944, and the Totman Medical Research Trust.
Hemorrhage‐induced increase in total peripheral resistance is blunted in conscious obese Zucker rats
Authors: Xiang Lusha , Clemmer John S , Lu Silu , Mittwede Peter N
Published: June 2021

Obesity is associated with increased morbidity and mortality after severe hemorrhage. We hypothesize that in obesity, the blood pressure compensation following severe hemorrhage is impaired due to blunted neurohormonal responses. Mean arterial pressure (MAP) and heart rate (HR) in conscious lean (LZ) and obese Zucker rats (OZ) were monitored before and after injection of SNP or prazosin (iv.) to estimate baroreflex sensitivity or basal sympathetic tone, respectively. Severe hemorrhage (a loss of 35% of total blood volume) was induced in additional groups of conscious LZ and OZ. The MAP, HR, cardiac output (CO), total peripheral resistance (TPR), and plasma renin activity (PRA) were measured before and one hour after hemorrhage. Basal values for MAP, CO, TPR, and PRA were not different between conscious LZ and OZ. However, under basal conditions, prazosin resulted in a larger fall in MAP in OZ (134 ± 3 to 85 ± 4 mmHg) than in LZ (129 ± 4 to 96 ± 4 mmHg). In addition, baroreflex control of HR was impaired in OZ. Following hemorrhage, MAP and HR recovery were more complete in LZ than in OZ. CO was similar in both groups but MAP, TPR, HR, and PRA were significantly lower in OZ than in LZ (Table). These results indicate that the diminished recovery of MAP after hemorrhage in OZ is due to a blunted increase in TPR associated with impaired renin secretion and baroreflex activity. Supported by AHA‐12SDG12050525, NIH HL‐51971, and HL‐89581
Head‐up tilt suppressed sympathetic nerve activity synchronized with cardiac cycle to skin but increased that to muscle in passively warmed men
Authors: Ogawa Yu , Kamijo Yoshi‐ichiro , Ikegawa Shigeki , Masuki Shizue , Morita Atsumi , Nose Hiroshi
Published: June 2021

We have suggested that a component of skin sympathetic nerve activity (SSNA) synchronized with cardiac cycle might be an active cutaneous vasodilator. However, the possibility that the component involves signals of muscle sympathetic nerve activity (MSNA) was not completely excluded. Since head‐up tilt (HUT) suppresses cutaneous vasodilation in hyperthermia while increases heart rate and arterial pressure, we hypothesized that 30°HUT reduced the SSNA component while enhanced MSNA with reduced right atrial and carotid artery distensions. In 12 men (22–42yr), wearing a perfusion suit, we measured right atrial volume (VRA) and carotid artery diameter (CAD; echocardiography), esophageal temperature (Tes), SSNA and MSNA (microneurography; the peroneal nerve; N=7) during supine and also 30°HUT while Tes was increased by 0.7°C with 47‐°C water perfusion into the suit. We found that HUT reduced the SSNA component (P=0.003) while enhanced MSNA (P=0.007) with reduced right atrial and carotid artery distensions (both P<0.0001). The latency of the SSNA component from R‐wave was 1.0s, shorter than that of MSNA (1.2s; P<0.01). Moreover, the latency of the SSNA component from peak of VRA and that of MSNA from valley of CAD were almost constant, 0.7s and 1.2s, respectively, as reported previously. Thus, we successfully distinguished the SSNA component from MSNA, which might be an active cutaneous vasodilator.
Cerebrovascular sensitivity to reductions in carbon dioxide tension during heat stress does not predict tolerance to a simulate hemorrhage
Authors: Lee Joshua F. , Christmas Kevin M. , Hurr Chansol , Harrison Michelle L. , Kim Kiyoung , Brothers R. Matthew
Published: June 2021

Heat stress (HS) reduces arterial carbon dioxide (PaCO2), as indexed by end‐tidal carbon dioxide (PETCO2), which contributes to the decreased cerebral perfusion (MCAVmean) and cerebral vascular conductance (CVC) in this thermal condition. Intra‐individual variability in cerebrovascular sensitivity to this HS induced hypocapnia may a key factor underlying variability in tolerance to a simulated hemorrhage during HS. This study tested the hypothesis that cerebral sensitivity to reductions in PETCO2 during HS would be related to tolerance to a simulated hemorrhage challenge during this thermal condition. Cerebral vascular sensitivity to HS driven reductions in PETCO2 was indexed as the change in cerebral vascular conductance (CVC) during hypocanpia induced by 30 s of hyperventilation during HS. The difference in cumulative stress index (CSI Diff) between NT and HS conditions was used to assess the effect of HS on tolerance to the simulated hemorrhage challenge. CVCi was reduced by 1.4±0.8 cm/s/mmHg/Torr during hyperventilation induced hypocapnia. However, there was no relationship between CSI Diff and cerebral vasomotor sensitivity to reductions in PETCO2 during HS (R=0.12, P=0.69). These data suggest that individual differences in cerebral vasomotor sensitivity in the hypocapnic range do not predict tolerance to a simulated hemorrhage challenge in heat stressed individuals.
Stress‐induced hyperthermia in mice is, at least in part, due to increased voluntary motor activity
Authors: Boily Patrice
Published: June 2021

Most higher vertebrates exhibit an increase in body temperature when exposed to acute stress. Because voluntary motor activity (VMA) can affect body temperature and because acute stress can affect VMA, I hypothesized that this stress‐induced hyperthermia (SIH) is an artifact of changes in VMA. Body temperature and motor activity of male C57BL/6 mice were monitored by telemetry while they were exposed to varying levels of stress (control, handling, spill, cage switch, clean cage). During daytime, the treatments resulted in an increasing SIH, which was correlated to VMA. The significant differences in SIH among the treatments disappeared when VMA was included as a covariate. Similar results were obtained at night when mice are normally active. Mice pre‐treated with varying doses (0 to 300mg/kg I.P.) of sodium salicylate prior to stress exposure (clean cage) exhibited a SIH that decreased with an increasing dose of salicylate and that was correlated to VMA. The differences in SIH between the doses disappeared when VMA was included as a covariate. Based on these results I conclude that SIH in mice is, at least in part, an artifact of changes in VMA. Funded by a CSU‐AAUP grant.
The effect of iron deficiency on AMPK subunit isoform composition in skeletal muscle
Authors: Hardman Shalene E , Merrill John F. , Thomson David M , Hancock Chad R
Published: June 2021

5′AMP‐activated protein kinase (AMPK) is a heterotrimeric protein activated in response to energetic stress. The AMPK heterotrimer is composed of different isoforms of the catalytic α subunit along with the regulatory β and γ subunits. The isoforms of the α, β, and γ subunits play different roles in regulating AMPK activation by regulating the AMP dependence and localization of AMPK. The predominant heterotrimeric composition activated in skeletal muscle is α2β2γ3. We have previously shown that iron deficiency (ID) results in decreased protein expression of the α2 catalytic isoform with no change in α1 expression. Furthermore, ID results in no difference in overall α2 activity in contrast to an increase in α1 isoform activity. To further assess the effects of ID on AMPK activation and signaling, the β and γ isoform protein expression was analyzed in fast‐twitch muscle (gastrocnemius). Rats were fed a control (C=50–58 mg/kg Fe) or iron deficient (ID=2–6 mg/kg Fe) diet for 6–8 wks. ID resulted in a 46.8% decrease in protein expression of the β2 isoform with no change in expression of the β1 isoform. Additionally, ID resulted in a 78.4% decrease in γ3 isoform protein expression with no change in expression of γ1 or γ2. This study indicates that there is an alteration in the predominant skeletal muscle heterotrimeric composition of AMPK in response to ID, which may contribute to altered sensitivity and activation in response to the energetic stress.
Improvement of Hypovolemic men's and women's orthostatic tolerance by a short exposure to artificial gravity
Authors: Evans Joyce McClendon , Ribeiro L Christine , Wang Siqi , Falvo Michael J , Serrador Jorge , Ferguson Connor R , Moore Fritz B , Smith Jeffrey D , Rask Jon C , Kostas Vladimir , Zhang Qingguang , Knapp Charles F
Published: June 2021

We used a combination of head up tilt and lower body negative pressure to test the orthostatic tolerance limit (OTL) of nine men and eight women, once following a 90 min exposure to artificial gravity (AG) and once following 90 min of head down bedrest (HDBR) In both cases (21 days apart), subjects were made hypovolemic by low salt diet plus 20 mg intravenous furosemide. Heart rate (from ECG), continuous blood pressure, stroke volume, cardiac output and peripheral resistance (Finometer), middle cerebral artery blood velocity (MCAv, transcranial Doppler), partial pressure of end‐tidal carbon dioxide (ETCO2, Novametrics) and body segmental impedance (UFI THRIM) were measured during supine control, during OTL to presyncope and supine recovery. Orthostatic tolerance on the day of AG exposure was significantly greater than on the day following HDBR (p<0.03), see figure. Mechanisms of improved tolerance on the AG day included higher values of stroke volume and cerebral artery velocity and lower values of blood pressure, peripheral vascular and cerebrovascular resistance in control and during tilt. By the time presyncope was reached, stroke volume was at the same level on each day of study. We conclude that AG exposure prolonged the onset of presyncope by increasing output of the heart and cerebral blood flow. Supported by KY NASA EPSCoR Grant #NNX07AT58A, KY State Matching Grants, NASA JSC Human Research Program and NASA Ames Research Center.
Hyperthermia does not affect the increase in cerebral perfusion during a cognitive task
Authors: Schlader Zachary J. , Lucas Rebekah A.I. , Pearson James , Crandall Craig G.
Published: June 2021

This study tested the hypotheses that hyperthermia impairs the capacity to increase cerebral perfusion to a cognitive task (i.e., activation‐flow coupling) and that changes in activation‐flow coupling are related to decrements in cognitive performance during hyperthermia. Changes in mean middle cerebral artery blood velocity (MCAvmean) served as an index of cerebral perfusion, while the nBack test (a test of working memory) was the measure of cognitive performance. The activation‐flow coupling response to the nBack test was compared between normothermia and hyperthermia. Hyperthermia increased intestinal temperature by 1.3 ± 0.1°C and reduced MCAvmean by 15 ± 14%. nBack test performance was unaffected by hyperthermia (P=0.28). The relative increase in MCAvmean to the nBack test was not different between thermal states (normothermia: 18 ± 12%; hyperthermia: 18 ± 11%, P=0.61); while activation‐flow coupling was unrelated to nBack test performance during normothermia (r=0.05, P=0.65) and hyperthermia (r=0.04, P=0.70). These data indicate that activation‐flow coupling to a cognitive challenge involving working memory is unaffected by hyperthermia. It remains to be determined whether heat stress alters activation‐flow coupling responses to tests involving different cognitive domains; particularly those that are impaired by hyperthermia.

Supported by NIH Grant HL061388
Effect of chronic heart failure on mitochondrial function and apoptotic susceptibility in rat skeletal muscle
Authors: Nguyen Linda M.‐D. , Carey‐Love Sean D. , Ahn Bumsoo , Ferreira Leonardo F. , Adhihetty Peter J.
Published: June 2021

Chronic heart failure (CHF) is marked by myocardial dysfunction and is also associated with skeletal muscle metabolic abnormalities but the underlying cellular mechanisms are not well understood. Thus, we investigated whether CHF alters mitochondrial function/content and apoptotic susceptibility in skeletal muscle. Young Lewis rats (8 wks) were subjected to either myocardial infarction to induce CHF or, Sham (Sh) operation, and hindlimb muscles were removed 16‐weeks post‐surgery (n=6/group). Mitochondrial function tended to be impaired in CHF as indicated by a reduced respiratory control ratio (RCR‐State 3/4 respiration). CHF‐induced impairments in respiration coincided with significant reductions in cytochrome c and the mitochondrial anti‐oxidant, MnSOD, in isolated mitochondria. Additionally, oxidative damage, indicated by protein carbonylation was significantly elevated in CHF. CHF animals tended to exhibit greater mitochondrial apoptotic susceptibility (Bax:Bcl‐2) but this surprisingly did not alter the vulnerability to exogenous H2O2‐ induced pro‐apoptotic release from isolated mitochondria. Our preliminary results indicate CHF impairs mitochondrial function and/or content, increases mitochondrial apoptotic susceptibility and enhances ROS‐induced damage in muscle, and these deleterious mitochondrial‐associated adaptations likely contribute towards CHF pathogenesis.
Role of the renal mineralocorticoid receptor for potassium homeostasis
Authors: Roesinger Marian , Loffing‐Cueni Dominique , Ronzaud Caroline , Canonica Jérémie , Debonneville Anne , Hummler Edith , Staub Olivier , Loffing Johannes
Published: June 2021

Aldosterone enhances renal K+ excretion via ROMK channels and stimulates apical epithelial Na+ channels (ENaC) to provide the electrochemical gradient for K+ secretion. Here we studied MRflox/AQP2cre knockout mice (KO) with targeted inactivation of the mineralocorticoid receptor (MR) in the renal collecting system (CS). The mice tolerate K+ loading (5% K+, 2d) without major illness, but show slightly reduced food intake indicating K+ avoidance. Immunoblotting and immunohistochemistry reveal a K+ diet‐induced increase in ROMK protein abundance and apical localization that is similar for the CS of control and KO mice. However, KO mice show less K+ diet‐induced α‐ and γENaC proteolytic activation and the apical translocation of ENaC is restricted to the remaining MR‐positive late DCT. KO mice have a reduced abundance and phosphorylation of the NaCl‐cotransporter (NCC) in the DCT. This NCC down‐regulation is observed already under basal conditions, but becomes even more pronounced on 5% K+ diet. Thus, the K+ diet‐induced activation of ENaC, but not of ROMK, appears to depend on MR. In KO mice, the loss of the MR‐dependent activation of ENaC in the CS might be compensated, at least in part, by down‐regulation of NCC, which increases Na+ delivery to cells with remaining ENaC activity, and hence improves the electrochemical gradient for K+ secretion.
Bioinformatic analysis of specificity in signaling that controls smooth muscle tone
Authors: Dippold Rachael P , Fisher Steven
Published: June 2021

Abnormal SMC force production is common to diseases including hypertension and asthma. Smooth muscle is phenotypically diverse and variable in its response to signals that regulate force production. We have focused on Myosin phosphatase (MP), the primary effector of SMC relaxation and a key target of signals that regulate SMC force. Variable splicing of Exon24 of the regulatory subunit Mypt1 results in variable expression of a leucine zipper (LZ) motif that is required for NO/cGMP signaling. Here we expanded our investigation of variation in this pathway using bioinformatic analysis of phylogenetic sequence conservation, tissue‐specific expression, and regulatory motifs, placing emphasis on alternative transcripts and LZ motifs. Mypt2 gives rise to numerous muscle subtype‐specific transcripts. Both Mypt2 and the upstream cGMP‐kinase generate mutually exclusive LZ motifs through alternative exons that show variable phylogenetic conservation. While the catalytic subunit of MP is highly conserved, the inhibitory subunits (PPP1R14a‐d) are less well conserved, have inter‐individual variability in sequence (SNPs), and great diversity in expression. These data suggest that variability in the regulatory subunits of MP may determine differences in SMC responses to dilator and constrictor signals between individuals and in disease states. This variability may be informative for drug therapy targeting.
Cardiorespiratory fitness affects polymorphism in ADRB3 Trp64Arg‐caused increase in common carotid intima‐media thickness
Authors: Fujie Shumpei , Iemitsu Motoyuki , Murakami Haruka , Sanada Kiyoshi , Kawano Hiroshi , Gando Yuko , Kawakami Ryoko , Miyachi Motohiko
Published: June 2021

PURPOSE

In the present study, a cross‐sectional investigation of 769 Japanese men and women (18–75 years old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between risk of cardiovascular disease and beta3‐adrenergic receptor (ADRB3) Trp64Arg gene polymorphism.

METHODS

Common carotid intima‐media thickness (ccIMT) was assessed as a risk of atherosclerosis. We measured peak oxygen uptake (VO2peak) during incremental cycle ergometer exercise test, and then the subjects were divided into high‐(High‐Fit) and low‐cardiorespiratory fitness (Low‐Fit) groups based on the median value of VO2peak in each sex and decade.

RESULTS

Body fat, triglyceride and plasma glucose levels were lower and HDL cholesterol levels and VO2peak were higher in High‐Fit subjects compared with in Low‐Fit subjects, but there were no significant effect of ADRB3 polymorphism. There was no significant effect of ADRB3 Trp64Arg polymorphism on ccIMT. In Low‐Fit subjects, ccIMT increased in ArgArg genotype individuals compared with TrpTrp and TrpArg genotype of ADRB3, however, had no effect on ADRB3 polymorphisms in High‐Fit subjects.

CONCLUSION

These results suggest that the higher cardiorespiratory fitness may attenuate a risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.

This work was supported by a Grant‐in‐Aid for Scientific Research of Japan (#20300231, #20700563).
Adult onset obesity and type 2 diabetes: a metabolic model
Authors: Bernardin Charles P. , Moller Aage
Published: June 2021

It is widely recognized that controlling obesity is one of the most effective means of treating Type 2 Diabetes. We are therefore very interested in defining the conditions that cause obesity. It is also well known that adult metabolisms decrease significantly with age. Yet, to our knowledge, these effects have not been fully described. We review the physiology of the pancreas as it relates to Type 2 Diabetes. We also discuss the relationship between ectopic fat deposition and Type 2 Diabetes in sedentary adults. We briefly present the benefits of lifestyle changes such as diet and exercise. We derive a first‐order metabolic model that describes the onset of adult obesity based on the recent calorimetric measurements of Mifflin et al. (1990). We compute the metabolic rate “constants” of sedentary US adults and show that they are actually slowly decreasing functions of age and height. We believe that this model helps describe the major mechanism behind the rapidly spreading obesity epidemic in our aging population. For example, we show that 20 year old people consuming a diet that is just adequate to maintain a normal weight at age 20 are nearly ensured to reach obesity by age 80 unless they significantly reduce their caloric intake as they age. We recommend this model to Doctors and Clinical Dieticians who need to design weight reduction plans with realistic loss goals and practical time horizons for their overweight patients.
The uremic molecule p‐cresol is lowered after supplementing the diet of chronic kidney disease patients with fiber
Authors: Salmean Younis , Dahl Wendy J
Published: June 2021

CKD patients suffer from uremic symptoms thought to be caused by accumulation of various uremic molecules. Our aim was to determine the effects of fiber on uremic symptoms, quality of life (QoL), p‐cresol and eGFR in CKD patients. A control period (2 wks) was followed a lower fiber period (4 wks; 10 g/d pea hull fiber) and a higher fiber intervention (6 wks; 10 g/d pea hull fiber and 15.0 g/d of inulin). Symptoms and QoL were determined by the KDQOL‐36™, bowel habits by 5‐day journals, plasma p‐cresol by GC‐MS, and kidney function was estimated with CKD‐EPI. Participants (n=13; 6M, 7F) completed the study. No significant changes in overall QoL were observed. “Dry Skin” improved (69±11 to 88±6, p<0.05), as did “Numbness in Hands and Feet” (65±9 to 83±6, p < 0.05). Daily bowel movement frequency increased from 1.4±0.2 to 1.9±0.3/d after 4 and 10 wks of treatment (p<0.05). p‐Cresol decreased from 7.25±1.74 μg/L to 5.82±1.72 μg/L (24%) with treatment (p<0.05 with transformed mean), and 37% in participants who consumed ≥70% of the inulin from 6.71±1.98 μg/L to 4.22±1.16 μg/L (p<0.05). eGFR improved from 42.4±5.0 mL/min/173m2 to 46.2±6 mL/min/173m2 (p<0.05) at 7 wks, but decreased to 44±5 mL/min/173m2 (p=0.07) at study end. Supplementing the diet of CKD patients with fiber may be a dietary therapy to reduce p‐cresol and may improve uremic symptoms. Supported by the Saskatchewan Pulse Growers.
Parental Perceptions of Healthy Beverage Alternatives to Sugar‐Sweetened Beverages
Authors: Welsh Jean A. , Healy Shannan K. , Vos Miriam B.
Published: June 2021

Background

Efforts to reduce child obesity risk often promote reduced intake of sugar‐sweetened beverages (SSBs). Our objective was to describe parents’ perception of a healthy beverage alternative to SSBs.

Methods

A convenience sample of parents of healthy (normal or overweight) children (n=61) awaiting a clinic appointment completed an interviewer‐assisted survey (in English or Spanish) to identify the top three beverages perceived to be healthy alternatives to SSBs consumed by their child (age ≥ 1 y) at meals. Parents selected from among a display of 8 bottled beverages including: water, whole milk, reduced‐fat milk (2% fat), non‐fat milk, flavored milk, 100% juice, fruit‐flavored drinks, and vitamin water. The frequency of selection of each beverage was determined.

Results

12% of parents described their children (mean age 8.5 y) as overweight; 40% as daily SSB consumers. Parents most frequently selected: water, 90% (95% confidence interval [CI]: 83, 98); 100% juice, 57% (CI: 45, 70); or reduced‐fat milk, 38% (CI: 25, 50) as one of their preferred alternatives to SSBs. Approximately one‐quarter of parents selected fruit‐flavored drinks, whole milk, or vitamin water and 11% (CI: 3.2, 19.7) selected fat‐free milk.

Conclusion

Water is recognized by nearly all parents as a healthy alternative to SSBs but non‐fat milk, the other beverage promoted in dietary guidelines for children, is not. Beverages discouraged in dietary guidelines, including fruit‐flavored drinks and whole milk, are perceived by many parents to be healthy alternatives to SSBs. These findings suggest that interventions to help parents identify healthy beverage options for their children are needed.
Intake of Antioxidants and Subsequent Decline in Physical Function
Authors: Bartali Benedetta , Curto Teresa , Maserejian Nancy , Araujo Andre
Published: June 2021

Background/Objectives

Oxidative stress is considered a risk factor for physical function (PF) decline with aging. The objective of this study was to examine the relation of antioxidant intake to change in self‐reported PF over a 5‐year period.

Methods

The Boston Area Community Health (BACH) Survey is a population‐based longitudinal study of a racially/ethnically diverse population. Change in PF from baseline (2002–2005) to follow‐up (2006–2010) was assessed using the SF‐12 questionnaire. Intake of antioxidants (combining dietary and supplemental) was estimated at baseline using the validated Block FFQ. In total, 2827 persons aged 29–80 years had complete assessments at both baseline and follow‐up. General linear models were used to examine the association between energy‐adjusted quartiles of vitamins A, C, E and change in PF, after adjustment for age, sex, race/ethnicity, SES, smoking, BMI, physical activity, depression and chronic conditions.

Results

A low intake (first quartile) of vitamins C and E was associated with a greater decline in PF compared with the highest quartile, with an adjusted mean difference in change in PF of −1.29 (95%CI:−2.34,−0.25) for vitamin C and of −1.21 (95%CI:−2.24, − 0.18) for vitamin E. PF decline was not significantly different in the lowest compared with the highest quartile of vitamin A (mean difference=−0.30,95%CI:−1.36,0.76).

Conclusions

A low intake of vitamins E and C plays a role in PF decline with aging. These results support the idea that oxidative stress contributes to PF decline and may help inform the development of intervention strategies aimed at reducing this important clinical and public health problem.
Effects of pulse physical form and digestive enzyme availability on postprandial glucose and appetite responses
Authors: Osei‐Boadi Katherene , Wonnell Brittany S. , Campbell Wayne W. , McCabe George P. , McCrory Megan A.
Published: June 2021

Background

Previous research has shown that whole pulses reduce glucose, hunger and appetite responses compared to other carbohydrate sources. However, it is not known if differential responses occur with consumption of blended pulses or when taking Beano® (which reduces GI discomfort) with pulses. We therefore tested the hypotheses that blended pulses and/or consuming Beano increase postprandial glucose and appetite.

Methods

Participants (n=12; BMI 23±3kg/m2; aged 28±10y (mean±SD)) consumed breakfast burritos containing ≥½c of whole (W), blended (B) or no lentils (C), each in combination with 3 Beano or placebo pills in a randomized, crossover, double‐blind, placebo‐controlled trial. AUCs over 3h were calculated.

Results

Preliminary results showed fullness (p=0.01) and hunger (p=0.04) were lower, and desire to eat (p=0.052) was higher, for Beano compared to placebo. There was a significant meal by Beano interaction effect on glucose (p=0.01), with Beano having 1.3, 1.2, 2.4% lower AUCs than placebo for W, B and C, respectively. Also, W and B lentils had 2.5 and 4.8% lower AUCs than C. Except for desire to eat, all results were in a direction where Beano gave lower values compared to placebo.

Conclusion

Blended and whole lentils have similar effects on lowering postprandial glucose compared to a control meal, and Beano has only small effects on postprandial glucose and appetite.

[USDBC; NIH RR025761]
A surveillance of micronutrient status in bariatric surgery patients
Authors: Wright Breanne Natasha , Myers Cathy‐Ann Mary , Van Meter Marnie A. , Mattar Samer G. , Gletsu‐Miller Nana
Published: June 2021

Roux‐en‐y gastric bypass surgery (RYGB) is effective for weight loss, but may promote malnutrition. To confirm our earlier findings of copper deficiency and further examine associated malnutrition following RYGB, we recruited 46 patients and determined blood concentrations of copper (Cu), hemoglobin, ferritin, folate, zinc (Zn), C‐reactive protein (hsCRP), and vitamins B1, B6, and B12. Plasma ceruloplasmin activity (Cp) was assayed using the oxidase method. Statistical analysis included mean ± S.E., Pearson correlations and p‐value < 0.05. Subjects were age 49 ± 1, 5.2 ± 0.7 years post RYGB, and predominantly female (91%) and Caucasian (80%). The prevalence (%) of nutrient deficiencies were: copper (Cu= 2, Cp= 13); anemia= 17; iron= 17; Zn= 22, B1= 4, B6= 6; B12= 4; and folate= 0, despite high self‐reported compliance in micronutrient supplementation (89%). Elevated hsCRP concentrations were observed (37%). Correlations were found between hsCRP and Cu (r = 0.33), Cp (r = 0.35) and Zn (r = −0.29). The biomarker Cp suggested a 13% prevalence of copper deficiency, similar to previous reports. The high prevalence of elevated hsCRP, and associations with copper and Zn, suggests that inflammation may mask copper deficiency and overestimate Zn deficiency. This study highlights the need for more sensitive measures of nutrition status in order to optimize post‐surgery health. Support by International Copper Association.

Grant Funding Source: International Copper Association