bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinant of fruit and vegetable intake in low income, Mexican children and their parents
Authors: Pérez‐Lizaur Ana , Plazas Maite , Kaufer‐Horwitz Martha 
Published: June 2021

BackgroundEpidemiological evidence suggests that populations with high vegetable and fruit (VF) consumption (>5 portions/day) have a lower risk for childhood obesity, cancer, and cardiovascular diseases. In Mexico we have few studies that identify the predictors of VF intake in children. So the aim of this study was to identify VF intake determinants in children and their parents attending Mexico City's Public Schools.MethodsA validated questionnaire (Cronbach's alpha 0.79) was used to assess the VF intake determinants in 142 pairs of children/parents (father or mother). Stepwise linear regression was performed.ResultsChildren consumed approximately 1.73 VF portions while parents reported 4.57 of VF/day. Girls consumed more VF than boys (p<0.01). Overweight or obesity (BMI p>85, NCHS) was greater in boys (55.1%, p<0.03). The mean age of parents was 35 years and had 8.4 years of education. The environmental factors that influenced a higher consumption of VF for parents were knowledge and accessibility (R²=0.12; p<0.000); for children were self efficacy, accessibility and knowledge (R²=0.74; p<0.000), and when parental variables were added to the model, expectative was also an explanatory variable (R²=0.74 p<0.002).ConclusionThe variables that determine VF consumption either in children or parents are knowledge and accessibility to VF; for children self efficacy as well as parental expectatives about the benefits of VF consumption was also important. These factors should be considered when designing programs aimed at increasing VF consumption in children.
Glutathione and riboflavin status in patients undergoing home nocturnal hemodialysis versus standard hemodialysis
Authors: Kanampuza JA , Donnelly S , McFarlane P , Chan C , House JD , Pencharz PB , Darling PB 
Published: June 2021

ObjectivesTo examine whether improved plasma cysteine (tCys) clearance in patients receiving home nocturnal hemodialysis (HNHD) (7 hrs/session, 6 nights/wk), influenced their erythrocyte (RBC) glutathione (GSH) concentration and riboflavin status, compared to patients on standard hemodialysis (SHD) (4 hrs/session, 3 d/wk).MethodsWe measured RBC GSH concentration by liquid chromatography tandem mass spectrometry & riboflavin status by RBC GSH reductase activity coefficient (EGRAC) in 15 HNHD, 15 SHD & 15 healthy controls (HC) participants. Estimated dietary protein intake (PRO), and plasma tCys, homocysteine (tHcy), C‐reactive protein (CRP) and vitamin C were also determined.Median (25th, 75th percentile)ConclusionRBC GSH and riboflavin status may be unaffected by hemodialysis modality in well nourished HD patients. Supported by Kidney Foundation of Canada
Lodenafil Carbonate: Reproductive and Developmental Evaluation
Authors: Taricano Ingrid , Costa Elaine Rodrigues , Bonamin Leoni , Afiune Jorge , Scivoletto Regina 
Published: June 2021

Lodenafil, is one new orally‐active, potent and selective inhibitor of the enzyme phosphodiesterase 5 (PDE5) developed in Brazil, with therapeutically application in erectile dysfunction. The objective of this study was to evaluate the reproduction toxicity and in offspring, evidencing specifically the occurrence of possible toxic effects in the fertility, gestation, maternal behavior and lactation, as well as growth and postnatal development of F1 since its birth, up to 4 days. Wistar rats received daily: metilcelulose, (2 control groups); 5,7mg/kg, 28,4mg/kg and 142mg/kg (2 groups of 10 males and 10 females in each dose).Drug administration occurred during 35 and 14 consecutive days for males and females, respectively. Animals had been observed for detention of possible clinical and behavior alterations, delivery, and other toxic signals including morbidity or mortality, gestation time, litter size number of each sex, total living pups and corporal weight of the offspring.Litter components had been analyzed in the maximum 24 h after the birth, and the evaluation repeated in all first 4 days after‐birth. No remarkable toxicity was found in the offspring even in the presence of maternal toxicity, no significant decrease in body weight gain was observed, decrease in offspring righting reflex and increase in litter size, were observed.FellowshipCristália Produtos Químicos e Farmacêuticos, Instituto Royal
Cannabinoid receptor‐independent actions of HU210 upon the viability and mobility of PC3 prostate cancer cells
Authors: Fowler Christopher John , Chung Sui Chu , Persson Emma 
Published: June 2021

Both CB receptor‐dependent and independent effects of cannabinoids upon cancer cell viability have been reported in the literature. Here, we reexamined cannabinoid effects upon PC3 cell viability and mobility in view of recent data indicating that prostate cancer CB1 receptor expression is associated with disease severity and outcome (Chung et al., Eur J Cancer, in press).PCA experiments showed that the PC3 cells had measurable, but low CB1 receptor expression, and no clear expression of CB2 receptors. Cell viability experiments, using 1% FBS and incubation times of 1‐6 days, indicated that the CB receptor agonists CP55,940 (0.3 and 1 µM) and HU210 (1 µM), the 2‐AG synthesis inhibitors orlistat (1 µM) and RHC‐80267 (30 µM) and MAFP (0.1 and 1 µM, an inhibitor of 2‐AG metabolism) did not affect cell viability. In contrast 3 and 10 µM HU210 rapidly blocked cell viability. PC3 mobility was assayed at 1% FBS by following the ability of cells to repopulate a scratched area of the well. No effects of CP55,940, orlistat, RHC‐80267, MAFP and 2‐AG itself were seen, whilst HU210 (10 but not 1 µM) and cytochalasin D, which disrupts actin cytoskeletons, completely halted cell mobility. The effect of HU210, due to reduced cell viability, was not blocked by concomitant incubation with AM251 (1 µM) or AM630 (1 µM). Thus under the experimental conditions used here, no CB receptor‐dependent effects upon PC3 cell viability and mobility are seen.
Postconditioning during reperfusion attenuates myocardial injury without improved mitochondrial oxidative phosphorylation
Authors: Chen Qun , Lesnefsky Edward J 
Published: June 2021

Postconditioning (PC) applied during reperfusion (REP) decreases myocardial injury. However, mitochondrial damage occurs during ischemia (ISC). We propose that PC can not improve ISC‐damaged mitochondrial function during REP. In the untreated group (UNT), isolated rat hearts were subjected to 30 min global ISC and 30 min REP at 37°C. In the PC group, 6 cycles of 10 sec ISC + 10 sec REP was applied at the onset of REP. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated at the end of REP. Maximal state 3 rates of oxidative phosphorylation (OXPHOS, nAO/mg/min) were measured. PC decreased LDH release (mu/g/60 min; UNT 1065±182 vs. PC 669±38 n=5 in each group P < 0.05) without improved functional recovery during REP. PC did not improve respiration in SSM and IFM using glutamate, succinate, and TMPD‐ascorbate as complex I, complex II, and cytochrome oxidase substrates, respectively. Thus, cardiac injury can still be attenuated even though OXPHOS are already compromised by ISC. The mechanism by which PC decreases myocardial injury is not through improved OXPHOS.±SEM; *p<0.05 vs. UNT (untreated), TC, time control
Coupling between cochlear fibrocytes and microvessels of spiral ligament in guinea pig cochlea
Authors: Nuttall Alfred L. , Shi Xiaorui 
Published: June 2021

The dynamic regulation of oxygen and the supply of glucose to match changes in metabolic demand are critical to the maintenance of cochlear homeostasis. Although spiral modiolar artery autoregulation is one control mechanism for the reaction to systemic blood pressure and energy changes of the whole cochlea, another local mechanism may be active at the level of capillaries. With transmission electron microscopy combined with fluorescence confocal imaging, we found that fibrocytes are uniquely positioned and spatially distributed near pre‐capillaries and post‐capillaries of the spiral ligament. Inter‐connected fibrocytes were positive to Na+/K+ ATPase β1 and connexin 40. With fluo‐4, a fluorescent calcium indicator, we found that connected fibrocytes contained relatively high calcium signals in comparison with other cells in cochlear lateral wall. Photolysis of the caged divalent ion chelator NP‐EGTA in fibrocytes resulted in calcium signal propagation to neighbor cells, including the vascular cells: pericytes and endothelial cells. The connection between the fibrocytes and the vascular cells suggests a "fibro‐vascular" coupling in the cochlear microvessel system in the spiral ligament. This signal pathway may be important for the local blood flow control to meet cellular metabolic needs.Supported: NIDCD DC 008888, NIDCDDC 00105, DC 005983
A Systems Model of HIF1α Dynamics in Ischemia
Authors: Qutub Amina Ann , Popel Aleksander S. 
Published: June 2021

During ischemia, a cell responds to changing oxygen levels by activation of a transcription factor, hypoxia‐inducible factor 1 (HIF1). HIF1, in response to hypoxia, upregulates genes involved in angiogenesis, cell growth, glycolysis and inflammation. To characterize this process, we used computational modeling to predict HIF1 signaling during ischemia, on multiple biological levels.We developed models based on extensive published experimental data on HIF1α in different microenvironments. Three intracellular models consist of ordinary differential equations that represent HIF1α hydroxylation, succinate product inhibition and reactive oxygen species effects. We also designed an experimentally‐based network model of HIF1α signaling pathways related to inflammation and angiogenesis; this model includes HIF1 modulation by NFκB, TGFβ, VEGF, and insulin. Finally, we developed a cellular rule‐based model that relates hypoxia to blood vessel formation. In these models, we studied the conditions of hypoxia and ischemia, for different durations.Model results predict relative expression of HIF1α in ischemic environments, intracellularly and at the tissue level. Results suggest an optimal window for therapeutic intervention following the onset of ischemia; during this time, inflammatory response could be minimized, while angiogenesis would still occur. This window depends on levels of HIF1α and H2O2 intracellularly, and the modulation of signaling responses in adjacent cells and tissue.In stroke, peripheral artery disease or wound‐healing, minimizing inflammation while maximizing angiogenesis is a means to restore health. The combined HIF1 systems models predict how this can be achieved through regulation of hypoxic pathways.
Neurotrophins in pulmonary artery smooth muscle
Authors: Meuchel Lucas William , Gates Benjamin , Thompson Michael , Pabelick Christina M , Prakash Y. S. 
Published: June 2021

Neurotrophins are growth factors traditionally associated with neuronal structure and function; however, neurotrophins and their receptors have been found throughout the lung, including airway, pulmonary artery and endothelium although their roles within the lung are still under investigation. We tested the hypothesis that brain derived neurotrophic factor (BDNF) enhances pulmonary artery constriction. In endothelium‐intact arterial rings, BDNF (acute 10nM, 1h; chronic 1nM, 18h) did not affect phenylephrine‐induced contraction, but enhanced subsequent ACh‐induced relaxation. These effects were blunted by endothelium‐denudation. In fura‐2 loaded human pulmonary artery smooth muscle cells, acute and chronic BDNF decreased the Ca2+ responses to 10 μM bradykinin. In human pulmonary artery exposed to TNFα (50 ng/mL, 18h), BDNF levels were decreased, compared to human airway, where previous studies under identical treatment resulted in increased levels. These data refute our hypothesis and suggest that neurotrophins, working via endothelial cells, enhance vasodilation in the pulmonary vasculature.Supported by FAMRI, NIH grant UL1RR024150, and the Department of Anesthesiology, Mayo Clinic.
Caveolae and neurotrophins in pulmonary artery smooth muscle
Authors: Gates Benjamin , Thompson Michael , Meuchel Lucas , Pabelick Christina , Prakash Y S 
Published: June 2021

The mechanisms underlying pulmonary hypertension are still being explored. Recent studies suggest a role for caveolae (pit‐like plasma membrane structures), although it is not entirely clear whether they enhance or blunt pulmonary hypertension. The proteins caveolins ‐1, and ‐2, and polymerase I and transcription release factor (PTRF) are essential to forming caveolae. In other tissues, growth factors called neurotrophins (e.g. brain‐derived neurotrophic factor, BDNF) are thought to affect cell proliferation and structure. This study investigated caveolins and neurotrophins in human pulmonary artery. Western analysis of artery from a patient with primary pulmonary hypertension showed decreased levels of caveolin‐1, caveolin‐2, PTRF and RhoA. Exposure of human pulmonary artery to 1 nM BDNF increased protein levels of caveolin‐1 and PTRF. Isolated pulmonary artery smooth muscle cells exposed to BDNF showed decreased [Ca2+]i response to bradykinin (10 nM) and histamine (10 μM), but no change in caveolin or PTRF levels. These data suggest that decreased caveolin levels may contribute to increased pulmonary vascular contractility, while neurotrophins (potentially by increasing caveolin levels) may alleviate excessive constriction. Further studies are required to determine whether neurotrophins affect caveolae in endothelial cells or smooth muscle.Supported by FAMRI, NIH grant UL1RR024150, and the Department of Anesthesiology, Mayo Clinic.
Inhibition of TRPC3 by PKG contributes to NO‐mediated vasorelaxation
Authors: Chen Jie , Crossland Randy F. , Noorani Muzamil M.Z. , Marrelli Sean P. 
Published: June 2021

Nitric oxide (NO) inhibits heterologously expressed TRPC3 channels via PKG‐dependent phosphorylation. We examined whether NO inhibition of TRPC3 occurs in freshly isolated smooth muscle cells (SMC) and, if so, whether TRPC3 channel inhibition contributes to NO‐mediated vasorelaxation. We used rat carotid artery (CA) as our model tissue.Whole cell patch clamp of CA SMC demonstrated a non‐selective cation current that was activated by extracellular uridine triphosphate (UTP; 60 µM) and completely inhibited by La3+ (100 µM). The UTP‐stimulated current (IUTP) was also inhibited by anti‐TRPC3 antibody in the pipette solution, demonstrating that TRPC3 is the channel of IUTP. Application of an NO‐donor (MAHMA NONOate) or 8Br‐cGMP caused inhibition of IUTP. Pre‐incubation with a PKG inhibitor (KT5823) prevented inhibition by 8Br‐cGMP, demonstrating the essential role for PKG. Next, intact CA segments (in an artery myograph) were contracted with UTP (100 µM) in the presence or absence of La3+ (100 µM) and then relaxed with SNP, an NO donor. Relaxation to SNP was significantly less in the presence of La3+.In summary, we demonstrate that rat CA SMC expresses functional TRPC3 channels and that these channels are inhibited by the NO/cGMP/PKG signaling pathway. Furthermore, our data suggests that NO inhibition of TRPC3 contributes to NO‐mediated vasorelaxation. Supported by: AHA 0665100Y and NIH HL088435 (SPM)
Voluntary wheel running abolishes vascular inflammation and restores endothelial function in old mice
Authors: Connell Melanie L , Durrant Jessica R , Russell Molly J , Donato Anthony J , Seals Douglas R , Lesniewski Lisa A 
Published: June 2021

Aging is associated with impaired endothelial dependent dilation (EDD) and vascular inflammation. Aerobic exercise improves EDD in older humans and rodents, but it's unknown if this is associated with reduced vascular inflammation. Inflammatory cytokines were measured using multiplex ELISA in aortas of young (YC, 4‐6 mo) and old (OC, 29‐34 mo) cage‐control and old voluntary wheel running (OVR, 1.1±0.6 km/d, 12 wk) B6D2F1 mice (N=4‐6/group). EDD to acetylcholine was measured in isolated femoral arteries (N=6‐8/group). Interleukin‐1β (IL‐1β: 3.7±0.9 vs 1.6±0.5 pg/ml, P<0.05), interferon γ (IFNγ: 45.1±8.4 vs 15.0±5.0 pg/ml, P<0.05) and tumor necrosis factor a (TNF a: 2.6±0.5 vs 1.2±0.4 pg/ml, P<0.05) were higher and maximal EDD was lower (85±4% vs 97±3%, P<0.01) in OC vs. YC. In OVR, IL‐1β (1.1±0.7 pg/ml), IFNγ (26.5±2.0 pg/ml), TNF a (1.2±0.3 pg/ml) and EDD (95±2%) were restored to levels similar to or better than YC. To determine if the absence of vascular inflammation in OVR is associated with reduced activation of the pro‐inflammatory transcription factor, nuclear factor κ B (NFκB), we measured aortic protein expression of the inhibitor of NFκB, IκBa (western blot). IκBa was 117% greater in aortas of OVR compared with OC mice 1.3±0.3 vs 0.6±0.2 AUs, P<0.05). This is the first evidence that habitual exercise may restore the loss of EDD with aging by abolishing vascular inflammation, possibly via inhibition of NFκB.NIH AG013038, AG006537, AG015897, AG029337, AG000279
Apnea is exacerbated following exposure to intermittent hypoxia and is mitigated following administration of an antioxidant cocktail
Authors: Yokhana Sanar , Lee Dorothy S , Badr M Safwan , Mateika Jason H 
Published: June 2021

PurposeTo determine whether exposure to intermittent hypoxia (IH) exacerbates apnea severity and whether administration of an antioxidant cocktail (AOX) mitigates this response.MethodsTwo studies were completed. Ten participants with OSA completed study 1 while 5 participants completed study 2. Study 1 required two visits while study 2 required 3 visits. For both studies, a baseline polysomnogram with no intervention was completed initially. During the remaining visits of both studies, participants were exposed to IH {12‐4 minute episodes of hypoxia (PETO2‐ 50 mmHg, PETCO2 ‐ 3 mmHg above baseline)} immediately followed by a sleep study. During visits 2 and 3 of study 2 participants were administered either an AOX or Placebo (PLB) in a randomized blinded fashion. Breathing events were scored during the initial 3 hours of sleep.ResultsStudy 1 ‐ The apnea/hypopnea index (AHI) after exposure to IH was greater compared to baseline (43.3 ± 5.3 vs. 34.6 ± 3.2 events/hr, p = 0.04). Study 2 ‐ Similar results were observed when the AHI during PLB was compared to baseline (43.4 ± 6.2 vs. 27.6 ± 7.8 events/hr, p = 0.01). In contrast, the AHI during the PLB trial was greater compared to the AHI following AOX administration (43.4 ± 6.2 vs. 31.8 ± 5.7 events/hr, p = 0.04).ConclusionsExposure to IH may lead to an increase in the AHI while administration of an antioxidant cocktail may mitigate the increase.FundingNIH (HL‐085537)
dAIH restores phrenic long‐term facilitation contralateral to cervical spinal injury
Authors: Vinit Stéphane , Mitchell Gordon S 
Published: June 2021

After C2 hemisection (C2HS), acute intermittent hypoxia (AIH) elicits phrenic long‐term facilitation (pLTF) ipsilateral (Golder and Mitchell, 2005), but not contralateral to injury (Doperalski and Fuller, 2006). Repetitive (daily) exposure to AIH (dAIH, 10‐5 min episodes of 11% O2, 5 min normoxic intervals, 7 days) nearly completely (>80%) restores breathing capacity 2 weeks post‐C2HS (Barr et al., 2007). Since dAIH also increases growth/trophic factor expression, including Brain Derived Neurotrophic Factor (BDNF) which is critical for AIH‐induced phrenic long‐term facilitation (pLTF), we tested the hypothesis that dAIH restores AIH‐induced pLTF contralateral to C2HS (15 days post‐injury). In urethane anesthetized, paralyzed, vagotomized and ventilated rats, integrated phrenic nerve activity was measured contralateral to C2HS following pretreatment with: 1) dAIH beginning 7 days post‐injury; and 2) normoxia (sham). Following AIH, pLTF was not observed in untreated rats contralateral to C2HS (7% ± 4% of hypoxic activity, 60 min post‐AIH; n=6; n.s.). In contrast, robust pLTF was observed contralateral to injury in dAIH treated rats (33% ± 11% % of hypoxic activity, 60 min post‐AIH; n=8; p<0.05). Thus, dAIH restores the capacity for AIH‐induced pLTF contralateral to C2HS. Repetitive AIH may be a useful treatment to induce functional recovery following cervical spinal injury.Supported by NIH HL69064.
Repetitive Hypercapnia and Hypercapnic Hypoxia Slows Disease Progression in a Rodent Model of Amyotrophic Lateral Sclerosis (ALS)
Authors: Nashold Lisa J , Schumacher Bryan T , Mitchell Gordon S 
Published: June 2021

Rats over‐expressing a mutated form of superoxide dismutase (SOD1G93A) exhibit progressive motor neuron degeneration and paralysis, and are a common model of familial ALS. We previously made the chance observation that weekly exposure to graded hypercapnia (5% and 7% CO2; 20 min) followed by hypercapnic hypoxia (7% CO2 in 10% O2 20 min) apparently delayed disease progression. In this uncontrolled comparison, treated rats were 16 days older at a defined end stage (>20% decrease in body mass) vs untreated littermates (p<0.05). Here we studied this protocol under controlled conditions. Eleven mutant SOD1G93A rats were paired with a mutant littermate of the same sex; within each pair, 1 rat was treated 3 times per week with the hypercapnia/hypoxia protocol and the other was exposed to air (sham). Exposures were performed from 82 days of age until one rat within the pair reached end‐stage. Rats were perfused to enable counts of surviving motor neurons (analysis underway). Decreases in body mass slowed in treated rats on the day of sacrifice (untreated: 19% +/‐2%, treated: 10% +/‐2%; p <0.05). In 7 of 11 pairs, untreated rats reached end‐stage first (p=0.06); treated rats tended to be older (164+/‐3; n = 4) vs untreated rats at end‐stage (149+/‐6; n = 7; p=0.11). Repetitive hypercapnia may slow disease progression and increase survival in SOD1G93A rats. Further studies to test this hypothesis are underway.NIH NS057778 and RR023916
Aerobic exercise training increases maximal in vivo cholinergic responsiveness but not sensitivity of eccrine sweat glands
Authors: Wilson Thad E. , Monahan Kevin D. , Kearney Matthew , Fogelman Amy , Sauder Charity L. , Ray Chester A. 
Published: June 2021

Aerobic exercise training increases maximal sweat capacity and sweat responses at a given internal temperature. However, the mechanisms underlying these effects are unknown. The purpose of this study was to determine if aerobic exercise training improves in vivo cholinergic sensitivity and responsiveness of eccrine sweat glands. Eleven previously sedentary subjects were tested before and after 8 weeks of aerobic training consisting of 4 bouts of exercise per week that elicited an ~20% increase in peak oxygen uptake. In vivo cholinergic sensitivity and responsiveness were determined by dose‐response curves of acetylcholine (ACh) to sweat secretion rate on two forearm sites. ACh was administered via intradermal microdialysis while measuring cutaneous water loss (capacitance hygrometry) directly above the microdialysis membrane. Exercise training did not alter the number of cholinergic activated sweat glands or the dose‐response derived ED50 (2.0±0.1 to 2.1±0.1 ‐logM dose of ACh; P>0.05). However, the maximal response to the highest dose of ACh was greater after exercise training (0.84±0.11 to 1.16±0.21 mg/cm2/min, P<0.05). These data indicate that 8 weeks of aerobic exercise training does not increase in vivo cholinergic sensitivity as indicated by the ED50 but does increase maximal in vivo cholinergic responsiveness of human eccrine sweat glands.Support: HL77670, AG24420, M01 RR10732, C06 RR016499