bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac and pulmonary arterial changes by fat embolization in the rat
Authors: Haileselassie Bereketeab , Adler Federico , McIff Terence , Poisner Alan , Herndon Betty , Molteni Agostino 
Published: June 2021

Fat embolization syndrome (FES) is a respiratory syndrome that may follow bone fractures with fat embolism. A model uses intravenous (iv) triolein. We found pulmonary arterial vasoconstriction in rats after triolein, improved by an ACE‐ inhibitor (captopril) or A2‐type 1 receptor blocker (losartan). We report cardiac morphology induced by triolein and drug treatment (5‐6 / group). Rats received 0.2 ml triolein with necropsy at 24, 48, 96, or 264 hrs. Others received triolein + 50 mg/kg captopril or 10 mg/kg losartan or both (5/group; 48 hr necropsy). Saline controls were necropsied at 24 hrs and 264 hrs (4‐5/group). Measurements were made on cardiac cross sections. Right ventricle (RV)/ left ventricle(LV) areas were analyzed. Triolein alone produced a time‐dependent pulmonary vasoconstriction. RV/LV ratio increased vs saline at 96 hrs (p<0.05) but returned to control values at 264 hr. At 48 hr, captopril, losartan or both groups showed RV/LV ratios comparable to controls, improved from ratios of groups receiving only triolein. The FES model produces RV dilation secondary to pulmonary vessel constriction, clearing without treatment by 264 hrs. Captopril and losartan preserve pulmonary arterial lumen patency and decrease RV dilation. This suggest both the reversibility of FES‐related cardiovascular changes and the role of the renin‐angiotensin system in its pathogenesis.Funding: MA & EJ Asher Ortho. Res. Endow.
Effect of Green Tea Flavonoid Supplementation on Features of Metabolic Syndrome (MeS)
Authors: Penugonda Kavitha , Sanchez Karah , Leyva Misti , Aston Christopher , Lyons Timothy , Basu Arpita 
Published: June 2021

Green tea, rich in flavonoids, has been shown to possess cardiovascular health benefits. This is a preliminary report on a randomized controlled trial investigating whether green tea beverage or extract supplementation improved the cardiovascular risk profile associated with MeS. Age and sex‐matched trios of participants with MeS were randomly assigned to control (4 cups water/day), green tea beverage (4 cups/day), or green tea supplement (2 capsules & 4 cups water/day) group for 8 weeks. Fasting blood samples, physical measurements were taken at screening, 4 & 8 weeks. Blood samples were analyzed for lipid, glucose, catechin and nitric oxide (NOx) levels. Body weight decreased in green tea (‐1.9 Kg) vs control (+0.1 Kg). There is an increasing trend in HDL cholesterol in green tea (+1.0 mg/dl) vs control. A decrease in ox‐LDL was found in green tea group vs baseline. Interestingly, no consistent effects were seen on glucose levels. No significant difference in the plasma catechin and serum NOx concentrations among the three groups. However, green tea beverage group showed a decreasing trend in serum NOx levels (p<0.1) compared to baseline, indicating anti‐ inflammatory effect. Green tea beverage or supplements may aid weight loss, raise HDL levels and may help in reducing ox‐LDL and NOx levels in MeS subjects. Thus, chronic green tea consumption may promote cardiovascular health by reducing oxidative stress and inflammation in at risk subjects.Funded by CHES, OSU
Structure‐activity relationships of diacetylene‐based LpxC inhibitors
Authors: Lee Chul-Jin , Liang Xiaofei , Park Eugene , Zeng Daina , Swanson Shauna , Chen Xin , Nicholas Robert A. , Raetz Christian R.H. , Toone Eric J. , Zhou Pei 
Published: June 2021

The LpxC enzyme in the lipid A biosynthesis pathway is one of most promising and yet clinically unexploited antibiotic targets for the treatment of multidrug‐resistant Gram‐negative infections. Unfortunately, extant LpxC inhibitors typically display large variations in potency against different Gram‐negative pathogens. Recently, structural studies in our laboratory revealed that significant structural variations exist among diverse LpxC orthologs. When LpxC orthologs bind to LPC‐009 inhibitor, the vicinity of the active site displays large conformational variations, creating different morphologies of the substrate‐binding hydrophobic passage. The LPC‐009 inhibitor whose pliable diacetylene scaffold is essential for its broad‐spectrum inhibition overcomes structural variations in the hydrophobic passages of LpxC orthologs. To further improve potency and antibiotic profiles of LPC‐009, a series of diacetylene‐based derivatives were designed from the lead compound LPC‐009, synthesized and evaluated for antibiotic profiles against diverse Gram‐negative pathogens. In addition, the crystal structures of LpxC in complex with newly designed LpxC inhibitors provide insights for structure‐activity relationships and future structure‐based optimization of LpxC inhibitors.This research was supported by National Institutes of Health Grants AI055588 (to P.Z.) and GM‐51310 (to C.RH.R).
CVT‐10216 selectively suppresses binge eating of palatable foods and attenuates dopamine release in the accumbens of rats
Authors: Bocarsly Miriam E , Avena Nicole M , Hoebel Bartley G , Paredes Daniel , Arolfo Maria P , Yao Lina , Fan4 Peidong , Diamond Ivan 
Published: June 2021

CVT‐10216 is a highly selective, reversible inhibitor of ALDH‐2 that reduces alcohol and cocaine intake in rats. Given overlaps in behavior and neurochemistry seen with binge eating and drug use, we examined the effects of CVT‐10216 on binge eating of palatable foods and subsequent dopamine (DA) release in the nucleus accumbens (NAc). Male Sprague‐Dawley rats (n=12/group) were maintained on 1) a binge schedule (12‐h deprivation then 12‐h access to chow and a 10% sucrose solution or vegetable shortening), 2) ad libitum chow with sucrose or shortening, or 3) only chow. After 25 days, CVT‐10216 (0, 7.5, or 15 mg/kg, i.p.) was administered. The 15 mg/kg dose decreased 1 h shortening and chow intake in binge eating rats (p<0.05) and decreased 24 h shortening intake in both the binge and ad libitum groups (p<0.05). This dose selectively decreased 1 h and 24 h intake of sugar in the sugar binge‐eating group (p<0.05). There was a slight decrease in 1 h chow intake for the ad libitum chow control group (p<0.05), but no effect on 24 h intake. In vivo microdialysis was performed in a new set of rats (n=8/group) fed binge sucrose or ad libitum sucrose and chow. CVT‐10216 (15 mg/kg) attenuated the rise in extracellular DA levels in rats binge eating sucrose (p<0.05). These preclinical findings suggest that selective, reversible ALDH‐2 inhibitors may have therapeutic potential to reduce binge eating behavior in clinical populations.Grant Funding Source : Gilead Sciences
Nitrogen metabolisms of dietary glutamate and the other nonessential amino acids in rats
Authors: Nakamura Hidehiro , Kawamata Yasuko , Kuwahara Tomomi , Torii Kunio , Sakai Ryosei 
Published: June 2021

Previous reports have shown that nitrogen (N) supply as nonessential amino acids (NEAAs) is required for normal growth in rats and that glutamate (Glu) is one of the most potent growth promoters among NEAAs. Our recent N‐balance study has also indicated that dietary Glu‐N was retained more than glycine‐N or glutamine‐N, suggesting differences in N‐metabolisms of these NEAAs. Thus, the present study aimed to compare N‐metabolism of dietary Glu with those of the other NEAAs using stable isotope techniques.Fischer strain male rats were given hourly meals containing [15N]Glu or other [15N]NEAAs. Concentrations and 15N‐enrichments of each amino acid (AA) in portal and arterial plasma were measured to estimate their first‐pass N‐metabolism and their N‐contribution for systemic AA.Virtually all of the dietary Glu‐N and aspartate‐N were metabolized in the gut for production of various AA such as alanine and citrulline. Meanwhile, substantial amount of the other dietary NEAAs were released into the portal vein directly without any metabolism in the gut. The incorporations of dietary Glu‐N in circulating AA were similar to those of aspartate‐N, alanine‐N and amino‐N of glutamine but greater than those of amide‐N of glutamine, glycine‐N, serine‐N. These results suggest efficient utilization of dietary Glu‐N for the intestinal synthesis of the other NEAAs and hence its significance as N‐source for whole body.Grant Funding Source: Ajinomoto Co., Inc.
Effects of retinoid catabolism on the gene expression in primary rat hepatocytes and hepatoma cells
Authors: Li Yang , Chen Guoxun 
Published: June 2021

Vitamin A (retinol, ROL) is reversibly oxidized into retinal (RAL) by retinol dehydrogenases; retinal is irreversibly oxidized by retinal dehydrogenases into retinoic acid (RA) in cells. RA regulates gene expression via activation of retinoic acid receptor (RAR) and retinoid X receptor (RXR). We have shown that retinoids synergize with insulin to induce Srebp‐1c expression in primary rat hepatocytes. Therefore, we hypothesize that RA production controls the regulation of hepatic gene expression.The expression of Cyp26a1 (an RA responsive gene) was examined using real‐time PCR and used as a marker for RA production from ROL and RAL in primary hepatocytes and hepatoma cells. Here, we show that retinol and retinal dose‐dependently induced Cyp26a1 expression via activation of RAR and RXR in those cells. The expression levels of Rdh2, Rdh10, Raldh1, and Raldh3 (major retinoid catabolic enzymes) were examined in hepatocytes from Zucker lean (ZL) and fatty (ZF) rats. Only Rdh2 and Raldh1 were expressed at comparable level as that of 36B4 gene (the invariable control gene) in hepatocytes and hepatoma cells. In addition, the hepatocytes from ZF rats had higher expression level of Raldh1 than that from ZL rats.We conclude that hepatocytes actively metabolize retinol into RA, which directly regulate gene expression. The elevated Raldh1 expression in ZF hepatocytes may contribute to the altered lipid metabolism in ZF liver.Sponsor: Guoxun Chen, 1215 W. Cumberland Ave. 229 Jessie Harris Building, Knoxville, TN 37996Grant Funding Source : AHA
SURVEY OF HUMAN MILK FATTY ACID LEVELS OF U.S. WOMEN WHO PROVIDE EXPRESSED MILK FOR FEEDING THEIR PRETERM INFANTS
Authors: Berseth Carol Lynn , Mitmesser Susan Hazels , Harris Cheryl , Hoffman Dennis R , Diersen-Schade Deborah 
Published: June 2021

BackgroundPreterm infants have reduced in utero accretion of docosahexaenoic acid (DHA) and arachidonic acid (ARA) due to early birth. Their postnatal DHA status is in part dependent upon the DHA content of their mother's milk, but DHA content of US human milk is among the lowest in the world, typically ≤0.2% of total fatty acids.ObjectiveTo characterize DHA, ARA, and eicosapentaenoic acid (EPA) levels in milk expressed by mothers of preterm infants.MethodsMothers of infants with a gestational age ≤30 3/7 weeks provided single milk samples during the first or second postnatal month. Fatty acids were determined by capillary column gas chromatography. Maternal consumption of fish and/or DHA supplements during the last 12 weeks of pregnancy was recorded.ResultsSixteen mothers consumed fish, 25 consumed a DHA supplement, 11 consumed both supplement and fish, and 76 did not consume either. DHA was higher among mothers consuming fish or supplement, and greatest for those consuming both (Table). Milk DHA trended higher than previously seen for U.S. mothers. There was little difference in ARA among the groups; EPA was highest among those using supplements and surprisingly, lowest for those consuming fish.ConclusionMilk levels of DHA are lowest among those mothers who did not consume fish or DHA supplements during pregnancy. Dietary counseling for mothers providing milk for their preterm infants may increase their infant's DHA intake.
Effect modifiers for the safety and efficacy of iron intervention in the context of malaria: A review of data for an individual patient based meta‐analysis
Authors: Namaste Sorrel , Ashour Fayrouz , Porter Alexandra , Raghavan Ramkripa , Pilch Susan , Raiten Daniel 
Published: June 2021

ObjectiveTo evaluate the safety and efficacy of iron interventions in regions with malaria, a review was undertaken to determine the extent of data that could be utilized in an individual patient data (IPD) meta‐analysis. IPDs are particularly useful in assessing the heterogeneity of treatment effects and thus lend themselves to examining the influence of risk modifiers.MethodsEligible randomized trials were identified using computerized and manual searches. Studies were stratified by iron status, age, malaria patterns, and iron mode. The number of studies and the upper/lower expected pooled sample size range was calculated.ResultsA total of 3,602 trials were screened, 523 underwent text review and 165 included. There were 106 supplementation and 50 fortification trials; mainly in meso (50%) and hyperendemic (29%) regions. Serum ferritin was the predominant iron biomarker (n=27, 12,122–17,671 >2yr; n=47, 17,891–34,305 >5yr; n=9, 3,026 pregnancy) and was rarely accompanied by CRP or AGP. Anthropometry was the most frequent health endpoint (52%), followed by morbidity (44%), and clinical malaria (12%).ConclusionThere are sufficient studies to warrant an IPD. However, the limitations in the number and nature of studies highlight the need for a more robust research agenda, including well designed protocols to support nutrition programs and policy.Support: Bill & Melinda Gates Foundation; NIH
The nicotinic subunit β4 plays a modulatory role on the antiaddictive action of varenicline
Authors: Dang Justin , Arias Hugo , Jackson Gary 
Published: June 2021

The role of β4‐containing nicotinic receptors (AChRs) in drug addiction and in the anti‐addictive effects of varenicline was studied. A cocaine‐induced locomotor sensitization model was developed to compare the anti‐addictive effect of varenicline between wild‐type (β4+/+) and mutant (β4−/−) mice, male and female. Mice were first habituated for 75 min, injected with saline (control) or cocaine (15 mg/kg), and then the locomotor activity was measured for 75 min. Mice were treated intermittently during days 1–5, 8, 11, 12, 14, 18, 19, 21, 28, 35, 42. Mice were pretreated with varenicline (1 mg/kg) before cocaine injection, or treated with varenicline alone. Two‐way ANOVA analyses indicate that varenicline decreases the cocaine activity in wild‐type and mutant males (p<0.05). The decreased activity produced by varenicline on wild‐type and mutant females was not statistically significant (p>0.36). Pretreated mutant males, but not mutant females, have lower activity compared to wild‐type mice (p<0.068). Varenicline alone had comparable results with saline. The results support the view that the anti‐addictive effect of varenicline is more pronounced in male than in female mice, and that the lack of the β4 subunit increases the anti‐cocaine effect of varenicline. In this regard, β4‐containing AChRs may play a modulatory role in cocaine addiction and could be a possible target for drug addiction treatment.Grant Funding Source: Science Foundation Arizona
Alpha1 and alpha2 adrenoceptors in the medial amygdaloid nucleus have different role on cardiovascular responses to acute restraint stress in rats
Authors: Fortaleza Eduardo Trindade , Scopinho América Augusto , Corrêa Fernando Morgan 
Published: June 2021

Introduction and GoalsMedial amygdaloid nucleus (MeA) is involved in the modulation of the cardiovascular responses during exposure by restraint stress (RS). We investigate the involvement of the alpha‐adrenoceptors into the MeA therein mediate cardiovascular responses to RS in rats.MethodsWe used Wistar rats. It was done implanting bilateral guide cannula into the MeA to microinjections of drugs or vehicle. The animals received a polyethylene catheter into the femoral artery for blood pressure (BP) recording.ResultsThe RS caused BP and heart rate (HR) increases in aCSF treated animals (n=8). RX821002 (alpha2‐ adrenoceptor antagonist) treatment significantly enhanced restraint‐evoked HR increase without significant effect on the BP response, when compared with control animals (ΔMAP: F1,66= 3,496, P= 0,0660, n=5; ΔHR: F1,66= 15,22, P= 0,0002, n=5; twoway ANOVA). In contrast, the treatment with WB4101 (alpha1‐adrenoceptor antagonist) significantly reduced restraint‐evoked HR increase without significant effect on the BP response, when compared with control animals (ΔMAP: F1,66= 0,8556, P= 0,3583, n=5, and ΔHR: F1,66= 3,558, P= 0,0637, n=5; two‐way ANOVA).ConclusionResults suggest that adrenoceptors either alpha(1) and alpha(2) have different roles into the MeA on the HR increase evoked by RS, enhance and reducing the cardiac responses.Financial Support: CNPq, CAPES.
Inhibition of calpain or caspase‐3 protects against immobilization‐induced muscle atrophy
Authors: Talbert Erin E , Smuder Ashley J , Min Kisuk , Kwon Oh-Sung , Powers Scott K. 
Published: June 2021

Increased proteolysis is crucial to disuse skeletal muscle atrophy. However, the roles that the proteases calpain and caspase‐3 play during inactivity‐induced muscle atrophy remain unclear. We hypothesized that administering either a calpain or caspase‐3 inhibitor would protect the soleus muscle against atrophy and mitochondrial dysfunction following 7 days of hindlimb immobilization (i.e. casting). Immobilization significantly (~13%) decreased the cross‐sectional area of soleus type I fibers. Importantly, independent inhibition of calpain or caspase‐3 prevented this atrophy. Casting decreased soleus mitochondrial coupling by ~52%. Inhibition of either calpain or caspase‐3 attenuated this casting‐induced mitochondrial dysfunction. Interestingly, inhibition of calpain prevented the casting‐induced activation of caspase‐3. Further, caspase‐3 inhibition prevented the immobilization‐induced activation of calpain. In conclusion, these results indicate that calpain and caspase‐3 play important roles during inactivity‐induced soleus muscle atrophy. Further, our data suggest that there is a regulatory cross‐talk signaling mechanism though which calpain and caspase‐3 regulate the activity of each other.Supported by NIH R01 HL087839 (SKP) and a UF Alumni Fellowship (EET).
Variation of global mRNA expression in biopsies from the same human muscle
Authors: Sundberg Carl Johan B , Lindholm Malene , Solnestam Beata Werne , Lundberg Joakim , Fischer Helene 
Published: June 2021

Human skeletal muscle biopsies obtained from the same muscle are commonly assumed to be very similar from a phenotypic and gene expression perspective, despite very few studies showing this. Therefore, our aim was to investigate differences in global gene expression pattern between and within legs of the same individual.Five sedentary subjects were included. 2 skeletal muscle samples from the vastus lateralis muscle were taken from each leg (i.e. 2 + 2 biopsies). The time between the first and last biopsy for each individual was 10 to 15 minutes. Isolated RNA was subjected to global mRNA sequencing by synthesis (RNAseq).In general, there was a very high degree of gene expression level similarity (>99 %) between biopsies within and between legs. Within the same leg, there were 7 genes with a significantly different expression for all subjects, e.g. STAT1, PRG4 (proteoglycan 4) and MYBPH (myosin binding protein H). Between legs, there were 18 differentially expressed genes. STAT1 and PRG4 were found here too, along with PDK4 and ABRA (actin‐binding Rho activating protein). Within the same leg, the number of genes with a significant differential expression varied from 119 to 4 genes. The same two individuals also had the largest and smallest variation comparing two legs.In conclusion, biopsies taken from the same individual have highly similar gene expression patterns. However, some individuals display larger variation.
Fructose‐rich Diet From Weaning To Adulthood: Effects On Sympathetic Activity In Rats
Authors: Andrade Romario Pacheco , Araujo Iara Cristina , Lopes Ingrid Jarzinski , Lopes Bruna Kogici , Santos Fernando , Irigoyen Maria Claudia , Fiorino Patricia , Farah Vera 
Published: June 2021

Administration of a diet rich in fructose initiates a series of metabolic events resulting in hypertriglyceridemia, hypertension and glucose intolerance. The purpose of this study was to evaluate the cardiovascular and autonomic modulation induced by fructose intake during 8 weeks. Weaned (21 days old) male Wistar rats (50–60g) were divided in 2 groups and they were followed for 8 weeks: Control (CG) and Fructose (FG, 10% in drinking water). Arterial pressure (AP) and heart rate (HR) were directly recorded using a data acquisition system (Windaq, 2 KHz) in conscious and awake rats. Cardiac autonomic modulation was evaluated using spectral analysis of HR variability and after pharmacological blockade (Atenolol, 8mg/Kg and Atropine, 4mg/Kg). FG showed an increase of mean AP (120±3.1 mmHg) when compared to CG (98±1.6 mmHg). No changes in heart rate were observed, although autonomic balance increased in FG (0.12±0.02) compared to CG (0.04±0.01). Sympathetic tonus was increased in FG (86±7.2 bpm) when compared with CG (49±3.6 bpm) with no differences in vagal tonus. However, intrinsic HR was significantly lower in FG (375±7.2 bpm) when compared with CG (405±8.2 bpm). In conclusion, these data suggest that metabolic changes induced by frutose‐rich diet during life spam in rats are accompanied by hypertension associated with sympathetic overactivity.Supported by: FAPESP(2009/52556‐7) and PIBIC/Mackpesquisa
Intravenous delivery of AAV9 encoding urocortin 2 increases cardiac function in normal mice
Authors: Lai N. Chin , Hammond H. Kirk , Tang Tong , Guo Tracy , Tang Rouying , Parikh Jay , Gao Meihua 
Published: June 2021

Gene transfer for the treatment of cardiovascular diseases is conceptually attractive, but difficulty in obtaining high yield expression in the heart in a manner that can be easily and safely applied has been an impediment to progress. In this study, we tested the efficacy of an adeno‐associated virus 9 (AAV9) vector encoding urocortin 2 (Ucn2), which is a vasoactive peptide in the corticotropin‐releasing factor family that has beneficial effects in animals and patients with heart failure. AAV9.Ucn2 (5×1011 genome copies) was delivered by intravenous injection. Four weeks after gene transfer, AAV9 vector DNA (qPCR) was increased by 115,854‐fold and Ucn2 mRNA by 10,523‐fold in liver vs control. Ucn2 DNA and mRNA were increased 15‐ and 34‐fold, respectively, in the left ventricle (LV). Also seen were increases in: plasma Ucn2, LV +dP/dt, LV −dP/dt, and LV developed pressure (Table).ConclusionIntravenous delivery of AAV9.Ucn2 provides sustained increases in serum Ucn2 and LV contractile function, indicating a potential role for paracrine‐based gene transfer for the treatment of heart failure.

Control
AAV9.Ucn2
Fold Δ*

Liver AAV9 DNA (copies/ng)
0.26±0.05
3×105±3906
115,854

Liver Ucn2 mRNA (relative copies)
166±17
17×105±15×104
10,523

LV AAV9 DNA (copies/ng)
18±6
301±45
15

LV Ucn2 mRNA (relative copies)
34±9
958±299
34

Plasma Ucn2 (ng/ml)
2.6±0.1
6.0 ±0.3
2.3

LV +dP/dt (mmHg/s)
4,103±335
6,115±334
1.5

LV −dP/dt (mmHg/s)
3,744±335
5,631±365
1.5

LV Pressure (mmHg)
70±3
88±3
1.3

Heart Rate (beats/min)
439±9
420±14
0.9

Control (n=14); AAV9.Ucn2 (n=9); except DNA: (n=9, ea group) & plasma Unc2 (n=4 ea group);
p<0.05 to <0.001, except for heart rate