bluuebunny/crossref_metadata_2025_split huggingface dataset:
30.5±1.5°C Is the Optimal Hypothermia to Protect Hypoxic/Ischemic Heart
Authors: Ning Xue-Han , Sekhar L N , Kupchik N L , Corson M A , Werrbach J H , Tylee T S , Soh YK , Wang E , Villet O M , Ge M , Fan LP , Yao L , Olson A K , Zhu C , Anderson D L , Chen SH , Portman M A 
Published: June 2021

ObjectiveTo determine an optimal temperature in hypothermia protection for myocardium.MethodsIsolated rabbit hearts infused with Langendorff model; Pig hearts in vivo infused with cardiopulmonary bypass; Patient treated with the cooling protocol at Harborview Med Ctr. The animal hearts were treated with a giving range of temperatures prior to and during cardioplegic ischemia. DP, dP/dtmax, cardiac power (CP), etc were monitored.ResultsFollowing reperfusion the off‐pump function of pig hearts returned to baseline (BL) level in the 29–30°C treatment group. In the 34–35°C group the recovery was significantly lower (P<0.05; DP=44.0± 9.4%, dP/dtmax =28.0±5.9%, CP=21.6±10.3% of BL). The 32.5°C treatment showed some recovery (P<0.05). The isolated rabbit hearts showed similar results to the pig hearts in vivo. One of the authors (XH Ning) suffered from a sudden cardiac arrest for more than 6 minutes in 2009. He was treated with Hypothermic Rescue (32°C central catheter) and had a remarkable recovery.Conclusion30.5±1.5°C is an optimal temperature in hypothermia protection. (Partial support from NIH HL‐60666 and CHRMC HR‐5836).
Rate of heat storage does not influence exercise intensity at a fixed rating of perceived exertion
Authors: Cramer Matthew N. , Molgat-Seon Yannick , Carlsen Anthony N. , Jay Ollie 
Published: June 2021

This study investigated whether different rates of decline in self‐selected work rate (W) were mediated by early differences in heat storage. Five males cycled at a W to maintain a perceived exertion of 16 (Borg scale) at 35°C and 25°C. Heat production (Hprod) was estimated via indirect calorimetry. Esophageal (Tes) and skin (Tsk) temperatures, as well as local sweat rates on the lower back (LSRback) and thigh (LSRthigh), were measured throughout. The level of muscle activation in vastus lateralis (VL) was assessed via integrated surface electromyography (iEMG). While dry heat loss was lower at 35°C (P<0.01), sweating responses were elevated, indicated by greater LSRthigh at 2 min (P<0.05), a trend toward greater LSRback (P=0.07), and earlier onsets at both sites (P=0.02). Similar Hprod and rates of change in Tes were found in both conditions (P>0.05), yet at 35°C, exercise time was shorter (35°C: 22.6±4.9 min; 25°C: 32.1±10.4 min; P=0.03), and W (% of initial W) declined more rapidly by 15 min (35°C: 89.2±8.2%; 25°C: 82.2±8.0%; P<0.01). Mean Tsk was lower throughout exercise at 25°C (P<0.01). Similar changes in VL iEMG activity were found at 25°C and 35°C (P=0.28). In conclusion, reductions in W occur without early differences in heat storage between air temperatures, implicating factors other than the rate of heat storage, such as Tsk, in the regulation of exercise intensity.Supported by a NSERC Discovery Grant (O. Jay)
Thermoregulatory responses are decreased by carbohydrate ingestion through hyperosmotic suppression while the effects were attenuated by insulin in passively heated men
Authors: Suzuki Akina , Okazaki Kazunobu , Imai Daiki , Takeda Ryosuke , Naghavi Nooshin , Matsumura Shinya , Miyagawa Toshiaki 
Published: June 2021

Plasma hyperosmolality with thermal sweating or hypertonic saline infusion increases esophageal temperature (Tes) threshold for sweating and cutaneous vasodilation. We assessed whether plasma hyperosmolality with carbohydrate (CHO) ingestion increased Tes threshold. Furthermore, we assessed the effects of insulin secreted with CHO ingestion which was known to modify the sensitivity of thermo‐sensitive neurons on Tes threshold.MethodsSeven healthy young men performed three trials in a sitting position in an artificial climate chamber (28°C of Ta, 40% of RH). After 10 min baseline, subjects drank water (CNT; water 300 ml), glucose (GLU; water 300 ml + glucose 75 g), or fructose solution (FRU; water 300 ml + fructose 75 g). Twenty min later, they were heated passively (lower legs immersion in 42°C water) for 60 min. Plasma insulin concentration ([Ins]p), plasma osmolality (Posm), percent change in plasma volume (%ΔPV), Tes, sweat rate and cutaneous vascular conductance at forearm and chest were measured.ResultsPosm in GLU and FRU were equally higher than CNT, though there was no difference in %ΔPV among trials. [Ins]p was higher in GLU than CNT and FRU. Tes threshold for cutaneous vasodilation was higher in FRU than CNT and GLU, while similar in CNT and GLU.ConclusionThermoregulatory responses are decreased after CHO ingestion via hyperosmotic suppression, while the effects were attenuated by insulin.
A molecular mechanism for frequency dependent skeletal muscle fiber plasticity
Authors: Jaimovich Enrique , Jorquera Gonzalo , Buvinic Sonja , Casas Mariana 
Published: June 2021

Frequency of stimulation determines slow or fast fiber type gene expression in muscle.Fibers isolated from mice flexor digitorium brevis were stimulated at 20 and 90 Hz (270, 0. 3 ms pulses). We analyzed gene expression (qPCR), ATP release (luciferase), IP3 production (ELISA) and calcium signals in Fluo‐4 loaded fibers.At 20 Hz there was an important, biphasic release of ATP from myofibers which was inhibited by blockers of pannexin channels and dihydropyridine receptors. This stimulation pattern induced a sequential biphasic IP3 increase; mRNA levels for slow troponin I (TnIs) increased and fast troponin I (TnIf) decreased. These changes were inhibited by apyrase, carbenoxolone and IP3R blockers (xestospongin B). We also saw an increase of citrate synthase and a decrease of enolase mRNAs, not inhibited by xestospongin B. At 90 Hz there was no ATP release and IP3 production was much reduced. In these conditions there was an IP3R‐independent increase in TnIf mRNA levels and a decrease in TnIs.Upon potassium depolarization, IP3‐dependent calcium signals at membrane potential values more negative than those described for calcium release from RyR, associate to an increase in mRNA of the slow isoform of TroponinI.Our data supports a mechanism involving frequency‐dependent ATP release and activation of P2Y receptors to induce the slow fiber phenotype in skeletal muscle.FONDECYT 11108467, FONDAP 15010006
Systemic administration of Interleukin‐1beta enhances thermal prolongation of the laryngeal chemoreflex in decerebrate piglets—implications for Sudden Infant Death Syndrome
Authors: Xia Luxi , Bartlett Donald , Leiter J. C. 
Published: June 2021

The laryngeal chemoreflex (LCR) causes apnea and may initiate the process leading to the Sudden Infant Death Syndrome (SIDS). Recent upper respiratory tract infection (URI) and thermal stress are risk factors for SIDS, and elevating body temperature in decerebrate piglets prolongs the duration of LCR apnea. We tested the hypothesis that administering interleukin‐1beta (IL‐1b), a cytokine that is elevated by URIs and in turn elevates body temperature, would enhance thermal prolongation of the LCR. Decerebrate piglets (P4 to P13) were tracheostomized, paralyzed and ventilated, and 0.1 ml of water was introduced into the larynx to elicit the LCR. We recorded the duration of phrenic apnea and respiratory disruption associated with the LCR at normal body temperature and when body temperature was elevated by 2 degrees C. Pretreatment by intraperitoneal (IP) administration of IL‐1b (3 microgm/Kg) enhanced thermal prolongation of the LCR compared to control animals treated simultaneously with 10 mg/Kg IP indomethacin and IL‐1b. We conclude that IL‐1b enhances thermal prolongation of the LCR through a mechanism that requires synthesis of additional inflammatory mediators.Support: grants 36379 & 42707 from the NICHD
Profile of nitric oxide synthases (NOS), antioxidants, and pro‐oxidant enzymes and oxidative stress (OS) markers in the kidney cortex (KC) during rat pregnancy
Authors: Cunningham Mark W. , Sasser Jennifer , Baylis Chris 
Published: June 2021

Normal pregnancy (P) involves increased renal sodium reabsorption, and the resultant increase in renal metabolism could cause increased OS, which could decrease renal nitric oxide (NO) bioavailability leading to suboptimal gestational renal vasodilation. Here, we examined enzymes and markers of NO and OS in early (E), mid‐(M) and late (L) pregnancy (P) (days 3, 12, 20) and post‐partum (PP) rats compared to virgins (V). Protein abundance of endothelial (e) NOS was unchanged and neuronal (n) NOSα fell at LP. In contrast, nNOSβ was elevated at MP, LP, and PP. There were no changes in cytosolic (CuZn) superoxide dismutase (SOD), while mitochondrial (Mn) SOD decreased at EP and extracellular (EC) SOD decreased at MP and LP. Despite reductions in SOD abundance, total antioxidant capacity (TAC) was elevated in EP, MP, and PP. Nitrotyrosine (NT) and the NADPH oxidase subunit p22phox abundance decreased in EP, and NT was low during LP and PP. No changes were seen in KC hydrogen peroxide (H2O2) levels.ConclusionThe gestational renal vasodilation is known to be NO‐dependent and this study supports a role for increased KC nNOSβ during normal P. Despite increased renal metabolism during P there is no evidence of increased OS since NT levels fall by LP and KC H2O2 levels are unchanged. This may in part be related to an early fall in the p22phox subunit of NADPH oxidase and most likely to the significant increase in KC TAC, which occurs despite reductions in total SOD abundance.

nNOSα
nNOSβ
Nitrotyrosine
p22phox
ecSOD
mnSOD
TAC (mM Trolox/mg)

V
100±15
100±9
100±4
100±9
100±7
100±14
131±9

EP
97±19
99±2
84±6*
66±8*
80±15
44±6*
183±12*

MP
85±14
149±9*
98±9
97±13
68±7*
81±26
191±12*

LP
54±13*
247±43*†
48±4*
93±4
57±9*
79±24
153±11

PP
116±22
138±7*
69±6*
84±3
81±6
113±41
174±10*

p<0.05 vs. V and
p< 0.05 vs. EP.
Regulation of ABC transporters by hypoxia in HK‐2 human proximal tubule epithelial cells
Authors: Chung Git , Brown Colin Douglas 
Published: June 2021

Hypoxia‐inducible factor‐1 (HIF‐1), a transcription factor that is stabilised during hypoxia, may influence the expression of ABC transporters in the kidney. The aim of this study was to use a proximal tubule epithelial cell line (HK‐2) as a kidney model to determine changes in ABC transporters at an mRNA and functional level when HK‐2 cells were exposed to a hypoxia‐mimetic compound, desferrioxamine (DFO).Western Blots were used to determine changes in protein levels of HIF‐1 between DFO treated and untreated HK‐2 cells. A qPCR approach was used to determine mRNA expression of ABC transporters in DFO treated and untreated HK‐2 cells. The functional expression of ABC transporters in HK‐2 cells was determined using Hoechst 33342 and CMFDA dye efflux assays.Western blots of HIF‐1 protein showed significantly increased expression in HK‐2 cells treated with DFO compared with untreated cells. The mRNA expression profiles of MDR1, MRP1 and MRP3 showed an up‐regulation fold change of 1.63, 2.04 and 1.58 respectively in DFO treated HK‐2 cells compared to untreated cells. The magnitudes of the fluorescence of retained Hoechst 33342 and CMFDA dyes were significantly lower in DFO treated HK‐2 cells compared to untreated cells (P<0.01).These results provide evidence to support the hypothesis that HIF‐1, stabilised with DFO, influences the regulation of ABC transporters in the kidney.
Early cardiovascular alterations induced by zinc deficiency during fetal life and lactation
Authors: Abregu Facundo Mendes Garrido , Sanchez Rodrigo , Veiras Luciana Cecilia , Costa Angeles , Tomat Analia Lorena , Arranz Cristina 
Published: June 2021

The aim was to evaluate early cardiovascular alterations in rats exposed to moderate zinc deficiency during fetal life and lactation, and compare the effects in males (m) and females (f).Wistar rats received low (L,8 ppm) or control (C,30 ppm) zinc diet from pregnancy until offspring weaning (day 21). At 21 days, we evaluate mayor (MM) and minor (mM) myocyte diameter (μm); aortic intima (Ai), media (Am) and perivascular collagen (Ac) thickness (μm); cardiac (C) and aortic (A) nitric oxide synthase (NOS) activity (pmol Cit/g.tissue.min); cardiac thiobarbituric acid substances (Tbars, nmol/mg protein), glutathione (G, mg/g protein), glutathione peroxidase (GPX, μmol/min/mg protein), catalase (CAT, pmol/mg protein) and superoxide dismutase (SOD, U/mg protein) activity in Lm, Lf, Cm and Cf rats.

Cm
Lm
Cf
Lf

MM
14±1
18±1*
15±1
15±1

mM
8,6±0,5
10,7±0,3*
9,4±0,5
10,1±0,3

Ai
23,3±0,2
18,3±0,1*
23,9±0,2
18,9±0,2†

Am
280±2
298±2
287±3
280±2

Ac
16±1
24±1*
12±1
23±2†

C NOS
249±5
205±5*
247±3
201±3†

A NOS
225±5
172±5*
211±6
179±6†

G
9±1
3±1*
10±1
6±1†

GPX
81±8
65±6*
85±6
68±8†

Tbars
0.41±0.05
0.32±0.02
0.22±0.04*
0.18±0.02

No differences were observed in cardiac SOD and CAT activity p<0.01:*vs Cm;†vs Cf; N=6/group

These early cardiovascular alterations may participate in the programming of adult diseasesSupported by University of Buenos Aires, CONICET, ANCyT, Argentina
Chronic estrogen and 5‐HT1A agonist treatment reduce sodium appetite in ovariectomized rats
Authors: Melo Roberto Laureano , Fonseca Fabricia Viana , Araujo Iracema Gomes , Silva-Almeida Claudio , Marcacini Victor Araujo , Mecawi Andre Souza , Reis Luis Carlos 
Published: June 2021

We have shown that ovarariectomized (OVX) rats exhibited higher salt intake compared to estrogen‐replaced rats (OVX+E2) particularly in models of induction of sodium appetite dependent on angiotensin II and low sodium plasma levels. This result was ascribed to enhanced AT1 receptors activity. In male rats we reported that repeated 5‐HT1A agonist administration reduced sodium appetite response related to somatodendritic 5‐HT1A autoreceptor desensitization. Therefore, we investigate the effect of systemic acute and chronic 8‐OH‐DPAT administration on the sodium appetite in normally hydrated or sodium‐depleted Wistar rats (furosemide, 20mg/kg, sc, 24h before experiment) in OVX+oil and OVX estrogen replaced (OVX+E2, estradiol cypionate, 10μg/animal) rats. Acute 8‐OH‐DPAT (250μg/kg, ip, during 7 days) induced an increase of 0.3M NaCl intake. OVX+E2 rats were not responsive to 5‐HT1A agonist in basal condition. Chronic administration of 8‐OH‐DPAT reduced the saline intake compared to OVX+vehicle, control group (2.3±0.17ml/100g vs 4.2±0.2ml/100g, at 120 min after fluids presentation) in sodium‐depleted rats. E2 replacement strengthened the antinatriorexigenic response of OVX+8‐OH‐DPAT treated rats (1.7±0.1ml/100g vs 4.2ml/100g, at 120 min after fluids presentation). Results suggest that chronic administration of 5‐HT1A agonist associated with E2 replacement therapy differentially trigger mechanisms for neural signaling to sodium satiety, possibly through recruitment of serotonergic pathways in the dorsal raphe nucleus.Support: FAPERJ & CNPq
Expression of intestinal mucins may be affected by the dietary protein source
Authors: Onyango Edward M , Habiyambere Bupe M 
Published: June 2021

Mucin glycoproteins cover epithelial surfaces of ducts, including the digestive tract, in the body. The study investigated the effect of dietary protein on the expression of mucins in intestinal epithelia of mice. Male weanling mice were randomized into 4 groups of 8 mice each. The source of protein (plant or animal origin) and the level of each protein (10% or 20% crude protein) were arranged in a factorial manner to produce 4 diets which were randomly assigned to the four groups of mice. Mice were provided the diets for 14 days and euthanized on the fifteenth day. Mucosa and histological sections were prepared from the jejunum and colon of the intestines. Total RNA was prepared from the mucosa using Trizol®. cDNA was prepared using random hexamers and specific primers were used for real time PCR amplification of the message for Muc2 and Muc3. Expression of Muc2 in the jejunum was higher (1.45 fold) in mice fed plant protein compared to those fed animal protein. There was no difference in expression of Muc2 in the colon with the different protein sources. Expression of Muc2 did not vary with the level of dietary protein in both the jejunum and colon. Expression of Muc3 in the jejunum and colon did not vary with the level or source of dietary protein. It is concluded that expression of intestinal mucins may be affected by the source of protein in the diet.Research was supported by a RDC grant from East Tennessee State University.
AQP9 and UT‐A facilitate hepatocyte basolateral membrane urea permeability in mouse
Authors: Jelen Sabina Katarzyna , Gena Patrizia , Lebeck Janne , Prætorius Jeppe , Fenton Robert , Frøkiaer Jørgen , Nielsen Søren , Calamita Giuseppe , Rützler Michael 
Published: June 2021

In mammals, nitrogen from protein degradation is disposed as urea. Several studies have investigated expression of urea transporters in hepatocytes, where urea is produced. Nevertheless, the role of protein facilitated urea transport in liver remains unknown. In the presented study we determine urea permeability in isolated basolateral hepatocyte membranes by stopped flow light scattering measurements. The urea channel inhibitors phloretin and dimethylurea reduced the urea permeability by 70% and 40%, respectively. In basolateral membranes isolated from AQP9 (AQP9−/−) and UT‐A (UT‐A−/−) single knockout, and AQP9−/−:UTA−/− double knockout mice, urea permeability (Purea) was decreased by 30%, 40%, and 76%, respectively, compared to wild type mice. In addition, we investigated the physiological role of AQP9 in mouse hepatocyte function following exposure to high oral glutamine doses or high protein diet. These conditions did not affect the concentrations of urea or ammonia in AQP9−/− mouse tissues and plasma, respectively. Similarly, hepatocyte urea synthesis of UT‐A−/− mice appeared normal. We currently conclude that both, AQP9 and a UT‐A gene product, constitute primary but redundant urea channels in hepatocytes.This study was supported by the Lundbeck Foundation.
Depletion of platelet serotonin with a selective serotonin reuptake inhibitor does not improve survival in a mouse model of thromboembolism
Authors: Liu Henry F , Campbell Christina , Hegde Sharath , McNamara Alexander 
Published: June 2021

Platelet serotonin (5‐hydroxytryptamine, 5‐HT) is released upon platelet activation and serves as a proaggregatory factor. Clinical and preclinical evidence suggest that selective serotonin reuptake inhibitors (SSRIs) deplete platelet 5‐HT and reduce platelet aggregation. The goal of this study was to determine if inhibition of the 5‐HT transporter (SERT) reduces platelet 5‐HT and improves survival in a mouse thromboembolism (MTE) model.C57/BL6 mice were treated with vehicle (veh), fluoxetine (FX, 30 mg/kg, PO x 1 & 7d), paroxetine (PX, 30 mg/kg, PO x 7d), escitalopram (EC, 2 mg/kg, SC x 7d) or norfluoxetine (NFX, 5 mg/kg, IV x 1d). Mice were anesthetized and the right jugular vein cannulated. Thromboembolisms were induced with an infusion of collagen 200 μg/epinephrine 10 μg (Col/EPI), survival was monitored over the next 15 min and whole blood 5‐HT was measured.Col/EPI produced mortality in vehicle‐treated mice (~66 %). FX (7d) and NFX significantly enhanced survival (69 & 70 %), whereas FX (1d), PX and ES offered no survival benefit (≤ veh). SSRI treatment reduced whole blood 5‐HT by 75 – 99%; however, the decreased concentration of 5‐HT did not correlate with improved survival. Thus, depletion of platelet 5‐HT through SERT inhibition does not prevent Col/EPI induced‐thromboembolism in the MTE model. The efficacy of FX and NFX in this model appears to be independent of their SSRI activity.Source of Funding: None
Structure‐based design of inhibitory peptide for End Binding proteins
Authors: Saqib Uzma , Geyer Melissa , Minshall Richard , Malik Asrar , Komarova Yulia 
Published: June 2021

The Microtubule (MT) cytoskeleton plays an important role in regulating paracellular permeability of the endothelium in the context of inflammation; however, the molecular mechanism involved in MT‐dependent increase in permeability is not yet fully understood. We have shown that End Binding (EB) protein 3, which binds to and regulates MT dynamics in the endothelium, interacts with ER associated inositol 1,4,5‐trisphosphate (IP3) receptor type 3 and facilitates thrombin‐induced release of calcium from ER stores. Based on the crystal structure of the EB interacting domain and using the computational alanine scan approach, we designed a 7‐amino acid synthetic inhibitory peptide that mimics interaction between EB3 and IP3R3. We have shown that treatment of human pulmonary artery endothelial cells with this peptide blocked the interaction between IP3R3 and EB3 and negatively regulated thrombin‐ and histamine‐induced increase in intracellular calcium. Consistent with this finding, EB inhibitory peptide attenuated histamine‐induced activation of endothelial nitric oxide synthase (eNOS), as determined by NO production but had no effect on basal level of NO. In an animal model of inflammation, EB peptide prevented histamine‐induces vasodilation. Our data suggests that EB proteins can be used as a potential target for development of novel therapies to prevent leaky vessel syndrome during inflammation.Funding source: RO1 HL103922 to Yulia Komarova
TRIACSIN C, A FATTY ACYL COA SYNTHETASE (FACS) INHIBITOR, IMPROVES CARDIAC PERFORMANCE FOLLOWING GLOBAL ISCHEMIA
Authors: Weis Margaret Teresa , Tolson Jasmine , Chen Qian , Young Lindon 
Published: June 2021

Extensive evidence shows that eNOS is protective in ischemia/reperfusion (I/R) injury. We have shown that triacsin C, a (FACS) inhibitor, increases eNOS activity in the post‐ischemic rat hind limb, suggesting that triacsin C might be useful in treatment of cardiac I/R. Isolated rat hearts, perfused at a constant pressure by the method of Langendorf, were subjected to a 30 minute period of global ischemia, followed by 45 minutes of reperfusion in the presence or absence of 5μM triacsin C.At 45 minutes of reperfusion, LVDP and dP/dt in treated hearts were significantly better than in vehicle controls. Coronary flow and heart rate were not changed by treatment. The infarct area, visualized with 1% 2,3,5‐triphenylterazolium, was significantly smaller in triacsin C treated hearts. The results support the hypothesis, and suggest that FACS inhibitors may represent a new category of drugs for I/R.
Effect of Vitamin A Fortified Milk Intake on Total Body Vitamin A Stores in Mexican Preschoolers
Authors: Lopez-Teros Veronica , Quihui-Cota Luis , Mendez-Estrada Rosa Olivia , Grijalva-Haro Maria Isabel , Valencia Mauro , Esparza-Romero Julian , Rascon-Duran Lucila , Tortoledo-Ortiz Orlando , Pacheco-Moreno Bertha , Green Michael H. , Astiazaran-Garcia Humberto 
Published: June 2021

In Mexico, vitamin A deficiency (VAD) is a public health problem for preschool children. Vitamin A (VA) fortified milk (Liconsa) is distributed nationally to fight VAD, nevertheless its effect has yet not been assessed. The aim of this study was to assess the effect of daily intake of VA fortified milk on the total body VA (TBVA) stores of preschoolers.We conducted a randomized controlled clinical trial in Mexico to assess the effect of daily intake of 250 mL of VA fortified Liconsa milk for 12 weeks on VA status of 24 VA‐deficient preschoolers. Subjects were randomly allocated to treatment (n=11) or control (n=13) groups respectively. TBVA stores were calculated using the Olson equation at baseline and three months after daily intake of VA fortified “Liconsa” milk.TBVA stores of the treatment group had a significant increase compared to their baseline value (P<0.05) and stores had a significant difference of 0.75 mmol in treatment vs control groups (P=0.01). Serum retinol concentration was significantly reduced compared to its baseline value in the control group (P<0.05) and serum retinol was 0.291μmol/L greater in the treatment vs control group (P=0.01).Daily intake of vitamin A fortified “Liconsa” milk during 12 weeks, significantly increased TBVA stores and serum retinol levels of Mexican preschoolers.Study supported by the IAEA. LTV received a fellowship from CONACyT.Grant Funding Source : IAEA‐CONACyT