bluuebunny/crossref_metadata_2025_split huggingface dataset:
Branched‐Chain‐Aminoacids content in food and nutritional supplements
Authors: Pereira Paula Cardoso , Vicente Ana Filipa , Cabrita António Silvério 
Published: June 2021

Exercising individuals need more protein that sedentary people and should make their efforts to choose high quality protein sources. An attempt should be made to achieve protein needs from whole foods but nutritional supplements, mainly protein powders, can be useful in crucial timings like after physical effort when recovery is first priority. Branched chain aminoacids (BCAA's) are one of the most important criteria to choose a protein source, because they are an important fuel to muscle cells and because of their role in delaying central fatigue.In the present study we compared different protein sources and evaluated protein and BCAA's content. The results showed that whey protein powders have more protein in one 30g serving that the same amount of beef, chicken and pork lean cuts, tuna, egg whites and whole eggs. And these nutritional supplements are richer in BCAA's and stand close to 2:1:1 ratio of leucine, isoleucine and valine.A balanced diet can be achieved if the athlete uses whole foods most of the time, but when in a crucial moment to recover or improve performance, protein powders can be more efficient and more convenient that normal foods that have to be cooked and can have other nutrients that delay protein and aminoacids absorption and utilization by muscle cells.
Metabolic Syndrome, Type 2 Diabetes and Controls: Comparisons and Contrast
Authors: Hubbard Richard W. , Westengard James , Guthrie George 
Published: June 2021

These metabolic comparisons were from a highly health motivated, self‐selected cohort (ages16–88) composed of four definable categories: Metabolic Syndrome (MS) (n=67), Type 1 (n=16) and Type 2 (n=155) Diabetics and Controls (n=123). The biological assays were performed at Quest‐Nichols Diagnostics. Statistical analysis was performed by one‐way ANOVA, with Bonferroni adjusted probabilities for multiple comparisons (Systat ver.10; SPSS Inc., 2000).The MS subjects show significantly higher Chol/HDL ratio (p= 0.028) and diastolic blood pressure (0.0004) while the Type 2 diabetics had significantly higher Hbg A1C (p< 0.00005) and higher fasting blood sugar (p<0.00005) values. The MS group and the Type 2 diabetics move together with respect to the Control group for Vitamin D deficiency (p = 0.00014), and with increased triglycerides (p<0.00005), and decreased HDL (p<0.00005), while there are also significantly increased BMI (p<0.00005), CRP (p=0.04326) and systolic BP (p=0.0003) values compared to the control group. New findings from the report by Reis, JP et al, (Diabetes Care 30 (21007) 1549) on hyperparathyroidism in MS, where this does not appear to be the case in Type 2 diabetics (Taylor WH. Khakeeli Dia Met Res Rev 17(3) (2001) 175. Additional studies, relative to weight control, vitamin D deficiency and normalizing parathyroid function in MS will be necessary to clarify this important issue.
Diallyl sulphide protects against N‐nitrosodiethylamine induced liver tumerogenesis
Authors: Nassar Noha , Ibrahim Safinaz 
Published: June 2021

Diallyl sulfide (DAS), a major constituent of garlic, has been documented as a potent inhibitor of tumerogenesis in various animal models. This study investigated the protective effect of DAS against N‐nitrosodiethylamine (NDEA) induced liver tumerogenesis. To this end, two groups of male Sprague Dawley rats (n= 12; 170–200 g each group) received either NDEA (10mg/kg/day for 8 weeks followed by 20 mg/kg/day for the next 6 weeks) to induce liver cancer or NDEA + DAS (200mg/kg/day) for all 14 weeks. Liver lactate/pyruvate ratio, lactate dehydrogenase and glucose‐6 phosphate dehydrogenase activities were measured (energy metabolism indices). Liver malondialdehyde, cytochrome oxidase activities (membrane disintegration biomarkers), DNA level and glutathione S‐transferase activity (DNA fragmentation indices) were also measured. Serum alkaline phosphatase and gama‐glutamyl transferase activities were investigated (liver function). Results showed that administration of NDEA significantly disturbed liver functions as well as most of the measured parameters. Treatment with DAS protected most of the measured liver parameters against the drastic damaging effects caused by NDEA. In summary, we provide evidence that DAS exerts a protective role on liver functions and tissue integrity in face of enhanced tumerogenesis caused by NDEA.This research is supported by Cairo University, Egypt
Exposure to a polluted urban environment and to chronic low doses of lipopolysaccharides produces neuroinflammation in mice, and is ameliorated by dark chocolate
Authors: Villarreal‐Calderon Rafael , Osnaya Norma , Garcia Raquel , Stone Ida , Calderon‐Garciduenas Lilian , Reed William 
Published: June 2021

Background: Air pollution is a serious environmental problem. Mexico City (MC) children exhibit upregulation of COX2, and IL1beta in the olfactory bulb, frontal cortex, SNC and vagus nervesObjectives: To test the hypothesis in Balb‐c mice that exposure to a polluted atmosphere and to low doses of LPS IP results in neuroinflammation, and that inflammation could be ameliorated by dark chocolateMethods: Balb‐c mice age 21 d: A. clean environment, no Rx, B. outdoor/indoor environment in SW or NWMC, C. SWMC mice Rx with dark chocolate 2g/9.5 mg polyphenols/3 times per week, D. lyophilized E coli 0111:B4, 10 muL 750 or 2250 EU/mL, IP/2 /week clean environment. RT‐PCR: COX2 and IL1betaResults: At 4 m the LPS 6x group had higher frontal levels of COX2 v the control (0.008) and there were significant differences in IL1beta between NW and SW mice in olfactory bulb and frontal (0.006) and level X (0.0001). The OB in the SWMC chocolate group had significantly lower levels of COX‐2 and IL1beta (0.03) compared to the untreated group. At 8m chocolate reduced COX2 in SW mice OB and frontal regions (0.01, 0.03), there was a significant X upregulation of COX2 in NW v SW mice(0.001), and of IL1beta and COX2 in LPS 2x mice (0.01,0.05).Conclusions: Neuroinflammation in target areas for Alzheimer and Parkinson is present in mice exposed to a polluted urban atmosphere, and in LPS IP exposed animals. Dark chocolate ameliorates neuroinflammation
Is 3D MR molecular imaging of neovasculature prognostic of tumor response to antiangiogenic therapy?
Authors: Caruthers Shelton D , Schmieder Anne , Winter Patrick , Williams Todd A , Allen John S , Hu Grace , Zhang Huiying , Wickline Samuel , Lanza Gregory 
Published: June 2021

αvβ3—targeted fumagillin nanoparticles suppress the neovasculature and inhibit tumor growth in Vx2 tumors. The objective of this study was to use MR molecular imaging and 3D neovascular mapping tools to quantify antiangiogenic and tumor growth responses to integrin‐targeted fumagillin nanoparticles in a xenograft tumor model.Methods:Nude mice implanted with MDA435 cells received ανβ3‐targeted fumagillin nanoparticles, α5β1‐targeted fumagillin nanoparticles, or saline on days 7, 11, 15, and 19 post implantation. On day 22, tumor volume and neovascularity were assessed using integrin‐targeted MR nanoparticles.Results:Neovascularity was sparser in the xenograft model than observed in Vx2 rabbits. α5β1–fumagillin‐nanoparticles decreased (p<0.05) angiogenesis relative to control (1.3±0.3%) to an almost negligible level (0.5±0.3 %) while αvβ3–fumagillin‐nanoparticles did not decrease (p>0.05) angiogenesis (1.0±0.3%, Fig). Neither treatment regimen affected tumor volume.Conclusion:Tumors expressing low levels of neovascularity have poor tumor growth response to antiangiogenic treatment. Nascent cancers responsive to antiangiogenic therapy may be differentiated with noninvasive high‐resolution MR molecular imaging, which may be clinically relevant in establishing personalized therapy regimens. Support NIH/NCI CA 119342
Observational studies of Dopamine D2‐family agonists in squirrel monkeys
Authors: Desai Rajeev I , Connolly Jennifer , Bergman Jack 
Published: June 2021

Dopamine D2‐family (D2) agonists and antagonists produce dose‐related increases in, respectively, scratching and catalepsy‐associated behavior (CAB) in squirrel monkeys.The effects of D2 ligands on observable behavior were further compared in the present study. Results show that D2 full agonists [(+)‐PHNO, R(−)‐NPA, quinelorane, PD 128907 and 7‐OH‐DPAT] produced dose‐dependent increases in scratching, with effects that varied in magnitude among drugs [R(−)‐NPA ≈ (+)‐PHNO (>35% of session) > quinelorane ≈ PD 128907 ≈ 7‐OH‐DPAT (<25%)]. D2 partial or mixed‐action agonists [terguride (TER), preclamol (PREC), talipexole (TAL), roxindole (ROX), aripiprazole (ARIP)] did not significantly increase scratching. Results also show that, like haloperidol (HAL), TAL, TER, ARIP and ROX produced dose‐related increases in CAB. HAL, TAL, and TER produced high levels of CAB (65–99% of session), whereas the mixed‐action D2 partial agonists ROX and ARIP produced lesser levels of CAB (<40%). The D2 full agonists (+)‐PHNO, 7‐OH‐DPAT and PD 128907 produced no evidence of CAB. Although the roles of D2 subtypes in agonist‐induced scratching or of intrinsic activity in CAB are not well understood, these behavioral endpoints serve as quantifiable measures of D2 receptor activation or blockade in primate species. (supported by NIH/NIDA RO1‐03774, RO1‐10566)
Concentration dependent contractile effect of methylene blue in human internal mammary artery.
Authors: Seyrek Melik , Ulusoy Hasan Basri , Yildiz Oguzhan , Gul Husamettin , Yildirim Vedat 
Published: June 2021

Objective: Methylene blue (MB), an inhibitor of soluble guanylate cyclase, may a lifesaving drug which improves hemodynamic parameters in vasoplegic syndrome. We investigated the relation between MB concentration and vascular responses to clarify the rationale of its use in vasoplegic syndrome.Methods. The study was performed in organ bath in human isolated internal mammary artery (IMA). The responses were recorded isometrically by a force‐displacement transducer.Results: MB (10 nM‐100 μM) produced concentration‐dependent contraction in the arteries. The maximal contraction to MB was 44.2% ± 3.8 of 45 mM KCl maximum contraction. pEC50 value was 5.5 ± 0.1. MB caused an insignificant leftward shift of the concentration‐response curve of norepinephrine. Acetylcholine‐induced relaxation in submaximal contracted rings with phenylephrine was recovered nearly six hours later than MB challenge.Conclusions: We showed that MB caused concentration‐dependent contraction in human IMA. MB inhibited ACh‐induced relaxation during six hours considering muscarinic receptor occupation. The contractile effect of MB is predominantly related to its own effect which proves a rationale for its use in cathecolamine refractory vasoplegic syndrome.
Angiotensin 1–7 decreases nerve stimulated Norepinephrine (NE) and Neuropeptide Y (NPY) overflow from the mesenteric arterial beds of SHR
Authors: Byku Mirnela , Macarthur Heather , Westfall Thomas C 
Published: June 2021

NPY is a cotransmitter with NE and ATP in sympathetic nerves. There is evidence for increased activity of the sympathetic nervous system and the renin‐angiotensin system (RAS) as well as a role for NPY in the development of hypertension in experimental animal models and in humans. Angiotensin II (Ang II) is known to facilitate sympathetic neurotransmission; an effect greater in Spontaneously Hypertensive Rats (SHR) than normotensive Wistar‐Kyoto (WKY) rats. A newly discovered product of the RAS is the peptide Angiotensin 1–7 (Ang 1–7). There is evidence suggesting that Ang 1–7 opposes the actions of Ang II resulting in hypotensive effects. The objective of this study was to investigate the role of Ang 1–7 on the nerve stimulated overflow of NE and NPY from the mesenteric arterial bed of SHR and the receptors mediating any effects produced.Ang 1–7 (0.001, 0.01, 0.1μM) decreased nerve stimulated NE and NPY overflow, as well as perfusion pressure in preparations obtained from SHR. This effect was greater in preparations of SHR than WKY controls. Administration of the Mas Receptor Antagonist (MRA), D‐Ala Ang 1–7, and the Angiotensin Type 2 Receptor Antagonist (AT2A), PD12339 attenuated this effect.Ang 1–7 decreases the nerve stimulated overflow of NE and NPY in preparations of SHR, while Ang II enhances it. Therefore, Ang 1–7 may counteract the effects of Ang II by acting on AT2 and Mas Receptors. (Sponsored by NIH HL60260 and AHA)
Increased expression of components of the Rho‐A/Rho‐kinase pathway does not compensate for its impaired activation in small mesenteric arteries from endotoxemic rats
Authors: Santos José Eduardo da Silva , Chiao Chin‐Wei , Leite Romulo , Webb R. Clinton 
Published: June 2021

Background:Hyporeactivity to vasoconstrictors is a hallmark of septic shock. Although activation of the Rho‐A/Rho‐kinase pathway has been shown as crucial for development of vascular contraction its role or involvement in septic shock is unknown.Methods:We evaluated the relaxation induced by the Rho‐kinase inhibitor Y‐27632 (1 nM to 30 μM) in first order mesenteric arteries from rats treated with lipopolysaccharide (LPS, 10 mg/kg, i.p.) for six or 24 h (or sterile saline; control group). Results: Relaxation induced by Y‐27632 (but not by acetylcholine) was enhanced in vessels from LPS‐treated rats (see figure). The EC50 of Y‐27632 was reduced from 2.8 μM in control rings to 700 and 25 nM in LPS 6 and 24 h, respectively (p<0.05). The potentiation in Y‐27632‐induced relaxation was abolished by L‐NAME (100 μM), or 1400W (1 μM) at 6 but not 24 h after LPS. ODQ (10 μM) was effective at both 6 and 24 h. Western‐blot analyses revealed that protein levels of Rho‐A and ROCK‐II are increased in LPS‐treated animals.Conclusions:In spite of increased expression of Rho‐A and ROCK‐II, activation of this pathway is impaired in endotoxemic rats. This effect could be explained by increased production of nitric oxide and cGMP. We speculate that impaired Rho‐kinase pathway is involved in the hyporeactivity to vasoconstrictors observed in septic shock.
Protective effect of sphingosine 1‐phosphate (S1P) in the cerebral microvasculature
Authors: Edmundson Carmen Lynne , Miller Donald W. 
Published: June 2021

Introduction: Sphingosine 1‐phosphate (S1P), an endogenous phospholipid, is involved in pre‐conditioning responses in the heart. The present study evaluated whether exogenous S1P could have a similar protective role in the cerebral microvasculature following hypoxic insult.Methods: Human brain microvessel endothelial cells (HBMECs) were exposed to oxygen‐glucose deprivation (OGD) for 0–6 hours. Cell viability was assessed using MTT assay immediately after OGD or following a 24‐hr re‐oxygenation period. The effects of S1P on OGD‐mediated cell toxicity was determined by pre‐treating the cells with various concentrations of S1P (0–10 μM) for 0, 1, or 24 hours.Results: Exposure of HBMECs to OGD resulted in a significant decrease (approximately 20%) in cell viability when assessed immediately after OGD. Pre‐treating HBMEC cells with S1P for 1 hr prior to OGD provided a dose dependent protection, with 1.0 and 10 μM S1P completely reversing the loss in cell viability associated with OGD at all time points examined. However, the protective effects of S1P were not apparent in the 24‐hour pre‐treatment protocol.Conclusion: Activation of S1P receptors within the brain microvasculature prior to hypoxic events may help prevent toxicity to the cerebral microvasculature.Funding support provided by Canadian Institutes of Health Research and Manitoba Health Research Council.
Inhibiting matrix metalloproteinase‐2 (MMP‐2 reduces endothelial damage in isolated rat hearts during ischemia‐reperfusion
Authors: Fert‐Bober Justyna , Leon Hernando , Sawicka Jolanta , Basran Paul , Schulz Richard , Sawicki Grzegorz 
Published: June 2021

Previous studies have shown disruption of the coronary endothelium and increase in its permeability during ischemia‐reperfusion (I/R) which can be linked with MMPs activity. Our group has shown that during I/R, increased activity of MMP‐2 is associated with cardiac dysfunction, which can be prevented by MMP inhibitors. Therefore, we hypothesize that MMPs inhibition reduces the MMP‐2 dependent disruption of the coronary endothelium during I/R.Isolated rat hearts were perfused in the Langendorff mode at a constant pressure and subjected to 15‐30 min of no‐flow ischemia followed by 30 min of reperfusion. o‐Phenanthroline (Phen), an inhibitor of MMPs, was used to protect the hearts from dysfunction. Endothelial integrity was evaluated by measuring coronary flow, and by measuring the interstitial albumin and serotransferrin in the effluent. MMP‐2 activity was measured in the hearts by zymography.MMP‐2 activity was increased in heart tissue at the end of ischemia and was correlated with duration of ischemia. The coronary flow was decreased and correlated with the disruption of the endothelial barrier (increased release of albumin and serotransferrin in the coronary effluent). Administration of Phen inhibited both reduction of coronary flow and endothelial barrier disruption.
In‐vitro metabolism studies with BLX‐1026, a novel Orexin‐2 agonist with anti‐obesity activity
Authors: Mukherjee Aparna , Sen Ananda , Neogi Partha , Dey Deben , Nag Abhijit , Nag Biswajit 
Published: June 2021

BLX‐1026 is a water soluble, amino‐acid conjugated small molecule with in vitro Orexin‐2 receptor agonist activity. Orexin receptors have been implicated in non‐exercise activity thermogenesis. Increased levels of Orexin‐2 receptors have been observed in obesity‐resistant rats and decreased Orexin‐A levels observed in obese humans.Phase I metabolism studies have been conducted with BLX‐1026 in rat, mice, dog, monkey and human liver microsomes and human liver S9 fractions. It is found to be stable in all five species liver microsomes but shows a 61% degradation in the human S9 fractions when incubated for 1 hour. When orally administered to dogs and rats, it is found to have one major metabolite. Upon oral administration to rats and analysis of bile, it converts into the same major metabolite and three minor metabolites of which one is observed to be a glucuronide conjugate indicating Phase II metabolism. Further in vitro studies are underway with BLX‐1026 to further characterize its metabolic pathway.
Hepatic ABC Transporter Expression in A Hemochromatosis‐Linked Murine Model of Porphyria Cutanea Tarda
Authors: Arch Dorinda D , Phillips John D , Kushner James P , Franklin Michael R 
Published: June 2021

Iron overload can lead to hepatic fibrogenesis and high liver iron is frequently associated with porphyria cutanea tarda (PCT), a disease characterized by hepatic accumulation of highly carboxylated porphyrins. To assess whether porphyrin accumulation could arise from impaired anion transport, ABC transporter expression in a porphyria‐susceptible mouse model was investigated by qPCR. Mice with the Urod+/– (uroporphyrinogen decarboxylase), Hfe−/− (hemochromatosis) genotype spontaneously develop PCT, with severely decreased UROD activity and hepatic iron overload. Control animals with only the Urod+/– genotype do not accumulate porphyrins and had no change in expression of twelve ABC transporters examined. Accompanying the high iron accumulation in the Hfe−/− animals, expression of Abca3, Abcb1a, and Abcc4 were increased and expression of Abcc2, Abcc6 and Abcg2 were decreased. In mice with the Urod+/–, Hfe−/− genotype, porphyrin accumulation was accompanied by elevated expression of Abca3 and Abcc4 while Abcc2 and Abcc6 expression was depressed. The elevation in expression of Abcb1a and depression of Abcc2 were no longer present. Novel in these animals was an elevation of Abcc1 expression. The porphyrin accumulation exacerbated the repression of Abcc2 and Abcc6 expression and attenuated the increase in Abca3 seen in Hfe−/− control mice.Supported USPHS Grants DK20503 and DK07115
Regulation of lung epithelial ATP release
Authors: Seminario‐Vidal Lucia , Lazarowski Eduardo 
Published: June 2021

Mucociliary clearance, the primary innate defense mechanism of the lung, is controlled by extracellular nucleotides (e.g., ATP) acting on cell surface purinergic receptors. However, the mechanisms by which ATP is released from epithelial cells are poorly understood. To identify signaling elements upstream of ATP release, we examined the effect of GPCR activation on ATP release from lung epithelial A549 cells. The protease activated receptor (PAR) agonist thrombin and the P2Y2‐R agonist UTP induced robust inositol phosphate formation and Ca2+mobilization. RT‐PCR analysis indicated P2Y2‐R and PAR3 mRNA expression. Thrombin elicited a rapid ATP release, which was inhibited by BAPTA‐AM, thapsigargin, or ML‐7 (inhibits Ca2+/CaM‐dependent MLCK). In contrast, UTP caused no ATP release. Thus, signaling elements in addition to Gq/PLCβ/Ca2+may be involved in GPCR‐induced ATP release. PAR‐induced ATP release was decreased by ROCK inhibitors (Y27632 and H1 152), suggesting involvement of Rho/ROCK downstream of G12/13. Mechanical perturbations relevant to the airways (e.g. hypotonic swelling, shear stress) cause robust epithelial ATP release. Pretreatement of cells with ML‐7, Y27632, or H1 152 impaired hypotonicity‐elicited ATP release. Our results suggest that MLCK and Rho activation participate in both receptor‐ and hypotonicity‐induced ATP release from lung epithelial cells.Supported by NIH P01HL34322
LC‐MS/MS identification of amino acids that are phosphorylated in the osmoprotective transcription factor, TonEBP/OREBP
Authors: Kunin Margarita , Simons Brigitte L. , Irarrazabal Carlos , Shen Rong‐Fong , Wang Guanghui , Burg Maurice B. , Ferraris Joan D. 
Published: June 2021

High NaCl increases the activity of TonEBP/OREBP, resulting in increased transcription of osmo‐protective genes. High NaCl increases phosphorylation of TonEBP, and there is evidence that the phosphorylation is involved in its activation. The goal of the present studies was aimed to identify which amino acids in TonEBP are phosphorylated and to test their roles. We used HEK293 cells transfected with TonEBP‐1‐547‐V5 or TonEBP‐1‐1531‐V5. The cells were cultured under 200 or 500 mosmol/kg for two hours, nuclear and cytoplasmic proteins were extracted and immunoprecipitated with antibody to TonEBP‐V5. The immunoprecipitate was subjected to in‐solution proteolytic digestion and the phosphopeptides were enriched by IMAC prior to LC‐MS/MS analysis. In order to maximize coverage of possible phosphorylation sites, several different proteolytic enzymes were used. We used Ascore, a probability‐based rating system (Beausoleil at el, 2006), to estimate the probability of correct identification of phosphorylation sites. We find a high probability that S120, S134, T135, S561, S744, S1168, S1364 and S1367 are phosphorylated in at least one of the conditions. An S to A mutation at aa 134, S134A, reduce high NaCl‐dependent nuclear localization of TonEBP, while the phosphorylation at T135 is confirmed by a phosphospecific antibody. Possible functions of the other sites and their confimation by phospho‐specific antibodies are currently in process.Supported by the Intramural Research Program of NHLBI.