bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hindlimb collateral growth after superficial femoral artery (SFA) ligation in the Ossabaw pig
Authors: Ziegler Matthew A , Alloosh Mouhamad , Bills Randal G , Miller Steven J , Sturek Michael , Unthank Joseph L 
Published: June 2021

Vascular compensation to femoral artery occlusion was assessed in the Ossabaw pig. In 6 pigs, the right SFA was ligated and 4 weeks later, angiograms of the proximal hindlimbs were obtained using fluoroscopy. An average of 7.2±1.6 collaterals identified as vessels responsible for reconstitution of distal femoral artery originated from the superficial femoral, profunda (deep femoral) and gluteal arteries. The greatest number originated from the profunda (4.0±0.8), but the most prominent (>1 mm diameter) from the gluteal. Histology of the collaterals showed a tremendous increase in a single layer of intimal cells, an intact internal elastic lamina and no neointima. The inner diameter of the common femoral determined by intravascular ultrasound was similar between limbs, 5.0±0.4 mm. Average peak velocity in the common femoral measured with a ComboWire™XT was similar between limbs (19±2 vs 20±2, p=0.68), but decreased ∼50% with acute compression of the SFA. MAP was 64±5 mm Hg at time of velocity measurement. In conclusion, remarkable collateral growth occurs in the young healthy Ossabaw pig, which is able to restore resting flow in the common femoral artery within 4 weeks post‐occlusion. The Ossabaw pig is an excellent model to assess the impact of vascular disease on collateral growth in vessels of comparable size and hemodynamics as in humans.Support: HL42898, RR013223, HL062552
Vascular proteomics for protein‐arginine‐methylation in metabolic syndrome
Authors: Adachi Takeshi , Ishiwata Kyoko , Yamamoto Michiko , Yamamoto Takehiro , Suematsu Makoto 
Published: June 2021

Objective: Zucker rat is widely employed as an experimental model of metabolic syndrome, which is characterized with obesity, hyperlipidemia and insulin resistance. Although atherosclerosis is related with the mortality of the syndrome, changes in the vascular post‐translational protein modifications in this pathological state had not been well examined. In this study, we analyzed the protein‐arginine‐methylation in aorta from Zucker rat.Methods: Aortic constriction with phenyrephrin (PE) was assessed with isometric tension measurement. Some rings were pre‐treated with an iNOS blocker, L‐NIL (10 □M). Plasma homocysteine levels were measured by HPLC with fluorescence detection. Proteome analysis of aortic proteins was performed with the differential display of two‐dimensional electrophoresis using Ettan Dige.Results: PE‐induced vasoconstriction was decreased in aorta from Zucker rat and pre‐treatment of L‐NIL improved it. Plasma homocysteine concentrations were higher in Zucker rat. The proteomics analysis for the protein‐arginine‐methylation with anti‐dimethyl‐arginine (ADMA) antibody revealed the decreased ADMA modifications on several protein spots in aorta from Zucker rat.Conclusion: Hypomethylation status can be related with early vascular changes in metabolic syndrome and the elevated plasma homocysteine levels and NO from iNOS can be involved.
Mechanism of the rigidity of pulmonary capillaries in avian lung
Authors: Watson Rebecca R. , Fu Zhenxing , West John B 
Published: June 2021

We have previously shown that the pulmonary capillaries in chicken lungs are extraordinarily rigid in that large alterations in the capillary transmural pressure result in only small changes in capillary diameter. For example, the capillaries remain wide open even when the pressure outside them is raised 35 cmH2O above the pressure inside them. Since the walls of the capillaries are exceedingly thin (mean thickness ca. 0.27 μ m) it seems unlikely that the rigidity can be explained by the walls themselves. However the capillary walls are tethered by epithelial bridges that form the walls of the surrounding air capillaries and these could provide the necessary support. The bridges themselves are composed of two epithelial sheets enclosing a small amount of tissue, presumably extracellular matrix, and their total thickness is as little as 0.1 μ m in some places. Therefore at first sight they do not seem strong enough to offer sufficient support. However because of the topographical arrangement of the bridges it is possible that the mechanical loads are shared in such a way that even these thin structures can provide the necessary support just as the thin spokes of a bicycle wheel confer remarkable rigidity to the wheel.Supported by NIH grants 5 RO1 HL60968 and 5 T32 HL07212.
Dynamic pressure‐flow relationships in the human cerebral circulation at rest with and without alpha1‐adrenoreceptor blockade
Authors: Ogoh Shigehiko , Brothers R. Matthew , Eubank Wendy L. , Raven Peter B. 
Published: June 2021

Dynamic pressure‐flow relationships observed within the cerebral circulation indicate that when the critical closing pressure (CCP; a functional index of cerebral vascular tone) is reached cerebral blood flow stops. The purpose of this study was to identify the influence of the alpha1‐adrenoreceptors on cerebral vascular tone at rest. This was accomplished by continuously measuring middle cerebral artery blood velocity (MCA V) and arterial pressure from the radial artery before and after Prazosin ingestion (1mg/20kg BW) in 6 healthy subjects. Subsequent calculations of the CCP were preformed for each condition by linear extrapolation from the steady‐state beat‐to‐beat waveforms of velocity and pressure. Prazosin decreased mean arterial pressure (Control: 92±4 mm Hg vs. Prazosin: 87±5 mm Hg; P=0.021), however, Prazosin had no effect on mean MCA V (Control: 61±5 cm/s vs. Prazosin: 58±5 cm/s; P=0.511) or cerebral vascular resistance index (Control: 1.72±0.14 mm Hg s/cm vs. Prazosin: 1.88±0.15 mm Hg s/cm; P=0.82). The correlation between the dynamic pressure‐flow relationship without Prazosin was r=0.96±0.01 while with Prazosin it was r=0.95±0.01. Prazosin did not significantly change CCP (Control:16.3±4.3 mm Hg vs Prazosin:14.4±3.1 mm Hg, P=0.32). These findings suggest that basal sympathetic activity has no effect on cerebral vascular tone at rest.Supported in part by NIH grant #HL045547.
Streptozotocin‐Induced Diabetic Animal Model Recapitulates Many Features of Frailty in Older Adults with Diabetes
Authors: Anderson‐Antle Lisa L , Bauer David J , Gopalakrishnan Sandeep , Lark Daniel S , Sandoval Christopher L , Eells Janis T , Snyder Ann C 
Published: June 2021

Frailty is defined as a decline in the neuromuscular system, abnormal aging, and loss of physiological reserve. It is difficult to conduct research in this population, therefore we sought to identify an animal model that would recapitulate many of the characteristics of frailty. Purpose: To test the hypothesis that streptozotocin‐induced diabetes in the Wistar rat would exhibit characteristics similar to those reported in frail diabetic older adults. Methods: Male Wistar rats were rendered diabetic with streptozotocin (STZ, 50 mg/kg, ip). Animals were weighed weekly and blood glucose values were determined twice a week for 14 weeks. At week 15, animals were euthanized, perfused with cold saline and tissues (heart, muscle, kidneys) were rapidly dissected and tissue and organ weights were determined on an analytical balance. Results: Tissue weights of the heart and rectus femoris muscle were significantly reduced in STZ‐treated animals compared to control. Heart: STZ = 1.43 ± 0.11 g vs CON 1.75 ± 0.05 g (p < .05); Rectus femoris: STZ = 0.85 ± 0.31 g vs CON 1.62 ± 0.27 g (p < .0001). In contrast, kidney weights were significantly greater in STZ treated animals [STZ = 2.20 ± 0.24 g vs CON = 1.69 ± 0.12 (p < .0001)]. Conclusions: These data support our hypothesis and are indicative of the induction of myocardial dilatation, sarcopenia and glomerulopathy in chronic STZ‐induced diabetes.Funding Source: BTA Award and UWM RGI.
GABAergic pump cells of solitary tract nucleus innervate retrotrapezoid nucleus chemoreceptors
Authors: Takakura Ana C , Moreira Thiago S , Stornetta Ruth L , Guyenet Patrice G 
Published: June 2021

The retrotrapezoid nucleus (RTN) contains chemosensitive neurons that are inhibited by lung inflation via slowly‐adapting pulmonary stretch receptors (SARs). Here we examine whether RTN inhibition by lung inflation could be mediated by a direct projection from SAR second‐order neurons (pump cells). Pump cells (N = 56 neurons, 13 rats) were recorded in the nucleus of solitary tract (NTS) of halothane‐anesthetized rats with intact vagus nerves. Pump cells had discharges that coincided with lung inflation as monitored by the tracheal pressure. Their activity increased when end‐expiratory pressure was raised and stopped instantly when ventilation was interrupted in expiration. Many pump cells could be antidromically activated from RTN (12/36). Nine of those were labeled with biotinamide. Of these 9 cells, eight contained glutamic acid decarboxylase67‐ (GAD67‐) mRNA and seven were found to reside in the lower half of the interstitial subnucleus of NTS (iNTS). Using the retrograde tracer cholera toxin‐B, we confirmed that neurons located in or close to iNTS innervate the RTN (2 rats). Many such neurons contained GAD67‐mRNA and a few contained glycine transporter2 (GLYT2) mRNA. Anterograde tract‐tracing with biotinylated dextranamide (4 rats) applied to iNTS also confirmed that this region innervates RTN via a predominantly GABAergic projection. This work confirms that, in rats many NTS pump cells are located in and around the interstitial subnucleus at area postrema level. We demonstrate that a GABAergic subset of these pump cells innervates the RTN region. We conclude that these inhibitory neurons probably contact RTN chemoreceptors and mediate their inhibition by lung inflation.Supported by: HL 74011 (PGG) & Capes‐BEX 4402/05‐7 (ACT).
Role of adenosine and nitric oxide in hypoxia‐induced skeletal muscle vasodilation in humans
Authors: Leuenberger Urs A. , Mascarenhas Vernon , Lninton‐Frazier Latoya , Steiner Jill , Hogeman Cynthia , Gray Kristen S. 
Published: June 2021

In humans, systemic hypoxia evokes vasodilation in resting skeletal muscle despite significant increases in sympathetic vasoconstrictor nerve activity. This is thought to be due to endogenous vasodilators such as adenosine and nitric oxide (NO). To test whether adenosine and NO act independently, we determined the forearm blood flow responses to systemic hypoxia (FiO2 0.1 for 10 min) during 1) inhibition of adenosine receptors (aminophylline), 2) inhibition of NO‐synthase (NG‐monomethyl‐L‐arginine, L‐NMMA), and 3) combined inhibition of adenosine receptors and NO‐synthase (aminophylline plus L‐NMMA) administered via brachial artery in healthy humans. Forearm blood flow (FBF, venous plethysmography) was compared in the infused (experimental) and opposite (control) forearms. During hypoxia (pO2 35±1 mmHg), FBF in the control forearm increased by ~50%. L‐NMMA alone (n=8) reduced hypoxia‐induced vasodilation by ~37% whereas aminophylline alone (n=9) reduced it by ~50%. Combined blockade with aminophylline plus L‐NMMA (n=8) did not inhibit hypoxia‐induced vasodilation more greatly than either agent alone. These data demonstrate that both adenosine and NO contribute to hypoxia‐induced skeletal muscle vasodilation. The lack of synergy between aminophylline and L‐NMMA suggests that adenosine and NO may be part of the same vasodilator signaling cascade.(Supported by P01 HL077670 and R01 HL068699)
Transendothelial migration of CD133+ hematopoietic progenitor cells isolated from human umbilical cord blood
Authors: Rastogi Prerna , Young Dawn M , White Maureen C , McHowat Jane 
Published: June 2021

Transmigration of hematopoietic progenitor cells across the vascular endothelium and subsequent maturation in the tissue helps to maintain the pool of resident mast cells. We determined the potential of CD133+ cells isolated from umbilical cord blood to migrate across an endothelial cell monolayer. CD133+ cells possess mRNA for several adhesion molecules that are critical in the process of neutrophil transmigration. Stem cell factor & its receptor CD117 are required for homing & differentiation of mast cells in the tissue. We detected the presence of CD34, CD117, CD29, & CD18 on the surface of CD133+ cells using flow cytometry. Tryptase stimulation leads to increased endothelial cell platelet activating factor (PAF) production that may facilitate the interaction between the endothelium & the PAF receptor (PTAFR) on circulating CD133+ cells. Treatment with the PTAFR antagonist CV3988 significantly reduced the percentage of transmigrating CD133+ cells across a tryptase stimulated endothelial monolayer. This suggests that CD133+ cell migration depends on the PAF/PTAFR interaction in a manner similar to that involved in neutrophil transmigration. Following transmigration there is the potential for a subset of these cells, in the presence of SCF & IL‐6, to mature into tissue mast cells.This work was supported by AHA Heartland Affiliate Grant # 0610118Z.
Coupling LCM to gene expression and microproteomics: Novel approaches to molecularly define pediatric coronary artery intimal occlusive lesions
Authors: Juraszek Amy L , Calicchio Monica L , Steen Hanno , Waldon Zachary , Smoot Leslie , Mayer John E , Jr  , Perez‐Atayde Antonio R , Collins Tucker 
Published: June 2021

Background‐Cardiac allografts fail due to post‐transplant vasculopathy, a progressive loss of the lumen in coronary arteries. The arterial injury is characterized pathologically by a concentric intimal expansion as a result of the proliferation of smooth muscle cells and the accumulation of extracellular matrix (ECM). The precise pathogenesis of graft arteriosclerosis is unknown.Methods and Results‐Samples from coronary artery occlusive lesions were captured using LCM. The tissue was then incubated in Liquid Tissue Reagent (Expression Pathology, Gaithersburg, MD), enabling subsequent proteolysis and LC‐MS/MS analysis using a nanoflow HPLC system and a linear ion trap/orbitrap mass spectrometer. Proteins for multiple ECM components were detected in the neointima, including a variety of collagens, fibrillin, laminin, fibronectin and specific proteoglycan core proteins. The findings were validated by immunohistochemical analysis.Conclusions‐Microproteomic analysis demonstrates multiple ECM components including collagens and specific proteoglycan core proteins in the intimal lesions of post‐transplant vasculopathy. This accumulation of ECM components was present in all lesions, suggesting it plays an important role in their pathogenesis. Further analysis of the ECM in these lesions may provide new insights into the pathobiology of post‐transplant arteriopathy.NIH/NHLBI 1 P50 HL74734
Biological effects of bacitracin as a therapeutic agent and growth promoting compound
Authors: Lin Jun , Van Hout Amber , Wolff Teddi , Erickson Alan , Francis David 
Published: June 2021

Bacitracin is a peptide antibiotic and it has several effects on the microbial population of the intestines that could account for its growth‐promoting ability. Enterotoxigenic E. coli is a major pathogen of weaned pigs and is responsible for significant death loss and retardation in weight gain. We found in in vitro studies that bacitracin at sub‐inhibitory concentrations (390 to 780 μg/ml) preferentially selected for the outgrowth of tetracycline sensitive bacteria from among a population of tetracycline resistant and tetracycline sensitive E. coli and Salmonella. Two E. coli strains were used and showed that bacitracin did select Tetracycline sensitive bacteria (P < 0.05). Nine tetracycline resistant and nine tetracycline sensitive Salmonella strains were pooled in this study. Twenty‐five percent more tetracycline sensitive bacteria were found in LB broth containing bacitracin at the sub‐inhibitory concentration (P < 0.01). These findings suggested that a possible benefit from using bacitracin as a feed additive might be to reduce the Tetrpopulation of pathogens in the intestinal tract. In studies utilizing newly weaned piglets, we established that a feed level concentration of bacitracin in the starter diet did enable piglets to clear a pathogenic bacterium at a faster rate than was the case when piglets were placed on antibiotic‐free feed.Supported by Alphamra Inc., the South Dakota Agricultural Experiment Station, and the South Dakota Center for Infectious Disease Research and Vaccinology
Short fasting prevents glucose‐dependent insulinotropic polypeptide (GIP) induced stimulation of intestinal electrolyte secretion
Authors: Flemström Gunnar , Jedstedt Gunilla , Bengtsson Magnus 
Published: June 2021

Glucose‐dependent insulinotropic polypeptide (GIP) and glucagon like peptide‐1 (GLP‐1) are important incretins, facilitating release of insulin from pancreatic islets. In addition, these peptides affect satiety and metabolism. Our aim was to study effects of GIP and GLP‐1 on duodenal mucosal bicarbonate secretion in fed and food‐deprived animals. Glucagon like peptide‐2 (GLP‐2) is not an incretin but was tested for comparison. Methods: Lewis x Dark Agouti rats had free access to water and, unless fasted overnight, free access to food. Animals were anesthetized (thiobarbiturate, 120 mg/kg) and a segment of proximal duodenum with intact blood supply cannulated in situ. Mucosal bicarbonate secretion (pH stat) was continuously recorded and peptides were administered to the duodenum by close intra‐arterial infusion. Results: Intra‐arterial infusion of GIP (60‐600 pmol/kg, h) caused dose‐dependent increases in duodenal bicarbonate secretion in fed animals (p<0.01) but not in fasted animals (p>0.05). At a higher dose (6000 pmol/kg, h), GLP‐1 induced a slight increase (p<0.05) in secretion. GLP‐2 did not affect the duodenal secretion. Conclusions: GIP and to a smaller extent GLP‐1, stimulate duodenal bicarbonate secretion in fed but not in overnight fasted rats. Studies of intestinal secretion may require particular evaluation with respect to feeding status.Supported by the Swedish Research Council
In chronic colitis exacerbation of altered motility induced by the bacterial peptide formyl‐Methionyl‐Leucyl‐Phenylalanine (fMLP) is associated with dysregulation of the immune system
Authors: Cruz Myrella L , Alvarado Zellinette , Coppola Domenico , Antonia Scott J , Appleyard Caroline B 
Published: June 2021

The pathophysiological role of bacterial peptides in the symptoms associated with colitis is unclear.Aim:To investigate the role of fMLP in chronic colitis.Methods:Colitis was induced in rats by administration of trinitrobenzene sulfonic acid (TNBS; 30mg in 50% ETOH ic). Chronic relapsed inflammation was induced 6 weeks later by TNBS (5mg/kg iv), with or without the bacterial peptide (1.0mM in 6% DMSO iv) at 24 hour time intervals over three days. The colons were assessed for macroscopic and microscopic damage, and immunohistochemistry. Tissue cytokine levels were measured by ELISA and real‐time RT‐PCR. Segments of longitudinal and circular smooth muscle from proximal and distal colon were mounted in tissue baths for isometric recording in response to Ach.Results:Administration of fMLP exacerbated both macroscopic and microscopic damage (p<0.05). Cellular infiltration and increased numbers of T‐cells and dendritic cells were found. These animals had more diarrhea and increased muscle tension in response to Ach. Levels of IFNγ and TNFα increased after administration of fMLP (p<0.05), while IL‐10 levels were decreased (p<0.05), with little change in TGFβ or IL‐18.Conclusions:Components of the intestinal microflora may drive a dysregulation of the immune system and influence the contractile responses of the colon in chronic colitis contributing to the symptoms observed in patients. NCRR/RCMI 2G12RR03050
Alterations in Toll‐like Receptor Regulation in the Liver from Horses with Laminitis
Authors: McGeachy Matthew , Bell Amy , Keowen Michael L , Peiro Juliana , Stokes Ashley M. 
Published: June 2021

Laminitis can occur secondary to an ischemic‐reperfusion injury of the GI tract. When the normal flora of the GI or pH is disrupted, stimulators of inflammation can be released into the GI bloodstream. The next point of organ contact is the liver via the portal blood stream potentially leading to increased expression of inflammatory mediators, such as Toll‐like receptors (TLR)‐2 and ‐4.Liver samples of normal (n=18) and horses with naturally‐acquired (n=5) and experimentally‐induced (n=7) laminitis were collected and TaqMan RT‐PCR was used to quantify TLR‐2 and ‐4. Beta‐Gus was used as the housekeeping gene and standard curves were utilized. Data is presented as delta‐delta CT.Equine TLR‐2 and ‐4 are upregulated in liver collected from laminitic compared to normal. Upregulation of TLR‐2 in laminitic horses is over 3‐fold higher than normal. Upregulation of TLR‐4 was only a minor increase. However, horses with experimentally‐induced laminitis (48 hours after induction) had the greatest increase compared to chronic cases having a 6‐fold TLR‐4 increase.Identification of inflammatory mediators may aid in the unraveling of equine laminitis, helping horses such as Barbaro. Also, pinpointing an earlier point in this cataclysmic reaction will help in the development of gene specific therapeutics as this technology is developed and utilized. Funded by Louisiana State University Equine Health Studies Program.
Temporal and dose‐dependent effects of hepcidin in cultured macrophages and intestinal epithelial cells
Authors: Sharp Paul , Chung Bomee , Chaston Timothy , Srai Surjit Kaila 
Published: June 2021

Hepcidin regulates iron homeostasis by inhibiting the release of iron from enterocytes and RE macrophages. To achieve this effect, it is proposed that hepcidin binds to the ferroportin transporter, triggering its internalization and degradation. In the present study, we have examined the effects of hepcidin in two human cell lines; Caco‐2 intestinal epithelial cells and THP‐1 macrophages. In THP‐1 cells there was a rapid (within 4h) decrease in ferroportin protein expression following exposure to 1μM hepcidin (control 1.1 ± 0.05 a.u.; +hepcidin 0.5 ± 0.06 a.u., P<0.001). The inhibitory effect of hepcidin on THP‐1 ferroportin levels was dose‐dependent with an IC50 of approximately 300nM hepcidin. In contrast, there was no effect of hepcidin on ferroportin expression in Caco‐2 cells, even when the hepcidin concentration was elevated to 3μM (control 1.0 ± 0.28 a.u.; +hepcidin 1.4 ± 0.26 a.u. P>0.1). These data support the hypothesis that iron‐recycling macrophages are more sensitive than enterocytes to changes in hepcidin levels, and is fully consistent with the paramount importance of macrophages in maintaining the supply of iron for erythropoiesis.This work was funded by the Biotechnology and Biological Sciences Research Council.