bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of FasL expression of rat Mesenteric Lymph Node Dendritic Cells during Inflammatory Bowel Disease (IBD)
Authors: Rivera Edelmarie , Rodriguez Freddy , Appleyard Caroline Barbara 
Published: June 2021

Strong evidence demonstrates that a breakdown of tolerance against intestinal microflora is a major factor in the pathogenesis of IBD. Dendritic cells (DCs) appear to play a role in modulating the innate and adaptive immune response. During IBD DCs are activated and the toll like receptors upregulated. The DC populations present in inflamed and control mesenteric lymph nodes (MLNs) are unknown.AIMTo examine the expression of FasL on MLN DC during acute colitis.METHODSAcute colitis was induced in Sprague Dawley rats by administration of trinitrobenzene sulfonic acid (TNBS i.c.). At 72 hours the rats were sacrificed and the colons removed and scored for macroscopic damage. The cecum and small intestine were exteriorized and the MLN chain identified. After dissection of overlying mesenteric fat, the MLN were removed. The lymph nodes adjacent to the cecum were also removed. Isolation of DC and phenotypic characterization of FasL expression were performed by flow cytometry.RESULTSAnimals receiving TNBS had significantly higher damage scores than untreated animals (p<0.0001). Expression of FasL on MLN DC was significantly higher in colitis animals (83%) than in controls (38% p<0.05).CONCLUSIONOur results suggest that loss of FasL expression on MLN DC may be one of the mechanisms that contribute to the inappropriate apoptosis and subsequent T cell accumulation that occurs in IBD. Supported by 5F31DK077584.
Downregulation of aging‐related Klotho gene in experimental colitis
Authors: Thurston Robert D , Larmonier Claire B , Majewski Pawel M , Ramalingam Rajalakshmy , Midura‐Kiela Monica T , Laubitz Daniel , Vandewalle Alain , Mühlbauer Marcus , Jobin Christian , Kiela Pawel R , Ghishan Fayez K 
Published: June 2021

Klotho (Kl) deficiency leads to premature senescence and impaired Ca2+/Pi homeostasis. Since osteopenia/osteoporosis are fequently associated with human IBD, we investigated the changes in Klotho gene expression as a consequence of experimental colitis. We utilized three models: TNBS colitis, microflora‐induced colitis in germ‐free IL‐10−/− mice, and adoptive CD4+CD45RBhigh T‐cell transfer colitis, followed by in vitro approaches using renal epithelial cells and the cloned murine Kl gene promoter. Renal expression of Kl mRNA and protein was suppressed in all three IBD models. The degree of inhibition correlated with colitis severity, and was reversed by anti‐TNF antibody. In vitro, TNF significantly inhibited Kl expression and was further potentiated by IFNγ. TNF/IFNγ combination resulted in increased iNOS expression and elevated NO production. The effect of IFNγ could be reproduced by SNAP (NO donor), and reversed by iNOS inhibition. These effects were transcriptionally mediated since Klotho mRNA stability remained unaffected, while reporter constructs with the mKl gene promoter was downreguled in transiently transfected renal epithelial cells. These novel findings could help explain several extraintestinal complications including abnormalities in bone homeostasis in patients with chronic colitis.Grant support: R37DK033209 (F.K.G.), 5R01DK067286 (P.R.K.), 2R56DK047700 (C.J.)
Effect of melatonin on the vestibulocollic reflex in humans
Authors: Cook Jonathan S , Chin‐Sang Stephanie A , Sauder Charity L , Ray Chester A 
Published: June 2021

Melatonin has been reported to decrease nerve activity of the medial vestibular nuclei in rats. The purpose of the present study was to determine if melatonin alters the vestibulocollic reflex (VCR) in humans. Based on our previous findings with melatonin's affect on the vestibulosympathetic reflex (VSR), we hypothesized that exogenous melatonin ingestion would attenuate the VCR. To test this hypothesis, vestibular evoked myogenic potentials (VEMP) were recorded in 10 healthy subjects (26 ± 1 yr; 4 male, 6 female) before and 45 min after ingestion of 3 mg melatonin. Additionally, we recorded VEMP in 8 healthy subjects (25 ± 1 yr; 1 male, 7 female) who underwent the same experiments but without melatonin to serve as time controls. Melatonin did not alter the timing of the first VEMP peak (13 ± 0.4 and 14 ± 0.3 ms, pre and post melatonin, respectively) nor the second VEMP peak (21 ± 0.6 and 21 ± 0.7 ms, pre and post melatonin, respectively). More importantly, VEMP interpeak amplitude was not altered by melatonin (before: 22 ± 5 vs. after: 23 ± 5 a.u.). Comparable results were observed in the control group (before: 26 ± 6 vs. after: 26 ± 7 a.u.) These data indicate that melatonin does not alter the VCR in humans. In conjunction with our previous findings demonstrating an attenuated VSR with exogenous melatonin, the present findings suggest that melatonin's affect on the VCR and VSR are different in humans.NIH HL077670, NASA Space Fellowship
Time Course of Urinary Concentrating Defect in Vitamin D‐Induced Hypercalcemic Rats
Authors: Khositseth Sookkasem , Sriwong Siriwan , Uawithya Panapat 
Published: June 2021

We studied the onset of hypercalcemia‐induced nephrogenic diabetes insipidus and its relationship to aquaporin‐2 (AQP2) and bumetanide‐sensitive Na‐K‐2Cl cotransporter (NKCC2) expression. Rats were treated with or without food supplement of 1mg dihydrotachysterol (DHT)/kg BW/day for 1, 2, 7 days. After treatment for 1 day, serum calcium was significantly increased (control: 9.7±0.3 vs. DHT: 10.8±0.2 mg/dl). Urine volume was also significantly increased (0.27±0.18 vs. 0.83±0.14 ml/gram BW/day). Urine osmolality was decreased after 2 days of DHT ingestion (1.53±0.5 vs. 0.91±0.00 osmol/kgH2O, P < 0.05), suggesting DHT rats lose their ability to concentrate urine. Immunoblotting showed that NKCC2 abundance in kidney outer medulla of DHT‐treated rats was decreased by 59% after 1 day treatment and remained decreased until day 7. The AQP2 abundance in inner medulla was decreased by 44% after 2 days of DHT diet and remained decreased until day 7. In conclusion, the onset of polyuria and hypercalcemia were found to occur within 1 day after DHT treatment. The early development of polyuria in association with hypercalcemia was most likely due to a downregulation of NKCC2 in medullary thick ascending limb, whereas the urinary concentrating defect after 2 days DHT treatment involved downregulation of both NKCC2 and AQP2.This study was supported by a grant from Thammasat University to SK and PU.
Activation of P2Y1 purinergic receptors (P2Y1Rs) induced calcium influx in rat supraoptic neurons (SON) through stretch inactivated cation (SIC) channels
Authors: Song Zhilin 
Published: June 2021

Activation of P2Y1Rs contributes to the ATP‐induced increase in intracellular calcium ([Ca++]i) in SON. Although activation of P2Y1Rs induced release of Ca++stores presumably as a result of IP3 production, it also induced a small Ca++ influx, possibly through plasma membrane IP3 receptors or modulation of other ion channels such as osmo‐sensitive SIC channels. Current studies evaluated the role of SIC channels in P2Y1R induced Ca++ influx by directly monitoring [Ca++]i changes using live cell calcium imaging. Hypothalamo‐neurohypophyseal explants were loaded with the Ca++‐sensitive dye, fura 2AM, and the change in [Ca++]i in SON was determined by ratiometric analysis of fluorescence emitted by excitation at 340 and 380 nm. Activation of P2Y1Rs by 2‐methyl‐thio‐ADP (2‐MeSADP, 100 μM) induced a large increase in [Ca++]i. The amplitude of the increase was reduced by ruthenium red (RR, 10 μM) and gadolinium (Gd, 100 μM), both of which block mechano‐sensitive channels including the SIC channels. Furthermore, the decay after peak response was much faster in the presence of RR and Gd. These results indicate that activation of P2Y1Rs may modulate SIC channels, thus inducing a small component of influx of extra‐cellular Ca++, in addition to release of Ca++ from intracellular stores. Further studies are ongoing to clarify the underlying mechanisms and functional importance of the Ca++ influx.Supported by AHA SDG 0735329N.
Enhanced oxidative and carbonyl stress predicts salt sensitivity in obese young adults
Authors: Mori Takefumi , Kawamata Akihiro , Hosoya Takuma , Yoneki Yoshimi , Mitui Eiko , Hasegawa Yoko , Ohta Michi , Ito Megumi , Sato Hiromi , Kabayama Shigeru , Ito Sadayoshi , Hida Wataru 
Published: June 2021

BackgroundMethylglyoxal (MGO), a carbonyl substance, is increased in CKD patients and can induce salt sensitive hypertension and insulin resistance together with enhanced oxidative stress in a rat model. The present study determined whether carbonyl/oxidative stress is enhanced in obese young adults and would associate with salt sensitivity.MethodsYoung adult students (2335students, male:1794, female:541, age:18to28)were enrolled for the study. Daily Na excretion (UNa, as a indicator of Na intake), albumin (UAE, as a marker of CKD), TBARS (U‐TBARS, as a marker of oxidative stress) and MGO (U‐MGO, as a marker of carbonyl stress) was analyzed. Correlations were determined among the parameters in the health checkup.ResultsAlthough, SBP, U‐TBARS, U‐MGO and UNa were increased with higher BMI or AC in male students, SBP was increased without increase in U‐TBARS and UNa in high BMI or AC female students. U‐TBARS and U‐MGO had a positive correlation with UNa, and UAE significantly increased with BMI of 30 and above compared to under 30 in either sex. Finally, SBP correlated with BMI of 30 and above in male students while no correlation was observed in those under 30.ConclusionThese results indicate that obese has a higher risk of salt sensitive hypertension and CKD in young adults which can be predicted by carbonyl/oxidative stress. Supported by the Grants‐in‐Aid from the Min. of ECSST of Japan (No.20590970)
Patterns of Coronary Atherosclerosis in a Hypercholesterolemic Swine Model
Authors: Arce‐Esquivel Arturo A. , Turk James R. , Laughlin M. Harold 
Published: June 2021

Inflammation and endothelial activation are the initial histological changes within the arterial wall that eventually lead to the development of advanced lesions of atherosclerosis. Atherosclerosis progresses at different rates among the arterial segments, especially in the coronary arteries. This study was designed primarily to characterize the anatomical patterns of atherosclerotic disease in the coronary arteries of hereditary hypercholesterolemic (HH) swine. We also tested the hypothesis that exercise training (ExT) would decrease the progression of initial changes in atherosclerotic lesions of HH swine. Fifteen HH pigs were randomly assigned into either exercise trained (EX) or sedentary groups (SED). Exercise training consisted of a 16 week progressive treadmill training program. At sacrifice left anterior descending (LAD) and right coronary artery (RCA) were harvested. Immunohistochemistry was used to quantify the presence of MCP‐1, VCAM‐1, iNOS and CD‐44 antibodies. The average percentage for MCP‐1, VCAM‐1, iNOS and CD‐44 staining tended to be greater in the LADs. ExT did not significantly reduce the prevalence of changes. We conclude that the patterns of coronary atherosclerosis in swine are similar to those in humans, and ExT does not significantly reduce the progression of initial morphologic changes in coronary arteries in this model of disease.Supported by NIH HL52940.
Multiple dosings wtih acidic retinoids increase retinol stores and expression of retinoid homeostatic genes in the lung of neonatal rats
Authors: Wu Lili , Ross A. Catharine 
Published: June 2021

Previously we have shown that vitamin A (VA) combined with acidic retinoids synergistically increases retinol uptake and retinyl ester (RE) formation in neonatal rat lung, concomitant with the expression of several retinoid homeostatic genes: LRAT (lecithin:retinol acyltransferase), CYP26B1 (a cytochrome P450), and Stra6 (stimulated by retinoic acid gene 6). In the present study we compared the response to VA alone or combined with retinoic acid (RA) or a analog, Am580, in two timing protocols: single early dosing (d 4) vs. multiple dosings throughout the period of lung septation (d 4, 7, 11, 14). Multiple dosing resulted in a higher, cumulative increase in lung RE content for all treatments: vehicle<RA≅VA<Am580<VARA<VAAm580. However, most of the retinoid homeostatic genes were up‐regulated by acidic retinoids to the same extent after a single vs. multiple dosings. Lung functional gene, surfactant protein‐A (SPA1) mRNA remained nearly constant with both treatment and timing. In conclusion, multiple treatments of VA and acidic retinoids in combination during the septation period greatly increased neonatal lung RE content in a synergistic and cumulative manner. Repeated but transient induction of retinoid homeostatic genes by acidic retinoids at the time of each dosing may explain the observed cumulative synergistic enhancement of RE formation.Support: NIH CA90214.Grant Funding Source: NIH CA90214
Whole Slide Imaging System: a Valuable Tool for Biorepositories
Authors: Handorf Charles R , Johns Cameila , Zhang Jie , Kulkarni Anand L 
Published: June 2021

Tissue biorepositories classically exist to support biomedical research and development by collecting, classifying, preserving, and supplying biological material. The advent of whole slide imaging (WSI) systems provides a new way to approach the information inherent in tissues. Archiving of static digital images from microscopic slides is of limited value for research, whereas digitizing all of the information on a slide opens up new avenues for collaboration and quantification of the information contained in a slide. We have evaluated 20 tissue cases representing a variety of tissue types and pathological conditions; data collected include evaluation of diagnostic suitability by a panel of pathologists, scanning quality at 20X and 40X magnification, total processing time, scanning time, and file size. Operational characteristics for WSI systems must be optimized; however, these systems will be a valuable tool for biorepositories to create digital archives, to establish the quality of tissues requested by researchers, and to augment data sharing.NCRR 1S10RR025665‐01
Sympathetic Nerves and Endothelium Influence the Vasoconstrictor Effect of Low Concentrations of Ouabain in Pressurized Small Arteries
Authors: Raina Hema , Zhang Qingli , Rhee Albert , Pallone Thomas L , Wier Withrow Gil 
Published: June 2021

Here, we tested the involvement of arterial endothelium and peri‐vascular sympathetic nerve terminals (NT) in ouabain‐induced vasoconstriction. Segments of rat arteries were pressurized and exposed to ouabain (10−11M–10−7M). Endothelium removal enhanced ouabain‐induced (10−9M) vasoconstriction as much as 2‐fold. A component of the ouabain‐induced vasoconstriction is due to enhanced spontaneous release of norepinephrine (NE) from NT's in the arterial wall. The α1‐adrenoceptor blocker, prazosin (10−6M) decreased ouabain induced vasoconstrictions by as much as 50%. The electrically evoked release of NE from sympathetic NT was not affected by ouabain (< 10−7M). However, neither the ouabain induced contraction nor the NE release (measured directly by carbon fiber amperometry) was increased by sympathetic nerve activity (SNA). However, following brief bursts of SNA, vasoconstrictor responses to ouabain were transiently increased (1.75‐fold). In arteries lacking endothelium and exposed to prazosin, ouabain (>10−11M) caused vasoconstriction, indicating a direct effect on arterial smooth muscle. Conclusions: Endothelium opposes ouabain induced vasoconstriction, which is caused by both enhanced spontaneous NE release and direct effects on smooth muscle. Ouabain does not enhance SNA mediated contractions, but SNA enhances ouabain‐induced contraction.NIH grants R01‐HL073094 & P01‐HL078870
High fructose diet and its effect on gene regulation in rat heart
Authors: Ojaimi Caroline , Huang Harer , Kertowidjojo Elizabeth , Olson Lauren , Hintze Thomas H 
Published: June 2021

High fructose consumption (FC) has been thought to be a contributing cause of insulin resistance, obesity, elevated LDL cholesterol and triglycerides, leading to metabolic and cardiovascular diseases. The effects of 21 days of a 60% purified fructose diet on gene expression, using Affymetric Rat Arrays, were investigated in cardiac tissues of female SD rats. Hemodynamic measurements showed significant increases in mean arterial pressure and insulin levels in FC. NO bioactivity was impaired by FC and this effect was reversed by tiron, which scavenges superoxide. These data suggest a role of superoxide in the heart during FC. The array data revealed 235 genes significantly regulated (p<0.05, ± 1.5 fold) in FC. The up regulated genes (n= 123) included caveolin 1 (limits NO production), PDE5A (increases NO breakdown), glucose‐fructose oxidoreductase, peroxisome proliferator activated receptor alpha, peroxisomal biogenesis factor 11 alpha, phosphatidylinositol 5‐kinase, granzyme A and stoning 2 (both shown to be expressed in diabetes). The down regulated genes (n= 112) included glucose‐6‐phosphate dehydrogenase, insulin‐like growth factor 2, N‐acetyltransferase 14, glutathione S‐transferase, ATPase, mitochondria ribosomal protein and UCP2. These results indicate that high fructose intake has a dramatic effect on the heart by regulating a large number of metabolic and energy producing genes.Supported by HL‐PO1‐43023 & HL 50142.
Rhythmic mechanical deformation of the human forearm increases venous plasma [ATP] and ATP release
Authors: Crecelius Anne R. , Kirby Brett S. , Richards Jennifer C. , Voyles Wyatt F. , Dinenno Frank A. 
Published: June 2021

Accumulating evidence indicates that circulating adenosine triphosphate (ATP) evokes vasodilation and assists in skeletal muscle blood flow regulation during exercise. Mechanical deformation of erythrocytes can stimulate ATP release in vitro, and we have demonstrated that rhythmic mechanical deformation of the forearm increases blood flow (FBF) via vasodilation. Thus, we tested the hypothesis that mechanical effects of muscle contractions increase [ATP] v and ATP release in vivo independent of changes in tissue metabolic demand. In 6 young adults, blood samples were obtained from a deep venous catheter and were mixed in stop solution to preserve [ATP] v for measurement. We measured FBF (Doppler ultrasound) and plasma [ATP] v and calculated forearm ATP release (FBF x [ATP] v) during rhythmic forearm compressions via a blood pressure cuff at 3 graded extravascular pressures (50, 100 and 200 mmHg). [ATP] v was significantly increased at each pressure compared with rest (range: 581–609 vs 237 ± 9 nmol/l; P < 0.05). Additionally, forearm compressions evoked a graded increase in FBF and thus ATP release was graded with extravascular pressure (P < 0.05). We conclude that rhythmic mechanical deformation of the forearm increases [ATP] v and ATP release, and that this mechanical effect of muscle contractions could contribute to the observed increases in [ATP] v and ATP release during exercise.Supported by HL‐087952
Estimation of vascular properties using noninvasive measurements and a mathematical model of the systemic arteries
Authors: Rose William C. , Edwards Jonathan W. , Johnson David A. , Stillabower Michael E. , Edwards David G. 
Published: June 2021

The estimation of vascular properties is useful for physiological and clinical assessment.PURPOSEThe purpose of this study was to estimate vascular properties under different physiological conditions using noninvasive measurements and a mathematical model of the arterial circulation.METHODSBlood pressure waveforms were recorded by applanation tonometry at the radial and femoral arteries in 21 individuals under control conditions, during a cold pressor test, and after administration of sublingual nitroglycerin. A mathematical model of the arterial circulation was used to predict femoral artery pressure wave from measured radial artery pressure wave. Three model parameters were adjusted to minimize the difference between estimated and measured femoral pressure.RESULTSResistance vessel diameter profile, arterial resistance, blood volume, and aortic pressure depended significantly on the perturbation given (ANOVA, p<0.01), but cardiac output and total arterial compliance did not (p>0.05). The root mean square difference between the predicted and measured femoral waveforms was 6.8 ± 4.5 mmHg.CONCLUSIONSVascular mechanical properties estimated under different conditions had realistic values. Some but not all estimated quantities showed significant variation when physiological conditions were altered.Supported by the University of Delaware Research Foundation.
Age‐related impairment in endothelium‐dependent dilation is related to diminished sirT deacetlylase expression and increased eNOS acetylation
Authors: Magerko Katherine Ann , Seals Douglas R , Durrant Jessica R , Lawson Brooke R , Lesniewski Lisa A , Donato Anthony J 
Published: June 2021

Aging impairs vascular endothelial function through diminished nitric oxide (NO) availability. The cellular deacetylases family, sirT, modulates endothelium‐dependent dilation (EDD) and NO availability via regulation of endothelial NO synthase (eNOS) acetylation/activation. Acetylcholine (Ach)‐induced peak EDD was lower in isolated femoral arteries of old (O: 30 mo, n = 12) vs. young (Y: 6 mo, n = 14) B6D2F1 mice (O: 85 ± 1%, Y: 95 ± 1%, P < 0.001) and was mediated by reduced NO availability related to lower aortic protein expression of sirT 1 & 3 (O: 0.6 ± 0.1, Y: 1.0 ± 0.1 sirT 1/GAPDH, P < 0.05; O: 0.5 ± 0.1, Y: 1.0 ± 0.3 sirT 3/GAPDH, P = 0.05). Aortic eNOS expression did not differ with age (O: 1.17 ± 0.11, Y: 1.00 ± 0.06, eNOS/GAPDH, P = 0.2), but acetylated eNOS was higher in old (O: 6.40 ± 4.64, Y: 1.00 ± 0.30 I.P. acetylated eNOS, P < 0.05). Incubation with SIRTINOL, a sirT inhibitor, reduced peak EDD and abolished age differences (O: 41 ± 8%, Y: 38 ± 4%, P = 0.4). Reductions in peak EDD with SIRTINOL + L‐NAME, an eNOS inhibitor, did not differ (O: 2 ± 5%, Y: 7 ± 3%, P = 0.5). Endothelium‐independent dilation (EID; sodium nitroprusside) was not altered with age (P = 0.8). In older (64 ± 1 yrs, n = 18) vs. young (25 ± 1 yrs, n = 14) healthy humans, Ach‐induced forearm EDD was impaired (P = 0.01) and associated with reduced sirT 1 protein expression in brachial artery endothelial cells (immunofluorescence; O: 0.37 ± 0.03, Y: 0.50 ± 0.05, sirT 1/HUVEC, P < 0.05), whereas EID did not differ (P = 0.9). Changes in sirT may play an important role in vascular endothelial dysfunction with aging.NIH AG029337, AG033755, AG013038