bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary fat intake in Europe
Authors: Elmadfa Ibrahim , Nowak Verena , Kornsteiner‐Krenn Margit 
Published: June 2021

The quantity and quality of fat have a major impact on coronary heart diseases (CHD), which contribute to morbidity and mortality. The objective of this study was to analyze fat intake data from the European Union. Data were collected in the context of the European Nutrition and Health Report (ENHR) 2009. Total fat intake (TFI) data were available from 22 countries, saturated fatty acids (SFA) from 18, and monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) from 15 countries.There was a great difference in the TFI ranging from 28.4 (Portugal, men) to 47.2 (Greece, women) %E. TFI of only 5 countries were in agreement with the FAO/WHO 2008 intake goals. Hence, only Portugal had a TFI < 30%E and the Czech Republic, Denmark, Finland, and Sweden < 35%E; Germany, Ireland, Italy, and Poland were at the borderline (~ 35%E). The remaining 11 countries had high TFI > 35%E. For SFA only Portugal reached the recommendation of < 10%E. The intake of MUFA ranged from 10.9 to 22.9%E. The PUFA intake varied from 4.7 to 9.2 %E. Only 7 countries showed a higher intake (> 6%E) which is targeted to prevent CHD.In summary, the majority of the countries showed an unfavorably high total fat (> 35%E) and SFA intake, whereas the PUFA intake should be increased. There is potential to improve the quantity and quality of fat intake.The ENHR 2009 was funded by the EC under the Public Health Program 2006, agreement nr. 2006128.
Portal Vein Ligation Accelerates Tumor Growth in Ligated, but not Contralateral Lobes
Authors: Sakai Nozomu , Clarke Callisia N , Tevar Amit D , Edwards Michael J , Lentsch Alex B 
Published: June 2021

BACKGROUNDPortal vein embolization (PVE) is a widely accepted procedure to induce hypertrophy of contralateral lobes prior to extensive liver resection. However, the manner in which PVE alters liver and/or tumor growth is unknown. We investigated the mechanisms of liver growth after portal vein ligation (PVL) as compared to partial hepatectomy (PH), and evaluated these effects on the growth of liver tumors.METHODSMice were subjected to PVL, PH, or sham surgery. Liver histology, activation of transcription factors, and expression of cytokines and growth factors involved in liver regeneration were evaluated. In some experiments, murine colorectal carcinoma cells were injected via the portal vein.RESULTSLiver regeneration of non‐ligated lobes after PVL was similar to that occurring after PH and was accompanied by similar changes in transcription factors, cytokines and growth factors. In comparison, ligated lobes had greatly increased activation of transcription factors, cytokines and growth factors, showed no proliferation and atrophied. When liver tumors were measured, the ligated lobes showed significantly greater tumor growth than non‐ligated lobes or PH.CONCLUSIONSThe data suggest that PVL results in acceleration of tumor growth in ligated but not contralateral lobes. Liver regeneration is similar in non‐ligated lobes and PH.
The role of mechanical forces in stem cell differentiation to vascular lineage
Authors: Nikmanesh Maria , Shi Zhong‐Dong , Tarbell John M 
Published: June 2021

The overall goal of our study is to evaluate the role of wall shear stress (WSS) and cyclic strain (CS) on the development of vascular cells from mouse embryonic stem cells (MESCs) differentiated in vitro. The aim is to generate an early marker of endothelial cells (ECs), platelet endothelial cell adhesion molecule‐1 (PECAM‐1+ cells), from ESCs differentiated in vitro, subjecting these cells to WSS and CS, and analyzing the functionality of these cells by testing their permeability to solutes of varying molecular weight and expression of key components of the inter‐endothelial tight junctions. If we are successful, the results will make an important contribution to vascular tissue regeneration.Results1) We have been able to sort PECAM‐1+ cells from the rest of the MESC culture; 2) The endothelial‐like cells display border staining for VE‐cadherin; 3) ES‐derived endothelial cells form multidimensional tubular structures on Matrigel; and 4) ES‐derived endothelial cells uptake acetylated low density lipoprotein (ac‐LDL).ConclusionOur sorting for PECAM‐1+ cells has been successful and these cells express hallmark of the endothelial phenotypes. We can use these cells for evaluating the role of WSS and CS on their development into mature endothelial cells.Supported by: NIH/NHLBI 1 RO1 HL086543‐01 and State of New York Department of Health (NYSTEM)
Nanoparticles attenuate P‐glycoprotein function in A549 cells
Authors: Salomon Johanna J , Ehrhardt Carsten 
Published: June 2021

P‐glycoprotein (P‐gp) is a well characterised membrane transporter relevant to drug disposition and multi‐drug resistance in cancer. Here we studied the effect of nanoparticles (NP) on uptake and release of the P‐gp substrate, rhodamine 123 (Rh123), in human alveolar epithelial cells (A549).For uptake experiments cell culture medium was removed and replaced with Rh123 (10 μM) in Krebs‐Ringer Buffer (KRB) also containing the different NP formulations (see below). In release studies cells were loaded with Rh123 for 30 min and subsequent release of the substrate from the cells into fresh KRB with NP was measured. NP studied were either carboxylated (CNP, 100 nm, −50 mV), amino‐modified (ANP, 50 nm, 60 mV) or latex‐based (LNP, 100 nm, −50 mV). In addition, selected pharmacological inhibitors of P‐gp function were investigated.Rh123 uptake was increased in the presence of CNP and LNP in a time‐dependent manner. No effect of ANP on Rh123 uptake was observed. The release of Rh123, however, was significantly (p<0.05) attenuated in the presence of CNP and ANP, but not LNP.Our findings suggest that nanomaterials interact with membrane transporter function in a complex fashion and hence, might influence disposition of xenobiotics as well as endogenous substrates.This work was supported by a Strategic Research Cluster grant (07/SRC/B1154) from Science Foundation Ireland.
Morphine regulates dopaminergic system via miR‐133b and Pitx3 in zebrafish embryos
Authors: Sanchez‐Simon Fatima Macho , Zeng Yan , Loh Horace H. , Lae Ping‐Yee , Rodriguez Raquel E. 
Published: June 2021

Current studies were initiated to address whether morphine could affect neural development via its regulation of miRs. By microarray analysis, we show that morphine decreases miR‐133b expression. miR‐133b targets Pitx3, a transcription factor that activates genes involved in dopaminergic differentiation, such as TH and DRD1. Exposure of 24 hpf zebrafish embryos to morphine resulted in a decrease in miR‐133b and an increase in Pitx3, TH and DRD1 mRNA levels. Injection of the 3′UTR region of Pitx3 did not alter miRNA‐133b expression, and increased the expression of Pitx3, TH and DRD1. When ZfMOR (zebrafish mu opioid receptor) was silenced in embryos via morpholino injection, miR‐133b level increased and the expression of Pitx3 decreased. Parallel morphine regulation of miR‐133b level can be observed in primary neuron cultures from rat hippocampus. Embryo treatment with MAPK inhibitors U0126 or PD98059 increased miR‐133b level and decreased Pitx3 level. These studies suggest that the dopaminergic system development could be controlled by morphine‐mediated activation of ZfMOR. As the dopaminergic system is essential in the development of addiction, our findings contribute to the better understanding of the pathway that leads to addictive disorders.Research funded by the Spanish MEC (SAF2007‐61581) and the NIH, USA (DA007339).
Fiber capillary regression and endothelial cell apoptosis in the soleus muscle of hindlimb unloaded rats: role of angiogenic regulators
Authors: Fujino Hidemi , Kondo Hiroyo , Murakami Shinichiro , Nagatomo Fumiko , Takeda Isao , Ishihara Akihiko , Roy Roland R 
Published: June 2021

The aim of present study was to determine the changes in the 3‐D architecture of the intramuscular endothelial networks and the responses of angiogenic and its inhibitory factors in atrophied soleus muscles. The hindlimbs of male Wistar rats were unloaded for 2 weeks by tail suspension. The endothelial network of soleus muscle was visualized by confocal microscopy. Apoptotic endothelial cells were identified by DNA fragmentation (TUNEL) using immunofluorescent staining. The mRNA levels of angiogenic factors (VEGF, KDR, Flt‐1, Ang‐1, Ang‐2, Tie‐2, HIF‐1 alpha) and inhibitory factors (TSP‐1 and caspase‐3) were determined by TaqMan probe‐based real‐time PCR. Chronic unloading resulted in a decrease in the number of anastomoses and tortuosity, appearance of TUNEL‐positive endothelial cells, a decrease in angiogenic factor mRNA, an increase in the Ang‐2‐to‐Ang‐1 ratio, and an increase in angiogenic inhibitor mRNA. The data suggest vasculature destabilization with chronic unloading and indicate that both a decrease in angiogenic factors and increase in angiogenic inhibitory factors play a role in this process.Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, no. 19300196.
Blood pressure response during recovery after moderate leg cycling exercise: the role of carotid baroreflex control
Authors: Yamada Masako , Endo Masako Y , Fukuba Yoshiyuki 
Published: June 2021

This study was to determine the characteristics of the carotid baroreflex (CBR) control of central and peripheral hemodynamics during the post‐exercise hypotension (PEH) using the neck chamber (NC) technique. 16 healthy young male subjects (age: 27+/−1 yr) undertook 60‐min moderate cycle ergometer exercise, followed by 30‐min of supine rest. Subjects remained at supine rest for a further 60‐min. During pre‐ and post‐exercise, the CBR control of the central (HR) and peripheral (vascular conductance, VC in popliteal and brachial arteries as the previously active and inactive muscles, respectively) circulations was evaluated using 5‐s periods of neck suction and pressure (−60, −40, 0, or +40 Torr). Eight subjects (responder (RE) group) showed substantial PEH during recovery from exercise (ΔBP, ~ −5 Torr; p<0.05). The other subjects (non‐RE group) did not exhibit the PEH but showed a significant post‐exercise CBR argumentation in HR, BP and VC, especially in response to −40, not +40 Torr. However, in RE group, pre‐ and post‐exercise CBR function was unchanged during PEH. Consequently, the subjects without PEH exhibit an augmented CBR control to central and peripheral hemodynamics following exercise ‐ especially to a high fluctuation of BP to the operating point. In conclusion, CBR control is not changed during PEH, while some normotensive individuals do not show the PEH.(Support: JSPS‐KAKENHI, 20700526, 21370111)
Dietary fat‐specific adaptations of mitochondrial function in skeletal muscle and liver of C57Bl/6J mouse
Authors: Ciapaite Jolita , van den Berg Sjoerd A.A. , Nicolay Klaas , van Dijk Ko Willems , Jeneson Jeroen A.L. 
Published: June 2021

The aim of this study was to asses the effects of high‐fat diets with different fatty acid composition on the function of skeletal muscle and liver mitochondria. 12 week old male C57Bl/6J mice were fed either low‐fat diet (LFD, 10 kcal% fat from palm oil) or one of three high‐fat diets (HFD, 45 kcal% fat from either lard (L), palm oil (PO) or palm oil supplemented with tristearin (POS) ad libitum for 5 weeks (n=8 per diet group)). The content of stearate was similar in HFD(L) and HFD(POS) (15.0% and 13.9%, respectively). Mitochondrial function was assessed using high‐resolution respirometry. After 5 weeks of diet body weight was ~20% higher (p<0.001) in all three HFD‐fed groups compared to LFD‐fed controls. The trend of HFD effects was comparable in skeletal muscle and liver mitochondria. Maximal ADP‐stimulated (state 3) oxygen consumption rates were similar in all diet groups when pyruvate plus malate or glutamate plus malate were used as the oxidizible substrates. HFD(L) feeding had no effect on palmitoyl‐L‐carnitine and stearoyl‐L‐carnitine‐driven oxygen consumption rate in state 3, while HFD(PO) and HFD(POS) feeding led to a significantly higher oxygen consumption rates compared to controls. This observation suggests that fatty acid composition of the dietary fat is important determinant in the HFD feeding‐induced mitochondrial adaptations.This work was financed by the Netherlands Consortium for Systems Biology.
Laminar Shear Stress Up‐regulates Endothelial CD73 Expression by Activating Calmodulin‐dependent Kinase Kinase
Authors: Li Weidong , Ohta Masanori , Nandedkar Sandhya , Fan Fan , Jo Hanjoong , Miura Hiroto 
Published: June 2021

Endothelial cell (EC) surface CD73, ecto‐5′ nucleotidase, extracellularly metabolizes AMP to adenosine, a potent anti‐inflammatory molecule. Since athero‐protective high laminar shear stress (LS) rises intracellular calcium levels and induces the release of adenine nucleotides in ECs, we hypothesized that LS increases CD73 expression by activating calmodulin‐dependent kinase kinase (CaMKK), leading to the extracellular production of adenosine in ECs.Cultured human coronary artery ECs were subjected to static, LS (15 dyne/cm2), or oscillatory shear (OS; ± 5 dyne/cm2) condition for 24 hours. Real‐time PCR showed that LS increased CD73 mRNA expression (2.1±0.3‐fold increase vs. static condition, p<0.05, n=10–17), whereas OS unchanged the mRNA expression (0.9±0.2 fold, p=ns, n=6). STO‐609 (a CaMKK inhibitor, 10μg/ml) suppressed LS‐induced increase in CD73 mRNA expression (1.1±0.2 fold, n=5). In contrast, U‐73122 (a phospholipase C inhibitor, 1μM) and KN‐62 (a calcium/calmodulin‐dependent kinase inhibitor, 10 μM) had no inhibitory effect (2.7±0.5 fold, n=3 and 2.1±0.3, n=8). HPLC analysis revealed that LS resulted in the accumulation of adenosine in the conditioned medium.These results indicate that LS elicits the generation of extracellular adenosine from ECs by upregulating CD73 expression via activating CaMKK. Thus, CD73 might contribute to the athero‐protective effects of LS in ECs.
Human arterial endothelial cells develop a mesenchymal phenotype with aging
Authors: Fleenor Bradley S , Marshall Kurt D , Rippe Catarina , Seals Douglas R 
Published: June 2021

Large elastic arteries stiffen with aging and this leads to multiple cardiovascular pathologies. Arterial endothelial cells are thought to contribute to this process possibly via age‐associated reductions in nitric oxide production and consequent increases in smooth muscle cell (SMC) tone. Here we test the novel hypothesis that these cells also may contribute by changing to a mesenchymal phenotype featuring development of fibroblast/SMC‐like migratory and secretory (synthetic) properties. Human aortic endothelial cells were studied at early (27.0 ± 0.54, mean±SE), intermediate (37.0 ± 0.59) and late (45.0 ± 1.18) population doublings (PDLs), representing “young” (Y), “middle‐aged” (MA) and “old” (O) cells, respectively. Smooth muscle alpha actin (SMαA) protein expression (western blots) was greater in MA and O cells compared with Y (MA: 1.30 ± 0.05, O: 1.28 ± 0.05 vs. Y: 1.00 ± 0.05 AU; P < 0.05). Moreover, mean expression of type I collagen increased progressively with aging (Y: 1.00 ± 0.31 vs. MA: 1.40 ± 0.30 vs. O: 2.70 ± 0.43 AU; Y vs. O and MA vs. O, P < 0.05). These preliminary data are consistent with the hypothesis that replicative aging induces a vascular endothelial to mesenchymal cell transition resulting in development of a synthetic, migratory phenotype that may contribute to intimal thickening and increases in stiffness of large elastic arteries.NIH AG013038 and HL007822, Swedish Research Council
Flow responses of human blood outgrowth endothelial cells adhered to bioartificial tissue
Authors: Tranquillo Robert T , Ahmann Katherine A 
Published: June 2021

Blood outgrowth endothelial cells (BOECs) are isolated by outgrowth of circulating progenitor cells from a patient blood sample and thus could provide a source of autologous endothelial cells for tissue‐engineered vascular grafts. To examine the suitability of these cells for use in vascular tissue engineering, late outgrowth endothelial cells isolated from human peripheral blood were seeded on tissue constructs formed from fibrin remodeled by entrapped neonatal human dermal fibroblasts (NHDFs). BOECs adhered to this surface and remained adherent when exposed to laminar shear flow of cell culture medium, at shear stresses of 15 dynes/cm2.We have examined shear stress effects on human BOEC activation state, by comparing VCAM‐1, ICAM‐1, and Thrombomodulin (TM) expression after activation with TNF‐α. These markers were chosen due to their reported response to changes in shear stress, as well as their implication in endothelial cell activation. BOECs seeded on collagen‐coated slides and tissue constructs were statically cultured or exposed to 5–15 dynes/cm2 shear stress for 24 hours. Expression of the activation markers was altered compared to static controls, while the cell densities did not vary significantly. TM expression was elevated by shear stress, while VCAM‐1 and ICAM‐1 showed decreased expression. These results illustrate the potential utility for BOECs in vascular tissue engineering, as not only do the cells adhere to fibrin‐based tissue constructs and remain adherent under physiological shear stress, they are also responsive to shear stress signaling. Funding from NIH R01 HL083880 (to RTT).
Inaccuracies introduced by single width blood pressure cuffs
Authors: Andrews Jeffrey , DeWitt Blake , Czerwien Terry , Bijelic Miro , Latman Neal S. 
Published: June 2021

Blood pressure (BP) cuff dimensions directly affects accuracy of BP measurements. For accurate BP measurements the width of the cuff must be proportional to arm circumference. A cuff that is too narrow results in falsely high BP values, and a cuff that is too wide results in falsely low values. Some BP standards permit a single cuff regardless of arm circumference.The purpose of this study was to evaluate whether 12 cm single width cuffs currently permitted by the British Hypertension Society (BHS) standard are sufficiently accurate.Each of 101 subjects was tested sequentially with both a single and a proportional width cuff in random order. Auscultatory BP was determined by 2 observers using a double binaural stethoscope.The single width cuff BP failed the Association for the Advancement of Medical Instrumentation and BHS standards for clinically acceptable accuracy. The magnitude of failures ranged from a mean of 6.6 to 11.3 mmHg.In conclusion, this could result in a significant number of people being misdiagnosed and mistreated for hypertension. Therefore, to avoid “cuff hypertension” and “cuff hypotension”, the cuff width should be proportional to arm circumference.
Hyperactivity and Associated Memory Deficit in Hyper‐ and Hypo‐tensive Mice
Authors: Stewart John Michael , Kamper Joel , Hartman Richard E , Goyal Ravi , Longo Lawrence D 
Published: June 2021

ObjectiveThe development of hypertension can lead to a vast array of physiological and behavioral complications. In mice, we tested the hypothesis that hyper‐ and hypo‐tension is associated with significant alterations in anxiety, activity, motor coordination, and spatial learning.MethodsTo test activity levels we used the open field test, anxiety levels using the standard elevated zero maze, motor coordination using a standard Rotarod testing setup, and spatial learning with the Morris water maze.ResultsWe found hypertensive mice had significantly increased activity levels compared to controls. Females showed statistically more evidence of anxiety than males on the elevated zero maze; however, there was no significant difference between blood pressure groups. When tested on the rotarod, hypotensive mice fell off much quicker than the other groups. In the water maze, both hypo‐ and hypertensive mice had deficits in spatial learning/memory performance, with hypotensive mice performing the worst.ConclusionsSpatial learning ability was significantly reduced with changes in blood pressure, especially with hypotension. Hypertension was associated with hyperactivity. We speculate that alterations in cerebral hemodynamics may be an underlying cause.
Risk factors for dvt of the lower extremities
Authors: Leci‐Tahiri Laura O , Bajraktari Sadri , Tahiri Afrim 
Published: June 2021

BackgroundDVT and her two complications, pulmonary emboli and post‐thrombotic syndrome are the main cause of intrahospital mortality and chronic morbidity. Studies says that there are around 100 to 160 new cases on 100 thousand habitans per year. For Kosova it means 2000 to 3000 new cases per year.The aimIt is the aim of the paper to analyse the epidemiology of the DVT, etiology and risk factors among the patients hospitalized at the Vascular Surgery Department.ResultsDuring two years study period, september 2002‐september 2004, at the Vascular Surgery Department of the University Clinical Center of Kosova due to DVT of the lower extremities were 194 patients or 45.64%. There was no difference between sex. The mean age was 49.92 years. From 204 extremities, DVT was localized on 85 extremities to the right (41.67%) and 119 extremities to the left (58.33%). Risk factors were presented at 145 patients. Surgery was often presented as risk factor, at 25 patients (12.89%); post‐partal state at 13 patients (6.70%), pregnancy 10 patients (5.15%), malignancy 10 patients (5.15%). Mean age of patients with DVT and malignancy was 54.4 years.ConclusionDVT is disease that is very hard to diagnose. First step is always to determine risk factors. Second step is to determine rate of clinical probability for DVT.
CaMKII Phosphorylation of RyR2 Mediates Heart Failure Development
Authors: van Oort Ralph Jeroen , Respress Jonathan L , De Almeida Angela C , Sarma Satyam , Li Na , Skapura Darlene G , Wehrens Xander H 
Published: June 2021

Abnormal regulation of cardiac ryanodine receptor RyR2 by Ca2+/calmodulin‐dependent protein kinase 2 (CaMKII) has been identified as a potential cause of Ca2+ leakage and contractile dysfunction in heart failure. To test the hypothesis that CaMKII phosphorylation of RyR2 is crucial for heart failure development, we generated RyR2 knockin mice in which the CaMKII phosphorylation site S2814 is either mutated into aspartate (SD) to mimic CaMKII phosphorylation, or into alanine (SA) to prevent phosphorylation. Echocardiography revealed a decrease in cardiac function in SD mice at 12 months of age. Both WT and SA mice were subjected to transverse aortic constriction (TAC) to induce pressure overload. At 8 weeks after TAC, SA mice displayed a similar hypertrophic response as WT TAC mice. At 16 weeks after TAC, however, ejection fraction was significantly higher in SA mice compared to WT TAC mice, indicating an inhibition of heart failure development. This rescue effect was further verified by a lower lung‐weight‐to‐tibia‐length ratio and a decrease in expression levels of cardiac stress genes in SA mice. Furthermore, Ca2+ imaging in isolated cardiomyocytes demonstrated a decreased SR Ca2+ leak in SA TAC mice. Our results demonstrate that CaMKII phosphorylation of RyR2 is both sufficient and necessary for heart failure development.R.J.v.O. is recipient of the APS Postdoctoral Fellowship in Physiological Genomics