bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats
Authors: Serizawa Ken-ichi , Yogo Kenji , Aizawa Ken , Tashiro Yoshihito , Ishizuka Nobuhiko 
Published: November 2011

Abstract

Background
Nicorandil, an anti-angina agent, reportedly improves outcomes even in angina patients with diabetes. However, the precise mechanism underlying the beneficial effect of nicorandil on diabetic patients has not been examined. We investigated the protective effect of nicorandil on endothelial function in diabetic rats because endothelial dysfunction is a major risk factor for cardiovascular disease in diabetes.

Methods
Male Sprague-Dawley rats (6 weeks old) were intraperitoneally injected with streptozotocin (STZ, 40 mg/kg, once a day for 3 days) to induce diabetes. Nicorandil (15 mg/kg/day) and tempol (20 mg/kg/day, superoxide dismutase mimetic) were administered in drinking water for one week, starting 3 weeks after STZ injection. Endothelial function was evaluated by measuring flow-mediated dilation (FMD) in the femoral arteries of anaesthetised rats. Cultured human coronary artery endothelial cells (HCAECs) were treated with high glucose (35.6 mM, 24 h) and reactive oxygen species (ROS) production with or without L-NAME (300 µM), apocynin (100 µM) or nicorandil (100 µM) was measured using fluorescent probes.

Results
Endothelial function as evaluated by FMD was significantly reduced in diabetic as compared with normal rats (diabetes, 9.7 ± 1.4%; normal, 19.5 ± 1.7%; n = 6-7). There was a 2.4-fold increase in p47phox expression, a subunit of NADPH oxidase, and a 1.8-fold increase in total eNOS expression in diabetic rat femoral arteries. Nicorandil and tempol significantly improved FMD in diabetic rats (nicorandil, 17.7 ± 2.6%; tempol, 13.3 ± 1.4%; n = 6). Nicorandil significantly inhibited the increased expressions of p47phox and total eNOS in diabetic rat femoral arteries. Furthermore, nicorandil significantly inhibited the decreased expression of GTP cyclohydrolase I and the decreased dimer/monomer ratio of eNOS. ROS production in HCAECs was increased by high-glucose treatment, which was prevented by L-NAME and nicorandil suggesting that eNOS itself might serve as a superoxide source under high-glucose conditions and that nicorandil might prevent ROS production from eNOS.

Conclusions
These results suggest that nicorandil improved diabetes-induced endothelial dysfunction through antioxidative effects by inhibiting NADPH oxidase and eNOS uncoupling.
The use of plasma aldosterone and urinary sodium to potassium ratio as translatable quantitative biomarkers of mineralocorticoid receptor antagonism
Authors: Eudy Rena J , Sahasrabudhe Vaishali , Sweeney Kevin , Tugnait Meera , King-Ahmad Amanda , Near Kristen , Loria Paula , Banker Mary Ellen , Piotrowski David W , Boustany-Kari Carine M 
Published: November 2011

Abstract

Background
Accumulating evidence supports the role of the mineralocorticoid receptor (MR) in the pathogenesis of diabetic nephropathy. These findings have generated renewed interest in novel MR antagonists with improved selectivity against other nuclear hormone receptors and a potentially reduced risk of hyperkalemia. Characterization of novel MR antagonists warrants establishing translatable biomarkers of activity at the MR receptor. We assessed the translatability of urinary sodium to potassium ratio (Na+/K+) and plasma aldosterone as biomarkers of MR antagonism using eplerenone (Inspra®), a commercially available MR antagonist. Further we utilized these biomarkers to demonstrate antagonism of MR by PF-03882845, a novel compound.

Methods
The effect of eplerenone and PF-03882845 on urinary Na+/K+ and plasma aldosterone were characterized in Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Additionally, the effect of eplerenone on these biomarkers was determined in healthy volunteers. Drug exposure-response data were modeled to evaluate the translatability of these biomarkers from rats to humans.

Results
In Sprague-Dawley rats, eplerenone elicited a rapid effect on urinary Na+/K+ yielding an EC50 that was within 5-fold of the functional in vitro IC50. More importantly, the effect of eplerenone on urinary Na+/K+ in healthy volunteers yielded an EC50 that was within 2-fold of the EC50 generated in Sprague-Dawley rats. Similarly, the potency of PF-03882845 in elevating urinary Na+/K+ in Sprague-Dawley rats was within 3-fold of its in vitro functional potency. The effect of MR antagonism on urinary Na+/K+ was not sustained chronically; thus we studied the effect of the compounds on plasma aldosterone following chronic dosing in SHR. Modeling of drug exposure-response data for both eplerenone and PF-03882845 yielded EC50 values that were within 2-fold of that estimated from modeling of drug exposure with changes in urinary sodium and potassium excretion. Importantly, similar unbound concentrations of eplerenone in humans and SHR rats yielded the same magnitude of elevations in aldosterone, indicating a good translatability from rat to human.

Conclusions
Urinary Na+/K+ and plasma aldosterone appear to be translatable biomarkers of MR antagonism following administration of single or multiple doses of compound, respectively.

Trial Registration
For clinical study reference EE3-96-02-004, this study was completed in 1996 and falls out scope for disclosure requirements.
Clinical study reference A6141115: http://clinicaltrials.gov, http://NIHclinicaltrails.gov; NCTID: NCT00990223
Characteristics of functionalized nano-hydroxyapatite and internalization by human epithelial cell
Authors: Yan-zhong Zhao , Yan-yan Huang , Jun Zhu , Shai-hong Zhu , Zhi-you Li , Ke-chao Zhou 
Published: November 2011

Abstract
Hydroxyapatite is the main inorganic component of biological bone and tooth enamel, and synthetic hydroxyapatite has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of arginine-functionalized and europium-doped hydroxyapatite nanoparticles (Arg-Eu-HAP). The synthesized nanoparticles characterized by transmission electron microscopy, X-ray diffractometry, Fourier transform infrared, and Zeta potential analyzer. Its biological properties with DNA binding, cell toxicity, cell binding and intracellular distribution were tested by agarose gel electrophoresis assay, flow cytometry, and fluorescence microscope and laser scanning confocal microscope. The synthesized Arg-Eu-HAP could effectively bind DNA without any cytotoxicity and be internalized into the cytoplasm and perinuclear of human lung epithelial cells.
One-dimensional silver nanostructures on single-wall carbon nanotubes
Authors: Mercado Eunice , Santiago Steven , Baez Luis , Rivera Daniel , Gonzalez Miguel , Rivera-Ramos Milton E , Leon Madeline , Castro Miguel E 
Published: November 2011

Abstract
We report the synthesis and characterization of one-dimensional silver nanostructures using single-wall carbon nanotubes (SWCNT) as a template material. Transmission electron microscopy and scanning tunneling microscopy are consistent with the formation of a one-dimensional array of silver particles on SWCNT. We observe evidence for the excitation of the longitudinal silver plasmon mode in the optical absorption spectra of Ag-SWCNT dispersions, even in the lowest silver concentrations employed. The results indicate that silver deposits on SWCNT may be candidates for light-to-energy conversion through the coupling of the electric field excited in arrays of plasmonic particles.
Mitigating preventable chronic disease: Progress report of the Cleveland Clinic's Lifestyle 180 program
Authors: Ricanati Elizabeth HW , Golubić Mladen , Yang Dongsheng , Saager Leif , Mascha Edward J , Roizen Michael F 
Published: November 2011

AbstractBackgroundPoor lifestyle choices are key in development and progression of preventable chronic diseases. The purpose of the study was to design and test a program to mitigate the physical and fiscal consequences of chronic diseases.MethodsHere we report the outcomes for 429 participants with one or more chronic conditions, including obesity, hypertension, hyperlipidemia and diabetes mellitus, many of whom had failed traditional disease management programs, who enrolled into a comprehensive lifestyle intervention. The Lifestyle 180 program integrates nutrition, physical activity and stress management interventions and was conducted at the Wellness Institute of the Cleveland Clinic, United States. An intensive 6 week immersion course, with 8 hours of group instruction per week, was followed by 3 follow-up, 4 hour-long sessions over the course of 6 months.ResultsChanges in biometric (weight, height, waist circumference, resting heart rate and blood pressure) and laboratory variables (fasting lipid panel, blood glucose, insulin, hemoglobin A1c, ultra sensitive C-reactive protein) at 6 months were compared with baseline (pre-post analysis). At week 30, biometric and laboratory data were available for 244 (57%) and 299 (70%) participants, respectively. These had a mean ± SD reduction in weight (6.8 ± 6.9 kg, P < 0.001), waist circumference (6.1 ± 7.3 cm, P < 0.001), glucose (4.5 ± 29.6 mg/dL or 0.25 ± 1.64 mmol/L, P = 0.009), triglycerides (26.4 ± 58.5 mg/dL or 0.30 ± 0.66 mmol/L, P < 0.001), low-density lipoprotein cholesterol (LDL) (7.9 ± 25.1 mg/dL or 0.2 ± 0.65 mmol/L, P < 0.001), hemoglobin A1c (HgbA1c) (0.20 ± 0.64%, P = 0.001), insulin (3.8 ± 11 microU/ml or 26.6 ± 76.4 ρmol, P < 0.001) and ultra sensitive C-reactive protein (US - CRP) (0.9 ± 4.8 mg/dL or 7.3 ± 40.2 nmol/L, P = 0.012), an increase in mean high-density lipoprotein cholesterol (HDL) (3.7 ± 8.4 mg/dL or 0.1 ± 0.22, P < 0.001), and decreased use of medications.ConclusionImplementation of a comprehensive lifestyle modification program among adults with common chronic conditions results in significant and clinically meaningful improvements in biometric and laboratory outcomes after 6 months.
Co-Induction of Cyclooxyenase-2 and Early Growth Response Gene (Egr-1) in Spinal Cord in a Clinical Model of Persistent Inflammation and Hyperalgesia
Authors: Dolan Sharron , Hastie Peter , Crossan Claire , Nolan Andrea M 
Published: November 2011

Background: This study characterised the effects of persistent peripheral inflammation of the foot on pain and spinal cord expression of cyclooxygenase-1 and −2 (COX-1 and COX-2) and early growth response gene 1 (Egr-1), known markers of neuronal plasticity, in a clinical model of naturally-occurring inflammatory disease and hyperalgesia in sheep (‘footrot’), before and after routine treatment (parenteral treatment with antibiotics and antiseptic footbathing). The temporal pattern of expression of COX-1, COX-2 and Egr-1 mRNA and protein were analysed using real-time PCR and Western blotting. Results: Animals affected with persistent peripheral inflammation displayed significant hyperalgesia and lameness (a proxy indicator of spontaneous pain) restricted to the inflamed limb. Hyperalgesia and lameness were significantly attenuated 1 day after treatment, and resolved further by day 7 and day 3, respectively. COX-2 but not COX-1, protein expression was up-regulated in spinal cord from lame animals on day 0, before treatment. Following treatment and attenuation of pain behaviours, levels of COX-2 returned to control levels. Significant induction of Egr-1 mRNA and protein were observed in spinal cord from lame animals. Three days after treatment, levels of Egr-1 mRNA returned to control levels, however, Egr-1 protein remained elevated. Conclusion: Elevated levels of spinal COX-2 and Egr-1 protein correlate with the presence of pain and hyperalgesia, and may underlie persistent pain, although a direct causal link has still to be established. Understanding the temporal pattern of expression of key mediators in clinical pain states may lead to better strategies to manage pain.
Importance of local knowledge in plant resources management and conservation in two protected areas from Trás-os-Montes, Portugal
Authors: Carvalho Ana Maria , Frazão-Moreira Amélia 
Published: November 2011

AbstractMany European protected areas were legally created to preserve and maintain biological diversity, unique natural features and associated cultural heritage. Built over centuries as a result of geographical and historical factors interacting with human activity, these territories are reservoirs of resources, practices and knowledge that have been the essential basis of their creation. Under social and economical transformations several components of such areas tend to be affected and their protection status endangered.Carrying out ethnobotanical surveys and extensive field work using anthropological methodologies, particularly with key-informants, we report changes observed and perceived in two natural parks in Trás-os-Montes, Portugal, that affect local plant-use systems and consequently local knowledge. By means of informants' testimonies and of our own observation and experience we discuss the importance of local knowledge and of local communities' participation to protected areas design, management and maintenance. We confirm that local knowledge provides new insights and opportunities for sustainable and multipurpose use of resources and offers contemporary strategies for preserving cultural and ecological diversity, which are the main purposes and challenges of protected areas. To be successful it is absolutely necessary to make people active participants, not simply integrate and validate their knowledge and expertise. Local knowledge is also an interesting tool for educational and promotional programs.
Extrapolation in the analysis of lung aeration by computed tomography: a validation study
Authors: Reske Andreas W , Rau Anna , Reske Alexander P , Koziol Manja , Gottwald Beate , Alef Michaele , Ionita Jean-Claude , Spieth Peter M , Hepp Pierre , Seiwerts Matthias , Beda Alessandro , Born Silvia , Scheuermann Gerik , Amato Marcelo BP , Wrigge Hermann 
Published: November 2011

Abstract
Introduction
Computed tomography (CT) is considered the gold standard for quantification of global or regional lung aeration and lung mass. Quantitative CT, however, involves the exposure to ionizing radiation and requires manual image processing. We recently evaluated an extrapolation method which calculates quantitative CT parameters characterizing the entire lung from only 10 reference CT-slices thereby reducing radiation exposure and analysis time. We hypothesized that this extrapolation method could be further validated using CT-data from pigs and sheep, which have a different thoracic anatomy.

Methods
We quantified volume and mass of the total lung and differently aerated lung compartments in 168 ovine and 55 porcine whole-lung CTs covering lung conditions from normal to gross deaeration. Extrapolated volume and mass parameters were compared to the respective values obtained by whole-lung analysis. We also tested the accuracy of extrapolation for all possible numbers of CT slices between 15 and 5. Bias and limits of agreement (LOA) were analyzed by the Bland-Altman method.

Results
For extrapolation from 10 reference slices, bias (LOA) for the total lung volume and mass of sheep were 18.4 (-57.2 to 94.0) ml and 4.2 (-21.8 to 30.2) grams, respectively. The corresponding bias (LOA) values for pigs were 5.1 (-55.2 to 65.3) ml and 1.6 (-32.9 to 36.2) grams, respectively. All bias values for differently aerated lung compartments were below 1% of the total lung volume or mass and the LOA never exceeded ± 2.5%. Bias values diverged from zero and the LOA became considerably wider when less than 10 reference slices were used.

Conclusions
The extrapolation method appears robust against variations in thoracic anatomy, which further supports its accuracy and potential usefulness for clinical and experimental application of quantitative CT.
Physiological responses to self-induced burrowing and metabolic rate depression in the ocean quahogArctica islandica
Authors: Strahl Julia , Brey Thomas , Philipp Eva E. R. , Thorarinsdóttir Gudrun , Fischer Natalie , Wessels Wiebke , Abele Doris 
Published: November 2011

SUMMARYArctica islandica is the longest-lived non-colonial animal found so far, and reaches individual ages of 150 years in the German Bight (GB) and more than 350 years around Iceland (IC). Frequent burrowing and physiological adjustments to low tissue oxygenation in the burrowed state are proposed to lower mitochondrial reactive oxygen species (ROS) formation. We investigated burrowing patterns and shell water partial pressure of oxygen (PO2) in experiments with live A. islandica. Furthermore, succinate accumulation and antioxidant defences were recorded in tissues of bivalves in the normoxic or metabolically downregulated state, as well as ROS formation in isolated gills exposed to normoxia, hypoxia and hypoxia/reoxygenation. IC bivalves burrowed more frequently and deeper in winter than in summer under in situ conditions, and both IC and GB bivalves remained burrowed for between 1 and 6 days in laboratory experiments. Shell water PO2 was &lt;5 kPa when bivalves were maintained in fully oxygenated seawater, and ventilation increased before animals entered the state of metabolic depression. Succinate did not accumulate upon spontaneous shell closure, although shell water PO2 was 0 kPa for over 24 h. A ROS burst was absent in isolated gills during hypoxia/reoxygenation, and antioxidant enzyme activities were not enhanced in metabolically depressed clams compared with normally respiring clams. Postponing the onset of anaerobiosis in the burrowed state and under hypoxic exposure presumably limits the need for elevated recovery respiration upon surfacing and oxidative stress during reoxygenation.
Patterns of coral ecological immunology: variation in the responses of Caribbean corals to elevated temperature and a pathogen elicitor
Authors: Palmer Caroline V. , McGinty Elizabeth S. , Cummings David J. , Smith Stephanie M. , Bartels Erich , Mydlarz Laura D. 
Published: November 2011

SUMMARY
Disease epizootics are increasing with climatic shifts, yet within each system only a subset of species are identified as the most vulnerable. Understanding ecological immunology patterns as well as environmental influences on immune defenses will provide insight into the persistence of a functional system through adverse conditions. Amongst the most threatened ecosystems are coral reefs, with coral disease epizootics and thermal stress jeopardizing their survival. Immune defenses were investigated within three Caribbean corals, Montastraea faveolata, Stephanocoenia intersepta and Porites astreoides, which represent a range of disease and bleaching susceptibilities. Levels of several immune parameters were measured in response to elevated water temperature and the presence of a commercial pathogen-associated molecular pattern (PAMP) – lipopolysaccharide (LPS) – as an elicitor of the innate immune response. Immune parameters included prophenoloxidase (PPO) activity, melanin concentration, bactericidal activity, the antioxidants peroxidase and catalase, and fluorescent protein (FP) concentration. LPS induced an immune response in all three corals, although each species responded differently to the experimental treatments. For example, M. faveolata, a disease-susceptible species, experienced significant decreases in bactericidal activity and melanin concentration after exposure to LPS and elevated temperature alone. Porites astreoides, a disease-resistant species, showed increased levels of enzymatic antioxidants upon exposure to LPS independently and increased PPO activity in response to the combination of LPS and elevated water temperature. This study demonstrates the ability of reef-building corals to induce immune responses in the presence of PAMPs, indicating activation of PAMP receptors and the transduction of appropriate signals leading to immune effector responses. Furthermore, these data address the emerging field of ecological immunology by highlighting interspecific differences in immunity and immunocompetences among Caribbean corals, which are reflected in their life-history characteristics, disease susceptibilities and bleaching-induced mortality.
Apnea stimulates the adaptive response to oxidative stress in elephant seal pups
Authors: Vázquez-Medina José Pablo , Zenteno-Savín Tania , Tift Michael S. , Forman Henry Jay , Crocker Daniel E. , Ortiz Rudy M. 
Published: November 2011

SUMMARY
Extended breath-hold (apnea) bouts are routine during diving and sleeping in seals. These apneas result in oxygen store depletion and blood flow redistribution towards obligatory oxygen-dependent tissues, exposing seals to critical levels of ischemia and hypoxemia. The subsequent reperfusion/reoxygenation has the potential to increase oxidant production and thus oxidative stress. The contributions of extended apnea to oxidative stress in adapted mammals are not well defined. To address the hypothesis that apnea in seals is not associated with increased oxidative damage, blood samples were collected from northern elephant seal pups (N=6) during eupnea, rest- and voluntary submersion-associated apneas, and post-apnea (recovery). Plasma 4-hydroxynonenal (HNE), 8-isoprostanes (8-isoPGF2α), nitrotyrosine (NT), protein carbonyls, xanthine and hypoxanthine (HX) levels, along with xanthine oxidase (XO) activity, were measured. Protein content of XO, superoxide dismutase 1 (Cu,ZnSOD), catalase and myoglobin (Mb), as well as the nuclear content of hypoxia inducible factor 1α (HIF-1α) and NF-E2-related factor 2 (Nrf2), were measured in muscle biopsies collected before and after the breath-hold trials. HNE, 8-iso PGF2α, NT and protein carbonyl levels did not change among eupnea, apnea or recovery. XO activity and HX and xanthine concentrations were increased at the end of the apneas and during recovery. Muscle protein content of XO, CuZnSOD, catalase, Mb, HIF-1α and Nrf2 increased 25–70% after apnea. Results suggest that rather than inducing the damaging effects of hypoxemia and ischemia/reperfusion that have been reported in non-diving mammals, apnea in seals stimulates the oxidative stress and hypoxic hormetic responses, allowing these mammals to cope with the potentially detrimental effects associated with this condition.