bluuebunny/crossref_metadata_2025 huggingface dataset:
Imatinib attenuates monocrotaline pulmonary hypertension and has potent vasodilator activity in pulmonary and systemic vascular beds in the rat
Authors: Pankey Edward A. , Thammasiboon Supat , Lasker George F. , Baber Syed , Lasky Joseph A. , Kadowitz Philip J.
Published: August 2013

Cardiovascular responses to the tyrosine kinase inhibitor imatinib were investigated in the rat. Intravenous injections of 0.3–30 mg/kg imatinib produced small decreases in pulmonary arterial pressure, larger dose-dependent decreases in systemic arterial pressure, and no change or small increases in cardiac output, suggesting that the systemic vasodilator response is more pronounced under baseline conditions. When pulmonary arterial pressure was increased with U-46619 or Nω-nitro-l-arginine methyl ester (l-NAME), intravenous injections of imatinib produced larger dose-dependent decreases in pulmonary arterial pressure. Imatinib attenuated the acute hypoxic pulmonary vasoconstrictor response. Vasodilator responses to imatinib were not inhibited by meclofenamate, glybenclamide, or rolipram, suggesting that cyclooxygenase, ATP-sensitive K+(KATP) channels, and cAMP were not involved in mediating the response. In a 21-day prevention study, imatinib treatment (50 mg/kg ip) attenuated the increase in pulmonary arterial pressure, right ventricular hypertrophy, and small vessel remodeling induced by monocrotaline. Imatinib reduced PDGF receptor phosphorylation and PDGF-stimulated thymidine incorporation in rat pulmonary artery smooth muscle cells. These data suggest that the beneficial effect of imatinib in pulmonary hypertension may involve inhibition of PDGF tyrosine kinase receptor-mediated effects on smooth muscle cell proliferation and on vasoconstrictor tone. These results indicate that imatinib has nonselective vasodilator activity in the pulmonary and systemic vascular beds similar to the Rho kinase inhibitor fasudil and the calcium entry antagonist isradipine. The present results are consistent with the hypothesis that imatinib may inhibit a constitutively active tyrosine kinase vasoconstrictor pathway in the pulmonary and systemic vascular beds in the rat.
Identification of small juvenile stem cells in aged bone marrow and their therapeutic potential for repair of the ischemic heart
Authors: Igura Koichi , Okada Motoi , Kim Ha Won , Ashraf Muhammad
Published: August 2013

Stem cell-mediated cardiac regeneration is impaired with age. In this study, we identified a novel subpopulation of small juvenile stem cells (SJSCs) isolated from aged bone marrow-derived stem cells (BMSCs) with high proliferation and differentiation potential. SJSCs expressed mesenchymal stem cell markers, CD29+/CD44+/CD59+/CD90+, but were negative for CD45−/CD117− as examined by flow cytometry analysis. SJSCs showed higher proliferation, colony formation, and differentiation abilities compared with BMSCs. We also observed that SJSCs significantly expressed cardiac lineage markers (Gata-4 and myocyte-specific enhancer factor 2C) and pluripotency markers (octamer-binding transcription factor 4, sex-determining region Y box 2, stage-specific embryonic antigen 1, and Nanog) as well as antiaging factors such as telomerase reverse transcriptase and sirtuin 1. Interestingly, SJSCs either from young or aged animals showed significantly longer telomere length as well as lower senescence-associated β-galactosidase expression, suggesting that SJSCs possess antiaging properties, whereas aged BMSCs have limited potential for proliferation and differentiation. Furthermore, transplantation of aged SJSCs into the infarcted rat heart significantly reduced the infarction size and improved left ventricular function, whereas transplantation of aged BMSCs was less effective. Moreover, neovascularization as well as cardiomyogenic differentiation in the peri-infarcted area were significantly increased in the SJSC-transplanted group compared with the BMSC-transplated group, as evaluated by immunohistochemical analysis. Taken together, these findings demonstrate that SJSCs possess characteristics of antiaging, pluripotency, and high proliferation and differentiation rates, and, therefore, these cells offer great therapeutic potential for repair of the injured myocardium.
Lack of specificity of fibroblast-specific protein 1 in cardiac remodeling and fibrosis
Authors: Kong Ping , Christia Panagiota , Saxena Amit , Su Ya , Frangogiannis Nikolaos G.
Published: August 2013

Understanding the role of fibroblasts in pathologic conditions is hampered by the absence of specific markers. Fibroblast-specific protein (FSP)1 has been suggested as a fibroblast-specific marker in normal and fibrotic tissues; FSP1 reporter mice and FSP1-Cre-driven gene deletion are considered reliable strategies to investigate fibroblast biology. Because fibroblasts are abundant in normal and injured mammalian hearts, we studied the identity of FSP1+ cells in the infarcted and remodeling myocardium using mice with green fluorescent protein (GFP) expression driven by the FSP1 promoter. Neonatal and adult mouse hearts had low numbers of FSP1+ cells. Myocardial infarction induced marked infiltration with FSP1-expressing cells that peaked after 72 h of reperfusion. Using flow cytometry, we identified 50% of FSP1+ cells as hematopoietic cells; many endothelial cells were also FSP1+. Increased infiltration with FSP1+ cells was also noted in the pressure-overloaded myocardium. Although some FSP1+ cells had fibroblast morphology, >30% were identified as hematopoietic cells, endothelial cells, or vascular smooth muscle cells. In contrast, periostin did not stain leukocytes or vascular cells but labeled spindle-shaped interstitial cells and, as a typical matricellular protein, was deposited in the matrix. CD11b+ myeloid cells sorted from the infarcted heart had higher FSP1 expression than corresponding CD11b-negative cells, highlighting the predominant expression by hematopoietic cells. FSP1 is not a specific marker for fibroblasts in cardiac remodeling and fibrosis.
Effects of acute vasodilation on the hemodynamic response to muscle metaboreflex
Authors: Marongiu Elisabetta , Piepoli Massimo , Milia Raffaele , Angius Luca , Pinna Marco , Bassareo Pierpaolo , Roberto Silvana , Tocco Filippo , Concu Alberto , Crisafulli Antonio
Published: August 2013

The aim of the present study was to test the contribution of stroke volume (SV) in hemodynamic response to muscle metaboreflex activation in healthy individuals. We hypothesized that an acute decrease in cardiac afterload and preload due to the administration of a vasodilating agent could reduce postexercise muscle ischemia (PEMI)-induced SV response. Ten healthy males (age 33.6 ± 1.3 yr) were enrolled and randomly assigned to the following study protocol: 1) PEMI session, 2) control exercise recovery (CER) session, 3) PEMI after sublingual administration of 5 mg of isosorbide dinitrate (ISDN), and 4) CER after ISDN. Central hemodynamics were evaluated by means of impedance cardiography. The main findings were a blunted SV response during metaboreflex following acute arterial and venous vasodilation, associated with a reduction in cardiac diastolic time and filling, and a decrement of systemic vascular resistance. These hemodynamic changes restrain blood pressure response during metaboreflex activation. Our results indicate that hemodynamic response to metaboreflex activation is a highly integrated phenomenon encompassing complex interplay between heart rate, cardiac performance, preload, and afterload and that impairment of one or more of these parameters leads to altered hemodynamic response to metaboreflex.
Melatonin attenuates the skin sympathetic nerve response to mental stress
Authors: Muller Matthew D. , Sauder Charity L. , Ray Chester A.
Published: August 2013

Melatonin attenuates muscle sympathetic nerve responses to sympathoexcitatory stimuli, but it is unknown whether melatonin similarly attenuates reflex changes in skin sympathetic nerve activity (SSNA). In this double-blind, placebo-controlled, crossover study, we tested the hypothesis that melatonin (3 mg) would attenuate the SSNA response to mental stress (mental arithmetic). Twelve healthy subjects underwent experimental testing on two separate days. Three minutes of mental stress occurred before and 45 min after ingestion of melatonin (3 mg) or placebo. Skin temperature was maintained at 34°C. Reflex increases in SSNA (peroneal nerve), mean arterial pressure, and heart rate (HR) to mental stress before and after melatonin were determined. Melatonin lowered HR (pre, 66 ± 3 beats/min; and post, 62 ± 3 beats/min, P = 0.046) and SSNA (pre, 14,282 ± 3,706 arbitrary units; and post, 9,571 ± 2,609 arbitrary units, P = 0.034) at rest. In response to mental stress, SSNA increases were significantly attenuated following melatonin ingestion (second minute, 114 ± 30 vs. 74 ± 14%; and third minute, 111 ± 29 vs. 54 ± 12%, both P < 0.05). The mean arterial pressure increase to mental stress was blunted in the third minute (20 ± 2 vs. 17 ± 2 mmHg, P = 0.032), and the HR increase was blunted in the first minute (33 ± 3 vs. 29 ± 3 beats/min, P = 0.034) after melatonin. In summary, exogenous melatonin attenuates the SSNA response to mental stress.
The bottleneck stent model for chronic myocardial ischemia and heart failure in pigs
Authors: Rissanen Tuomas T. , Nurro Jussi , Halonen Paavo J. , Tarkia Miikka , Saraste Antti , Rannankari Markus , Honkonen Krista , Pietilä Mikko , Leppänen Olli , Kuivanen Antti , Knuuti Juhani , Ylä-Herttuala Seppo
Published: August 2013

A large animal model of chronic myocardial ischemia and heart failure is crucial for the development of novel therapeutic approaches. In this study we developed a novel percutaneous one- and two-vessel model for chronic myocardial ischemia using a stent coated with a polytetrafluoroethylene tube formed in a bottleneck shape. The bottleneck stent was implanted in the proximal left anterior descending (LAD) or proximal circumflex artery (LCX), or in both proximal LCX and mid LAD 1 wk later (2-vessel model), and pigs were followed for 4–5 wk. Ejection fraction (EF), infarct size, collateral growth, and myocardial perfusion were assessed. Pigs were given antiarrhythmic medication to prevent sudden death. The occlusion time of the bottleneck stent and the timing of myocardial infarction could be modulated by the duration of antiplatelet medication. Fractional flow reserve measurements and positron emission tomography imaging showed severe ischemia after bottleneck stenting covering over 50% of the left ventricle in the proximal LAD model. Complete coronary occlusion was necessary for significant collateral growth, which mostly had occurred already during the first wk after the stent occlusion. Dynamic and competitive collateral growth patterns were observed. EF declined from 64 to 41% in the LCX model and to 44% in the LAD model 4 wk after stenting with 12 and 21% infarcted left ventricle in the LCX and LAD models, respectively. The mortality was 32 and 37% in the LCX and LAD models but very (71%) high in the two-vessel disease model. The implantation of a novel bottleneck stent in the proximal LAD or LCX is a novel porcine model of reversible myocardial ischemia (open stent) and ischemic heart failure (occluded stent) and is feasible for the development of new therapeutic approaches.
Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice
Authors: Roos Carolyn M. , Hagler Michael , Zhang Bin , Oehler Elise A. , Arghami Arman , Miller Jordan D.
Published: August 2013

The purpose of this study was to characterize changes in antioxidant and age-related gene expression in aorta and aortic valve with aging, and test the hypothesis that increased mitochondrial oxidative stress accelerates age-related endothelial and aortic valve dysfunction. Wild-type (MnSOD+/+) and manganese SOD heterozygous haploinsufficient (MnSOD+/−) mice were studied at 3 and 18 mo of age. In aorta from wild-type mice, antioxidant expression was preserved, although there were age-associated increases in Nox2 expression. Haploinsufficiency of MnSOD did not alter antioxidant expression in aorta, but increased expression of Nox2. When compared with that of aorta, age-associated reductions in antioxidant expression were larger in aortic valves from wild-type and MnSOD haploinsufficient mice, although Nox2 expression was unchanged. Similarly, sirtuin expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT3, SIRT4, and SIRT6 were significantly reduced in the aortic valve. Expression of p16ink4a, a marker of cellular senescence, was profoundly increased in both aorta and aortic valve from MnSOD+/+ and MnSOD+/− mice. Functionally, we observed comparable age-associated reductions in endothelial function in aorta from both MnSOD+/+ and MnSOD+/− mice. Interestingly, inhibition of NAD(P)H oxidase with apocynin or gp91ds-tat improved endothelial function in MnSOD+/+ mice but significantly impaired endothelial function in MnSOD+/− mice at both ages. Aortic valve function was not impaired by aging or MnSOD haploinsufficiency. Changes in antioxidant and sirtuin gene expression with aging differ dramatically between aorta and aortic valve. Furthermore, although MnSOD does not result in overt cardiovascular dysfunction with aging, compensatory transcriptional responses to MnSOD deficiency appear to be tissue specific.
Role of renin-angiotensin system in activation of macrophages by modified lipoproteins
Authors: Rafatian Naimeh , Milne Ross W. , Leenen Frans H. H. , Whitman Stewart C.
Published: August 2013

Angiotensin II favors the development of atherosclerosis. Our goal was to determine if foam cell formation increases angiotensin II generation by the endogenous renin-angiotensin system (RAS) and if endogenously produced angiotensin II promotes lipid accumulation in macrophages. Differentiated THP-1 cells were treated with acetylated low-density lipoproteins (ac-LDL), native LDL (n-LDL), or no LDL. Expression of RAS genes was assessed and angiotensin I/II levels were quantified in media and cell lysate. Ac-LDL increased angiotensin I/II levels and the angiotensin II/I ratio in cells and media after foam cell formation. Renin mRNA or activity did not change, but renin blockade completely inhibited the increase in angiotensin II. Angiotensinogen mRNA but not protein level was increased. Angiotensin-converting enzyme (ACE) and cathepsin G mRNA and activities were enhanced by ac-LDL. Inhibition of renin, ACE, or the angiotensin II receptor 1 (AT1-receptor) largely abolished cholesteryl ester formation in cells exposed to ac-LDL and decreased scavenger receptor A (SR-A) and acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT-1) protein levels. Inhibition of renin or the AT1-receptor in cells treated with oxidized LDL also decreased SR-A and ACAT-1 protein and foam cell formation. ac-LDL also increased angiotensin II by human peripheral blood monocyte-derived macrophages, whereas blockade of renin decreased cholesterol ester formation in these macrophages. These findings indicate that, during foam cell formation, angiotensin II generation by the endogenous RAS is stimulated and that endogenously generated angiotensin II is crucial for cholesterol ester accumulation in macrophages exposed to modified LDL.
Maximum shortening velocity of lymphatic muscle approaches that of striated muscle
Authors: Zhang Rongzhen , Taucer Anne I. , Gashev Anatoliy A. , Muthuchamy Mariappan , Zawieja David C. , Davis Michael J.
Published: August 2013

Lymphatic muscle (LM) is widely considered to be a type of vascular smooth muscle, even though LM cells uniquely express contractile proteins from both smooth muscle and cardiac muscle. We tested the hypothesis that LM exhibits an unloaded maximum shortening velocity ( Vmax) intermediate between that of smooth muscle and cardiac muscle. Single lymphatic vessels were dissected from the rat mesentery, mounted in a servo-controlled wire myograph, and subjected to isotonic quick release protocols during spontaneous or agonist-evoked contractions. After maximal activation, isotonic quick releases were performed at both the peak and plateau phases of contraction. Vmax was 0.48 ± 0.04 lengths ( L)/s at the peak: 2.3 times higher than that of mesenteric arteries and 11.4 times higher than mesenteric veins. In cannulated, pressurized lymphatic vessels, shortening velocity was determined from the maximal rate of constriction [rate of change in internal diameter (−d D/d t)] during spontaneous contractions at optimal preload and minimal afterload; peak −d D/d t exceeded that obtained during any of the isotonic quick release protocols (2.14 ± 0.30 L/s). Peak −d D/d t declined with pressure elevation or activation using substance P. Thus, isotonic methods yielded Vmax values for LM in the mid to high end (0.48 L/s) of those the recorded for phasic smooth muscle (0.05–0.5 L/s), whereas isobaric measurements yielded values (>2.0 L/s) that overlapped the midrange of values for cardiac muscle (0.6–3.3 L/s). Our results challenge the dogma that LM is classical vascular smooth muscle, and its unusually high Vmax is consistent with the expression of cardiac muscle contractile proteins in the lymphatic vessel wall.
Club cell secretory protein improves survival in a murine obliterative bronchiolitis model
Authors: Wendt Christine , Tram Kevin , Price Andrew , England Kristen , Stiehm Andrew , Panoskaltsis-Mortari Angela
Published: August 2013

Club cell secretory protein (CCSP) is an indirect phospholipase A2 inhibitor with some immunosuppressive and antiproliferative properties that is expressed in bronchiolar Club cells. In our murine bone marrow transplant (BMT) model of obliterative bronchiolitis (OB), CCSP is diminished; however, its role is unknown. To determine the role of CCSP, B6 wild-type (WT) or CCSP-deficient (CCSP−/−) mice were lethally conditioned and given allogeneic bone marrow with a sublethal dose of allogeneic splenic T cells to induce OB. We found that CCSP−/−mice demonstrated a higher mortality following BMT-induced OB compared with WT mice. Mice were analyzed 60 days post-BMT for protein expression, pulmonary function, and histology. CCSP levels were reduced in WT mice with BMT-induced OB, and lower levels correlated to decreased lung compliance. CCSP−/−had a higher degree of injury and fibrosis as measured by hydroxy proline, along with an increased lung resistance and the inflammatory markers, leukotriene B4 and CXCL1. Replacement with recombinant intravenous CCSP partially reversed the weight loss and improved survival in the CCSP−/−mice. In addition, CCSP replacement improved histology and decreased inflammatory cells and markers. These findings indicate that CCSP has a regulatory role in OB and may have potential as a preventive therapy.
Age-related increases in ozone-induced injury and altered pulmonary mechanics in mice with progressive lung inflammation
Authors: Groves Angela M. , Gow Andrew J. , Massa Christopher B. , Hall LeRoy , Laskin Jeffrey D. , Laskin Debra L.
Published: August 2013

In these studies we determined whether progressive pulmonary inflammation associated with aging in surfactant protein D ( Sftpd)−/−mice leads to an exacerbated response to ozone. In Sftpd−/−mice, but not wild-type (WT) mice, age-related increases in numbers of enlarged vacuolated macrophages were observed in the lung, along with alveolar wall rupture, type 2 cell hyperplasia, and increased bronchoalveolar lavage protein and cell content. Numbers of heme oxygenase+ macrophages also increased with age in Sftpd−/−mice, together with classically (iNOS+) and alternatively (mannose receptor+, YM-1+, or galectin-3+) activated macrophages. In both WT and Sftpd−/−mice, increasing age from 8 to 27 wk was associated with reduced lung stiffness, as reflected by decreases in resistance and elastance spectra; however, this response was reversed in 80-wk-old Sftpd−/−mice. Ozone exposure (0.8 ppm, 3 h) caused increases in lung pathology, alveolar epithelial barrier dysfunction, and numbers of iNOS+ macrophages in 8- and 27-wk-old Sftpd−/−, but not WT mice at 72 h postexposure. Conversely, increases in alternatively activated macrophages were observed in 8-wk-old WT mice following ozone exposure, but not in Sftpd−/−mice. Ozone also caused alterations in both airway and tissue mechanics in Sftpd−/−mice at 8 and 27 wk, but not at 80 wk. These data demonstrate that mild to moderate pulmonary inflammation results in increased sensitivity to ozone; however, in senescent mice, these responses are overwhelmed by the larger effects of age-related increases in baseline inflammation and lung injury.
The receptor for advanced glycation end-products supports lung tissue biomechanics
Authors: Al-Robaiy Samiya , Weber Bettina , Simm Andreas , Diez Claudius , Rolewska Paulina , Silber Rolf-Edgar , Bartling Babett
Published: August 2013

The receptor for advanced glycation end-products (RAGE) and its soluble forms are predominantly expressed in lung but its physiological importance in this organ is not yet fully understood. Since RAGE acts as a cell adhesion molecule, we postulated its physiological importance in the respiratory mechanics. Respiratory function in a buffer-perfused isolated lung system and biochemical parameters of the lung were studied in young, adult, and old RAGE knockout (RAGE-KO) mice and wild-type (WT) mice. Lungs from RAGE-KO mice showed a significant increase in the dynamic lung compliance and a decrease in the maximal expiratory air flow independent of age-related changes. We also determined lower mRNA and protein levels of elastin in lung tissue of RAGE-KO mice. RAGE deficiency did not influence the collagen protein level, lung capillary permeability, and inflammatory parameters (TNF-α, high-mobility group box protein 1) in lung. Overexpressing RAGE as well as soluble RAGE in lung fibroblasts or cocultured lung epithelial cells increased the mRNA expression of elastin. Moreover, immunoprecipitation studies indicated a trans interaction of RAGE in lung epithelial cells. Our findings suggest the physiological importance of RAGE and its soluble forms in supporting the respiratory mechanics in which RAGE trans interactions and the influence on elastin expression might play an important role.
Sequestration of mitochondrial iron by silica particle initiates a biological effect
Authors: Ghio Andrew J. , Tong Haiyan , Soukup Joleen M. , Dailey Lisa A. , Cheng Wan-Yun , Samet James M. , Kesic Matthew J. , Bromberg Philip A. , Turi Jennifer L. , Upadhyay Daya , Scott Budinger G. R. , Mutlu Gökhan M.
Published: August 2013

Inhalation of particulate matter has presented a challenge to human health for thousands of years. The underlying mechanism for biological effect following particle exposure is incompletely understood. We tested the postulate that particle sequestration of cell and mitochondrial iron is a pivotal event mediating oxidant generation and biological effect. In vitro exposure of human bronchial epithelial cells to silica reduced intracellular iron, which resulted in increases in both the importer divalent metal transporter 1 expression and metal uptake. Diminished mitochondrial 57Fe concentrations following silica exposure confirmed particle sequestration of cell iron. Preincubation of cells with excess ferric ammonium citrate increased cell, nuclear, and mitochondrial metal concentrations and prevented significant iron loss from mitochondria following silica exposure. Cell and mitochondrial oxidant generation increased after silica incubation, but pretreatment with iron diminished this generation of reactive oxygen species. Silica exposure activated MAP kinases (ERK and p38) and altered the expression of transcription factors (nF-κB and NF-E2-related factor 2), proinflammatory cytokines (interleukin-8 and -6), and apoptotic proteins. All of these changes in indexes of biological effect were either diminished or inhibited by cell pretreatment with iron. Finally, percentage of neutrophils and total protein concentrations in an animal model instilled with silica were decreased by concurrent exposure to iron. We conclude that an initiating event in the response to particulate matter is a sequestration of cell and mitochondrial iron by endocytosed particle. The resultant oxidative stress and biological response after particle exposure are either diminished or inhibited by increasing the cell iron concentration.
Active α-macroglobulin is a reservoir for urokinase after fibrinolytic therapy in rabbits with tetracycline-induced pleural injury and in human pleural fluids
Authors: Komissarov Andrey A. , Florova Galina , Azghani Ali , Karandashova Sophia , Kurdowska Anna K. , Idell Steven
Published: August 2013

Intrapleural processing of prourokinase (scuPA) in tetracycline (TCN)-induced pleural injury in rabbits was evaluated to better understand the mechanisms governing successful scuPA-based intrapleural fibrinolytic therapy (IPFT), capable of clearing pleural adhesions in this model. Pleural fluid (PF) was withdrawn 0–80 min and 24 h after IPFT with scuPA (0–0.5 mg/kg), and activities of free urokinase (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA complexed with α-macroglobulin (αM) were assessed. Similar analyses were performed using PFs from patients with empyema, parapneumonic, and malignant pleural effusions. The peak of uPA activity (5–40 min) reciprocally correlated with the dose of intrapleural scuPA. Endogenous active PAI-1 (10–20 nM) decreased the rate of intrapleural scuPA activation. The slow step of intrapleural inactivation of free uPA ( t1/2β= 40 ± 10 min) was dose independent and 6.7-fold slower than in blood. Up to 260 ± 70 nM of αM/uPA formed in vivo [second order association rate ( kass) = 580 ± 60 M−1·s−1]. αM/uPA and products of its degradation contributed to durable intrapleural plasminogen activation up to 24 h after IPFT. Active PAI-1, active α2M, and α2M/uPA found in empyema, pneumonia, and malignant PFs demonstrate the capacity to support similar mechanisms in humans. Intrapleural scuPA processing differs from that in the bloodstream and includes 1) dose-dependent control of scuPA activation by endogenous active PAI-1; 2) two-step inactivation of free uPA with simultaneous formation of αM/uPA; and 3) slow intrapleural degradation of αM/uPA releasing active free uPA. This mechanism offers potential clinically relevant advantages that may enhance the bioavailability of intrapleural scuPA and may mitigate the risk of bleeding complications.
Joseph Barcroft's studies of high-altitude physiology
Authors: West John B.
Published: August 2013

Joseph Barcroft (1872–1947) was an eminent British physiologist who made contributions to many areas. Some of his studies at high altitude and related topics are reviewed here. In a remarkable experiment he spent 6 days in a small sealed room while the oxygen concentration of the air gradually fell, simulating an ascent to an altitude of nearly 5,500 m. The study was prompted by earlier reports by J. S. Haldane that the lung secreted oxygen at high altitude. Barcroft tested this by having blood removed from an exposed radial artery during both rest and exercise. No evidence for oxygen secretion was found, and the combination of 6 days incarceration and the loss of an artery was heroic. To obtain more data, Barcroft organized an expedition to Cerro de Pasco, Peru, altitude 4,300 m, that included investigators from both Cambridge, UK and Harvard. Again oxygen secretion was ruled out. The protocol included neuropsychometric measurements, and Barcroft famously concluded that all dwellers at high altitude are persons of impaired physical and mental powers, an assertion that has been hotly debated. Another colorful experiment in a low-pressure chamber involved reducing the pressure below that at the summit of Mt. Everest but giving the subjects 100% oxygen to breathe while exercising as a climber would on Everest. The conclusion was that it would be possible to reach the summit while breathing 100% oxygen. Barcroft was exceptional for his self-experimentation under hazardous conditions.
Identification of dedifferentiation and redevelopment phases during postpneumonectomy lung growth
Authors: Kho Alvin T. , Liu Kaifeng , Visner Gary , Martin Thomas , Boudreault Francis
Published: August 2013

Surgical resection of pulmonary tissue exerts a proregenerative stretch stimulus in the remaining lung units. Whether this regeneration process reenacts part or whole of lung morphogenesis developmental program remains unclear. To address this question, we analyzed the stretch-induced regenerating lung transcriptome in mice after left pneumonectomy (PNX) in its developmental context. We created a C57BL/6 mice lung regeneration transcriptome time course at 3, 7, 14, 28, and 56 days post-PNX, profiling the cardiac and medial lobes and whole right lung. Prominent expression at days 3 and 7 of genes related to cell proliferation (Ccnb1, Bub1, and Cdk1), extracellular matrix (Col1a1, Eln, and Tnc), and proteases (Serpinb2 and Mmp9) indicated regenerative processes that tapered off after 56 days. We projected the post-PNX transcriptomic time course into the transcriptomic principal component space of the C57BL/6 mouse developing lungs time series from embryonic day 9.5 to postnatal day 56. All post-PNX samples were localized around the late postnatal stage of developing lungs. Shortly after PNX, the temporal trajectory of regenerating lobes and right lung reversed course relative to the developing lungs in a process reminiscent of dedifferentiation. This reversal was limited to the later postnatal stage of lung development. The post-PNX temporal trajectory then moves forward in lung development time close to its pre-PNX state after days 28 to 56 in a process resembling redevelopment. A plausible interpretation is that remaining pulmonary tissue reverts to a more primitive stage of development with higher potential for growth to generate tissue in proportion to the loss.
Crossing Reliability of Electric Bike Riders at Urban Intersections
Authors: Mei Huan , Xiaobao Yang , Bin Jia
Published: August 2013

This paper presents a crossing reliability model of electric bike riders at urban intersections using survival analysis approach. Riders’ crossing behavior was collected by video cameras. Waiting times in the red-light phase were modeled by reliability-based model that recognizes the covariate effects. Three parametric models by the exponential, Weibull, and log-logistic distributions were proposed to analyze when and why electric bike riders cross against the red light. The results indicate that movement information and situation factors have significant effects on riders’ crossing reliability. The findings of this paper provide an important demonstration of method and an empirical basis to assess crossing reliability of electric bike riders at the intersection.
Staphylococcus aureusClinical Isolates: Antibiotic Susceptibility, Molecular Characteristics, and Ability to Form Biofilm
Authors: Indrawattana N. , Sungkhachat O. , Sookrung N. , Chongsa-nguan M. , Tungtrongchitr A. , Voravuthikunchai S. P. , Kong-ngoen T. , Kurazono H. , Chaicumpa W.
Published: August 2013

Periodic monitoring ofStaphylococcus aureuscharacteristics in a locality is imperative as their drug-resistant variants cause treatment problem. In this study, antibiograms, prevalence of toxin genes (sea-see, seg-ser, seu, tsst-1, eta, etb, andetd), PFGE types, accessory gene regulator (agr) groups, and ability to form biofilm of 92S. aureusThailand clinical isolates were investigated. They were classified into 10 drug groups: groups 1–7 (56 isolates) were methicillin resistant (MRSA) and 8–10 (36 isolates) were methicillin sensitive (MSSA). One isolate did not have any toxin gene, 4 isolates carried one toxin gene (seq), and 87 isolates had two or more toxin genes. No isolate hadsee, etb, ortsst-1; six isolates hadetaoretd. Combinedseg-sei-sem-sen-seoof the highly prevalentegclocus was 26.1%. Theseb, sec, sel, seu, andetaassociated significantly with MSSA;sekwas more in MRSA. Thesek-seqassociation was 52.17% while combinedsed-sejwas not found. Twenty-three PFGE types were revealed, no association of toxin genes with PFGE types. All fouragrgroups were present;agrgroup 1 was predominant (58.70%) butagrgroup 2 strains carried more toxin genes and were more frequent toxin producers. Biofilm formation was found in 72.83% of the isolates but there was no association with antibiograms. This study provides insight information on molecular and phenotypic markers of ThailandS. aureusclinical isolates which should be useful for future active surveillance that aimed to control a spread of existing antimicrobial resistant bacteria and early recognition of a newly emerged variant.
Microwave Assisted Rapid and Green Synthesis of Silver Nanoparticles Using a Pigment Produced byStreptomyces coelicolorklmp33
Authors: Manikprabhu Deene , Lingappa K.
Published: August 2013

Traditional synthesis of silver nanoparticles using chemical methods produces toxic substances. In contrast biological synthesis is regarded as a safe and nontoxic process but the major drawback of biological synthesis is, this process is slow. In the present investigation, we developed a rapid and green synthesis of silver nanoparticles employing a pigment produced byStreptomyces coelicolorklmp33 in just 90 s. The silver nanoparticles were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The biobased synthesis developed in this method is a safe, rapid, and appropriate way for bulky synthesis of silver nanoparticles.
Modeling and Verification of a Heterogeneous Sky Surveillance Visual Sensor Network
Authors: Ahmad Naeem , Khursheed Khursheed , Imran Muhammad , Lawal Najeem , O'Nils Mattias
Published: August 2013

A visual sensor network (VSN) is a distributed system of a large number of camera nodes and has useful applications in many areas. The primary difference between a VSN and an ordinary scalar sensor network is the nature and volume of the information. In contrast to scalar sensor networks, a VSN generates two-dimensional data in the form of images. In this paper, we design a heterogeneous VSN to reduce the implementation cost required for the surveillance of a given area between two altitude limits. The VSN is designed by combining three sub-VSNs, which results in a heterogeneous VSN. Measurements are performed to verify full coverage and minimum achieved object image resolution at the lower and higher altitudes, respectively, for each sub-VSN. Verification of the sub-VSNs also verifies the full coverage of the heterogeneous VSN, between the given altitudes limits. Results show that the heterogeneous VSN is very effective to decrease the implementation cost required for the coverage of a given area. More than 70% decrease in cost is achieved by using a heterogeneous VSN to cover a given area, in comparison to homogeneous VSN.
The Evaluation of Varying Ductile Fracture Criteria for 3Cr20Ni10W2 Austenitic Heat-Resistant Alloy
Authors: Xia Yu-Feng , Luo Gui-Chang , Wu Dong-Sen , Quan Guo-Zheng , Zhou Jie
Published: August 2013

Most bulk metal forming processes may be limited by ductile fracture, such as an internal or surface fracture developing in the workpiece. Finding a way to evaluate the ductile fracture criteria (DFC) and identify the relationships between damage evolution and strain-softening behavior of 3Cr20Ni10W2 heat-resistant alloy is very important, which, however, is a nontrivial issue that still needs to be addressed in greater depth. Based on cumulative damage theory, an innovative approach involving heat physical compression experiments, numerical simulations, and mathematical computations provides mutual support to evaluate ductile damage cumulating process and DFC diagram along with deformation conditions. It is concluded that, as for strain-softening material, ductile damage starts at work hardening phase, and the damage cumulation is more sensitive in work hardening phase than in work softening phase. In addition, DFC of 3Cr20Ni10W2 heat-resistant alloy in a wide temperature range of 1203∼1403 K and the strain rate of 0.01∼10 s−1 are not constant but change in a range of 0.099∼0.197; thus they have been defined as varying ductile fracture criteria (VDFC) and characterized by a function of strain rate and temperature. According to VDFC diagram, the exact fracture moment and position during various forming processes will be predicted conveniently.
Is Health-Related Quality of Life Associated with Upper and Lower Airway Inflammation in Asthmatics?
Authors: Scichilone Nicola , Braido Fulvio , Taormina Salvatore , Pozzecco Elena , Paternò Alessandra , Baiardini Ilaria , Casolaro Vincenzo , Canonica Giorgio Walter , Bellia Vincenzo
Published: August 2013

Background.Allergic diseases impair health-related quality of life (HR-QoL). However, the relationship between airway inflammation and HR-QoL in patients with asthma and rhinitis has not been fully investigated. We explored whether the inflammation of upper and lower airways is associated with HR-QoL.Methods.Twenty-two mild allergic asthmatics with concomitant rhinitis (10 males, 38 ± 17 years) were recruited. The Rhinasthma was used to identify HR-QoL, and the Asthma Control Test (ACT) was used to assess asthma control. Subjects underwent lung function and exhaled nitric oxide (eNO) test, collection of exhaled breath condensate (EBC), and nasal wash.Results.The Rhinasthma Global Summary score (GS) was 25 ± 11. No relationships were found between GS and markers of nasal allergic inflammation (% eosinophils: , ; ECP: , ) or bronchial inflammation (pH of the EBC: , ; bronchial NO: , ; alveolar NO: , ). The mean ACT score was 18. When subjects were divided into controlled (ACT ≥ 20) and uncontrolled (ACT < 20), the alveolar NO significantly correlated with GS in uncontrolled asthmatics (, ).Conclusions.Upper and lower airways inflammation appears unrelated to HR-QoL associated with respiratory symptoms. These preliminary findings suggest that, in uncontrolled asthma, peripheral airway inflammation could be responsible for impaired HR-QoL.
Positive Solutions of Advanced Differential Systems
Authors: Diblík Josef , Kúdelčíková Mária
Published: August 2013

We study asymptotic behavior of solutions of general advanced differential systems , where F : Ω → ℝn is a continuous quasi‐bounded functional which satisfies a local Lipschitz
condition with respect to the second argument and Ω is a subset in , ,
yt∈, and yt(θ) = y(t + θ), θ ∈ [0, r]. A monotone iterative method is proposed to prove
the existence of a solution defined for t → ∞ with the graph coordinates lying between
graph coordinates of two (lower and upper) auxiliary vector functions. This result is applied to scalar advanced linear differential equations. Criteria of existence of positive solutions are given and their asymptotic behavior is discussed.
The First Negative Moment of Skew-tand Generalized Student'st-Distributions in the Principal Value Sense
Authors: Peng Chien-Yu
Published: August 2013

The (Cauchy) principal value is a method for assigning values to certain improper integrals which would otherwise be undefined. Using the principal value sense, this study derives an explicit expression of the first negative moment of skew-tand generalized Student'st-distributions for practical applications. Some applications obtained from the FNM of skew-tand generalized Student'st-distributions are also discussed.
Breast Cancer Characterization Based on Image Classification of Tissue Sections Visualized under Low Magnification
Authors: Loukas C. , Kostopoulos S. , Tanoglidi A. , Glotsos D. , Sfikas C. , Cavouras D.
Published: August 2013

Rapid assessment of tissue biopsies is a critical issue in modern histopathology. For breast cancer diagnosis, the shape of the nuclei and the architectural pattern of the tissue are evaluated under high and low magnifications, respectively. In this study, we focus on the development of a pattern classification system for the assessment of breast cancer images captured under low magnification (×10). Sixty-five regions of interest were selected from 60 images of breast cancer tissue sections. Texture analysis provided 30 textural features per image. Three different pattern recognition algorithms were employed (kNN, SVM, and PNN) for classifying the images into three malignancy grades: I–III. The classifiers were validated with leave-one-out (training) and cross-validation (testing) modes. The average discrimination efficiency of the kNN, SVM, and PNN classifiers in the training mode was close to 97%, 95%, and 97%, respectively, whereas in the test mode, the average classification accuracy achieved was 86%, 85%, and 90%, respectively. Assessment of breast cancer tissue sections could be applied in complex large-scale images using textural features and pattern classifiers. The proposed technique provides several benefits, such as speed of analysis and automation, and could potentially replace the laborious task of visual examination.
Cavernous Hemangioma of the Tongue
Authors: Kripal Krishna , Rajan Senthil , Ropak Beena , Jayanti Ipsita
Published: August 2013

Hemangioma is a benign tumor of dilated blood vessels. It is most commonly seen in the head and neck region and rarely in the oral cavity. Hemangiomas in the oral cavity are always of clinical importance and require appropriate treatment. We report here a case of a 34-year-old female patient with a swelling on the lateral surface of tongue which did not respond to the sclerosing agent and was finally confirmed as cavernous hemangioma on histological evaluation.
Morphology, Thermal, and Mechanical Characterization of Bark Cloth from Ficus natalensis
Authors: Rwawiire Samson , Luggya George William , Tomkova Blanka
Published: August 2013

The United Nations Educational, Scientific and Cultural Organization (UNESCO) proclaimed in 2005 that Ugandan bark cloth is largely produced from mutuba tree (Ficus natalensis) as a “Masterpiece of the Oral and Intangible Heritage of Humanity.” An exploratory investigation of bark cloth a nonwoven material produced through a series of pummeling processes from mutuba tree in Uganda is fronted as a prospective engineering natural fabric. Bark cloth was obtained from Ficus natalensis trees in Nsangwa village, Buyijja parish in Mpigi district, Central Uganda. The morphology of the fabric was investigated using scanning electron microscope (SEM). thermal behavior of the fabric was studied using thermagravimetric analysis (TGA) and differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy was used to evaluate the surface functional groups. The fabric was subjected to alkaline treatment for six hours at room temperature in order to study the change in fabric thermal properties so as to set a base for applications in biodegradable composites. Findings show that the natural nonwoven fleece is stable below 200°C; alkaline treatment positively influences the thermal behavior by increasing the onset of cellulose degradation temperature. The fabric morphology showed that it is made up of fairly ordered microfibers which can be beneficial for nanocomposites.
A Simulation Model Design Method for Cloud-Based Simulation Environment
Authors: Hu Chunsheng , Xu Chengdong , Fan Guochao , Li He , Song Dan
Published: August 2013

Simulation technologies provide necessary validation tools for the conceptual design of complex products involving multiple disciplines. A variety of simulation models are developed in specific organizations or enterprises to verify the design plan, while they are hard to be shared and to be reused. Based on the analysis of several typical solutions to share and reuse different kinds of resources, a simulation model design method is proposed to provide a simple implementation of simulation model reuse for cloud-based simulation environment. This paper firstly creates the simulation models' metamodel and ontology for their universal description. Secondly, four rules are proposed to design/reprogram a simulation model into service-oriented form for its interoperability, and the ontology of service-oriented simulation model is established. Thirdly, the way to call one simulation model and the way to compose several simulation models into a simulation process are elaborated. Finally, a simple case of using this method to design an aircraft dynamic model is elaborated, and a prototype simulation system is constructed, and then a simple simulation process is composed to verify the practicability of the method. The result shows that the new design/reprogram method has big advantages on the compatibility, expansibility, and reusability despite the decreasing efficiency.
Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy
Authors: Stratakis Stavros , Stylianou Kostas , Petrakis Ioannis , Mavroeidi Vasiliki , Poulidaki Rafaela , Petra Christina , Moisiadis Demitrios , Stratigis Spyros , Vardaki Eleftheria , Nakopoulou Lydia , Daphnis Eugene
Published: August 2013

Objective. Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated.Methods. Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in 12 Sprague-Dawley male rats. One week later, six of these rats were commenced on daily treatment with subcutaneous rapamycin 0.5 mgr/kg (PHN-Rapa). The remaining six rats were used as the proteinuric control group (PHN) while six more rats without PHN were given the rapamycin solvent and served as the healthy control group (HC). All rats were sacrificed at the end of the 7th week.Results. Rapamycin significantly reduced proteinuria during the autologous phase of PHN. Histological lesions were markedly improved by rapamycin. Immunofluorescence revealed attenuated deposits of autologous alloantibodies in treated rats. Untreated rats showed decreased glomerular content of both nephrin and podocin whereas rapamycin restored their expression.Conclusions. Rapamycin monotherapy significantly improves proteinuria and histological lesions in experimental membranous nephropathy. This beneficial effect may be mediated by inhibition of the alloimmune response during the autologous phase of PHN and by restoration of the normal expression of the podocyte proteins nephrin and podocin.
Breaking the Code of Amyloid-βOligomers
Authors: Lesné Sylvain E.
Published: August 2013

Departing from the original postulates that defined various neurodegenerative disorders, accumulating evidence supports a major role for soluble forms of amyloid proteins as initiator toxins in Alzheimer’s disease, Parkinson’s disease, frontotemporal dementias, and prion diseases. Soluble multimeric assemblies of amyloid-β, tau,α-synuclein, and the prion protein are generally englobed under the term oligomers. Due to their biophysical properties, soluble amyloid oligomers can adopt multiple conformations and sizes that potentially confer differential biological activities. Therein lies the problem: with sporadic knowledge and limited tools to identify, characterize, and study amyloid oligomers, how can we solve the enigma of their respective role(s) in the pathogenesis of neurodegenerative disorders? To further our understanding of these devastating diseases, the code of the amyloid oligomers must be broken.