Science.gov

Sample records for characterizing pulmonary blood

  1. Characterizing pulmonary blood flow distribution measured using arterial spin labeling.

    PubMed

    Henderson, A Cortney; Prisk, G Kim; Levin, David L; Hopkins, Susan R; Buxton, Richard B

    2009-12-01

    The arterial spin labeling (ASL) method provides images in which, ideally, the signal intensity of each image voxel is proportional to the local perfusion. For studies of pulmonary perfusion, the relative dispersion (RD, standard deviation/mean) of the ASL signal across a lung section is used as a reliable measure of flow heterogeneity. However, the RD of the ASL signals within the lung may systematically differ from the true RD of perfusion because the ASL image also includes signals from larger vessels, which can reflect the blood volume rather than blood flow if the vessels are filled with tagged blood during the imaging time. Theoretical studies suggest that the pulmonary vasculature exhibits a lognormal distribution for blood flow and thus an appropriate measure of heterogeneity is the geometric standard deviation (GSD). To test whether the ASL signal exhibits a lognormal distribution for pulmonary blood flow, determine whether larger vessels play an important role in the distribution, and extract physiologically relevant measures of heterogeneity from the ASL signal, we quantified the ASL signal before and after an intervention (head-down tilt) in six subjects. The distribution of ASL signal was better characterized by a lognormal distribution than a normal distribution, reducing the mean squared error by 72% (p < 0.005). Head-down tilt significantly reduced the lognormal scale parameter (p = 0.01) but not the shape parameter or GSD. The RD increased post-tilt and remained significantly elevated (by 17%, p < 0.05). Test case results and mathematical simulations suggest that RD is more sensitive than the GSD to ASL signal from tagged blood in larger vessels, a probable explanation of the change in RD without a statistically significant change in GSD. This suggests that the GSD is a useful measure of pulmonary blood flow heterogeneity with the advantage of being less affected by the ASL signal from tagged blood in larger vessels.

  2. Modelling pulmonary blood flow.

    PubMed

    Tawhai, Merryn H; Burrowes, Kelly S

    2008-11-30

    Computational model analysis has been used widely to understand and interpret complexity of interactions in the pulmonary system. Pulmonary blood transport is a multi-scale phenomenon that involves scale-dependent structure and function, therefore requiring different model assumptions for the microcirculation and the arterial or venous flows. The blood transport systems interact with the surrounding lung tissue, and are dependent on hydrostatic pressure gradients, control of vasoconstriction, and the topology and material composition of the vascular trees. This review focuses on computational models that have been developed to study the different mechanisms contributing to regional perfusion of the lung. Different models for the microcirculation and the pulmonary arteries are considered, including fractal approaches and anatomically-based methods. The studies that are reviewed illustrate the different complementary approaches that can be used to address the same physiological question of flow heterogeneity.

  3. Determinants of pulmonary blood volume

    PubMed Central

    Lewis, Milena L.; Gnoj, Julian; Fisher, Vincent J.; Christianson, Lynn C.

    1970-01-01

    Pulmonary blood volume was determined by the radiocardiographic technique in 49 patients coming to cardiac catheterization. Since this method has not been directly compared with the more commonly used double injection of dye. 25 comparisons were carried out in 13 patients of the series. Agreement was good over a range of 4.5-21.1 heart cycles since there was no statistically significant difference between transit time values measured by the two methods. The relation of pulmonary blood volume to other hemodynamic factors in these 49 patients, with and without cardiac or pulmonary disease, was evaluated by means of multiple regression analysis. The analysis carried out for mean transit time indicates that this parameter varies predominately with flow. Pulmonary blood volume, in this series of resting recumbent individuals, varies to a significant degree only with total blood volume and with pulmonary venous pressure. No parameters of vascular distensibility, such as pulmonary vascular resistance, were found to affect the volume of blood in the lungs. The fact that variations in pulmonary blood volume among the subjects could be described by a multiple regression equation linear with respect to total blood volume and pulmonary venous pressure indicates that these variations are the result of passive distention of components of the vascular bed. PMID:4902826

  4. Vascular structure determines pulmonary blood flow distribution

    NASA Technical Reports Server (NTRS)

    Hlastala, M. P.; Glenny, R. W.

    1999-01-01

    Scientific knowledge develops through the evolution of new concepts. This process is usually driven by new methodologies that provide observations not previously available. Understanding of pulmonary blood flow determinants advanced significantly in the 1960s and is now changing rapidly again, because of increased spatial resolution of regional pulmonary blood flow measurements.

  5. Isolation and Characterization of Two Novel Bacteria Afipia cberi and Mesorhizobium hominis from Blood of a Patient Afflicted with Fatal Pulmonary Illness

    PubMed Central

    Lo, Shyh-Ching; Li, Bingjie; Hung, Guo-Chiuan; Lei, Haiyan; Li, Tianwei; Zhang, Jing; Nagamine, Kenjiro; Tsai, Shien; Zucker, Mark J.; Olesnicky, Ludmilla

    2013-01-01

    We recently isolated and discovered new Bradyrhizobiaceae microbes from the cryopreserved culture broth of blood samples from 3 patients with poorly defined illnesses using modified SP4 media and culture conditions coupled with genomic sequencing. Using a similar protocol, we studied a previously cryopreserved culture broth of blood sample from a patient who had succumbed to an acute onset of fulminant pulmonary illness. We report that two phases of microbial growth were observed in the re-initiated culture. Biochemical and genomic characterization revealed microbes isolated from the first phase of growth were new Afipia species of Bradyrhizobiaceae, tentatively named A. cberi with a ~ 5 MB chromosome that was different from those of all previously known Afipia microbes including the newly discovered A. septicemium. The microbes isolated from the second phase of growth were prominent sugar assimilators, novel Phyllobacteriaceae, phylogenetically most closely related to Mesorhizobium and tentatively named M. hominis with a ~ 5.5 MB chromosome. All A. cberi isolates carry a circular ~ 140 KB plasmid. Some M. hominis isolates possess a circular ~ 412 KB plasmid that can be lost in prolonged culture or passage. No antibiotics resistant genes could be identified in both of the A. cberi and M. hominis plasmids. Antibiotic susceptibility studies using broth culture systems revealed isolates of A. cberi could be sensitive to some antibiotics, but all isolates of M. hominis were resistant to essentially all tested antibiotics. However, the cell-free antibiotics susceptibility test results may not be applicable to clinical treatment against the microbes that are known to be capable of intracellular growth. It remains to be determined if the 2 previously unknown Rhizobiales were indeed pathogenic and played a role in the pulmonary disease process in this patient. Specific probes and methods will be developed to re-examine the diseased lungs from patient's autopsy. PMID

  6. Pulmonary blood flow distribution after banding of pulmonary artery.

    PubMed Central

    Samánek, M; Fiser, B; Ruth, C; Tůma, S; Hucín, B

    1975-01-01

    Radioisotope lung scanning was used to investigate the distribution of pulmonary blood flow after banding of the pulmonary artery in children with a left-to-right shunt and pulmonary hypertension. An abnormal distribution of blood flow in the lung on the side of the operation approach was observed in all patients in the first three weeks following surgery. Abnormalities were still observed in 17 of 21 children 10 months to more than 8 years after the banding operation. There was no significant relation between the occurrence of these abnormalities and time after surgery. Diminished flow to the zones of the right lung was observed less frequently. The incidence of abnormalities in flow distribution was also high preoperatively. Respiratory complications in infants with large left-to-right shunts were considered to be responsible for most of the abnormal blood flow distributions observed. Radioactive lung scanning was found to be a valuable diagnostic method in the early and late postoperative period in infants and small children. It was more sensitive than the other techniques used in revealing deviation of blood flow from one lung in those cases with shifting of the applied band. Images PMID:1111558

  7. Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation.

    PubMed

    Jiang, Chunling; Qian, Hong; Luo, Shuhua; Lin, Jing; Yu, Jerry; Li, Yajiao; An, Qi; Luo, Nanfu; Du, Lei

    2017-05-01

    Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 μg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 μg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.

  8. Measuring blood delivery to solitary pulmonary nodules using perfusion magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Zheng, Wei; Wang, Zhifeng; Shen, Li; Gao, Ling; Ford, James C.; Makedon, Fillia S.; Pearlman, Justin D.

    2006-03-01

    With perfusion magnetic resonance imaging (pMRI), perfusion describes the amount of blood passing through a block of tissue in a certain period of time. In pMRI, the tissue having more blood passing through will show higher intensity value as more contrast-labeled blood arrives. Perfusion reflects the delivery of essential nutrients to a block of tissue, and is an important parameter for the tissue status. Considering solitary pulmonary nodules (SPN), perfusion differences between malignant and benign nodules have been studied by different techniques. Much effort has been put into its characterization. In this paper, we proposed and implemented extraction of the SPN time intensity profile to measure blood delivery to solitary pulmonary nodules, describing their perfusion effects. In this method, a SPN time intensity profile is created based on intensity values of the solitary pulmonary nodule in lung pMRI images over time. This method has two steps: nodule tracking and profile clustering. Nodule tracking aligns the solitary pulmonary nodule in pMRI images taken at different time points, dealing with nodule movement resulted from breathing and body movement. Profile clustering implements segmentation of the nodule region and extraction of the time intensity profile of a solitary pulmonary nodule. SPN time intensity profiles reflect patterns of blood delivery to solitary pulmonary nodules, giving us a description of perfusion effect and indirect evidence of tumor angiogenesis. Analysis on SPN time intensity profiles will help the diagnosis of malignant nodules for early lung cancer detection.

  9. Cardiovascular and blood coagulative effects of pulmonary zinc exposure

    SciTech Connect

    Gilmour, Peter S.; Nyska, Abraham; Schladweiler, Mette C.; McGee, John K.; Wallenborn, J. Grace; Richards, Judy H.; Kodavanti, Urmila P. . E-mail: kodavanti.urmila@epa.gov

    2006-02-15

    Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Male Wistar Kyoto rats were instilled intratracheally with saline or zinc sulfate, 131 {mu}g/kg (2 {mu}mol/kg); the alterations were determined at 1, 4, 24, and 48 h postexposure. High-dose zinc enabled us to show changes in circulating levels of zinc above normal and induce significant pulmonary inflammation/injury such that cardiac impairments were likely. At 1-24 h postexposure, plasma levels of zinc increased to nearly 20% above the base line. Significant pulmonary inflammation and injury were determined by analysis of bronchoalveolar lavage fluid and histopathology in zinc-exposed rats at all time points. Starting at 4 h postexposure, pulmonary damage was accompanied by persistently increased gene expressions of tissue factor (TF) and plasminogen activator-inhibitor-1 (PAI-1), but not thrombomodulin (TM). Cardiac tissues demonstrated similar temporal increases in expressions of TF, PAI-1, and TM mRNA following pulmonary instillation of zinc. In contrast to extensive pulmonary edema and inflammation, only mild, and focal acute, myocardial lesions developed in a few zinc-exposed rats; no histological evidence showed increased deposition of fibrin or disappearance of troponin. At 24 and 48 h postexposure to zinc, increases occurred in levels of systemic fibrinogen and the activated partial thromboplastin time. These data suggest that cardiovascular blood coagulation impairments are likely following pulmonary zinc exposure and associated pulmonary injury and inflammation.

  10. Abnormal distribution of pulmonary blood flow in aortic valve disease

    PubMed Central

    Goodenday, Lucy S.; Simon, George; Craig, Hazel; Dalby, Lola

    1970-01-01

    Wasted ventilatory volume (VD) and its ratio to tidal volume (VD/VT) were measured at rest and during exertion in 17 patients with aortic valve disease. We considered VD/VT to indicate abnormal ventilation: perfusion relations if it did not decrease on exertion, or if the exercising value was greater than 40 per cent. Plain chest radiographs were independently examined for evidence of diversion of pulmonary blood to the upper lobes. There was significant agreement (p<0·05) between radiographic and pulmonary function estimations of abnormality. This suggests that the raised pulmonary venous pressure associated with left ventricular failure creates an abnormal pattern of blood flow through the lung, which is responsible for causing inadequate perfusion with respect to ventilation. Images PMID:5420086

  11. Immunological characterization of pulmonary intravascular macrophages

    NASA Technical Reports Server (NTRS)

    Chitko-McKown, C. G.; Reddy, D. N.; Chapes, S. K.; McKown, R. D.; Blecha, F.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

  12. Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

    PubMed Central

    Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

    2013-01-01

    Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the

  13. Does pulmonary rehabilitation reduce peripheral blood pressure in patients with chronic obstructive pulmonary disease?

    PubMed

    Canavan, Jane L; Kaliaraju, Djeya; Nolan, Claire M; Clark, Amy L; Jones, Sarah E; Kon, Samantha S C; Polkey, Michael I; Man, William D-C

    2015-08-01

    Pulmonary rehabilitation (PR) can improve aerobic exercise capacity, health-related quality of life and dyspnoea in patients with chronic obstructive pulmonary disease (COPD). Recent studies have suggested that exercise training may improve blood pressure and arterial stiffness, albeit in small highly selected cohorts. The aim of the study was to establish whether supervised outpatient or unsupervised home PR can reduce peripheral blood pressure. Resting blood pressure was measured in 418 patients with COPD before and after outpatient PR, supervised by a hospital-based team (HOSP). Seventy-four patients with COPD undergoing an unsupervised home-based programme acted as a comparator group (HOME). Despite significant improvements in mean (95% confidence interval) exercise capacity in the HOSP group (56 (50-60) m, p < 0.001) and HOME group (30 (17-42) m, p < 0.001) systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) did not change in either the HOSP (SBP: p = 0.47; DBP: p = 0.06; MAP: p = 0.38) or HOME group (SBP: p = 0.67; DBP: p = 0.38; MAP: p = 0.76). Planned subgroup analysis of HOSP patients with known hypertension and/or cardiovascular disease showed no impact of PR upon blood pressure. PR is unlikely to reduce blood pressure, and by implication, makes a mechanism of action in which arterial stiffness is reduced, less likely.

  14. Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis

    PubMed Central

    Roe, Jennifer K; Thomas, Niclas; Gil, Eliza; Best, Katharine; Tsaliki, Evdokia; Morris‑Jones, Stephen; Stafford, Sian; Simpson, Nandi; Witt, Karolina D; Chain, Benjamin; Miller, Robert F; Martineau, Adrian

    2016-01-01

    BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 (BATF2) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1–negative individuals, and 0.85 in HIV-1–infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR

  15. Pulmonary emboli from blood-biomaterial interaction

    SciTech Connect

    Coleman, J.E.; Ramberg, K.; McEnroe, C.S.; Connolly, R.J.; Callow, A.D.

    1988-07-01

    The problem of surface thrombosis and subsequent embolization remains entrenched as a yet incompletely surmounted barrier to the development of truly satisfactory intravascular prosthetic devices. A baboon ex vivo shunt was used to determine the interaction of Indium-111 platelets and potential biomaterials. The uptake of Indium-111 platelets was monitored continuously by gamma camera scanning. Several of the materials tested demonstrated a saw-toothed pattern of platelet activity, with accumulation followed by rapid decline. Neither PTFE nor Dacron exhibited this pattern. Post shunt scans of the animals' chests showed discrete foci of platelet activity in the lungs, corresponding to each embolic event noted on the material's scan. In conclusion, the search for a smooth surface as a blood material interface may produce a material which accumulates and then sloughs significant platelet aggregates. It is crucial that these materials be subjected to vigorous testing to determine their safety prior to initiation of clinical trials.

  16. Peculiarities of Blood Flow Changes in Venae Cavae during Experimental Pulmonary Embolism.

    PubMed

    Evlakhov, V I; Poyassov, I Z; Shaidakov, E V

    2016-10-01

    The model of acute pulmonary embolism in rabbits demonstrated reduced pulmonary blood flow, cardiac output, left atrial pressure, and blood flow in venae cavae against the background of elevated left pulmonary artery pressure and increased pulmonary vascular resistance. Simultaneously, the blood flow in the superior vena cava decreased to a lesser extent than that in the inferior vena cava, which was a characteristic feature of the model of pulmonary pathology. In contrast, when histamine was infused into the left jugular vein to equally elevate pressure in pulmonary artery as in the above model, the blood flow in the superior vena cava decreased to a greater extent than that in inferior vena cava. During stenosis of inferior vena cava that decreased the cardiac output to the level observed during modeled pulmonary embolism, the blood flows in both venae cavae dropped equally.

  17. Biodegradable radiopaque microspheres for the evaluation of regional pulmonary blood flow distribution using electron-beam computed tomography

    NASA Astrophysics Data System (ADS)

    Workman, Michael J.; Tajik, Jehangir K.; Robinson, Miguel T.; Hoffman, Eric A.

    1994-05-01

    Accurate measurement of regional pulmonary blood flow distribution is of interest both as a research and diagnostic tool. Measurements of regional pulmonary perfusion via x-ray CT offer the possibility of detecting perfusion deficits due to pulmonary embolus while maintaining a high degree of anatomic detail. Use of bolus injection of conventional radiopaque contrast with associated short mean transit times (5 - 7 seconds), requires a high degree of temporal resolution offered clinically only by electron beam x-ray CT (Imatron). The present study was intended to characterize biodegradable radiopaque microspheres as an alternative contrast agent which would allow for measurement of regional pulmonary blood flow with scanning times associated with conventional or spiral thin slice, volumetric x-ray CT protocols. To test this, a dog was scanned at 6 slice levels and 13 time points with image acquisition gated to the cardiac cycle. Lung volumes were maintained at functional residual capacity.

  18. CARDIOVASCULAR AND BLOOD COAGULATION EFFECTS OF PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily, from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Mal...

  19. Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures.

    PubMed

    Skovgaard, Nini; Abe, Augusto S; Andrade, Denis V; Wang, Tobias

    2005-11-01

    Low O2 levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved.

  20. How the python heart separates pulmonary and systemic blood pressures and blood flows.

    PubMed

    Jensen, Bjarke; Nielsen, Jan M; Axelsson, Michael; Pedersen, Michael; Löfman, Carl; Wang, Tobias

    2010-05-01

    The multiple convergent evolution of high systemic blood pressure among terrestrial vertebrates has always been accompanied by lowered pulmonary pressure. In mammals, birds and crocodilians, this cardiac separation of pressures relies on the complete division of the right and left ventricles by a complete ventricular septum. However, the anatomy of the ventricle of most reptiles does not allow for complete anatomical division, but the hearts of pythons and varanid lizards can produce high systemic blood pressure while keeping the pulmonary blood pressure low. It is also known that these two groups of reptiles are characterised by low magnitudes of cardiac shunts. Little, however, is known about the mechanisms that allow for this pressure separation. Here we provide a description of cardiac structures and intracardiac events that have been revealed by ultrasonic measurements and angioscopy. Echocardiography revealed that the atrioventricular valves descend deep into the ventricle during ventricular filling and thereby greatly reduce the communication between the systemic (cavum arteriosum) and pulmonary (cavum pulmonale) ventricular chambers during diastole. Angioscopy and echocardiography showed how the two incomplete septa, the muscular ridge and the bulbuslamelle - ventricular structures common to all squamates - contract against each other in systole and provide functional division of the anatomically subdivided ventricle. Washout shunts are inevitable in the subdivided snake ventricle, but we show that the site of shunting, the cavum venosum, is very small throughout the cardiac cycle. It is concluded that the python ventricle is incapable of the pronounced and variable shunts of other snakes, because of its architecture and valvular mechanics.

  1. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow.

    PubMed

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.

  2. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow

    PubMed Central

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH. PMID:25755701

  3. Pulmonary blood volume (PRV) in rats with chronic mountain sickness

    SciTech Connect

    Ou, L.C.; Sardella, G.L.; Hill, N.S.; Tenney, S.M.

    1986-03-05

    Upon chronic exposure to severe hypoxia, Hilltop (H) strain of Sprague-Dawley rats develops excessive polycythemia, severe hypervolemia and marked elevation in pulmonary arterial pressure (PAP), whereas Madison (M) strain develops only moderate responses. Hypervolemia is expected to increase the PBV which might contribute to the development of severe pulmonary hypertension. Two groups of 6 animals each of the H and M strains were exposed to sea level (SL) and a simulated altitude of 18,000 ft for 14 days. At the end of exposure each animal was measured for RBC volume (RBCV), total blood volume (TBV), PBV and PAP under normoxia for control and under hypoxia (10% O/sub 2/) for the hypoxic groups. RBCV was determined by /sup 51/Cr-RBC dilution and PBV was trapped by tightening an implanted loose ligature around the ascending aorta and PA. There were not strain differences in all parameters studied at SL. RBCV, TBV and PAP increased with hypoxia in both strains but significantly more so in H than M. PBV per g lung WT decreased in both strains despite elevated TBV and PAP, but more so in M than H. There were good correlations between the PBV and TBV, and between PAP and PBV in the hypoxic H and M rats. The data suggest that chronic hypoxia reduced the distensibility and perhaps the vascular capacity of the lungs such that small relative increase in PBV could significantly contribute to the rise in PAP.

  4. Expression of peptide fragments from proADM and involvement of mitogen-activated protein kinase signaling pathways in pulmonary remodeling induced by high pulmonary blood flow.

    PubMed

    Li, Wei; Guo, Aili; Wang, Lijuan; Kong, Qingyu; Wang, Rong; Han, Li; Zhao, Cuifen

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary arterial remodeling and right ventricular failure. Despite recent advances in pathophysiological mechanism exploration and new therapeutic approaches, PAH remains a challenging condition. In this study, we investigated the roles of the peptide fragments from proadrenomedullin (proADM) such as adrenomedullin (ADM), adrenotensin (ADT), and proadrenomedullin N-terminal 20 peptide (PAMP) during pulmonary remodeling caused by high pulmonary blood flow, and probed the possible involvement of mitogen-activated protein kinase (MAPK) signal transduction pathways. Sixteen rat models of PAH were artificially established by surgically connecting the left common carotid artery to the external jugular vein. We subcutaneously injected an extracellular signal-regulated protein kinase (ERK1/2) inhibitor, PD98059, in eight rats, treated another eight rats with an equal volume of saline. Eight rats without connections served as the control group. We observed that mRNA expression levels of ADM, stress-activated protein kinase (SAPK), and ERK1/2 were significantly elevated in the shunted rats; furthermore, ERK1/2 levels were significantly inhibited by PD98059. Protein levels of ADM, PAMP, p-SAPK, and p-ERK1/2 were significantly higher ADT was lower, and p-p38 remained unchanged in the rat models compared with the controls. However, the protein expression of both ADM and p-ERK1/2 was significantly inhibited by PD98059. Our results suggest that levels of ADM, ADT, and PAMP respond to pulmonary remodeling, and that activation of the SAPK and ERK1/2 signaling pathways is involved in pulmonary hypertension and artery remodeling caused by high pulmonary blood flow.

  5. Pulmonary blood flow redistribution by increased gravitational force

    NASA Technical Reports Server (NTRS)

    Hlastala, M. P.; Chornuk, M. A.; Self, D. A.; Kallas, H. J.; Burns, J. W.; Bernard, S.; Polissar, N. L.; Glenny, R. W.

    1998-01-01

    This study was undertaken to assess the influence of gravity on the distribution of pulmonary blood flow (PBF) using increased inertial force as a perturbation. PBF was studied in unanesthetized swine exposed to -Gx (dorsal-to-ventral direction, prone position), where G is the magnitude of the force of gravity at the surface of the Earth, on the Armstrong Laboratory Centrifuge at Brooks Air Force Base. PBF was measured using 15-micron fluorescent microspheres, a method with markedly enhanced spatial resolution. Each animal was exposed randomly to -1, -2, and -3 Gx. Pulmonary vascular pressures, cardiac output, heart rate, arterial blood gases, and PBF distribution were measured at each G level. Heterogeneity of PBF distribution as measured by the coefficient of variation of PBF distribution increased from 0.38 +/- 0.05 to 0.55 +/- 0.11 to 0.72 +/- 0.16 at -1, -2, and -3 Gx, respectively. At -1 Gx, PBF was greatest in the ventral and cranial and lowest in the dorsal and caudal regions of the lung. With increased -Gx, this gradient was augmented in both directions. Extrapolation of these values to 0 G predicts a slight dorsal (nondependent) region dominance of PBF and a coefficient of variation of 0.22 in microgravity. Analysis of variance revealed that a fixed component (vascular structure) accounted for 81% and nonstructure components (including gravity) accounted for the remaining 19% of the PBF variance across the entire experiment (all 3 gravitational levels). The results are inconsistent with the predictions of the zone model.

  6. Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study

    PubMed Central

    Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A.; Austin, John H. M.; Bluemke, David A.; Carr, James; Choi, Jiwoong; Goldstein, Thomas A.; Gomes, Antoinette S.; Hoffman, Eric A.; Kawut, Steven M.; Lima, Joao; Michos, Erin D.; Post, Wendy S.; Po, Ming Jack; Prince, Martin R.; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M.; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M.

    2015-01-01

    Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below −950 Hounsfield units (−950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema−950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature. PMID:26067761

  7. Effect of Pulmonary Blood Flow upon Lung Mechanics*

    PubMed Central

    Giannelli, Stanley; Ayres, Stephen M.; Buehler, M. E.

    1967-01-01

    Airway pressure was continuously recorded in an isolated horizontally mounted canine heart-lung preparation during abrupt, stepwise 100-200 ml inflations to 20-25 cm water pressure, and subsequent deflations. With each change in volume there was a steep rise or fall in pressure, followed by stress relaxation to a static equilibrium airway pressure. Comparison was made between the nonperfused state and during perfusion with whole blood at 100 ml/kg dog wt per min, and left atrial pressure of 10 mm Hg. Pressure tracings were similar during deflation in the perfused and the nonperfused lung. During inflation, in the middle range of lung inflation volumes, the peak inflation and equilibrium airway pressures were greater in the nonperfused state; maximum difference of static pressures in nine preparations averaged 146% of perfused values and the average stress relaxation difference from eight of these was 276%. Lung distensibility was the same with packed red cells or plasma perfusates and was not changed by varying the perfusion rate up to 220 ml/kg per min. During cyclic ventilation, dynamic compliance was similarly greater in the perfused than in the nonperfused state in the middle range of inflation volumes. Static distention of the vascular bed produced similar results with progressive improvement in distensibility in mid-inflation range up to a hydrostatic pressure of 15 cm blood. These data suggest that the distended pulmonary vascular bed provides structural airway support which facilitates entry of gas into the terminal respiratory units at diminished pressure. PMID:6061740

  8. Blood gas analysis in dogs with pulmonary heartworm disease.

    PubMed

    Kitagawa, H; Yasuda, K; Sasaki, Y

    1993-04-01

    Blood gases were analyzed in dogs with pulmonary heartworm (HW) disease. The arterial oxygen tension (PaO2) in dogs with mild signs of dirofilariasis (mildly affected group, n = 48, 85.7 +/- 8.2 mmHg) and in dogs with signs of right heart failure (severely affected group, n = 13, 76.4 +/- 11.6 mmHg) was lower (p < 0.01) than in dogs without HW infection (HW-free group, n = 19, 91.5 +/- 7.3 mmHg). Only 2 dogs in the severely affected group had a PaO2 less than 60 mmHg. The arterial carbon dioxide tension (PaCO2, p < 0.01) and mixed venous O2 (p < 0.01) and CO2 (p < 0.01) tensions were lower, and alveolar-arterial oxygen difference (AaDO2, p < 0.01) was greater in the severely affected group than in the HW-free and mildly affected groups. Arterial pH and bicarbonate (HCO3-) concentrations were lower (p < 0.01) in both affected groups than in the HW-free groups. The anion gap level was not different among the 3 groups. Serum lactic acid level in the severely affected group was higher (p < 0.01) than in the HW-free and mildly affected groups. However, a slightly higher serum lactic acid concentration was found only in 2 dogs of the severely affected group (3.84 mmol/l and 3.82 mmol/l). The PaO2 (r = -0.62) and AaDO2 (r = 0.66) correlated significantly (p < 0.01) with mean pulmonary arterial pressure. One week after HW removal, blood gases, pH and HCO3- concentration remained unchanged in the mildly affected group. In the severely affected group, blood gas values were the same, but pH and HCO3- concentration improved slightly.

  9. Altered Immune Phenotype in Peripheral Blood Cells of Patients with Scleroderma-Associated Pulmonary Hypertension

    PubMed Central

    Risbano, Michael G; Meadows, Christina A; Coldren, Christopher D; Jenkins, Tiffany J.; Edwards, Michael G; Collier, David; Huber, Wendy; Mack, Douglas G; Fontenot, Andrew P; Geraci, Mark W; Bull, Todd M

    2010-01-01

    Pulmonary arterial hypertension is a common and fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. Our goal is to identify differentially expressed genes in peripheral blood mononuclear cells in scleroderma patients with and without pulmonary hypertension as biomarkers of disease. Gene expression analysis was performed on a Microarray Cohort of scleroderma patients with (n=10) and without (n=10) pulmonary hypertension. Differentially expressed genes were confirmed in the Microarray Cohort and validated in a Validation Cohort of scleroderma patients with (n=15) and without (n=19) pulmonary hypertension by RT-qPCR. We identified inflammatory and immune-related genes including interleukin-7 receptor (IL-7R) and chemokine receptor 7 as differentially expressed in patients with scleroderma-associated pulmonary hypertension. Flow cytometry confirmed decreased expression of IL-7R on circulating CD4+ T-cells from scleroderma patients with pulmonary hypertension. Differences exist in the expression of inflammatory and immune-related genes in peripheral blood cells from patients with scleroderma-related pulmonary hypertension compared to those with normal pulmonary artery pressures. These findings may have implications as biomarkers to screen at-risk populations for early diagnosis and provide insight into mechanisms of scleroderma-related pulmonary hypertension. PMID:20973920

  10. Pulmonary Manifestations of the Pre-Engraftment Syndrome after Umbilical Cord Blood Transplantation

    PubMed Central

    Brownback, Kyle R.; Simpson, Steven Q.; McGuirk, Joseph P.; Lin, Tara L.; Abhyankar, Sunil; Ganguly, Siddhartha; Aljitawi, Omar S.

    2014-01-01

    Pre-engraftment syndrome (PES) is a condition occurring after umbilical cord blood transplantation (UCBT) characterized by fever and erythematous skin rash prior to neutrophil engraftment. We sought to determine the incidence and characterize the pulmonary manifestations of PES. A retrospective review of patients who underwent UCBT at the University of Kansas Medical Center over a 5 year period was performed. Data collected included patient baseline characteristics, presence of PES, pulmonary findings, treatments and survival. Forty-four patients underwent UCBT with 22 of those patients developing PES. Full-intensity myeloablative conditioning regimen was found to be a risk factor for development of PES. Of those 22 patients, 13 had resting hypoxemia. The most common radiographic findings included diffuse ground glass opacities with pleural effusions. Fifteen patients with PES received corticosteroids, of which twelve had improvement in fevers and rash. These patients had a trend towards worse mortality than those not receiving corticosteroids. There was a non-significant trend towards worse survival in patients with PES and hypoxemia compared to those without hypoxemia. PES is a common complication following cord blood transplantation, with hypoxemia being present in over half of patients with PES. Hypoxemia with PES and treatment with corticosteroids may portend a worse prognosis. PMID:24346710

  11. Pulmonary edema

    MedlinePlus

    ... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

  12. Pulmonary and systemic blood flow contributions to upper airways in canine lung

    SciTech Connect

    Barman, S.A.; Ardell, J.L.; Parker, J.C.; Perry, M.L.; Taylor, A.E. )

    1988-11-01

    The blood flow contributions and drainage patterns of the pulmonary and systemic circulations in the upper airways (trachea and main bronchi) were assessed in anesthetized dogs by injecting 15-{mu}m radiolabeled microspheres into the right and left heart, respectively. After the animals were killed, the tracheal cartilage, tracheal muscle-mucosa, and main bronchi were excised. The tracheal cartilage and tracheal muscle-mucosa were divided into lower, middle, and upper segments for blood flow determinations. The pulmonary contribution to tracheal blood flow was very small, being higher in the lower segments. The systemic contribution to these same tracheal regions was significantly higher, and higher in the upper segments. The pulmonary and systemic circulations each contributed {approximately}50% to the main bronchi blood flow. The pulmonary blood flow contribution alone to the trachea and main bronchi was also determined in subsequent experiments that utilized the isolated lung, and these blood flows were not significantly different from the pulmonary contribution measured in the intact lungs. The present results indicate that the systemic (bronchial) circulation is the primary source of tracheal blood flow and that both the pulmonary and systemic circulations may contribute {approximately}50% of the blood flow to the main bronchi in dog lungs.

  13. Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.

    PubMed

    Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad

    2015-10-01

    Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment.

  14. Abnormal distribution of pulmonary blood flow in aortic valve disease. Relation between pulmonary function and chest radiograph.

    PubMed

    Goodenday, L S; Simon, G; Craig, H; Dalby, L

    1970-05-01

    Wasted ventilatory volume (V(D)) and its ratio to tidal volume (V(D)/V(T)) were measured at rest and during exertion in 17 patients with aortic valve disease. We considered V(D)/V(T) to indicate abnormal ventilation: perfusion relations if it did not decrease on exertion, or if the exercising value was greater than 40 per cent. Plain chest radiographs were independently examined for evidence of diversion of pulmonary blood to the upper lobes. There was significant agreement (p<0.05) between radiographic and pulmonary function estimations of abnormality. This suggests that the raised pulmonary venous pressure associated with left ventricular failure creates an abnormal pattern of blood flow through the lung, which is responsible for causing inadequate perfusion with respect to ventilation.

  15. Bidirectional Glenn with interruption of antegrade pulmonary blood flow: Which is the preferred option: Ligation or division of the pulmonary artery?

    PubMed Central

    Chowdhury, Ujjwal Kumar; Kapoor, Poonam Malhotra; Rao, Keerthi; Gharde, Parag; Kumawat, Mukesh; Jagia, Priya

    2016-01-01

    We report a rare complication of massive aneurysm of the proximal ligated end of the main pulmonary artery which occurred in the setting of a patient with a functionally univentricular heart and increased pulmonary blood flow undergoing superior cavopulmonary connection. Awareness of this possibility may guide others to electively transect the pulmonary artery in such a clinical setting. PMID:27397472

  16. Elevated Low-Shear Blood Viscosity is Associated with Decreased Pulmonary Blood Flow in Children with Univentricular Heart Defects.

    PubMed

    Cheng, Andrew L; Takao, Cheryl M; Wenby, Rosalinda B; Meiselman, Herbert J; Wood, John C; Detterich, Jon A

    2016-04-01

    After the Fontan procedure, patients with univentricular hearts can experience long-term complications due to chronic low-shear non-pulsatile pulmonary blood flow. We sought to evaluate hemorheology and its relationship to hemodynamics in children with univentricular hearts. We hypothesized that low-shear blood viscosity and red blood cell (RBC) aggregation would be associated with increased pulmonary vascular resistance (PVR) and decreased pulmonary blood flow (PBF). We performed a cross-sectional analysis of 62 children undergoing cardiac catheterization-20 with isolated atrial septal defect (ASD), 22 status post Glenn procedure (Glenn), and 20 status post Fontan procedure (Fontan). Shear-dependent blood viscosity, RBC aggregation and deformability, complete blood count, coagulation panel, metabolic panel, fibrinogen, and erythrocyte sedimentation rate were measured. PVR and PBF were calculated using the Fick equation. Group differences were analyzed by ANOVA and correlations by linear regression. Blood viscosity at all shear rates was higher in Glenn and Fontan, partially due to normocytic anemia in ASD. RBC aggregation and deformability were similar between all groups. Low-shear viscosity negatively correlated with PBF in Glenn and Fontan only (R (2) = 0.27, p < 0.001); it also negatively correlated with pulmonary artery pressure in Glenn (R (2) = 0.15, p = 0.01), and positively correlated with PVR in Fontan (R (2) = 0.28, p = 0.02). Our data demonstrate that elevated low-shear blood viscosity is associated with negative hemodynamic perturbations in a passive univentricular pulmonary circulation, but not in a pulsatile biventricular pulmonary circulation.

  17. [Measurement of the blood flow velocity in the pulmonary arteries using the magnetic resonance technique].

    PubMed

    Gamroth, A H; Schad, L R; Wacker, C M; Gehling, U; Knopp, M V; Betsch, B; Clorius, J H; van Kaick, G

    1992-04-01

    MR blood velocity measurements were performed by the RACE technique in a plane perpendicular to the flow of the pulmonary arteries. MR findings were correlated with those of perfusion scintigraphy, Doppler US and right heart catheter (thermodilution). The ratio of MR blood flow measurements of right and left pulmonary arteries correlated well with the results of perfusion scintigraphy (RPA to LPA) and Doppler. Poor correlation was found when comparing MR blood flow measurements with right heart catheter since absolute flow measurements can be superimposed by neighboring blood vessels in complex anatomic situations.

  18. Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow.

    PubMed

    Ghorishi, Zahra; Milstein, Jay M; Poulain, Francis R; Moon-Grady, Anita; Tacy, Theresa; Bennett, Stephen H; Fineman, Jeffery R; Eldridge, Marlowe W

    2007-06-01

    Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d(0) and daughters d(1) >or= d(2) with alpha < 2 in (d(1)/d(0))(alpha) + (d(2)/d(0))(alpha) and area ratio beta < 1 in beta = (d(1)(2)+ d(2)(2))/ d(0)(2)] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D(0) approximately alpha delineates hemodynamic reactivity. Fetus and Control twin D(0) differed: fetus D(0)=1.72, a high-resistance/shear stress amplifying condition; control twin D(0) = 2.02, an area-preserving transport configuration. The Shunt twin (D(0)=1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.

  19. Pulmonary blood flow distribution in sheep: effects of anesthesia, mechanical ventilation, and change in posture

    NASA Technical Reports Server (NTRS)

    Walther, S. M.; Domino, K. B.; Glenny, R. W.; Hlastala, M. P.

    1997-01-01

    BACKGROUND: Recent studies providing high-resolution images of pulmonary perfusion have questioned the classical zone model of pulmonary perfusion. Hence the present work was undertaken to provide detailed maps of regional pulmonary perfusion to examine the influence of anesthesia, mechanical ventilation, and posture. METHODS: Pulmonary perfusion was analyzed with intravenous fluorescent microspheres (15 microm) in six sheep studied in four conditions: prone and awake, prone with pentobarbital-anesthesia and breathing spontaneously, prone with anesthesia and mechanical ventilation, and supine with anesthesia and mechanical ventilation. Lungs were air dried at total lung capacity and sectioned into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed and assigned spatial coordinates. Fluorescence was read on a spectrophotometer, and signals were corrected for piece weight and normalized to mean flow. Pulmonary blood flow heterogeneity was assessed using the coefficient of variation of flow data. RESULTS: Pentobarbital anesthesia and mechanical ventilation did not influence perfusion heterogeneity, but heterogeneity increased when the animals were in the supine posture (P < 0.01). Gravitational flow gradients were absent in the prone position but present in the supine (P < 0.001 compared with zero). Pulmonary perfusion was distributed with a hilar-to-peripheral gradient in animals breathing spontaneously (P < 0.05). CONCLUSIONS: The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary perfusion heterogeneity is small compared with the effect of changes in posture. Analysis of flow gradients indicate that gravity plays a small role in determining pulmonary blood flow distribution.

  20. Blood cell characterization by light scattering

    NASA Astrophysics Data System (ADS)

    Magnin, Olivier

    2004-09-01

    In this paper we are going to introduce optical methods for blood cell characterization performed by standard hematology analyzers. As a consequence, we are going to focus on methods that are, or will be, compatible with an average cost, commercial, blood cell counter.

  1. Doppler echocardiographic evaluation of pulmonary blood flow after the Fontan operation: the role of the lungs.

    PubMed Central

    Penny, D J; Redington, A N

    1991-01-01

    OBJECTIVE--To document whether the act of respiration influences pulmonary blood flow in patients after the Fontan operation. DESIGN--Prospective study in which patients acted as their own controls. SETTING--Supraregional paediatric cardiology centre. PATIENTS--Sixteen patients who had undergone atriopulmonary anastomosis (Fontan operation) for the treatment of congenital heart disease. INTERVENTION--Doppler assessment of pulmonary artery flow patterns with a simultaneous respirometer, electrocardiogram and phonocardiogram. RESULTS--Total (mean (1SD) ) forward pulmonary flow was 63.6 (35)% higher during inspiratory cardiac cycles than during expiratory ones. CONCLUSIONS--The act of breathing provides an additional energy supply to pulmonary blood flow in patients after the Fontan operation. Images PMID:1747298

  2. Blood gas partition coefficient and pulmonary extraction ratio for propofol in goats and pigs.

    PubMed

    Grossherr, M; Hengstenberg, A; Dibbelt, L; Igl, B-W; Noel, R; Knesebeck, A v d; Schmucker, P; Gehring, H

    2009-10-01

    The interpretation of continuously measured propofol concentration in respiratory gas demands knowledge about the blood gas partition coefficient and pulmonary extraction ratio for propofol. In the present investigation we compared both variables for propofol between goats and pigs during a propofol anaesthesia. In ten goats and ten pigs, expired alveolar gas and arterial and mixed venous blood samples were simultaneously drawn during total intravenous anaesthesia with propofol. The blood gas partition coefficient and pulmonary extraction ratio were calculated for both species. Non-parametric methods were used for statistical inference. The blood gas partition coefficient ranged between 7000 and 646,000 for goats and between 17,000 and 267,000 for pigs. The pulmonary extraction ratio ranged between 32.9% and 98.1% for goats and was higher for pigs, which ranged between -106.0% and 39.0%. The blood gas partition coefficient for propofol exceeded those for other known anaesthetic compounds so that it takes longer to develop a steady-state. The different pulmonary extraction rates in two species suggest that there are different ways to distribute propofol during the lung passage on its way from the blood to breathing gas. This species-specific difference has to be considered for methods using the alveolar gas for monitoring the propofol concentration in plasma.

  3. Lung function, transfusion, pulmonary capillary blood volume and sickle cell disease.

    PubMed

    Lunt, Alan; McGhee, Emily; Robinson, Polly; Rees, David; Height, Susan; Greenough, Anne

    2016-02-01

    Lung function abnormalities occur in children with sickle cell disease (SCD) and may be associated with elevated pulmonary blood volume. To investigate that association, we determined whether blood transfusion in SCD children acutely increased pulmonary capillary blood volume (PCBV) and increased respiratory system resistance (Rrs5). Measurements of Rrs5 and spirometry were made before and after blood transfusion in 18 children, median age 14.2 (6.6-18.5) years. Diffusing capacity for carbon monoxide and nitric oxide were assessed to calculate the PCBV. Post transfusion, the median Rrs5 had increased from 127.4 to 141.3% predicted (p<0.0001) and pulmonary capillary blood volume from 39.7 to 64.1 ml/m2 (p<0.0001); forced expiratory volume in one second (p=0.0056) and vital capacity (p=0.0008) decreased. The increase in Rrs5 correlated with the increase in PCBV (r=0.50, p=0.0493). Increased pulmonary capillary blood volume may at least partially explain the lung function abnormalities in SCD children.

  4. Pulmonary Vascular Impedance in Chronic Pulmonary Hypertension.

    DTIC Science & Technology

    PULMONARY HYPERTENSION , *PULMONARY BLOOD CIRCULATION, BLOOD CIRCULATION, LUNG, PATHOLOGY, VASCULAR DISEASES, ARTERIES, OBSTRUCTION(PHYSIOLOGY...EMBOLISM, HISTOLOGY, DOGS, LABORATORY ANIMALS, BLOOD PRESSURE , EXPERIMENTAL DATA, PHYSIOLOGY.

  5. Non-invasive pulmonary blood flow analysis and blood pressure mapping derived from 4D flow MRI

    NASA Astrophysics Data System (ADS)

    Delles, Michael; Rengier, Fabian; Azad, Yoo-Jin; Bodenstedt, Sebastian; von Tengg-Kobligk, Hendrik; Ley, Sebastian; Unterhinninghofen, Roland; Kauczor, Hans-Ulrich; Dillmann, Rüdiger

    2015-03-01

    In diagnostics and therapy control of cardiovascular diseases, detailed knowledge about the patient-specific behavior of blood flow and pressure can be essential. The only method capable of measuring complete time-resolved three-dimensional vector fields of the blood flow velocities is velocity-encoded magnetic resonance imaging (MRI), often denoted as 4D flow MRI. Furthermore, relative pressure maps can be computed from this data source, as presented by different groups in recent years. Hence, analysis of blood flow and pressure using 4D flow MRI can be a valuable technique in management of cardiovascular diseases. In order to perform these tasks, all necessary steps in the corresponding process chain can be carried out in our in-house developed software framework MEDIFRAME. In this article, we apply MEDIFRAME for a study of hemodynamics in the pulmonary arteries of five healthy volunteers. The study included measuring vector fields of blood flow velocities by phase-contrast MRI and subsequently computing relative blood pressure maps. We visualized blood flow by streamline depictions and computed characteristic values for the left and the right pulmonary artery (LPA and RPA). In all volunteers, we observed a lower amount of blood flow in the LPA compared to the RPA. Furthermore, we visualized blood pressure maps using volume rendering and generated graphs of pressure differences between the LPA, the RPA and the main pulmonary artery. In most volunteers, blood pressure was increased near to the bifurcation and in the proximal LPA, leading to higher average pressure values in the LPA compared to the RPA.

  6. Effect of gravitational and inertial forces on vertical distribution of pulmonary blood flow

    NASA Technical Reports Server (NTRS)

    Chevalier, P. A.; Reed, J. H., Jr.; Vandenberg, R. A.; Wood, E. H.

    1978-01-01

    Vertical distribution of pulmonary blood flow (VDPBF) was studied, using radioactive microsphere emboli, in dogs without thoracotomy in the right decubitus position during exposure to lateral accelerations of 1, 2, 4, and 6 G. At all levels of force environment studied, an inverse linear relationship was observed between vertical height in the thorax and pulmonary blood flow (ml/min/ml lung tissue) with a decrease in flow to the most dependent region of the lung despite large increases in intravascular pressures at this site. Changes in blood flow were smallest at the mid-lung level, the hydrostatic 'balance point' for vascular and pleural pressures. These force environment-dependent changes in VDPBF are not readily explainable by the Starling resistor analog. Gravity-dependent regional differences in pleural and associated interstitial pressures, plus possible changes in vascular tone resulting from inadequate aeration of blood in the most dependent regions of the lung, probably also affect VDPBF.

  7. Automated Measurement of Microcirculatory Blood Flow Velocity in Pulmonary Metastases of Rats

    PubMed Central

    Fontanella, Andrew N.; Palmer, Gregory M.; Boico, Alina; Min, Hooney; Dewhirst, Mark W.; Irwin, David C.; Zhao, Yulin; Schroeder, Thies

    2014-01-01

    Because the lung is a major target organ of metastatic disease, animal models to study the physiology of pulmonary metastases are of great importance. However, very few methods exist to date to investigate lung metastases in a dynamic fashion at the microcirculatory level, due to the difficulty to access the lung with a microscope. Here, an intravital microscopy method is presented to functionally image and quantify the microcirculation of superficial pulmonary metastases in rats, using a closed-chest pulmonary window and automated analysis of blood flow velocity and direction. The utility of this method is demonstrated to measure increases in blood flow velocity in response to pharmacological intervention, and to image the well-known tortuous vasculature of solid tumors. This is the first demonstration of intravital microscopy on pulmonary metastases in a closed-chest model. Because of its minimized invasiveness, as well as due to its relative ease and practicality, this technology has the potential to experience widespread use in laboratories that specialize on pulmonary tumor research. PMID:25490280

  8. Pulmonary microthromboembolism by injection of sonicated autologous blood in rabbits with splenic artery ligations.

    PubMed

    Kietthubthew, S; Kisanuki, A; Asada, Y; Marutsuka, K; Funahara, Y; Sumiyoshi, A

    1997-01-01

    Chronic pulmonary thromboembolism (PTE) has been reported to play an important role in cardiac failure in thalassemic patients after splenectomy. However, the mechanism of PTE in these patients remains unclear. In this study, we attempted to establish an animal model of PTE seen in thalassemic patients after splenectomy. We divided New Zealand white rabbits into three groups: Group 1 was injected sonicated blood, II was injected non-sonicated blood after ligation of the splenic artery, and III was injected sonicated blood after ligation of the splenic artery. After injection of the sonicated blood, we counted the platelet number until 1 hour and the rabbits were sacrificed for histological examination. Platelets significantly decreased in number immediately after injection of the sonicated blood in Groups I and III. Many pulmonary thromboemboli composed mainly of platelets were found in Group III but not in other groups. These pathological changes seem to be partly similar to those of thalassemic patients after splenectomy. This animal model is thought to be useful to study the pathogenesis of pulmonary thromboembolism, especially in thalassemic patients after splenectomy.

  9. Intravenous injection of sonicated blood induces pulmonary microthromboembolism in rabbits with ligation of the splenic artery.

    PubMed

    Kisanuki, A; Kietthubthew, S; Asada, Y; Marutsuka, K; Funahara, Y; Sumiyoshi, A

    1997-01-15

    Pulmonary thromboembolism (PTE) is found in long hospitalized patients. Chronic PTE has been reported to play an important role in cardiac failure in thalassemic patients after splenectomy. However, the mechanism of PTE in these patients remains unclear. In this study, we attempted to establish an animal model of PTE. We divided New Zealand white rabbits into three groups: Group I was injected sonicated blood, II was injected non-sonicated blood after ligation of the splenic artery, and III was injected sonicated blood after ligation of the splenic artery. After injection of the sonicated blood, we examined the platelet counts every 10 minutes until 1 hour and the rabbits were sacrificed for histological examination. Platelets significantly decreased in number immediately after the injection of sonicated blood in Groups I and III. Many pulmonary thromboemboli composed mainly of platelets were found in Group III but not in other groups. These pathological changes seem to be partly similar to those of thalassemic patients after splenectomy. This animal model is thought to be useful to study the pathogenesis of pulmonary thromboembolism, especially in thalassemic patients after splenectomy.

  10. Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses

    NASA Technical Reports Server (NTRS)

    Erickson, H. H.; Bernard, S. L.; Glenny, R. W.; Fedde, M. R.; Polissar, N. L.; Basaraba, R. J.; Walther, S. M.; Gaughan, E. M.; McMurphy, R.; Hlastala, M. P.

    1999-01-01

    We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

  11. Characterization of red blood cell deformability change during blood storage.

    PubMed

    Zheng, Yi; Chen, Jun; Cui, Tony; Shehata, Nadine; Wang, Chen; Sun, Yu

    2014-02-07

    Stored red blood cells (RBCs) show progressive deformability changes during blood banking/storage. Their deformability changes over an 8 weeks' storage period were measured using a microfluidic device. Hydrodynamic focusing controls the orientation and position of individual RBCs within the microchannel. High-speed imaging (5000 frames s(-1)) captures the dynamic deformation behavior of the cells, and together with automated image analysis, enables the characterization of over 1000 RBCs within 3 minutes. Multiple parameters including deformation index (DI), time constant (shape recovery rate), and RBC circularity were quantified. Compared to previous studies on stored RBC deformability, our results include a significantly higher number of cells (>1000 cells per sample vs. a few to tens of cells per sample) and, for the first time, reveal deformation changes of stored RBCs when traveling through human-capillary-like microchannels. Contrary to existing knowledge, our results demonstrate that the deformation index of RBCs under folding does not change significantly over blood storage. However, significant differences exist in time constants and circularity distribution widths, which can be used to quantify stored RBC quality or age.

  12. Pulmonary diffusing capacity, capillary blood volume, and cardiac output during sustained microgravity

    NASA Technical Reports Server (NTRS)

    Prisk, G. K.; Guy, Harold J. B.; Elliott, Ann R.; Deutschman, Robert A., III; West, John B.

    1993-01-01

    We measured pulmonary diffusing capacity (DL), diffusing capacity per unit lung volume, pulmonary capillary blood volume (Vc), membrane diffusing capacity (Dm), pulmonary capillary blood flow or cardiac output (Qc), and cardiac stroke volume (SV) in four subjects exposed to nine days of microgravity. DL in microgravity was elevated compared with preflight standing values and was higher than preflight supine because of the elevation of both Vc and Dm. The elevation in Vc was comparable to that measured supine in 1 G, but the increase in Dm was in sharp contrast to the supine value. We postulate that, in 0 G, pulmonary capillary blood is evenly distributed throughout the lung, providing for uniform capillary filling, leading to an increase in the surface area available for diffusion. By contrast, in the supine 1-G state, the capillaries are less evenly filled, and although a similar increase in blood volume is observed, the corresponding increase in surface area does not occur. DL and its subdivisions showed no adaptive changes from the first measurement 24 h after the start of 0 G to eight days later. Similarly, there were no trends in the postflight data, suggesting that the principal mechanism of these changes was gravitational. The increase in Dm suggests that subclinical pulmonary edema did not result from exposure to 0 G. Qc was modestly increased inflight and decreased postflight compared with preflight standing. Compared with preflight standing, SV was increased 46 percent inflight and decreased 14 percent in the 1st week postflight. There were temporal changes in Qc and SV during 0 G, with the highest values recorded at the first measurement, 24 h into the flight. The lowest values of Qc and SV occurred on the day of return.

  13. Blood characterization using UV/vis spectroscopy

    NASA Astrophysics Data System (ADS)

    Mattley, Yvette D.; Mitrani-Gold, F.; Orton, S.; Bacon, Christina P.; Leparc, German F.; Bayona, M.; Potter, Robert L.; Garcia-Rubio, Luis H.

    1995-05-01

    The current methods used for typing blood involve an agglutination reaction which results from the association of specific antibodies with antigens present on the erythrocyte cell surface. While this method is effective, it requires involved laboratory procedures to detect the cell surface antigens. As an alternative technique, uv/vis spectroscopy has been investigated as a novel way to characterize and differentiate the blood types. Typing with this technique is based on spectral differences which appear throughout portions of both the ultraviolet and visible range. The origin of these spectral differences is unknown and presently under investigation. They may be due to intrinsic absorption differences at the molecular level, and/or they may be due to scattering differences brought about by either subtle variation in cell surface characteristics, cell shape or state of aggregation. As the background optical density in these samples is identified and accounted for, the spectral differences become more defined. This work and the continuation of this project will be included in a general database encompassing a wide range of blood samples. In addition, long term goals involve the investigation of diseased blood with the potential of providing a more rapid diagnosis for blood borne pathogens.

  14. The mechanical properties of the systemic and pulmonary arteries of Python regius correlate with blood pressures.

    PubMed

    van Soldt, Benjamin J; Danielsen, Carl Christian; Wang, Tobias

    2015-12-01

    Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study.

  15. Patient-specific computational modeling of blood flow in the pulmonary arterial circulation.

    PubMed

    Kheyfets, Vitaly O; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J; Finol, Ender A

    2015-07-01

    Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right Heart Catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R(2)=0.77, P<0.05) and arterial compliance (C) (R(2)=0.63, P<0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained

  16. Patient-Specific Computational Modeling of Blood Flow in the Pulmonary Arterial Circulation

    PubMed Central

    Kheyfets, Vitaly O.; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J.; Finol, Ender A.

    2015-01-01

    Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right heart catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear Stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R2 = 0.77, P < 0.05) and arterial compliance (C) (R2 = 0.63, P < 0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained

  17. 129Xe chemical shift in human blood and pulmonary blood oxygenation measurement in humans using hyperpolarized 129Xe NMR

    PubMed Central

    Norquay, Graham; Leung, General; Stewart, Neil J.; Wolber, Jan

    2016-01-01

    Purpose To evaluate the dependency of the 129Xe‐red blood cell (RBC) chemical shift on blood oxygenation, and to use this relation for noninvasive measurement of pulmonary blood oxygenation in vivo with hyperpolarized 129Xe NMR. Methods Hyperpolarized 129Xe was equilibrated with blood samples of varying oxygenation in vitro, and NMR was performed at 1.5 T and 3 T. Dynamic in vivo NMR during breath hold apnea was performed at 3 T on two healthy volunteers following inhalation of hyperpolarized 129Xe. Results The 129Xe chemical shift in RBCs was found to increase nonlinearly with blood oxygenation at 1.5 T and 3 T. During breath hold apnea, the 129Xe chemical shift in RBCs exhibited a periodic time modulation and showed a net decrease in chemical shift of ∼1 ppm over a 35 s breath hold, corresponding to a decrease of 7–10 % in RBC oxygenation. The 129Xe‐RBC signal amplitude showed a modulation with the same frequency as the 129Xe‐RBC chemical shift. Conclusion The feasibility of using the 129Xe‐RBC chemical shift to measure pulmonary blood oxygenation in vivo has been demonstrated. Correlation between 129Xe‐RBC signal and 129Xe‐RBC chemical shift modulations in the lung warrants further investigation, with the aim to better quantify temporal blood oxygenation changes in the cardiopulmonary vascular circuit. Magn Reson Med 77:1399–1408, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:27062652

  18. Blood lead levels of the battery and exhaust workers and their pulmonary function tests.

    PubMed

    Bagci, C; Bozkurt, A I; Cakmak, E A; Can, S; Cengiz, B

    2004-06-01

    In an attempt to understand the impact of inhaled lead on the pulmonary functions, we assessed the blood lead levels and pulmonary functions of the battery and exhaust workers who are potential candidates for lead inhalation. The hospital staff served as control group. The measurements of lead levels were performed using atomic absorption spectrophotometry. Pulmonary function tests (PFTs) were performed using a portable spirometer. The blood lead levels of the battery workers, exhaust workers and controls were found to be 36.83, 26.94 and 14.81 microg/dl, respectively. The values of the workers were significantly higher than the controls (p < 0.001). The lead levels of the battery workers were also significantly higher than the exhaust workers (p < 0.001). PFT results (maximum voluntary ventilation, forced expiration flow and first forced expiration volume values of the workers) were significantly worse than the controls, and their pulmonary function test results were consistent with restrictive problems in the airways.

  19. Major contribution of central pulmonary reservoir discharge to increased pulmonary arterial diastolic blood flow after birth in near-term lambs.

    PubMed

    Smolich, Joseph J; Mynard, Jonathan P

    2016-10-01

    Recent fetal lamb data have suggested that the pulmonary trunk (PT) region displays a reservoir function and that a pharmacologically induced fall in pulmonary vascular resistance (PVR) increases and redistributes diastolic discharge from this central pulmonary reservoir toward the lungs, thereby producing a positive diastolic offset in the pulmonary arterial (PA) blood flow profile. As a similar offset in PA flow characteristically occurs after birth, this study tested the hypotheses that 1) central pulmonary reservoir discharge is both redistributed toward the lungs and increased in magnitude during the birth transition and 2) discharge from this reservoir constitutes a major component of increased PA diastolic blood flow after birth. Six anesthetized near-term fetal lambs were instrumented with PT, ductal and left PA transit-time flow probes, and aortic, PT and left atrial catheters. Hemodynamic data were recorded in fetuses and at regular intervals during 2-h mechanical ventilation following cesarean section delivery. Diastolic PA blood flow rose from near zero in fetuses to 468 ± 188 ml/min by 15 min (P < 0.001). Central pulmonary reservoir discharge in fetuses (99 ± 44 ml/min) passed primarily right-to-left across the ductus. However, this reservoir discharge redistributed entirely to the lungs by 1 min after birth, and then doubled to a peak of 214 ± 167 ml/min at 15 min (P < 0.001). Reservoir discharge subsequently stabilized at 151 ± 60 ml/min at 30-120 min, which comprised ∼50% of diastolic and ∼20% of mean PA blood flow. These findings suggest that enhanced diastolic central pulmonary reservoir discharge plays a major role in supporting an increased pulmonary perfusion after birth.

  20. Spatial distribution of pulmonary blood flow in dogs in increased force environments

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. F.; Ritman, E. L.; Chevalier, P. A.; Sass, D. J.; Wood, E. H.

    1978-01-01

    Spatial distribution of pulmonary blood flow during 2- to 3-min exposures to 6-8 Gy acceleration was studied, using radioactive microspheres in dogs, and compared to previously reported 1 Gy control distributions. Isotope distributions were measured by scintiscanning individual 1-cm-thick cross sections of excised, fixed lungs. Results indicate: (1) the fraction of cardiac output traversing left and right lungs did not change systematically with the duration and magnitude of acceleration; but (2) the fraction is strongly affected by the occurrence or absence of fast deep breaths, which cause an increase or decrease, respectively, in blood flow through the dependent lung; and (3) Gy acceleration caused a significant increase in relative pulmonary vascular resistance (PVR) in nondependent and dependent regions of the lung concurrent with a decrease in PVR in the midsagittal region of the thorax.

  1. Effects of posture on blood flow diversion by hypoxic pulmonary vasoconstriction in dogs

    NASA Technical Reports Server (NTRS)

    Walther, S. M.; Domino, K. B.; Hlastala, M. P.

    1998-01-01

    We used differential excretion of sulphur hexafluoride from the left and right lung to measure blood flow diversion by hypoxic pulmonary vasoconstriction (HPV) in the prone and supine positions in dogs (n = 9). Gas exchange was assessed using the multiple inert gas elimination technique. Blood flow diversion from the hypoxic (3% oxygen) left lung was mean 70.7 (SD 11.2)% in the supine compared with 57.0 (12.1)% in the prone position (P < 0.02). The supine position was associated with increased perfusion to low VA/Q regions (P < 0.05). The increased flow diversion with hypoxia in the supine position was associated with more ventilation to high VA/Q regions (P < 0.05). We conclude that flow diversion by hypoxic pulmonary vasoconstriction is greater in the supine position. This effect could contribute to the variable response in gas exchange with positioning in patients with ARDS.

  2. Regional pulmonary blood flow in sitting and supine man during and after acute hypoxia

    PubMed Central

    Dawson, Arthur

    1969-01-01

    Regional pulmonary blood flow was measured by external counting of intravenously injected 133Xe during 20 min of breathing 14.2% oxygen and during 20 min of recovery from hypoxia. 16 normal human volunteers were studied, nine sitting and seven supine. During hypoxia there was a slight but significant increase in relative perfusion of the upper portions of the lungs in both the sitting and supine subjects. During recovery from hypoxia, blood flow distribution differed significantly from the control. The erect subjects showed increased relative perfusion of the lung bases and the supine subjects showed increased relative perfusion of the upper zones. Comparison of the distribution of inhaled and intravenously injected isotope showed that in the sitting subjects the altered distribution during hypoxia tended to make alveolar oxygen tension more uniform. In the supine subjects, however, the shift in blood flow increased the perfusion of the regions with the lowest ventilation/perfusion, tending to accentuate uneven alveolar oxygen tension. Therefore it does not seem that the altered blood flow distribution during hypoxia was due to selective vasoconstriction in the regions of lowest alveolar oxygen tension, but rather that vasoconstriction was greatest in the lower lung zones because the vessels there are more responsive to hypoxia. During mild acute hypoxia, vasoconstrictor tone does not seem to effectively match ventilation and perfusion. The altered distribution of pulmonary blood flow during recovery from hypoxia suggests the occurrence of posthypoxic vasodilation. Failure to consider this possibility may lead to erroneous interpretation of pulmonary hemodynamic measurements made after the inspired oxygen concentration has been changed. PMID:5764012

  3. Assessing the calf pulmonary function during a long-term biventricular assist device study with a centrifugal blood pump.

    PubMed

    Nonaka, Kenji; Linneweber, Joerg; Ichikawa, Seiji; Kawahito, Shinji; Motomura, Tadashi; Ishitoya, Hiroshi; Oestmann, Daniel; Glueck, Julia; Nosé, Yukihiko

    2002-11-01

    Pulmonary congestion due to inappropriate pump flow management is one major problem necessary to avoid during long-term biventricular assist device (BVAD) implantation. Our objective was to assess the effects of pulmonary arterial flow rate and flow rates of both (right and left) bypass pumps. Six healthy calves, which had been implanted with a BVAD system, were selected for this retrospective study. Pulmonary artery flows, both pump flow rates, oxygen saturation of the arterial blood, and pulmonary arterial pressures were assessed as parameters of pulmonary function as was routine clinical evaluation of respiratory rate and character and chest auscultation. The average pulmonary artery flow rate (PAF), systolic pressure of pulmonary artery (sPAP), and oxygen saturation were 148.8 ml/kg per min, 35.1 mm Hg, and 95.3%, respectively. Pulmonary dysfunction occurred in one case, in which the mean PAF, sPAP, and oxygen saturation were 169 ml/kg per min, 66.1 mm Hg, and 90.9%, respectively. The ratio for the right/left pump flow rate (R/L ratio) for the case having pulmonary dysfunction was 1.57 even though the ratio for the other cases was less than 1. Maintaining an R/L ratio less than 1 and/or PAF less than 160 ml/kg per min and PAP less than 50 mm Hg is recommended as the initial conditions to target to avoid pulmonary dysfunction during a BVAD implantation with a beating heart condition.

  4. Age-dependent neutrophil and blood flow responsiveness in acute pulmonary inflammation in rabbits.

    PubMed

    Hyde, D M; Downey, G P; Tablin, F; Rosengren, S; Giclas, P C; Henson, P M; Worthen, G S

    1997-03-01

    Diminished ability of neonatal neutrophils to orient and move in a chemotactic gradient has been linked to compromised pulmonary host defense. We investigated whether deficiency of neonatal neutrophil function in vitro was evident in acute pulmonary inflammation. Analysis of neutrophils in vitro showed impaired chemotaxis in 4-wk-old compared with adult rabbits. In vivo-directed migration of labeled neutrophils into the alveolar space of adult rabbits in response to C5f instillation was significantly less for neutrophils donated from 4-wk-old rabbits compared with those from adults. In contrast, there were no differences in the alveolar accumulation of 4-wk-old and adult labeled neutrophils in 4-wk-old rabbits in response to C5f instillation, although the response showed a shorter time course than seen in adult rabbits. Adult rabbits diverted 46% of the blood away from the right cranial lung lobe, whereas 4-wk-old rabbits showed no change in blood flow after C5f instillation. Megakaryocytes (a source of blood flow mediators) were 3.2-fold greater in adult compared with 4-wk-old lung. These data suggest that the lack of blood flow diversion from inflamed neonatal lung increases neutrophil migration into alveoli, allowing for preservation of an inflammatory response despite neutrophil deficiencies in chemotaxis.

  5. Phasic reflux of pulmonary blood flow in atelectasis: influence of systemic PO2.

    PubMed

    Newell, J C; Levitzky, M G; Krasney, J A; Dutton, R E

    1976-06-01

    In 16 dogs ventilated with 100% O2, control blood flow to the left lung was 35 +/- 2% of aortic flow. When left lung atelectasis was induced, left pulmonary artery flow fell to 19 +/- 2% of aortic flow. A large retrograde component of flow developed in this pulmonary artery, suggesting that blood flows into the pulmonary arteries of both lungs during systole, but flows back out of the collapsed lung and into the uncollapsed lung during diastole. Systemic PaO2 remained above 78 mmHg. Subsequently, when the ventilation of the right lung was changed from oxygen to room air, systemic PaO2 fell to 64 +/- 3 mmHg and atelectatic left lung flow rose from 19 +/- 2% to 28 +/- 2% f aortic flow. This was associated with a reduction in reflux from the atelectatic lung. These results suggest that the attenuation of flow to an atelectatic lung is more pronounced if systemic normoxemia is maintained by adequate oxygenation of the normal lung.

  6. Blood Perfusion in Microfluidic Models of Pulmonary Capillary Networks: Role of Geometry and Hematocrit

    NASA Astrophysics Data System (ADS)

    Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration

    2015-11-01

    Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.

  7. A modified Verhoeff's elastin histochemical stain to enable pulmonary arterial hypertension model characterization.

    PubMed

    Percival, K R; Radi, Z A

    2016-02-11

    Optimal histochemical staining is critical to ensure excellent quality stained sections to enable light microscopic and histomorphometric image analysis.  Verhoeff-van Gieson is the most widely used histochemical stain for the visualization of vascular elastic fibers. However, it is notoriously difficult to differentiate fine elastic fibers of small vasculature to enable histomorphometric image analysis of vasculature size characterization especially in organs such as the lung. A tissue fixation regime of 10% neutral buffered formalin with subsequent fixation in 70% ethanol further compounds the problem of small vessel staining and identification.  Therefore, a modified Verhoeff's elastin stain was developed as a reliable method to optimally highlight the internal and external elastic lamina of small arteries (50-100 µm) and intra-acinar vessels (10-50 µm) in 3 µm thick lung tissue sections from models of pulmonary arterial hypertension.  This modified Verhoeff's elastin stain demonstrated optimal staining of fine elastic fibers of pulmonary blood vessels. As a result, high-quality histomorphometric image analysis evaluation of vessel wall thickness in small arteries and intra-acinar vessels was successfully accomplished.  In conclusion, modification of the standard Verhoeff-van Gieson histochemical stain is needed to visualize small caliber vessels' elastic fibers especially in tissues not fixed in 10% neutral buffered formalin only.

  8. Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

    PubMed Central

    Qureshi, M. Umar; Vaughan, Gareth D.A.; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S.; Olufsen, Mette S.; Hill, N.A.

    2014-01-01

    A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen and coworkers (Ottesen et al., 2003; Olufsen et al., 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50µm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment of circulatory diseases within the lung. PMID:24610385

  9. Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution.

    PubMed

    Clewe, Oskar; Karlsson, Mats O; Simonsson, Ulrika S H

    2015-12-01

    Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs.

  10. The Time Course of Pulmonary Function Tests in COPD Patients with Different Levels of Blood Eosinophils

    PubMed Central

    Rogliani, Paola; Puxeddu, Ermanno; Ciaprini, Chiara; Ora, Josuel; Onorato, Angelo; Pezzuto, Gabriella; Calzetta, Luigino

    2016-01-01

    Only very few studies have investigated the influence of eosinophils on the functional progression of COPD. We aimed at retrospectively analyzing the trend of pulmonary function tests over time in patients with COPD according to two baseline blood eosinophil cell count strata (<2% [EOS−] and ≥2% [EOS+]). We used the last 9-year data present in the database of our outpatient clinic and selected only those who had two blood counts that would guarantee the stability of the value of eosinophils and serial spirometry for 4 consecutive years. The analysis of the time course of the spirometric variables analysed showed differences in FEV1 and FVC decline between the subjects of the EOS− group and those of the EOS+ group. The integrated evaluation of our results suggests that the different level of blood eosinophils in the two groups may have influenced independently the time course of the pulmonary function tests and identify two subgroups of subjects with specific disease characteristics: the hyperinflator and the rapid decliner, respectively. PMID:27822474

  11. Comparative physiology of the pulmonary blood-gas barrier: the unique avian solution

    PubMed Central

    2009-01-01

    Two opposing selective pressures have shaped the evolution of the structure of the blood-gas barrier in air breathing vertebrates. The first pressure, which has been recognized for 100 years, is to facilitate diffusive gas exchange. This requires the barrier to be extremely thin and have a large area. The second pressure, which has only recently been appreciated, is to maintain the mechanical integrity of the barrier in the face of its extreme thinness. The most important tensile stress comes from the pressure within the pulmonary capillaries, which results in a hoop stress. The strength of the barrier can be attributed to the type IV collagen in the extracellular matrix. In addition, the stress is minimized in mammals and birds by complete separation of the pulmonary and systemic circulations. Remarkably, the avian barrier is about 2.5 times thinner than that in mammals and also is much more uniform in thickness. These advantages for gas exchange come about because the avian pulmonary capillaries are unique among air breathers in being mechanically supported externally in addition to the strength that comes from the structure of their walls. This external support comes from epithelial plates that are part of the air capillaries, and the support is available because the terminal air spaces in the avian lung are extremely small due to the flow-through nature of ventilation in contrast to the reciprocating pattern in mammals. PMID:19793953

  12. Blood and tissue distribution of posaconazole in a rat model of invasive pulmonary aspergillosis.

    PubMed

    Cendejas-Bueno, E; Forastiero, A; Ruiz, I; Mellado, E; Gavaldà, J; Gomez-Lopez, A

    2017-02-01

    Posaconazole is the recommended prophylactic agent in patients at high risk of invasive fungal infection, since adequate drug levels seem to be reached in target sites despite the relatively low levels detected in blood. The objective of this study is to obtain pharmacokinetic (PK) information associated to blood and tissue distribution of posaconazole in an animal model of invasive pulmonary aspergillosis. The PK parameters in lung samples were systematically higher than in serum. After multiple-dose administration of posaconazole, a significant accumulation of the drug was evident in lung tissue. The PK behavior of posaconazole in this particular experimental model is similar to that observed in humans. Thus, we believe this model could be a valid tool to evaluate posaconazole exposure-response relationship.

  13. An analysis of estimation of pulmonary blood flow by the single-breath method

    NASA Technical Reports Server (NTRS)

    Srinivasan, R.

    1986-01-01

    The single-breath method represents a simple noninvasive technique for the assessment of capillary blood flow across the lung. However, this method has not gained widespread acceptance, because its accuracy is still being questioned. A rigorous procedure is described for estimating pulmonary blood flow (PBF) using data obtained with the aid of the single-breath method. Attention is given to the minimization of data-processing errors in the presence of measurement errors and to questions regarding a correction for possible loss of CO2 in the lung tissue. It is pointed out that the estimations are based on the exact solution of the underlying differential equations which describe the dynamics of gas exchange in the lung. The reported study demonstrates the feasibility of obtaining highly reliable estimates of PBF from expiratory data in the presence of random measurement errors.

  14. Blood Level of Polymorphonuclear Neutrophil Leukocytes and Bronchial Hyperreactivity in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Cukic, Vesna

    2015-01-01

    Introduction: Polymorphonuclear neutrophil leukocytes (PMNL) have an important defensive role against various microorganisms and other agents, but by liberating various substances, first of all the superoxide anion (O 2¯), they can damage the bronchial mucosa and influence the development of bronchial inflammation which is the fundamental of bronchial hyperreactivity (BHR). Objective: to show the role of the PMNL for development and level of BHR in patients with chronic obstructive pulmonary disease (COPD). Material and methods: We observed 160 patients with COPD treated in Clinic for Pulmonary Diseases and TB “Podhrastovi” Sarajevo during three years :from 2012 to 2014. They were divided into groups and subgroups according to the first registration of BHR in the course of illness and to the number of exacerbations of the disease in one year. The number of blood PMNL was measured in a stable state of disease at the begging and at the end of investigation. Results: The number of blood PMNL was significantly greater in patients with 3 or more exacerbations per one year (p <0.01). Patients with BHR had significantly greater number blood PMNL than patients without BHR (p< 0.05). Patients with 3 exacerbations per year had a statistically significant increase of number of PMNL between first and last examination (p<0.01). Conclusion: There is statistically significant correlation between the number of blood PMNL and the level of BHR in COPD, but future examination need to be done to determine real role and mode of action of PMNL for these processes. PMID:26543311

  15. Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow.

    PubMed

    Datar, Sanjeev A; Johnson, Eric G; Oishi, Peter E; Johengen, Michael; Tang, Eric; Aramburo, Angela; Barton, Jubilee; Kuo, Hsuan-Chang; Bennett, Stephen; Xoinis, Konstantine; Reel, Bhupinder; Kalkan, Gokhan; Sajti, Eniko; Osorio, Oscar; Raff, Gary W; Matthay, Michael A; Fineman, Jeffrey R

    2012-03-15

    Abnormalities of the lymphatic circulation are well recognized in patients with congenital heart defects. However, it is not known how the associated abnormal blood flow patterns, such as increased pulmonary blood flow (PBF), might affect pulmonary lymphatic function and structure. Using well-established ovine models of acute and chronic increases in PBF, we cannulated the efferent lymphatic duct of the caudal mediastinal node and collected and analyzed lymph effluent from the lungs of lambs with acutely increased PBF (n = 6), chronically increased PBF (n = 6), and age-matched normal lambs (n = 8). When normalized to PBF, we found that lymph flow was unchanged following acute increases in PBF but decreased following chronic increases in PBF. The lymph:plasma protein ratio decreased with both acute and chronic increases in PBF. Lymph bioavailable nitric oxide increased following acute increases in PBF but decreased following chronic increases in PBF. In addition, we found perturbations in the transit kinetics of contrast material through the pleural lymphatics of lambs with chronic increases in PBF. Finally, there were structural changes in the pulmonary lymphatic system in lambs with chronic increases in PBF: lymphatics from these lambs were larger and more dilated, and there were alterations in the expression of vascular endothelial growth factor-C, lymphatic vessel endothelial hyaluronan receptor-1, and Angiopoietin-2, proteins known to be important for lymphatic growth, development, and remodeling. Taken together these data suggest that chronic increases in PBF lead to both functional and structural aberrations of lung lymphatics. These findings have important therapeutic implications that warrant further study.

  16. Pulmonary Hypertension in Scleroderma

    MedlinePlus

    PULMONARY HYPERTENSION IN SCLERODERMA PULMONARY HYPERTENSION Pulmonary hypertension (PH) is high blood pressure in the blood vessels ... with scleroderma are at increased risk for developing PH from several mechanisms. Frequently patients with scleroderma have ...

  17. Chemoreceptor influence on pulmonary blood flow during unilateral hypoxia in dogs.

    PubMed

    Levitzky, M G; Newell, J C; Krasney, J A; Dutton, R E

    1977-12-01

    Dogs anesthetized with 30 mg/kg pentobarbital were artificially respired after differential cannulation of the main stem bronchi. Following median sternotomy, blood flow was monitored by electromagnetic flow probes on the left pulmonary artery (QL) and on the pulmonary trunk or aorta, QT. Following 10 min of bilateral 100% O2, QL was 42.5 +/- 7% of QT. When 6% O2, was substituted as the gas mixture inspired by the left lung while the right lung remained on 100% O2, PaO2 was above 70 mm Hg and QL fell to 24.5 +/- 5% of QT. Room air was then used to ventilate the right lung while the left lung remained on 6% O2. This caused PaO2 to fall to 42.3 +/- 3 MM Hg and QL to rise to 38.3 +/- 6% QT. This increase in blood flow to the unilaterally hypoxic lung during systemic hypoxemia did not occur in dogs after peripheral chemoreceptor denervation. Therefore, interference with the local response to alveolar hypoxia during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.

  18. Impact of ambient air pollution on the differential white blood cell count in patients with chronic pulmonary disease.

    PubMed

    Brüske, Irene; Hampel, Regina; Socher, Martin M; Rückerl, Regina; Schneider, Alexandra; Heinrich, Joachim; Oberdörster, Günter; Wichmann, H-Erich; Peters, Annette

    2010-02-01

    Epidemiologic studies report associations between particulate air pollution and increased mortality from pulmonary diseases. This study was performed to examine whether the exposure to ambient gaseous and particulate air pollution leads to an alteration of the differential white blood cell count in patients with chronic pulmonary diseases like chronic bronchitis, chronic obstructive pulmonary disease, and asthma. A prospective panel study was conducted in Erfurt, Eastern Germany, with 12 repeated differential white blood cell counts in 38 males with chronic pulmonary diseases. Hourly particulate and gaseous air pollutants and meteorological data were acquired. Mixed models with a random intercept adjusting for trend, meteorology, weekday, and other risk variables were used. In this explorative analysis, we found an immediate decrease of polymorphonuclear leukocytes in response to an increase of most gaseous and particulate pollutants. Lymphocytes increased within 24 h in association with all gaseous pollutants but showed only minor effects in regard to particulate air pollution. Monocytes showed an increase associated with ultrafine particles, and nitrogen monoxide. The effect had two peaks in time, one 0-23 h before blood withdrawal and a second one with a time lag of 48-71 h. The increase of particulate and gaseous air pollution was associated with multiple changes in the differential white blood cell count in patients with chronic pulmonary diseases.

  19. Pulmonary Embolism

    MedlinePlus

    ... pulmonary embolism is a sudden blockage in a lung artery. The cause is usually a blood clot ... loose and travels through the bloodstream to the lung. Pulmonary embolism is a serious condition that can ...

  20. Pulmonary fibrosis: tissue characterization using late-enhanced MRI compared with unenhanced anatomic high-resolution CT

    PubMed Central

    Lavelle, Lisa P.; Brady, Darragh; McEvoy, Sinead; Murphy, David; Gibney, Brian; Gallagher, Annika; Butler, Marcus; Shortt, Fionnula; McMullen, Marie; Fabre, Aurelie; Lynch, David A.; Keane, Michael P.; Dodd, Jonathan D.

    2017-01-01

    PURPOSE We aimed to prospectively evaluate anatomic chest computed tomography (CT) with tissue characterization late gadolinium-enhanced magnetic resonance imaging (MRI) in the evaluation of pulmonary fibrosis (PF). METHODS Twenty patients with idiopathic pulmonary fibrosis (IPF) and twelve control patients underwent late-enhanced MRI and high-resolution CT. Tissue characterization of PF was depicted using a segmented inversion-recovery turbo low-angle shot MRI sequence. Pulmonary arterial blood pool nulling was achieved by nulling main pulmonary artery signal. Images were read in random order by a blinded reader for presence and extent of overall PF (reticulation and honeycombing) at five anatomic levels. Overall extent of IPF was estimated to the nearest 5% as well as an evaluation of the ratios of IPF made up of reticulation and honeycombing. Overall grade of severity was dependent on the extent of reticulation and honeycombing. RESULTS No control patient exhibited contrast enhancement on lung late-enhanced MRI. All IPF patients were identified with late-enhanced MRI. Mean signal intensity of the late-enhanced fibrotic lung was 31.8±10.6 vs. 10.5±1.6 for normal lung regions, P < 0.001, resulting in a percent elevation in signal intensity from PF of 204.8%±90.6 compared with the signal intensity of normal lung. The mean contrast-to-noise ratio was 22.8±10.7. Late-enhanced MRI correlated significantly with chest CT for the extent of PF (R=0.78, P = 0.001) but not for reticulation, honeycombing, or coarseness of reticulation or honeycombing. CONCLUSION Tissue characterization of IPF is possible using inversion recovery sequence thoracic MRI. PMID:28067202

  1. Comparison of Aryl Hydrocarbon Hydroxylase Induction in Cultured Blood Lymphocytes and Pulmonary Macrophages

    PubMed Central

    McLemore, Theodore L.; Martin, R. Russell; Toppell, Kenneth L.; Busbee, David L.; Cantrell, Elroy T.

    1977-01-01

    Aryl hydrocarbon hydroxylase induction was studied in cultured peripheral blood lymphocytes and pulmonary alveolar macrophages from 15 smokers and 8 nonsmokers with a variety of pulmonary diseases. Enzyme levels in lymphocytes from cigarette smokers cultured in medium without an inducing agent were 57±6 mU/106 cells (mean±SEM), while enzyme levels in lymphocytes from nonsmokers were 20±2 mU/106 cells (P < 0.001). When lymphocytes were cultured in the presence of the inducing agent, benzo-(a)anthracene, enzyme activity was increased to 168±23 mU/106 cells in smokers' cells and 99±22 mU/106 cells in lymphocytes from nonsmokers (P < 0.04). When noninduced enzyme values in cultured macrophages were compared, smokers' cells had enzyme levels of 45±5 mU/106 cells, whereas nonsmokers had enzyme activity of 24±2 mU/106 cells (P < 0.002). However, pulmonary macrophages from smokers or nonsmokers, cultured in the presence of benzo(a)-anthracene, had similar levels of induced enzyme activity (P > 0.1). A positive correlation was observed for nonsmokers (r = 0.596, P > 0.1 <0.2) or smokers (r = 0.640, P < 0.04), when enzyme values for noninduced cultures of macrophages and lymphocytes from individual patients were simultaneously compared. Enzyme values for macrophages and lymphocytes cultured in the presence of an inducer also revealed a positive correlation for individual smokers (r = 0.801, P < 0.001) or nonsmokers (r = 0.785, P < 0.01). Inducibility (expressed as fold-induction) for macrophages and lymphocytes from individual patients was also positively correlated (r = 0.889, P < 0.001 for nonsmokers and r = 0.942, P < 0.001 for smokers). These results indicate that the capacity for aryl hydrocarbon hydroxylase induction is similar whether tested in lymphocytes or pulmonary macrophages from this group of pulmonary disease patients. PMID:908748

  2. IDENTIFICATION AND CHARACTERIZATION OF DISEASE USING PULMONARY FUNCTION TESTS

    EPA Science Inventory

    Abstract
    Pulmonary function testing is used routinely in human medicine to objectively define functional deficits in individuals with respiratory disease. Despite the fact that respiratory disease is a common problem in veterinary medicine, evaluation of the small animal pa...

  3. A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV

    PubMed Central

    Attia, Engi F.; Akgün, Kathleen M.; Soo Hoo, Guy W.; Freiberg, Matthew S.; Butt, Adeel A.; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T.; Graber, Christopher J.; Huang, Laurence; Crothers, Kristina

    2017-01-01

    Objectives The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. Methods We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Results Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1–39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). Conclusions A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era. PMID:28122034

  4. Increase in pulmonary blood flow at birth: role of oxygen and lung aeration.

    PubMed

    Lang, Justin A R; Pearson, James T; Binder-Heschl, Corinna; Wallace, Megan J; Siew, Melissa L; Kitchen, Marcus J; te Pas, Arjan B; Fouras, Andreas; Lewis, Robert A; Polglase, Graeme R; Shirai, Mikiyasu; Hooper, Stuart B

    2016-03-01

    Lung aeration stimulates the increase in pulmonary blood flow (PBF) at birth, but the spatial relationships between PBF and lung aeration and the role of increased oxygenation remain unclear. Using simultaneous phase-contrast X-ray imaging and angiography, we have investigated the separate roles of lung aeration and increased oxygenation in PBF changes at birth using near-term (30 days of gestation) rabbit kits (n = 18). Rabbits were imaged before ventilation, then the right lung was ventilated with 100% nitrogen (N2), air or 100% O2 (oxygen), before all kits were switched to ventilation in air, followed by ventilation of both lungs using air. Unilateral ventilation of the right lung with 100% N2 significantly increased heart rate (from 69.4 ± 4.9 to 93.0 ± 15.0 bpm), the diameters of both left and right pulmonary axial arteries, number of visible vessels in both left and right lungs, relative PBF index in both pulmonary arteries, and reduced bolus transit time for both left and right axial arteries (from 1.34 ± 0.39 and 1.81 ± 0.43 s to 0.52 ± 0.17 and 0.89 ± 0.21 s in the left and right axial arteries, respectively). Similar changes were observed with 100% oxygen, but increases in visible vessel number and vessel diameter of the axial arteries were greater in the ventilated right lung during unilateral ventilation. These findings confirm that PBF increase at birth is not spatially related to lung aeration and that the increase in PBF to unventilated regions is unrelated to oxygenation, although oxygen can potentiate this increase.

  5. In vivo support for the new concept of pulmonary blood flow-mediated CO2 gas excretion in the lungs.

    PubMed

    Kawai, Yoshiko; Ajima, Kumiko; Kaidoh, Maki; Sakaguchi, Masao; Tanaka, Satoshi; Kawamata, Mikito; Kimura, Hiroko; Ohhashi, Toshio

    2015-06-15

    To further examine the validity of the proposed concept of pulmonary blood flow-dependent CO2 gas excretion in the lungs, we investigated the effects of intramediastinal balloon catheterization-, pulmonary artery catheterization-, or isoprenaline (ISP)-induced changes in pulmonary blood flow on the end-expiratory CO2 gas pressure (PeCO2 ), the maximal velocity of the pulmonary artery (Max Vp), systemic arterial pressure, and heart rate of anesthetized rabbits. We also evaluated the changes in the PeCO2 in clinical models of anemia or pulmonary embolism. An almost linear relationship was detected between the PeCO2 and Max Vp. In an experiment in which small pulmonary arteries were subjected to stenosis, the PeCO2 fell rapidly, and the speed of the reduction was dependent on the degree of stenosis. ISP produced significant increases in the PeCO2 of the anesthetized rabbits. Conversely, treatment with piceatannol or acetazolamide induced significant reductions in the PeCO2 . Treatment with a cell surface F1/FO ATP synthase antibody caused significant reductions in the PeCO2 itself and the ISP-induced increase in the PeCO2 . Neither the PeCO2 nor SAP was significantly influenced by marked anemia [%hematocrit (Ht), 70 ∼ 47%]. On the other hand, in the presence of less severe anemia (%Ht: 100 ∼ 70%) both the PeCO2 and SAP fell significantly when the rabbits' blood viscosity was decreased. The rabbits in which pulmonary embolisms were induced demonstrated significantly reduced PeCO2 values, which was compatible with the lowering of their Max Vp. In conclusion, we reaffirm the validity of the proposed concept of CO2 gas exchange in the lungs.

  6. L-Carnitine Preserves Endothelial Function in a Lamb Model of Increased Pulmonary Blood Flow

    PubMed Central

    Sharma, Shruti; Aramburo, Angela; Rafikov, Ruslan; Sun, Xutong; Kumar, Sanjiv; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Xoinis, Kon; Kalkan, Gohkan; Fratz, Sohrab; Fineman, Jeffrey R.; Black, Stephen M.

    2013-01-01

    Background In our model of congenital heart disease (CHD) with increased pulmonary blood flow (Shunt), we have recently shown a disruption in carnitine homeostasis, associated with mitochondrial dysfunction and decreased eNOS/Hsp90 interactions that contribute to eNOS uncoupling, increased superoxide levels, and decreased bioavailable NO. Thus, we undertook this study to test the hypothesis that L-carnitine therapy would maintain mitochondrial function, and NO signaling. Methods Thirteen fetal lambs underwent in utero placement of an aortopulmonary graft. Immediately following delivery, lambs received daily treatment with oral L-carnitine or its vehicle. Results L-carnitine-treated lambs had decreased levels of acyl carnitine, and a reduced acyl carnitine: free carnitine ratio compared to vehicle treated Shunt lambs. These changes correlated with increased carnitine acetyl transferase (CrAT) protein and enzyme activity and decreased levels of nitrated CrAT. The lactate: pyruvate ratio was also decreased in L-carnitine-treated lambs. Hsp70 protein levels were significantly decreased and this correlated with increases in eNOS/Hsp90 interactions, NOS activity, NOx levels, and a significant decrease in eNOS-derived superoxide. Further, acetylcholine significantly decreased left pulmonary vascular resistance (PVR) only in L-carnitine-treated lambs. Conclusion L-carnitine therapy may improve the endothelial dysfunction noted in children with CHD, and has important clinical implications that warrant further investigation. PMID:23628882

  7. Red blood cell dynamics in biomimetic microfluidic networks of pulmonary alveolar capillaries

    PubMed Central

    Stauber, Hagit; Waisman, Dan; Korin, Netanel; Sznitman, Josué

    2017-01-01

    The pulmonary capillary networks (PCNs) embody organ-specific microvasculatures, where blood vessels form dense meshes that maximize the surface area available for gas exchange in the lungs. With characteristic capillary lengths and diameters similar to the size of red blood cells (RBCs), seminal descriptions coined the term “sheet flow” nearly half a century ago to differentiate PCNs from the usual notion of Poiseuille flow in long straight tubes. Here, we revisit in true-scale experiments the original “sheet flow” model and devise for the first time biomimetic microfluidic platforms of organ-specific PCN structures perfused with RBC suspensions at near-physiological hematocrit levels. By implementing RBC tracking velocimetry, our measurements reveal a wide range of heterogonous RBC pathways that coexist synchronously within the PCN; a phenomenon that persists across the broad range of pressure drops and capillary segment sizes investigated. Interestingly, in spite of the intrinsic complexity of the PCN structure and the heterogeneity in RBC dynamics observed at the microscale, the macroscale bulk flow rate versus pressure drop relationship retains its linearity, where the hydrodynamic resistance of the PCN is to a first order captured by the characteristic capillary segment size. To the best of our knowledge, our in vitro efforts constitute a first, yet significant, step in exploring systematically the transport dynamics of blood in morphologically inspired capillary networks. PMID:28090238

  8. Red blood cell dynamics in biomimetic microfluidic networks of pulmonary alveolar capillaries.

    PubMed

    Stauber, Hagit; Waisman, Dan; Korin, Netanel; Sznitman, Josué

    2017-01-10

    The pulmonary capillary networks (PCNs) embody organ-specific microvasculatures, where blood vessels form dense meshes that maximize the surface area available for gas exchange in the lungs. With characteristic capillary lengths and diameters similar to the size of red blood cells (RBCs), seminal descriptions coined the term "sheet flow" nearly half a century ago to differentiate PCNs from the usual notion of Poiseuille flow in long straight tubes. Here, we revisit in true-scale experiments the original "sheet flow" model and devise for the first time biomimetic microfluidic platforms of organ-specific PCN structures perfused with RBC suspensions at near-physiological hematocrit levels. By implementing RBC tracking velocimetry, our measurements reveal a wide range of heterogonous RBC pathways that coexist synchronously within the PCN; a phenomenon that persists across the broad range of pressure drops and capillary segment sizes investigated. Interestingly, in spite of the intrinsic complexity of the PCN structure and the heterogeneity in RBC dynamics observed at the microscale, the macroscale bulk flow rate versus pressure drop relationship retains its linearity, where the hydrodynamic resistance of the PCN is to a first order captured by the characteristic capillary segment size. To the best of our knowledge, our in vitro efforts constitute a first, yet significant, step in exploring systematically the transport dynamics of blood in morphologically inspired capillary networks.

  9. Inhaled NO therapy increases blood nitrite, nitrate and S-nitrosohemoglobin concentrations in infants with pulmonary hypertension

    PubMed Central

    Ibrahim, Yomna I.; Ninnis, Janet R.; Hopper, Andrew O.; Deming, Douglas D.; Zhang, Amy X.; Herring, Jason L.; Sowers, Lawrence C.; McMahon, Timothy J.; Power, Gordon G.; Blood, Arlin B.

    2011-01-01

    Objective To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity following inhaled NO therapy in infants with pulmonary hypertension. Study design In this single center study five sequential blood samples were collected from infants with pulmonary hypertension before, during and after therapy with iNO (n=17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n=16) and from healthy adults for comparison (n=12). Results After beginning iNO (20 ppm) whole blood nitrite increased about two-fold within two hours (P<0.01). Whole blood nitrate increased to four-fold higher than baseline during treatment with 20ppm iNO (P<0.01). S-nitrosohemoglobin (SNO-Hb) increased measurably after beginning iNO (P<0.01) whereas iron nitrosyl hemoglobin and total Hb-bound NO-species compounds did not change. Conclusion Treatment of pulmonary hypertensive infants with iNO results in increases in nitrite, nitrate, and SNO-Hb in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart and other organs. PMID:21907348

  10. Pulmonary Hypertension

    MedlinePlus

    ... on Twitter. What Is Pulmonary Hypertension? Pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), or PH, is increased pressure in the pulmonary arteries. These arteries carry blood from your heart to your lungs to pick up oxygen. PH causes symptoms such as shortness of ...

  11. Characterization of optimal resting tension in human pulmonary arteries

    PubMed Central

    Hussain, Azar; Bennett, Robert T; Chaudhry, Mubarak A; Qadri, Syed S; Cowen, Mike; Morice, Alyn H; Loubani, Mahmoud

    2016-01-01

    AIM To determine the optimum resting tension (ORT) for in vitro human pulmonary artery (PA) ring preparations. METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution (Krebs). The pulmonary arteries were then cut into 2 mm long rings. PA rings were mounted in 25 mL organ baths or 8 mL myograph chambers containing Krebs compound (37 °C, bubbled with 21% O2: 5% CO2) to measure changes in isometric tension. The resting tension was set at 1-gram force (gf) with vessels being left static to equilibrate for duration of one hour. Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf. Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension (1.2, 1.4, 1.6, 1.8 and 2.0 gf). RESULTS Twenty PA rings of internal diameter between 2-4 mm were prepared from 4 patients. In human PA rings incrementing the tension during rest stance by 0.6 gf, up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension. Further enhancement of active tension by 0.4 gf, up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction. Both Myograph and the organ bath demonstrated identical conclusions, supporting that the radial optimal resting tension for human PA ring was 1.61 g. CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf (15.78 mN) for human PA rings. PMID:27721938

  12. Redistribution of pulmonary blood flow during unilateral hypoxia in prone and supine dogs

    NASA Technical Reports Server (NTRS)

    Mann, C. M.; Domino, K. B.; Walther, S. M.; Glenny, R. W.; Polissar, N. L.; Hlastala, M. P.

    1998-01-01

    We used fluorescent-labeled microspheres in pentobarbital-anesthetized dogs to study the effects of unilateral alveolar hypoxia on the pulmonary blood flow distribution. The left lung was ventilated with inspired O2 fraction of 1.0, 0.09, or 0.03 in random order; the right lung was ventilated with inspired O2 fraction of 1.0. The lungs were removed, cleared of blood, dried at total lung capacity, then cubed to obtain approximately 1,500 small pieces of lung ( approximately 1.7 cm3). The coefficient of variation of flow increased (P < 0.001) in the hypoxic lung but was unchanged in the hyperoxic lung. Most (70-80%) variance in flow in the hyperoxic lung was attributable to structure, in contrast to only 30-40% of the variance in flow in the hypoxic lung (P < 0.001). When adjusted for the change in total flow to each lung, 90-95% of the variance in the hyperoxic lung was attributable to structure compared with 70-80% in the hypoxic lung (P < 0.001). The hilar-to-peripheral gradient, adjusted for change in total flow, decreased in the hypoxic lung (P = 0.005) but did not change in the hyperoxic lung. We conclude that hypoxic vasoconstriction alters the regional distribution of flow in the hypoxic, but not in the hyperoxic, lung.

  13. Very Small Embryonic-like Stem Cells Are Mobilized in Human Peripheral Blood during Hypoxemic COPD Exacerbations and Pulmonary Hypertension.

    PubMed

    Guerin, Coralie L; Blandinières, Adeline; Planquette, Benjamin; Silvestre, Jean-Sébastien; Israel-Biet, Dominique; Sanchez, Olivier; Smadja, David M

    2017-03-11

    Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells involved in vascular and tissue regeneration and constitute a recruitable pool of stem/progenitor cells with putative instrumental role in organ repair. Here, we hypothesized that VSELs might be mobilized from the bone marrow (BM) to peripheral blood (PB) in patients with hypoxic lung disease or pulmonary hypertension (PH). The objective of the present study was then to investigate the changes in VSELs number in peripheral blood of patients with hypoxic lung disease and PH. We enrolled 26 patients with Chronic Obstructive Pulmonary Disease (COPD) with or without hypoxemia, 13 patients with PH and 20 controls without any respiratory or cardiovascular diseases. In PH patients, VSELs levels have been determined during right heart catheterization in pulmonary blood and PB. For this purpose, mononuclear cells were separated by density gradient and VSELs have been quantified by using a multiparametric flow cytometry approach. The number of PB-VSELs in hypoxic COPD patients was significantly increased compared with non-hypoxic COPD patients or controls (p = 0.0055). In patients with PH, we did not find any difference in VSELs numbers between arterial pulmonary blood and venous PB (p = 0.93). However, we found an increase in VSELs in the peripheral blood of patients with PH (p = 0.03). In conclusion, we unraveled that circulating VSELs were increased in peripheral blood of patients with hypoxic COPD or with PH. Thus, VSELs may serve as a reservoir of pluripotent stem cells that can be recruited into PB and may play an important role in promoting lung repair.

  14. Characterization of primary pulmonary adenosquamous carcinoma-associated pleural effusion.

    PubMed

    Stewart, Jennifer; Holloway, Andrew; Rasotto, Roberta; Bowlt, Kelly

    2016-03-01

    A 10-year-old, female spayed Shih Tzu was presented due to weight loss, increased respiratory effort and lethargy, determined to be secondary to a congenital para-esophageal diaphragmatic defect with partial herniation of the stomach and spleen. Four days following reduction surgery of the displaced abdominal organs thoracic effusion developed. Thoracic fluid evaluation revealed a cell-rich, protein-poor modified transudate with neutrophils, reactive mesothelial cells, and atypical epitheloid cells which occasionally appeared to be keratinizing, consistent with neoplastic exfoliation. Thoracic effusion recurred 2 days later, with similar characteristics as the initial sample. Computed tomography (CT) indicated consolidation and displacement of the right middle and accessory lung lobes. Exploratory thoracic surgery demonstrated a thickened, hyperemic right middle lung lobe, and thickened pericardial diaphragmatic ligament. Histologic evaluation of these tissues identified a primary pulmonary adenosquamous carcinoma with intravascular and pleural invasion. Based on these cytologic, histologic, and clinical findings, we conclude that primary pulmonary carcinomas may involve superficial thoracic structures and exfoliate into a thoracic effusion.

  15. Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

    PubMed Central

    Benito, Natividad; Moreno, Asunción; Filella, Xavier; Miró, José M.; González, Julià; Pumarola, Tomás; Valls, María Eugenia; Luna, Montserrat; García, Felipe; Rañó, Ana; Torres, Antoni; Gatell, José M.

    2004-01-01

    We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-α, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1β, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-α levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5). PMID:15138189

  16. Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease.

    PubMed

    Rossman, Matthew J; Trinity, Joel D; Garten, Ryan S; Ives, Stephen J; Conklin, Jamie D; Barrett-O'Keefe, Zachary; Witman, Melissa A H; Bledsoe, Amber D; Morgan, David E; Runnels, Sean; Reese, Van R; Zhao, Jia; Amann, Markus; Wray, D Walter; Richardson, Russell S

    2015-09-01

    The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population.

  17. Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease

    PubMed Central

    Rossman, Matthew J.; Trinity, Joel D.; Garten, Ryan S.; Ives, Stephen J.; Conklin, Jamie D.; Barrett-O'Keefe, Zachary; Witman, Melissa A. H.; Bledsoe, Amber D.; Morgan, David E.; Runnels, Sean; Reese, Van R.; Zhao, Jia; Amann, Markus; Wray, D. Walter

    2015-01-01

    The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population. PMID:26188020

  18. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  19. Role of Rho-kinase signaling and endothelial dysfunction in modulating blood flow distribution in pulmonary hypertension.

    PubMed

    Schwenke, Daryl O; Pearson, James T; Sonobe, Takashi; Ishibashi-Ueda, Hatsue; Shimouchi, Akito; Kangawa, Kenji; Umetani, Keiji; Shirai, Mikiyasu

    2011-04-01

    Rho-kinase-mediated vasoconstriction and endothelial dysfunction are considered two primary instigators of pulmonary arterial hypertension (PAH). However, their contribution to the adverse changes in pulmonary blood flow distribution associated with PAH has not been addressed. This study utilizes synchrotron radiation microangiography to assess the specific role, and contribution of, Rho-kinase-mediated vasoconstriction and endothelial dysfunction in PAH. Male adult Sprague-Dawley rats were injected with saline (Cont-rats) or monocrotaline (MCT-rats) 3 wk before microangiography was performed on the left lung. We assessed dynamic changes in vessel internal diameter (ID) in response to 1) the Rho-kinase inhibitor fasudil (10 mg/kg iv); or 2) ACh (3 μg · kg⁻¹ · min⁻¹), sodium nitroprusside (SNP, 5 μg · kg⁻¹ · min⁻¹), and N(ω)-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg iv). We observed that MCT-rats had fewer vessels of the microcirculation compared with Cont-rats. The fundamental result of this study is that fasudil improved pulmonary blood flow distribution and reduced pulmonary pressure in PAH rats, not only by dilating already-perfused vessels (ID > 100 μm), but also by restoring blood flow to vessels that had previously been constricted closed (ID < 100 μm). Endothelium-dependent vasodilation was impaired in MCT-rats primarily in vessels with an ID < 200 μm. Moreover the vasoconstrictor response to l-NAME was accentuated in MCT-rats, but only in the 200- to 300-μm vessels. These results highlight the importance of Rho-kinase-mediated control and endothelial control of pulmonary vascular tone in PAH. Indeed, an effective therapeutic strategy for treating PAH should target both the smooth muscle Rho-kinase and endothelial pathways.

  20. Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome

    PubMed Central

    Maissen-Villiger, Carla A.; Schweighauser, Ariane; van Dorland, H. Anette; Morel, Claudine; Bruckmaier, Rupert M.; Zurbriggen, Andreas; Francey, Thierry

    2016-01-01

    Background Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form. Methodology and Principal Findings The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury. Conclusion The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance

  1. Characterization of the human blood plasma proteome

    SciTech Connect

    Shen, Yufeng; Kim, Jeongkwon; Strittmatter, Eric F.; Jacobs, Jon M.; Camp, David G.; Fang, Ruihua; Tolic, Nikola; Moore, Ronald J.; Smith, Richard D.

    2005-10-15

    We describe methods for broad characterization of the human plasma proteome. The combination of stepwise IgG and albumin protein depletion by affinity chromatography and ultrahigh-efficiency capillary liquid chromatography separations coupled to ion trap-tandem mass spectrometry enabled identification of 2392 proteins from a single plasma sample with an estimated confidence level of >94%, and an additional 2198 proteins with an estimated confidence level of 80%. The relative abundances of the identified proteins span a range of over eight orders of magnitude in concentration (<30 pg/mL to {approx}30 mg/mL), facilitated by the attomole-level sensitivity of the analysis methods. More than 80% of the observed proteins demonstrate interactions with IgG and/or albumin. The results from this study provide a basis for a wide range of plasma proteomics studies, including broad quantitation of relative abundances in comparative studies for the identification of novel protein disease markers, as well as further studies of protein-protein interactions.

  2. Characterization of pulmonary sigma receptors by radioligand binding

    PubMed Central

    Lever, John R.; Litton, Tyler P.; Fergason-Cantrell, Emily A.

    2015-01-01

    This study establishes the expression of appreciable populations of sites on mouse lung membranes that exhibit radioligand binding properties and pharmacology consistent with assignment as sigma1 and sigma2 receptors. Specific binding of the sigma1 receptor radioligand [3H](+)-pentazocine reached steady state within 6 h at 37 °C. Saturation studies revealed high affinity binding to a single class of sites (Kd 1.36 ± 0.04 nM; Bmax 967 ± 11 fmol / mg protein). Inhibition studies showed appropriate sigma1 receptor pharmacology, including higher affinity for (+)-N-allylnormetazocine with respect to the (−)-enantiomer, and positive allosteric modulation of dextromethorphan binding by phenytoin. Using [3H]1,3-di(2-tolyl)guanidine in the presence of (+)-pentazocine to assess sigma2 receptor binding, steady state was achieved within 2 min at 25 °C. Cold saturation studies revealed one high affinity, low capacity binding site (Kd 31.8 ± 8.3 nM; Bmax 921 ± 228 fmol / mg protein) that displayed sigma2 receptor pharmacology. A very low affinity, high capacity interaction also was observed that represents saturable, but not sigma receptor specific, binding. A panel of ligands showed rank order inhibition of radioligand binding appropriate for the sigma2 receptor, with ifenprodil displaying the highest apparent affinity. In vivo, dextromethorphan inhibited the specific binding of a radioiodinated sigma1 receptor ligand in lung with an ED50 of 1.2 µmol / kg, a value near the recommended dosage for the drug as a cough suppressant. Overall, the present work provides a foundation for studies of drug interactions with pulmonary sigma1 and sigma2 receptors in vitro and in vivo. PMID:26004528

  3. Pulmonary Hemorrhage: Imaging with a New Magnetic Resonance Blood Pool Agent in Conjunction with Breathheld Three-Dimensional Magnetic Resonance Angiography

    SciTech Connect

    Weishaupt, Dominik; Hilfiker, Paul R.; Schmidt, Michaela; Debatin, Joerg F.

    1999-07-15

    Purpose: To describe the three-dimensional magnetic resonance angiography (3D MRA) imaging appearance of the pulmonary arteries following administration of a superparamagnetic iron oxide blood pool agent to human volunteers, and to demonstrate in an animal model (pigs) how this technique can be used to detect pulmonary parenchymal hemorrhage. Methods: Two volunteers were examined following the intravenous administration of a superparamagnetic iron oxide blood pool agent (NC100150 Injection, Nycomed Amersham Imaging, Wayne, PA, USA). T1-weighted 3D gradient recalled echo (GRE) image sets (TR/TE 5.1/1.4 msec, flip angle 30 deg.) were acquired breathheld over 24 sec. To assess the detectability of pulmonary bleeding with intravascular MR contrast, pulmonary parenchymal injuries were created in two animals under general anesthesia, and fast T1-weighted 3D GRE image sets collected before and after the injury. Results: Administration of the intravascular contrast in the two volunteers resulted in selective enhancement of the pulmonary vasculature permitting complete visualization and excellent delineation of central, segmental, and subsegmental arteries. Following iatrogenic injury in the two animals, pulmonary hemorrhage was readily detected on the 3D image sets. Conclusion: The data presented illustrate that ultrafast 3D GRE MR imaging in conjunction with an intravenously administered intravascular blood pool agent can be used to perform high-quality pulmonary MRA as well as to detect pulmonary hemorrhage.

  4. Development and Characterization of Acellular Porcine Pulmonary Valve Scaffolds for Tissue Engineering

    PubMed Central

    Korossis, Sotirios A.; Wilshaw, Stacy-Paul; Jennings, Louise M; Fisher, John; Ingham, Eileen

    2014-01-01

    Currently available replacement heart valves all have limitations. This study aimed to produce and characterize an acellular, biocompatible porcine pulmonary root conduit for reconstruction of the right ventricular outflow tract e.g., during Ross procedure. A process for the decellularization of porcine pulmonary roots was developed incorporating trypsin treatment of the adventitial surface of the scraped pulmonary artery and sequential treatment with hypotonic Tris buffer (HTB; 10 mM Tris pH 8.0, 0.1% (w/v) EDTA, and 10 KIU aprotinin), 0.1% (w/v) sodium dodecyl sulfate in HTB, two cycles of DNase and RNase, and sterilization with 0.1% (v/v) peracetic acid. Histology confirmed an absence of cells and retention of the gross histoarchitecture. Immunohistochemistry further confirmed cell removal and partial retention of the extracellular matrix, but a loss of collagen type IV. DNA levels were reduced by more than 96% throughout all regions of the acellular tissue and no functional genes were detected using polymerase chain reaction. Total collagen levels were retained but there was a significant loss of glycosaminoglycans following decellularization. The biomechanical, hydrodynamic, and leaflet kinematics properties were minimally affected by the process. Both immunohistochemical labeling and antibody absorption assay confirmed a lack of α-gal epitopes in the acellular porcine pulmonary roots and in vitro biocompatibility studies indicated that acellular leaflets and pulmonary arteries were not cytotoxic. Overall the acellular porcine pulmonary roots have excellent potential for development of a tissue substitute for right ventricular outflow tract reconstruction e.g., during the Ross procedure. PMID:24786313

  5. Pulmonary arteriovenous malformation in patients with total cavopulmonary shunt: what role does lack of hepatic venous blood flow to the lungs play?

    PubMed

    Shinohara, T; Yokoyama, T

    2001-01-01

    We examined the etiology of a long-term postoperative complication, pulmonary arteriovenous malformation (PAVM), in a patient who underwent total cavopulmonary shunt (TCPS). The patient underwent TCPS at the age of 3 years and 1 month, and a PAVM developed. At the age of 10 years, TCPS was switched to total cavopulmonary connection to facilitate circulation of hepatic venous blood to the pulmonary artery. As a result, oxygen saturation increased. These findings suggest that the absence of pulmonary circulation of hepatic venous blood is involved in the development of PAVM.

  6. 3D pulmonary perfusion MRI and MR angiography of pulmonary embolism in pigs after a single injection of a blood pool MR contrast agent.

    PubMed

    Fink, Christian; Ley, Sebastian; Puderbach, Michael; Plathow, Christian; Bock, Michael; Kauczor, Hans-Ulrich

    2004-07-01

    The purpose of this study was to assess the feasibility of contrast-enhanced 3D perfusion MRI and MR angiography (MRA) of pulmonary embolism (PE) in pigs using a single injection of the blood pool contrast Gadomer. PE was induced in five domestic pigs by injection of autologous blood thrombi. Contrast-enhanced first-pass 3D perfusion MRI (TE/TR/FA: 1.0 ms/2.2 ms/40 degrees; voxel size: 1.3 x 2.5 x 4.0 mm3; TA: 1.8 s per data set) and high-resolution 3D MRA (TE/TR/FA: 1.4 ms/3.4 ms/40 degrees; voxel size: 0.8 x 1.0 x 1.6 mm3) was performed during and after a single injection of 0.1 mmol/kg body weight of Gadomer. Image data were compared to pre-embolism Gd-DTPA-enhanced MRI and post-embolism thin-section multislice CT (n = 2). SNR measurements were performed in the pulmonary arteries and lung. One animal died after induction of PE. In all other animals, perfusion MRI and MRA could be acquired after a single injection of Gadomer. At perfusion MRI, PE could be detected by typical wedge-shaped perfusion defects. While the visualization of central PE at MRA correlated well with the CT, peripheral PE were only visualized by CT. Gadomer achieved a higher peak SNR of the lungs compared to Gd-DTPA (21 +/- 8 vs. 13 +/- 3). Contrast-enhanced 3D perfusion MRI and MRA of PE can be combined using a single injection of the blood pool contrast agent Gadomer.

  7. Central venous catheter-related blood stream infections in patients receiving intravenous iloprost for pulmonary hypertension.

    PubMed

    Sammut, D; Elliot, C A; Kiely, D G; Armstrong, I J; Martin, L; Wilkinson, J; Sephton, P; Jones, J; Hamilton, N; Hurdman, J; McLellan, E; Sabroe, I; Condliffe, R

    2013-07-01

    Catheter-related blood stream infection (CR-BSI) in patients with pulmonary hypertension (PH) receiving intravenous iloprost via an indwelling central line has previously not been fully described. Recent studies have suggested a link between the pH of prostanoid infusions and the rate and nature of CR-BSI. We have investigated CR-BSI in patients receiving intravenous iloprost at our unit. Databases and hospital records were interrogated for all patients receiving intravenous iloprost between September 2007 and June 2012. Fifty-nine patients received intravenous iloprost via an indwelling central catheter with a total of 23,072 treatment days. There were 15 episodes of CR-BSI, identified using a systematic screening protocol, involving 11 patients giving an overall CR-BSI rate of 0.65/1,000 treatment days. CR-BSI rate for Gram-positive organisms was 0.26/1,000 treatment-days and for Gram-negative organisms was 0.39/1,000 treatment-days. The pH of iloprost in typical dosing regimens was comparable to the pH used in standard-diluent treprostinil and dissimilar to alkaline epoprostenol infusions. The proportion of Gram-negative CR-BSI was similar to that reported for standard-diluent treprostinil. CRP was normal on admission in 33 % of cases of confirmed CR-BSI and remained normal in 13 % of cases. CR-BSI rates with intravenous iloprost are comparable to those observed for other prostanoids. The high proportion of Gram-negative organisms observed and the neutral pH of iloprost infusions support the previously hypothesised link between pH and antimicrobial activity. Although usually elevated during a CR-BSI, CRP may be normal in early infection and a normal result cannot completely exclude infection.

  8. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    SciTech Connect

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  9. Increased Regulatory and Decreased CD8+ Cytotoxic T Cells in the Blood of Patients with Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Ulrich, Silvia; Nicolls, Mark R.; Taraseviciene, Laima; Speich, Rudolf; Voelkel, Norbert

    2008-01-01

    Background An association between pulmonary arterial hypertension (PAH) and various immune disorders is well established. Recently, the role of an intact immune system in protecting against pulmonary angioproliferation was shown in an animal model. Objective To elucidate the role of T cells in human PAH, we comparatively studied T cell subclasses with emphasis on regulatory T cells (Treg) in the peripheral blood of patients with idiopathic pulmonary arterial hypertension (IPAH) and healthy controls. Methods Isolated peripheral blood mononuclear cells from 36 patients diagnosed with IPAH and 33 healthy controls were stained with fluorescently labeled monoclonal antibodies against superficial T cell markers (CD3, CD4, CD8, CD25) and FoxP3, the intracellular marker of Treg cells. The relative cell distribution was analyzed by flow cytometry. The functionality of patient and control Treg cells was assessed by coculture of Treg with nonregulatory T cells from the same individual. Results Significantly less CD8+ T cells (p = 0.02) and more CD25hi+ and FoxP3+CD4+ T cells were found in the peripheral blood of patients compared with controls (p = 0.009 and p < 0.001, respectively). The percentage of FoxP3+ cells within the CD25hi+CD4+ Treg cells was similar. Treg cell functionality was equal in patients and controls. Conclusion Our findings of decreased CD8+ T cells and increased Treg cells in the peripheral blood of patients with IPAH are novel and may have implications for directing future research in the field to elucidate the differential role of T cells and the immune system in IPAH. PMID:18025812

  10. Normal values for single exhalation diffusing capacity and pulmonary capillary blood flow in sitting, supine positions, and during mild exercise.

    PubMed

    Huang, Y C; Helms, M J; MacIntyre, N R

    1994-02-01

    Previous approaches to the measurements of pulmonary diffusing capacity (DL) and pulmonary capillary blood flow (QC) utilized either the rebreathing or the single inhalation technique in conjunction with radioisotope gas and mass spectrometry. In the present study, we utilized a newly developed rapid infrared analyzer in conjunction with the slow single exhalation technique on 100 healthy volunteers to establish normal values for DL and QC under sitting, supine, and exercise conditions. The exercise level was determined by a target heart rate: HRex = ([HRmax - HRrest]/3) + HRrest. Prediction equations based on regressions on age, sex, height, or weight were then computed for sitting, supine, and exercise values. We found that mean DL and QC increased by approximately 12 percent and 8 percent, respectively, from sitting to supine posture, and by approximately 30 percent and 100 percent, respectively, from sitting (rest) to mild exercise. These results provided a database for further studies in the single exhalation method in various clinical settings.

  11. Teaching the effects of gravity and intravascular and alveolar pressures on the distribution of pulmonary blood flow using a classic paper by West et al.

    PubMed

    Levitzky, Michael G

    2006-03-01

    "Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures" by J. B. West, C. T. Dollery, and A. Naimark (J Appl Physiol 19: 713-724, 1964) is a classic paper, although it has not yet been included in the Essays on the American Physiological Society Classic Papers Project (http://www.the-aps.org/publications/classics/). This is the paper that originally described the "zones of the lung." The final figure in the paper, which synthesizes the results and discussion, is now seen in most textbooks of physiology or respiratory physiology. The paper is also a model of clear, concise writing. The paper and its final figure can be used to teach or review a number of physiological concepts. These include the effects of gravity on pulmonary blood flow and pulmonary vascular resistance; recruitment and distention of pulmonary vessels; the importance of the transmural pressure on the diameter of collapsible distensible vessels; the Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and alveolar pressures; and the vascular waterfall. In addition, the figure can be used to generate discovery learning and discussion of several physiological or pathophysiological effects on pulmonary vascular resistance and the distribution of pulmonary blood flow.

  12. Pharmacological characterization of histamine H3 receptors in isolated guinea pig pulmonary artery and ileum.

    PubMed

    Rizzo, C A; Tozzi, S; Monahan, M E; Hey, J A

    1995-12-27

    We characterized the histamine H3 receptors involved in the modulation of electrical field stimulated neurogenic contraction of guinea pig pulmonary artery sympathetic, and guinea pig ileum parasympathetic preparations. Simultaneous measures of electrical field stimulation-evoked 3H overflow and tension in [3H]norepinephrine-loaded pulmonary artery were sensitive to tetrodotoxin (300 nM) and insensitive to hexamethonium (100 microM). Only the contractile response was inhibited by prazosin (100 nM). (R)-alpha-Methylhistamine's inhibition of the pulmonary artery contraction and 3H overflow were dose-dependently antagonized by thioperamide (30-100 nM). (R)-alpha-Methylhistamine also inhibited the neurogenic contractions of the isolated ileum (pD2 = 8.2). In the pulmonary artery, the relative potency of the histamine H3 receptor antagonists vs. (R)-alpha-methylhistamine inhibition of neurogenic contractions (pD2 = 7.1) was thioperamide (pA2 = 8.6 +/- 0.1) > burimamide (pA2 = 7.6 +/- 0.2) > impromidine (pA2 = 6.9 +/- 0.02). Similarly, the relative potency of histamine H3 receptor antagonists in the isolated ileum was thioperamide > burimamide > or = impromidine, with pA2 estimates of 8.7 +/- 0.1, 7.3 +/- 0.1 and 7.1 +/- 0.1, respectively. Antagonist potencies suggest a predominant histamine H3A-like receptor population on postganglionic sympathetic neurons innervating the pulmonary artery and parasympathetic neurons innervating the ileum longitudinal muscle.

  13. Development of pulmonary blood flow evaluation method with a dynamic flat-panel detector: quantitative correlation analysis with findings on perfusion scan.

    PubMed

    Tanaka, Rie; Sanada, Shigeru; Fujimura, Masaki; Yasui, Masahide; Hayashi, Norio; Tsuji, Shiro; Okamoto, Hiroyuki; Nanbu, Yuko; Matsui, Osamu

    2010-01-01

    Pulmonary blood flow is reflected in dynamic chest radiographs as changes in X-ray translucency, i.e., pixel values. Thus, decreased blood flow should be observed as a reduction of the variation of X-ray translucency. We performed the present study to investigate the feasibility of pulmonary blood flow evaluation with a dynamic flat-panel detector (FPD). Sequential chest radiographs of 14 subjects were obtained with a dynamic FPD system. The changes in pixel value in each local area were measured and mapped on the original image by use of a gray scale in which small and large changes were shown in white and black, respectively. The resulting images were compared to the findings in perfusion scans. The cross-correlation coefficients of the changes in pixel value and radioactivity counts in each local area were also computed. In all patients, pulmonary blood flow disorder was indicated as a reduction of changes in pixel values on the mapping image, and a correlation was observed between the distribution of changes in pixel value and those in radioactivity counts (0.7 pulmonary blood flow. The present method is potentially useful for evaluating pulmonary blood flow as an additional examination in conventional chest radiography.

  14. Prospective study of ABO blood type and the risk of pulmonary embolism in two large cohort studies.

    PubMed

    Wolpin, Brian M; Kabrhel, Christopher; Varraso, Raphaëlle; Kraft, Peter; Rimm, Eric B; Goldhaber, Samuel Z; Camargo, Carlos A; Fuchs, Charles S

    2010-11-01

    Prior studies have suggested an association of ABO blood type and the risk of venous thromboembolism; however, most studies were retrospective and lacked important covariates or validated endpoints. Moreover, risk estimates varied widely across studies. Therefore, we prospectively examined the association of blood type and the risk of incident pulmonary embolism (PE) in two large cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study. During 1,010,378 person-years of follow-up among 77,025 women and 30,105 men, 499 participants developed PE. Compared to those with O-blood type, participants with non-O blood type had multivariable-adjusted hazard ratios (HR) of 1.86 (95% CI, 1.35-2.57) for idiopathic PE, 1.29 (95% CI, 1.03-1.62) for non-idiopathic PE, and 1.46 (95% CI, 1.22-1.76) for any PE. Hazard ratios were similar for participants with blood types A, B, and AB. Age-adjusted absolute rates of idiopathic PE over 10 years of follow-up differed by blood type: 0.11% for O, 0.20% for A, 0.19% for AB, and 0.21% for B. For idiopathic PE, the population attributable fraction was 33% for inheritance of non-O blood type. Among past and current smokers, participants with non-O vs. O-blood type had a HR for idiopathic PE of 2.56 (95% CI, 1.61-4.08). Among never smokers, the HR for idiopathic PE was 1.30 (95% CI, 0.82-2.05; P interaction=0.04). In two large, prospective cohorts, ABO blood type was significantly associated with the risk of idiopathic and non-idiopathic PE, with even greater risk for idiopathic PE among current and past smokers with non-O blood type.

  15. Increase in blood viscosity in the sprinting horse: can it account for the high pulmonary arterial pressure?

    PubMed

    Fedde, M R; Erickson, H H

    1998-07-01

    Blood was taken from 49 Thoroughbred horses before and after racing at the track to determine if frusemide modified the apparent viscosity of the blood and to determine the effects of changes in shear rate and packed cell volume (PCV), associated with strenuous exercise, on apparent and relative viscosities. Small increases in apparent viscosity of the blood (at a specified PCV and shear rate) occurred in horses given frusemide compared to those receiving no frusemide; however, no differences were seen in relative viscosity. Although 2 groups of horses, those receiving frusemide before racing and those not receiving this drug were studied, the results suggest no influence of frusemide on any red blood cell variable that might modify apparent blood viscosity. Apparent viscosity of the blood was slightly (but significantly) higher after racing than before racing at any given PCV and shear rate, but relative viscosity was lower in the post race than in the prerace blood sample. The most important contributing factor to the increase in apparent viscosity in blood during racing is the increase in PCV, because the blood becomes nearly shear rate independent at shear rates likely to exist in the cardiovascular system during exercise. With an increase in PCV from 40 to 65% at shear rates above 225/s, apparent viscosity approximately doubled. However, this increase alone cannot account for the elevated pulmonary vascular pressure in the running horse, and additional factors, especially those causing the high left atrial pressure, must be considered. The cause of the elevated pressure may be multifactorial in nature.

  16. Pulmonary atresia

    MedlinePlus

    ... blood flow from the right ventricle (right side pumping chamber) to the lungs. In pulmonary atresia, a ... Reconstructing the heart as a single ventricle (1 pumping chamber instead of 2) Heart transplant Outlook (Prognosis) ...

  17. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  18. Detection and Characterization of Carcinoma Cells in the Blood

    NASA Astrophysics Data System (ADS)

    Racila, Emilian; Euhus, David; Weiss, Arthur J.; Rao, Chandra; McConnell, John; Terstappen, Leon W. M. M.; Uhr, Jonathan W.

    1998-04-01

    A highly sensitive assay combining immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis has been developed to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 ml) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls was examined by flow cytometry for the presence of circulating epithelial cells defined as nucleic acid+, CD45-, and cytokeratin+. Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with cancer including 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytospin preparations were made after immunomagnetic enrichment and were analyzed. Epithelial cells from patients with breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast, no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consistent with that of neoplastic cells. Of 8 patients with breast cancer followed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemotherapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.

  19. Guidelines for the prevention of central venous catheter-related blood stream infections with prostanoid therapy for pulmonary arterial hypertension.

    PubMed

    Doran, A K; Ivy, D D; Barst, R J; Hill, N; Murali, S; Benza, R L

    2008-07-01

    Intravenous prostanoids are the backbone of therapy for advanced pulmonary arterial hypertension (PAH) and have improved long-term outcome and quality of life. Currently, two prostanoids are approved by the US Food and Drug administration for parenteral administration: epoprostenol (Flolan) and treprostinil (Remodulin). Chronic intravenous therapy presents considerable challenges for patients and caregivers who must learn sterile preparation of the medication, operation of the pump, and care of the central venous catheter. Patients are routinely counseled and advised regarding the risks of CR-BSIs and catheter care before central line insertion. Central line infections as well as bacteremia are well documented risks of chronic intravenous therapy and may significantly contribute to morbidity and mortality. Recent reports have suggested a possible increase in CR-BSI; therefore, the Scientific Leadership Council of the Pulmonary Hypertension Association decided to provide guidelines for good clinical practice regarding catheter care. Although data exits regarding patients with central venous catheters and the risk of blood stream infections in patients with cancer or other disorders, there is little data regarding the special needs of patients with pulmonary arterial hypertension requiring central venous access. These guidelines are extrapolated from the diverse body of literature regarding central venous catheter care.

  20. Characterization of intestinal collateral blood flow in the developing piglet.

    PubMed

    Crissinger, K D; Granger, D N

    1988-10-01

    Interest in the pathogenesis of neonatal necrotizing enterocolitis has prompted study of the intestinal circulation in developing animals. It is conceivable that poorly developed collateral channels may predispose the neonatal intestine to ischemic insults. We therefore characterized intestinal collateral blood flow in anesthetized and ventilated 1-day and 1-month-old piglets. Intestinal blood flow was measured with radioactive microspheres (15 micron diameter) before and after either 1) total occlusion of the superior mesenteric artery (SMA) or 2) occlusion of a distal (jejunoileal) branch of the SMA. After total SMA occlusion in 1-day and 1-month-old piglets, perfusion of the intestine via collaterals from the celiac and inferior mesenteric arteries was not evident. Jejunal, ileal, and colonic (except rectal) blood flows fell to zero 30 min after ligation of the SMA. Ligation of a distal branch of the SMA in 1-month-old animals significantly reduced total wall (by 25%) and mucosal/submucosal (by 25%) blood flows in the occluded segment. Similar experiments in 1-day-old piglets produced significantly greater reduction in total (70%) and mucosa/submucosa (70%) blood flows. Muscle/serosa blood flows in both groups were not significantly different from control values. In conclusion, collateral perfusion of the intestine via the celiac and inferior mesenteric arteries is insignificant during acute SMA occlusion in the developing piglet. Although there is significant collateral blood flow within the SMA vascular network, perfusion between adjacent gut segments is less effective in preventing intestinal ischemia after occlusion of a branch of the SMA in neonates than in 1-month-old piglets.

  1. Bosentan Pharmacokinetics in Pediatric Patients with Pulmonary Arterial Hypertension: Comparison of Dried Blood Spot and Plasma Analysis.

    PubMed

    Géhin, Martine; Sidharta, Patricia N; Dingemanse, Jasper

    2016-01-01

    FUTURE-3, a phase III pediatric pharmacokinetic (PK) trial conducted to compare 2 bosentan dosing regimens in 64 patients with pulmonary arterial hypertension, offered the opportunity to compare dried blood spot (DBS)-derived data to plasma data. Bosentan PK parameters obtained with both methods were compared by the geometric mean ratio (GMR; DBS/plasma) and its 90% CI after correction for the blood-to-plasma partition ratio (0.6). Bosentan GMRs were 1.10 (1.03, 1.16) and 1.12 (1.04, 1.20) for AUCτ and Cmax, respectively. Bosentan concentrations measured by DBS were therefore good estimations of bosentan plasma concentrations. DBS can be considered a valid alternative to bosentan assessed in plasma.

  2. Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model

    PubMed Central

    Ishikawa, Kiyotake; Hadri, Lahouaria; Santos-Gallego, Carlos; Fish, Kenneth; Hammoudi, Nadjib; Chaanine, Antoine; Torquato, Samantha; Naim, Charbel; Ibanez, Borja; Pereda, Daniel; García-Alvarez, Ana; Fuster, Valentin; Sengupta, Partho P.; Leopold, Jane A.; Hajjar, Roger J.

    2014-01-01

    In pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure is the main determinant of a poor prognosis. We aimed to characterize RV structural and functional differences during adaptive RV remodeling and progression to RV failure in a large animal model of chronic PH. Postcapillary PH was created surgically in swine (n = 21). After an 8- to 14-wk follow-up, two groups were identified based on the development of overt heart failure (HF): PH-NF (nonfailing, n = 12) and PH-HF (n = 8). In both groups, invasive hemodynamics, pressure-volume relationships, and echocardiography confirmed a significant increase in pulmonary pressures and vascular resistance consistent with PH. Histological analysis also demonstrated distal pulmonary arterial (PA) remodeling in both groups. Diastolic dysfunction, defined by a steeper RV end-diastolic pressure-volume relationship and longitudinal strain, was found in the absence of HF as an early marker of RV remodeling. RV contractility was increased in both groups, and RV-PA coupling was preserved in PH-NF animals but impaired in the PH-HF group. RV hypertrophy was present in PH-HF, although there was evidence of increased RV fibrosis in both PH groups. In the PH-HF group, RV sarcoplasmic reticulum Ca2+-ATPase2a expression was decreased, and endoplasmic reticulum stress was increased. Aldosterone levels were also elevated in PH-HF. Thus, in the swine pulmonary vein banding model of chronic postcapillary PH, RV remodeling occurs at the structural, histological, and molecular level. Diastolic dysfunction and fibrosis are present in adaptive RV remodeling, whereas the onset of RV failure is associated with RV-PA uncoupling, defective calcium handling, and hyperaldosteronism. PMID:25158063

  3. Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension

    PubMed Central

    Rose, Jonathan A.; Wanner, Nicholas; Cheong, Hoi I.; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V.; Erzurum, Serpil; Asosingh, Kewal

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH. PMID:27270458

  4. Physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) for pulmonary application.

    PubMed

    Paranjpe, M; Finke, J H; Richter, C; Gothsch, T; Kwade, A; Büttgenbach, S; Müller-Goymann, C C

    2014-12-10

    For the development of any colloidal system, thorough characterization is extremely essential. This article discusses the physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) including stability analysis over 6 months time period for possible pulmonary administration for the treatment of pulmonary arterial hypertension (PAH). SLN consisting of phospholipid and triglycerides were manufactured using a novel microchannel homogenization method. These sildenafil-loaded SLN were then subjected to physicochemical characterization namely, particle size and distribution over shelf life, differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and analysis of nebulization performance of these SLN by the means of next generation impactor (NGI). Additionally, the morphology of nebulized particles was assessed by transmission electron microscopy using negative staining technique. The solubility of sildenafil citrate and base in the lipid matrix was determined and was 0.1% w/w and 1% w/w, respectively. From the particle size measurements, it was observed that SLN without sildenafil demonstrated consistent particle sizes over 6 months. For the sildenafil-loaded SLN, increased particle sizes were found after manufacturing and further increased within weeks. From WAXD studies, after 6 months high intensity reflections corresponding to the stable β modification were observed. From DSC results, the peak minimum temperatures increased upon storage, hinting at a transformation to the stable β modification of triglycerides in the case of sildenafil-loaded SLN. Hence, it can be concluded that even small drug concentration influences particle size and stability.

  5. Association of air pollution sources and aldehydes with biomarkers of blood coagulation, pulmonary inflammation, and systemic oxidative stress.

    PubMed

    Altemose, Brent; Robson, Mark G; Kipen, Howard M; Ohman Strickland, Pamela; Meng, Qingyu; Gong, Jicheng; Huang, Wei; Wang, Guangfa; Rich, David Q; Zhu, Tong; Zhang, Junfeng

    2016-07-20

    Using data collected before, during, and after the 2008 Summer Olympic Games in Beijing, this study examines associations between biomarkers of blood coagulation (vWF, sCD62P and sCD40L), pulmonary inflammation (EBC pH, EBC nitrite, and eNO), and systemic oxidative stress (urinary 8-OHdG) with sources of air pollution identified utilizing principal component analysis and with concentrations of three aldehydes of health concern. Associations between the biomarkers and the air pollution source types and aldehydes were examined using a linear mixed effects model, regressing through seven lag days and controlling for ambient temperature, relative humidity, gender, and day of week for the biomarker measurements. The biomarkers for pulmonary inflammation, particularly EBC pH and eNO, were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The biomarkers for blood coagulation, particularly vWF and sCD62p, were most consistently associated with oil combustion. Systemic oxidative stress biomarker (8-OHdG) was most consistently associated with vehicle and industrial combustion. The associations of the biomarkers were generally not significant or consistent with secondary formation of pollutants and with the aldehydes. The findings support policies to control anthropogenic pollution sources rather than natural soil or road dust from a cardio-respiratory health standpoint.Journal of Exposure Science and Environmental Epidemiology advance online publication, 20 July 2016; doi:10.1038/jes.2016.38.

  6. IBN NAFIS – A FORGOTTEN GENIUS IN THE DISCOVERY OF PULMONARY BLOOD CIRCULATION

    PubMed Central

    Akmal, M; Zulkifle, M; Ansari, AH

    2010-01-01

    Scientific theories take centuries to come into existence and they keep on evolving. Uncountable intellectual minds work on these theories; some fail to do anything about it; some add a little after tremendous efforts, and some people give remarkable and unforgettable contribution. As far as credit is concerned, the person who is able to prove the theory by his facts and who clears the maximum doubts by his observations, experimentations, facts and reasoning, gets the credit for that theory, and this should be done with honesty. The theory of pulmonary circulation took more than 2000 years to come into existence as we know it today. With the passage of time different people were given credit. Some say that it was given to Galen; some say it was Michael Servetus; others say that Realdus Columbus was the real discoverer; some gave the credit to Ibn Nafis, and finally people gave the credit to William Harvey. But after the rediscovery of Ibn Nafis’ manuscript no.62243 titled Sharah al Tashreeh al Qanoon, or “Commentary on the anatomy of Canon of Avicenna” in 1924 AD in Europe, it became clear that Ibn Nafis had described the pulmonary circulation almost 300 years before Harvey, and the historians like Aldo Mieli, Max Mayrhoff, Edward Coppola etc. clearly state that Ibn Nafis is the real discoverer of the pulmonary circulation and that he should be given the credit for the discovery of the pulmonary circulation. PMID:21042463

  7. Changes in systemic and pulmonary blood flow distribution in normal adult volunteers in response to posture and exercise: a phase contrast magnetic resonance imaging study.

    PubMed

    Wong, Derek T H; Lee, Kyong-Jin; Yoo, Shi-Joon; Tomlinson, George; Grosse-Wortmann, Lars

    2014-03-01

    Hemodynamics are usually evaluated in the supine position at rest. This is only a snapshot of an individual's daily activities. This study describes circulatory adaptation, as assessed by magnetic resonance imaging, to changes in position and exercise. Phase contrast magnetic resonance imaging of blood flow within systemic and pulmonary arteries and veins was performed in 24 healthy volunteers at rest in the prone and supine position and with bicycle exercise in the supine position. No change was seen in systemic blood flow when moving from prone to supine. Exercise resulted in an increased percentage of cardiac output towards the lower body. Changes in position resulted in a redistribution of blood flow within the left lung--supine positioning resulted in decreased blood flow to the left lower pulmonary vein. With exercise, both the right and left lower lobes received increased blood flow, while the upper lobes received less.

  8. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  9. Preparation and Characterization of Magnetic Nano-in-Microparticles for Pulmonary Delivery.

    PubMed

    McBride, Amber A; Price, Dominique N; Muttil, Pavan

    2017-01-01

    The purpose of this chapter is to detail the formulation and characterization of a magnetically-targeted drug delivery vehicle, termed nano-in-microparticles (NIMs), for pulmonary drug delivery. Currently, chemotherapeutics and antibiotics are delivered systemically and result in whole body side-effects. NIMs are formulated with superparamagnetic iron oxide nanoparticles, termed SPIONs, making these particles targetable to specific lung regions using a strong external magnet. Additionally, these particles can be formulated to contain any drug or therapeutic agent, such that a therapeutic dose can be delivered to a specific tissue location using the SPIONs-magnet interaction. Finally, these particles are in the appropriate size range for pulmonary delivery, making NIMs therapeutics feasibly inhalable.To generate these particles a solution containing lactose, SPIONs, and a microsphere dye (used as a drug surrogate) is spray-dried using a laboratory-scale spray dryer. The resulting dry powder microparticles (NIMs) can be characterized for their size and morphological properties by various techniques that are presented in this chapter.The utility of NIMs as a magnetic field-dependent targeting delivery platform in an in vivo mouse model has been demonstrated, and a protocol detailing the intratracheal delivery of NIMs dry powder is included as a separate chapter in this book.

  10. Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

    PubMed Central

    2012-01-01

    Background Alpha 1- antitrypsin (α1AT) belongs to the superfamily of serpins and inhibits different proteases. α1AT protects the lung from cellular inflammatory enzymes. In the absence of α1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized α1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide) (PLGA) is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. Results Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD), encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC). To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1μ. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that α1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of α1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release %60 of the drug within 8

  11. Tracking pulmonary gas exchange by breathing control during exercise: role of muscle blood flow

    PubMed Central

    Haouzi, Philippe

    2014-01-01

    Populations of group III and IV muscle afferent fibres located in the adventitia of the small vessels appear to respond to the level of venular distension and to recruitment of the vascular bed within the skeletal muscles. The CNS could thus be informed on the level of muscle hyperaemia when the metabolic rate varies. As a result, the magnitude and kinetics of the change in peripheral gas exchange – which translates into pulmonary gas exchange – can be sensed. We present the view that the respiratory control system uses these sources of information of vascular origin, among the numerous inputs produced by exercise, as a marker of the metabolic strain imposed on the circulatory and the ventilatory systems, resulting in an apparent matching between pulmonary gas exchange and alveolar ventilation. PMID:23981720

  12. Pulmonary Vasculitis

    PubMed Central

    Brown, Kevin K.

    2006-01-01

    Pulmonary vasculitis describes a number of distinct disorders that are pathologically characterized by the destruction of blood vessels. The clinical manifestations of each disorder are defined by the size, type, and location of the affected vasculature. The clinical approach to these disorders rests upon an astute clinician considering the diagnosis and identifying the specific patterns of clinical, radiologic, laboratory, and pathologic abnormalities. Lung involvement is most commonly seen with the primary, idiopathic, small-vessel, or antineutrophil cytoplasmic antibody–associated vasculitides; Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. However, primary, idiopathic medium and large-vessel vasculitis, primary immune complex–mediated vasculitis, and secondary vasculitis are all capable of presenting with lung involvement. In this article, we focus on the more common, antineutrophil cytoplasmic antibody–associated disorder, vasculitides. PMID:16493151

  13. Blood gases and pulmonary blood flow during resuscitation of very preterm lambs treated with antenatal betamethasone and/or Curosurf: effect of positive end-expiratory pressure.

    PubMed

    Crossley, Kelly J; Morley, Colin J; Allison, Beth J; Polglase, Graeme R; Dargaville, Peter A; Harding, Richard; Hooper, Stuart B

    2007-07-01

    Resuscitation of very premature lambs with positive end-expiratory pressure (PEEP) improves oxygenation and reduces pulmonary blood flow (PBF). However, the effects of PEEP on blood gases and PBF have not been studied in preterm lambs receiving antenatal corticosteroids or postnatal surfactant. Lambs were delivered at 125 d of gestation (term 147 d) and ventilated with a tidal volume (VT) of 5 mL/kg using different levels of PEEP. Four treatment groups were studied: (1) antenatal betamethasone 24 and 36 h before delivery; (2) postnatal Curosurf; (3) antenatal betamethasone and postnatal Curosurf; (4) untreated controls. Blood gases, PBF, and ventilator parameters were recorded during the first 2 h. Increasing PEEP improved oxygenation even after antenatal betamethasone and postnatal Curosurf, without adverse effects on arterial PCO2. Increasing PEEP reduced PBF; this effect was not altered by betamethasone and/or Curosurf. In very preterm lambs ventilated with fixed VT, increasing levels of PEEP improved oxygenation after antenatal glucocorticoids and/or postnatal surfactant. These treatments do not alter the deleterious effects of high levels of PEEP on PBF.

  14. Pulmonary hypertension - at home

    MedlinePlus

    Pulmonary hypertension (PAH) is abnormally high blood pressure in the arteries of the lungs. With PAH, the right side ... Chin K, Channick RN. Pulmonary hypertension. In: Broaddus VC, Mason ... Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: ...

  15. Living with Pulmonary Embolism

    MedlinePlus

    ... on Twitter. Living With Pulmonary Embolism Pulmonary embolism (PE) usually is treated in a hospital. After leaving ... you're taking medicine. Medicines used to treat PE can thin your blood too much. This can ...

  16. Relationship of cerebral blood flow to aortic-to-pulmonary collateral/shunt flow in single ventricles

    PubMed Central

    Fogel, Mark A; Li, Christine; Wilson, Felice; Pawlowski, Tom; Nicolson, Susan C; Montenegro, Lisa M; Berenstein, Laura Diaz; Spray, Thomas L; Gaynor, J William; Fuller, Stephanie; Keller, Marc S; Harris, Matthew A; Whitehead, Kevin K; Clancy, Robert; Elci, Okan; Bethel, Jim; Vossough, Arastoo; Licht, Daniel J

    2016-01-01

    Objective Patients with single ventricle can develop aortic-to-pulmonary collaterals (APCs). Along with systemic-to-pulmonary artery shunts, these structures represent a direct pathway from systemic to pulmonary circulations, and may limit cerebral blood flow (CBF). This study investigated the relationship between CBF and APC flow on room air and in hypercarbia, which increases CBF in patients with single ventricle. Methods 106 consecutive patients with single ventricle underwent 118 cardiac magnetic resonance (CMR) scans in this cross-sectional study; 34 prior to bidirectional Glenn (BDG) (0.50±0.30 years old), 50 prior to Fontan (3.19±1.03 years old) and 34 3–9 months after Fontan (3.98±1.39 years old). Velocity mapping measured flows in the aorta, cavae and jugular veins. Analysis of variance (ANOVA) and multiple linear regression were used. Significance was p<0.05. Results A strong inverse correlation was noted between CBF and APC/shunt both on room air and with hypercarbia whether CBF was indexed to aortic flow or body surface area, independent of age, cardiopulmonary bypass time, Po2 and Pco2 (R=−0.67–−0.70 for all patients on room air, p<0.01 and R=−0.49–−0.90 in hypercarbia, p<0.01). Correlations were not different between surgical stages. CBF was lower, and APCs/shunt flow was higher prior to BDG than in other stages. Conclusions There is a strong inverse relationship between CBF and APC/shunt flow in patients with single ventricle throughout surgical reconstruction on room air and in hypercarbia independent of other factors. We speculate that APC/shunt flow may have a negative impact on cerebral development and neurodevelopmental outcome. Interventions on APC may modify CBF, holding out the prospect for improving neurodevelopmental trajectory. Trial Registration Number NCT02135081. PMID:26048877

  17. Redispersible liposomal-N-acetylcysteine powder for pulmonary administration: development, in vitro characterization and antioxidant activity.

    PubMed

    Ourique, Aline Ferreira; Chaves, Paula Dos Santos; Souto, Gabriele Dadalt; Pohlmann, Adriana Raffin; Guterres, Silvia Stanisçuaski; Beck, Ruy Carlos Ruver

    2014-12-18

    Liposomal dry powders of N-acetylcysteine (SD-NAC-Lip) were developed for pulmonary administration. Liposomes were prepared by reverse phase evaporation and spray dried using lactose (10%, w/w) as drying adjuvant. The powders were characterized according to process yield, drug content, residual water content, particle size distribution, morphology and redispersion behavior. In vitro aerosol performance was evaluated using an eight-stage Andersen Cascade Impactor. Moreover, in vitro antioxidant activity was determined by measuring thiobarbituric acid reactive species (TBARS) present in the lungs of healthy Wistar rats after induction of oxidation by iron/EDTA. The spray-drying process had a high yield (71%±2), drug content (mg/g) according to the expected value, moisture content below 9%, geometric mean diameter under 3μm with span value lower than 1. Spherical particles were observed by scanning electron microscopy. Liposomal dry-powders were able to recover the nanometric size of the original dispersion after their redispersion in aqueous medium, as shown by laser diffraction and transmission electron microscopy. Furthermore, the powders presented aerodynamic diameter of about 7μm and respirable fraction above 30%, indicating suitable properties for pulmonary use. The encapsulation of N-acetylcysteine in liposomes was essential to maintain its in vitro antioxidant activity after the drying process. In addition, the powder containing the encapsulated drug had better in vitro antioxidant activity than the liquid and solid formulations containing the non-encapsulated drug, which makes it a good candidate for the treatment of pulmonary diseases associated with oxidative stress.

  18. Characterization of amphotericin B aerosols for inhalation treatment of pulmonary aspergillosis.

    PubMed

    Roth, C; Gebhart, J; Just-Nübling, G; von Eisenhart-Rothe, B; Beinhauer-Reeb, I

    1996-01-01

    In recent years, the incidence of invasive pulmonary aspergillosis has increased in patients receiving immunosuppressive therapy and/or organ transplantation. For prophylaxis against Aspergillus infections, amphotericin B may be a useful drug when inhaled as aerosol. In this study, the aerosolization of amphotericin B was investigated using eight different medical nebulizers under various operating conditions and with different amphotericin B concentrations in the solution. The output of each nebulizer was characterized by the mass flow of spray (drug) leaving the mouthpiece and by the size distribution of the droplets. An effective prevention of pulmonary aspergillosis via amphotericin B inhalation requires a high pulmonary deposition of the drug within an acceptable time of administration associated with a low deposition in the oropharyngeal region. To evaluate the dosages of drug delivered by various types of nebulizers to different regions of the respiratory tract, a semi-empirical deposition model was applied which is based on experimental aerosol deposition data from over 20 normal adults. The main results of the study are: Solutions with amphotericin B concentrations up to 10 mg/ml can be converted into sprays by means of medical nebulizers without any problems. For most nebulizers, the slight foaming of the amphotericin B solution has no effect on the production of the aerosol. To optimize amphotericin B treatment of the lungs via inhalation, sprays with mass flows above 100 mg/min and with mass median aerodynamic diameters (MMAD) below 3 microns should be slowly inhaled by the subject. Applying these criteria to the nebulizers investigated, three out of eight devices have proved suitable for amphotericin B treatment via inhalation.

  19. Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice.

    PubMed

    Singh, Pramila; DeMarini, David M; Dick, Colin A J; Tabor, Dennis G; Ryan, Jeff V; Linak, William P; Kobayashi, Takahiro; Gilmour, M Ian

    2004-06-01

    Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 micro g of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor alpha, macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 micro g) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975.

  20. Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment.

    PubMed

    Aragon, Mario J; Topper, Lauren; Tyler, Christina R; Sanchez, Bethany; Zychowski, Katherine; Young, Tamara; Herbert, Guy; Hall, Pamela; Erdely, Aaron; Eye, Tracy; Bishop, Lindsey; Saunders, Samantha A; Muldoon, Pretal P; Ottens, Andrew K; Campen, Matthew J

    2017-03-07

    Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis. However, pronounced BBB permeation was noted, with frank albumin leakage around larger vessels (>10 µm), overlain by a dose-dependent astroglial scar-like formation and recruitment of phagocytic microglia. As affirmed by elevated inflammatory marker transcription, MWCNT-induced BBB disruption and neuroinflammation were abrogated by pretreatment with the rho kinase inhibitor fasudil. Serum from MWCNT-exposed mice induced expression of adhesion molecules in primary murine cerebrovascular endothelial cells and, in a wound-healing in vitro assay, impaired cell motility and cytokinesis. Serum thrombospondin-1 level was significantly increased after MWCNT exposure, and mice lacking the endogenous receptor CD36 were protected from the neuroinflammatory and BBB permeability effects of MWCNTs. In conclusion, acute pulmonary exposure to MWCNTs causes neuroinflammatory responses that are dependent on the disruption of BBB integrity.

  1. Right ventricular remodeling in pulmonary hypertension.

    PubMed

    Franco, Veronica

    2012-07-01

    The right ventricle (RV) is in charge of pumping blood to the lungs for oxygenation. Pulmonary arterial hypertension (PAH) is characterized by high pulmonary vascular resistance and vascular remodeling, which results in a striking increase in RV afterload and subsequent failure. There is still unexploited potential for therapies that directly target the RV with the aim of supporting and protecting the right side of the heart, striving to prolong survival in patients with PAH.

  2. A novel platform for pulmonary and cardiovascular toxicological characterization of inhaled engineered nanomaterials

    PubMed Central

    SOTIRIOU, GEORGIOS A.; DIAZ, EDGAR; LONG, MARK S.; GODLESKI, JOHN; BRAIN, JOSEPH; PRATSINIS, SOTIRIS E.; DEMOKRITOU, PHILIP

    2013-01-01

    A novel method is presented which is suitable for assessing in-vivo the link between the physico-chemical properties of engineered nanomaterials (ENMs) and their biological outcomes. The ability of the technique to generate a variety of industry-relevant, property-controlled ENM exposure atmospheres for inhalation studies was systematically investigated. The primary particle size for Fe2O3, SiO2, Ag and Ag/SiO2 was controlled from 4 to 25 nm, while the corresponding agglomerate mobility diameter of the aerosol was also controlled and varied from 40 to 120 nm. The suitability of the technique to characterize the pulmonary and cardiovascular effects of inhaled ENMs in intact animal models is also demonstrated using in-vivo chemiluminescence (IVCL). The IVCL technique is a highly sensitive method for identifying cardiopulmonary responses to inhaled ENMs under relatively small doses and acute exposures. It is shown that moderate and acute exposures to inhaled nanostructured Fe2O3 can cause both pulmonary and cardiovascular effects. PMID:21809902

  3. PPAR-γ Regulates Carnitine Homeostasis and Mitochondrial Function in a Lamb Model of Increased Pulmonary Blood Flow

    PubMed Central

    Rafikov, Ruslan; Kumar, Sanjiv; Hou, Yali; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Fineman, Jeffrey R.; Black, Stephen M.

    2012-01-01

    Objective Carnitine homeostasis is disrupted in lambs with endothelial dysfunction secondary to increased pulmonary blood flow (Shunt). Our recent studies have also indicated that the disruption in carnitine homeostasis correlates with a decrease in PPAR-γ expression in Shunt lambs. Thus, this study was carried out to determine if there is a causal link between loss of PPAR-γ signaling and carnitine dysfunction, and whether the PPAR-γ agonist, rosiglitazone preserves carnitine homeostasis in Shunt lambs. Methods and Results siRNA-mediated PPAR-γ knockdown significantly reduced carnitine palmitoyltransferases 1 and 2 (CPT1 and 2) and carnitine acetyltransferase (CrAT) protein levels. This decrease in carnitine regulatory proteins resulted in a disruption in carnitine homeostasis and induced mitochondrial dysfunction, as determined by a reduction in cellular ATP levels. In turn, the decrease in cellular ATP attenuated NO signaling through a reduction in eNOS/Hsp90 interactions and enhanced eNOS uncoupling. In vivo, rosiglitazone treatment preserved carnitine homeostasis and attenuated the development of mitochondrial dysfunction in Shunt lambs maintaining ATP levels. This in turn preserved eNOS/Hsp90 interactions and NO signaling. Conclusion Our study indicates that PPAR-γ signaling plays an important role in maintaining mitochondrial function through the regulation of carnitine homeostasis both in vitro and in vivo. Further, it identifies a new mechanism by which PPAR-γ regulates NO signaling through Hsp90. Thus, PPAR-γ agonists may have therapeutic potential in preventing the endothelial dysfunction in children with increased pulmonary blood flow. PMID:22962578

  4. Characterizing blood cells by biophysical measurements in flow.

    PubMed

    Groner, W; Tycko, D

    1980-01-01

    One effect of automation in the hematology laboratory has been to introduce new characterizations of blood cells. Resistive pulse sensing (Coulter) and light scatter measurements in flow provide rapid and reproducible cell counts. They also provide information about red cell size, shape, and deformability. Thus, they have provided new characterization of these cells in terms of their biophysical properties. Leukocytes have been classified by optical scatter and absorption measurements in flow after being stained cytochemically. This provides rapid and precise WBC differential counts. However, here again, additional information about relative cell-enzyme content or activity is also accessible to provide a new characterization of the leukocytes. The ultimate range of utility of this expanding technology in the automated hematology laboratory of the future will, of course, depend upon establishing relations between the biophysical parameters and the functions of the cells. This, in turn, must depend upon the use of the technology by researchers and clinicians in studying cell function and the aberrations of these functions which define disease.

  5. Three-dimensional MR pulmonary perfusion imaging and angiography with an injection of a new blood pool contrast agent B-22956/1.

    PubMed

    Zheng, J; Carr, J; Harris, K; Saker, M B; Cavagna, F M; Maggioni, F; Laub, G; Li, D; Finn, J P

    2001-10-01

    Initial evaluation of a new blood pool agent, B-22956/1, for pulmonary imaging was performed in five domestic pigs with artificial embolism. Pre-embolism 3D pulmonary perfusion images were first acquired by injecting an extravascular agent, gadoteridol. The pulmonary arteries of the pigs were then occluded by the artificial emboli. Post-embolism perfusion scans were subsequently performed by injecting B-22956/1. Additional post-embolism high-spatial-resolution angiograms were also acquired. Parenchyma perfusion deficits were well depicted in the post-embolism perfusion maps. The post-embolism angiography clearly revealed the location and extent of the filling defects in the pulmonary vessels. Signal intensities of perfusion maps on the normal parenchyma were significantly improved (30%) by using B-22956/1, in comparison with perfusion images using gadoteridol (P < 0.01). Many pulmonary angiograms with approximately equal contrast could be obtained even at 22 minutes after the injection of B-22956/1. Our initial results indicate that blood pool agent B-22956/1 may provide opportunities for whole-lung-coverage perfusion mapping and additional high-resolution target angiograms after a single injection.

  6. Organic cation transporters in the blood-air barrier: expression and implications for pulmonary drug delivery.

    PubMed

    Salomon, Johanna Jessica; Ehrhardt, Carsten

    2012-06-01

    Studies concerning the impact that hepatic, renal and intestinal transporters have on drug disposition have been frequently reported in the literature. Surprisingly, however, little is known regarding the distribution and function of drug-transporter proteins of the lung epithelium. Many drugs (delivered to the lung) have a net positive charge and, thus, are potential substrates of organic cation transporters; currently marketed compounds (e.g., bronchodilators), as well as novel drug candidates in development, are such substrates. It is the aim of this review to summarize the current state of organic cation-transporter expression analysis in the lung and in in vitro models of bronchial and alveolar barriers. Moreover, activity of selected transporters in lung epithelium in situ and in vitro will be highlighted, and their potential role in pulmonary drug disposition will be addressed. One example included here is the transporter-dependent absorption of beta2-agonists in respiratory epithelial cells.

  7. Relationship between changes in pulmonary V̇O₂ kinetics and autonomic regulation of blood flow.

    PubMed

    McNarry, M A; Kingsley, M I C; Lewis, M J

    2014-08-01

    Various regulatory mechanisms of pulmonary oxygen uptake (V̇O2) kinetics have been postulated. The purpose of this study was to investigate the relationship between vagal withdrawal, measured using RMSSDRR, the root mean square of successive differences in cardiac interval (RR) kinetics, a mediator of oxygen delivery, and V̇O2 kinetics. Forty-nine healthy adults (23 ± 3 years; 72 ± 13 kg; 1.80 ± 0.08 m) performed multiple repeat transitions to moderate- and heavy-intensity exercise. Electrocardiography, impedance cardiography, and pulmonary gas exchange parameters were measured throughout; time domain measures of heart rate variability were subsequently derived. The parameters describing the dynamic response of V̇O2, cardiac output (Q) and RMSSDRR were determined using a mono-exponential model. During heavy-intensity exercise, the phase II τ of V̇O2 was significantly correlated with the τ of RR (r = 0.36, P < 0.05), Q (r = 0.67, P < 0.05), and RMSSDRR (r = 0.38, P < 0.05). The τ describing the rise in Q explained 47% of the variation in V̇O2 τ, with 30% of the rate of this rise in Q explained by the τ of RR and RMSSDRR. No relationship was evident between V̇O2 kinetics and those of Q, RR, or RMSSDRR during moderate exercise. Vagal withdrawal kinetics support the concept of a centrally mediated oxygen delivery limitation partly regulating V̇O2 kinetics during heavy-, but not moderate-, intensity exercise.

  8. Imbalance between subsets of CD8+ peripheral blood T cells in patients with chronic obstructive pulmonary disease

    PubMed Central

    Zhang, Ming-Qiang; Liu, Hong-Ju; Xin, Jian-Bao; Zhang, Jian-Chu; Wu, Jiang-Hua; Meng, Zhao-Ji; Sun, Sheng-Wen

    2016-01-01

    Background. CD8+ T lymphocytes are known to play a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, systematic analyses of CD8+ T cell (Cytotoxic T cells, Tc) subsets in COPD patients have yet to be well conducted. Methods. The whole Tc subsets, including Tc1/2/10/17, CD8+ regulatory T cells (Tregs) and CD8+α7+ T cells, were quantified by flow cytometry in peripheral blood from 24 stable COPD subjects (SCOPD), 14 patients during acute exacerbations (AECOPD), and 14 healthy nonsmokers (HN). Results. Acute exacerbations of COPD were accompanied by elevated levels of circulating CD8+ T cells. Tc1 cells were increased in both SCOPD and AECOPD patients, whereas the percentage of Tc2 cells was decreased in SCOPD patients but remained normal in AECOPD patients. Tc17 cells were increased only in AECOPD patients, and the percentage of Tc10 cells was reduced in both SCOPD and AECOPD patients. The imbalances of pro/anti-inflammatory Tc subsets observed in COPD may be caused by the lack of Tc10 cells and the impaired anti-inflammatory capacity of CD8+ Tregs. Conclusions. The imbalances between subsets of CD8+ peripheral blood T cells contribute to the immune response dysfunction in COPD pathogenesis. PMID:27547589

  9. Oxidant-antioxidant balance in the blood of patients with chronic obstructive pulmonary disease after smoking cessation.

    PubMed

    Woźniak, Alina; Górecki, Dariusz; Szpinda, Michał; Mila-Kierzenkowska, Celestyna; Woźniak, Bartosz

    2013-01-01

    The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed. We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II). Blood was taken once in Control I and 4 times (every month) in Control II. In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01), respectively. Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I. In Control II, the similar differences as compared to Control I were observed throughout the study. Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E. COPD is accompanied by oxidative stress. A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters.

  10. Pulmonary surfactant augments cytotoxicity of silica nanoparticles: Studies on an in vitro air-blood barrier model.

    PubMed

    Kasper, Jennifer Y; Feiden, Lisa; Hermanns, Maria I; Bantz, Christoph; Maskos, Michael; Unger, Ronald E; Kirkpatrick, C James

    2015-01-01

    The air-blood barrier is a very thin membrane of about 2.2 µm thickness and therefore represents an ideal portal of entry for nanoparticles to be used therapeutically in a regenerative medicine strategy. Until now, numerous studies using cellular airway models have been conducted in vitro in order to investigate the potential hazard of NPs. However, in most in vitro studies a crucial alveolar component has been neglected. Before aspirated NPs encounter the cellular air-blood barrier, they impinge on the alveolar surfactant layer (10-20 nm in thickness) that lines the entire alveolar surface. Thus, a prior interaction of NPs with pulmonary surfactant components will occur. In the present study we explored the impact of pulmonary surfactant on the cytotoxic potential of amorphous silica nanoparticles (aSNPs) using in vitro mono- and complex coculture models of the air-blood barrier. Furthermore, different surface functionalisations (plain-unmodified, amino, carboxylate) of the aSNPs were compared in order to study the impact of chemical surface properties on aSNP cytotoxicity in combination with lung surfactant. The alveolar epithelial cell line A549 was used in mono- and in coculture with the microvascular cell line ISO-HAS-1 in the form of different cytotoxicity assays (viability, membrane integrity, inflammatory responses such as IL-8 release). At a distinct concentration (100 µg/mL) aSNP-plain displayed the highest cytotoxicity and IL-8 release in monocultures of A549. aSNP-NH2 caused a slight toxic effect, whereas aSNP-COOH did not exhibit any cytotoxicity. In combination with lung surfactant, aSNP-plain revealed an increased cytotoxicity in monocultures of A549, aSNP-NH2 caused a slightly augmented toxic effect, whereas aSNP-COOH did not show any toxic alterations. A549 in coculture did not show any decreased toxicity (membrane integrity) for aSNP-plain in combination with lung surfactant. However, a significant augmented IL-8 release was observed, but no

  11. Characterization of red blood cells (RBCs) using dual Brillouin/Raman micro-spectroscopy

    NASA Astrophysics Data System (ADS)

    Meng, Zhaokai; Bustamante-Lopez, Sandra C.; Yakovlev, Vladislav V.; Meissner, Kenith E.

    2016-04-01

    Erythrocytes, or red blood cells, transport oxygen to and carbon dioxide from the body's tissues and organs. Red blood cell mechanical properties are altered in a number of diseases such as sickle cell anaemia and malaria. Additionally, mechanically modified red blood cell ghosts are being considered as a long-term, biocompatible carrier for drug delivery and for blood analyte sensing. Brillouin spectroscopy enables viscoelastic characterization of samples at the microscale. In this report, Brillouin spectroscopy is applied to characterize the mechanical properties of red blood cells and red blood cell ghosts.

  12. A water-filled body plethysmograph for the measurement of pulmonary capillary blood flow during changes of intrathoracic pressure

    PubMed Central

    Kawakami, Yoshikazu; Menkes, Harold A.; DuBois, Arthur B.

    1970-01-01

    A water-filled body plethysmograph was constructed to measure gas exchange in man. As compared to an air-filled plethysmograph, its advantages were greater sensitivity, less thermal drift, and no change from adiabatic to isothermal conditions after a stepwise change of pressure. When five subjects were completely immersed within it and were breathing to the ambient atmosphere, they had a normal heart rate, oxygen consumption, CO2 output, and functional residual capacity. Pulmonary capillary blood flow ([unk]Qc) during and after Valsalva and Mueller maneuvers was calculated from measurements of N2O uptake. Control measurements of [unk]Qc were 2.58 liters/min per m2 at rest and 3.63 liters/min per m2 after moderate exercise. During the Valsalva maneuver at rest (intrapulmonary pressure: 24, SD 3.0, mm Hg), [unk]Qc decreased from a control of 2.58, SD 0.43, liters/min per m2 to 1.62, SD 0.26, liters/min per m2 with a decrease in pulmonary capillary stroke volume from a control of 42.4, SD 8.8, ml/stroke per m2 to 25.2, SD 5.5, ml/stroke per m2. After release of the Valsalva, there was an overshoot in [unk]Qc averaging +0.78, SD 0.41, liter/min per m2 accompanied by a significant increase in heart rate. Similar changes occurred during and after the Valsalva following moderate exercise. During the Mueller maneuver at rest and after exercise, [unk]Qc, heart rate, and central stroke volume did not change significantly. Images PMID:5422025

  13. The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review.

    PubMed

    Schuetz, Philipp; Marlowe, Robert J; Mueller, Beat

    2015-03-01

    Plasma proadrenomedullin (ProADM) is a blood biomarker that may aid in multidimensional risk assessment of patients with chronic obstructive pulmonary disease (COPD). Co-secreted 1:1 with adrenomedullin (ADM), ProADM is a less biologically active, more chemically stable surrogate for this pluripotent regulatory peptide, which due to biological and ex vivo physical characteristics is difficult to reliably directly quantify. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress and expressed widely in pulmonary cells and ubiquitously throughout the body, ADM exerts or mediates vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects. Observational data from four separate studies totaling 1366 patients suggest that as a single factor, ProADM is a significant independent, and accurate, long-term all-cause mortality predictor in COPD. This body of work also suggests that combined with different groups of demographic/clinical variables, ProADM provides significant incremental long-term mortality prediction power relative to the groups of variables alone. Additionally, the literature contains indications that ProADM may be a global cardiopulmonary stress marker, potentially supplying prognostic information when cardiopulmonary exercise testing results such as 6-min walk distance are unavailable due to time or other resource constraints or to a patient's advanced disease. Prospective, randomized, controlled interventional studies are needed to demonstrate whether ProADM use in risk-based guidance of site-of-care, monitoring, and treatment decisions improves clinical, quality-of-life, or pharmacoeconomic outcomes in patients with COPD.

  14. Segmentation of blood clot from CT pulmonary angiographic images using a modified seeded region growing algorithm method

    NASA Astrophysics Data System (ADS)

    Park, Bumwoo; Furlan, Alessandro; Patil, Amol; Bae, Kyongtae T.

    2010-03-01

    Pulmonary embolism (PE) is a medical condition defined as the obstruction of pulmonary arteries by a blood clot, usually originating in the deep veins of the lower limbs. PE is a common but elusive illness that can cause significant disability and death if not promptly diagnosed and effectively treated. CT Pulmonary Angiography (CTPA) is the first line imaging study for the diagnosis of PE. While clinical prediction rules have been recently developed to associate short-term risks and stratify patients with acute PE, there is a dearth of objective biomarkers associated with the long-term prognosis of the disease. Clot (embolus) burden is a promising biomarker for the prognosis and recurrence of PE and can be quantified from CTPA images. However, to our knowledge, no study has reported a method for segmentation and measurement of clot from CTPA images. Thus, the purpose of this study was to develop a semi-automated method for segmentation and measurement of clot from CTPA images. Our method was based on Modified Seeded Region Growing (MSRG) algorithm which consisted of two steps: (1) the observer identifies a clot of interest on CTPA images and places a spherical seed over the clot; and (2) a region grows around the seed on the basis of a rolling-ball process that clusters the neighboring voxels whose CT attenuation values are within the range of the mean +/- two standard deviations of the initial seed voxels. The rollingball propagates iteratively until the clot is completely clustered and segmented. Our experimental results revealed that the performance of the MSRG was superior to that of the conventional SRG for segmenting clots, as evidenced by reduced degrees of over- or under-segmentation from adjacent anatomical structures. To assess the clinical value of clot burden for the prognosis of PE, we are currently applying the MSRG for the segmentation and volume measurement of clots from CTPA images that are acquired in a large cohort of patients with PE in an on

  15. Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

    PubMed

    Lehnert, Per; Johansson, Pär I; Ostrowski, Sisse R; Møller, Christian H; Bang, Lia E; Olsen, Peter Skov; Carlsen, Jørn

    2017-02-01

    Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

  16. Usefulness of D-dimer, blood gas, and respiratory rate measurements for excluding pulmonary embolism

    PubMed Central

    Egermayer, P.; Town, G; Turner, J.; Heaton, D.; Mee, A.; Beard, M.

    1998-01-01

    BACKGROUND—A study was undertaken to assess the usefulness of the SimpliRED D-dimer test, arterial oxygen tension, and respiratory rate measurement for excluding pulmonary embolism (PE) and venous thromboembolism (VTE).
METHODS—Lung scans were performed in 517 consecutive medical inpatients with suspected acute PE over a one year period. Predetermined end points for objectively diagnosed PE in order of precedence were (1) a post mortem diagnosis, (2) a positive pulmonary angiogram, (3) a high probability ventilation perfusion lung scan when the pretest probability was also high, and (4) the unanimous opinion of an adjudication committee. Deep vein thrombosis (DVT) was diagnosed by standard ultrasound and venography.
RESULTS—A total of 40 cases of PE and 37 cases of DVT were objectively diagnosed. The predictive value of a negative SimpliRED test for excluding objectively diagnosed PE was 0.99 (error rate 2/249), that of PaO2 of ⩾80 mm Hg (10.7 kPa) was 0.97 (error rate 5/160), and that of a respiratory rate of ⩽20/min was 0.95 (error rate 14/308). The best combination of findings for excluding PE was a negative SimpliRED test and PaO2⩾80 mm Hg, which gave a predictive value of 1.0 (error rate 0/93). The predictive value of a negative SimpliRED test for excluding VTE was 0.98 (error rate 5/249).
CONCLUSIONS—All three of these observations are helpful in excluding PE. When any two parameters were normal, PE was very unlikely. In patients with a negative SimpliRED test and PaO2 of ⩾80 mm Hg a lung scan is usually unnecessary. Application of this approach for triage in the preliminary assessment of suspected PE could lead to a reduced rate of false positive diagnoses and considerable resource savings.

 PMID:10193368

  17. Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands

    PubMed Central

    Ning, Fangkun; Wang, Chao; Berry, Karin Zemski; Kandasamy, Pitchaimani; Liu, Haolin; Murphy, Robert C.; Voelker, Dennis R.; Nho, Chu Won; Pan, Choel-Ho; Dai, Shaodong; Niu, Liwen; Chu, Hong-Wei; Zhang, Gongyi

    2014-01-01

    The short palate, lung and nasal epithelial clone 1 (SPLUNC1) protein is a member of the palate, lung, and nasal epithelium clone (PLUNC) family, also known as bactericidal/permeability-increasing (BPI) fold-containing protein, family A, member 1 (BPIFA1). SPLUNC1 is an abundant protein in human airways, but its function remains poorly understood. The lipid ligands of SPLUNC1 as well as other PLUNC family members are largely unknown, although some reports provide evidence that lipopolysaccharide (LPS) could be a lipid ligand. Unlike previous hypotheses, we found significant structural differences between SPLUNC1 and BPI. Recombinant SPLUNC1 produced in HEK 293 cells harbored several molecular species of sphingomyelin and phosphatidylcholine as its ligands. Significantly, in vitro lipid-binding studies failed to demonstrate interactions between SPLUNC1 and LPS, lipoteichoic acid, or polymyxin B. Instead, one of the major and most important pulmonary surfactant phospholipids, dipalmitoylphosphatidylcholine (DPPC), bound to SPLUNC1 with high affinity and specificity. We found that SPLUNC1 could be the first protein receptor for DPPC. These discoveries provide insight into the specific determinants governing the interaction between SPLUNC1 and lipids and also shed light on novel functions that SPLUNC1 and other PLUNC family members perform in host defense.—Ning, F., Wang, C., Berry, K. Z., Kandasamy, P., Liu, H., Murphy, R. C., Voelker, D. R., Nho, C. W., Pan, C.-H., Dai, S., Niu, L., Chu, H.-W., Zhang, G. Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands. PMID:25223608

  18. Effect of gravitational overloads, hypokinesia and hypodynamia on the vessels of the pulmonary blood circuit

    NASA Technical Reports Server (NTRS)

    Kasimtsev, A. A.

    1980-01-01

    Vessels of the pulmonary circuit are studied under normal conditions, in exposure to single stress or continuous threshold endurable chestspine gravitational stresses, and one to eight weak hypokinesia and hypodynamic effects followed by stress. Examination methods include rentgenography and microrentgenography, clearing, and histology. In exposure to gravitational stress the distal portions of the arterial vessels of the 3 and 4 orders constrict, while all veins dilate. Sinuosity of all vessels is noted. The volume of the capillary bed increases and signs of perivascular edema occur. Due to hypokinesia and hypodynamia the arteries constricted and the arterial bed becomes poor. The veins of all orders dilate and the volume of the capillary bed increases. The changes grew greater the longer the terms of hypodyamic effects. Successive combination of hypokinesia and hypodynamia and gravitational stresses cause more pronounced changes than separate effects of these two factors and result in great deformity of the vascular walls, including their rupture and penetration of formed elements beyond the limits of the vascular bed.

  19. Enhanced characterization of solid solitary pulmonary nodules with Bayesian analysis-based computer-aided diagnosis

    PubMed Central

    Perandini, Simone; Soardi, Gian Alberto; Motton, Massimiliano; Augelli, Raffaele; Dallaserra, Chiara; Puntel, Gino; Rossi, Arianna; Sala, Giuseppe; Signorini, Manuel; Spezia, Laura; Zamboni, Federico; Montemezzi, Stefania

    2016-01-01

    The aim of this study was to prospectively assess the accuracy gain of Bayesian analysis-based computer-aided diagnosis (CAD) vs human judgment alone in characterizing solitary pulmonary nodules (SPNs) at computed tomography (CT). The study included 100 randomly selected SPNs with a definitive diagnosis. Nodule features at first and follow-up CT scans as well as clinical data were evaluated individually on a 1 to 5 points risk chart by 7 radiologists, firstly blinded then aware of Bayesian Inference Malignancy Calculator (BIMC) model predictions. Raters’ predictions were evaluated by means of receiver operating characteristic (ROC) curve analysis and decision analysis. Overall ROC area under the curve was 0.758 before and 0.803 after the disclosure of CAD predictions (P = 0.003). A net gain in diagnostic accuracy was found in 6 out of 7 readers. Mean risk class of benign nodules dropped from 2.48 to 2.29, while mean risk class of malignancies rose from 3.66 to 3.92. Awareness of CAD predictions also determined a significant drop on mean indeterminate SPNs (15 vs 23.86 SPNs) and raised the mean number of correct and confident diagnoses (mean 39.57 vs 25.71 SPNs). This study provides evidence supporting the integration of the Bayesian analysis-based BIMC model in SPN characterization. PMID:27648166

  20. Genetic characterization of hantaviruses associated with sigmodontine rodents in an endemic area for hantavirus pulmonary syndrome in southern Brazil.

    PubMed

    de Oliveira, Renata Carvalho; Padula, Paula J; Gomes, Raphael; Martinez, Valeria P; Bellomo, Carla; Bonvicino, Cibele R; Freire e Lima, Danúbia Inês; Bragagnolo, Camila; Caldas, Antônio C S; D'Andrea, Paulo S; de Lemos, Elba R S

    2011-03-01

    An ecological assessment of reservoir species was conducted in a rural area (Jaborá) in the mid-west of the state of Santa Catarina in southern Brazil, where hantavirus pulmonary syndrome is endemic, to evaluate the prevalence of hantavirus infection in wild rodents. Blood and tissue samples were collected from 507 rodents during seven field trips from March 2004 to April 2006. Some of the animals were karyotyped to confirm morphological identification. Phylogenetic reconstructions of rodent specimens, based on the mitochondrial DNA cytochrome b gene sequences, were also obtained. Hantavirus antibody was found in 22 (4.3%) of the 507 rodents: 5 Akodon montensis, 2 Akodon paranaensis, 14 Oligoryzomys nigripes, and 1 Sooretamys angouya. Viral RNAs detected in O. nigripes and A. montensis were amplified and sequenced. O. nigripes virus genome was 97.5% (nt) and 98.4% (nt) identical to sequences published for Araucaria (Juquitiba-like) virus based on N and G2 fragment sequences. Viral sequences from A. montensis strain showed 89% and 88% nucleotide identities in a 905-nt fragment of the nucleocapsid (N) protein-coding region of the S segment when it was compared with two other Akodontine rodent-associated viruses from Paraguay, A. montensis and Akodon cursor, respectively. Phylogenetic analysis showed the cocirculation of two genetic hantavirus lineages in the state of Santa Catarina, one from O. nigripes and the other from A. montensis, previously characterized in Brazil and Paraguay, respectively. The hantavirus associated with A. montensis, designed Jaborá virus, represents a distinct phylogenetic lineage among the Brazilian hantaviruses.

  1. Effect of cage vs. floor litter environments on the pulmonary hypertensive response to intravenous endotoxin and on blood-gas values in broilers.

    PubMed

    Wang, W; Erf, G F; Wideman, R F

    2002-11-01

    Intravenous endotoxin has been shown to trigger a delayed pulmonary hypertensive response that varies widely in magnitude and duration among individual broilers. It was proposed that this individual variability may reflect immunological differences acquired during previous respiratory challenges that might have subsequently altered the endotoxin-initiated biochemical cascade. In Experiment 1, we tested the hypothesis that, when compared with broilers reared in clean stainless steel cages (Cage group), broilers reared on floor litter (Floor group) should experience a greater respiratory challenge and therefore may consistently exhibit a more enhanced pulmonary hypertensive response to intravenous endotoxin. Birds in the Cage group were grown in stainless steel cages at a low density (72 birds/8 m2 chamber), and fecal and dander materials were removed daily. Birds in the Floor group were reared on wood-shavings litter at a higher density (110 birds/8 m2 chamber). Pulmonary and systemic mean arterial pressures and blood-gas values were evaluated prior to and following the intravenous administration of 1 mg Salmonella typhimurium endotoxin. Broilers in the Floor and Cage groups exhibited pulmonary hypertensive responses to endotoxin that were very similar in terms of time of onset, duration, and magnitude, as well as variability in the response among individuals. Systemic hypotension also developed similarly in both groups following endotoxin injection. Blood-gas values indicated that the partial pressure of CO2 and the HCO3- concentration in arterial blood were higher (P < 0.05) in the Floor group than in the Cage group prior to and subsequent to the endotoxin injection. In Experiment 2, we reevaluated the effect of a dirty vs. a clean environment on blood-gas values using a different strain of broilers, and confirmed the negative impact of floor rearing on blood-gas values. We conclude that broilers reared on the floor inhaled litter dust and noxious fumes, which

  2. Repeatability and noise robustness of spicularity features for computer aided characterization of pulmonary nodules in CT

    NASA Astrophysics Data System (ADS)

    Wiemker, Rafael; Opfer, Roland; Bülow, Thomas; Kabus, Sven; Dharaiya, Ekta

    2008-03-01

    Computer aided characterization aims to support the differential diagnosis of indeterminate pulmonary nodules. A number of published studies have correlated automatically computed features from image processing with clinical diagnoses of malignancy vs. benignity. Often, however, a high number of features was trained on a relatively small number of diagnosed nodules, raising a certain skepticism as to how salient and numerically robust the various features really are. On the way towards computer aided diagnosis which is trusted in clinical practice, the credibility of the individual numerical features has to be carefully established. Nodule volume is the most crucial parameter for nodule characterization, and a number of studies are testing its repeatability. Apart from functional parameters (such as dynamic CT enhancement and PET uptake values), the next most widely used parameter is the surface characteristic (vascularization, spicularity, lobulation, smoothness). In this study, we test the repeatability of two simple surface smoothness features which can discriminate between smoothly delineated nodules and those with a high degree of surface irregularity. Robustness of the completely automatically computed features was tested with respect to the following aspects: (a) repeated CT scan of the same patient with equal dose, (b) repeated CT scan with much lower dose and much higher noise, (c) repeated automatic segmentation of the nodules using varying segmentation parameters, resulting in differing nodule surfaces. The tested nodules (81) were all solid or partially solid and included a high number of sub- and juxtapleural nodules. We found that both tested surface characterization features correlated reasonably well with each other (80%), and that in particular the mean-surface-shape-index showed an excellent repeatability: 98% correlation between equal dose CT scans, 93% between standard-dose and low-dose scan (without systematic shift), and 97% between varying HU

  3. Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant

    SciTech Connect

    Singh, Anurag K. . E-mail: singan@mail.nih.gov; Karimpour, Shervin E.; Savani, Bipin N.; Guion, Peter M.S.; Hope, Andrew J.; Mansueti, John R.; Ning, Holly; Altemus, Rosemary M. Ph.D.; Wu, Colin O.; Barrett, A. John

    2006-10-01

    Purpose: To determine the value of pulmonary function tests (PFTs) done before peripheral blood stem cell transplant (PBSCT) in predicting mortality after total body irradiation (TBI) performed with or without dose reduction to the lung. Methods and Materials: From 1997 to 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. With regimen A (n = 85), patients were treated without lung dose reduction to 13.6 gray (Gy). In regimen B (n = 35), total body dose was decreased to 12 Gy (1.5 Gy twice per day for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In regimen C (n = 26), lung dose was reduced to 6 Gy. All patients received PFTs before treatment, 90 days after treatment, and annually. Results: Median follow-up was 44 months (range, 12-90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV{sub 1}) and a diffusion capacity of carbon dioxide (DLCO) <100% predicted. In this group, there was a 20% improvement in one-year overall survival with lung dose reduction (70 vs. 50%, log-rank test p = 0.042). Conclusion: Among those with combined ventilation/diffusion capacity deficits, lung dose reduction during TBI significantly improved survival.

  4. Pretreatment neutrophil-to-lymphocyte ratio in peripheral blood was associated with pulmonary tuberculosis retreatment

    PubMed Central

    Yin, Yongmei; Kuai, Shougang; Liu, Jun; Zhang, YingYing; Shan, Zhongbao; Gu, Lan; Huang, Qiusheng

    2016-01-01

    Introduction The neutrophil-to-lymphocyte ratio (NLR) is a readily available biomarker associated with recurrence and survival in various diseases. The objective of this study was to investigate the relationship between NLR and pulmonary tuberculosis (PTB) retreatment. Material and methods This was a case-control study that included 306 newly diagnosed cases of PTB in the clinical database of the Infectious Hospital of Wuxi from December 2009 to December 2011. Of the 306 patients, a total of 68 cases were followed up with TB retreatment. The remaining 238 PTB patients who completed anti-TB treatment and were cured without retreatment were selected as controls. Results According to the ROC curve, the best cut-off value of NLR was 2.53, with a sensitivity of 70.6% and a specificity of 45.4%. The NLR ≥ 2.53 before anti-TB treatment was associated with PTB retreatment (OR = 1.994, 95% CI: 1.116–3.564; adjusted OR (AOR) = 2.409, 95% CI: 1.212–4.788). The retreatment rates with NLR ≥ 2.53 and NLR < 2.53 were 27.1% and 15.5%, respectively, with a significant difference (log-rank test; p = 0.010). Additionally, cavitation on chest X-ray (OR = 2.922, 95% CI: 1.654–5.411; AOR = 2.482, 95% CI: 1.230–5.007), history of smoking (OR = 2.202, 95% CI: 1.158–3.493; AOR = 2.321, 95% CI: 1.135–4.745) and age ≥ 60 (OR = 3.828, 95% CI: 1.626–9.015; AOR = 2.931, 95% CI: 1.122–7.653) were also associated with PTB retreatment. Conclusions NLR ≥ 2.53 is predictive of PTB retreatment. Otherwise, initial cavitation on chest X-ray, history of smoking, and age of ≥ 60 are also risk factors for PTB retreatment. PMID:28261295

  5. Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Kim, Deog Kyeom; Cho, Michael H.; Hersh, Craig P.; Lomas, David A.; Miller, Bruce E.; Kong, Xiangyang; Bakke, Per; Gulsvik, Amund; Agustí, Alvar; Wouters, Emiel; Celli, Bartolome; Coxson, Harvey; Vestbo, Jørgen; MacNee, William; Yates, Julie C.; Rennard, Stephen; Litonjua, Augusto; Qiu, Weiliang; Beaty, Terri H.; Crapo, James D.; Riley, John H.; Tal-Singer, Ruth

    2012-01-01

    Rationale: A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. Objectives: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. Methods: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-α) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P < 1 × 10−8), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. Measurements and Main Results: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P = 0.009–0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P = 0.001–0.049), although these COPD associations were not replicated in two additional cohorts. Conclusions: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID

  6. Reproducibility of pulmonary blood flow measurements by phase-contrast MRI using different 1.5 T MR scanners at two institutions

    PubMed Central

    Iraha, Rin; Tsuchiya, Nanae; Yamashiro, Tsuneo; Iwasawa, Tae

    2017-01-01

    Background Magnetic resonance imaging (MRI) can be beneficial for diagnosis of disease by offering quantitative information. However, reproducibility can be a major problem when there is a numerical threshold in multi-institution, multi-vendor situations. Purpose To measure pulmonary blood flow with phase-contrast (PC) imaging using two different MR scanners (1.5 T) at different institutions in the same participants and to examine the reproducibility of the measurements. Material and Methods Participants were 10 healthy volunteers (5 men; age range, 27–36 years). The measurements included the mean and maximal blood velocities, the mean blood flow volume, and the acceleration time and volume (AT and AV), derived from the time-flow curve of the PC-MRI. Simultaneously obtained maximal, minimal, and mean areas from regions of interest set in the pulmonary artery were also calculated. In order to calculate the reproducibility of the quantitative variables, intra-class correlation coefficients (ICCs) were employed. When an adequate ICC was obtained, Bland–Altman analysis was conducted to identify any systematic bias. Results The ICCs were almost perfect for the mean blood flow volume and the AV (r = 0.82 and 0.80), and were substantial in the mean and maximal areas, and the AT (r = 0.63, 0.74, and 0.64, respectively). However, there was a fixed bias in the area measurement between the two scanners. Also, the AV had a proportional bias. Conclusion Our results reveal that various indices derived from PC-MRI on different MR scanners are promising as common indices for pulmonary flow assessment. Research and clinical use of PC-MRI for the pulmonary artery is expected to extend to multi-institution situations. PMID:28210495

  7. A fatal case of Nocardia otitidiscaviarum pulmonary infection and brain abscess: taxonomic characterization by molecular techniques

    PubMed Central

    Pelaez, Ana Isabel; del Mar Garcia-Suarez, Maria; Manteca, Angel; Melon, Ovidio; Aranaz, Carlos; Cimadevilla, Rafael; Mendez, Francisco Javier; Vazquez, Fernando

    2009-01-01

    We report on a rare case of pulmonary Nocardiosis and brain abscess caused by Nocardia otitidiscaviarum in an elderly woman with chronic obstructive pulmonary disease. Taxonomic identification involved phenotypic testing, restriction fragment length polymorphism (RFLP), and complete 16S rRNA gene sequencing. PMID:19366439

  8. A fatal case of Nocardia otitidiscaviarum pulmonary infection and brain abscess: taxonomic characterization by molecular techniques.

    PubMed

    Pelaez, Ana Isabel; Garcia-Suarez, Maria del Mar; Manteca, Angel; Melon, Ovidio; Aranaz, Carlos; Cimadevilla, Rafael; Mendez, Francisco Javier; Vazquez, Fernando

    2009-04-14

    We report on a rare case of pulmonary Nocardiosis and brain abscess caused by Nocardia otitidiscaviarum in an elderly woman with chronic obstructive pulmonary disease. Taxonomic identification involved phenotypic testing, restriction fragment length polymorphism (RFLP), and complete 16S rRNA gene sequencing.

  9. Quantitative photoacoustic characterization of blood clot in blood: A mechanobiological assessment through spectral information

    NASA Astrophysics Data System (ADS)

    Biswas, Deblina; Vasudevan, Srivathsan; Chen, George C. K.; Sharma, Norman

    2017-02-01

    Formation of blood clots, called thrombus, can happen due to hyper-coagulation of blood. Thrombi, while moving through blood vessels can impede blood flow, an important criterion for many critical diseases like deep vein thrombosis and heart attacks. Understanding mechanical properties of clot formation is vital for assessment of severity of thrombosis and proper treatment. However, biomechanics of thrombus is less known to clinicians and not very well investigated. Photoacoustic (PA) spectral response, a non-invasive technique, is proposed to investigate the mechanism of formation of blood clots through elasticity and also differentiate clots from blood. Distinct shift (increase in frequency) of the PA response dominant frequency during clot formation is reported. In addition, quantitative differentiation of blood clots from blood has been achieved through parameters like dominant frequency and spectral energy of PA spectral response. Nearly twofold increases in dominant frequency in blood clots compared to blood were found in the PA spectral response. Significant changes in energy also help in quantitatively differentiating clots from blood, in the blood. Our results reveal that increase in density during clot formation is reflected in the PA spectral response, a significant step towards understanding the mechanobiology of thrombus formation. Hence, the proposed tool, in addition to detecting thrombus formation, could reveal mechanical properties of the sample through quantitative photoacoustic spectral parameters.

  10. Preparation, characterization and pulmonary pharmacokinetics of a new inhalable zanamivir dry powder.

    PubMed

    Cai, Xingshi; Yang, Yang; Xie, Xiangyang; Yu, Fanglin; Yang, Yanfang; Yang, Zhenbo; Zhang, Tao; Mei, Xingguo

    2016-07-01

    This work describes a new dry powder for inhalation containing zanamivir, which is less hygroscopic than Relenza®. The powders were prepared via a spray-drying technique using mannitol as the carrier. A 5(3) central composite design was used to optimize the formulations. The final optimized powders, characterized with an angle of repose 37.48°, an aerodynamic diameter of 2.346 μm and in vitro deposition of 58.54%, were obtained by using the predicted variable values. Relenza® absorbed a significant amount of water at 66%, 75% and 85% relative humidity (RH; weight changes of approximately 1.38%, 2.18% and 3.72%, respectively). In contrast, the weight change for the zanamivir dry powder inhalation (DPI) was negligible when the RH was increased to 66%. The in vivo potential for the optimized powders was studied further in rats via the endotracheal administration of an 8.4 mg/kg dose. The bioavailability was 116% relative to Relenza®. Fluorescence imaging monitored the zanamivir dry powder inhalers in rats. The results indicated that the zanamivir DPIs were effectively delivered to the lung. These results indicate that the spray-dried zanamivir DPIs were promising for pulmonary delivery.

  11. Intravoxel incoherent motion diffusion-weighted MR imaging in assessing and characterizing solitary pulmonary lesions

    PubMed Central

    Wan, Qi; Deng, Ying-Shi; Zhou, Jia-Xuan; Yu, Yu-Dong; Bao, Ying-Ying; Lei, Qiang; Chen, Hou-Jin; Peng, Ya-Hui; Mei, Ying-Jie; Zeng, Qing-Si; Li, Xin-Chun

    2017-01-01

    This study aimed to investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in assessing solitary pulmonary lesions (SPLs). Sixty-two patients with pathologically confirmed SPLs, including 51 and 11 cases of malignant and benign lesions, respectively, were assessed. Diffusion weighted imaging (DWI) with 13 b values was used to derive apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Our results showed that, there was an excellent inter-observer agreement on the measurements of D and ADC between observers (inter-class correlation coefficient, ICC = 0.902 and 0.884, respectively). Meanwhile, f and D* showed good and substantial reproducibility (ICC = 0.787 and 0.623, respectively). D and ADC of malignant lesions were significantly lower than those of benign lesions (both P ≤ 0.001), while similar values were obtained in both groups for D* and f (both P > 0.05). In receiver operating characteristic (ROC) analysis, D showed the highest area under curve (AUC) for distinguishing malignant from benign lesions, followed by ADC. Accompanying signs of SPLs have specific features on IVIM maps. In conclusion, IVIM provides functional information in characterizing SPLs which is helpful to differential diagnosis. D and ADC have a significantly higher diagnostic value than f and D*. PMID:28225064

  12. Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors.

    PubMed

    Voortman, Johannes; Lee, Jih-Hsiang; Killian, Jonathan Keith; Suuriniemi, Miia; Wang, Yonghong; Lucchi, Marco; Smith, William I; Meltzer, Paul; Wang, Yisong; Giaccone, Giuseppe

    2010-07-20

    The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. In SCLC tumors, as well as bronchial carcinoids and carcinoids of gastrointestinal origin, recurrent CN alterations were observed in 203 genes, including the RB1 gene and 59 microRNAs of which 51 locate in the DLK1-DIO3 domain. These findings suggest the existence of partially shared CN alterations in these tumor types. In contrast, CN alterations of the TP53 gene and the MYC family members were predominantly observed in SCLC. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resembles that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics-based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.

  13. Characterization of the postjunctional α2C-adrenoceptor mediating vasoconstriction to UK14304 in porcine pulmonary veins

    PubMed Central

    Görnemann, T; von Wenckstern, H; Kleuser, B; Villalón, C M; Centurión, D; Jähnichen, S; Pertz, H H

    2007-01-01

    Background and purpose: In terms of postjunctional α2-adrenoceptors in the pulmonary circulation, no evidence is available with regard to the receptor subtypes mediating vasoconstriction. Therefore, we characterized the α2-adrenoceptor subtypes mediating contraction in isolated porcine pulmonary veins. Experimental approach: α-adrenoceptor-mediated vasoconstriction was studied using a tissue bath protocol. mRNA profile and relative quantification of α2-adrenoceptor subtypes were determined in porcine pulmonary veins using reverse-transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. Key results: In porcine pulmonary veins, noradrenaline, phenylephrine (α1-adrenoceptor agonist), UK14304 and clonidine (α2-adrenoceptor agonists) caused concentration-dependent contractions. The rank order of agonist potency was: NA≈UK14304≈clonidine > phenylephrine. UK14304 responses were antagonised by MK912 (noncompetitive antagonist parameter pD'2: 10.1), rauwolscine (pKB: 9.5), yohimbine (pKB: 9.1), WB4101 (pKB: 8.7), ARC239 (pKB: 7.5), prazosin (pKB: 7.1) and BRL44408 (pKB: 7.0). Antagonist potencies fitted best with radioligand binding data (pKi) at the human recombinant α2C-adrenoceptor (r2 = 0.96, P = 0.0001). Correlation with α2B-adrenoceptors was lower (r2 = 0.74, P > 0.01) and no correlation was obtained with α2A-adrenoceptors. Moreover, RT-PCR studies in porcine pulmonary veins showed mRNA signals for α2A- and α2C-adrenoceptors, but not for α2B-adrenoceptors, whilst real-time PCR studies indicated a prominent expression of α2C-adrenoceptor mRNA. Conclusions and Implications: Postjunctional α2C-adrenoceptors mediated contraction in porcine pulmonary veins. α1-Adrenoceptors also seem to be present in this tissue. Since α2-adrenoceptor responsiveness is increased when pulmonary vascular tone is elevated, α2C-adrenoceptor antagonists may be beneficial in diseases such as pulmonary hypertension or congestive heart failure. PMID:17375080

  14. Characterization of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension From REVEAL

    PubMed Central

    Liu, Juliana; Parsons, Lori; Hassoun, Paul M.; McGoon, Michael; Badesch, David B.; Miller, Dave P.; Nicolls, Mark R.; Zamanian, Roham T.

    2010-01-01

    Background: REVEAL (the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) is the largest US cohort of patients with pulmonary arterial hypertension (PAH) confirmed by right-sided heart catheterization (RHC), providing a more comprehensive subgroup characterization than previously possible. We used REVEAL to analyze the clinical features of patients with connective tissue disease-associated PAH (CTD-APAH). Methods: All newly and previously diagnosed patients with World Health Organization (WHO) group 1 PAH meeting RHC criteria at 54 US centers were consecutively enrolled. Cross-sectional and 1-year mortality and hospitalization analyses from time of enrollment compared CTD-APAH to idiopathic disease and systemic sclerosis (SSc) to systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). Results: Compared with patients with idiopathic disease (n = 1,251), patients with CTD-APAH (n = 641) had better hemodynamics and favorable right ventricular echocardiographic findings but a higher prevalence of pericardial effusions, lower 6-min walk distance (300.5 ± 118.0 vs 329.4 ± 134.7 m, P = .01), higher B-type natriuretic peptide (BNP) levels (432.8 ± 789.1 vs 245.6 ± 427.2 pg/mL, P < .0001), and lower diffusing capacity of carbon monoxide (Dlco) (44.9% ± 18.0% vs 63.6% ± 22.1% predicted, P < .0001). One-year survival and freedom from hospitalization were lower in the CTD-APAH group (86% vs 93%, P < .0001; 67% vs 73%, P = .03). Compared with patients with SSc-APAH (n = 399), those with other CTDs (SLE, n = 110; MCTD, n = 52; RA, n = 28) had similar hemodynamics; however, patients with SSc-APAH had the highest BNP levels (552.2 ± 977.8 pg/mL), lowest Dlco (41.2% ± 16.3% predicted), and poorest 1-year survival (82% vs 94% in SLE-APAH, 88% in MCTD-APAH, and 96% in RA-APAH). Conclusions: Patients with SSc-APAH demonstrate a unique phenotype with the highest BNP levels, lowest Dlco

  15. The effect of supine exercise on the distribution of regional pulmonary blood flow measured using proton MRI

    PubMed Central

    Hall, E. T.; Sá, R. C.; Holverda, S.; Arai, T. J.; Dubowitz, D. J.; Theilmann, R. J.; Prisk, G. K.

    2013-01-01

    The Zone model of pulmonary perfusion predicts that exercise reduces perfusion heterogeneity because increased vascular pressure redistributes flow to gravitationally nondependent lung, and causes dilation and recruitment of blood vessels. However, during exercise in animals, perfusion heterogeneity as measured by the relative dispersion (RD, SD/mean) is not significantly decreased. We evaluated the effect of exercise on pulmonary perfusion in six healthy supine humans using magnetic resonance imaging (MRI). Data were acquired at rest, while exercising (∼27% of maximal oxygen consumption) using a MRI-compatible ergometer, and in recovery. Images were acquired in most of the right lung in the sagittal plane at functional residual capacity, using a 1.5-T MR scanner equipped with a torso coil. Perfusion was measured using arterial spin labeling (ASL-FAIRER) and regional proton density using a fast multiecho gradient-echo sequence. Perfusion images were corrected for coil-based signal heterogeneity, large conduit vessels removed and quantified (in ml·min−1·ml−1) (perfusion), and also normalized for density and quantified (in ml·min−1·g−1) (density-normalized perfusion, DNP) accounting for tissue redistribution. DNP increased during exercise (11.1 ± 3.5 rest, 18.8 ± 2.3 exercise, 13.2 ± 2.2 recovery, ml·min−1·g−1, P < 0.0001), and the increase was largest in nondependent lung (110 ± 61% increase in nondependent, 63 ± 35% in mid, 70 ± 33% in dependent, P < 0.005). The RD of perfusion decreased with exercise (0.93 ± 0.21 rest, 0.73 ± 0.13 exercise, 0.94 ± 0.18 recovery, P < 0.005). The RD of DNP showed a similar trend (0.82 ± 0.14 rest, 0.75 ± 0.09 exercise, 0.81 ± 0.10 recovery, P = 0.13). In conclusion, in contrast to animal studies, in supine humans, mild exercise decreased perfusion heterogeneity, consistent with Zone model predictions. PMID:24356515

  16. Dissociation between the time courses of femoral artery blood flow and pulmonary VO2 during repeated bouts of heavy knee extension exercise in humans.

    PubMed

    Fukuba, Yoshiyuki; Ohe, Yukie; Miura, Akira; Kitano, Asami; Endo, Masako; Sato, Hironori; Miyachi, Motohiko; Koga, Shunsaku; Fukuda, Osamu

    2004-05-01

    It has frequently been demonstrated that prior heavy cycling exercise facilitates pulmonary O(2) kinetics at the onset of subsequent heavy exercise. This might be due to improved muscle perfusion via acidosis-induced vasodilating effects. However, it is difficult to measure the blood flow (BF) to the working muscles (via the femoral artery) during cycling exercise. We therefore selected supine knee extension (KE) exercise as an alternative, and investigated whether the faster O(2) kinetics in the 2nd bout was matched by proportionally faster BF kinetics to the exercising muscle. Nine healthy subjects (aged 21-44 years) volunteered to participate in this study. The protocol consisted of two consecutive 6-min KE exercise bouts in a supine position (work rate: 70-75% of peak power) separated by a 6-min baseline rest (EX1 to EX2). During the protocol, a pulsed Doppler ultrasound technique was utilized to continuously measure the BF in the right femoral artery. The protocol was repeated at least 6 times to characterize the precise kinetics. In agreement with previous studies using cycling exercise, the O(2) kinetics in the 2nd bout were facilitated compared with that in the 1st bout [mean +/-s.d. of the 'effective' time constant (tau): EX1, 68.6 +/- 15.9, versus EX2, 58.0 +/- 14.4 s. Phase II-tau: EX1, 48.7 +/- 9.0, versus EX2, 41.2 +/- 13.3 s. Empirical index of the slow component (Delta O(2(6-3))): EX1, 78 +/- 44, versus EX2, 57 +/- 36 ml min(-1) (P < 0.05)]. However, no substantial difference was observed for the facilitation of the femoral artery BF response to the 1st and 2nd exercise bouts [i.e. the 'effective'tau of the femoral artery BF: EX1, 40.8 +/- 16.9, versus EX2, 39.0 +/- 17.1 s (P > 0.05)]. It was concluded that the faster pulmonary O(2) kinetics during heavy KE exercise following prior heavy exercise was not associated with a similar modulation in the BF to the working muscles.

  17. Pulmonary O2 uptake and leg blood flow kinetics during moderate exercise are slowed by hyperventilation-induced hypocapnic alkalosis

    PubMed Central

    Chin, Lisa M. K.; Heigenhauser, George J. F.; Paterson, Donald H.

    2010-01-01

    The effect of hyperventilation-induced hypocapnic alkalosis (Hypo) on the adjustment of pulmonary O2 uptake (V̇o2p) and leg femoral conduit artery (“bulk”) blood flow (LBF) during moderate-intensity exercise (Mod) was examined in eight young male adults. Subjects completed four to six repetitions of alternate-leg knee-extension exercise during normal breathing [Con; end-tidal partial pressure of CO2 (PetCO2) ∼40 mmHg] and sustained hyperventilation (Hypo; PetCO2 ∼20 mmHg). Increases in work rate were made instantaneously from baseline (3 W) to Mod (80% estimated lactate threshold). V̇o2p was measured breath by breath by mass spectrometry and volume turbine, and LBF (calculated from mean femoral artery blood velocity and femoral artery diameter) was measured simultaneously by Doppler ultrasound. Concentration changes of deoxy (Δ[HHb])-, oxy (Δ[O2Hb])-, and total hemoglobin-myoglobin (Δ[HbTot]) of the vastus lateralis muscle were measured continuously by near-infrared spectroscopy (NIRS). The kinetics of V̇o2p, LBF, and Δ[HHb] were modeled using a monoexponential equation by nonlinear regression. The time constants for the phase 2 V̇o2p (Hypo, 49 ± 26 s; Con, 28 ± 8 s) and LBF (Hypo, 46 ± 16 s; Con, 23 ± 6 s) were greater (P < 0.05) in Hypo compared with Con. However, the mean response time for the overall Δ[HHb] response was not different between conditions (Hypo, 23 ± 5 s; Con, 24 ± 3 s), whereas the Δ[HHb] amplitude was greater (P < 0.05) in Hypo (8.05 ± 7.47 a.u.) compared with Con (6.69 ± 6.31 a.u.). Combined, these results suggest that hyperventilation-induced hypocapnic alkalosis is associated with slower convective (i.e., slowed femoral artery and microvascular blood flow) and diffusive (i.e., greater fractional O2 extraction for a given ΔV̇o2p) O2 delivery, which may contribute to the hyperventilation-induced slowing of V̇o2p (and muscle O2 utilization) kinetics. PMID:20339012

  18. Impairment of Wnt/β-catenin signaling in blood cells of patients with severe cavitary pulmonary tuberculosis

    PubMed Central

    Huang, Huichang; Yang, Rui; Yao, Lan

    2017-01-01

    Tuberculosis (TB) remains as a leading infectious disease worldwide. Our previous study showed interferon (IFN)-γ and CD3 T cell impairment in patients with severe cavitary pulmonary TB (PTB). However, the cause of the change in immune responses during the progression of TB is still poorly understood. In this study, eight newly diagnosed patients with severe cavitary and mild lesion non-cavity PTB were recruited, and three healthy volunteers were recruited as the control. RNA extracted from blood was tested by whole genome oligo microarrays. A PCR array was used to further test the same samples. Two additional groups of patients were recruited according to the same criteria with healthy control(HC) recruited as well and subjected to peripheral blood mononuclear cell isolation (PBMC)and analysis of TCF-7, β-catenin, cyclin D2, IFN-γ, and tumor necrosis factor (TNF)-α expression in CD14- cells (lymphocytes) and CD14+ cells by quantitative PCR. The changes of expression of β-catenin, CD69+ and IFN-γ by CD3+, CD14- and CD14+ cells in vitro with stimulation of LiCl were tested by flow cytometry. Whole genome oligo microarrays showed a significant decrease in expression of the Wnt signaling pathway in severe PTB patients. Further analysis of the Wnt pathway by PCR array indicated that TCF-7, β-catenin, and cyclin D2 expression was significantly reduced in severe PTB patients compared with mild PTB patients. In the additionally recruited patients, TCF-7, β-catenin, and cyclin D2 were expressed in both CD14+ and CD14- cells, while β-catenin was decreased significantly in CD14- cells compared with CD14+ cells in severe PTB patients, and IFN-γ and TNF-α expression in CD14- cells was also reduced significantly in severe PTB patients. β-catenin can directly trigger T cell activation and IFN-γsecretion in PBMCs stimulated for 24 hours. These findings indicate that Wnt pathway and its key genes, such as β-catenin, were impaired in blood cells of patients with

  19. Dielectrophoretic characterization of erythrocytes: positive ABO blood types.

    PubMed

    Srivastava, Soumya K; Daggolu, Prashant R; Burgess, Shane C; Minerick, Adrienne R

    2008-12-01

    Dielectrophoretic manipulation of erythrocytes/red blood cells is investigated as a tool to identify blood type for medical diagnostic applications. Positive blood types of the ABO typing system (A+, B+, AB+ and O+) were tested and cell responses quantified. The dielectrophoretic response of each blood type was observed in a platinum electrode microdevice, delivering a field of 0.025V(pp)/microm at 1 MHz. Responses were recorded via video microscopy for 120 s and erythrocyte positions were tabulated at 20-30 s intervals. Both vertical and horizontal motions of erythrocytes were quantified via image object recognition, object tracking in MATLAB, binning into appropriate electric field contoured regions (wedges) and statistical analysis. Cells of O+ type showed relatively attenuated response to the dielectrophoretic field and were distinguished with greater than 95% confidence from all the other three blood types. AB+ cell responses differed from A+ and B+ blood types likely because AB+ erythrocytes express both the A and B glycoforms on their membrane. This research suggests that dielectrophoresis of untreated erythrocytes beyond simple dilution depends on blood type and could be used in portable blood typing devices.

  20. Development and Characterization of an Inducible Rat Model of Chronic Thromboembolic Pulmonary Hypertension.

    PubMed

    Arias-Loza, Paula-Anahi; Jung, Pius; Abeßer, Marco; Umbenhauer, Sandra; Williams, Tatjana; Frantz, Stefan; Schuh, Kai; Pelzer, Theo

    2016-05-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is an entity of PH that not only limits patients quality of life but also causes significant morbidity and mortality. The treatment of choice is pulmonary endarterectomy. However numerous patients do not qualify for pulmonary endarterectomy or present with residual vasculopathy post pulmonary endarterectomy and require specific vasodilator treatment. Currently, there is no available specific small animal model of CTEPH that could serve as tool to identify targetable molecular pathways and to test new treatment options. Thus, we generated and standardized a rat model that not only resembles functional and histological features of CTEPH but also emulates thrombi fibrosis. The pulmonary embolism protocol consisted of 3 sequential tail vein injections of fibrinogen/collagen-covered polystyrene microspheres combined with thrombin and administered to 10-week-old male Wistar rats. After the third embolism, rats developed characteristic features of CTEPH including elevated right ventricular systolic pressure, right ventricular cardiomyocyte hypertrophy, pulmonary artery remodeling, increased serum brain natriuretic peptide levels, thrombi fibrosis, and formation of pulmonary cellular-fibrotic lesions. The current animal model seems suitable for detailed study of CTEPH pathophysiology and permits preclinical testing of new pharmacological therapies against CTEPH.

  1. Characterization of an epizootic of pulmonary edema in swine associated with fumonisin in corn screenings.

    PubMed

    Osweiler, G D; Ross, P F; Wilson, T M; Nelson, P E; Witte, S T; Carson, T L; Rice, L G; Nelson, H A

    1992-01-01

    In 1989, corn screenings were associated with acute interstitial pulmonary edema, hydrothorax, and death in swine. Attack rate was 5-50%, case fatality rate was 50-90%, and clinical course was 1-2 days. Screenings from farms with pigs affected with pulmonary edema contained 20-330 micrograms fumonisin B1 per gram. Screenings containing 92 micrograms fumonisin B1 per gram fed to weanling pigs caused pulmonary edema and death. Sterilized corn inoculated with Fusarium moniliforme and diluted 1:1 with clean corn contained fumonisin B1 (17 micrograms/g) and caused acute pulmonary edema when fed for 5 days. Survivors developed subacute hepatotoxicosis with individual hepatocellular necrosis, hepatomegalocytosis, and increased numbers of mitotic figures. Similar liver lesions occurred in pigs given fumonisin B1 intravenously at 0.8 mg/kg body weight for 14 days.

  2. Efficacy of Liposomal Amphotericin B with Prolonged Circulation in Blood in Treatment of Severe Pulmonary Aspergillosis in Leukopenic Rats

    PubMed Central

    Van Etten, Els W. M.; Stearne-Cullen, Lorna E. T.; Ten Kate, Marian T.; Bakker-Woudenberg, Irma A. J. M.

    2000-01-01

    The therapeutic efficacy of long-circulating polyethylene glycol-coated liposomal amphotericin B (AMB) (PEG-AMB-LIP) was compared with that of AMB desoxycholate (Fungizone) in a model of severe invasive pulmonary aspergillosis in persistently leukopenic rats as well as in temporarily leukopenic rats. PEG-AMB-LIP treatment (intravenous administration) consisted of a single, or double (every 72 h), or triple (every 72 h) dose of 10 mg of AMB/kg of body weight, a double dose (every 72 h) of 14 mg of AMB/kg, or a 5-day treatment (every 24 h) with 6 mg/kg/dose. AMB desoxycholate was administered for 10 consecutive days at 1 mg of AMB/kg/dose. Treatment was started 30 h after fungal inoculation, at which time mycelial growth was firmly established. Both persistently and temporarily leukopenic rats died between 4 and 9 days after Aspergillus fumigatus inoculation when they were left untreated or after treatment with a placebo. In persistently leukopenic rats, a single dose of PEG-AMB-LIP (10 mg/kg) was as effective as the 10-day treatment with AMB desoxycholate (at 1 mg/kg/dose) in significantly prolonging the survival of rats infected with A. fumigatus and in reducing the dissemination of A. fumigatus to the liver. Prolongation of PEG-AMB-LIP treatment (double or triple dose or 5-day treatment) did not further improve efficacy. For temporarily leukopenic rats no major advances in efficacy were achieved compared to those for persistently leukopenic rats, probably because the leukocyte numbers in blood were restored too late in the course of infection. PMID:10681315

  3. How Is Pulmonary Embolism Treated?

    MedlinePlus

    ... Twitter. How Is Pulmonary Embolism Treated? Pulmonary embolism (PE) is treated with medicines, procedures, and other therapies. The main goals of treating PE are to stop the blood clot from getting ...

  4. How Is Pulmonary Embolism Diagnosed?

    MedlinePlus

    ... Doctors can use computed tomography (to-MOG-rah-fee) scans, or CT scans, to look for blood ... Pulmonary Angiography Pulmonary angiography (an-jee-OG-rah-fee) is another test used to diagnose PE. This ...

  5. Radionuclide analysis of pulmonary blood volume: the response to spontaneous angina pectoris and sublingual nitroglycerin in patients with coronary artery disease.

    PubMed

    Slutsky, R; Mancini, G B; Costello, D; Hooper, W; Verba, J; Nelson, T; Shabetai, R; LeWinter, M M

    1983-02-01

    By manually assigning pulmonary regions of interest and deriving pulmonary time-activity (volume) curves, we were able to make count estimates of pulmonary blood volume (PBV) from gated cardiac blood pool scans. Five patients with coronary heart disease developed angina spontaneously while under a gamma camera. This produced an increase in cardiac volumes (p less than 0.05), a reduction in left ventricular ejection fraction (p less than 0.01), along with a marked increase in PBV (0.010 +/- 0.003 to 0.015 +/- 0.002 units, p less than 0.05). Nitroglycerin was then administered and reduced PBV in association with a return to normal in cardiac systolic function and size. In patients with stable chronic ischemic heart disease, sublingual nitroglycerin also reduced PBV (p less than 0.05), although not as much as when administered during an anginal episode. We conclude that gated imaging of the chest can be utilized to follow changes in PBV serially. These changes can be utilized to evaluate clinically important changes in hemodynamic status and the response to pharmacologic interventions.

  6. A Murine Inhalation Model to Characterize Pulmonary Exposure to Dry Aspergillus fumigatus Conidia

    PubMed Central

    Buskirk, Amanda D.; Green, Brett J.; Lemons, Angela R.; Nayak, Ajay P.; Goldsmith, W. Travis; Kashon, Michael L.; Anderson, Stacey E.; Hettick, Justin M.; Templeton, Steven P.; Germolec, Dori R.; Beezhold, Donald H.

    2014-01-01

    Most murine models of fungal exposure are based on the delivery of uncharacterized extracts or liquid conidia suspensions using aspiration or intranasal approaches. Studies that model exposure to dry fungal aerosols using whole body inhalation have only recently been described. In this study, we aimed to characterize pulmonary immune responses following repeated inhalation of conidia utilizing an acoustical generator to deliver dry fungal aerosols to mice housed in a nose only exposure chamber. Immunocompetent female BALB/cJ mice were exposed to conidia derived from Aspergillus fumigatus wild-type (WT) or a melanin-deficient (Δalb1) strain. Conidia were aerosolized and delivered to mice at an estimated deposition dose of 1×105 twice a week for 4 weeks (8 total). Histopathological and immunological endpoints were assessed 4, 24, 48, and 72 hours after the final exposure. Histopathological analysis showed that conidia derived from both strains induced lung inflammation, especially at 24 and 48 hour time points. Immunological endpoints evaluated in bronchoalveolar lavage fluid (BALF) and the mediastinal lymph nodes showed that exposure to WT conidia led to elevated numbers of macrophages, granulocytes, and lymphocytes. Importantly, CD8+ IL17+ (Tc17) cells were significantly higher in BALF and positively correlated with germination of A. fumigatus WT spores. Germination was associated with specific IgG to intracellular proteins while Δalb1 spores elicited antibodies to cell wall hydrophobin. These data suggest that inhalation exposures may provide a more representative analysis of immune responses following exposures to environmentally and occupationally prevalent fungal contaminants. PMID:25340353

  7. Blood

    MedlinePlus

    ... The liquid part, called plasma, is made of water, salts, and protein. Over half of your blood is plasma. The solid part of your blood contains red blood cells, white blood cells, and platelets. Red ...

  8. Characterization of thermoplastic microfiltration chip for the separation of blood plasma from human blood.

    PubMed

    Chen, Pin-Chuan; Chen, Chih-Chun; Young, Kung-Chia

    2016-09-01

    In this study, we developed a fully thermoplastic microfiltration chip for the separation of blood plasma from human blood. Spiral microchannels were manufactured on a PMMA substrate using a micromilling machine, and a commercial polycarbonate membrane was bonded between two thermoplastic substrates. To achieve an excellent bonding between the commercial membrane and the thermoplastic substrates, we used a two-step injection and curing procedure of UV adhesive into a ring-shaped structure around the microchannel to efficiently prevent leakage during blood filtration. We performed multiple filtration experiments using human blood to compare the influence of three factors on separation efficiency: hematocrit level (40%, 23.2%, and 10.9%), membrane pore size (5 μm, 2 μm, and 1 μm), and flow rate (0.02 ml/min, 0.06 ml/min, 0.1 ml/min). To prevent hemolysis, the pressure within the microchannel was kept below 0.5 bars throughout all filtration experiments. The experimental results clearly demonstrated the following: (1) The proposed microfiltration chip is able to separate white blood cells and red blood cells from whole human blood with a separation efficiency that exceeds 95%; (2) no leakage occurred during any of the experiments, thereby demonstrating the effectiveness of bonding a commercial membrane with a thermoplastic substrate using UV adhesive in a ring-shaped structure; (3) separation efficiency can be increased by using a membrane with smaller pore size, by using diluted blood with lower hematocrit, or by injecting blood into the microfiltration chip at a lower flow rate.

  9. Characterization of sarcoma-like cells derived from endarterectomized tissues from patients with CTEPH and establishment of a mouse model of pulmonary artery intimal sarcoma.

    PubMed

    Jujo, Takayuki; Sakao, Seiichiro; Kantake, Masashi; Maruoka, Miki; Tanabe, Nobuhiro; Kasahara, Yasunori; Kurosu, Katsushi; Masuda, Masahisa; Harigaya, Kenichi; Tatsumi, Koichiro

    2012-08-01

    In general, intravascular thrombus formation in the pulmonary arteries is considered to be the most common cause of chronic thromboembolic pulmonary hypertension (CTEPH). The current mainstay of therapy for patients with CTEPH is pulmonary endarterectomy (PEA). Recently, the existence of myofibroblast-like cells in endarterectomized tissues has been demonstrated. At the 2nd passage of these myofibroblast-like cells, a pleomorphic cell type was isolated. Pulmonary intimal sarcoma is a very uncommon neoplastic tumor thought to originate from subendothelial-mesenchymal cells of the pulmonary vascular wall. Because these pleomorphic cells were isolated from the pulmonary vascular beds, it is believed that the analysis of these cells may contribute to the understanding of pulmonary intimal sarcoma. We isolated cells from the endarterectomized tissue from patients with CTEPH and identified one type as sarcoma-like cells (SCLs). The SCLs were characterized as hyperproliferative, anchorage-independent, invasive and serum-independent. Moreover, C.B-17/lcr-scid/scidJcl mice injected subcutaneously with SCLs developed solid, undifferentiated tumors at the site of injection, and those injected intravenously with SCLs via the tail vein developed tumors which grew along the intimal surface of the pulmonary vessels, thus, demonstrating the high tumorigenic potential of these cells. The behavior of SCLs indicated that these cells may have a vascular cell-like potential which can affiliate them with the intimal surface of the pulmonary artery, and which may be shared with pulmonary intimal sarcoma. A further investigation of this mouse model with SCLs may elucidate the mechanism(s) underlying the development of pulmonary intimal sarcoma.

  10. Ultrasonic Measurement of Fluid Viscosity for Blood Characterization

    NASA Astrophysics Data System (ADS)

    Nitta, Naotaka; Homma, Kazuhiro

    2005-06-01

    Although plaque rupture in arteriosclerosis is affected by not only its strength but also by hemodynamic factors, such as blood pressure and shear stress, in particular, the viscous coefficient which directly controls the magnitude of shear stress might be a risk factor in plaque rupture. Therefore, if the viscous coefficient can be assessed noninvasively, it can be a useful index for prediction of a plaque rupture and assessment of various diseases. In this work, an ultrasonic methodology to estimate the viscous coefficient was investigated by numerical simulation and flow-phantom experiment as the fundamental investigation for noninvasively assessing the viscous characteristics of blood. These results show that the proposed method is useful for estimating the kinematic viscosity coefficient in the viscous evaluation of blood.

  11. High-resolution CT in simple coal workers' pneumoconiosis. Lack of correlation with pulmonary function tests and arterial blood gas values

    SciTech Connect

    Collins, L.C.; Willing, S.; Bretz, R.; Harty, M.; Lane, E.; Anderson, W.H. )

    1993-10-01

    We examined 21 miners by means of standard chest radiography, high-resolution computerized tomography (HRCT), pulmonary function tests, and resting arterial blood gas levels. Using the ILO/UC classification of pneumoconiosis, 7 miners had category 1/0 or 2/1 simple coal workers' pneumoconiosis (CWP). By HRCT, nodules were identified in 12 miners; 4 of 9 were classified as category 0/0 CWP; 2 of 5, 0/1 CWP; 5 of 6, 1/0 CWP; and 1 of 1, 2/1 CWP by chest radiograph. Focal emphysema was identified by HRCT in 7 miners; 4 of 9 were classified as 0/0 CWP; 2 of 5, 0/1 CWP; and 1 of 6, 1/0 CWP by standard chest radiography. Four miners with definite nodules confirmed by HRCT had focal emphysema, while three without nodules had focal emphysema. Pulmonary function testing was not different between miners with or without CWP by standard chest radiography, nor was it different between miners with or without definite nodules evidenced by HRCT. No difference in resting oxygenation was found between any group of miners. The presence of focal emphysema confirmed by HRCT did not significantly affect pulmonary function tests on resting arterial blood gas values. There was, however, a significantly lower FEV1 and mean forced expiratory flow during the middle half of forced vital capacity with lifetime nonsmoking miners. The presence of CWP on chest radiography was significantly correlated with smoking cigarettes but not the years of mining. The presence of nodules on HRCT approached a significant correlation with cigarette smoking, but focal emphysema did not. For detecting evidence of coal dust accumulation in lung parenchyma and identifying focal emphysema, HRCT was more sensitive than standard chest radiography. However, despite earlier detection of parenchymal abnormalities, abnormal pulmonary function attributable to coal dust could not be identified.

  12. Intra- and inter-reader reproducibility of blood flow measurements on the ascending aorta and pulmonary artery using cardiac magnetic resonance.

    PubMed

    Di Leo, Giovanni; D'Angelo, Ida Daniela; Alì, Marco; Cannaò, Paola Maria; Mauri, Giovanni; Secchi, Francesco; Sardanelli, Francesco

    2017-03-01

    The aim of our study was to estimate the intra- and inter-reader reproducibility of blood flow measurements in the ascending aorta and main pulmonary artery using cardiac magnetic resonance (CMR) and a semi-automated segmentation method. The ethics committee approved this retrospective study. A total of 50 consecutive patients (35 males and 15 females; mean age±standard deviation 27±13 years) affected by congenital heart disease were reviewed. They underwent CMR for flow analysis of the ascending aorta and main pulmonary artery (1.5 T, through-plane phase-contrast sequences). Two independent readers (R1, trained radiology resident; R2, lower-trained technician student) obtained segmented images twice (>10-day interval), using a semi-automated method of segmentation. Peak velocity, forward and backward flows were obtained. Bland-Altman analysis was used and reproducibility was reported as complement to 100% of the ratio between the coefficient of repeatability and the mean. R1 intra-reader reproducibility for the aorta was 99% (peak velocity), 95% (forward flow) and 49% (backward flow); for the pulmonary artery, 99%, 91% and 90%, respectively. R2 intra-reader reproducibility was 92%, 91% and 38%; 98%, 86% and 87%, respectively. Inter-reader reproducibility for the aorta was 91%, 85% and 20%; for the pulmonary artery 96%, 75%, and 82%, respectively. Our results showed a good to excellent reproducibility of blood flow measurements of CMR together with a semiautomated method of segmentation, for all variables except the backward flow of the ascending aorta, with a limited impact of operator's training.

  13. Evaluation of a whole-blood chemiluminescent immunoassay of IFN-γ, IP-10, and MCP-1 for diagnosis of active pulmonary tuberculosis and tuberculous pleurisy patients.

    PubMed

    Liang, Yan; Wang, Ying; Li, Hang; Yang, Yourong; Liu, Jianyang; Yu, Ting; Wu, Xueqiong

    2016-10-01

    The study explored the use of IP-10, MCP-1, and IFN-γ as biomarkers to improve the diagnoses of active pulmonary tuberculosis and tuberculous pleurisy. We enrolled 267 individuals, including 134 TB patients, 93 patients with non-tuberculous pulmonary diseases, and 40 healthy controls. Whole bloods were stimulated in vitro with rCFP-10/ESAT-6 protein antigen of Mycobacterium tuberculosis. The levels of IFN-γ, IP-10, and MCP-1 in cultured supernatants of whole bloods were detected by a chemiluminescence immunoassay. A receiver operating characteristic (ROC) curve was drawn to determine the cutoff value for diagnosing TB and to evaluate the diagnostic efficacies of the IFN-γ, IP-10, and MCP-1 for TB. The antigen-specific release of each cytokine, IFN-γ, IP-10, and MCP-1, was significantly higher in the TB groups than in either the non-tuberculous pulmonary disease group (p < 0.001) or the healthy control group (p < 0.001). The ROC curves indicated cutoff values for IFN-γ, IP-10, and MCP-1 at 147.8, 160.4, and 496.4 pg/mL, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic efficiency for IFN-γ were 85.8%, 70.7%, 74.7%, 83.2%, and 78.3%, respectively; for IP-10 were 72.4%, 75.9%, 75.2%, 73.2%, and 74.2%, respectively; and for MCP-1 were 90.3%, 97.0%, 96.8%, 90.8%, and 93.6%, respectively. IFN-γ combined MCP-1 improved the sensitivity to 97.8% compared with IFN-γ (p < 0.001). Our findings indicate high sensitivity and specificity of MCP-1 as novel biomarkers for the diagnosis of active pulmonary tuberculosis and tuberculous pleurisy.

  14. Pulmonary Rehabilitation: MedlinePlus Health Topic

    MedlinePlus

    ... better in your daily life. NIH: National Heart, Lung, and Blood Institute Start Here Pulmonary Rehabilitation (American Thoracic Society) - PDF Pulmonary Rehabilitation (National Heart, Lung, and Blood Institute) What Are the Benefits and Risks of ...

  15. Genetic characterization of the ABO blood group in Neandertals

    PubMed Central

    2008-01-01

    Background The high polymorphism rate in the human ABO blood group gene seems to be related to susceptibility to different pathogens. It has been estimated that all genetic variation underlying the human ABO alleles appeared along the human lineage, after the divergence from the chimpanzee lineage. A paleogenetic analysis of the ABO blood group gene in Neandertals allows us to directly test for the presence of the ABO alleles in these extinct humans. Results We have analysed two male Neandertals that were retrieved under controlled conditions at the El Sidron site in Asturias (Spain) and that appeared to be almost free of modern human DNA contamination. We find a human specific diagnostic deletion for blood group O (O01 haplotype) in both Neandertal individuals. Conclusion These results suggest that the genetic change responsible for the O blood group in humans predates the human and Neandertal divergence. A potential selective event associated with the emergence of the O allele may have therefore occurred after humans separated from their common ancestor with chimpanzees and before the human-Neandertal population divergence. PMID:19108732

  16. Phenotypic, ultra-structural and functional characterization of bovine peripheral blood dendritic cell subsets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dendritic cells (DC) are multifunctional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets...

  17. [Cardiopulmonary exercise testing in chronic obstructive pulmonary disease (COPD) - breath-functional characterization and disease severity assessment].

    PubMed

    Mühle, A; Obst, A; Winkler, J; Ewert, R

    2015-09-01

    COPD is a heterogeneous disease with a wide range of clinical phenotypes and breath-functional dysfunctions. Cardiopulmonary exercise testing (CPET) allows describing all component parts of breathing and determining exercise capacity and the mechanisms of exercise limitation. From these aspects 64 COPD patient stages II, III and IV according to the conventional GOLD classification were examined by means of CPET to evaluate whether CPET can provide a better functional characterization of COPD than the standard investigation procedures in pulmonary practice.We could show that in pulmonary practice CPET is safely and effectively practicable in stable COPD patients of all GOLD stages. This method allowed a clinical and prognostic disease severity assessment of all patients, proving important differences of peak oxygen uptake in each GOLD stage, so that patients in spite of identical GOLD disease severity were to be assigned to different prognostic groups according CPET criteria. Furthermore, we found relevant differences of individual breath-functional patterns in exercise, which can neither be objectified nor be prognosticated by standard investigation procedures at rest.Therefore CPET allows, aside from an objective clinical and prognostic disease severity assessment, also a breath-functional evaluation in a subtly way in COPD patients reflecting the multidimensional background of the disease with variable dysfunctions in pulmonary ventilation, gas exchange, circulation and muscular function as well as associated cardio vascular comorbidities. The breath-functional phenotyping of the COPD patient seems to be meaningful in particular for an individualised therapy management.

  18. Characterization of Blood Properties from Coagulating Blood of Different Hematocrits Using Ultrasonic Backscatter and Attenuation

    NASA Astrophysics Data System (ADS)

    Huang, Chih-Chung; Wang, Shyh-Hau

    2006-09-01

    The influence of hematocrit on the change of blood properties during coagulating was extensively investigated using ultrasonic integrated backscatter and attenuation. Measurements were performed with porcine blood at hematocrits ranging from 25 to 55% using a 10 MHz transducer. Results showed that both integrated backscatter and attenuation are able to sensitively differentiate various stages of blood properties during coagulating. The slopes of integrated backscatter (Sr, dB/S) and attenuation (αr, dB\\cdotcm-1\\cdotMHz-1\\cdotmS-1) are increased relative to hematocrit. The best fits for Sr and αr as a function of hematocrit (H) equal to Sr=0.0357+1.62e-0.108H and αr=0.0281+0.003H, respectively. Variations of clotting time (Ts) and reaction time (Tα), estimated respectively from ultrasonic integrated backscatter and attenuation, associated with clot formation are also increased with hematocrit. This study demonstrates that blood hematocrit is a substantial factor affecting viscosity and backscattering properties of blood during coagulation capable of being discerned by ultrasonic backscattering and attenuation.

  19. Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors

    PubMed Central

    2014-01-01

    Background Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa. The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined. To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients. Methods A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year. High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients. P. aeruginosa isolates were genotyped by PFGE. Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis. Results P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%). Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization. In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation. Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75). In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients. Conclusions The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics. Over 10% of these patients fulfilled criteria for

  20. Calculating alveolar capillary conductance and pulmonary capillary blood volume: comparing the multiple- and single-inspired oxygen tension methods

    PubMed Central

    Ceridon, Maile L.; Beck, Kenneth C.; Olson, Thomas P.; Bilezikian, Jordan A.

    2010-01-01

    Key elements for determining alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) from the lung diffusing capacity (Dl) for carbon monoxide (DlCO) or for nitric oxide (DlNO) are the reaction rate of carbon monoxide with hemoglobin (θCO) and the DmCO/DlNO relationship (α-ratio). Although a range of values have been reported, currently there is no consensus regarding these parameters. The study purpose was to define optimal parameters (θCO, α-ratio) that would experimentally substantiate calculations of Dm and Vc from the single-inspired O2 tension [inspired fraction of O2 (FiO2)] method relative to the multiple-FiO2 method. Eight healthy men were studied at rest and during moderate exercise (80-W cycle). Dm and Vc were determined by the multiple-FiO2 and single-FiO2 methods (rebreathe technique) and were tabulated by applying previously reported θCO equations (both methods) and by varying the α-ratio (single-FiO2 method) from 1.90 to 2.50. Values were then compared between methods throughout the examined α-ratios. Dm and Vc were critically dependent on the applied θCO equation. For the multiple-FiO2 method, Dm was highly variable between θCO equations (rest and exercise); the range of Vc was less widespread. For the single-FiO2 method, the θCO equation by Reeves and Park (1992) combined with an α-ratio between 2.08 and 2.26 gave values for Dm and Vc that most closely matched those from the multiple-FiO2 method and were also physiologically plausible compared with predicted values. We conclude that the parameters used to calculate Dm and Vc values from the single-FiO2 method (using DlCO and DlNO) can significantly influence results and should be evaluated within individual laboratories to obtain optimal values. PMID:20538842

  1. Blood

    MedlinePlus

    ... that die or are lost from the body. White Blood Cells White blood cells (WBCs, and also ... of severe pain. previous continue Diseases of the White Blood Cells Neutropenia (pronounced: new-truh-PEE-nee- ...

  2. Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pulmonary neuroendocrine cells (PNECs) are proposed to be the first specialized cell type to appear in the lung, but their ontogeny remains obscure. Although studies of PNECs have suggested their involvement in a number of lung functions, neither their in vivo significance nor the molecular mechanis...

  3. IDENTIFICATION AND CHARACTERIZATION OF AN IDIOPATHIC PULMONARY FIBROSIS-LIKE CONDITION IN CATS

    EPA Science Inventory

    Interstitial lung diseases are a heterogeneous group of disorders due to a variety of causes. In veterinary medicine, those with a prominent fibrotic component of unknown etiology are often called idiopathic pulmonary fibrosis (IPF). In human medicine, this term is reserved for ...

  4. Characterization of the pulmonary inflammatory response to an anaerobic bacterial challenge.

    PubMed

    Nelson, S; Laughon, B E; Summer, W R; Eckhaus, M A; Bartlett, J G; Jakab, G J

    1986-02-01

    Anaerobic bacteria from the oral flora are important causes of aspiration pneumonia and lung abscess. However, the pulmonary antibacterial response to these organisms has not been well described. To define this, mice were intratracheally inoculated with 10(9) Bacteroides gingivalis, a member of the B. melaninogenicus group, and a common clinical isolate from periodontal disease and anaerobic pulmonary infections. Studies after intratracheal challenge included bacteriologic and histopathologic examination, pulmonary cellular response, lactic dehydrogenase (LDH) and albumin levels in lung lavage fluid, and wet lung weight. Overall mortality was 25%. In the surviving animals, pulmonary lavage showed a marked recruitment of polymorphonuclear leukocytes that was associated with significant bacterial killing by 48 h. Histopathologic examination showed an acute, severe necrotizing bronchopneumonia. Pulmonary abscess formation occurred in 37% of animals. Severe parenchymal damage was further documented by a marked increase in LDH levels in lavage fluids. Mean LDH levels in lavage fluid increased to 850 +/- 25 units/first lavage at 24 h postchallenge compared with control values of 65 +/- 10 units/first lavage. Lung lavage also demonstrated an extensive influx of serum albumin consistent with injury to the alveolar capillary membrane. Albumin levels in lung lavage were highest at 24 h after intratracheal challenge (3.25 +/- 0.3 mg/first lavage), whereas lavage fluid from control mice had nondetectable albumin levels. Wet lung weights maximally increased from 0.12 +/- 0.01 g in control mice to 0.28 +/- 0.03 g 24 h after bacterial-challenge. These data demonstrate tht B. gingivalis causes marked inflammation in the lung that progresses to severe bronchopneumonia and lung abscess.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Handbook of pulmonary emergencies

    SciTech Connect

    Spaquolo, S.V.; Medinger, A

    1986-01-01

    This book presents information on the following topics: clinical assessment of the patient with pulmonary disease; interpretation of arterial blood gases in the emergency patient; life-threatening pneumonia; extrapulmonic ventilatory failure; acute inhalation lung disease; pulmonary edema; near drowning; chest trauma; upper airway emergencies; chronic lung disease with acute respiratory decompensation; acute respiratory failure in the patient with chronic airflow obstruction; asthma; hemoptysis; embolic pulmonary disease; superior vena cava syndrome; catastrophic pleural disease; ventilatory assistance and its complications; and ventilator emergencies.

  6. Genetics Home Reference: pulmonary arterial hypertension

    MedlinePlus

    ... Home Health Conditions pulmonary arterial hypertension pulmonary arterial hypertension Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

  7. Cross-sectional study on respiratory effect of toner-exposed work in manufacturing plants, Japan: pulmonary function, blood cells, and biochemical markers.

    PubMed

    Kitamura, H; Terunuma, N; Kurosaki, S; Hata, K; Ide, R; Kuga, H; Kakiuchi, N; Masuda, M; Totsuzaki, T; Osato, A; Uchino, B; Kitahara, K; Iwasaki, A; Yoshizumi, K; Morimoto, Y; Kasai, H; Murase, T; Higashi, T

    2009-06-01

    The aim of the study is to examine the relationship between toner-exposed work and health indices related to respiratory disorders and to confirm the baseline of a cohort study to clarify the effect of toner exposure in manufacturing plants. Subjects were 1614 male workers (809 toner-exposed workers and 805 referents) who were engaged in toner manufacturing plants in Japan (Fuji Xerox Co., Ltd). The age of subjects was from 19 to 59 years, and the average age was 40.2 years(median 40 years, SD 7.67). We conducted a pulmonary function test (PEFR, VC, FVC, FEV(1.0)%, V25/Ht) and a blood cell test (RBC, Hb, Hct, Plt, WBC, cell contents of WBC) and measured biochemical indices in blood (ALT, AST, gamma-GTP, CRP, IgE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine. Student t-test and logistic regression analysis were applied to compare between the toner-exposed workers and the referents and to analyze the relationship among indices of effects and independent factors. There was no significant difference between the two groups in blood cell count and biochemical indices. Inflammation- and allergy-related markers such as 8OHdG and IgE also showed no significant difference between toner-exposed workers and the referents. The influence of smoking on pulmonary function indices was observed, but there was no relationship between the pulmonary function and toner-exposed work. In this article, we report a preliminary cross-sectional analysis in the subjects of a cohort study. No difference in pulmonary function indices was observed between the toner-exposed workers and the referents, and there was no consistent relationship between the exposure status and examined indices; however, the prevalence of subjective respiratory symptoms was higher in the exposed workers as presented in another report. Further analysis is important in the ongoing cohort study to clarify the effect of toner exposure on respiratory systems.

  8. Histochemical analyses and quantum dot imaging of microvascular blood flow with pulmonary edema in living mouse lungs by "in vivo cryotechnique".

    PubMed

    Saitoh, Yurika; Terada, Nobuo; Saitoh, Sei; Ohno, Nobuhiko; Jin, Takashi; Ohno, Shinichi

    2012-02-01

    Light microscopic imaging of blood vessels and distribution of serum proteins is essential to analyze hemodynamics in living animal lungs under normal respiration or respiratory diseases. In this study, to demonstrate dynamically changing morphology and immunohistochemical images of their living states, "in vivo cryotechnique" (IVCT) combined with freeze-substitution fixation was applied to anesthetized mouse lungs. By hematoxylin-eosin staining, morphological features, such as shapes of alveolar septum and sizes of alveolar lumen, reflected their respiratory conditions in vivo, and alveolar capillaries were filled with variously shaped erythrocytes. Albumin was usually immunolocalized in the capillaries, which was confirmed by double-immunostaining for aquaporin-1 of endothelium. To capture accurate time-courses of blood flow in peripheral pulmonary alveoli, glutathione-coated quantum dots (QDs) were injected into right ventricles, and then IVCT was performed at different time-points after the QD injection. QDs were localized in most arterioles and some alveolar capillaries at 1 s, and later in venules at 2 s, reflecting a typical blood flow direction in vivo. Three-dimensional QD images of microvascular networks were reconstructed by confocal laser scanning microscopy. It was also applied to lungs of acute pulmonary hypertension mouse model. Erythrocytes were crammed in blood vessels, and some serum components leaked into alveolar lumens, as confirmed by mouse albumin immunostaining. Some separated collagen fibers and connecting elastic fibers were still detected in edematous tunica adventitia near terminal bronchioles. Thus, IVCT combined with histochemical approaches enabled us to capture native images of dynamically changing structures and microvascular hemodynamics of living mouse lungs.

  9. [Interpretation and use of routine pulmonary function tests: Spirometry, static lung volumes, lung diffusion, arterial blood gas, methacholine challenge test and 6-minute walk test].

    PubMed

    Bokov, P; Delclaux, C

    2016-02-01

    Resting pulmonary function tests (PFT) include the assessment of ventilatory capacity: spirometry (forced expiratory flows and mobilisable volumes) and static volume assessment, notably using body plethysmography. Spirometry allows the potential definition of obstructive defect, while static volume assessment allows the potential definition of restrictive defect (decrease in total lung capacity) and thoracic hyperinflation (increase in static volumes). It must be kept in mind that this evaluation is incomplete and that an assessment of ventilatory demand is often warranted, especially when facing dyspnoea: evaluation of arterial blood gas (searching for respiratory insufficiency) and measurement of the transfer coefficient of the lung, allowing with the measurement of alveolar volume to calculate the diffusing capacity of the lung for CO (DLCO: assessment of alveolar-capillary wall and capillary blood volume). All these pulmonary function tests have been the subject of an Americano-European Task force (standardisation of lung function testing) published in 2005, and translated in French in 2007. Interpretative strategies for lung function tests have been recommended, which define abnormal lung function tests using the 5th and 95th percentiles of predicted values (lower and upper limits of normal values). Thus, these recommendations need to be implemented in all pulmonary function test units. A methacholine challenge test will only be performed in the presence of an intermediate pre-test probability for asthma (diagnostic uncertainty), which is an infrequent setting. The most convenient exertional test is the 6-minute walk test that allows the assessment of walking performance, the search for arterial desaturation and the quantification of dyspnoea complaint.

  10. Effect of blood pH on pulmonary artery pressure, left atrial pressure and fluid filtration rate in isolated rabbit lung.

    PubMed

    Pinto-Plata, V M; Pozo-Parilli, J C; Baum-Agay, A; Curiel, C; Sánchez de León, R

    1995-09-01

    To determine the effects of pH changes on Pulmonary Artery Pressure (PAP), 18 isolated rabbit lung preparations, perfused with autologous blood mixture and constant PaCO2 have been studied. Each preparation was studied under 3 conditions: Baseline: 30 minutes equilibration period. Acidosis: pH was decreased by 0.2 N HCl infusion, the ventilatory rate was changed and different CO2 mixtures were used to maintain the PCO2 within the initial parameters. Compensated Acidosis (CA): pH was returned to normal values by 0.7 N NaHCO3 infusion maintaining PCO2 in its initial values. The decrease in pH (acidosis) from 7.36 +/- 0.05 to 7.18 +/- 0.06 at constant PCO2, generated a significant increase in PAP (13.6 +/- 3.2 cm H2O to 18.8 +/- 5.2 cm H2O, p < 0.01). The pH increase (CA) from 7.18 +/- 0.06 to 7.40 +/- 0.09 caused the PAP to decrease (18.8 +/- 5.2 cm H2O to 15.9 +/- 4.2 cm H2O); the fluid filtration rate remained unchanged during the whole experiment. It is concluded that blood pH changes at constant PCO2 result in significant changes of PAP. Acidemia produces pulmonary vasoconstriction, which may be a contributing factor in the genesis of pulmonary hypertension in clinical conditions with increased hydrogen ion concentration [H+].

  11. Characterization of differences between blood sample matrices in untargeted metabolomics.

    PubMed

    Denery, Judith R; Nunes, Ashlee A K; Dickerson, Tobin J

    2011-02-01

    Large-scale proteomic and metabolomic technologies are increasingly gaining attention for their use in the diagnosis of human disease. In order to ensure the statistical power of relevant markers, such analyses must incorporate a large number of representative samples. While in a best-case scenario these samples are collected through a study design that is specifically tailored for the desired analysis, often studies must rely upon the analysis of large numbers of previously banked samples that may or may not have complete and accurate documentation of their associated collection and storage methods. In this study, several human blood matrices were analyzed and compared for the quality of metabolomic output. The sample types that were tested include plasma prepared with a variety of anticoagulants and serum collected by venipuncture and capillary blood collection protocols. Analysis with liquid chromatography-mass spectrometry (LC-MS) revealed only subtle differences between the various plasma preparation methods. Differences between the serum and plasma samples appear to be largely peptide/protein-based and are consistent with the biological distinction of the two matrices. Interestingly, the small molecule lysophosphatidylinositol was found to be in higher abundance in plasma, as a possible consequence of the effect of the intrinsic clotting cascade on adjacent metabolic pathways. Comparison of the small-molecule profiles of the capillary- and venipuncture-collected samples revealed 23 statistically significant compound differences between these sample types. Most of these features can be attributed to surfactants and detergents used to pretreat the skin in order to maintain the sterility of sample collection. However, several have identical mass and molecular formulas as endogenous human metabolites and could be erroneously attributed to actual metabolic perturbations. Understanding the extent of these matrix effects is important for control of systematic bias

  12. Prevalence and characterization of opportunistic candidal infections among patients with pulmonary tuberculosis

    PubMed Central

    Astekar, Madhusudan; Bhatiya, Priyanka Sharma; Sowmya, GV

    2016-01-01

    Background: Although Candida albicans remains the most common cause of human candidiasis, the frequency of infection attributed to other members of the genus is also increasing. Hence, the present study was carried out to know the prevalence of opportunistic candidal infection in tuberculosis, and if positive, the species of Candida that is most commonly associated. Materials and Methods: The present study comprised sixty pulmonary tuberculosis patients who were divided into (1) fresh or untreated group, (2A) chronic or treated group having no complications and (2B) having complications, comprising twenty patients each, respectively. The collected sputum samples were initially stained with Ziehl–Neelsen stain for confirmation of presence of tubercle Bacilli. Primary isolation was done on Sabouraud Dextrose Agar (SDA). The candidal colonies were confirmed microscopically for the presence of pseudohyphae. Further speciation of the positive candidal samples was carried out using ChromAgar. Result: The total fungal prevalence among 60 patients with pulmonary tuberculosis on SDA was 33 (55%) Candida and 3 (5%) Aspergillus. The prevalence of different candidal species on ChromAgar showed C. albicans as the predominant one, followed by Candida tropicalis and Candida krusei. Freshly diagnosed or untreated group was less commonly associated with pulmonary mycoses than chronic or treated group. The prevalence of Candida had increased with treatment, duration and age, and it was more in males than females. Conclusion: The present study confirms the phenomenon of opportunistic candidal infections in pulmonary tuberculosis patients. Rapid and reliable identification of Candida species is essential as they differ in their virulence and sensitivity to antifungal drugs. PMID:27601806

  13. Quantification of the Blood Platelet Reactivity in the ADP-Induced Model of Non-Lethal Pulmonary Thromboembolism in Mice with the Use of Laser Doppler Flowmetry

    PubMed Central

    Przygodzki, Tomasz; Talar, Marcin; Blazejczyk, Agnieszka; Kalchenko, Vyacheslav; Watala, Cezary

    2016-01-01

    Introduction The paper describes an alternative method for quantification of in vivo ADP-induced thromboembolism. The aim of the studies was to develop a method of quantification which would not require either extravasation or labelling of platelets. Our proposed approach is based on the monitoring of changes of blood flow with the use of laser Doppler flowmetry. Materials and Methods Mice of C57Bl strain were used in the study. ADP was injected to the vena cava and blood flow was monitored with the use of a laser Doppler flowmeter in the mesentery. Measurements in platelet-depleted mice, mice pretreated with cangrelor, an ADP receptor antagonist, and eptifibatide, a blocker of fibrinogen binding to GPIIbIIIa, were conducted as the proof-of-concept in the performed experiments. Intravital microscopy and ex vivo imaging of organs was performed to identify the sites of aggregate formation resulting from ADP injection. Results The injection of ADP resulted in a dose-dependent reduction of the blood flow in the mesentery. These responses were fully attributable to blood platelet aggregation, as shown by the lack of the effect in platelet-depleted mice, and significantly reduced responses in mice pretreated with cangrelor and eptifibatide. No platelet aggregate formation in mesenteric vessels was revealed by intravital microscopy, while ex vivo imaging showed accumulation of fluorescent labelled platelets in the lung. Conclusions Injection of ADP to the venous system results in the formation of platelet aggregates predominantly in the lung. This results in reversible blood flow cessation in peripheral blood vessels. The measurement of this blood flow cessation in the mesentery allows indirect measurement of ADP-induced pulmonary thromboembolism. We suggest that this approach can be useful for in vivo screening for antiplatelet drug candidates. PMID:26751810

  14. The Numerical Predominance and Large Transcriptome Differences of Neutrophils in Peripheral Blood Together Inevitably Account for a Reported Pulmonary Tuberculosis Signature

    PubMed Central

    Deng, Wang-Long; Zhang, Hao

    2017-01-01

    Previous transcriptomic analysis revealed a 393-transcript signature (PTBsig), which is dominated by interferon inducible genes, in whole blood of pulmonary tuberculosis (PTB) patients. Comparisons with a limited set of interferon-driven genes among separated monocytes, CD4+ T cells, CD8+ T cells, and neutrophils indicated that the signature is due to changes in neutrophils, the overwhelmingly predominant cell type. By extending the analysis to the entire 393 transcripts of PTBsig and by switching the cell proportions between separated monocytes, CD4+ T cells, CD8+ T cells, and neutrophils, we create putative PTBsig for whole blood (pPTBsig) in which CD4+ or CD8+ T cells or monocytes predominated or in which the cell proportions were unchanged. These putative signatures are then compared to the actual reported PTBsig. We show that, because of their predominance in peripheral blood and their larger transcriptional responses, neutrophils were indeed almost exclusively responsible for PTBsig. We caution that the functional significance of changes in other cell types might escape notice in transcriptome analysis that is based upon whole blood. PMID:28265564

  15. Pulmonary embolus

    MedlinePlus

    ... clot - lung; Embolus; Tumor embolus; Embolism - pulmonary; DVT-pulmonary embolism; Thrombosis - pulmonary embolism ... Main symptoms of a pulmonary embolism include chest pain that may be any of the following: Under the breastbone or on one side Sharp or stabbing ...

  16. Miliary pulmonary cryptococcosis.

    PubMed

    Kelly, Shane; Marriott, Deborah

    2014-10-01

    A 32-year-old HIV positive male presents with fevers and a non-productive cough. Initial X-ray and subsequent computerised tomography of the chest shows a bilateral miliary pattern of pulmonary infiltration highly suggestive of disseminated tuberculosis. However subsequent results were consistent with disseminated cryptococcosis, including pulmonary involvement, with cryptococcus identified on transbronchial tissue biopsy, and on blood and cerebrospinal fluid cultures. Imaging features of pulmonary cryptococcosis are generally of well-defined pleural-based nodules and less commonly alveolar infiltrates, lymphadenopathy, pleural effusions or cavitating lesions. Miliary pulmonary infiltrates are an exceptionally rare presentation.

  17. Molecular characterization of the early B cell response to pulmonary Cryptococcus neoformans infection.

    PubMed

    Rohatgi, Soma; Pirofski, Liise-anne

    2012-12-15

    The role of B cells in host defense against fungi has been difficult to establish. We quantified and determined the molecular derivation of B-1a, B-1b, and B-2 B cell populations in C57BL/6 mice after pulmonary infection with Cryptococcus neoformans. Total B-1 and B-2 cell numbers increased in lungs and peritoneal cavity as early as day 1 postinfection, but lacked signs of clonal expansion. Labeled capsular (24067) and acapsular (Cap67) C. neoformans strains were used to identify C. neoformans-binding B cell subsets by flow cytometry. Peritoneal cavity B-1a B cells exhibited the most acapsular and capsular C. neoformans binding in C. neoformans-infected mice, and C. neoformans-selected B-1 B cells secreted laminarin- and C. neoformans-binding IgM. Single-cell PCR-based sequence analysis of B-1a, B-1b, and B-2 cell IgH V region H chain (V(H)) genes revealed increased usage of V(H)11 and V(H)12, respectively, in acapsular and capsular C. neoformans-selected B-1a cells. Germline V(H) segments were used, with capsular C. neoformans-selected cells having less junctional diversity than acapsular C. neoformans-selected cells. Further studies in B-1 B cell-depleted mice showed that these mice had higher brain and lung fungal burdens and less alveolar macrophage phagocytosis of C. neoformans than did control and B-1a B cell-reconstituted mice. Taken together, these results establish a mechanistic role for B-1 B cells in the innate B cell response to pulmonary infection with C. neoformans and reveal that IgM-producing B-1a cells, which express germline V(H) genes, bind C. neoformans and contribute to early fungal clearance. Thus, B-1a B cells provide a first line of defense during pulmonary C. neoformans infection in mice.

  18. Cell surface alterations during blood-storage characterized by artificial aggregation of washed red blood cells.

    PubMed

    Hessel, E; Lerche, D

    1985-01-01

    Aggregation measurement of washed human erythrocytes (RBC) were carried out in a NaCl-PBS solution under laminar shear conditions. Artificial aggregation of fresh and stored erythrocytes was caused by decreased pH and reduced ionic strength and characterized by collision efficiency alpha. Generally, the collision efficiency alpha of stored erythrocytes rises with the increased storage time. Such an aggregation technique might be useful to detect and quantify changes of the membrane and/or the surface structure due to aging and/or storage.

  19. Thromboembolism in pulmonary artery sarcoma.

    PubMed

    Farsad, Mohsen; Pernter, Patrizia; Triani, Antonio; Osele, Luzian; Wiedermann, Christian J

    2009-04-01

    Pulmonary artery sarcoma, although rare, must be considered in the differential diagnosis of pulmonary thromboembolism. Clinically and radiologically, it may imitate pulmonary embolism, making diagnosis difficult and delaying treatment. Patients often have no symptom resolution despite therapeutic anticoagulation. Visualization of filling defects within a pulmonary artery on contrast-enhanced CT cannot reliably differentiate between pulmonary thromboembolism and malignant lesions like leiomyosarcoma. FDG PET-CT offers the potential for identification of malignant lesions. The authors report a case with pulmonary artery thromboembolism due to thrombi formed on a pulmonary artery leiomyosarcoma. Integrated FDG PET-CT showed no FDG-uptake along the major part of the filling defect within the right main pulmonary artery suggesting blood clot and increased uptake along the posterior wall of the right main pulmonary artery and the left lower lobar artery suggesting malignancy.

  20. The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway: characterization and significance.

    PubMed Central

    Zeldin, D C; Plitman, J D; Kobayashi, J; Miller, R F; Snapper, J R; Falck, J R; Szarek, J L; Philpot, R M; Capdevila, J H

    1995-01-01

    Cytochrome P450 metabolizes arachidonic acid to several unique and biologically active compounds in rabbit liver and kidney. Microsomal fractions prepared from rabbit lung homogenates metabolized arachidonic acid through cytochrome P450 pathways, yielding cis-epoxyeicosatrienoic acids (EETs) and their hydration products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using polyclonal antibodies prepared against purified CYP2B4 demonstrated 100% inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted in the presence of NADPH-cytochrome P450 reductase and cytochrome b5, metabolized arachidonic acid, producing primarily EETs. EETs were detected in lung homogenate using gas chromatography/mass spectroscopy, providing evidence for the in vivo pulmonary cytochrome P450 epoxidation of arachidonic acid. Chiral analysis of these lung EETs demonstrated a preference for the 14(R),15(S)-, 11(S),12(R)-, and 8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were detected in bronchoalveolar lavage fluid. At micromolar concentrations, methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic acid epoxygenase and that these locally produced, biologically active eicosanoids may be involved in maintaining homeostasis within the lung. Images PMID:7738183

  1. In-Situ Characterization of Tissue Blood Flow, Blood Content, and Water State Using New Techniques in Magnetic Resonance Imaging.

    NASA Astrophysics Data System (ADS)

    Conturo, Thomas Edward

    Tissue blood flow, blood content, and water state have been characterized in-situ with new nuclear magnetic resonance imaging techniques. The sensitivities of standard techniques to the physiologic tissue parameters spin density (N_{rm r}) and relaxation times (T_1 and T_2 ) are mathematically defined. A new driven inversion method is developed so that tissue T_1 and T_2 changes produce cooperative intensity changes, yielding high contrast, high signal to noise, and sensitivity to a wider range of tissue parameters. The actual tissue parameters were imaged by automated collection of multiple-echo data having multiple T _1 dependence. Data are simultaneously fit by three-parameters to a closed-form expression, producing lower inter-parameter correlation and parameter noise than in separate T_1 or T_2 methods or pre-averaged methods. Accurate parameters are obtained at different field strengths. Parametric images of pathology demonstrate high sensitivity to tissue heterogeneity, and water content is determined in many tissues. Erythrocytes were paramagnetically labeled to study blood content and relaxation mechanisms. Liver and spleen relaxation were enhanced following 10% exchange of animal blood volumes. Rapid water exchange between intracellular and extracellular compartments was validated. Erythrocytes occupied 12.5% of renal cortex volume, and blood content was uniform in the liver, spleen and kidney. The magnitude and direction of flow velocity was then imaged. To eliminate directional artifacts, a bipolar gradient technique sensitized to flow in different directions was developed. Phase angle was reconstructed instead of intensity since the former has a 2pi -fold higher dynamic range. Images of flow through curves demonstrated secondary flow with a centrifugally-biased laminar profile and stationary velocity peaks along the curvature. Portal vein flow velocities were diminished or reversed in cirrhosis. Image artifacts have been characterized and removed. The

  2. Changes in ventilatory capacity, exercise capacity, and pulmonary blood flow after lobectomy in patients with lung cancer--which lobectomy has the most loss in exercise capacity?

    PubMed

    Kushibe, Keiji; Kawaguchi, Takeshi; Kimura, Michitaka; Takahama, Makoto; Tojo, Takashi; Taniguchi, Shigeki

    2008-12-01

    The aim of this study was to compare the changes in ventilatory capacity, exercise capacity, and pulmonary blood flow (PBF) in the operated lung after lobectomy according to the lobe resected. Thirty-one patients underwent right upper lobectomy (RUL), 26 left upper lobectomy (LUL), 24 right lower lobectomy (RLL), and 25 left lower lobectomy (LLL). Pulmonary function tests, exercise capacity tests, and perfusion lung scans were performed preoperatively and six months to one year after lobectomy. RUL was associated with significantly less loss in forced vital capacity (FVC) than RLL or LLL (P<0.05). LUL was associated with the greatest loss in maximum oxygen consumption (VO2) (P<0.05). LUL was associated with significantly greater loss in PBF in the operated lung than RUL (P<0.05). LUL had a significantly higher negative value in percentage change in (VO2) --percentage change in FVC, and percentage change in PBF--percentage change in FVC than RLL or LLL (P<0.05). LUL was not associated with the greatest loss in ventilatory capacity or PBF, although it was associated with the greatest loss in . Each lobectomy has its own peculiarity in magnitude of loss in (VO2), PBF or FVC.

  3. Isolation and Characterization of Nontuberculous Mycobacteria from Patients with Pulmonary Tuberculosis in Ghana

    PubMed Central

    Otchere, ID; Asante-Poku, A; Osei-Wusu, S; Aboagye, SY; Yeboah-Manu, D

    2017-01-01

    Background Nontuberculous mycobacterial (NTM) species are assuming public health importance in pulmonary diseases; they are increasingly being isolated, and importantly, most NTMs do not respond to routine tuberculosis (TB) drugs. This study aimed to identify NTMs isolated from pulmonary TB cases and also determine their susceptibility to streptomycin (STR), isoniazid (INH), and rifampicin (RIF). Methods A total of 1755 mycobacterial isolates, obtained between August 2012 and July 2014, from 2036 smear-positive pulmonary cases were identified using polymerase chain reaction amplification of IS6110, and hsp65 gene sequencing analysis. Drug susceptibility testing (DST) was then performed for the identified NTMs against STR, INH, and RIF using microplate Alamar blue assay. The results were analyzed against patients’ biodata for statistical associations. Results Of the 1755 analyzed isolates, we identified 43 (2.5%) NTMs, which included 18 (41.9%) Mycobacterium intracellulare, 13 (30.2%) Mycobacterium avium subs. paratuberculosis, 5 (11.3%) Mycobacterium abscessus, 3 (7.0%) each of Mycobacterium mucogenicum and Mycobacterium colombiense, and 1 (2.3%) Mycobacterium simiae. Patients infected with NTMs (52.0%) were more likely to be human immunodeficiency virus-positive (P = 0.001, odds ratio = 6.6, 95% confidence interval = 2.7–16.2) than those infected with M. tuberculosis complex (5.8%). All the 43 (100%) NTMs were resistant to INH, whereas 32 (74%) and 19 (44%) were resistant to RIF and STR, respectively. Furthermore, 16 (37.2%) NTMs were resistant to all three drugs, 20 were resistant to INH and RIF, and 3 were resistant to STR and INH. All the M. abscessus isolates were resistant to all the three drugs, whereas all the M. avium isolates were resistant to INH and RIF, but only three were resistant to STR. Among the M. intracellulare isolates, 8, 18, and 15 isolates were resistant to STR, INH, and RIF, respectively. Conclusion The observed high-resistance level to

  4. Characterization of the normal pulmonary surface and pneumonectomy space by reflected ultrasound

    PubMed Central

    Sperandeo, M.; Varriale, A.; Sperandeo, G.; Bianco, M.R.; Piattelli, M.L.; Bizzarri, M.; Ghittoni, G.; Copetti, M.; Vendemiale, G.

    2011-01-01

    Interest has been increasing in the use of transthoracic ultrasound for the study of the pleuropulmonary disease. US imaging depends mainly on the physical interactions between ultrasound waves and the tissues being examined. In the thoracic region, the prescence of the chest wall and the air-containing pulmonary tissues cause various artifacts that strongly influence the resulting images. At the interface between tissues and air, the ultrasound beam is totally reflected and produces simple reverberation, comet-tail artifacts, and ring-down artifacts. We report the findings of transthoracic ultrasound in normal healthy subjects and in those who had undergone pneumonectomy.This experience shows that, in terms of the ultrasound artifacts mentioned above, the postpneumonectomy cavity is not significantly different from the healthy lung. PMID:23396639

  5. Characterization of IL-22 and antimicrobial peptide production in mice protected against pulmonary Cryptococcus neoformans infection.

    PubMed

    Wozniak, Karen L; Hole, Camaron R; Yano, Junko; Fidel, Paul L; Wormley, Floyd L

    2014-07-01

    Cryptococcus neoformans is a significant cause of fungal meningitis in patients with impaired T cell-mediated immunity (CMI). Experimental pulmonary infection with a C. neoformans strain engineered to produce IFN-γ, H99γ, results in the induction of Th1-type CMI, resolution of the acute infection, and protection against challenge with WT Cryptococcus. Given that individuals with suppressed CMI are highly susceptible to pulmonary C. neoformans infection, we sought to determine whether antimicrobial peptides were produced in mice inoculated with H99γ. Thus, we measured levels of antimicrobial peptides lipocalin-2, S100A8, S100A9, calprotectin (S100A8/A9 heterodimer), serum amyloid A-3 (SAA3), and their putative receptors Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE) in mice during primary and recall responses against C. neoformans infection. Results showed increased levels of IL-17A and IL-22, cytokines known to modulate antimicrobial peptide production. We also observed increased levels of lipocalin-2, S100A8, S100A9 and SAA3 as well as TLR4(+) and RAGE(+) macrophages and dendritic cells in mice inoculated with H99γ compared with WT H99. Similar results were observed in the lungs of H99γ-immunized, compared with heat-killed C. neoformans-immunized, mice following challenge with WT yeast. However, IL-22-deficient mice inoculated with H99γ demonstrated antimicrobial peptide production and no change in survival rates compared with WT mice. These studies demonstrate that protection against cryptococcosis is associated with increased production of antimicrobial peptides in the lungs of protected mice that are not solely in response to IL-17A and IL-22 production and may be coincidental rather than functional.

  6. Characterization of the early pulmonary inflammatory response associated with PTFE fume exposure

    NASA Technical Reports Server (NTRS)

    Johnston, C. J.; Finkelstein, J. N.; Gelein, R.; Baggs, R.; Oberdorster, G.; Clarkson, T. W. (Principal Investigator)

    1996-01-01

    Heating of polytetrafluoroethylene (PTFE) has been described to release fumes containing ultrafine particles (approximately 18 nm diam). These fumes can be highly toxic in the respiratory tract inducing extensive pulmonary edema with hemorrhagic inflammation. Fischer-344 rats were exposed to PTFE fumes generated by temperatures ranging from 450 to 460 degrees C for 15 min at an exposure concentration of 5 x 10(5) particles/cm3, equivalent to approximately 50 micrograms/m3. Responses were examined 4 hr post-treatment when these rats demonstrated 60-85% neutrophils (PMNs) in their lung lavage. Increases in abundance for messages encoding the antioxidants manganese superoxide dismutase and metallothionein (MT) increased 15- and 40-fold, respectively. For messages encoding the pro- and anti-inflammatory cytokines: inducible nitric oxide synthase, interleukin 1 alpha, 1 beta, and 6 (IL-1 alpha, IL-1 beta, and IL-6), macrophage inflammatory protein-2, and tumor necrosis factor-alpha (TNF alpha) increases of 5-, 5-, 10-, 40-, 40-, and 15-fold were present. Vascular endothelial growth factor, which may play a role in the integrity of the endothelial barrier, was decreased to 20% of controls. In situ sections were hybridized with 33P cRNA probes encoding IL-6, MT, surfactant protein C, and TNF alpha. Increased mRNA abundance for MT and IL-6 was expressed around all airways and interstitial regions with MT and IL-6 demonstrating similar spatial distribution. Large numbers of activated PMNs expressed IL-6, MT, and TNF alpha. Additionally, pulmonary macrophages and epithelial cells were actively involved. These observations support the notion that PTFE fumes containing ultrafine particles initiate a severe inflammatory response at low inhaled particle mass concentrations, which is suggestive of an oxidative injury. Furthermore, PMNs may actively regulate the inflammatory process through cytokine and antioxidant expression.

  7. Characterization of oxidative stress in blood from diabetic vs. hypercholesterolaemic patients, using a novel synthesized marker.

    PubMed

    Szuchman, Andrea; Aviram, Michael; Musa, Ramadan; Khatib, Soliman; Vaya, Jacob

    2008-02-01

    In the present study, we extend our novel concept of designing and using exogenous markers for the characterization of oxidative stress (OS) and OS-associated diseases. The aim was to use such a synthetic compound as a tool for studying OS in blood from diabetic and hypercholesterolaemic (Hc) patients. The marker used N-linoleoyl tyrosine (LT) was constructed from tyrosine and linoleic acid (LA); both components are known to be easily oxidized upon exposure to different types of reactive oxygen/nitrogen species (ROS/RNS), and to generate specific oxidized products, depending on the type of oxidants present in vivo. Using the LT probe, we showed that the ratios of oxidized LT to total LT (Ox-LT/LT) is significantly higher in blood samples obtained from diabetic patients, than in Hc patients or healthy control subjects. LC/MS analysis revealed that blood from diabetic patients oxidizes the marker with predominant formation of Ox-LT hydroperoxide (LT-OOH) and epoxide (epoxy-LT), where the LA moiety is oxidized to hydroperoxide and to epoxide, respectively. Analysis of oxysterol levels in these samples (GC/MS) revealed that the blood of both diabetic and Hc patients contained significantly more oxysterols than blood of control subjects. Consumption of pomegranate juice by diabetic patients for 3 months suppressed their blood capacity to oxidize the LT and similarly also reduced their blood oxysterol/total cholesterol ratio by 93%. The use of an exogenous marker to characterize OS in blood samples yields important information on the extent of OS, and can provide a fingerprint for the early identification of different pathological conditions associated with OS.

  8. Pulmonary arterial hypertension in congenital heart diseases.

    PubMed

    Beghetti, Maurice; Tissot, Cecile

    2009-08-01

    Pulmonary hypertension complicates the course of many children and adults with congenital heart diseases (CHDs). The increase in pulmonary pressure associated with CHD is secondary to either increased pulmonary blood flow or increased postcapillary pressures. Pulmonary arterial hypertension is in the vast majority associated with congenital cardiac shunts. Despite major advances in the understanding of the regulation of the pulmonary vascular bed and the pulmonary endothelial lesions leading to pulmonary vascular disease, despite the advances in surgical repair and the discovery of potential therapies in the pre- and postoperative period, pulmonary hypertension still carries a significant mortality and morbidity in patients with CHD. The recent introduction of targeted therapies in other forms of pulmonary arterial hypertension has led to a renewed interest in pulmonary hypertension associated with CHD and this particularly for the most advanced form, the so-called Eisenmenger syndrome (ES). This review summarizes the current knowledge on pulmonary hypertension associated with CHD, focusing on the pathophysiology and treatment of ES.

  9. Pulmonary angiography

    MedlinePlus

    ... Pulmonary arteriography; Pulmonary angiogram; Angiogram of the lungs Images Pulmonary arteries References Jackson JE, Meaney JFM. Angiography. ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  10. Pulmonary Rehabilitation

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... people who have COPD (chronic obstructive pulmonary disease), sarcoidosis (sar-koy-DOE-sis), idiopathic pulmonary fibrosis , or ...

  11. Characterizing human skin blood flow regulation in response to different local skin temperature perturbations.

    PubMed

    Wu, Y; Nieuwenhoff, M D; Huygen, F J P M; van der Helm, F C T; Niehof, S; Schouten, A C

    2017-05-01

    Small nerve fibers regulate local skin blood flow in response to local thermal perturbations. Small nerve fiber function is difficult to assess with classical neurophysiological tests. In this study, a vasomotor response model in combination with a heating protocol was developed to quantitatively characterize the control mechanism of small nerve fibers in regulating skin blood flow in response to local thermal perturbation. The skin of healthy subjects' hand dorsum (n=8) was heated to 42°C with an infrared lamp, and then naturally cooled down. The distance between the lamp and the hand was set to three different levels in order to change the irradiation intensity on the skin and implement three different skin temperature rise rates (0.03°C/s, 0.02°C/s and 0.01°C/s). A laser Doppler imager (LDI) and a thermographic video camera recorded the temporal profile of the skin blood flow and the skin temperature, respectively. The relationship between the skin blood flow and the skin temperature was characterized by a vasomotor response model. The model fitted the skin blood flow response well with a variance accounted for (VAF) between 78% and 99%. The model parameters suggested a similar mechanism for the skin blood flow regulation with the thermal perturbations at 0.03°C/s and 0.02°C/s. But there was an accelerated skin vasoconstriction after a slow heating (0.01°C/s) (p-value<0.05). An attenuation of the skin vasodilation was also observed in four out of the seven subjects during the slow heating (0.01°C/s). Our method provides a promising way to quantitatively assess the function of small nerve fibers non-invasively and non-contact.

  12. Label-free characterization of white blood cells by measuring 3D refractive index maps

    PubMed Central

    Yoon, Jonghee; Kim, Kyoohyun; Park, HyunJoo; Choi, Chulhee; Jang, Seongsoo; Park, YongKeun

    2015-01-01

    The characterization of white blood cells (WBCs) is crucial for blood analyses and disease diagnoses. However, current standard techniques rely on cell labeling, a process which imposes significant limitations. Here we present three-dimensional (3D) optical measurements and the label-free characterization of mouse WBCs using optical diffraction tomography. 3D refractive index (RI) tomograms of individual WBCs are constructed from multiple two-dimensional quantitative phase images of samples illuminated at various angles of incidence. Measurements of the 3D RI tomogram of WBCs enable the separation of heterogeneous populations of WBCs using quantitative morphological and biochemical information. Time-lapse tomographic measurements also provide the 3D trajectory of micrometer-sized beads ingested by WBCs. These results demonstrate that optical diffraction tomography can be a useful and versatile tool for the study of WBCs. PMID:26504637

  13. Inhaled treprostinil and pulmonary arterial hypertension

    PubMed Central

    Nadler, Samuel T; Edelman, Jeffrey D

    2010-01-01

    Multiple conditions result in development of pulmonary hypertension. Pulmonary arterial hypertension (PAH) is the subclassification of pulmonary hypertension, in which known or unknown underlying conditions lead to similar intrinsic alterations in the pulmonary vasculature. PAH is a progressive condition characterized by restricted blood flow through the pulmonary circulation leading to poor survival in the absence of effective therapy. Over the last two decades, new therapeutic agents have substantially improved the course and prognosis for PAH patients. Three available classes of drugs, ie, prostacyclins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors provide multiple options for treatment of PAH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors are administered orally, whereas prostacyclin therapies are delivered by continuous intravenous or subcutaneous infusion, or as aerosols by nebulization. Because of the risks and inconveniences associated with administration, prostacyclins are typically reserved for patients with more advanced disease or progression despite oral therapy. Inhaled administration may be a safer and easier route for prostacyclin administration. Treprostinil is a prostacyclin analog that has been demonstrated to be effective when administered by continuous subcutaneous or intravenous infusion, and more recently by nebulization. PMID:21191432

  14. Characterization of retinal blood vessel by laser speckle correlation time constant (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Lin, Meng-Chieh; Lai, Wan-Huseh; Tien, Chung-Hao

    2016-09-01

    Laser speckle imaging is an optical metrology technique for examining various forms of object motion in fields from material engineering to bio-medical. As highly coherent illumination encounters the rough surface or scattering medium, due to the multiple interference, the randomly distributed black and white spots formed and are known as speckles. By analyzing speckle images, surface information or scattering medium motion could be recovered. In this study, an optical system for acquiring speckle images from rabbit retina is built for characterizing the blood vessel properties with speckle correlation time constant. As laser illuminates onto the rabbit retina, speckles are formed due to the moving red blood cells inside the retinal blood vessel. The intensity of speckles fluctuate along time and are recorded with high speed CMOS at frame rate 150 frames per second. Speckle correlation time constant describe the relation between frames as the decay rate. Two approaches are used for the processing of image sequences for correlation time constant, one is utilizing asymptotic equation from speckle contrast result, and another is correlation based approach. To determine the performance of our system and algorithms, we compare two regions on the retina with different properties, one region contains faster blood flow while another with slower blood flow. Both approaches shows distinct differences in the value of correlation time constant of two regions.

  15. Feasibility of Doppler variance imaging for red blood cell aggregation characterization

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Ahn, Yeh-Chan; Chen, Zhongping

    2009-11-01

    An abnormal level of red blood cell (RBC) aggregation is a clinical condition associated with many pathologies. Our purpose is to investigate the feasibility of spectral domain phase-resolved optical Doppler tomography incorporated with Doppler variance imaging to characterize RBC aggregation in flowing blood. Variance/standard deviation (SD) of the Doppler frequency spectrum of porcine blood flowing through a glass tube (diameter 300 μm) at 4.7 mm/s is measured. For nonaggregating RBCs with hematocrits of 20, 40, and 60%, the mean centerline SD values were 34.2+/-1.2, 47.8+/-1.0, and 47.2+/-0.5, respectively. After dextran 500 induction, the SD value decreased significantly to 29.9+/-0.7, 37.9+/-3.0, and 40.1+/-0.6 (P<0.01) in the aggregated blood, respectively. The results demonstrate that Doppler variance imaging using the SD value is capable of differentiating normal and aggregated blood.

  16. Blood

    MedlinePlus

    ... increased red blood cell destruction can affect teens: G6PD deficiency. G6PD is an enzyme that helps to protect ... can cause red cells to hemolyze, or burst. G6PD deficiency is a common hereditary disease among people of ...

  17. Pulmonary artery sarcoma mimicking pulmonary embolism.

    PubMed

    El-Sayed Ahmed, Magdy M; Aftab, Muhammad; Al-Najjar, Raed M; de la Cruz, Kim I; Benjamin, Robert S; Hallman, Charles H

    2014-10-01

    Primary sarcomas that arise from major blood vessels are exceedingly rare, and some of the published cases have been autopsy reports. Most patients are adults. We report a case of pulmonary artery sarcoma in a 77-year-old man who presented with acute onset of dyspnea. Magnetic resonance imaging of the chest revealed a large mass within the pulmonary trunk and its main branches. Because massive pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, which then necessitated resection of both the mass and the pulmonary valve. A bioprosthetic porcine valve replaced the native valve, and we reconstructed the right ventricular outflow tract with a Dacron patch. Histopathologic examination revealed a high-grade sarcoma with focal myogenic and chondrogenic differentiation. The patient tolerated the procedure well and was discharged from the hospital on postoperative day 7. He was subsequently treated with chemotherapy and radiation and continued to show no evidence of disease. The diagnosis of pulmonary artery sarcoma should be suspected in patients who present with manifestations of pulmonary embolism, especially when there is no evidence of deep venous thrombosis and poor response to anticoagulant therapy. Multimodal therapy can provide prolonged survival.

  18. Pulmonary Artery Sarcoma Mimicking Pulmonary Embolism

    PubMed Central

    Aftab, Muhammad; Al-Najjar, Raed M.; de la Cruz, Kim I.; Benjamin, Robert S.; Hallman, Charles H.

    2014-01-01

    Primary sarcomas that arise from major blood vessels are exceedingly rare, and some of the published cases have been autopsy reports. Most patients are adults. We report a case of pulmonary artery sarcoma in a 77-year-old man who presented with acute onset of dyspnea. Magnetic resonance imaging of the chest revealed a large mass within the pulmonary trunk and its main branches. Because massive pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, which then necessitated resection of both the mass and the pulmonary valve. A bioprosthetic porcine valve replaced the native valve, and we reconstructed the right ventricular outflow tract with a Dacron patch. Histopathologic examination revealed a high-grade sarcoma with focal myogenic and chondrogenic differentiation. The patient tolerated the procedure well and was discharged from the hospital on postoperative day 7. He was subsequently treated with chemotherapy and radiation and continued to show no evidence of disease. The diagnosis of pulmonary artery sarcoma should be suspected in patients who present with manifestations of pulmonary embolism, especially when there is no evidence of deep venous thrombosis and poor response to anticoagulant therapy. Multimodal therapy can provide prolonged survival. PMID:25425986

  19. Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice.

    PubMed

    Izzotti, Alberto; Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Longobardi, Mariagrazia; Pulliero, Alessandra; Geretto, Marta; Micale, Rosanna T; La Maestra, Sebastiano; Miller, Mark Steven; Steele, Vernon E; De Flora, Silvio

    2016-12-20

    Cigarette smoke (CS) is known to dysregulate microRNA expression profiles in the lungs of mice, rats, and humans, thereby modulating several pathways involved in lung carcinogenesis and other CS-related diseases. We designed a study aimed at evaluating (a) the expression of 1135 microRNAs in the lung of Swiss H mice exposed to mainstream CS during the first 4 months of life and thereafter kept in filtered air for an additional 3.5 months, (b) the relationship between lung microRNA profiles and histopathological alterations in the lung, (c) intergender differences in microRNA expression, and (d) the comparison with microRNA profiles in blood serum. CS caused multiple histopathological alterations in the lung, which were almost absent in sham-exposed mice. An extensive microRNA dysregulation was detected in the lung of CS-exposed mice. Modulation of microRNA profiles was specifically related to the histopathological picture, no effect being detected in lung fragments with non-neoplastic lung diseases (emphysema or alveolar epithelial hyperplasia), whereas a close association occurred with the presence and multiplicity of preneoplastic lesions (microadenomas) and benign lung tumors (adenomas). Three microRNAs regulating estrogen and HER2-dependent mechanisms were modulated in the lung of adenoma-bearing female mice. Blood microRNAs were also modulated in mice affected by early neoplastic lesions. However, there was a poor association between lung microRNAs and circulating microRNAs, which can be ascribed to an impaired release of mature microRNAs from the damaged lung. Studies in progress are evaluating the feasibility of analyzing blood microRNAs as a molecular tool for lung cancer secondary prevention.

  20. Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice

    PubMed Central

    Izzotti, Alberto; Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Longobardi, Mariagrazia; Pulliero, Alessandra; Geretto, Marta; Micale, Rosanna T.; La Maestra, Sebastiano; Miller, Mark Steven; Steele, Vernon E.; De Flora, Silvio

    2016-01-01

    Cigarette smoke (CS) is known to dysregulate microRNA expression profiles in the lungs of mice, rats, and humans, thereby modulating several pathways involved in lung carcinogenesis and other CS-related diseases. We designed a study aimed at evaluating (a) the expression of 1135 microRNAs in the lung of Swiss H mice exposed to mainstream CS during the first 4 months of life and thereafter kept in filtered air for an additional 3.5 months, (b) the relationship between lung microRNA profiles and histopathological alterations in the lung, (c) intergender differences in microRNA expression, and (d) the comparison with microRNA profiles in blood serum. CS caused multiple histopathological alterations in the lung, which were almost absent in sham-exposed mice. An extensive microRNA dysregulation was detected in the lung of CS-exposed mice. Modulation of microRNA profiles was specifically related to the histopathological picture, no effect being detected in lung fragments with non-neoplastic lung diseases (emphysema or alveolar epithelial hyperplasia), whereas a close association occurred with the presence and multiplicity of preneoplastic lesions (microadenomas) and benign lung tumors (adenomas). Three microRNAs regulating estrogen and HER2-dependent mechanisms were modulated in the lung of adenoma-bearing female mice. Blood microRNAs were also modulated in mice affected by early neoplastic lesions. However, there was a poor association between lung microRNAs and circulating microRNAs, which can be ascribed to an impaired release of mature microRNAs from the damaged lung. Studies in progress are evaluating the feasibility of analyzing blood microRNAs as a molecular tool for lung cancer secondary prevention. PMID:27713172

  1. Unbiased Characterization of Anopheles Mosquito Blood Meals by Targeted High-Throughput Sequencing

    PubMed Central

    Logue, Kyle; Keven, John Bosco; Cannon, Matthew V.; Reimer, Lisa; Siba, Peter; Walker, Edward D.; Zimmerman, Peter A.; Serre, David

    2016-01-01

    Understanding mosquito host choice is important for assessing vector competence or identifying disease reservoirs. Unfortunately, the availability of an unbiased method for comprehensively evaluating the composition of insect blood meals is very limited, as most current molecular assays only test for the presence of a few pre-selected species. These approaches also have limited ability to identify the presence of multiple mammalian hosts in a single blood meal. Here, we describe a novel high-throughput sequencing method that enables analysis of 96 mosquitoes simultaneously and provides a comprehensive and quantitative perspective on the composition of each blood meal. We validated in silico that universal primers targeting the mammalian mitochondrial 16S ribosomal RNA genes (16S rRNA) should amplify more than 95% of the mammalian 16S rRNA sequences present in the NCBI nucleotide database. We applied this method to 442 female Anopheles punctulatus s. l. mosquitoes collected in Papua New Guinea (PNG). While human (52.9%), dog (15.8%) and pig (29.2%) were the most common hosts identified in our study, we also detected DNA from mice, one marsupial species and two bat species. Our analyses also revealed that 16.3% of the mosquitoes fed on more than one host. Analysis of the human mitochondrial hypervariable region I in 102 human blood meals showed that 5 (4.9%) of the mosquitoes unambiguously fed on more than one person. Overall, analysis of PNG mosquitoes illustrates the potential of this approach to identify unsuspected hosts and characterize mixed blood meals, and shows how this approach can be adapted to evaluate inter-individual variations among human blood meals. Furthermore, this approach can be applied to any disease-transmitting arthropod and can be easily customized to investigate non-mammalian host sources. PMID:26963245

  2. Unbiased Characterization of Anopheles Mosquito Blood Meals by Targeted High-Throughput Sequencing.

    PubMed

    Logue, Kyle; Keven, John Bosco; Cannon, Matthew V; Reimer, Lisa; Siba, Peter; Walker, Edward D; Zimmerman, Peter A; Serre, David

    2016-03-01

    Understanding mosquito host choice is important for assessing vector competence or identifying disease reservoirs. Unfortunately, the availability of an unbiased method for comprehensively evaluating the composition of insect blood meals is very limited, as most current molecular assays only test for the presence of a few pre-selected species. These approaches also have limited ability to identify the presence of multiple mammalian hosts in a single blood meal. Here, we describe a novel high-throughput sequencing method that enables analysis of 96 mosquitoes simultaneously and provides a comprehensive and quantitative perspective on the composition of each blood meal. We validated in silico that universal primers targeting the mammalian mitochondrial 16S ribosomal RNA genes (16S rRNA) should amplify more than 95% of the mammalian 16S rRNA sequences present in the NCBI nucleotide database. We applied this method to 442 female Anopheles punctulatus s. l. mosquitoes collected in Papua New Guinea (PNG). While human (52.9%), dog (15.8%) and pig (29.2%) were the most common hosts identified in our study, we also detected DNA from mice, one marsupial species and two bat species. Our analyses also revealed that 16.3% of the mosquitoes fed on more than one host. Analysis of the human mitochondrial hypervariable region I in 102 human blood meals showed that 5 (4.9%) of the mosquitoes unambiguously fed on more than one person. Overall, analysis of PNG mosquitoes illustrates the potential of this approach to identify unsuspected hosts and characterize mixed blood meals, and shows how this approach can be adapted to evaluate inter-individual variations among human blood meals. Furthermore, this approach can be applied to any disease-transmitting arthropod and can be easily customized to investigate non-mammalian host sources.

  3. Identification of guinea pig gammadelta T cells and characterization during pulmonary tuberculosis.

    PubMed

    Xiong, Xiaowei; Morita, Craig T; Bukowski, Jack F; Brenner, Michael B; Dascher, Christopher C

    2004-11-01

    Guinea pigs are an alternative small animal model for many disease studies. Here we describe a pan-gammadelta monoclonal antibody (anti-TCRdelta1) specific for the constant region of human T cell receptor delta chains that cross-reacts with a subpopulation of guinea pig (Cavia porcellus) lymphocytes. The phenotype and distribution of this subpopulation is consistent with the guinea pig gammadelta T cell subset. FACS analysis of fresh PBMC and splenocytes from naïve guinea pigs revealed the presence of a subset of cells that stained with the anti-TCRdelta1 mAb. The relative percentage of anti-TCRdelta1 positive cells in PBMC and tissues is similar to that described for gammadelta T cells in other species. Immunohistochemistry of tissues also revealed a distribution of anti-TCRdelta1 positive cells consistent with gammadelta T cells. These data are further supported by staining of a polyclonal guinea pig T cell line that became progressively CD4 and CD8 negative in long-term culture. Analysis of PBMC from guinea pigs following aerosol infection with virulent Mycobacterium tuberculosis revealed no apparent changes in the steady-state percentage of blood gammadelta+ T cells. Taken together, these data suggest that the anti-TCRdelta1 antibody recognizes the gammadelta T cell subset in guinea pigs. This reagent may be useful for examining gammadelta T cells in various disease models where the guinea pig is a more desirable model for study.

  4. Development and characterization of a blood mimicking fluid for high intensity focused ultrasound.

    PubMed

    Liu, Yunbo; Maruvada, Subha; King, Randy L; Herman, Bruce A; Wear, Keith A

    2008-09-01

    A blood mimicking fluid (BMF) has been developed for the acoustic and thermal characterizations of high intensity focused ultrasound (HIFU) ablation devices. The BMF is based on a degassed and de-ionized water solution dispersed with low density polyethylene microspheres, nylon particles, gellan gum, and glycerol. A broad range of physical parameters, including attenuation coefficient, speed of sound, viscosity, thermal conductivity, and diffusivity, were characterized as a function of temperature (20-70 degrees C). The nonlinear parameter B/A and backscatter coefficient were also measured at room temperature. Importantly, the attenuation coefficient is linearly proportional to the frequency (2-8 MHz) with a slope of about 0.2 dB cm(-1) MHz(-1) in the 20-70 degrees C range as in the case of human blood. Furthermore, sound speed and bloodlike backscattering indicate the usefulness of the BMF for ultrasound flow imaging and ultrasound-guided HIFU applications. Most of the other temperature-dependent physical parameters are also close to the reported values in human blood. These properties make it a unique HIFU research tool for developing standardized exposimetry techniques, validating numerical models, and determining the safety and efficacy of HIFU ablation devices.

  5. Real-time characterization of the uterine blood flow in mares before and after artificial insemination.

    PubMed

    Ferreira, J C; Ignácio, F S; Rocha, N S; Thompson, D L; Pinto, C R; Meira, C

    2015-09-01

    The present experiment was divided into two studies to investigate the effect of age and endometrial degeneration on uterine blood flow of mares throughout the immediate post-breeding period. In study 1, uterine blood flow was characterized in mares (n = 7 mares/group) with minimal, moderate or severe endometrial degenerative changes (GI, GII and GIII, respectively). In study 2, the effect of age was investigated using young (≤ 6 years) and old (≥ 15 years) mares (n = 7 mares/group). Uterine vascular perfusion and mesometrial pulsatility index (PI) were evaluated every hour from H0 (moment immediately before AI) to H12. In study 1, a pronounced and transitory increase on uterine vascular perfusion was detected (P < 0.001) between H1 and H3 in the three endometrial groups. In addition, GIII mares had greater (P < 0.05) mesometrial PI than GI mares during the post-breeding period, denoting reduced uterine blood flow. In study 2, a transitory increase on uterine vascular perfusion was also observed in both age groups during the first hour after mating. However, mesometrial PI of young and old mares was similar (P > 0.05) and constant (P > 0.7) through the first 12h after AI. Results demonstrated, for the first time, the immediate changes on uterine vascular perfusion and mesometrial PI in response to semen infusion. Moreover, reduced blood flow of the uterus during the post-breeding period was strongly associated with endometrial degenerative changes in mares, regardless of age.

  6. Quantification of pulmonary blood flow (PBF): validation of perfusion MRI and nonlinear contrast agent (CA) dose correction with H(2)15O positron emission tomography (PET).

    PubMed

    Neeb, Daniel; Kunz, Rainer Peter; Ley, Sebastian; Szábo, Gábor; Strauss, Ludwig G; Kauczor, Hans-Ulrich; Kreitner, Karl-Friedrich; Schreiber, Laura Maria

    2009-08-01

    Validation of quantification of pulmonary blood flow (PBF) with dynamic, contrast-enhanced MRI is still missing. A possible reason certainly lies in difficulties based on the nonlinear dependence of signal intensity (SI) from contrast agent (CA) concentration. Both aspects were addressed in this study. Nine healthy pigs were examined by first-pass perfusion MRI using gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) and H(2)(15)O positron emission tomography (PET) imaging. Calculations of hemodynamic parameters were based on a one-compartment model (MR) and a two-compartment model (PET). Simulations showed a significant error when assuming a linear relation between MR SI and CA dose in the arterial input function (AIF), even at low doses of 0.025 mmol/kg body weight (BW). To correct for nonlinearity, a calibration curve was calculated on the basis of the signal equation. The required accuracy of equation parameters (like longitudinal relaxation time) was evaluated. Error analysis estimates <5% over-/underestimation of the corrected SI. Comparison of PET and MR flow values yielded a significant correlation (P < 0.001) in dorsal regions where signal-to-noise ratio (SNR) was sufficient. Changes in PBF due to the correction method were significant (P < 0.001) and resulted in a better agreement: mean values (standard deviation) in units of ml/min/100 ml lung tissue were 59 (15) for PET, 112 (28) for uncorrected MRI, and 80 (21) for corrected MRI.

  7. Clinical value of whole-blood interferon-gamma assay in patients with suspected pulmonary tuberculosis and AFB smear- and polymerase chain reaction-negative bronchial aspirates.

    PubMed

    Lee, Jaehee; Lee, Shin Yup; Yoo, Seung Soo; Cha, Seung Ick; Won, Dong Il; Park, Jae Yong; Lee, Won-Kil; Kim, Chang Ho

    2012-07-01

    Combining a polymerase chain reaction (PCR) test with bronchoscopy is frequently performed to allow a rapid diagnosis of smear-negative pulmonary tuberculosis (PTB). However, limited data are available concerning clinical judgment in patients with suspected PTB and AFB smear- and PCR-negative bronchial aspirates (BA). The present study evaluated the usefulness of whole-blood QuantiFERON-TB Gold In-Tube (QFT) testing in these patients. Of 166 patients with suspected PTB who had undergone bronchoscopy because of smear-negative sputum or inadequate sputum production, 93 (56%) were diagnosed with culture-positive PTB. Seventy-four patients were either AFB smear- or PCR-positive. In the 75 patients whose BA AFB smear and PCR results were both negative, 19 were finally diagnosed with PTB by culture. The QFT test had a negative predictive value of 91% for PTB. The QFT test may be useful for excluding PTB in patients with suspected PTB whose BA AFB smear and PCR results are both negative.

  8. Magnetic characterization of human blood in the atherosclerotic process in coronary arteries

    NASA Astrophysics Data System (ADS)

    Janus, B.; Bućko, M. S.; Chrobak, A.; Wasilewski, J.; Zych, M.

    2011-03-01

    In the last decades there has been an increasing interest in biomagnetism—a field of biophysics concerned with the magnetic properties of living organisms. Biomagnetism focuses on the measurement of magnetic properties of biological samples in the clinical environment. Progress in this field can provide new data for the understanding of the pathomechanism of atherosclerosis and support the diagnostic options for the evaluation and treatment of atherothrombotic complications. Lyophilized human blood samples from patients with atherosclerotic lesions (calcium scoring (CS) CS>0) and without atherosclerotic lesions (CS=0) were magnetically investigated. Magnetic measurements (performed in room and low temperature) indicated significant magnetic differences between these two groups of patients. Atherosclerotic blood samples are characterized by higher concentration of ferrimagnetic particles (magnetite and/or maghemite) and significant changes in the superparamagnetic behaviour. This research presents that magnetometry, in combination with medical research can lead to a better understanding of iron physiology in the atherosclerotic process.

  9. Pulmonary vascular and ventricular dysfunction in the susceptible patient (2015 Grover Conference series)

    PubMed Central

    Maron, Bradley A.; Machado, Roberto F.

    2016-01-01

    Abstract Pulmonary blood vessel structure and tone are maintained by a complex interplay between endogenous vasoactive factors and oxygen-sensing intermediaries. Under physiological conditions, these signaling networks function as an adaptive interface between the pulmonary circulation and environmental or acquired perturbations to preserve oxygenation and maintain systemic delivery of oxygen-rich hemoglobin. Chronic exposure to hypoxia, however, triggers a range of pathogenetic mechanisms that include hypoxia-inducible factor 1α (HIF-1α)–dependent upregulation of the vasoconstrictor peptide endothelin 1 in pulmonary endothelial cells. In pulmonary arterial smooth muscle cells, chronic hypoxia induces HIF-1α-mediated upregulation of canonical transient receptor potential proteins, as well as increased Rho kinase-Ca2+ signaling and pulmonary arteriole synthesis of the profibrotic hormone aldosterone. Collectively, these mechanisms contribute to a contractile or hypertrophic pulmonary vascular phenotype. Genetically inherited disorders in hemoglobin structure are also an important etiology of abnormal pulmonary vasoreactivity. In sickle cell anemia, for example, consumption of the vasodilator and antimitogenic molecule nitric oxide by cell-free hemoglobin is an important mechanism underpinning pulmonary hypertension. Contemporary genomic and transcriptomic analytic methods have also allowed for the discovery of novel risk factors relevant to sickle cell disease, including GALNT13 gene variants. In this report, we review cutting-edge observations characterizing these and other pathobiological mechanisms that contribute to pulmonary vascular and right ventricular vulnerability. PMID:28090285

  10. Bosentan for pulmonary hypertension secondary to idiopathic pulmonary fibrosis.

    PubMed

    Onda, Naomi; Tanaka, Yosuke; Hino, Mitsunori; Gemma, Akihiko

    2015-01-01

    Pulmonary hypertension is a poor prognostic factor in patients with interstitial lung disease. No established treatment exists for pulmonary hypertension secondary to interstitial pneumonia. We describe the case of an 81-year-old woman with idiopathic pulmonary fibrosis (IPF), who was admitted to our hospital due to aggravation of dyspnea and decreased oxygen saturation, as well as onset of orthopnea and rapidly progressing edema. The transthoracic echocardiography and right heart catheterization showed the mean pulmonary artery pressure was 39 mmHg and the mean pulmonary capillary wedge pressure was 9 mmHg. After various examinations, the diagnoses of pulmonary hypertension (PH) due to IPF and of congestive heart failure secondary to PH were established. Diuretic therapy was started, but the patient's condition showed poor improvement. Subsequent initiation of oral bosentan therapy led to improvement in symptoms and findings. At the follow-up assessment one year later her pulmonary function showed no significant changes and no apparent worsening of arterial blood gases, with evident improvement of PH, WHO functional class, maximum exercise tolerance on treadmill exercise testing, right heart catheterization, and transthoracic echocardiography. This report describes a case of successful treatment with bosentan for severe pulmonary hypertension in a patient with idiopathic pulmonary fibrosis. We also present a review of the literature on treatment of pulmonary hypertension in patients with chronic lung disease. Bosentan appears to be efficacious in some patients with pulmonary hypertension secondary to idiopathic interstitial pneumonitis.

  11. Quantitative characterization of circadian rhythm of pulmonary function in asthmatic patients treated with inhaled corticosteroids.

    PubMed

    Zhou, Di; Li, Hongshan; Wang, Yaning; Hochhaus, Guenther; Sinha, Vikram; Zhao, Liang

    2015-08-01

    The aim of this study was to characterize the circadian rhythm observed for forced expiratory volume in 1 s (FEV1) in patients with persistent asthma being treated with inhaled corticosteroids. The database included 3379 FEV1 measurements from 189 patients with mild to moderate asthma. A model using the sum of two Sine functions with periods of 12 and 24 h and a constant component of mean circadian rhythm adequately described the circadian rhythm in FEV1 measurements over time. The model adequateness was evaluated by various approaches including visual predictive check (VPC), prediction-corrected VPC, standardized VPC and normalized prediction distribution error. Covariates tested included age, body weight, height, body mass index, baseline FEV1, and sex. Age and height were found to have significant effects on the mean FEV1 level and no covariate was found to have an effect on the magnitude and timing of circadian rhythm. The model predicted that a minimum FEV1 occurred in the early morning and maximum FEV1 occurred in the early afternoon, with a population mean fluctuation of 170 mL, which is consistent with the finding that asthma symptoms usually exacerbate in the early morning for patients with persistent asthma. This developed model provides the first quantitative approach to describing FEV1 circadian rhythm with ICS background treatment and provided insight in designing future registration trials for asthma drug development.

  12. Characterization of the cellular responses of the pulmonary and hepatic phases of primary murine Schistosoma mansoni infections.

    PubMed

    Khoury, P B; Phillips, S M

    1981-03-01

    Lymphocytes from the mediastinal lymph nodes (draining the pulmonary phase of the infection), the hepatic lymph nodes (draining the hepatic phase of the infection), and the spleen of C57BL/6 mice exposed to Schistosoma mansoni were characterized relative to their capacity to interact with a soluble immunogen prepared from the adult worm (SWI). B or T RFC (rosette forming cells), RAFC (rosette-antibody forming cells), and PFC (plaque forming cells) were assayed. The RFC responses of the mediastinal and hepatic nodes were predominantly B cell in character and were maximal at that period which corresponded to the anatomic exposure which would be predicted from the migratory pattern of the parasite. High levels of T RFC and predominantly IgM B-responsive cells were generated in the mediastinal nodes during the presence of the schistosomulum in the lung parenchyma. Immunoglobulin-responsive (IgM greater than IgG greater than IgE) B cells were initially detected in the hepatic nodes during the lung-to-liver migration of the schistosomulum and its maturation to the adult form. However, elevated levels of T RFC and IgG greater than IgM greater than or equal to IgE-responsive B cells were maximally present in the hepatic nodes during optimal egg production and egg-induced granuloma formation in the liver. In contrast to the responses of the lymph nodes, the splenic responses were predominantly T cell in nature for the first 8 weeks of infection. Splenic lymphocytes expressed a biphasic response, the first represented by T RFC and IgM-responsive B cells and coincided with the migration of the schistosomulum out of the lung and the second was also represented by T RFC but with predominance of IgG-responsive B cells and correlated with the production of eggs and maximal granuloma formation at the hepatic level.

  13. Immunohistochemical Characterization of the Chemosensory Pulmonary Neuroepithelial Bodies in the Naked Mole-Rat Reveals a Unique Adaptive Phenotype

    PubMed Central

    Pan, Jie; Park, Thomas J.; Cutz, Ernest; Yeger, Herman

    2014-01-01

    The pulmonary neuroepithelial bodies (NEBs) constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+) via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT), and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR), Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates). The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR) to identify similarities and differences that could explain the NMR’s adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1) NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2) NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3) NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4) NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA) and the neurogenic gene (MASH1) indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional and

  14. Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

    PubMed

    Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

    2015-02-01

    Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

  15. Unbiased Identification of Blood-based Biomarkers for Pulmonary Tuberculosis by Modeling and Mining Molecular Interaction Networks.

    PubMed

    Sambarey, Awanti; Devaprasad, Abhinandan; Mohan, Abhilash; Ahmed, Asma; Nayak, Soumya; Swaminathan, Soumya; D'Souza, George; Jesuraj, Anto; Dhar, Chirag; Babu, Subash; Vyakarnam, Annapurna; Chandra, Nagasuma

    2017-02-01

    Efficient diagnosis of tuberculosis (TB) is met with multiple challenges, calling for a shift of focus from pathogen-centric diagnostics towards identification of host-based multi-marker signatures. Transcriptomics offer a list of differentially expressed genes, but cannot by itself identify the most influential contributors to the disease phenotype. Here, we describe a computational pipeline that adopts an unbiased approach to identify a biomarker signature. Data from RNA sequencing from whole blood samples of TB patients were integrated with a curated genome-wide molecular interaction network, from which we obtain a comprehensive perspective of variations that occur in the host due to TB. We then implement a sensitive network mining method to shortlist gene candidates that are most central to the disease alterations. We then apply a series of filters that include applicability to multiple publicly available datasets as well as additional validation on independent patient samples, and identify a signature comprising 10 genes - FCGR1A, HK3, RAB13, RBBP8, IFI44L, TIMM10, BCL6, SMARCD3, CYP4F3 and SLPI, that can discriminate between TB and healthy controls as well as distinguish TB from latent tuberculosis and HIV in most cases. The signature has the potential to serve as a diagnostic marker of TB.

  16. [Pathophysiology and classification of pulmonary hypertension].

    PubMed

    Sládková, H; Jansa, P; Susa, Z; Aschermann, M

    2004-09-01

    Pulmonary hypertension is present when the mean pulmonary pressure is increased above 25 mm Hg in a rest or above 30 mm Hg during exercise. It is possible to divide it from different point of view. Well known is pathophysiologic classification and Venice classification suggested by WHO symposium 2003. The rise of arterial pulmonary pressure is caused by three essential abnormalities, these are elevated pulmonary vascular resistance, blood flow and pulmonary artery wedge pressure. Vasoconstriction, remodeling of vessels and in situ trombosis are pathogenetic mechanism which contribute to rise of pulmonary hypertension.

  17. Main pulmonary arterial wall shear stress correlates with invasive hemodynamics and stiffness in pulmonary hypertension

    PubMed Central

    Kheyfets, Vitaly O.; Schroeder, Joyce D.; Dunning, Jamie; Shandas, Robin; Buckner, J. Kern; Browning, James; Hertzberg, Jean; Hunter, Kendall S.; Fenster, Brett E.

    2016-01-01

    Abstract Pulmonary hypertension (PH) is associated with proximal pulmonary arterial remodeling characterized by increased vessel diameter, wall thickening, and stiffness. In vivo assessment of wall shear stress (WSS) may provide insights into the relationships between pulmonary hemodynamics and vascular remodeling. We investigated the relationship between main pulmonary artery (MPA) WSS and pulmonary hemodynamics as well as markers of stiffness. As part of a prospective study, 17 PH patients and 5 controls underwent same-day four-dimensional flow cardiac magnetic resonance imaging (4-D CMR) and right heart catheterization. Streamwise velocity profiles were generated in the cross-sectional MPA in 45° increments from velocity vector fields determined by 4-D CMR. WSS was calculated as the product of hematocrit-dependent viscosity and shear rate generated from the spatial gradient of the velocity profiles. In-plane average MPA WSS was significantly decreased in the PH cohort compared with that in controls (0.18 ± 0.07 vs. 0.32 ± 0.08 N/m2; P = 0.01). In-plane MPA WSS showed strong inverse correlations with multiple hemodynamic indices, including pulmonary resistance (ρ = −0.74, P < 0.001), mean pulmonary pressure (ρ = −0.64, P = 0.006), and elastance (ρ = −0.70, P < 0.001). In addition, MPA WSS had significant associations with markers of stiffness, including capacitance (ρ = 0.67, P < 0.001), distensibility (ρ = 0.52, P = 0.013), and elastic modulus (ρ = −0.54, P = 0.01). In conclusion, MPA WSS is decreased in PH and is significantly associated with invasive hemodynamic indices and markers of stiffness. 4-D CMR–based assessment of WSS may represent a novel methodology to study blood-vessel wall interactions in PH. PMID:27076906

  18. Rheological characterization of a gel produced using human blood plasma and alginate mixtures.

    PubMed

    Malagón-Romero, Dionisio; Hernández, Nicolás; Cardozo, Carmen; Godoy-Silva, Rubén D

    2014-06-01

    Human blood plasma is a material used to generate tissue equivalents due to presence of fibrinogen. However, gels formed using human blood plasma has weak mechanical properties. In this study, different mixtures of sodium alginate and blood plasma were performed and evaluated. By determining ζ potential can be established the stability of the plasma-alginate mixture and by dynamic rheology can determine the most suitable parameters for the gelation of the above mixtures, when calcium chloride is used as a crosslinker. Experimental results evidence an increment in ζ potential at alginate concentrations of 0.8% and 1.6% with a resulting pseudoplastic behavior of evaluated mixtures, which described the homogenization of the mixture. On the other hand, mixtures were gelled by using aspersion of calcium chloride and characterized by dynamic rheology. Solid behavior is dominant in all range of frequency sweep test between 0.1Hz and 100Hz. Finally, the ultimate tensile strength of a gel reach 6.36938±0.24320kPa, which is enough for manual handling of the gel. Between the tasks of the gel would be used for cell entrapment, for controlled release of drugs or in the manufacture of wound dressings.

  19. Characterization of porcine peripheral blood leukocytes by light-scattering flow cytometry.

    PubMed Central

    Wang, F I; Williams, T J; el-Awar, F Y; Pang, V F; Hahn, E C

    1987-01-01

    As a basis for other experiments using flow cytometry of porcine peripheral blood leukocytes, cell fractions were isolated by various methods and analyzed by forward angle light scatter and 90 degree light scatter. Cytospin smears of cell samples were also studied by leukocyte differential counts and nonspecific esterase staining. Three main populations of peripheral blood leukocytes [lymphocytes, monocytes, and granulocytes (primarily neutrophils)], were defined in the log 90 degree light scatter by forward angle light scatter histogram. Partial overlap was observed between lymphocyte and monocyte, and between monocyte and granulocyte domains. Correlation between leukocyte differential counts and flow cytometric quantification based on bitmap statistics of appropriate domains was between r = 0.872-0.892 for lymphocyte and granulocyte. Percoll density gradients were used for subfractionation of leukocyte populations, especially for the enrichment of granulocytes. The specific densities were calculated for lymphocytes (1.0585-1.0819 g/cc), monocytes (1.0585-1.0702 g/cc), granulocyte (1.0819-1.0936 g/cc), and erythrocytes (greater than 1.0952 g/cc). We suggest that light scatter characterization is a basis for future studies of porcine blood by flow cytometry. PMID:3453262

  20. Fabrication and characterization of 3C-silicon carbide micro sensor for wireless blood pressure measurements

    NASA Astrophysics Data System (ADS)

    Basak, Nupur

    A potentially implantable single crystal 3C-SiC pressure sensor for blood pressure measurement was designed, simulated, fabricated, characterized and optimized. This research uses a single crystal 3C-SiC, for the first time, to demonstrate its application as a blood pressure measurement sensor. The sensor, which uses the epitaxial grown 3C-SiC membrane to measure changes in pressure, is designed to be wireless, biocompatible and linear. The SiC material was chosen for its superior physical, chemical and mechanical properties; the capacitive sensor uses a 3C-SiC membrane as one of the electrodes; and, the sensor system is wireless for comfort and to allow for convenient reading of real-time pressure data (wireless communication is enabled by connecting the sensor parallel to a planar inductor). Together, the variable capacitive sensor and planar inductor create a pressure sensitive resonant circuit. The sensor system described above allows for implantation into a human patient's body, after which the planar inductor can be coupled with an external inductor to receive data for real-time blood pressure measurement. Electroplating, thick photo-resist characterization, RIE etching, oxidation, CVD, chemical mechanical polishing and wafer bonding were optimized during the process of fabricating the sensor system and, in addition to detailing the sensor system simulation and characterization; the optimized processes are detailed in the dissertation. This absolute pressure sensor is designed to function optimally within the human blood pressure range of 50-350mmHg. The layout and modeling of the sensor uses finite element analysis (FEA) software. The simulations for membrane deflection, stress analysis and electro-mechanical analysis are performed for 100 μm2 and 400μm2sensors. The membrane deflection-pressure, capacitance-pressure and resonant frequency-pressure graphs were obtained, and detailed in the dissertation, along with the planar inductor simulation for

  1. Human whole-blood culture system for ex vivo characterization of designer-cell function.

    PubMed

    Schukur, Lina; Geering, Barbara; Fussenegger, Martin

    2016-03-01

    Encapsulated designer cells implanted into mice are currently used to validate the efficacy of therapeutic gene networks for the diagnosis and treatment of various human diseases in preclinical research. Because many human conditions cannot be adequately replicated by animal models, complementary and alternative procedures to test future treatment strategies are required. Here we describe a novel approach utilizing an ex vivo human whole-blood culture system to validate synthetic biology-inspired designer cell-based treatment strategies. The viability and functionality of transgenic mammalian designer cells co-cultured with primary human immune cells were characterized. We demonstrated that transgenic mammalian designer cells required adequate insulation from the human blood microenvironment to maintain viability and functionality. The biomaterial alginate-(poly-l-lysine)-alginate used to encapsulate the transgenic designer cells did neither affect the viability of primary granulocytes and lymphocytes nor the functionality of lymphocytes. Additionally, alginate-encapsulated transgenic designer cells remained responsive to the release of the pro-inflammatory cytokine tumor necrosis factor (TNF) from the whole-blood culture upon exposure to bacterial lipopolysaccharide (LPS). TNF diffused into the alginate capsules, bound to the specific TNF receptors on the transgenic designer cells' surface and triggered the expression of the reporter gene SEAP (human placental secreted alkaline phosphatase) that was rewired to the TNF-specific signaling cascade. Human whole-blood culture systems can therefore be considered as valuable complementary assays to animal models for the validation of synthetic circuits in genetically modified mammalian cells and may speed up preclinical research in a world of personalized medicine.

  2. What Is Pulmonary Hypertension?

    MedlinePlus

    ... for a referral to a counselor. A support group for people living with pulmonary hypertension can be invaluable in learning how to cope with the illness. This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP Introduction What ...

  3. Pulmonary Hypertension and Pulmonary Vasodilators.

    PubMed

    Keller, Roberta L

    2016-03-01

    Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities.

  4. Pulmonary Edema

    MedlinePlus

    ... suddenly or develop over time. Sudden (acute) pulmonary edema symptoms Extreme shortness of breath or difficulty breathing ( ... fatal if not treated. Long-term (chronic) pulmonary edema symptoms Having more shortness of breath than normal ...

  5. Pulmonary Rehabilitation

    MedlinePlus

    Pulmonary Rehabilitation If you have shortness of breath because of lung problems, you may have asked yourself: • Can I ... medications do I really need to take? Pulmonary rehabilitation can help answer these and other questions. Enrolling ...

  6. Pulmonary Fibrosis

    MedlinePlus

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This tissue ... may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  7. Characterization of blood drawn rapidly for use in blood volume expansion studies: An animal model for simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Chenault, V. Michelle; Lynch, Colleen D.; Morris, Mariana; Clodfelter, Jill; Hutchins, Phillip M.

    1990-01-01

    It was demonstrated that up to 8ml of blood can be drawn from donar rats without significantly increasing volume and stress sensitive hormones, and thus can be used for volume expansion studies. Infusion of whole blood allows more physiological changes that can be seen with volume expansion by saline or other ionic solutions. The infusion of whole blood to induce hypervolemia may provide an improved model to study the fluid balance and control mechanisms operative in weightlessness. Blood samples were drawn as quickly as possible from femoral artery catheters chronically implanted in Sprague Dawley rats and analyzed for hematocrit, plasma sodium, potassium, osmolality, corticosterone, epinepherine, norepinephrine, and vasopressin. The levels were found to be comparable to those of normal rats.

  8. Atrial septal defect combined with partial anomalous pulmonary venous return: complete anatomic and functional characterization by cardiac magnetic resonance.

    PubMed

    Dellegrottaglie, Santo; Pedrotti, Patrizia; Pedretti, Stefano; Mauri, Francesco; Roghi, Alberto

    2008-11-01

    The presented case regards a 17-year-old male with new-onset right bundle branch block and significantly enlarged right-heart sections as the only pathologic finding on transthoracic echocardiography. Cardiac magnetic resonance (CMR) revealed the presence of a superior sinus venosus atrial septal defect associated with a partial anomalous pulmonary venous return, with the right upper lobe pulmonary vein draining into the superior vena cava. CMR has developed in recent years into an accurate modality for non-invasive evaluation of patients with congenital heart disease, especially through improvements in quality and speed of image acquisition. With echocardiography, sinus venosus defects and anomalous pulmonary vein drainage may be more easily detected by a transoesophageal approach because of the proximity of the transducer to the atrial septum. CMR may be specifically recommended as an alternative to transoesophageal echocardiography in any patient with an unexplained dilatation of the right ventricle.

  9. Preparation and characterization of spray-dried inhalable powders containing nanoaggregates for pulmonary delivery of anti-tubercular drugs.

    PubMed

    Kaur, Ranjot; Garg, Tarun; Das Gupta, Umesh; Gupta, Pushpa; Rath, Goutam; Goyal, Amit Kumar

    2016-01-01

    This study aims to prepare spray-dried inhalable powders containing anti-tubercular drugs-loaded HPMC nanoaggregates for sustained delivery of drugs to the lung. Nanoaggregates were prepared by precipitation technique. Results showed that the powders obtained had excellent aerosolization property. High drug encapsulation efficiency was achieved in HPMC nano aggregates, ranging from 60% to 70%. A single pulmonary dose resulted in therapeutic drug concentrations 40% to 60% in the lungs and in other organs (< 5%) for 24 h. From this study, we can conclude that delivering drugs through pulmonary route is advantageous for local action in lungs.

  10. Temporal and spatial characterization of mononuclear phagocytes in circulating, lung alveolar and interstitial compartments in a mouse model of bleomycin-induced pulmonary injury.

    PubMed

    Ji, Wen-Jie; Ma, Yong-Qiang; Zhou, Xin; Zhang, Yi-Dan; Lu, Rui-Yi; Sun, Hai-Ying; Guo, Zhao-Zeng; Zhang, Zhuoli; Li, Yu-Ming; Wei, Lu-Qing

    2014-01-31

    The mononuclear phagocyte system, including circulating monocytes and tissue resident macrophages, plays an important role in acute lung injury and fibrosis. The detailed dynamic changes of mononuclear phagocytes in the circulating, lung alveolar and interstitial compartments in bleomycin-induced pulmonary injury model have not been fully characterized. The present study was designed to address this issue and analyzed their relationships with pulmonary pathological evolution after bleomycin challenge. A total of 100 male C57BL/6 mice were randomly divided to receive bleomycin (2.5mg/kg, n=50) or normal saline (n=50) via oropharyngeal approach, and were sacrificed on days 1, 3, 7, 14 and 21. Circulating monocyte subsets, polarization state of bronchoalveolar lavage fluid (BALF)-derived alveolar macrophages (AMφ) and lung interstitial macrophages (IMφ, derived from enzymatically digested lung tissue) were analyzed by flow cytometry. There was a rapid expansion of circulating Ly6C(hi) monocytes which peaked on day 3, and its magnitude was positively associated with pulmonary inflammatory response. Moreover, an expansion of M2-like AMφ (F4/80+CD11c+CD206+) peaked on day 14, and was positively correlated with the magnitude of lung fibrosis. The polarization state of IMφ remained relatively stable in the early- and mid-stage after bleomycin challenge, expect for an increase of M2-like (F4/80+CD11c-CD206+) IMφ on day 21. These results support the notion that there is a Ly6C(hi)-monocyte-directed pulmonary AMφ alternative activation. Our result provides a dynamic view of mononuclear phagocyte change in three compartments after bleomycin challenge, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.

  11. Multifractal characterization of morphology of human red blood cells membrane skeleton.

    PubMed

    Ţălu, Ş; Stach, S; Kaczmarska, M; Fornal, M; Grodzicki, T; Pohorecki, W; Burda, K

    2016-04-01

    The purpose of this paper is to show applicability of multifractal analysis in investigations of the morphological changes of ultra-structures of red blood cells (RBCs) membrane skeleton measured using atomic force microscopy (AFM). Human RBCs obtained from healthy and hypertensive donors as well as healthy erythrocytes irradiated with neutrons (45 μGy) were studied. The membrane skeleton of the cells was imaged using AFM in a contact mode. Morphological characterization of the three-dimensional RBC surfaces was realized by a multifractal method. The nanometre scale study of human RBCs surface morphology revealed a multifractal geometry. The generalized dimensions Dq and the singularity spectrum f(α) provided quantitative values that characterize the local scale properties of their membrane skeleton organization. Surface characterization was made using areal ISO 25178-2: 2012 topography parameters in combination with AFM topography measurement. The surface structure of human RBCs is complex with hierarchical substructures resulting from the organization of the erythrocyte membrane skeleton. The analysed AFM images confirm a multifractal nature of the surface that could be useful in histology to quantify human RBC architectural changes associated with different disease states. In case of very precise measurements when the red cell surface is not wrinkled even very fine differences can be uncovered as was shown for the erythrocytes treated with a very low dose of ionizing radiation.

  12. Pulmonary gas exchange during intermittent ventilation in the American alligator.

    PubMed

    Hicks, J W; White, F N

    1992-01-01

    The present study characterized pulmonary gas exchange in the American alligator, Alligator mississipiensis during ventilation and apnea at a body temperature (Tb) of 25 degrees C. Pulmonary gas exchange parameters were measured on a breath-by-breath basis utilizing a computer-assisted data acquisition system. In addition, paired blood samples were analyzed from left and right atrium during ventilation and voluntary apneas (1, 2, 5 and 10 min). Measurements of lung PO2 and PCO2 indicated that as apnea progressed, CO2 flux into the lung decreased rapidly while O2 was continuously removed at a constant and steady rate. The reduction in VCO2 resulted in a decrease in R (less than 0.4). Blood gas measurements indicated that the pulmonary arterial-pulmonary venous PCO2 difference, (Ppa-Ppv)CO2 was 4.9 +/- 0.9 mmHg during ventilation, decreased and became negative within 2 min of apnea, reaching -3.9 +/- 0.6 mmHg after 10 min. It is postulated that during apnea the Haldane effect accounts for both the blood gas behavior across the lung and insures a continued CO2 flux into the lung during apnea.

  13. Persistent Pulmonary Hypertension of the Newborn

    PubMed Central

    Lakshminrusimha, Satyan; Keszler, Martin

    2015-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is often secondary to parenchymal lung disease (such as meconium aspiration syndrome) or lung hypoplasia (with congenital diaphragmatic hernia) but can also be idiopathic. PPHN is characterized by elevated pulmonary vascular resistance, resulting in right-to-left shunting of blood and hypoxemia. The diagnosis of PPHN is based on clinical evidence of labile hypoxemia often associated with differential cyanosis and confirmed by echocardiography. Lung volume recruitment with optimal use of positive end-expiratory pressure or mean airway pressure and/or surfactant is very important in secondary PPHN due to parenchymal lung disease. Other management strategies include optimal oxygenation, avoiding respiratory and metabolic acidosis, blood pressure stabilization, sedation, and pulmonary vasodilator therapy. Failure of these measures leads to consideration of extracorporeal membrane oxygenation, although this rescue therapy is needed less frequently with advances in medical management. Randomized clinical trials with long-term follow-up are required to evaluate various therapeutic strategies in PPHN. PMID:26783388

  14. Persistent pulmonary hypertension of the newborn.

    PubMed

    Sharma, Vinay; Berkelhamer, Sara; Lakshminrusimha, Satyan

    2015-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is characterized by elevated pulmonary vascular resistance resulting in right-to-left shunting of blood and hypoxemia. PPHN is often secondary to parenchymal lung disease (such as meconium aspiration syndrome, pneumonia or respiratory distress syndrome) or lung hypoplasia (with congenital diaphragmatic hernia or oligohydramnios) but can also be idiopathic. The diagnosis of PPHN is based on clinical evidence of labile hypoxemia often associated with differential cyanosis. The diagnosis is confirmed by the echocardiographic demonstration of - (a) right-to-left or bidirectional shunt at the ductus or foramen ovale and/or, (b) flattening or leftward deviation of the interventricular septum and/or, (c) tricuspid regurgitation, and finally (d) absence of structural heart disease. Management strategies include optimal oxygenation, avoiding respiratory and metabolic acidosis, blood pressure stabilization, sedation and pulmonary vasodilator therapy. Failure of these measures would lead to consideration of extracorporeal membrane oxygenation (ECMO); however decreased need for this rescue therapy has been documented with advances in medical management. While trends also note improved survival, long-term neurodevelopmental disabilities such as deafness and learning disabilities remain a concern in many infants with severe PPHN. Funded by: 1R01HD072929-0 (SL).

  15. Characterization at the individual cell level and in whole blood samples of shear stress preventing red blood cells aggregation.

    PubMed

    Lee, K; Kinnunen, M; Danilina, A V; Ustinov, V D; Shin, S; Meglinski, I; Priezzhev, A V

    2016-05-03

    The aggregation of red blood cells (RBC) is an intrinsic feature of blood that has a strong impact on its microcirculation. For a number of years it has been attracting a great attention in basic research and clinical studies. Here, we study a relationship between the RBC aggregation parameters measured at the individual cell level and in a whole blood sample. The home made optical tweezers were used to measure the aggregating and disaggregating forces for a pair of interacting RBCs, at the individual cell level, in order to evaluate the corresponding shear stresses. The RheoScan aggregometer was used for the measurements of critical shear stress (CSS) in whole blood samples. The correlation between CSS and the shear stress required to stop an RBC pair from aggregating was found. The shear stress required to disaggregate a pair of RBCs using the double channel optical tweezers appeared to be about 10 times higher than CSS. The correlation between shear stresses required to prevent RBCs from aggregation at the individual cell level and in whole blood samples was estimated and assessed quantitatively. The experimental approach developed has a high potential for advancing hemorheological studies.

  16. The role of inflammation and autoimmunity in the pathophysiology of pulmonary arterial hypertension.

    PubMed

    Kherbeck, Nada; Tamby, Mathieu C; Bussone, Guillaume; Dib, Hanadi; Perros, Frederic; Humbert, Marc; Mouthon, Luc

    2013-02-01

    Pulmonary arterial hypertension is characterized by a remodeling of pulmonary arteries with endothelial cell, fibroblast, and vascular smooth muscle cell activation and proliferation. Since pulmonary arterial hypertension occurs frequently in autoimmune conditions such as systemic sclerosis, inflammation and autoimmunity have been suspected to play a critical role in both idiopathic pulmonary arterial hypertension and systemic sclerosis-associated pulmonary arterial hypertension. High levels of pro-inflammatory cytokines such as interleukin-1 and interleukin-6, platelet-derived growth factor, or macrophage inflammatory protein 1 have been found in lung samples of patients with pulmonary arterial hypertension, along with inflammatory cell infiltrates mainly composed of macrophages and dendritic cells, T and B lymphocytes. In addition, circulating autoantibodies are found in the peripheral blood of patients. Thus, autoimmunity and inflammation probably play a role in the development of pulmonary arterial hypertension. In this setting, it would be important to set-up new experimental models of pulmonary arterial hypertension, in order to define novel therapeutics that specifically target immune disturbances in this devastating condition.

  17. Acute right ventricular failure caused by concomitant coronary and pulmonary embolism: successful treatment with endovascular coronary and pulmonary thrombectomy

    PubMed Central

    Koul, Sasha; Roijer, Anders; Holmqvist, Jasminka; Keussen, Inger; Cwikiel, Wojciech; Öhlin, Bertil; Erlinge, David

    2013-01-01

    Patent foramen ovale (PFO) is present in approximately 25% of the general population. PFO is characterized by intermittent shunting of blood from the right to the left atrium, especially in the context of increased right-sided filling pressures, with risk of paradoxical embolism. We describe a 69-year-old woman presenting with acute chest pain, severe dyspnoea, and acute inferolateral ST-segment elevation on the electrocardiogram. The patient was diagnosed with myocardial infarction and failure of the right cardiac ventricle, which was considered to be secondary to extensive pulmonary embolism leading to increased filling pressures and paradoxical coronary embolism. The patient underwent emergent percutaneous interventions with coronary thrombus extraction and pulmonary thrombus fragmentation and local thrombolysis. The patient was free of symptoms at follow up 6 months later and echocardiography showed substantially improved right ventricular function. We discuss issues related to the diagnosis, treatment, and secondary prevention for patients with concomitant pulmonary and coronary arterial thrombosis. PMID:24222822

  18. Molecular characterization, distribution, and dynamics of hepatitis C virus genotypes in blood donors in Colombia.

    PubMed

    Mora, Mónica Viviana Alvarado; Romano, Camila Malta; Gomes-Gouvêa, Michele Soares; Gutiérrez, Maria Fernanda; Carrilho, Flair José; Pinho, João Renato Rebello

    2010-11-01

    Hepatitis C virus (HCV) is a frequent cause of acute and chronic hepatitis and a leading cause for cirrhosis of the liver and hepatocellular carcinoma. HCV is classified in six major genotypes and more than 70 subtypes. In Colombian blood banks, serum samples were tested for anti-HCV antibodies using a third-generation ELISA. The aim of this study was to characterize the viral sequences in plasma of 184 volunteer blood donors who attended the "Banco Nacional de Sangre de la Cruz Roja Colombiana," Bogotá, Colombia. Three different HCV genomic regions were amplified by nested PCR. The first of these was a segment of 180 bp of the 5'UTR region to confirm the previous diagnosis by ELISA. From those that were positive to the 5'UTR region, two further segments were amplified for genotyping and subtyping by phylogenetic analysis: a segment of 380 bp from the NS5B region; and a segment of 391 bp from the E1 region. The distribution of HCV subtypes was: 1b (82.8%), 1a (5.7%), 2a (5.7%), 2b (2.8%), and 3a (2.8%). By applying Bayesian Markov chain Monte Carlo simulation, it was estimated that HCV-1b was introduced into Bogotá around 1950. Also, this subtype spread at an exponential rate between about 1970 to about 1990, after which transmission of HCV was reduced by anti-HCV testing of this population. Among Colombian blood donors, HCV genotype 1b is the most frequent genotype, especially in large urban conglomerates such as Bogotá, as is the case in other South American countries.

  19. Characterization of imidazoline receptors in blood vessels for the development of antihypertensive agents.

    PubMed

    Chen, Mei-Fen; Tsai, Jo-Ting; Chen, Li-Jen; Wu, Tung-Pi; Yang, Jia-Jang; Yin, Li-Te; Yang, Yu-Lin; Chiang, Tai-An; Lu, Han-Lin; Wu, Ming-Chang

    2014-01-01

    It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R) may reduce the blood pressure in spontaneously hypertensive rats (SHRs). Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s). Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP) channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to open KATP channels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future.

  20. Characterization of Imidazoline Receptors in Blood Vessels for the Development of Antihypertensive Agents

    PubMed Central

    Chen, Mei-Fen; Chen, Li-Jen; Wu, Tung-Pi; Yang, Jia-Jang; Yin, Li-Te; Yang, Yu-lin; Chiang, Tai-An; Lu, Han-Lin; Wu, Ming-Chang

    2014-01-01

    It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R) may reduce the blood pressure in spontaneously hypertensive rats (SHRs). Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s). Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP) channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to open KATP channels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future. PMID:24800210

  1. Characterization of peripheral blood human immunodeficiency virus isolates from Hispanic women with cognitive impairment.

    PubMed

    Nieves, Dianedis M Toro; Plaud, Marinés; Wojna, Valerie; Skolasky, Richard; Meléndez, Loyda M

    2007-08-01

    Human immunodeficiency virus type 1 (HIV-1) tropism plays an important role in HIV-associated dementia. In this study, aimed at determining if the tropism and coreceptor usage of circulating viruses correlates with cognitive function, the authors isolated and characterized HIV from the peripheral blood of 21 Hispanic women using antiretroviral therapy. Macrophage tropism was determined by inoculation of HIV isolates onto monocyte-derived macrophages and lymphocyte cultures. To define coreceptor usage, the HIV isolates were inoculated onto the U87.CD4 glioma cell lines with specific CCR5 and CXCR4 coreceptors. HIV isolates from cognitively impaired patients showed higher levels of replication in mitogen-stimulated peripheral blood mononuclear cells than did isolates from patients with normal cognition (P < .05). The viral growth of HIV primary isolates in macrophages and lymphocytes did not differ between patients with and those without cognitive impairment. However, isolates from the cognitively impaired women preferentially used the X4 coreceptor (P < .05). These phenotypic studies suggest that cognitively impaired HIV-infected women receiving treatment may have a more highly replicating and more pathogenic X4 virus in the circulation that could contribute to their neuropathogenesis.

  2. Molecular characterization of porcine Siglec-10 and analysis of its expression in blood and tissues.

    PubMed

    Escalona, Z; Álvarez, B; Uenishi, H; Toki, D; Yuste, M; Revilla, C; del Moral, M Gómez; Alonso, F; Ezquerra, A; Domínguez, J

    2015-01-01

    Siglecs are sialic acid binding Ig-like proteins involved in the control of leukocyte responses. In this study we describe the characterization of a porcine orthologue of Siglec-10. A cDNA clone was obtained from a porcine library which encodes a protein with sequence homology to human Siglec-10. This cDNA codes for a type I transmembrane protein containing four Ig-like domains, a transmembrane region, and a cytoplasmic tail with three tyrosine-based motifs, including a membrane-proximal Grb2-binding motif, and two ITIM motifs. When expressed on transfected cells, porcine Siglec-10 was able to bind red blood cells in a sialic acid-dependent manner. Monoclonal antibodies were developed against this protein and used to examine its cell and tissue distribution in the pig. Siglec-10 was found to be expressed on blood B cells and B cell areas of the spleen and lymph nodes. A weak expression was also detected on monocytes.

  3. Experimental ultrasound characterization of red blood cell aggregation using the structure factor size estimator.

    PubMed

    Yu, François T H; Cloutier, Guy

    2007-07-01

    The frequency dependence of the ultrasonic backscattering coefficient (BSC) was studied to assess the level of red blood cell (RBC) aggregation. Three monoelement focused wideband transducers were used to insonify porcine blood sheared in a Couette flow from 9 to 30 MHz. A high shear rate was first applied to promote disaggregation. Different residual shear rates were then used to promote formation of RBC aggregates. The structure factor size estimator (SFSE), a second-order data reduction model based on the structure factor, was applied to the frequency-dependent BSC. Two parameters were extracted from the model to describe the level of aggregation at 6% and 40% hematocrits: W, the packing factor, and D the aggregate diameter, expressed in number of RBCs. Both parameters closely matched theoretical values for nonaggregated RBCs. W and D increased during aggregation with stabilized values modulated by the applied residual shear rate. Furthermore, parameter D during the kinetics of aggregation at 6% hematocrit under static conditions correlated with an optical RBC aggregate size estimation from microscopic images (r(2)=0.76). To conclude, the SFSE presents an interesting framework for tissue characterization of partially correlated dense tissues such as aggregated RBCs.

  4. Characterizations of individual human red blood cells from patients with diabetes mellitus (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Lee, SangYun; Jang, Seongsoo; Park, HyunJoo; Park, YongKeun

    2016-03-01

    We systematically measure the morphological, biochemical, and biomechanical properties of individual human red blood cells (RBCs) from patients with diabetes mellitus using quantitative phase imaging technique to characterize the diabetic red cells with respect to those of the healthy. The 3-D refractive index tomograms and 2-D dynamic membrane fluctuation maps of individual RBCs are reconstructed from a set of the retrieved complex optical fields at various laser incidence angles using the Common-path diffraction optical tomography, from which volume, surface area, sphericity, hemoglobin (Hb) concentration, Hb content, and membrane fluctuation are obtained simultaneously. The correlative relations among the retrieved red cell indices of diabetic and healthy RBCs are also investigated with capabilities of individual cell measurement. As expected, there are no significant alterations in morphologies (cellular volumes, surface area, and sphericity) between diabetic and healthy RBCs. However, despite the minute mean corpuscular Hb differences in cell blood count datasheet, the measured Hb concentrations and Hb contents of diabetic RBCs are statistically higher than those of healthy RBCs, which might be related to the glycation of Hb molecules by hyperglycemia. Meanwhile, the membrane fluctuations of diabetic RBCs are clearly diminished compared to healthy red cells, implying the significantly decreased RBC deformability. In particular, it seems that the membrane fluctuations have mild negative relationships with the reported HbA1c levels.

  5. Light-scattering flow cytometry for identification and characterization of blood microparticles

    NASA Astrophysics Data System (ADS)

    Konokhova, Anastasiya I.; Yurkin, Maxim A.; Moskalensky, Alexander E.; Chernyshev, Andrei V.; Tsvetovskaya, Galina A.; Chikova, Elena D.; Maltsev, Valeri P.

    2012-05-01

    We describe a novel approach to study blood microparticles using the scanning flow cytometer, which measures light scattering patterns (LSPs) of individual particles. Starting from platelet-rich plasma, we separated spherical microparticles from non-spherical plasma constituents, such as platelets and cell debris, based on similarity of their LSP to that of sphere. This provides a label-free method for identification (detection) of microparticles, including those larger than 1 μm. Next, we rigorously characterized each measured particle, determining its size and refractive index including errors of these estimates. Finally, we employed a deconvolution algorithm to determine size and refractive index distributions of the whole population of microparticles, accounting for largely different reliability of individual measurements. Developed methods were tested on a blood sample of a healthy donor, resulting in good agreement with literature data. The only limitation of this approach is size detection limit, which is currently about 0.5 μm due to used laser wavelength of 0.66 μm.

  6. [New surgical approach "intrapulmonary septation technic" for Fontan candidates with unilateral pulmonary arterial hypoplasia and/or pulmonary venous obstruction].

    PubMed

    Sakamoto, K; Nishioka, M; Fujimoto, K; Ohta, N; Murata, M; Nakada, T; Sekine, Y; Yokota, M

    2003-04-01

    Unilateral pulmonary arterial hypoplasia and/or pulmonary venous obstruction are serious hazards for Fontan candidates. For these patients, we have started new surgical approach "intrapulmonary septation technic". This consists of 3 components; (A) partial right heart bypass to well-grown side, (B) mandatory pulmonary blood flow to low-capacity side, (aorto-pulmonary shunt or others) and (C) a patch between partial right heart bypass and mandatory pulmonary blood flow. Thirteen patients underwent the approach. The source of partial right heart bypass was brought from superior vena cava (11 patients), inferior vena cava (1 patient) and fenestrated Fontan (1 patient). The mandatory pulmonary blood flow was supplied by aorto-pulmonary shunt (11 patients), pulmonary arterial banding (1 patient) and native pulmonary valve stenosis (1 patient). We added pulmonary artery enlargement (9 patients), release of pulmonary venous obstruction (8 patients) and/or atrio-ventricular valve plasty (5 patients), simultaneously. No hospital death. Early post-operative course was uneventful in all cases except 1, as pulmonary blood flow to low-capacity side had increased gradually after this intervention. Eight patients had reached Fontan operation. In this approach, nearly whole pulmonary artery can grow without any affect of volume overload through well-grown side from collateral arteries of low-capacity side. All procedures of "intrapulmonary septation technic" and reconstruction of pulmonary artery in Fontan operation can be easily performed in larger pulmonary artery of well-grown side, eliminating need for extensive dissection.

  7. Pulmonary varix: A case report.

    PubMed

    Haddad, Jorge; Badran, André; Pavão, Rafael; de Padua, Adriana I; Lago, Igor; Marin Neto, Jose A

    2016-01-01

    The authors report a case of multiple pulmonary varices, a rare disease characterized by aneurysmatic venous dilatations, which can be present at any age and without gender predominance, occurring in isolation or associated with obstruction of the pulmonary veins. This condition usually manifests as a lung mass with variable clinical consequences.

  8. Serological Patterns and Molecular Characterization of Occult Hepatitis B Virus Infection among Blood Donors

    PubMed Central

    Lin, Hong; Zhao, Hong; Tang, Xinyi; Hu, Wenjia; Jiang, Nizheng; Zhu, Shaowen; Huang, Chengyin

    2016-01-01

    Background Hepatitis B infections, characterized by the presence of a viral genome without detectable hepatitis B surface antigen (HBsAg; Occult hepatitis B infection [OBI]), have been reported recently. Objectives We performed serological and molecular characterization of OBI among blood donors at Jiangsu province blood center during years 2013 and 2014. Methods All donor samples were routinely screened by double enzyme-linked immunosorbent assay (ELISA) for hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), Treponema pallidum (TP), and alanine aminotransferase (ALT). Single-reactive, nonreactive, and ALT-elevated samples were pooled or resolved by nucleic acid testing (NAT). Seromarkers were examined in HBsAg-/DNA+ samples. After 1 to 12 months of follow up, seromarkers were screened again to verify OBI samples. Results We studied 157119 samples from blood donors. A total of 154397 ELISA nonreactive donor samples were identified, and HBV DNA was detected in 81 samples; no samples were positive for HIV or HCV RNA. Hepatitis B virus viral loads in most donors were less than 20 - 200 IU/mL. There was only one HBsAg-positive sample. Eighty HBsAg-/DNA+ samples were evaluated further. Of these samples, 85% (68/80) were reactive for anti-HBc and 36.2% (29/800) were reactive for anti-HBc and anti-HBs; 11.3% (9/80) did not have any detectable serological markers. Twenty-nine donors were followed up. One was HBsAg ELISA positive, and of six seronegative donors, all had anti-HBc and anti-HBs, but were negative for DNA. Samples were HBV genotypes B, C and D. Mutations in the S region of HBV DNA included S114T, G119R, P120S, T125M, C139Y, T140I, C147W, T148A, A159V/G, E164D, V168A, and R169C. Conclusions Overall, we found that OBI was rare, but that the prevalence of OBI was slightly higher in Jiangsu than in other areas of China. PMID:27882070

  9. Isolation and characterization of ovine mesenchymal stem cells derived from peripheral blood

    PubMed Central

    2012-01-01

    Background Mesenchymal stem cells (MSCs) are multipotent stem cells with capacity to differentiate into several mesenchymal lineages. This quality makes MSCs good candidates for use in cell therapy. MSCs can be isolated from a variety of tissues including bone marrow and adipose tissue, which are the most common sources of these cells. However, MSCs can also be isolated from peripheral blood. Sheep has been proposed as an ideal model for biomedical studies including those of orthopaedics and transmissible spongiform encephalopathies (TSEs). The aim of this work was to advance these studies by investigating the possibility of MSC isolation from ovine peripheral blood (oPB-MSCs) and by subsequently characterizing there in vitro properties. Results Plastic-adherent fibroblast-like cells were obtained from the mononuclear fraction of blood samples. These cells were analysed for their proliferative and differentiation potential into adipocytes, osteoblasts and chondrocytes, as well as for the gene expression of cell surface markers. The isolated cells expressed transcripts for markers CD29, CD73 and CD90, but failed to express the haematopoietic marker CD45 and expressed only low levels of CD105. The expression of CD34 was variable. The differentiation potential of this cell population was evaluated using specific differentiation media. Although the ability of the cultures derived from different animals to differentiate into adipocytes, osteoblasts and chondrocytes was heterogeneous, we confirmed this feature using specific staining and analysing the gene expression of differentiation markers. Finally, we tested the ability of oPB-MSCs to transdifferentiate into neuronal-like cells. Morphological changes were observed after 24-hour culture in neurogenic media, and the transcript levels of the neurogenic markers increased during the prolonged induction period. Moreover, oPB-MSCs expressed the cellular prion protein gene (PRNP), which was up-regulated during neurogenesis

  10. MR phase-contrast imaging in pulmonary hypertension.

    PubMed

    Reiter, Ursula; Reiter, Gert; Fuchsjäger, Michael

    2016-07-01

    Pulmonary hypertension (PH) is a life-threatening, multifactorial pathophysiological haemodynamic condition, diagnosed when the mean pulmonary arterial pressure equals or exceeds 25 mmHg at rest during right heart catheterization. Cardiac MRI, in general, and MR phase-contrast (PC) imaging, in particular, have emerged as potential techniques for the standardized assessment of cardiovascular function, morphology and haemodynamics in PH. Allowing the quantification and characterization of macroscopic cardiovascular blood flow, MR PC imaging offers non-invasive evaluation of haemodynamic alterations associated with PH. Techniques used to study the PH include both the routine two-dimensional (2D) approach measuring predominant velocities through an acquisition plane and the rapidly evolving four-dimensional (4D) PC imaging, which enables the assessment of the complete time-resolved, three-directional blood-flow velocity field in a volume. Numerous parameters such as pulmonary arterial mean velocity, vessel distensibility, flow acceleration time and volume and tricuspid regurgitation peak velocity, as well as the duration and onset of vortical blood flow in the main pulmonary artery, have been explored to either diagnose PH or find non-invasive correlates to right heart catheter parameters. Furthermore, PC imaging-based analysis of pulmonary arterial pulse-wave velocities, wall shear stress and kinetic energy losses grants novel insights into cardiopulmonary remodelling in PH. This review aimed to outline the current applications of 2D and 4D PC imaging in PH and show why this technique has the potential to contribute significantly to early diagnosis and characterization of PH.

  11. Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations

    PubMed Central

    Mobarrez, Fariborz; Vikerfors, Anna; Gustafsson, Johanna T.; Gunnarsson, Iva; Zickert, Agneta; Larsson, Anders; Pisetsky, David S.; Wallén, Håkan; Svenungsson, Elisabet

    2016-01-01

    Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls. MPs were measured with flow cytometry and phenotyped according to phosphatidylserine expression (PS+/PS−), cellular origin and inflammatory markers. MPs, regardless of phenotype, are 2–10 times more abundant in SLE blood compared to controls. PS− MPs predominated in SLE, but not in controls (66% vs. 42%). Selectively in SLE, PS− MPs were more numerous in females and smokers. MP numbers decreased with declining renal function, but no clear association with disease activity was observed. The striking abundance of MPs, especially PS− MPs, suggests a generalized disturbance in SLE. MPs may be regarded as “liquid biopsies” to assess the production and clearance of dead, dying and activated cells, i.e. pivotal events for SLE pathogenesis. PMID:27777414

  12. Characterization and Optimization of Trans-Blood-Brain Barrier Diffusion In Vivo

    NASA Astrophysics Data System (ADS)

    Konofagou, Elisa E.; Choi, James; Baseri, Babak; Lee, Ann

    2009-04-01

    Current treatments of neurological and neurodegenerative diseases are limited due to the lack of a truly noninvasive, transient, and regionally selective brain drug delivery method. The brain is particularly difficult to deliver drugs to because of the blood-brain barrier (BBB). Over the past few years, we have been developing methods that combine Focused Ultrasound (FUS) and microbubbles in order to noninvasively, locally and transiently open the BBB so as to treat neurodegenerative diseases. In this paper, we will focus on the characterization of the type of molecular delivery that can be induced through the opened BBB. More specifically, we will characterize important properties of the BBB opening such as its reversibility and permeability using fluorescence and MR imaging techniques, respectively. Results on both wildtype and Alzheimer's model mice showed that the timeline of BBB opening is very similar between the presence and absence of amyloid plaques. The permeability change induced by BBB opening was found to increase by up to a 10-fold and to similar levels with those found in literature for glioma tumors.

  13. Identification and characterization of Daldinia eschscholtzii isolated from skin scrapings, nails, and blood

    PubMed Central

    Ng, Kee Peng; Chan, Chai Ling; Yew, Su Mei; Yeo, Siok Koon; Toh, Yue Fen; Looi, Hong Keat; Na, Shiang Ling; Lee, Kok Wei; Yee, Wai-Yan

    2016-01-01

    Background Daldinia eschscholtzii is a filamentous wood-inhabiting endophyte commonly found in woody plants. Here, we report the identification and characterization of nine D. eschscholtzii isolates from skin scrapings, nail clippings, and blood. Methods The nine isolates were identified based on colony morphology, light microscopy, and internal transcribed spacer (ITS)-based phylogeny. In vitro antifungal susceptibility of the fungal isolates was evaluated by the Etest to determine the minimum inhibitory concentration (MIC). Results The nine isolates examined were confirmed as D. eschscholtzii. They exhibited typical features of Daldinia sp. on Sabouraud Dextrose Agar, with white felty colonies and black-gray coloration on the reverse side. Septate hyphae, branching conidiophore with conidiogenous cells budding from its terminus, and nodulisporium-like conidiophores were observed under the microscope. Phylogenetic analysis revealed that the nine isolates were clustered within the D. eschscholtzii species complex. All the isolates exhibited low MICs against azole agents (voriconazole, posaconazole, itraconazole, and ketoconazole), as well as amphotericin B, with MIC of less than 1 µg/ml. Discussion Early and definitive identification of D. eschscholtzii is vital to reducing misuse of antimicrobial agents. Detailed morphological and molecular characterization as well as antifungal profiling of D. eschscholtzii provide the basis for future studies on its biology, pathogenicity, and medicinal potential. PMID:28028453

  14. Elevated blood plasma levels of epinephrine, norepinephrine, tyrosine hydroxylase, TGFβ1, and TNFα associated with high-altitude pulmonary edema in an Indian population

    PubMed Central

    Pandey, Priyanka; Ali, Zahara; Mohammad, Ghulam; Pasha, M A Qadar

    2016-01-01

    Biomarkers are essential to unravel the locked pathophysiology of any disease. This study investigated the role of biomarkers and their interactions with each other and with the clinical parameters to study the physiology of high-altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) against adapted highlanders (HLs) and healthy sojourners, HAPE-controls (HAPE-c). For this, seven circulatory biomarkers, namely, epinephrine, norepinephrine, tyrosine hydroxylase, transforming growth factor beta 1, tumor necrosis factor alpha (TNFα), platelet-derived growth factor beta beta, and C-reactive protein (CRP), were measured in blood plasma of the three study groups. All the subjects were recruited at ~3,500 m, and clinical features such as arterial oxygen saturation (SaO2), body mass index, and mean arterial pressure were measured. Increased levels of epinephrine, norepinephrine, tyrosine hydroxylase, transforming growth factor-beta 1, and TNFα were observed in HAPE-p against the healthy groups, HAPE-c, and HLs (P<0.0001). CRP levels were decreased in HAPE-p against HAPE-c and HLs (P<0.0001). There was no significant difference or very marginal difference in the levels of these biomarkers in HAPE-c and HLs (P>0.01). Correlation analysis revealed a negative correlation between epinephrine and norepinephrine (P=4.6E−06) in HAPE-p and positive correlation in HAPE-c (P=0.004) and HLs (P=9.78E−07). A positive correlation was observed between TNFα and CRP (P=0.004) in HAPE-p and a negative correlation in HAPE-c (P=4.6E−06). SaO2 correlated negatively with platelet-derived growth factor beta beta (HAPE-p; P=0.05), norepinephrine (P=0.01), and TNFα (P=0.005) and positively with CRP (HAPE-c; P=0.02) and norepinephrine (HLs; P=0.04). Body mass index correlated negatively with epinephrine (HAPE-p; P=0.001) and positively with norepinephrine and tyrosine hydroxylase in HAPE-c (P<0.05). Mean arterial pressure correlated positively with TNFα in HAPE-p and norepinephrine in

  15. Elevated blood plasma levels of epinephrine, norepinephrine, tyrosine hydroxylase, TGFβ1, and TNFα associated with high-altitude pulmonary edema in an Indian population.

    PubMed

    Pandey, Priyanka; Ali, Zahara; Mohammad, Ghulam; Pasha, M A Qadar

    2016-01-01

    Biomarkers are essential to unravel the locked pathophysiology of any disease. This study investigated the role of biomarkers and their interactions with each other and with the clinical parameters to study the physiology of high-altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) against adapted highlanders (HLs) and healthy sojourners, HAPE-controls (HAPE-c). For this, seven circulatory biomarkers, namely, epinephrine, norepinephrine, tyrosine hydroxylase, transforming growth factor beta 1, tumor necrosis factor alpha (TNFα), platelet-derived growth factor beta beta, and C-reactive protein (CRP), were measured in blood plasma of the three study groups. All the subjects were recruited at ~3,500 m, and clinical features such as arterial oxygen saturation (SaO2), body mass index, and mean arterial pressure were measured. Increased levels of epinephrine, norepinephrine, tyrosine hydroxylase, transforming growth factor-beta 1, and TNFα were observed in HAPE-p against the healthy groups, HAPE-c, and HLs (P<0.0001). CRP levels were decreased in HAPE-p against HAPE-c and HLs (P<0.0001). There was no significant difference or very marginal difference in the levels of these biomarkers in HAPE-c and HLs (P>0.01). Correlation analysis revealed a negative correlation between epinephrine and norepinephrine (P=4.6E-06) in HAPE-p and positive correlation in HAPE-c (P=0.004) and HLs (P=9.78E-07). A positive correlation was observed between TNFα and CRP (P=0.004) in HAPE-p and a negative correlation in HAPE-c (P=4.6E-06). SaO2 correlated negatively with platelet-derived growth factor beta beta (HAPE-p; P=0.05), norepinephrine (P=0.01), and TNFα (P=0.005) and positively with CRP (HAPE-c; P=0.02) and norepinephrine (HLs; P=0.04). Body mass index correlated negatively with epinephrine (HAPE-p; P=0.001) and positively with norepinephrine and tyrosine hydroxylase in HAPE-c (P<0.05). Mean arterial pressure correlated positively with TNFα in HAPE-p and norepinephrine in HLs (P

  16. Inflammatory cytokines in pulmonary hypertension

    PubMed Central

    2014-01-01

    Pulmonary hypertension is an “umbrella term” used for a spectrum of entities resulting in an elevation of the pulmonary arterial pressure. Clinical symptoms include dyspnea and fatigue which in the absence of adequate therapeutic intervention may lead to progressive right heart failure and death. The pathogenesis of pulmonary hypertension is characterized by three major processes including vasoconstriction, vascular remodeling and microthrombotic events. In addition accumulating evidence point to a cytokine driven inflammatory process as a major contributor to the development of pulmonary hypertension. This review summarizes the latest clinical and experimental developments in inflammation associated with pulmonary hypertension with special focus on Interleukin-6, and its role in vascular remodeling in pulmonary hypertension. PMID:24739042

  17. Ultrastructural characterization of the pulmonary cellular defences in the lung of a bird, the rock dove, Columba livia

    PubMed Central

    Maina, J. N.; Cowley, H. M.

    1998-01-01

    Free (surface) avian respiratory macrophages (FARMs) were harvested by lavage of the lung/air-sac system of the rock dove, Columba livia. The presence of FARMs in the atria and infundibula was confirmed by scanning electron microscopy. The respiratory system has developed several cellular defence lines that include surface macrophages, epithelial, subepithelial and interstitial phagocytes, and pulmonary intravascular macrophages (PIMs). Hence, C. livia appears to have a multiple pulmonary cellular protective armoury. Ultrastructurally, the FARMs and the PIMs were similar to the corresponding cells of mammals. The purported high susceptibility of birds to respiratory diseases, a state that has largely been deduced from morbidities and mortalities of commercial birds, and which has chiefly been attributed to paucity of the FARMs, is not supported by the present observations.

  18. Diagnosis of Intra-Abdominal Extralobar Pulmonary Sequestration by means of Ultrasound in a Neonate

    PubMed Central

    Pires, Claudio Rodrigues; Czapkowski, Adriano; Zanforlin Filho, Sebastião Marques

    2013-01-01

    Pulmonary sequestration is a congenital abnormality consisting of a mass of pulmonary tissue that presents an abnormal connection with the tracheobronchial tree, with a blood supply coming from an anomalous artery derived from the systemic circulation. Extralobar pulmonary sequestration is characterized by having pleural coverings that are independent of the normal lungs, with vascular supply usually coming from the aorta or from one of its branches. This diagnosis can be suspected prenatally if an abdominal mass, generally below the diaphragm, is seen. Here, we present a case of a neonate on the second day of life, with ultrasonography showing extralobar pulmonary sequestration located above the left adrenal gland that prenatally simulated a neuroblastoma. PMID:23762717

  19. Asymptomatic Pulmonary Vein Stenosis: Hemodynamic Adaptation and Successful Ablation

    PubMed Central

    Weinberg, Denis

    2016-01-01

    Pulmonary vein stenosis is a well-established possible complication following an atrial fibrillation ablation of pulmonary veins. Symptoms of pulmonary vein stenosis range from asymptomatic to severe exertional dyspnea. The number of asymptomatic patients with pulmonary vein stenosis is greater than originally estimated; moreover, only about 22% of severe pulmonary vein stenosis requires intervention. We present a patient with severe postatrial fibrillation (AF) ablation pulmonary vein (PV) stenosis, which was seen on multiple imaging modalities including cardiac computed tomography (CT) angiogram, lung perfusion scan, and pulmonary angiogram. This patient did not have any pulmonary symptoms. Hemodynamic changes within a stenosed pulmonary vein might not reflect the clinical severity of the obstruction if redistribution of pulmonary artery flow occurs. Our patient had an abnormal lung perfusion and ventilation (V/Q) scan, suggesting pulmonary artery blood flow redistribution. The patient ultimately underwent safe repeat atrial fibrillation ablation with successful elimination of arrhythmia. PMID:28105376

  20. Microarray analysis in pulmonary hypertension

    PubMed Central

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea

    2016-01-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  1. Microarray analysis in pulmonary hypertension.

    PubMed

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea; Kwapiszewska, Grazyna

    2016-07-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance.

  2. Detection and characterization of red blood cell (RBC) aggregation with photoacoustics

    NASA Astrophysics Data System (ADS)

    Hysi, Eno; Saha, Ratan K.; Rui, Min; Kolios, Michael C.

    2012-02-01

    Red blood cells (RBCs) aggregate in the presence of increased plasma fibrinogen and low shear forces during blood flow. RBC aggregation has been observed in deep vein thrombosis, sepsis and diabetes. We propose using photoacoustics (PA) as a non-invasive imaging modality to detect RBC aggregation. The theoretical and experimental feasibility of PA for detecting and characterizing aggregation was assessed. A simulation study was performed to generate PA signals from non-aggregated and aggregated RBCs using a frequency domain approach and to study the PA signals' dependence on hematocrit and aggregate size. The effect of the finite bandwidth nature of transducers on the PA power spectra was also investigated. Experimental confirmation of theoretical results was conducted using porcine RBC samples exposed to 1064 nm optical wavelength using the Imagio Small Animal PA imaging system (Seno Medical Instruments, Inc., San Antonio, TX). Aggregation was induced with Dextran-70 (Sigma-Aldrich, St. Louis, MO) and the effect of hematocrit and aggregation level was investigated. The theoretical and experimental PA signal amplitude increased linearly with increasing hematocrit. The theoretical dominant frequency content of PA signals shifted towards lower frequencies (<30 MHz) and 9 dB enhancements in spectral power were observed as the size of aggregates increased compared to non-aggregating RBCs. Calibration of the PA spectra with the transducer response obtained from a 200 nm gold film was performed to remove system dependencies. Analysis of the spectral parameters from the calibrated spectra suggested that PA can assess the degree of aggregation at multiple hematocrit and aggregation levels.

  3. Fluid dynamic characterization of operating conditions for continuous flow blood pumps.

    PubMed

    Wu, Z J; Antaki, J F; Burgreen, G W; Butler, K C; Thomas, D C; Griffith, B P

    1999-01-01

    As continuous flow pumps become more prominent as long-term ventricular assist devices, the wide range of conditions under which they must be operated has become evident. Designed to operate at a single, best-efficiency, operating point, continuous flow pumps are required to perform at off-design conditions quite frequently. The present study investigated the internal fluid dynamics within two representative rotary fluid pumps to characterize the quality of the flow field over a full range of operating conditions. A Nimbus/UoP axial flow blood pump and a small centrifugal pump were used as the study models. Full field visualization of flow features in the two pumps was conducted using a laser based fluorescent particle imaging technique. Experiments were performed under steady flow conditions. Flow patterns at inlet and outlet sections were visualized over a series of operating points. Flow features specific to each pump design were observed to exist under all operating conditions. At off-design conditions, an annular region of reverse flow was commonly observed within the inlet of the axial pump, while a small annulus of backflow in the inlet duct and a strong disturbed flow at the outlet tongue were observed for the centrifugal pump. These observations were correlated to a critical nondimensional flow coefficient. The creation of a "map" of flow behavior provides an additional, important criterion for determining favorable operating speed for rotary blood pumps. Many unfavorable flow features may be avoided by maintaining the flow coefficient above a characteristic critical coefficient for a particular pump, whereas the intrinsic deleterious flow features can only be minimized by design improvement. Broadening the operating range by raising the band between the critical flow coefficient and the designed flow coefficient, is also a worthy goal for design improvement.

  4. A rare case of human pulmonary dirofilariasis with a growing pulmonary nodule after migrating infiltration shadows, mimicking primary lung carcinoma

    PubMed Central

    Haro, Akira; Tamiya, Sadafumi; Nagashima, Akira

    2016-01-01

    Introduction Pulmonary dirofilariasis is a rare pulmonary parasitic infection by the nematode Dirofilaria immitis. It is characterized by an asymptomatic pulmonary nodule usually seen on chest X-ray. The differential diagnosis of pulmonary dirofilariasis includes other pulmonary diseases, primary lung carcinoma and metastatic lung tumor. Case presentation Pulmonary dirofilariasis was diagnosed in a woman who presented with interstitial pneumonia. Growth of the pulmonary nodule was detected subsequent to hemoptysis. The histological diagnosis was made based on a wedge resection performed under video-associated thoracic surgery (VATS). Conclusion Pulmonary dirofilariasis often varies in its clinical course. The diagnosis is best made using wedge resection under VATS. PMID:27015012

  5. Pulmonary intimal sarcoma treated by a left pneumonectomy with pulmonary arterioplasty under cardiopulmonary bypass: report of a case.

    PubMed

    Nakajima, Jun; Morota, Tetsuro; Matsumoto, Jun; Takazawa, Yutaka; Murakawa, Tomohiro; Fukami, Takeshi; Yamamoto, Tetsufumi; Takamoto, Shinichi

    2007-01-01

    Intimal sarcoma of the pulmonary artery is a rare disease. This neoplasm was characterized by an aggressive extension to the lumen of the pulmonary artery, thus mimicking a pulmonary thromboembolism. We herein report a 44-year-old woman who was diagnosed as having primary intimal sarcoma of the left lung preoperatively by transbronchial biopsy. The tumor originated in the pulmonary artery in the left lung, extending to the main pulmonary trunk via the pulmonary arterial lumen, thus resulting in stenosis of the main pulmonary trunk. A complete resection of the tumor with the left pneumonectomy and the pulmonary arterioplasty was successfully performed under cardiopulmonary bypass with vacuum assisted venous drainage.

  6. Poststreptococcal glomerulonephritis with pulmonary edema presenting as respiratory distress.

    PubMed

    Chiu, Chih-Yung; Huang, Yhu-Chering; Wong, Kin-Sun; Hsia, Shao-Hsuan; Lin, Chi-Jen; Lin, Tzou-Yien

    2004-11-01

    Acute poststreptococcal glomerulonephritis(PSGN) is characterized by an abrupt onset of edema,hypertension, and hematuria. Although the association of pulmonary edema with acute glomerulonephritis has been established, it is uncommon for children with PSGN to present with respiratory distress due to pulmonary edema. We encountered six such patients, aged 6-10 years, during a 10-month period. The demographic data, clinical manifestations, laboratory data, radiographic pictures, and clinical courses were collected. All patients presented to the primary pediatricians with dyspnea and alveolar infiltrates with bilateral pleural effusions on plain chest radiographs that were misinterpreted as pneumonia initially. The diagnosis of PSGN was de-layed until the awareness of the presence of pulmonary edema complicating PSGN. Subsequent urinalysis and blood pressure measurement all showed microscopic hematuria and hypertension. Elevated serum antistreptolysin 0 titers and depressed serum complement C3 levels confirmed the diagnosis of PSGN. Two patients progressed to respiratory failure because of a delayed diagnosis of PSGN. All patients recovered without sequelae following appropriate diuresis and antihypertensive therapy. We conclude that in preschool and school-age children who present with dyspneic respirations and a chest radiograph showing radiographic features of pulmonary edema, proper evaluation including blood pressure recording and urinalysis should be performed immediately. Prompt diagnosis and early therapy of PSGNmay avoid mortality and unnecessary therapeutic intervention.

  7. ["Flash" pulmonary edema as a clinical manifestation of renovascular hypertension].

    PubMed

    Kalimonovska-Ostrić, Dimitra; Ivanović, Branislava; Ostrić, Vladimir; Knezivić, Vesna; Stojanov, Vesna; Simić, Dragan

    2003-01-01

    One of the clinical manifestations of renovascular hypertension (RVH) may be a recurrent pulmonary oedema both in the absence or in the presence of systolic left ventricular dysfunction. This type of pulmonary oedema characterized as "flash" pulmonary oedema is ascribed to elevated angiotensin II concentrations with consequent hypertension as well as to volume overload resulting from decreased pressor natriuresis when there are significant stenoses of both or one renal arteries. The investigation included 30 patients with RVH treated by percutaneous transluminal angioplasty of the stenosed renal artery (PTRA) and/or stent implantation (PTR-ST) and 30 patients with surgical resection of the abdominal aortic aneurysm (AAA). The first group was divided in two subgroups according to the etiology of renal artery stenosis (RAS). In the subgroup with fibromuscular dysplasia (FMD) the mean age was 37.5 years, in the subgroup with atherosclerotic renal artery stenosis (ARAS) 54.8 years and in the group with operated AAA 68.6 years. There were more females than males only in the FMD subgroup (10:3). Two patients of the first group experienced pulmonary oedema, both in the subgroup with atherosclerotic renal artery stenosis associated with atherosclerosis of other arteries. Normalization of the blood pressure following PTRA in both and an uncomplicated course after a surgical myocardial revascularization in one of them illustrates the importance of renal revascularization. Pulmonary oedema occurred preoperatively in four out of 30 patients with abdominal aortic aneurysm in whom significant renal artery stenoses coexisted. Two patients died despite surgery, one patient is clinically stable and the medicament treatment of heart failure is inevitable in the fourth with a left ventricular aneurysm following myocardial infarction. The occurrence or recurrence of pulmonary oedema in the absence of other explanation should suggest the possibility of bilateral or unilateral renal

  8. Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery

    PubMed Central

    Duan, Jinghua; Vogt, Frederick G; Li, Xiaojian; Hayes, Don; Mansour, Heidi M

    2013-01-01

    The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders. PMID:24092972

  9. Pulmonary Embolism

    MedlinePlus

    ... for the Public » Health Topics » Pulmonary Embolism Explore Pulmonary Embolism What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Arrhythmia Deep Vein Thrombosis Lung VQ Scan Overweight and Obesity Send a ...

  10. Spectral feature characterization methods for blood stain detection in crime scene backgrounds

    NASA Astrophysics Data System (ADS)

    Yang, Jie; Mathew, Jobin J.; Dube, Roger R.; Messinger, David W.

    2016-05-01

    Blood stains are one of the most important types of evidence for forensic investigation. They contain valuable DNA information, and the pattern of the stains can suggest specifics about the nature of the violence that transpired at the scene. Blood spectral signatures containing unique reflectance or absorption features are important both for forensic on-site investigation and laboratory testing. They can be used for target detection and identification applied to crime scene hyperspectral imagery, and also be utilized to analyze the spectral variation of blood on various backgrounds. Non-blood stains often mislead the detection and can generate false alarms at a real crime scene, especially for dark and red backgrounds. This paper measured the reflectance of liquid blood and 9 kinds of non-blood samples in the range of 350 nm - 2500 nm in various crime scene backgrounds, such as pure samples contained in petri dish with various thicknesses, mixed samples with different colors and materials of fabrics, and mixed samples with wood, all of which are examined to provide sub-visual evidence for detecting and recognizing blood from non-blood samples in a realistic crime scene. The spectral difference between blood and non-blood samples are examined and spectral features such as "peaks" and "depths" of reflectance are selected. Two blood stain detection methods are proposed in this paper. The first method uses index to denote the ratio of "depth" minus "peak" over"depth" add"peak" within a wavelength range of the reflectance spectrum. The second method uses relative band depth of the selected wavelength ranges of the reflectance spectrum. Results show that the index method is able to discriminate blood from non-blood samples in most tested crime scene backgrounds, but is not able to detect it from black felt. Whereas the relative band depth method is able to discriminate blood from non-blood samples on all of the tested background material types and colors.

  11. Pulmonary blastomycosis.

    PubMed

    Bariola, J Ryan; Vyas, Keyur S

    2011-12-01

    Blastomyces dermatitidis is acquired in almost all cases via inhalation, and pulmonary disease is the most frequent clinical manifestation of blastomycosis. Pulmonary disease can range from asymptomatic infection to rapidly severe and fatal disease. Most cases will present as pneumonia, either acute or chronic, or as a lung mass. In rare cases pulmonary blastomycosis is associated with the acute respiratory distress syndrome. Blastomycosis can present as isolated pulmonary disease or along with coexisting extrapulmonary disease that usually will involve the skin, bony structures, genitourinary tract, or central nervous system. Diagnosis is largely based on isolation of the organism via culture or visualization of the organism in clinical specimens. Detection of urinary Blastomyces antigen is a recent addition to diagnostic options. Itraconazole is the drug of choice for most forms of the disease; amphotericin B is reserved for the more severe forms. Newer azoles such as voriconazole and posaconazole have a limited role in the treatment of pulmonary blastomycosis.

  12. Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood.

    PubMed

    Zhang, Qian; Wang, Lili; Luo, Chenghan; Shi, Zanyang; Cheng, Xinru; Zhang, Zhen; Yang, Yi; Zhang, Yi

    2014-11-01

    Cord blood has gradually become an important source for hematopoietic stem cell transplantation (HSCT) in the human, particularly in pediatric patients. Adoptive cellular immunotherapy of patients with hematologic malignancies after umbilical cord blood transplant is crucial. Cytokine‑induced killer (CIK) cells derived from cord blood are a new type of antitumor immune effector cells in tumor prevention and treatment and have increasingly attracted the attention of researchers. On the other hand, it has been suggested that preterm infant cord blood retains an early differentiation phenotype suitable for immunotherapy. Therefore, we determined the phenotypic and functional characterization of CIK cells derived from preterm infant cord blood (PCB-CIK) compared with CIK cells from term infant cord blood (TCB-CIK). Twenty cord blood samples were collected and classified into two groups based on gestational age. Cord blood mononuclear cells (CBMCs) were isolated, cultured and induced to CIK cells in vitro. We used flow cytometry to detect cell surface markers, FlowJo software to analyze the proliferation profile and intracellular staining to test the secretion of cytokines. Finally, we evaluated the antitumor activity of CIK cells against K562 in vitro. Compared with TCB-CIK, PCB-CIK cells demonstrated faster proliferation and higher expression of activated cell surface markers. The secretion of IL-10 was lower in PCB-CIK cells while the expression of perforin and CD107a had no significant difference between the two cell groups. PCB-CIK cells exhibited a high proliferation rate while the cytotoxic activity had no difference between the PCB-CIK and TCB-CIK cells. Hence preterm infant cord blood may be a potential source for immunotherapy.

  13. Pulmonary function in space

    NASA Technical Reports Server (NTRS)

    West, J. B.; Elliott, A. R.; Guy, H. J.; Prisk, G. K.

    1997-01-01

    The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth.

  14. A case of negative pressure pulmonary edema in an asthmatic patient after laparoscopic cholecystectomy

    PubMed Central

    Rasheed, Asim; Palaria, Urmila; Rani, Dolly; Sharma, Shatrunjay

    2014-01-01

    Negative pressure pulmonary edema is often misdiagnosed or can go clinically unrecognized by anesthesiologists. It is characterized by a markedly low intrapleural pressure which leads to exudation of fluid and red blood cells in the interstitium. Recognition of patients with predisposing factors for upper airway obstruction is important in the diagnosis which is often confused with pulmonary aspiration of gastric contents. Signs and symptoms are subtle and edema is usually self-limited. Our patient was management conservatively with maintenance of a patent airway and administration of supplemental oxygen and had a successful outcome. PMID:25886111

  15. Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients.

    PubMed

    do Nascimento, Eloisa Sanches Pereira; Sampaio, Luciana Maria Malosá; Peixoto-Souza, Fabiana Sobral; Dias, Fernanda Dultra; Gomes, Evelim Leal Freitas Dantas; Greiffo, Flavia Regina; Ligeiro de Oliveira, Ana Paula; Stirbulov, Roberto; Vieira, Rodolfo Paula; Costa, Dirceu

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal inspiratory pressure, improvements on two components from the health-related quality-of-life questionnaire, and a decrease in plasma IL-8 levels after the intervention. The HBPR is an important and viable alternative to pulmonary rehabilitation for the treatment of patients with COPD; it improves exercise tolerance, inspiratory muscle strength, quality of life, and systemic inflammation in COPD patients.

  16. Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients

    PubMed Central

    do Nascimento, Eloisa Sanches Pereira; Sampaio, Luciana Maria Malosá; Peixoto-Souza, Fabiana Sobral; Dias, Fernanda Dultra; Gomes, Evelim Leal Freitas Dantas; Greiffo, Flavia Regina; Ligeiro de Oliveira, Ana Paula; Stirbulov, Roberto; Vieira, Rodolfo Paula; Costa, Dirceu

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal inspiratory pressure, improvements on two components from the health-related quality-of-life questionnaire, and a decrease in plasma IL-8 levels after the intervention. The HBPR is an important and viable alternative to pulmonary rehabilitation for the treatment of patients with COPD; it improves exercise tolerance, inspiratory muscle strength, quality of life, and systemic inflammation in COPD patients. PMID:25848241

  17. Characterizing the Blood Oxygen Level-Dependent Fluctuations in Musculoskeletal Tumours Using Functional Magnetic Resonance Imaging

    PubMed Central

    Duan, Li-Sha; Wang, Meng-Jun; Sun, Feng; Zhao, Zhen-Jiang; Xing, Mei; Zang, Yu-Feng; Louis, Steven; Cui, Sheng-Jie; Cui, Jian-Ling; Zhang, Han

    2016-01-01

    This study characterized the blood oxygen level-dependent (BOLD) fluctuations in benign and malignant musculoskeletal tumours via power spectrum analyses in pre-established low-frequency bands. BOLD MRI and T1-weighted imaging (T1WI) were collected for 52 patients with musculoskeletal tumours. Three ROIs were drawn on the T1WI image in the tumours’ central regions, peripheral regions and neighbouring tissue. The power spectrum of the BOLD within each ROI was calculated and divided into the following four frequency bands: 0.01–0.027 Hz, 0.027–0.073 Hz, 0.073–0.198 Hz, and 0.198–0.25 Hz. ANOVA was conducted for each frequency band with the following two factors: the location of the region of interest (LoR, three levels: tumour “centre”, “peripheral” and “healthy tissue”) and tumour characteristic (TC, two levels: “malignant” and “benign”). There was a significant main effect of LoR in the frequencies of 0.073–0.198 Hz and 0.198–0.25 Hz. These data were further processed with post-hoc pair-wise comparisons. BOLD fluctuations at 0.073–0.198 Hz were stronger in the peripheral than central regions of the malignant tumours; however, no such difference was observed for the benign tumours. Our findings provide evidence that the BOLD signal fluctuates with spatial heterogeneity in malignant musculoskeletal tumours at the frequency band of 0.073–0.198 Hz. PMID:27845359

  18. Microcontroller-based system for collecting anaerobic blood samples from a running greyhound.

    PubMed

    Schmalzried, R T; Toll, P W; Devore, J J; Fedde, M R

    1992-04-01

    Many physiological variables change rapidly in the blood during sprint exercise. To characterize the dynamics and extent of these changes, blood samples must be obtained during exercise. We describe herein a portable, microcontroller-based system used to automatically obtain repeated, anaerobic, arterial blood samples from greyhounds before, during, and following a race on a track. In addition, the system also records the blood temperature in the pulmonary artery each time a blood sample is taken. The system has been tested for more than 2 years and has proven to be reliable and effective.

  19. Phylogenetic characterization of hantaviruses from wild rodents and hantavirus pulmonary syndrome cases in the state of Parana (southern Brazil).

    PubMed

    Raboni, Sonia Mara; Hoffmann, Federico G; Oliveira, Renata C; Teixeira, Bernardo R; Bonvicino, Cibele R; Stella, Vanessa; Carstensen, Suzana; Bordignon, Juliano; D'Andrea, Paulo S; Lemos, Elba R S; Duarte Dos Santos, Claudia Nunes

    2009-09-01

    Over 1,100 cases of hantavirus pulmonary syndrome (HPS) have occurred in Brazil since 1993, but little is known about Brazilian hantaviruses, and many of their rodent hosts remain unknown. The Araucaria hantavirus (ARAUV) was described recently from HPS patients from Paraná, in southern Brazil, but its host could not be identified. In this study, rodents were captured from regions with high HPS prevalence to address this issue. ARAUV RNA was detected in three distantly related rodent species: Oligoryzomys nigripes, Oxymycterus judex and Akodon montensis. Furthermore, a specimen of A. montensis was infected with a Jaborá-like virus, implying that A. montensis can be infected by at least two different hantaviruses. The presence of the same hantavirus strain in three different rodent species and the co-circulation of two different strains in the same rodent species highlight the potential for genomic reassortment, which could have an impact on hantavirus transmission dynamics in nature and on human epidemiology.

  20. An Elevated Peripheral Blood Monocyte-to-Lymphocyte Ratio Predicts Poor Prognosis in Patients with Primary Pulmonary Lymphoepithelioma-Like Carcinoma.

    PubMed

    Wang, Liang; Long, Wen; Li, Peng-fei; Lin, Yong-bin; Liang, Ying

    2015-01-01

    Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer. In this study, we retrospectively reviewed the data from 74 consecutive patients with pulmonary LELC and investigated the prognostic value of pretreatment monocyte-to-lymphocyte ratio (MLR). The cut-off value determined by ROC curve for MLR was 0.262. According to this cut-off value, 36 (48.6%) patients had lower MLR value (<0.262) at diagnosis. There was no significant correlation between MLR level and gender, age, smoking history, stage, and lactate dehydrogenase (LDH) level. The 2-year, 5-year, and 10-year OS rate were 86%, 72%, and 61%, respectively; the 2-year, 5-year, and 10-year PFS rate were 71%, 63%, and 49%, respectively. In univariate analysis, advanced stage, elevated LDH level, and higher MLR value (> = 0.262) were significantly associated with poor OS and PFS. In a multivariate Cox regression model that included stage, LDH and MLR level, all of these three factors were found to be independent prognostic factors for both PFS and OS. In patients who received radical surgery, MLR level remained significantly correlated with OS and PFS. In conclusion, we firstly demonstrated that pretreatment MLR can be used as a useful independent prognostic marker in patients with pulmonary LELC, and might guide us to optimize the treatment strategies. However, due to the relatively rarity of this disease and the limitation of a retrospective study, further prospective studies performed in multicenter are necessary to validate the prognostic value of MLR in pulmonary LELC.

  1. [Inhaled nitric oxide: a physiologic treatment of persistent pulmonary arterial hypertension in the newborn].

    PubMed

    Thébaud, B; Mercier, J C

    1997-10-01

    Fetal pulmonary circulation is characterized by high resistance and low pulmonary blood flow. Right-to-left shunting through the foramen ovale and/or patent ductus arteriosus is necessary to perfuse the placenta and insure fetal life. At birth, pulmonary arterial blood flow increases immediately by 8- to 10-fold, and allows pulmonary gas exchange and postnatal life. In some circumstances, this adaptation to extra-uterine life is inadequate, because of persistent high pulmonary resistance (PPHN). Due to the lack of a selective pulmonary vasodilator, the treatment of this syndrome remained purely symptomatic using high oxygen levels and barotraumatic mechanical hyperventilation. When this medical treatment failed, the only alternative was extracorporeal membrane oxygenation (ECMO). The discovery of the major role of various endothelium-derived factors including nitric oxide (NO) in the control of vascular reactivity led to dramatic switches in the concepts of severe neonatal respiratory failure and the therapeutic approach of PPHN. It was shown, first in experimental animals then in a few infants with hypoxemic respiratory failure, that NO inhalation selectively vasodilated the vasoconstricted pulmonary vessels, and reversed right-to-left shunting and refractory hypoxemia. Whether inhaled NO also reduces mortality and/or morbidity in hypoxic infants remains to be proven by appropriate randomized clinical trials. However, not only PPHN is associated with pulmonary diseases of various etiologies and underlying pathophysiologic mechanisms, but also inhaled NO is used in conjunction with other validated therapeutic strategies including ante- or postnatal steroids, exogenous surfactants, and high-frequency oscillatory ventilation. Thus, the relevant primary endpoint might be not only crude survival but the most physiological and economical way of obtaining it.

  2. Polymer Brushes Containing Sulfonated Sugar Repeat Units: Synthesis, Characterization and In Vitro Testing of Blood Coagulation Activation

    PubMed Central

    Ayres, N.; Holt, D. J.; Jones, C.F.; Corum, L. E.; Grainger, D. W.

    2009-01-01

    A new polymer brush chemistry containing sulfonated carbohydrate repeat units has been synthesized from silicon substrates using ATRP methods and characterized both in bulk and using surface analysis. The polymer brush was designed to act as a mimic for the naturally occurring sulfonated glycosaminoglycan, heparin, commonly used for modifying blood-contacting surfaces both in vitro and in vivo. Surface analysis showed conversion of brush saccharide precursor chemistry to the desired sulfonated polymer product. The sulfonated polymer brush surface was further analyzed using three conventional in vitro tests for blood compatibility -- plasma recalcification times, complement activation, and thrombin generation. The sulfonated polymer brush films on silicon oxide wafers exhibited better assay performance in these blood component assays than the unsulfonated sugar functionalized polymer brush in all tests performed. PMID:19859552

  3. Pulmonary aspergilloma

    MedlinePlus

    ... Coccidioidomycosis Cystic fibrosis Histoplasmosis Lung abscess Lung cancer Sarcoidosis The most common species of fungus that causes ... fibrosis Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Review Date 7/31/2016 Updated by: Jatin ...

  4. Pulmonary Agenesis.

    PubMed

    Chawla, Rakesh K; Madan, Arun; Chawla, Aditya; Arora, Harsh Nandini; Chawla, Kiran

    2015-01-01

    Unilateral opaque lung with ipsilateral mediastinal shift is an uncommon cause of respiratory distress in newborn which can be found on simple radiograph of the chest. Pulmonary agenesis is a rare cause of unilateral opaque lung in the newborn. Nearly 50% cases of pulmonary agenesis are associated with other congenital defects including cardiovascular, skeletal, gastrointestinal or genitourinary systems. We report an infant with agenesis of the right lung associated with other congenital anomalies.

  5. In Vivo Noninvasive Characterization of Brown Adipose Tissue Blood Flow by Contrast Ultrasound in Mice

    PubMed Central

    Baron, David M.; Clerte, Maeva; Brouckaert, Peter; Raher, Michael J.; Flynn, Aidan W.; Zhang, Haihua; Carter, Edward A.; Picard, Michael H.; Bloch, Kenneth D.; Buys, Emmanuel S.; Scherrer-Crosbie, Marielle

    2012-01-01

    Background Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow. After validation, CU was used to study the role of uncoupling protein 1 (UCP1) and nitric oxide synthases in the acute regulation of BAT blood flow. Methods and Results Blood flow of interscapular BAT was assessed in mice (n=64) with CU by measuring the signal intensity of continuously infused contrast microbubbles. Blood flow of BAT estimated by CU was 0.5±0.1 (mean±SEM) dB/s at baseline and increased 15-fold during BAT stimulation by norepinephrine (NE, 1 μg·kg−1·min−1). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R2=0.86, p<0.001). To evaluate whether intact BAT activation is required to increase BAT blood flow, CU was performed in UCP1-deficient (UCP1−/−) mice with impaired BAT activation. Norepinephrine infusion induced a smaller increase in BAT blood flow in UCP1−/− mice than in wild-type mice. Finally, we investigated whether NOS played a role in acute NE-induced changes of BAT blood flow. Genetic and pharmacologic inhibition of NOS3 attenuated the NE-induced increase in BAT blood flow. Conclusions These results indicate that CU can detect BAT in mice, and estimate BAT blood flow in mice with functional differences in BAT. PMID:22776888

  6. [Left pulmonary agenesis diagnosed late].

    PubMed

    Deleanu, Oana; Pătraşcu, Natalia; Nebunoiu, Ana-Maria; Vintilă, V; Ulmeanu, Ruxandra; Mihălţan, F D

    2010-01-01

    We present the case of a 51 years old female-patient, with severe dextroscoliosis, having like unique symptom progressive dyspnea. The blood samples reveals polycythemia, the radiological exam shows the opacification of 2/3 of the left thorax, the absence of the lung structure in the other 1/3, the deviation of the mediastinum, and dextroscoliosis; the computed tomography reveals the absence of the left lung artery and the left airways, compensatory hyperinflation of the right lung and dilatation of the trunk and right pulmonary artery; the bronchoscopy does not visualize the carina or the left main bronchus, typical for pulmonary agenesis. Echocardiography confirmed the absence of left pulmonary artery and shows mild pulmonary hypertension (systolic pressure in the pulmonary artery of 33 mmHg) with dilatation of the right cavities, but good cinetics. We face a case of pulmonary agenesis lately diagnosed, with modest functional cardiologic implications, limited therapeutic options and good survival, justified by the late appearance of the pulmonary hypertension of low severity and without worsening in time.

  7. Characterization of t1 relaxation and blood-myocardial contrast enhancement of NC100150 injection in cardiac MRI.

    PubMed

    Wagenseil, J E; Johansson, L O; Lorenz, C H

    1999-11-01

    A new ultrasmall superparamagnetic iron oxide (Clariscan; NC100150 Injection) was studied in domestic farm pigs. The T1 effects were characterized for blood and myocardium and the blood-myocardial contrast was measured in T1-weighted cine images. The contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were measured at baseline and contrast doses of 1 and 5 mg Fe/kg body weight (bw) at end diastole and late systole. The T1 values for blood and myocardium were reduced by 97 and 43%, respectively, from baseline to 5 mg Fe/kg bw. The CNR was significantly improved with contrast at end diastole and late systole. The maximum improvement shown was 202% at 5 mg Fe/kg bw in late systole. The percent SNR enhancement was significantly higher in blood than myocardium at late systole. NC100150 Injection is an effective T1 shortening agent and can be used to improve blood-myocardial contrast in cine images of the heart. J. Magn. Reson. Imaging 1999;10:784-789.

  8. Preparation, characterization and in vivo investigation of blood-compatible hemoglobin-loaded nanoparticles as oxygen carriers.

    PubMed

    Lu, Mingzi; Zhao, Caiyan; Wang, Quan; You, Guoxing; Wang, Ying; Deng, Hongzhang; Chen, Gan; Xia, Sha; Zhao, Jingxiang; Wang, Bo; Li, Xianlei; Shao, Leihou; Wu, Yan; Zhao, Lian; Zhou, Hong

    2016-03-01

    Although many attempts have been made to design advanced hemoglobin-based oxygen carriers (HBOCs), no clinically viable product has been widely approved, because they do not perform normal blood functions, such as coagulation, hematologic reactions and stability. Additionally, the in vivo oxygenation of hemoglobin-loaded nanoparticles (HbPs) encapsulated with polymers has seldom been proved. Herein, HbPs of approximately 200nm with good stability were successfully fabricated and exhibited oxygen-carrying capacity. The HbPs preserve the biological and structure features of hemoglobin according to UV-vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy and circular dichroism (CD) spectral analysis. In vitro, the HbPs showed a viscosity comparable to that of blood with no obvious effects on red blood cell aggregation. At the same time, blood compatibility was characterized in terms of platelet function, clot strength, speed of clot formation, degree of fibrin cross-linking and hemolysis rate. After intravenous administration of HbPs to mice with controlled hemorrhages, blood flow recovery and maintenance of systemic oxygenation were observed.

  9. Characterization of blood flow rate in dental pulp by speckle patterns of backscattered light from an in vivo tooth

    NASA Astrophysics Data System (ADS)

    Dick, Sergey K.; Chistyakova, Galina G.; Terekh, Alex S.; Smirnov, Alex V.; Salimi Zadeh, Mehrnush M.; Barun, Vladimir V.

    2014-10-01

    Experimental data on the hemodynamics of dental pulp at different stages of caries treatment are given. Observations of speckle patterns in backscattered laser light are used as a measurement method to qualitatively characterize changes in blood flow rate through the dental pulp. The measurements were made by the author-designed experimental setup. Theoretical estimations showed that stationary reflected light from an in vivo tooth contains a negligibly small information body on changes in the pulpal blood flow due to the shadowing of the pulp by optically thick enamel and dentin. Therefore, the temporal variations in the speckle patterns are the only possible way that can provide monitoring of blood conditions in the pulp by using backscattered light. Various statistical characteristics of the random reflected light fields are studied as indicators of blood flow rate changes. There were selected five statistical parameters of backscattered speckle images that give self-consistent data on these changes. The parameters include four combinations of integrals of the Fourier transforms of the observed temporal variations as well as the speckle image contrast. The selected parameters are shown to qualitatively agree with general considerations on the effects of reduced or increased blood flow rates on the selected integral quantities.

  10. Pulmonary Hypertension: Types and Treatments

    PubMed Central

    Rose-Jones, Lisa J; Mclaughlin, Vallerie V

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a panvasculopathy that affects the distal pulmonary arteries and leads to restricted blood flow. This increased afterload leads to adaptive mechanisms of the right ventricle, with eventual failure once it can no longer compensate. Pulmonary hypertension from associated conditions, most importantly left heart disease, i.e. heart failure, can also lead to the same sequela. Patients often experience early vague symptoms of dyspnea and exercise intolerance, and thus PH can elude clinicians until right heart failure symptoms predominate. Evidence-based treatment options with pulmo-nary vasodilators are available for those with PAH and should be employed early. It is essential that patients be accurately categorized by their etiology of PH, as treatment strategies differ, and can potentially be dangerous if employed in the wrong clinical scenario. PMID:24251459

  11. Newly recognized hantaviruses associated with hantavirus pulmonary syndrome in northern Brazil: partial genetic characterization of viruses and serologic implication of likely reservoirs.

    PubMed

    Rosa, Elizabeth S T; Mills, James N; Padula, Paula J; Elkhoury, Mauro R; Ksiazek, Thomas G; Mendes, Wellington S; Santos, Elizabeth D; Araújo, Gisele C B; Martinez, Valeria P; Rosa, Jorge F S T; Edelstein, Alexis; Vasconcelos, Pedro F C

    2005-01-01

    Following the occurrence of the first laboratory-confirmed cases of hantavirus pulmonary syndrome (HPS) in Maranhao State, Brazil, rodents were trapped and rodent materials screened by ELISA for antibodies to Sin Nombre and Andes hantaviruses. Antibody-positive samples were tested by RT-PCR, amplified products were sequenced, and phylogenetic trees were constructed for comparison with known hantaviruses. From 104 rodent blood samples collected (40 Bolomys lasiurus, 52 Holochilus sciureus, 12 Oligoryzomys fornesi, and one Proechimys guyannensis), 21 (20.2%) were antibody-positive (one B. lasiurus, five O. fornesi, and 15 H. sciureus). Hantavirus RNA was amplified by PCR from two O. fornesi and four H. sciureus. Viral sequencing identified two hantavirus genotypes. The genotype recovered from O. fornesi, is designated herein as Anajatuba (ANAJ) and the genotype recovered from H. sciureus is designated Rio Mearim (RIME). Phylogenetic analysis of a 643-nucleotide region of the N segment showed both viruses to be most closely related (94-96% nucleotide homology) to Río Mamoré virus, a virus associated with Oligoryzomys microtis in Bolivia and Peru, but not found in northern Brazil. O. fornesi was frequently captured in and around human dwellings. H. sciureus, is a semi-aquatic rodent captured only in remote areas rarely frequented by humans.

  12. Direct current insulator-based dielectrophoretic characterization of erythrocytes: ABO-Rh human blood typing.

    PubMed

    Srivastava, Soumya K; Artemiou, Andreas; Minerick, Adrienne R

    2011-09-01

    A microfluidic platform developed for quantifying the dependence of erythrocyte (red blood cell, RBC) responses by ABO-Rh blood type via direct current insulator dielectrophoresis (DC-iDEP) is presented. The PDMS DC-iDEP device utilized a 400 x 170 μm² rectangular insulating obstacle embedded in a 1.46-cm long, 200-μm wide inlet channel to create spatial non-uniformities in direct current (DC) electric field density realized by separation into four outlet channels. The DC-iDEP flow behaviors were investigated for all eight blood types (A+, A-, B+, B-, AB+, AB-, O+, O-) in the human ABO-Rh blood typing system. Three independent donors of each blood type, same donor reproducibility, different conductivity buffers (0.52-9.1 mS/cm), and DC electric fields (17.1-68.5 V/cm) were tested to investigate separation dependencies. The data analysis was conducted from image intensity profiles across inlet and outlet channels in the device. Individual channel fractions suggest that the dielectrophoretic force experienced by the cells is dependent on erythrocyte antigen expression. Two different statistical analysis methods were conducted to determine how distinguishable a single blood type was from the others. Results indicate that channel fraction distributions differ by ABO-Rh blood types suggesting that antigens present on the erythrocyte membrane polarize differently in DC-iDEP fields. Under optimized conductivity and field conditions, certain blind blood samples could be sorted with low misclassification rates.

  13. Characterization of the attachment mechanisms of tissue-derived cell lines to blood-compatible polymers.

    PubMed

    Hoshiba, Takashi; Nikaido, Mayo; Tanaka, Masaru

    2014-05-01

    Recent advances in biomedical engineering require the development of new types of blood-compatible polymers that also allow non-blood cell attachment for the isolation of stem cells and circulating tumor cells (CTCs) from blood and for the development of artificial organs for use under blood-contact conditions. Poly(2-methoxyethyl acrylate) (PMEA) and poly(tetrafurfuryl acrylate) (PTHFA) were previously identified as blood-compatible polymers. Here, it is demonstrated that cancer cells can attach to the PMEA and PTHFA substrates, and the differences in the attachment mechanisms to the PMEA and PTHFA substrates between cancer cells and platelets are investigated. It is also found that the adsorption-induced deformation of fibrinogen, which is required for the attachment and activation of platelets, does not occur on the PMEA and PTHFA substrates. In contrast, fibronectin is deformed on the PMEA and PTHFA substrates. Therefore, it is concluded that cancer cells and not platelets can attach to the PMEA and PTHFA substrates based on this protein-deformation difference between these substrates. Moreover, it is observed that cancer cells attach to the PMEA substrate via both integrin-dependent and -independent mechanisms and attach to the PTHFA substrate only through an integrin-dependent mechanism. It is expected that PMEA and PTHFA will prove useful for blood-contact biomedical applications.

  14. Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs) from Clinical Blood Samples.

    PubMed

    Gogoi, Priya; Sepehri, Saedeh; Zhou, Yi; Gorin, Michael A; Paolillo, Carmela; Capoluongo, Ettore; Gleason, Kyle; Payne, Austin; Boniface, Brian; Cristofanilli, Massimo; Morgan, Todd M; Fortina, Paolo; Pienta, Kenneth J; Handique, Kalyan; Wang, Yixin

    2016-01-01

    Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization.

  15. Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs) from Clinical Blood Samples

    PubMed Central

    Gogoi, Priya; Sepehri, Saedeh; Zhou, Yi; Gorin, Michael A.; Paolillo, Carmela; Capoluongo, Ettore; Gleason, Kyle; Payne, Austin; Boniface, Brian; Cristofanilli, Massimo; Morgan, Todd M.; Fortina, Paolo; Pienta, Kenneth J.; Handique, Kalyan; Wang, Yixin

    2016-01-01

    Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization. PMID:26808060

  16. Test Your Blood Pressure IQ

    MedlinePlus

    ... How High Blood Pressure is Diagnosed BP vs. Heart Rate Low Blood Pressure Resistant Hypertension Pulmonary Hypertension High Blood Pressure Myths ... Healthy 6 What are the Symptoms of High Blood Pressure? 7 All About Heart Rate (Pulse) 8 Tachycardia | Fast Heart Rate 9 Warning ...

  17. Characterization of Transition to Turbulence for Blood in a Straight Pipe Under Steady Flow Conditions.

    PubMed

    Biswas, Dipankar; Casey, David M; Crowder, Douglas C; Steinman, David A; Yun, Yang H; Loth, Francis

    2016-07-01

    Blood is a complex fluid that, among other things, has been established to behave as a shear thinning, non-Newtonian fluid when exposed to low shear rates (SR). Many hemodynamic investigations use a Newtonian fluid to represent blood when the flow field of study has relatively high SR (>200 s-1). Shear thinning fluids have been shown to exhibit differences in transition to turbulence (TT) compared to that of Newtonian fluids. Incorrect prediction of the transition point in a simulation could result in erroneous hemodynamic force predictions. The goal of the present study was to compare velocity profiles near TT of whole blood and Newtonian blood analogs in a straight rigid pipe with a diameter 6.35 mm under steady flow conditions. Rheology was measured for six samples of whole porcine blood and three samples of a Newtonian fluid, and the results show blood acts as a shear thinning non-Newtonian fluid. Measurements also revealed that blood viscosity at SR = 200 s-1 is significantly larger than at SR = 1000 s-1 (13.8%, p < 0.001). Doppler ultrasound (DUS) was used to measure velocity profiles for blood and Newtonian samples at different flow rates to produce Reynolds numbers (Re) ranging from 1000 to 3300 (based on viscosity at SR = 1000 s-1). Two mathematically defined methods, based on the velocity profile shape change and turbulent kinetic energy (TKE), were used to detect TT. Results show similar parabolic velocity profiles for both blood and the Newtonian fluid for Re < 2200. However, differences were observed between blood and Newtonian fluid velocity profiles for larger Re. The Newtonian fluid had blunt-like velocity profiles starting at Re = 2403 ± 8 which indicated transition. In contrast, blood did not show this velocity profile change until Re = 2871 ± 104. The Newtonian fluid had large velocity fluctuations (root mean square (RMS) > 20%) with a maximum TKE near the pipe center at Re = 2316 ± 34

  18. Extralobar pulmonary sequestration as a cause of recurrent pulmonary hemorrhage in a neonate.

    PubMed

    Akdag, Arzu; Arici, Sule; Kaya, Mete; Turgut, Ahmet

    2016-02-01

    Pulmonary sequestration is acystic or solid congenital lung malformation comprised of non functional lung tissue that does not communicate with the normal tracheobronchial tree and has a systemic arterial blood supply. There are two forms of sequestration: intralobar and extralobar. Its treatment is surgical resection. Here we presented a case of premature neonate with extralobar pulmonary sequestration who had respiratory failure and recurrent pulmonary hemorrhage. Following surgery, the patient showed significant clinical improvement.

  19. Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure

    SciTech Connect

    Halbrook, R.S.; Shugart, L.R.; Watson, A.P.; Munro, N.B.; Linnabary, R.D. )

    1992-09-01

    A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. A framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.

  20. Extended characterization of a new class of membranes for blood purification: the high cut-off membranes.

    PubMed

    Boschetti-de-Fierro, Adriana; Voigt, Manuel; Storr, Markus; Krause, Bernd

    2013-07-01

    High cut-off membranes are a new class of blood purification membranes whose particular characteristics present challenges for commonly-used characterization methods. Dextran sieving curves for representative blood purification membranes of the high-flux and high cut-off types were measured and compared to curves for the glomerular filtration barrier (GFB). The performance was also determined after blood exposure for the most permeable synthetic membranes. High cut-off membranes were observed to be more open than the GFB before blood exposure, but become tighter and more selective after the exposure, keeping the permeation for low and middle molecules while restraining the filtration of large species. Based on dextran sieving experiments for a variety of commercially available blood purification membranes, we present a novel method for classifying blood purification membranes. By using a well-established technique and introducing a new characteristic parameter for the sieving curve--the molecular weight retention onset (MWRO)--a graph of molecular weight cut-off versus molecular weight retention onset provides the landscape of dialysis membrane types. This meaningful representation is based on only one in vitro method, and allows the membrane classification by indirectly considering two structural parameters: pore size and pore size distribution. In this way, the families of low-flux, high-flux, protein leaking, and high cut-off membranes are clearly differentiated. The differentiation allows for the definition of MWCO/MWRO regions for the different types, so that further classification of newly developed membranes can be easily achieved.

  1. Characterization of blood biochemical markers during aging in the Grey Mouse Lemur (Microcebus murinus): impact of gender and season

    PubMed Central

    2012-01-01

    Background Hematologic and biochemical data are needed to characterize the health status of animal populations over time to determine the habitat quality and captivity conditions. Blood components and the chemical entities that they transport change predominantly with sex and age. The aim of this study was to utilize blood chemistry monitoring to establish the reference levels in a small prosimian primate, the Grey Mouse Lemur (Microcebus murinus). Method In the captive colony, mouse lemurs may live 10–12 years, and three age groups for both males and females were studied: young (1–3 years), middle-aged (4–5 years) and old (6–10 years). Blood biochemical markers were measured using the VetScan Comprehensive Diagnostic Profile. Because many life history traits of this primate are highly dependent on the photoperiod (body mass and reproduction), the effect of season was also assessed. Results The main effect of age was observed in blood markers of renal functions such as creatinine, which was higher among females. Additionally, blood urea nitrogen significantly increased with age and is potentially linked to chronic renal insufficiency, which has been described in captive mouse lemurs. The results demonstrated significant effects related to season, especially in blood protein levels and glucose rates; these effects were observed regardless of gender or age and were likely due to seasonal variations in food intake, which is very marked in this species. Conclusion These results were highly similar with those obtained in other primate species and can serve as references for future research of the Grey Mouse Lemur. PMID:23131178

  2. Development and characterization of a rat model of chronic obstructive pulmonary disease (COPD) induced by sidestream cigarette smoke.

    PubMed

    Zheng, Hongao; Liu, Yuening; Huang, Tian; Fang, Zheman; Li, Guishuang; He, Shaoheng

    2009-09-28

    Cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in China. However, lack of appropriate animal model slows down the progress in understanding pathogenesis of the disease. The aim of current study is to establish and evaluate a more adequate rat model of COPD. Study was performed with rats exposed to sidestream cigarette smoke 2h/d and 7d/wk for 2, 4, 6, 8, 10, 12, 24 and 36 wk in a CS chamber (carbon monoxide concentration was 231+/-11ppm). The lung function was determined by using the forced oscillation technique. Pathologic changes were determined by using histological analyses and mucin measurement. Following 36-wk exposure, airway resistance (Raw) and respiratory system elastance (Ers) in CS group rats was elevated by 28.5% and 37.5%, respectively. Up to 4.1-, 2.3- and 1.4-fold increase in the number of neutrophils, macrophages and lymphocytes was observed in the BALF of CS rats. Using quantitative histomorphology techniques, it was found that mean linear intercept (MLI) and mean alveolar airspace (MAA) of CS rats increased by 44.8% and 43.7%, respectively, indicating the occurrence of emphysema. The characteristics of chronic bronchitis including hyperplasia of bronchial epithelial cells, hypersecretion of mucus and development of peribronchial fibrosis were also found in rat lungs. CS group rats showed 43% body weight gain reduction. To conclude, a more adequate sidestream cigarette smoke rat COPD model was established, which will be beneficial for understanding the pathogenesis of the disease and for evaluation of drug effectiveness.

  3. [Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock].

    PubMed

    Sánchez Marteles, Marta; Urrutia, Agustín

    2014-03-01

    Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease.

  4. Identification and Characterization of Circular RNAs As a New Class of Putative Biomarkers in Human Blood

    PubMed Central

    Peters, Oliver; Rajewsky, Nikolaus

    2015-01-01

    Covalently closed circular RNA molecules (circRNAs) have recently emerged as a class of RNA isoforms with widespread and tissue specific expression across animals, oftentimes independent of the corresponding linear mRNAs. circRNAs are remarkably stable and sometimes highly expressed molecules. Here, we sequenced RNA in human peripheral whole blood to determine the potential of circRNAs as biomarkers in an easily accessible body fluid. We report the reproducible detection of thousands of circRNAs. Importantly, we observed that hundreds of circRNAs are much higher expressed than corresponding linear mRNAs. Thus, circRNA expression in human blood reveals and quantifies the activity of hundreds of coding genes not accessible by classical mRNA specific assays. Our findings suggest that circRNAs could be used as biomarker molecules in standard clinical blood samples. PMID:26485708

  5. Dielectric properties of human diabetic blood: Thermodynamic characterization and new prospective for alternative diagnostic techniques

    NASA Astrophysics Data System (ADS)

    Farsaci, F.; Ficarra, S.; Russo, A.; Galtieri, A.; Tellone, E.

    2015-07-01

    In this paper, we will show the possibility of studying physical properties and irreversible phenomena that occur in blood by applying the dielectric Kluitenberg's nonequilibrium thermodynamic theory. Namely, we shall use some recent extensions of this theory that allow to infer its main characteristic parameters from experimental measures. Applying these results to the study of normal and diabetic blood we show, by comparing them, that it is possible to determine the difference, in some details, of the amount of particular phenomena occurring inside them and give a biological meaning to these phenomena. Moreover, observing a correspondence between a particular value of the frequency for which state coefficients are equal and glucose levels we introduce an alternative diagnostic method to measure the values of the glucose in the blood by determining only this frequency value. The thermodynamic description will be completed by determining the trend of the entropy production.

  6. Characterization of pH variation in lysed blood by near-infrared spectroscopy

    SciTech Connect

    Alam, M. Kathleen; Maynard, John D.; Robinson, M. Ries Niemczyk, Thomas M.; Eaton, R. Philip

    1998-03-01

    Near-infrared spectra (1300{endash}2500 nm) collected from lysed blood solutions were shown to correlate with the pH of the solutions measured potentiometrically. Cross-validated partial least-squares (PLS) models were developed from these spectral data, which provided standard error of prediction (SEP) values below 0.05 pH units for a pH range of 1.0 (6.8{endash}7.8). Experiments were designed to eliminate possible correlation between pH and other components in the blood in order to ensure that variations in the spectral data correlated to pH were due to hydrogen ion changes only. Further work was performed to discern the primary source of pH information in the lysed blood spectra by using spectra collected from plasma and histidine solutions. The blood, plasma, and histidine data sets were compared with the use of loading vectors from principal component analysis (PCA). These loading vectors show that variations in the spectra of the titrated amino acid histidine mimic those seen in lysed blood, but not those seen in plasma. These results suggest that histidine residues of hemoglobin are providing the spectral variation necessary for pH modeling in the lysed blood solutions. It is further shown that the observed pH-sensitive histidine bands do not arise from the exchangeable proton on the imidazole ring of histidine; rather they arise from the variation in the C{endash}H bonds of the C2 and/or the C4 carbons of the imidazole ring as they are influenced by the titration of the nitrogen-bound proton of the imidazole ring. {copyright} {ital 1998} {ital Society for Applied Spectroscopy}

  7. Primary pulmonary hypertension.

    PubMed

    Rashid, A; Lehrman, S; Romano, P; Frishman, W; Dobkin, J; Reichel, J

    2000-01-01

    Primary pulmonary hypertension (PPH) is a condition characterized by sustained elevation of pulmonary artery pressure (PAP) without demonstrable cause. The most common symptom at presentation is dyspnea. Other complaints include fatigue, chest pain, syncope, leg edema, and palpitations. Right heart catheterization is diagnostic, showing a mean PAP >25 mmHg at rest and >30 mmHg during exercise, with a normal pulmonary capillary wedge pressure. In the National Institutes of Health-PPH registry, the median survival period was 2.8 years. Treatment is aimed at lowering PAP, increasing cardiac output, and decreasing in situ thrombosis. Vasodilators have been used with some success in the treatment of PPH. They include prostacyclin, calcium-channel blockers, nitric oxide and adenosine. Anticoagulation has also been advised for the prevention of deep vein thrombosis, pulmonary embolism, and in situ thromboses of the lungs. New drug treatments under investigation include L-arginine, plasma endothelin-I, and bosentan. Use of oxygen, digoxin, and diuretics for symptomatic relief have also been recommended. Patients with severe PPH refractory to medical management should be considered for surgery.

  8. Morphological and biochemical characterization of mitochondria in Torpedo red blood cells.

    PubMed

    Pica, A; Scacco, S; Papa, F; De Nitto, E; Papa, S

    2001-02-01

    A study is presented on the morphology and respiratory functions of mitochondria from Torpedo marmorata red blood cells. In vivo staining of red blood cells and transmission electron microscopy showed the existence of a considerable number of vital and orthodox mitochondria which decreased from young erythroblasts to mature erythrocytes from 60-50 to 30-20 per cell. In erythrocytes mitochondria exhibited a canonical, functional respiratory chain. The content and activity of cytochromes in erythrocytes were, however, significantly lower as compared to mammalian tissues.

  9. Biochemical characterization of blood orange, sweet orange, lemon, bergamot and bitter orange.

    PubMed

    Moufida, Saïdani; Marzouk, Brahim

    2003-04-01

    This paper reports on the composition of aroma compounds and fatty acids and some physico-chemical parameters (juice percentage, acidity and total sugars) in five varieties of citrus: blood orange, sweet orange, lemon, bergamot and bitter orange. Volatile compounds and methyl esters have been analyzed by gas chromatography. Limonene is the most abundant compound of monoterpene hydrocarbons for all of the examined juices. Eighteen fatty acids have been identified in the studied citrus juices, their quantification points out that unsaturated acids predominate over the saturated ones. Mean concentration of fatty acids varies from 311.8 mg/l in blood orange juice to 678 mg/l in bitter orange juice.

  10. Right Ventricular Hemodynamics in Patients with Pulmonary Hypertension

    NASA Astrophysics Data System (ADS)

    Browning, James; Fenster, Brett; Hertzberg, Jean; Schroeder, Joyce

    2012-11-01

    Recent advances in cardiac magnetic resonance imaging (CMR) have allowed for characterization of blood flow in the right ventricle (RV), including calculation of vorticity and circulation, and qualitative visual assessment of coherent flow patterns. In this study, we investigate qualitative and quantitative differences in right ventricular hemodynamics between subjects with pulmonary hypertension (PH) and normal controls. Fifteen (15) PH subjects and 10 age-matched controls underwent same day 3D time resolved CMR and echocardiography. Echocardiography was used to determine right ventricular diastolic function as well as pulmonary artery systolic pressure (PASP). Velocity vectors, vorticity vectors, and streamlines in the RV were visualized in Paraview and total RV Early (E) and Atrial (A) wave diastolic vorticity was quantified. Visualizations of blood flow in the RV are presented for PH and normal subjects. The hypothesis that PH subjects exhibit different RV vorticity levels than normals during diastole is tested and the relationship between RV vorticity and PASP is explored. The mechanics of RV vortex formation are discussed within the context of pulmonary arterial pressure and right ventricular diastolic function coincident with PH.

  11. Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans

    PubMed Central

    McLachlan, Stela; Giambartolomei, Claudia; Charoen, Pimphen; Wong, Andrew; Finan, Chris; Engmann, Jorgen; Shah, Tina; Hersch, Micha; Cavadino, Alana; Jefferis, Barbara J.; Dale, Caroline E.; Hypponen, Elina; Morris, Richard W.; Casas, Juan P.; Kumari, Meena; Ben-Shlomo, Yoav; Gaunt, Tom R.; Drenos, Fotios; Langenberg, Claudia; Kuh, Diana; Kivimaki, Mika; Rueedi, Rico; Waeber, Gerard; Hingorani, Aroon D.; Price, Jacqueline F.

    2016-01-01

    Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms. We performed meta-analysis of Metabochip association results for six RBC traits—hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and red blood cell count (RCC)—in 11 093 Europeans from seven studies of the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium. We identified 394 non-overlapping SNPs in five loci at genome-wide significance: 6p22.1-6p21.33 (with HFE among others), 6q23.2 (with HBS1L among others), 6q23.3 (contains no genes), 9q34.3 (only ABO gene) and 22q13.1 (with TMPRSS6 among others), replicating previous findings of association with RBC traits at these loci and extending them by imputation to 1000 Genomes. We further characterized associations between ABO SNPs and three traits: hemoglobin, hematocrit and red blood cell count, replicating them in an independent cohort. Conditional analyses indicated the independent association of each of these traits with ABO SNPs and a role for blood group O in mediating the association. The 15 most significant RBC-associated ABO SNPs were also associated with five cardiometabolic traits, with discordance in the direction of effect between groups of traits, suggesting that ABO may act through more than one mechanism to influence cardiometabolic risk. PMID:27280446

  12. Automated microscopy system for detection and genetic characterization of fetal nucleated red blood cells on slides

    NASA Astrophysics Data System (ADS)

    Ravkin, Ilya; Temov, Vladimir

    1998-04-01

    The detection and genetic analysis of fetal cells in maternal blood will permit noninvasive prenatal screening for genetic defects. Applied Imaging has developed and is currently evaluating a system for semiautomatic detection of fetal nucleated red blood cells on slides and acquisition of their DNA probe FISH images. The specimens are blood smears from pregnant women (9 - 16 weeks gestation) enriched for nucleated red blood cells (NRBC). The cells are identified by using labeled monoclonal antibodies directed to different types of hemoglobin chains (gamma, epsilon); the nuclei are stained with DAPI. The Applied Imaging system has been implemented with both Olympus BX and Nikon Eclipse series microscopes which were equipped with transmission and fluorescence optics. The system includes the following motorized components: stage, focus, transmission, and fluorescence filter wheels. A video camera with light integration (COHU 4910) permits low light imaging. The software capabilities include scanning, relocation, autofocusing, feature extraction, facilities for operator review, and data analysis. Detection of fetal NRBCs is achieved by employing a combination of brightfield and fluorescence images of nuclear and cytoplasmic markers. The brightfield and fluorescence images are all obtained with a single multi-bandpass dichroic mirror. A Z-stack of DNA probe FISH images is acquired by moving focus and switching excitation filters. This stack is combined to produce an enhanced image for presentation and spot counting.

  13. Molecular Characterization of a Catalase-Negative Staphylococcus aureus Blood Culture Isolate

    PubMed Central

    Kum, Steven; Jureen, Roland; Lin, Raymond T. P.

    2015-01-01

    Here we report a catalase-negative methicillin-sensitive Staphylococcus aureus isolate collected from a blood culture. Sequencing through the gene encoding catalase, katA, demonstrated a 2-bp insertion. The resulting frameshift mutation generates a protein that has lost 26 amino acids (aa) at its C-terminal domain. PMID:26354811

  14. Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis.

    PubMed

    Cleland, Timothy P; Schroeter, Elena R; Zamdborg, Leonid; Zheng, Wenxia; Lee, Ji Eun; Tran, John C; Bern, Marshall; Duncan, Michael B; Lebleu, Valerie S; Ahlf, Dorothy R; Thomas, Paul M; Kalluri, Raghu; Kelleher, Neil L; Schweitzer, Mary H

    2015-12-04

    Structures similar to blood vessels in location, morphology, flexibility, and transparency have been recovered after demineralization of multiple dinosaur cortical bone fragments from multiple specimens, some of which are as old as 80 Ma. These structures were hypothesized to be either endogenous to the bone (i.e., of vascular origin) or the result of biofilm colonizing the empty osteonal network after degradation of original organic components. Here, we test the hypothesis that these structures are endogenous and thus retain proteins in common with extant archosaur blood vessels that can be detected with high-resolution mass spectrometry and confirmed by immunofluorescence. Two lines of evidence support this hypothesis. First, peptide sequencing of Brachylophosaurus canadensis blood vessel extracts is consistent with peptides comprising extant archosaurian blood vessels and is not consistent with a bacterial, cellular slime mold, or fungal origin. Second, proteins identified by mass spectrometry can be localized to the tissues using antibodies specific to these proteins, validating their identity. Data are available via ProteomeXchange with identifier PXD001738.

  15. Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis

    PubMed Central

    Cleland, Timothy P.; Schroeter, Elena R.; Zamdborg, Leonid; Zheng, Wenxia; Lee, Ji Eun; Tran, John C.; Bern, Marshall; Duncan, Michael B.; Lebleu, Valerie S.; Ahlf, Dorothy R.; Thomas, Paul M.; Kalluri, Raghu; Kelleher, Neil L.; Schweitzer, Mary H.

    2016-01-01

    Structures similar to blood vessels in location, morphology, flexibility, and transparency have been recovered after demineralization of multiple dinosaur cortical bone fragments from multiple specimens, some of which are as old as 80 Ma. These structures were hypothesized to be either endogenous to the bone (i.e., of vascular origin) or the result of biofilm colonizing the empty osteonal network after degradation of original organic components. Here, we test the hypothesis that these structures are endogenous and thus retain proteins in common with extant archosaur blood vessels that can be detected with high-resolution mass spectrometry and confirmed by immunofluorescence. Two lines of evidence support this hypothesis. First, peptide sequencing of Brachylophosaurus canadensis blood vessel extracts is consistent with peptides comprising extant archosaurian blood vessels and is not consistent with a bacterial, cellular slime mold, or fungal origin. Second, proteins identified by mass spectrometry can be localized to the tissues using antibodies specific to these proteins, validating their identity. Data are available via ProteomeXchange with identifier PXD001738. PMID:26595531

  16. Mechanical characteristics of the pulmonary artery in beagle dogs with hepatopulmonary syndrome and portopulmonary hypertension.

    PubMed

    Yan, Guozhen; He, Junfeng; Yu, Yueli; Liu, Yang; Yuan, Yanfen; Guo, Zhiyong

    2016-01-01

    The continuous changes in pulmonary hemodynamic properties in hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) have not been fully characterized in large animal models of HPS and PoPH. Beagle dog models of HPS and PoPH were induced by chronic common bile duct ligation and Sephadex microspheres, respectively. The model was validated by catheter examination and pathological analyses, and the hemodynamic characteristics of the models were observed. The results revealed that the cross-sectional area of the blood vessel was significantly increased in HPS models, but it was significantly decreased in the PoPH models. Furthermore, the resistance of pulmonary circulation was elevated in models of HPS, but it was decreased in models of PoPH. The present findings renew the traditional view that pulmonary hypertension is due to the enhanced peripheral resistance.

  17. PULMONARY TOXICOLOGY

    EPA Science Inventory

    Pulmonary disease and dysfunction exact a tremendous health burden on society. In a recent survey of lung disease published by the American Lung Association in 2012, upwards of 10 million Americans were diagnosed with chronic bronchitis while over 4 million Americans had emphysem...

  18. Anticoagulation in Pulmonary Arterial Hypertension.

    PubMed

    Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B

    2016-06-01

    Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH.

  19. Pulmonary consequences of transfusion: TRALI and TACO.

    PubMed

    Popovsky, Mark A

    2006-06-01

    Transfusion-related acute lung injury and transfusion-associated circulatory overload are important, life-threatening complications of transfusion. Each adversely impact hospital length of stay and cost of healthcare. TRALI is clinically indistinguishable from the adult respiratory distress syndrome but it has a more favorable prognosis. Approximately 10% of TRALI patients die from this complication. The at-risk patient for TRALI has not been identified. The most commonly cited incidence is 1:5000 plasma-containing blood component transfusions. Although several pathways may lead to TRALI, passive transfusion of leukocyte antibodies is currently the most important association. TACO occurs in 1-8% of patients undergoing hip or knee arthroplasty. It is precipitated by positive fluid balance and high transfusion flow rates. TACO is characterized by respiratory distress and acute pulmonary edema.

  20. The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis

    PubMed Central

    Blankley, Simon; Graham, Christine M.; Turner, Jacob; Berry, Matthew P. R.; Bloom, Chloe I.; Xu, Zhaohui; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien; Breen, Ronan; Santis, George; Blankenship, Derek M.; Lipman, Marc; O’Garra, Anne

    2016-01-01

    Background Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis. Methods A novel cohort of patients with extra-pulmonary TB and sarcoidosis was recruited and the transcriptional response of these patients compared to those with pulmonary TB using a variety of transcriptomic approaches including testing a previously defined 380 gene meta-signature of active TB. Results The 380 meta-signature broadly differentiated active TB from healthy controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The top 15 genes from this meta-signature had a lower sensitivity for differentiating extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found the blood transcriptional responses in pulmonary and extra-pulmonary TB to be heterogeneous and to reflect the extent of symptoms of disease. Conclusions The transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of gene expression reflective of symptom status, while the signature of pulmonary TB was distinct, based on a higher proportion of symptomatic individuals. These findings are of importance for the rational design and implementation of mRNA based TB diagnostics. PMID:27706152

  1. Prevalence and characterization of occult hepatitis B infection among blood donors in central Saudi Arabia

    PubMed Central

    Alshayea, Areej I.; Eid, Gamal E.; El-Hazmi, Malak M.; Alhetheel, Abdulkarim F.

    2016-01-01

    Objectives: To evaluate the prevalence of occult hepatitis B viral infections (OBIs) among blood donors considering the clinical and epidemiological importance of identifying OBIs. Methods: A cross-sectional study conducted at King Khalid University Hospital, Riyadh, Saudi Arabia between January 2011 and January 2012. Blood donors (n=8501) were screened for Hepatitis B virus surface antigen (HBsAg) and hepatitis B core antibodies (HBcAb). All HBsAg-negative and HBcAb-positive samples were tested further for hepatitis B surface antibodies (HBsAb), hepatitis B virus (HBV)-DNA, and HBV genotyping. Results: Of the 8501 serum samples tested, 56 (0.7%) were positive and 8445 (99.3%) were negative for HBsAg. Among the HBsAg-negative samples, 198 (2.3%) were positive for HBcAb and these patients were suspected to have OBIs. Among the HBcAb-positive samples, 119 (60.1%) were positive while 79 (39.9%) were negative for HBsAb. Analysis of HBV-DNA for the suspected OBIs showed that 17 out of 198 samples (8.6%) yielded positive results, and all of them were HBsAb-negative. The viral load was low (<20-186 IU/mL) in all OBIs. Hepatitis B virus genotyping showed that 15 out of 17 samples (88.2%) were genotype D, and the other 2 samples (11.8%) were genotype E. Conclusion: The prevalence of OBIs among blood donors in Riyadh was 0.2%. Therefore, it is recommended that HBV molecular testing should be incorporated with serological assays for screening of blood donors. PMID:27652363

  2. Electrophoretic characterization of aldehyde-fixed red blood cells, kidney cells, lynphocytes and chamber coatings

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Ground-based electrokinetic data on the electrophoresis flight experiment to be flown on the Apollo-Soyuz Test Project experiment MA-011 are stipulated. Aldehyde-fixed red blood cells, embryonic kidney cells and lymphocytes were evaluated by analytical particle electrophoresis. The results which aided in the interpretation of the final analysis of the MA-011 experiment are documented. The electrophoresis chamber surface modifications, the buffer, and the material used in the column system are also discussed.

  3. Activity of α1-antitrypsin and some lysosomal enzymes in the blood serum of patients with chronic obstructive pulmonary disease after smoking cessation.

    PubMed

    Woźniak, Bartosz; Woźniak, Alina; Konca, Jacek; Górecki, Dariusz; Mila-Kierzenkowska, Celestyna; Szpinda, Michał; Sutkowy, Paweł; Wesołowski, Roland

    2015-01-01

    The activity of α1-antitrypsin (AAT) and the lysosomal enzymes, cathepsin D (CTS D), arylsulfatase (ASA), and acid phosphatase, (AcP) was determined in patients with COPD (GOLD category A). Moreover, the diagnostic usefulness of these parameters in blood serum was assessed along with establishing whether smoking cessation affects these parameters. The study included 70 patients with COPD who ceased smoking (study group) and two control groups of 33 subjects each: nonsmokers without COPD (control I) and patients with COPD who continued smoking (control II). In control I, blood was taken once and in control II, at the start of the experiment and after the 1st, 2nd, and 3rd months. AAT in the patients exhibited higher activity than in the healthy subjects at all time points. AAT activity in the patients before the start of the experiment was ~80% higher (P < 0.001) than in control I. No statistically significant differences in CTS D, ASA, and AcP activity were found. COPD involves increased AAT activity and unchanged activities of the assessed lysosomal enzymes. Three-month tobacco abstinence does not affect these parameters in peripheral blood. Determining the AAT levels in blood serum can be used in the diagnostics of COPD.

  4. Characterization of rubella seronegative females in the zambian blood donor community.

    PubMed

    Mazaba, Mazyanga L; Monze, Mwaka; Babaniyi, Olusegun A; Siziya, Seter; Michelo, Charles

    2015-01-01

    Rubella is an acute, contagious viral infection caused by a teratogenic enveloped single-stranded RNA virus, rubella virus, a member of the togaviridae family. Though causing generally mild infections in children and adults, it is a disease of public health importance in pregnant women causing major problems including abortions, miscarriages, and congenital rubella syndrome in more than 20% of the susceptible population. This study was carried out to determine the characteristics associated with rubella seronegativity among female blood donors in Zambia. Rubella-specific IgG antibody levels were measured in the blood serum. Proportions were compared using the Chi-squared test at the 5% significance level, and magnitudes of associations were determined using the odds ratio and its 95% confidence interval. Of the 124 female blood donors tested for rubella IgG 46.0% were aged <20 years. Overall, 66.7% of the participants had never been married. More than half (62.1%) of the participants resided in rural areas of the country. Of the 114 participants with recorded level of education, 50.1% had at least completed secondary school. Out of 43 participants with recorded current employment status, 44.2% were not working for pay. A total of 10 (8.1%) participants were seronegative to rubella IgG antibodies. No factors were associated with seronegativity. Protection against rubella through natural infection appears inadequate to protect the population, increasing the risk of CRS.

  5. Comprehensive characterization of chondrocyte cultures in plasma and whole blood biomatrices for cartilage tissue engineering.

    PubMed

    Schulz, Ronny M; Haberhauer, Marcus; Zernia, Göran; Pösel, Claudia; Thümmler, Christian; Somerson, Jeremy S; Huster, Daniel

    2014-07-01

    Many synthetic polymers and biomaterials have been used as matrices for 3D chondrocyte seeding and transplantation in the field of cartilage tissue engineering. To develop a fully autologous carrier for chondrocyte cultivation, we examined the feasibility of allogeneic plasma and whole blood-based matrices and compared them to agarose constructs. Primary articular chondrocytes isolated from 12-month-old pigs were embedded into agarose, plasma and whole blood matrices and cultivated under static-free swelling conditions for up to four weeks. To evaluate the quality of the synthesized extracellular matrix (ECM), constructs were subjected to weekly examinations using histological staining, spectrophotometry, immunohistochemistry and biochemical analysis. In addition, gene expression of cartilage-specific markers such as aggrecan, Sox9 and collagen types I, II and X was determined by RT-PCR. Chondrocyte morphology was assessed via scanning electron microscopy and viability staining, including proliferation and apoptosis assays. Finally, (13)  C NMR spectroscopy provided further evidence of synthesis of ECM components. It was shown that chondrocyte cultivation in allogeneic plasma and whole-blood matrices promoted sufficient chondrocyte viability and differentiation behaviour, resulting in neo-formation of a hyaline-like cartilage matrix.

  6. Synthesis and characterization of nanocrystalline apatites from solution modeling human blood

    NASA Astrophysics Data System (ADS)

    Solodyankina, Anna; Nikolaev, Anton; Frank-Kamenetskaya, Olga; Golovanova, Olga

    2016-09-01

    Present paper is devoted to the research of the calcification processes in the blood plasma of human body. Spontaneous crystallization from the solution modeling the inorganic part of the blood plasma has been carried out. Obtained precipitates were studied by the various instrumental methods (X-ray powder diffraction, Fourier-transformed infrared spectroscopy, scanning electron microscopy, electron probe microanalysis and gas-volumetric method). All gathered data allow to summarize that nonstoichiometric carbonated hydroxyapatite with low crystallinity (CSD lengths 18-28 nm), high water content and small amount of chlorine ion was obtained throughout the syntheses. Part of vacancies at the Ca sites varies from 0.17 to 0.87; the value of the Cat/(P + C) ratio-from 1.52 to 1.64 (where Cat = Ca2+ + Na+ + K+ + Mg2+). The poor crystallized synthetic apatites with high carbonate ion content (from 4.34 to 5.54 wt%) and c parameter (6.888-6.894 Å) are analogues of the apatites of the pathological cardiovascular deposits. They can be obtained from the solution modeling human blood plasma by the inorganic components with calcium phosphate supersaturation 25 and 50 and with 10 and 12 weeks experiment time.

  7. Combined Pulmonary Fibrosis and Emphysema Syndrome

    PubMed Central

    Rounds, Sharon I. S.

    2012-01-01

    There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

  8. Pulmonary arterial hypertension: Basic knowledge for clinicians.

    PubMed

    Santos-Ribeiro, Diana; Mendes-Ferreira, Pedro; Maia-Rocha, Carolina; Adão, Rui; Leite-Moreira, Adelino F; Brás-Silva, Carmen

    2016-10-01

    Pulmonary arterial hypertension is a progressive syndrome based on diverse aetiologies, which is characterized by a persistent increase in pulmonary vascular resistance and overload of the right ventricle, leading to heart failure and death. Currently, none of the available treatments is able to cure pulmonary arterial hypertension; additional research is therefore needed to unravel the associated pathophysiological mechanisms. This review summarizes current knowledge related to this disorder, and the several experimental animal models that can mimic pulmonary arterial hypertension and are available for translational research.

  9. Hantavirus pulmonary syndrome.

    PubMed

    Macneil, Adam; Nichol, Stuart T; Spiropoulou, Christina F

    2011-12-01

    Hantavirus pulmonary syndrome (HPS) is a severe disease characterized by a rapid onset of pulmonary edema followed by respiratory failure and cardiogenic shock. The HPS associated viruses are members of the genus Hantavirus, family Bunyaviridae. Hantaviruses have a worldwide distribution and are broadly split into the New World hantaviruses, which includes those causing HPS, and the Old World hantaviruses [including the prototype Hantaan virus (HTNV)], which are associated with a different disease, hemorrhagic fever with renal syndrome (HFRS). Sin Nombre virus (SNV) and Andes virus (ANDV) are the most common causes of HPS in North and South America, respectively. Case fatality of HPS is approximately 40%. Pathogenic New World hantaviruses infect the lung microvascular endothelium without causing any virus induced cytopathic effect. However, virus infection results in microvascular leakage, which is the hallmark of HPS. This article briefly reviews the knowledge on HPS-associated hantaviruses accumulated since their discovery, less than 20 years ago.

  10. [Place of surgery in pulmonary aspergillosis and other pulmonary mycotic infections].

    PubMed

    Pagès, P-B; Abou Hanna, H; Caillot, D; Bernard, A

    2012-04-01

    Surgery is part of the therapeutic strategy of aspergillosis and mucormycosis. The aspergilloma is defined as a rounded mass, developing in a cavity by the proliferation of spores of Aspergillus. The most common complication was haemoptysis reported in 50-95% of cases. The pleuropulmonary lesions predisposing are: tuberculosis, residual pleural space, emphysema and lung destroyed by fibrosis or radiotherapy or bronchiectasis. The indications for surgery depend on symptoms, respiratory function, the parenchyma and the type of aspergilloma (simple or complex). In a patient with an intrapulmonary aspergilloma, lung resection preceded by embolization is recommended based on respiratory function. For intrapleural aspergilloma, thoracoplasty is recommended according to the patient's general condition. The invasive pulmonary aspergillosis (IPA) is characterized by an invasion of lung tissue and blood vessels by hyphae in immunocompromised patients. The death rate of patients who have an API after treatment for leukemia or lymphoma was 30 to 40%, after bone marrow transplantation 60%, after solid organ transplantation from 50 to 60% and after any other cause of immunocompromising from 70 to 85%. The main cause of these deaths is massive hemoptysis. Surgery (lobectomy) is indicated for the prevention of hemoptysis when the mass is in contact with the pulmonary artery or one of its branches, and if it increases in size with the disappearance of border security between the mass and the vessel wall. The patient will be operated in an emergency before the white blood cells do not exceed the threshold of 1000 cells/μl. A persistent residual mass after antifungal treatment may justify a lung resection (lobectomy or wedge) before a new aggressive therapy. Mucormycosis affects patients following immunocompromising states--haematologic malignancy, diabetes mellitus, transplantation, burns and malnutrition. The treatment of pulmonary mucormycosis combines surgical and medical

  11. Asthma Outcomes: Pulmonary Physiology

    PubMed Central

    Tepper, Robert S.; Wise, Robert S.; Covar, Ronina; Irvin, Charles G.; Kercsmar, Carolyn M.; Kraft, Monica; Liu, Mark C.; O’Connor, George T.; Peters, Stephen P.; Sorkness, Ronald; Togias, Alkis

    2014-01-01

    Background Outcomes of pulmonary physiology have a central place in asthma clinical research. Objective At the request of National Institutes of Health (NIH) institutes and other federal agencies, an expert group was convened to provide recommendations on the use of pulmonary function measures as asthma outcomes that should be assessed in a standardized fashion in future asthma clinical trials and studies to allow for cross-study comparisons. Methods Our subcommittee conducted a comprehensive search of PubMed to identify studies that focused on the validation of various airway response tests used in asthma clinical research. The subcommittee classified the instruments as core (to be required in future studies), supplemental (to be used according to study aims and in a standardized fashion), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011. Results A list of pulmonary physiology outcomes that applies to both adults and children older than 6 years was created. These outcomes were then categorized into core, supplemental, and emerging. Spirometric outcomes (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC) are proposed as core outcomes for study population characterization, for observational studies, and for prospective clinical trials. Bronchodilator reversibility and pre- and post-bronchodilator FEV1 also are core outcomes for study population characterization and observational studies. Conclusions The subcommittee considers pulmonary physiology outcomes of central importance in asthma and proposes spirometric outcomes as core outcomes for all future NIH-initiated asthma clinical research. PMID:22386510

  12. Characterization, phylogenetic analysis and cDNA cloning of natterin-like gene from the blood of lamprey, Lampetra japonica.

    PubMed

    Xue, Zhuang; Liu, Xin; Pang, Yue; Yu, Tao; Xiao, Rong; Jin, Minli; Han, Yinglun; Su, Peng; Wang, Jihong; Lv, Li; Wu, Fenfang; Li, Qingwei

    2012-01-01

    Lamprey as a "living fossil" of immunological origin and "rich treasure" of biological pharmaceutical development has caused attention of scholars. The cDNA library construction and EST sequencing of blood had been done previously in our lab, and bioinformatics analysis provided a gene fragment which is highly homologous with natterin family, named natterin-like. To elucidate the characterization and phylogeny of natterin-like genes in early evolution, we cloned the full-length cDNA of natterin-like gene from the blood of Lampetra japonica. The open reading frame of this sequence contained 942bp and encoded 313 amino acids, including a lectin-like domain and a pore-forming toxin-like domain. Using reverse transcription PCR, natterin-like mRNA was also detected in lamprey blood, kidney, heart, liver, medullary, gonad, but absent in lamprey intestine and gill. Our results suggested that in lampreys and most of other species, there might be only one natterin-like gene, which was fused by certain sequences during evolution and encoded proteins with more functions. It is similar between C terminal of natterin-like protein and Aerolysin in space structure and the lectin-like domain of natterin-like equivalent to glycoprotein binding motif of Aerolysin in function. We also propose that the defense mechanism against specific predators in historical evolution of lamprey. Our findings may provide insights into the function and characterization of natterin-like genes as well as other gene families in vertebrates and provide a foundation for identification and structural, functional, and evolutionary analyses of more natterin-like genes and other gene families.

  13. In-Depth Comparative Characterization of Hemoglobin Glycation in Normal and Diabetic Bloods by LC-MSMS

    NASA Astrophysics Data System (ADS)

    Wang, Shih-Hao; Wang, Tzu-Fan; Wu, Chih-Hsing; Chen, Shu-Hui

    2014-05-01

    The glycation level at β-Val-1 of the hemoglobin β chain in human blood (HbA1c%) is used to diagnose diabetes and other diseases. However, hemoglobin glycation occurs on multiple sites on different isoforms with different kinetics, but its differential profile has not been clearly demonstrated. In this study, hemoglobin was extracted from the blood of normal and diabetic individuals by protein precipitation. Triplicate solutions prepared from each sample were directly analyzed or digested with multiple enzymes and then analyzed by nano-LC/MS via bottom-up approach for side-by-side characterization. Intact hemoglobin analysis indicated a single glucose-dominant glycation, which showed good correlation with the HbA1c% values. Moreover, full sequence (100 %) of α/β globin was mapped and seven glycation sites were unambiguously assigned. In addition to β-Val-1, two other major sites at α-Lys-61 and β-Lys-66, which contain the common sequence HGK K, and four minor sites (<1 %) on α-Val-1, β-Lys-132, α-Lys-127, and α-Lys-40 were identified. All sites were shown to exhibit similar patterns of site distribution despite different glucose levels. Both the intact mass measurement and bottom-up data consistently indicated that the total glycation percentage of the β-globin was twice higher than the α-globin. Using molecular modeling, the 3D structure of the consensus sequence (HGK K) was shown to contain a phosphate triangle cavity, which helps to catalyze the glycation reaction. For the first time, hemoglobin glycation in normal and diabetic bloods was comparatively characterized in-depth with 100 % sequence coverage. The results provide insight about the HbA1c parameter and help define the new and old markers.

  14. Epoprostenol Therapy for Pulmonary Arterial Hypertension.

    PubMed

    Akagi, Satoshi; Nakamura, Kazufumi; Matsubara, Hiromi; Ogawa, Aiko; Sarashina, Toshihiro; Ejiri, Kentaro; Ito, Hiroshi

    2015-01-01

    Pulmonary arterial hypertension (PAH) is characterized by elevation of pulmonary artery pressure caused by pulmonary vasoconstriction and vascular remodeling, which leads to right heart failure and death. Epoprostenol (prostaglandin I2) has a potent short-acting vasodilator property, and intravenous continuous epoprostenol is therefore used for treatment of PAH. Here we review evidence for the usefulness of intravenous continuous epoprostenol therapy in patients with PAH. Epoprostenol therapy is effective in idiopathic PAH patients and in patients with PAH associated with connective tissue disease, portal hypertension or congenital heart diseases, but it is not effective in patients with pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. High-dose epoprostenol therapy markedly improved hemodynamics in some patients with PAH, possibly due to reverse remodeling of pulmonary arteries. This therapy has several side effects and complications such as headache, hypotension and catheter-related infections. Intravenous continuous epoprostenol is an effective treatment, but there are still some problems to be resolved.

  15. Characterization of the Humoral Immune Response during Staphylococcus aureus Bacteremia and Global Gene Expression by Staphylococcus aureus in Human Blood

    PubMed Central

    den Reijer, Paul Martijn; Lemmens-den Toom, Nicole; Kant, Samantha; Snijders, Susan V.; Boelens, Hélène; Tavakol, Mehri; Verkaik, Nelianne J.; van Belkum, Alex; Verbrugh, Henri A.; van Wamel, Willem J. B.

    2013-01-01

    Attempts to develop an efficient anti-staphylococcal vaccine in humans have so far been unsuccessful. Therefore, more knowledge of the antigens that are expressed by Staphylococcus aureus in human blood and induce an immune response in patients is required. In this study we further characterize the serial levels of IgG and IgA antibodies against 56 staphylococcal antigens in multiple serum samples of 21 patients with a S. aureus bacteremia, compare peak IgG levels between patients and 30 non-infected controls, and analyze the expression of 3626 genes by two genetically distinct isolates in human blood. The serum antibody levels were measured using a bead-based flow cytometry technique (xMAP®, Luminex corporation). Gene expression levels were analyzed using a microarray (BµG@s microarray). The initial levels and time taken to reach peak IgG and IgA antibody levels were heterogeneous in bacteremia patients. The antigen SA0688 was associated with the highest median initial-to-peak antibody fold-increase for IgG (5.05-fold) and the second highest increase for IgA (2.07-fold). Peak IgG levels against 27 antigens, including the antigen SA0688, were significantly elevated in bacteremia patients versus controls (P≤0.05). Expression of diverse genes, including SA0688, was ubiquitously high in both isolates at all time points during incubation in blood. However, only a limited number of genes were specifically up- or downregulated in both isolates when cultured in blood, compared to the start of incubation in blood or during incubation in BHI broth. In conclusion, most staphylococcal antigens tested in this study, including many known virulence factors, do not induce uniform increases in the antibody levels in bacteremia patients. In addition, the expression of these antigens by S. aureus is not significantly altered by incubation in human blood over time. One immunogenic and ubiquitously expressed antigen is the putative iron-regulated ABC transporter SA0688. PMID

  16. Pulmonary Renal Syndrome After Streptococcal Pharyngitis

    PubMed Central

    Mara-Koosham, Gopi; Stoltze, Karl; Aday, Jeffrey; Rendon, Patrick

    2016-01-01

    Pulmonary renal syndrome is a class of small vessel vasculitides that are characterized by the dual presentation of diffuse alveolar hemorrhage (DAH) and glomerulonephritis. Pulmonary renal syndrome has multiple etiologies, but its development has been rarely reported following infection with group A streptococcus. We present the case of a 36-year-old Native American male who was transferred to our facility due to refractory hypoxic respiratory failure. He had been diagnosed with streptococcal pharyngitis 2 weeks prior to admission. Given the presence of hemoptysis, bronchoscopy was performed and was consistent with DAH. Urinalysis demonstrated hematuria and proteinuria, in the setting of elevated creatinine and blood urea nitrogen. Additionally, antistreptolysin O titer was positive. Given the constellation of laboratory findings and history of streptococcal pharyngitis, the patient was diagnosed with PRS secondary to streptococcal infection. High-dose methylprednisolone was initiated with concomitant plasmapheresis. He was extubated successfully after his respiratory status improved and was eventually discharged home after making a full recovery within 2 weeks after admission. This case illustrates the importance of clinically relevant sequelae of streptococcal infection as well as the appropriate treatment of PRS secondary to streptococcal pharyngitis with plasmapheresis and intravenous corticosteroids. PMID:27231692

  17. Perfusion visualization and analysis for pulmonary embolism

    NASA Astrophysics Data System (ADS)

    Vaz, Michael S.; Kiraly, Atilla P.; Naidich, David P.; Novak, Carol L.

    2005-04-01

    Given the nature of pulmonary embolism (PE), timely and accurate diagnosis is critical. Contrast enhanced high-resolution CT images allow physicians to accurately identify segmental and sub-segmental emboli. However, it is also important to assess the effect of such emboli on the blood flow in the lungs. Expanding upon previous research, we propose a method for 3D visualization of lung perfusion. The proposed method allows users to examine perfusion throughout the entire lung volume at a single glance, with areas of diminished perfusion highlighted so that they are visible independent of the viewing location. This may be particularly valuable for better accuracy in assessing the extent of hemodynamic alterations resulting from pulmonary emboli. The method also facilitates user interaction and may help identify small peripheral sub-segmental emboli otherwise overlooked. 19 patients referred for possible PE were evaluated by CT following the administration of IV contrast media. An experienced thoracic radiologist assessed the 19 datasets with 17 diagnosed as being positive for PE with multiple emboli. Since anomalies in lung perfusion due to PE can alter the distribution of parenchymal densities, we analyzed features collected from histograms of the computed perfusion maps and demonstrate their potential usefulness as a preliminary test to suggest the presence of PE. These histogram features also offer the possibility of distinguishing distinct patterns associated with chronic PE and may even be useful for further characterization of changes in perfusion or overall density resulting from associated conditions such as pneumonia or diffuse lung disease.

  18. Effectiveness of Multiple Blood-Cleansing Interventions in Sepsis, Characterized in Rats

    PubMed Central

    Stojkovic, Ivan; Ghalwash, Mohamed; Cao, Xi Hang; Obradovic, Zoran

    2016-01-01

    Sepsis is a serious, life-threatening condition that presents a growing problem in medicine, but there is still no satisfying solution for treating it. Several blood cleansing approaches recently gained attention as promising interventions that target the main site of problem development–the blood. The focus of this study is an evaluation of the theoretical effectiveness of hemoadsorption therapy and pathogen reduction therapy. This is evaluated using the mathematical model of Murine sepsis, and the results of over 2,200 configurations of single and multiple intervention therapies simulated on 5,000 virtual subjects suggest the advantage of pathogen reduction over hemoadsorption therapy. However, a combination of two approaches is found to take advantage of their complementary effects and outperform either therapy alone. The conducted computational experiments provide unprecedented evidence that the combination of two therapies synergistically enhances the positive effects beyond the simple superposition of the benefits of two approaches. Such a characteristic could have a profound influence on the way sepsis treatment is conducted. PMID:27097769

  19. Surface-emitting superconductor laser spectroscopy for characterizing normal and sickled red blood cells

    SciTech Connect

    Gourley, P.L.; Meissner, K.E.; Brennan, T.M.; Hammons, B.E.; Gourley, M.F.

    1995-02-01

    We have developed a new intracavity laser technique that uses a living or a fixed cell as an integral component of the laser. The cells are placed on an AlGaAs/GaAs surface-emitting semiconductor wafer and covered with a glass dielectric mirror to form a laser resonator. In this arrangement, the cells serve as optical waveguides (or lens elements) to confine (or focus) light generated in the resonator by the semiconductor. Because of the high transparency, the cells aid the lasing process to generate laser light. This ultra sensitive laser provides a novel imaging/spectroscopic technique for histologic examination which we demonstrate with normal and sickled human red blood cells. Extremely high contrast microscopic images of the cells are observed near 830-850 nm. These images correspond to electromagnetic modes of cell structures and are sensitive to shape of the cell. Using a high resolution spectrometer, we resolve the light emitted from these images into very narrow spectral peaks associated with the lasing modes. Analysis of the spectra reveals that the distribution of peaks is quite different for normal and sickled red blood cells. This technique, in a more developed form, may be useful for the rapid analysis of other kinds of normal and abnormal cells.

  20. Purification and characterization of metabolically active capillaries of the blood-brain barrier.

    PubMed Central

    Dallaire, L; Tremblay, L; Béliveau, R

    1991-01-01

    Microvessels were isolated from bovine and rat cerebral cortex by simple procedures involving mechanical homogenization, differential and density-gradient centrifugation, and chromatography on a column of glass beads. The preparations were composed of short capillaries with a diameter of 1-10 microns. Both purifications were monitored by assaying the activity of the marker enzyme gamma-glutamyl transpeptidase (gamma-GTase). The final bovine and rat preparations were enriched 20- and 14-fold over the homogenate respectively. gamma-GTase activity was measured in different fractions after bovine and rat membranes were solubilized with 0.5% and 0.3% Triton X-100 respectively. Measurement of 5'-nucleotidase and acetylcholinesterase activities indicated very low levels of contamination of the microvessel preparations by glial cells and neurons. The integrity of the capillary membranes was confirmed by the assay of a cytosolic marker enzyme, lactate dehydrogenase. Viability of the microvessels was demonstrated by the presence of detectable levels of adenylates and by tissue respiration induced by glucose and succinate. Comparison of the proteins of homogenized bovine and rat brain cortex with those of purified capillaries separated by SDS/PAGE revealed enrichment of at least three predominant proteins of 14, 16 and 18 kDa in the capillary preparations. It is concluded that these methods allow rapid isolation of small blood vessels of the blood-brain barrier which are suitable for metabolic and structural studies in vitro. Images Fig. 2. Fig. 4. PMID:1712199

  1. The characterization of exosome from blood plasma of patients with colorectal cancer

    NASA Astrophysics Data System (ADS)

    Yunusova, N. V.; Tamkovich, S. N.; Stakheeva, M. N.; Afanas'ev, S. G.; Frolova, A. Y.; Kondakova, I. V.

    2016-08-01

    Exosomes are extracellular membrane structures involved in many physiological and pathological processes including cancerogenesis and metastasis. The clarification of the criteria for exosome isolating and identifying is the purpose of this study. Exosome samples from the plasma of patients with colorectal cancer and healthy donors were examined using transmission electron microscopy and flow cytometry in accordance with the minimum requirements of "International Society for Extracellular Vesicles". The choice of the method for isolation of exosomes from the blood plasma by ultrafiltration and ultracentrifugation allowed obtaining highly purified samples of exosomes, in which all the structural components were clearly seen. The results obtained with flow cytometry suggest that exosomes of blood plasma from patients with colorectal cancer can be produced by epithelial cells. Moreover, cells produce different types of exosomes, which correspond to different mechanisms in sorting macromolecules in the membrane of multivesicular bodies. Determination of significant differences in the expression of specific exosomal proteins from colorectal cancer patients compared to healthy donors suggests a high diagnostic potential significance of circulating exosomes.

  2. Imaging findings in pulmonary vasculitis.

    PubMed

    Castañer, Eva; Alguersuari, Anna; Andreu, Marta; Gallardo, Xavier; Spinu, Cristina; Mata, Josep M

    2012-12-01

    Vasculitis is a destructive inflammatory process affecting blood vessels. Pulmonary vasculitis may develop secondary to other conditions or constitute a primary idiopathic disorder. Thoracic involvement is most common in primary idiopathic large-vessel vasculitides (Takayasu arteritis, giant cell arteritis, Behçet disease) and primary antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitides (Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome). Primary pulmonary vasculitides are rare, and their signs and symptoms are nonspecific, overlapping with those of infections, connective tissue diseases, and malignancies. The radiologic findings in primary pulmonary vasculitis vary widely and can include vessel wall thickening, nodular or cavitary lesions, ground-glass opacities, and consolidations, among others. Diffuse alveolar hemorrhage usually results from primary small-vessel vasculitis in the lungs. To diagnose vasculitis, medical teams must recognize characteristic combinations of clinical, radiologic, laboratory, and histopathologic features.

  3. Genetic characterization of HIV-1 from semen and blood from clade C-infected subjects from India and effect of therapy in these body compartments

    PubMed Central

    Shen, Chengli; Ding, Ming; Craigo, Jodi K.; Tarwater, Patrick; Chatterjee, Ramdas; Roy, Pratima; Guha, Subhasish K; Saha, Bibhuti; Modak, Dolonchapa; Neogi, Dhruba; Chen, Yue; Gupta, Phalguni

    2010-01-01

    Biologic and genetic differences between HIV-1 clade C in India and clade B in US suggest that the effect of anti-viral therapy in various body compartments may differ between these two clades. We examined the effect of therapy viral loads in semen and blood of HIV-1-clade C infected subjects from India and evaluated whether HIV-1 in the semen is different from that in blood in these subjects. HIV-1 RNA was detected in semen and blood at all stages of the disease. Viral loads in semen and blood were strongly correlated with each other, but not with the CD4+ T cell count. Antiviral treatment reduced viral load drastically in blood and semen within one month of post therapy. Genetic characterization of HIV-1 in the semen and blood demonstrated that they were highly compartmentalized. These data have important implications of sexual transmission of HIV-1 in clade C HIV-1 infected subjects. PMID:20231027

  4. Influence of disease severity on nitrite and cytokine production by peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis (TB).

    PubMed

    Dlugovitzky, D; Bay, M L; Rateni, L; Fiorenza, G; Vietti, L; Farroni, M A; Bottasso, O A

    2000-12-01

    Earlier studies in patients with pulmonary TB have revealed a higher production of Th1 cell type cytokines in moderate TB, with predominant Th2-like responses in advanced disease. Given the influence of IL-12 in T cell differentiation, as well as the roles of transforming growth factor-beta (TGF-beta), nitric oxide and tumour necrosis factor-alpha (TNF-alpha) in the immune response against intracellular pathogens, we decided to analyse the interferon-gamma (IFN-gamma), IL-4, IL-12, TGF-beta, TNF-alpha and nitrite concentrations in culture supernatants of PBMC from TB patients showing different degrees of lung involvement. The sample population comprised 18 untreated TB patients with either moderate (n = 9) or advanced (n = 9) disease and 12 age- and sex-matched healthy controls (total population (patients and controls) 12 women, 18 men, aged 37 +/- 13 years (mean +/- s.d.)). PBMC were stimulated with whole sonicate from Mycobacterium tuberculosis and the supernatants were collected on day 4 for measurement of cytokine and nitrite levels. Antigen-stimulated IFN-gamma, TGF-beta and TNF-alpha production was found to be significantly increased in TB patients, both moderate and advanced, compared with the controls. Levels of IFN-gamma were significantly higher in moderate disease than advanced cases, whereas advanced cases showed significantly higher IL-12, TGF-beta and TNF-alpha concentrations when compared with cases of moderate TB. Nitrite levels were also increased in TB patients and the increase was statistically significant when advanced cases were compared with controls. These findings may contribute to a clearer picture of the net effect of cytokine interactions in TB, essential for a better understanding of the immunopathological mechanisms underlying the distinct clinical forms of the disease.

  5. Influence of disease severity on nitrite and cytokine production by peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis (TB)

    PubMed Central

    Dlugovitzky, D; Bay, M L; Rateni, L; Fiorenza, G; Vietti, L; Farroni, M A; Bottasso, O A

    2000-01-01

    Earlier studies in patients with pulmonary TB have revealed a higher production of Th1 cell type cytokines in moderate TB, with predominant Th2-like responses in advanced disease. Given the influence of IL-12 in T cell differentiation, as well as the roles of transforming growth factor-beta (TGF-β), nitric oxide and tumour necrosis factor-alpha (TNF-α) in the immune response against intracellular pathogens, we decided to analyse the interferon-gamma (IFN-γ), IL-4, IL-12, TGF-β, TNF-α and nitrite concentrations in culture supernatants of PBMC from TB patients showing different degrees of lung involvement. The sample population comprised 18 untreated TB patients with either moderate (n = 9) or advanced (n = 9) disease and 12 age- and sex-matched healthy controls (total population (patients and controls) 12 women, 18 men, aged 37 ± 13 years (mean ±s.d.)). PBMC were stimulated with whole sonicate from Mycobacterium tuberculosis and the supernatants were collected on day 4 for measurement of cytokine and nitrite levels. Antigen-stimulated IFN-γ, TGF-β and TNF-α production was found to be significantly increased in TB patients, both moderate and advanced, compared with the controls. Levels of IFN-γ were significantly higher in moderate disease than advanced cases, whereas advanced cases showed significantly higher IL-12, TGF-β and TNF-α concentrations when compared with cases of moderate TB. Nitrite levels were also increased in TB patients and the increase was statistically significant when advanced cases were compared with controls. These findings may contribute to a clearer picture of the net effect of cytokine interactions in TB, essential for a better understanding of the immunopathological mechanisms underlying the distinct clinical forms of the disease. PMID:11122239

  6. [Expression of miR-21 in peripheral blood serum and mononuclear cells in patients with chronic obstructive pulmonary disease and its clinical significance].

    PubMed

    Xie, Lihua; Yang, Fangying; Sun, Shenghua

    2016-03-28

    目的:通过研究miR-21在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者外周血清及单个核细胞中的表达,探讨miR-21在COPD发病中的意义及机制。方法:将研究对象分为健康对照组(n=41)和COPD组(n=49),收集两组外周血清,分离其外周血单个核细胞并收集临床资料。运用实时荧光定量PCR法检测各组外周血清及单个核细胞中miR-21的表达水平。分析COPD组miR-21与肺功能的关系,并对miR-21与COPD患者一秒用力呼气容积(forced expiratory volume in one second,FEV1)进行相关性分析。结果:COPD组外周血清及单个核细胞中miR-21表达水平较健康对照组增高;COPD外周血清及单个核细胞中miR-21差异表达与肺功能相关;COPD患者miR-21表达水平与FEV1呈正相关。结论:COPD患者外周血清及单个核细胞中miR-21表达升高可能与COPD发病过程及病情严重程度相关。.

  7. Familial Pulmonary Fibrosis

    MedlinePlus

    ... Training Home Conditions Familial Pulmonary Fibrosis Familial Pulmonary Fibrosis Make an Appointment Find a Doctor Ask a ... members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial ...

  8. Pulmonary Hypertension

    PubMed Central

    Kim, John S.; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

    2015-01-01

    Objective Review the pharmacologic treatment options for pulmonary arterial hypertension (PAH) in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Data Sources and Study Selection Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of PAH therapies. Data Extraction Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Data Synthesis Specific targeted therapies developed for the treatment of adult patients with PAH have been applied for the benefit of children with PAH. With the exception of inhaled nitric oxide, there are no PAH medications approved for children in the US by the FDA. Unfortunately, data on treatment strategies in children with PAH are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for PAH in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with PAH. Prostacyclins provide adjunctive therapy for the treatment of PAH as infusions (intravenous and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first line vasodilator therapy in persistent pulmonary hypertension of the newborn, and is commonly used in the treatment of PAH in the Intensive Care Unit (ICU). Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with PAH. Soluble Guanylate Cyclase Stimulators are the first drug class to be FDA approved for the treatment of chronic thromboembolic pulmonary hypertension. Conclusions Literature and data supporting the

  9. Comparison of computed tomography pulmonary angiography and point-of-care tests for pulmonary thromboembolism diagnosis in dogs

    PubMed Central

    Goggs, R; Chan, D L; Benigni, L; Hirst, C; Kellett-Gregory, L; Fuentes, V L

    2014-01-01

    Objectives To evaluate the feasibility of CT pulmonary angiography for identification of naturally occurring pulmonary thromboembolism in dogs using predefined diagnostic criteria and to assess the ability of echocardiography, cardiac troponins, D-dimers and kaolin-activated thromboelastography to predict the presence of pulmonary thromboembolism in dogs. Methods Twelve dogs with immune-mediated haemolytic anaemia and evidence of respiratory distress were prospectively evaluated. Dogs were sedated immediately before CT pulmonary angiography using intravenous butorphanol. Spiral CT pulmonary angiography was performed with a 16 detector-row CT scanner using a pressure injector to infuse contrast media through peripheral intravenous catheters. Pulmonary thromboembolism was diagnosed using predefined criteria. Contemporaneous tests included echocardiography, arterial blood gas analysis, kaolin-activated thromboelastography, D-dimers and cardiac troponins. Results Based on predefined criteria, four dogs were classified as pulmonary thromboembolism positive, three dogs were suspected to have pulmonary thromboembolism and the remaining five dogs had negative scans. The four dogs identified with pulmonary thromboembolism all had discrete filling defects in main or lobar pulmonary arteries. None of the contemporaneous tests was discriminant for pulmonary thromboembolism diagnosis, although the small sample size was limiting. Clinical Significance CT pulmonary angiography can be successfully performed in dogs under sedation, even in at-risk patients with respiratory distress and can both confirm and rule out pulmonary thromboembolism in dogs. PMID:24521253

  10. Absent or occult pulmonary artery.

    PubMed Central

    Presbitero, P; Bull, C; Haworth, S G; de Leval, M R

    1984-01-01

    Of 12 patients with angiographically absent pulmonary artery, 11 were investigated surgically. The previously occult pulmonary artery was found in 10 patients, in five of whom a vestige of an intrapericardial artery was present and in five the artery was patent only at the hilus, a gap existing between the main pulmonary artery and the hilar vessel, and no artery was found in one. All patients with an intrapericardial artery had right ventricular outflow tract obstruction and a ductus descending vertically from underneath the aortic arch. In those without an intrapericardial vessel the occult artery was on the side opposite the aortic arch, and there was evidence of a ductus coming from the innominate artery on the side of the interruption. The occult pulmonary artery, where identified at operation, was usually joined initially to the systemic circulation. Ultimately, continuity between the hilar and main pulmonary artery may be established surgically. Where no intrapericardial vessel exists, however, a conduit may be required to bridge the gap. It seems advisable to search for the occult artery as early in life as is feasible in the hope that providing a blood supply will ensure development of the vessel and normal lung growth. Images PMID:6743435

  11. Pulmonary emphysema: when more is less.

    PubMed

    Morris, David G; Sheppard, Dean

    2006-12-01

    Pulmonary emphysema results from the loss of intricate alveolar architecture and progressive simplification of small and highly effective gas-exchanging units into large, inefficient cyst-like spaces. Because of the loss of alveolar gas-exchanging units and the capillary bed within them, blood oxygen levels eventually fall and pressures within the pulmonary circulation rise. Recent insights from genetically manipulated mouse models have refined our understanding of the molecular events that prevent or promote the development of pulmonary emphysema. Capitalizing on an improved molecular understanding of emphysema with improved therapeutics has the potential to enhance both the survival and quality of life of patients with this common lung disease.

  12. Characterizing Blood Metabolomics Profiles Associated with Self-Reported Food Intakes in Female Twins

    PubMed Central

    Pallister, Tess; Jennings, Amy; Mohney, Robert P.; Yarand, Darioush; Mangino, Massimo; Cassidy, Aedin; MacGregor, Alexander; Spector, Tim D.; Menni, Cristina

    2016-01-01

    Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non-targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [≥1 SD apart] for food group intake) with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]). Significant results were then replicated (non-targeted: P<0.05; targeted: same direction) in the MZ discordant twin group and results from both analyses meta-analyzed. We identified and replicated 180 significant associations with 39 food groups (P<1.17x10-6), overall consisting of 106 different metabolites (74 known and 32 unknown), including 73 novel associations. In particular we identified trans-4-hydroxyproline as a potential marker of red meat intake (0.075[0.009]; P = 1.08x10-17), ergothioneine as a marker of mushroom consumption (0.181[0.019]; P = 5.93x10-22), and three potential markers of fruit consumption (top association: apple and pears): including metabolites derived from gut bacterial transformation of phenolic compounds, 3-phenylpropionate (0.024[0.004]; P = 1.24x10-8) and indolepropionate (0.026[0.004]; P = 2.39x10-9), and threitol (0.033[0.003]; P = 1.69x10-21). With the largest nutritional metabolomics dataset to date, we have identified 73 novel candidate biomarkers of food intake for potential use in nutritional epidemiological studies. We compiled our findings into the Diet

  13. Characterizing Blood Metabolomics Profiles Associated with Self-Reported Food Intakes in Female Twins.

    PubMed

    Pallister, Tess; Jennings, Amy; Mohney, Robert P; Yarand, Darioush; Mangino, Massimo; Cassidy, Aedin; MacGregor, Alexander; Spector, Tim D; Menni, Cristina

    2016-01-01

    Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non-targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [≥1 SD apart] for food group intake) with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]). Significant results were then replicated (non-targeted: P<0.05; targeted: same direction) in the MZ discordant twin group and results from both analyses meta-analyzed. We identified and replicated 180 significant associations with 39 food groups (P<1.17x10-6), overall consisting of 106 different metabolites (74 known and 32 unknown), including 73 novel associations. In particular we identified trans-4-hydroxyproline as a potential marker of red meat intake (0.075[0.009]; P = 1.08x10-17), ergothioneine as a marker of mushroom consumption (0.181[0.019]; P = 5.93x10-22), and three potential markers of fruit consumption (top association: apple and pears): including metabolites derived from gut bacterial transformation of phenolic compounds, 3-phenylpropionate (0.024[0.004]; P = 1.24x10-8) and indolepropionate (0.026[0.004]; P = 2.39x10-9), and threitol (0.033[0.003]; P = 1.69x10-21). With the largest nutritional metabolomics dataset to date, we have identified 73 novel candidate biomarkers of food intake for potential use in nutritional epidemiological studies. We compiled our findings into the Diet

  14. Pulmonary artery sarcoma mimicking pulmonary thromboembolism.

    PubMed

    Celik, Gökhan; Ciledağ, Aydin; Yüksel, Cabir; Yenigün, Bülent Mustafa; Kutlay, Hakan; Yazicıoğlu, Levent; Perçinel, Sibel; Kaya, Akin

    2011-01-01

    A 30 years old male patient was referred to our hospital with a diagnosis of pulmonary thromboembolism due to thorax-computerized tomography (CT) angiography, revealing a thrombus totally occluding left main pulmonary artery. The lesion was evaluated as tumoural mass. Positron emission tomography (PET)-CT revealed pathologic uptake at pulmonary artery mass. Due to localization of tumour, left pneumonectomy was performed. The pathological diagnosis revealed to be pulmonary artery sarcoma. The patient was presented because pulmonary artery sarcomas are very rare tumors and can mimick pulmonary thromboembolism. The true prevalence is underestimated as many pulmonary artery sarcomas are misdiagnosed as pulmonary thromboembolism. PET-CT may help to make a differential diagnosis.

  15. Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Gladwin, Mark T.; Machado, Roberto F.; Wood, Bradford J.

    2008-03-01

    Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.

  16. Bioinformatic Characterization of Genes and Proteins Involved in Blood Clotting in Lampreys.

    PubMed

    Doolittle, Russell F

    2015-10-01

    Lampreys and hagfish are the earliest diverging of extant vertebrates and are obvious targets for investigating the origins of complex biochemical systems found in mammals. Currently, the simplest approach for such inquiries is to search for the presence of relevant genes in whole genome sequence (WGS) assemblies. Unhappily, in the past a high-quality complete genome sequence has not been available for either lampreys or hagfish, precluding the possibility of proving gene absence. Recently, improved but still incomplete genome assemblies for two species of lamprey have been posted, and, taken together with an extensive collection of short sequences in the NCBI trace archive, they have made it possible to make reliable counts for specific gene families. Particularly, a multi-source tactic has been used to study the lamprey blood clotting system with regard to the presence and absence of genes known to occur in higher vertebrates. As was suggested in earlier studies, lampreys lack genes for coagulation factors VIII and IX, both of which are critical for the "intrinsic" clotting system and responsible for hemophilia in humans. On the other hand, they have three each of genes for factors VII and X, participants in the "extrinsic" clotting system. The strategy of using raw trace sequence "reads" together with partial WGS assemblies for lampreys can be used in studies on the early evolution of other biochemical systems in vertebrates.

  17. Analytical characterization and comparison of the blood-brain barrier permeability of eight opioid peptides.

    PubMed

    Van Dorpe, Sylvia; Adriaens, Antita; Polis, Ingeborgh; Peremans, Kathelijne; Van Bocxlaer, Jan; De Spiegeleer, Bart

    2010-07-01

    Opioid drugs, including the newly developed peptides, should penetrate the blood-brain barrier (BBB) for pain management activity. Although BBB transport is fragmentarily described for some mu-opioid peptides, a complete and comparative overview is currently lacking. In this study, the BBB transport of eight opioid peptides (EM-1, EM-2, CTAP, CTOP, DAMGO, dermorphin, TAPP and TAPS) is described and compared. In addition, the metabolic stability in plasma and brain was evaluated. The highest influx rate was obtained for dermorphin (K(in)=2.18 microl/(g x min)), followed by smaller rates for EM-1, EM-2 and TAPP (K(in)=1.06-1.14 microl/(g x min)). Negligible influx was observed for DAMGO, CTOP and TAPS (K(in)=0.18-0.40 microl/(g x min)) and no influx for CTAP. Capillary depletion revealed that all peptides reached brain parenchyma for over 75%. Efflux was shown for TAPP (t(1/2)=2.82 min) and to a lesser extent for EM-1, EM-2 and DAMGO (t(1/2)=10.66-21.98 min), while no significant efflux was observed for the other peptides. All peptides were stable in mouse plasma and brain, with generally higher stability in brain, except for EM-1 and EM-2 which showed plasma half-life stabilities of a few minutes only.

  18. Characterization of monoclonal gammopathy of undetermined significance by calorimetric analysis of blood serum proteome.

    PubMed

    Barceló, Francisca; Cerdà, Joan J; Gutiérrez, Antonio; Jimenez-Marco, Teresa; Durán, M Antonia; Novo, Andrés; Ros, Teresa; Sampol, Antonia; Portugal, José

    2015-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant proliferative disorder that may progress to multiple myeloma, a malignant plasma cell neoplasia. We evaluated differential scanning calorimetry (DSC) as an experimental tool for differentiating serum samples of MGUS patients from healthy individuals. DSC thermograms can be used for monitoring changes in the serum proteome associated with MGUS. MGUS patients showed great variability in serum thermogram characteristics, which depended on the IgG, IgA or IgM isotypes and/or the κ or λ light chains. Thermogram feature parameters distinguished patients with MGUS from healthy people. Serum samples, named as non-MGUS, were also collected from patients with subjacent immunological pathologies who were discarded of having MGUS through serum immunofixation. They were used to verify the sensitivity of DSC for discriminating MGUS from related blood dyscrasias. Only some DSC thermogram feature parameters differentiated, to a lesser extent, between MGUS and non-MGUS individuals. We contemplate DSC as a tool for early diagnosis and monitoring of MGUS.

  19. Characterization of Monoclonal Gammopathy of Undetermined Significance by Calorimetric Analysis of Blood Serum Proteome

    PubMed Central

    Barceló, Francisca; Cerdà, Joan J.; Gutiérrez, Antonio; Jimenez-Marco, Teresa; Durán, M. Antonia; Novo, Andrés; Ros, Teresa; Sampol, Antonia; Portugal, José

    2015-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant proliferative disorder that may progress to multiple myeloma, a malignant plasma cell neoplasia. We evaluated differential scanning calorimetry (DSC) as an experimental tool for differentiating serum samples of MGUS patients from healthy individuals. DSC thermograms can be used for monitoring changes in the serum proteome associated with MGUS. MGUS patients showed great variability in serum thermogram characteristics, which depended on the IgG, IgA or IgM isotypes and/or the κ or λ light chains. Thermogram feature parameters distinguished patients with MGUS from healthy people. Serum samples, named as non-MGUS, were also collected from patients with subjacent immunological pathologies who were discarded of having MGUS through serum immunofixation. They were used to verify the sensitivity of DSC for discriminating MGUS from related blood dyscrasias. Only some DSC thermogram feature parameters differentiated, to a lesser extent, between MGUS and non-MGUS individuals. We contemplate DSC as a tool for early diagnosis and monitoring of MGUS. PMID:25794164

  20. Cloning, characterization and localization of CHS gene from blood orange, Citrus sinensis (L.) Osbeck cv. Ruby.

    PubMed

    Lu, Xu; Zhou, Wei; Gao, Feng

    2009-09-01

    Chalcone synthase (CHS) is involved in the biosynthesis of anthocyanin. In this study, a full-length DNA of CHS gene (named as CsCHS-bo) was cloned from the blood orange, Citrus sinensis (L.) Osbeck cv. Ruby. The gene was 1,512 bp in size containing an open reading frame (1,176 bp) encoding 391 amino acids. Comparative and bioinformatic analyses revealed that the deduced protein of CsCHS-bo was highly homologous to CHS from other plant species. The protein of CsCHS-bo had four CHS-specific conserved motifs and a CHS-family signature sequence GFGPG. Phylogenetic analysis indicated that the protein of CsCHS-bo was in a subgroup with CHS of Ruta Palmatum. The CsCHS-bo was localized to the chromosomes 2p, 4p and 6p by an improved fluorescence in situ hybridization technique, indicating that at least three copies of CsCHS-bo were present in the genome.

  1. Ceramides as possible nutraceutical compounds: characterization of the ceramides of the Moro blood orange ( Citrus sinensis ).

    PubMed

    Valsecchi, Manuela; Mauri, Laura; Casellato, Riccardo; Ciampa, Maria Grazia; Rizza, Luisa; Bonina, Andrea; Bonina, Francesco; Sonnino, Sandro

    2012-10-10

    Ceramides are presented as nutraceutical compounds for protection of colon carcinoma and as important cosmetic preparation components, increasing absorption through the skin. Therefore, the ceramide (Cer) content of Moro blood oranges was determined by mass spectrometry. A total of 114 Cer species were identified: ∼160 mg in the peels and ∼140 mg in the pulp per kilogram of oranges, expressed as "milligram equivalents of d18:1,17:0 Cer". The predominant ceramides contained 4-hydroxy-8-sphingenine (t18:1(Δ8)) and 4-hydroxysphinganine (t18:0) as long-chain bases (LCBs) and fatty acids (FAs) with different structures. In the pulp, t18:1(Δ8)- and t18:0-containing Cer species comprised 50.5 and 33.5% of the total, respectively, 11.5 and 3.5% non-hydroxylated FAs, respectively, 32.0 and 21.0% α-hydroxylated FAs, respectively, and 7.0 and 9.0% α,β-hydroxylated FAs, respectively. In the peels, t18:1(Δ8)- and t18:0-containing species comprised 49.5 and 34.5% of the total, respectively, 16.0 and 1.5% non-hydroxylated FAs, respectively, 31.5 and 29.0% α-hydroxylated FAs, respectively, and 2.0 and 4.0% α,β-hydroxylated FAs, respectively.

  2. Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis.

    PubMed

    Moignard, Victoria; Macaulay, Iain C; Swiers, Gemma; Buettner, Florian; Schütte, Judith; Calero-Nieto, Fernando J; Kinston, Sarah; Joshi, Anagha; Hannah, Rebecca; Theis, Fabian J; Jacobsen, Sten Eirik; de Bruijn, Marella F; Göttgens, Berthold

    2013-04-01

    Cellular decision-making is mediated by a complex interplay of external stimuli with the intracellular environment, in particular transcription factor regulatory networks. Here we have determined the expression of a network of 18 key haematopoietic transcription factors in 597 single primary blood stem and progenitor cells isolated from mouse bone marrow. We demonstrate that different stem/progenitor populations are characterized by distinctive transcription factor expression states, and through comprehensive bioinformatic analysis reveal positively and negatively correlated transcription factor pairings, including previously unrecognized relationships between Gata2, Gfi1 and Gfi1b. Validation using transcriptional and transgenic assays confirmed direct regulatory interactions consistent with a regulatory triad in immature blood stem cells, where Gata2 may function to modulate cross-inhibition between Gfi1 and Gfi1b. Single-cell expression profiling therefore identifies network states and allows reconstruction of network hierarchies involved in controlling stem cell fate choices, and provides a blueprint for studying both normal development and human disease.

  3. Characterization of the cation-binding capacity of a potassium-adsorption filter used in red blood cell transfusion.

    PubMed

    Suzuki, Takao; Muto, Shigeaki; Miyata, Yukio; Maeda, Takao; Odate, Takayuki; Shimanaka, Kimio; Kusano, Eiji

    2015-06-01

    A K(+) -adsorption filter was developed to exchange K(+) in the supernatant of stored irradiated red blood cells with Na(+) . To date, however, the filter's adsorption capacity for K(+) has not been fully evaluated. Therefore, we characterized the cation-binding capacity of this filter. Artificial solutions containing various cations were continuously passed through the filter in 30 mL of sodium polystyrene sulfonate at 10 mL/min using an infusion pump at room temperature. The cation concentrations were measured before and during filtration. When a single solution containing K(+) , Li(+) , H(+) , Mg(2+) , Ca(2+) , or Al(3+) was continuously passed through the filter, the filter adsorbed K(+) and the other cations in exchange for Na(+) in direct proportion to the valence number. The order of affinity for cation adsorption to the filter was Ca(2+) >Mg(2+) >K(+) >H(+) >Li(+) . In K(+) -saturated conditions, the filter also adsorbed Na(+) . After complete adsorption of these cations on the filter, their concentration in the effluent increased in a sigmoidal manner over time. Cations that were bound to the filter were released if a second cation was passed through the filter, despite the different affinities of the two cations. The ability of the filter to bind cations, especially K(+) , should be helpful when it is used for red blood cell transfusion at the bedside. The filter may also be useful to gain a better understanding of the pharmacological properties of sodium polystyrene sulfonate.

  4. Pulmonary Paragonimiasis Mimicking Tuberculous Pleuritis

    PubMed Central

    Luo, Jian; Wang, Mao-Yun; Liu, Dan; Zhu, Hui; Yang, Sai; Liang, Bin-Miao; Liang, Zong-An

    2016-01-01

    Abstract Pulmonary paragonimiasis is a food-borne zoonosis with a wide variety of radiologic findings, which sometimes can be confused with tuberculosis and carcinoma. Therefore, differential diagnosis is always warranted. A 43-year-old male farmer, with productive cough, blood-tinged sputum and chest pain, as well as patchy consolidation and pleural effusions in chest computer tomography, was misdiagnosed of community-acquired pneumonia and tuberculosis. Complete blood cell count, sputum smear and culture, chest computer tomography, thoracoscopy, and biopsy. The diagnosis of pulmonary paragonimiasis was established due to the finding of Charcot–Leyden crystals in the pleural necrosis, and antibodies against Paragonimus westermani in enzyme-linked immunosorbent assay. Paragonimiasis should be considered as a possibility in the differential diagnosis of tuberculosis. Thoracoscopy is an effective and valuable technology that can help make an accurate diagnosis. PMID:27082624

  5. [Pulmonary strongyloidiasis].

    PubMed

    Lozada, Heiler; Daza, Jorge E

    2016-10-01

    Strongyloidiasis is an infection caused by the parasite Strongyloides stercoralis, which can be asymptomatic and means a high morbidity and mortality in immunocompromised hosts, severe malnutrition and coinfection with HTLV-1 virus. The parasite has the potential to produce and multiply internal autoinfection in humans, thus an hyperinfection can be developed. A case of pulmonary infection by this parasite is presented in this study, infection which advanced into a respiratory failure and required mechanical ventilation and hemodynamic support in an intensive care unit. The standard treatment combined with ivermectin and albendazole was provided, achieving an appropriate response.

  6. Synthesis and characterization of PEGylated polyethylenimine-entrapped gold nanoparticles for blood pool and tumor CT imaging.

    PubMed

    Zhou, Benqing; Zheng, Linfeng; Peng, Chen; Li, Du; Li, Jingchao; Wen, Shihui; Shen, Mingwu; Zhang, Guixiang; Shi, Xiangyang

    2014-10-08

    The synthesis and characterization of gold nanoparticles (AuNPs) entrapped within polyethylene glycol (PEG)-modified polyethylenimine (PEI) for blood pool and tumor computed tomography (CT) imaging are reported. In this approach, partially PEGylated PEI was used as a template for AuNP synthesis, followed by acetylating the PEI remaining surface amines. The synthesized PEGylated PEI-entrapped AuNPs (Au PENPs) were characterized via different methods. Our results reveal that the synthesized Au PENPs can be tuned to have an Au core size in a range of 1.9-4.6 nm and to be water-soluble, stable, and noncytotoxic in a studied concentration range. With a demonstrated better X-ray attenuation property than that of clinically used iodinated small molecular contrast agent (e.g., Omnipaque) and the prolonged half-decay time (11.2 h in rat) confirmed by pharmacokinetics studies, the developed PEGylated Au PENPs enabled efficient and enhanced blood pool CT imaging with imaging time up to 75 min. Likewise, thanks to the enhanced permeability and retention effect, the PEGylated Au PENPs were also able to be used as a contrast agent for effective CT imaging of a tumor model. With the proven organ biocompatibility by histological studies, the designed PEGylated Au PENPs may hold great promise to be used as contrast agents for CT imaging of a variety of biological systems. The significance of this study is that rather than the use of dendrimers as templates, cost-effective branched polymers (e.g., PEI) can be used as templates to generate functionalized AuNPs for CT imaging applications.

  7. Characterization of pulmonary lesions in patients with suspected lung cancer: computed tomography versus [¹⁸F] fluorodeoxyglucose-positron emission tomography/computed tomography.

    PubMed

    Harders, Stefan Walbom; Madsen, Hans Henrik; Hjorthaug, Karin; Arveschoug, Anne Kirstine; Rasmussen, Torben Riis; Meldgaard, Peter; Andersen, Johanne Bach; Pilegaard, Hans Kristian; Hager, Henrik; Rehling, Michael; Rasmussen, Finn

    2012-10-16

    Pulmonary nodules are of high clinical importance, given they may prove to be an early manifestation of lung cancer. Pulmonary nodules are small, focal, radiographic opacities that may be solitary or multiple. A solitary pulmonary nodule is a single, small (<-30 mm in diameter) opacity. Larger opacities are called masses and are often malignant. As imaging techniques improve and more nodules are detected, the optimal management of pulmonary nodules remains unclear. However, the question of malignancy of any given nodule remains the same. A standard contrast-enhanced computed tomography (CT) scan is often the first examination, followed by a number of other examinations. The purpose of this study was to examine the clinical feasibility of CT versus integrated [18F]fluorodeoxyglucose-positron emission tomography (PET)/low-dose CT scan in patients with suspected lung cancer and pulmonary lesions on CT. All results were controlled for reproducibility. We found that when used early in the work-up of the lesions, CT raised the prevalence of lung cancer in the population to the point where further diagnostic imaging examination could be considered futile. We also found that the overall diagnostic accuracy, as well as the classification probabilities and predictive values of the two modalities were not significantly different; the reproducibility of these results was substantial.

  8. [Idiopathic pulmonary hemosiderosis with dendriform pulmonary ossification].

    PubMed

    Barrera, Ana Madeleine; Vargas, Leslie

    2016-12-01

    Pulmonary ossification is a rare and usually asymptomatic finding reported as incidental in lung biopsies. Similarly, idiopathic pulmonary hemosiderosis is a rare cause of pulmonary infiltrates. We report the case of a 64-year old man with chronic respiratory symptoms in whom these two histopathological findings converged.

  9. Pulmonary oedema following exercise in humans.

    PubMed

    Hodges, Alastair N H; Mayo, John R; McKenzie, Donald C

    2006-01-01

    Pulmonary physiologists have documented many transient changes in the lung and the respiratory system during and following exercise, including the incomplete oxygen saturation of arterial blood in some subjects, possibly due to transient pulmonary oedema. The large increase in pulmonary arterial pressure during exercise, leading to either increased pulmonary capillary leakage and/or pulmonary capillary stress failure, is likely to be responsible for any increase in extravascular lung water during exercise. The purpose of this article is to summarise the studies to date that have specifically examined lung water following exercise. A limited number of studies have been completed with the specific purpose of identifying pulmonary oedema following exercise or a similar intervention. Of these, approximately 50% have observed a positive change and the remaining have provided results that are either inconclusive or show no change in extravascular lung water. While it is difficult to draw a firm conclusion from these studies, we believe that pulmonary oedema does occur in some humans following exercise. As such, this is a phenomenon of significance to pulmonary and exercise physiologists. This possibility warrants further study in the area with more precise measurement tools than has previously been undertaken.

  10. [Pulmonary hemodynamics and hemostasis in rabbits exposed to high altitude].

    PubMed

    Almerekova, A A; Tartakovskiĭ, V N; Isakova, Zh T

    1993-01-01

    Pulmonary hemodynamics, homeostasis and red blood parameters were studied in 77 rabbits in the mountains of the Tien Shan (3200 m above sea-level). Exposure of animals in alpine environment gave rise to pulmonary hypertension, polycythemia, alterations of homeostasis by the pattern of hyper- and hypocoagulation syndrome. On certain stages of adaptation products of paracoagulation were observed in blood as well as intravascular aggregation of formed elements, increased sensitivity of blood plates to platelet activation, increased fibrinolysis. Given existing hypothesis about involvement of changes in homeostasis and red blood in the pathogenesis of altitude pulmonary hypertension, the coefficients of paired linear correlation between indices of pulmonary hemodynamics and blood have been calculated. These coefficients are valid only for low values of the ratio.

  11. Characterization of cerebral blood flow response to sciatic nerve stimulation using laser speckle imaging

    NASA Astrophysics Data System (ADS)

    Wang, Zheng; Luo, Qingming; Cheng, Haiying; Lu, Qiang

    2003-12-01

    Laser speckle imaging (LSI) through a thinned skull over the somatosensory cortex was utilized to map the spatiotemporal characteristics of local cerebral flood flow (CBF) in anesthetized rats during sciatic nerve stimulation. Region-of-interest selection and Temporal clustering analysis (TCA) method was illustrated on the dataset from high-resolution optical imaging to detect the timing and location of CBF activation. Contralateral hindlimb sensory cortical microflow was activated to increase promptly in less than 1 s after the onset of 2 s electrical stimulation then evolved in different discrete regions. Individual arteries, veins and capillaries in different diameters were activated with the time going. This pattern is similar but slightly elaborated to the results obtained from laser Doppler flowmetry (LDF), functional magnetic resonance imaging (fMRI). We presented this combination to characterize the behaviors of CBF response to neuronal activity, which might possibly lead to a better understanding of neurovascular coupling and fMRI signals.

  12. Kinetic characterization of the protein Z-dependent protease inhibitor reaction with blood coagulation factor Xa.

    PubMed

    Huang, Xin; Swanson, Richard; Broze, George J; Olson, Steven T

    2008-10-31

    Protein Z-dependent protease inhibitor (ZPI) is a recently identified member of the serpin superfamily that functions as a cofactor-dependent regulator of blood coagulation factors Xa (FXa) and XIa. Here we show that ZPI and its cofactor, protein Z (PZ), inhibit procoagulant membrane-bound factor Xa by the branched pathway acyl-intermediate trapping mechanism used by other serpins, but with significant variations of this mechanism that are unique to ZPI. Rapid kinetic analyses showed that the reaction proceeded by the initial assembly of a membrane-associated PZ-ZPI-FXa Michaelis complex (K(M) 53+/-5 nM) followed by conversion to a stable ZPI-FXa complex (k(lim) 1.2+/-0.1 s(-1)). Cofactor premixing experiments together with independent kinetic analyses of ZPI-PZ and factor Xa-PZ-membrane complex formation suggested that assembly of the Michaelis complex through either ZPI-PZ-lipid or factor Xa-PZ-lipid intermediates was rate-limiting. Reaction stoichiometry analyses and native PAGE showed that for every factor Xa molecule inhibited by ZPI, two serpin molecules were cleaved. Native PAGE and immunoblotting showed that PZ dissociated from ZPI once ZPI forms a stable complex with FXa, and kinetic analyses confirmed that PZ acted catalytically to accelerate the membrane-dependent ZPI-factor Xa reaction. The ZPI-FXa complex was only transiently stable and dissociated with a rate constant that showed a bell-shaped pH dependence indicative of participation of factor Xa active-site residues. The complex was detectable by SDS-PAGE when denatured at low pH, consistent with it being a kinetically trapped covalent acyl-intermediate. Together our findings show that ZPI functions like other serpins to regulate the activity of FXa but in a manner uniquely dependent on protein Z, procoagulant membranes, and pH.

  13. Post thaw characterization of umbilical cord blood: markers of storage lesion

    PubMed Central

    Hubel, Allison; Spindler, Ralf; Curtsinger, Julie M.; Lindgren, Bruce; Wiederoder, Sara; McKenna, David H.

    2014-01-01

    BACKGROUND The continued growth in the uses of umbilical cord blood (UCB) will require the development of meaningful post-thaw quality assays. This study examines both conventional and new measures for assessing UCB quality after long-term storage. STUDY DESIGN AND METHODS The first arm of the study involved thawing UCB in storage for short (~1 year) and long period of time (> 11 years). Conventional post thaw measures (CFU, TNC, CD34+45+) were quantified in addition to apoptosis. The second arm of the study involved taking units stored in liquid nitrogen and imposing a storage lesion by storing the units in −80°C for various periods of time. After storage lesion, the units were thawed and assessed. RESULTS In the first arm of the study, there was little difference in the post thaw measures between UCB stored for short and long periods of time. There was a slight increase in the percentage of CD34+45+ cells with time in storage and a reduction in the number of cells expressing apoptosis markers. When moved from liquid nitrogen to −80°C storage, the nucleated cell count varied little but there was a distinct drop in frequency of CFU and increase in percentage of cells expressing both early and late markers of apoptosis. CONCLUSION Nucleated cell counts do not reflect damage to hematopoietic progenitors during long-term storage. Expression of caspases and other markers of apoptosis provide an early biomarker of damage during storage, which is consistent with other measures such as CFU and percentage of CD34+45+ cells. PMID:25522958

  14. Optical and surface characterization of amorphous boron nitride thin films for use as blood compatible coatings

    NASA Astrophysics Data System (ADS)

    Lousinian, S.; Kalfagiannis, N.; Logothetidis, S.

    2009-10-01

    The aim of this work is the investigation of the haemocompatibility properties of homogeneous and amorphous boron nitride (a-BN) thin films, through the adsorption of two basic blood plasma proteins, human serum albumin (HSA) and fibrinogen (Fib). The a-BN thin films were grown onto c-Si(100) substrates under different values of substrate bias voltage, employing the radio frequency (RF) magnetron sputtering technique. For the consideration of the optical, compositional and structural properties of the films, Spectroscopic Ellipsometry (SE) in the Vis-UV spectral region was used, while for the study of surface topography and surface charge distribution as well as of the wetting properties of the a-BN thin films, Atomic Force Microscopy (AFM), Electric Force Microscopy (EFM) and Contact Angle measurements were additionally employed. The properties of the thin films were correlated with their haemocompatibility, through the estimation of the ratio of HSA/Fib surface concentration. The sp 3 content of the samples does not seem to correlate with the haemocompatibility of the a-BN thin films. However, the surface properties determine the thrombogenicity potential of the studied samples. More precisely, the a-BN films with a less negatively charged surface exhibit the smallest possibility of clot formation, possibly due to the interactions between the charged chains of the Fib molecules and the a-BN surface, while slight changes in the surface roughness do not affect their haemocompatibility properties. The wetting properties determine the thickness of the adsorbed Fib as well as the ratio of HSA/Fib surface concentration.

  15. Automated characterization of blood vessels as arteries and veins in retinal images.

    PubMed

    Mirsharif, Qazaleh; Tajeripour, Farshad; Pourreza, Hamidreza

    2013-01-01

    In recent years researchers have found that alternations in arterial or venular tree of the retinal vasculature are associated with several public health problems such as diabetic retinopathy which is also the leading cause of blindness in the world. A prerequisite for automated assessment of subtle changes in arteries and veins, is to accurately separate those vessels from each other. This is a difficult task due to high similarity between arteries and veins in addition to variation of color and non-uniform illumination inter and intra retinal images. In this paper a novel structural and automated method is presented for artery/vein classification of blood vessels in retinal images. The proposed method consists of three main steps. In the first step, several image enhancement techniques are employed to improve the images. Then a specific feature extraction process is applied to separate major arteries from veins. Indeed, vessels are divided to smaller segments and feature extraction and vessel classification are applied to each small vessel segment instead of each vessel point. Finally, a post processing step is added to improve the results obtained from the previous step using structural characteristics of the retinal vascular network. In the last stage, vessel features at intersection and bifurcation points are processed for detection of arterial and venular sub trees. Ultimately vessel labels are revised by publishing the dominant label through each identified connected tree of arteries or veins. Evaluation of the proposed approach against two different datasets of retinal images including DRIVE database demonstrates the good performance and robustness of the method. The proposed method may be used for determination of arteriolar to venular diameter ratio in retinal images. Also the proposed method potentially allows for further investigation of labels of thinner arteries and veins which might be found by tracing them back to the major vessels.

  16. COMPARISON BETWEEN SEDATION AND GENERAL ANESTHESIA FOR HIGH RESOLUTION COMPUTED TOMOGRAPHIC CHARACTERIZATION OF CANINE IDIOPATHIC PULMONARY FIBROSIS IN WEST HIGHLAND WHITE TERRIERS.

    PubMed

    Roels, Elodie; Couvreur, Thierry; Farnir, Frédéric; Clercx, Cécile; Verschakelen, Johny; Bolen, Géraldine

    2017-02-23

    Canine idiopathic pulmonary fibrosis is a progressive interstitial lung disease mainly affecting West Highland white terriers. Thoracic high-resolution computed tomographic (T-HRCT) findings for Canine idiopathic pulmonary fibrosis acquired under general anesthesia have been described previously. However, the use of general anesthesia may be contraindicated for some affected dogs. Sedation may allow improved speed and safety, but it is unknown whether sedation would yield similar results in identification and grading of Canine idiopathic pulmonary fibrosis lesions. The aim of this prospective, observational, method-comparison, case-control study was to compare findings from T-HRCT images acquired under sedation versus general anesthesia for West Highland white terriers affected with Canine idiopathic pulmonary fibrosis (n = 11) and age-matched controls (n = 9), using the glossary of terms of the Fleischner Society and a scoring system. Ground-glass opacity was identified in all affected West Highland white terriers for both sedation and general anesthesia acquisitions, although the Ground-glass opacity extent varied significantly between the two acquisitions (P < 0.001). Ground-glass opacity was the sole lesion observed in control dogs (n = 6), but was less extensive compared with affected West Highland white terriers. Identification and grading of a mosaic attenuation pattern differed significantly between acquisitions (P < 0.001). Identification of lesions such as consolidations, nodules, parenchymal and subpleural bands, bronchial wall thickening, and bronchiectasis did not differ between acquisitions. The present study demonstrated that T-HRCT obtained under sedation may provide different information than T-HRCT obtained under general anesthesia for identification and grading of some Canine idiopathic pulmonary fibrosis lesions, but not all of them. These differences should be taken into consideration when general anesthesia is contraindicated and sedation is

  17. Characterizing the Mechanistic Pathways of the Instant Blood-Mediated Inflammatory Reaction in Xenogeneic Neonatal Islet Cell Transplantation

    PubMed Central

    Liuwantara, David; Chew, Yi Vee; Favaloro, Emmanuel J.; Hawkes, Joanne M.; Burns, Heather L.; O'Connell, Philip J.; Hawthorne, Wayne J.

    2016-01-01

    Introduction The instant blood-mediated inflammatory reaction (IBMIR) causes major loss of islets after transplantation and consequently represents the initial barrier to survival of porcine neonatal islet cell clusters (NICC) after xenotransplantation. Methods This study used novel assays designed to characterize the various immunologic components responsible for xenogeneic IBMIR to identify initiators and investigate processes of IBMIR-associated coagulation, complement activation and neutrophil infiltration. The IBMIR was induced in vitro by exposing NICC to platelet-poor or platelet-rich human plasma or isolated neutrophils. Results We found that xenogeneic IBMIR was characterized by rapid, platelet-independent thrombin generation, with addition of platelets both accelerating and exacerbating this response. Platelet-independent complement activation was observed as early as 30 minutes after NICC exposure to plasma. However, membrane attack complex formation was not observed in NICC histopathology sections until after 60 minutes. We demonstrated for the first time that NICC-mediated complement activation was necessary for neutrophil activation in the xenogeneic IBMIR setting. Finally, using the Seahorse extracellular flux analyzer, we identified substantial loss of islet function (up to 40%) after IBMIR with surviving NICC showing evidence of mitochondrial damage. Conclusions This study used novel assays to describe multiple key pathways by which xenogeneic IBMIR causes islet destruction, allowing further refinement of future interventions aimed at resolving the issue of IBMIR in xenotransplantation. PMID:27500267

  18. Molecular linkage of hantavirus pulmonary syndrome to the white-footed mouse, Peromyscus leucopus: genetic characterization of the M genome of New York virus.

    PubMed Central

    Hjelle, B; Lee, S W; Song, W; Torrez-Martinez, N; Song, J W; Yanagihara, R; Gavrilovskaya, I; Mackow, E R

    1995-01-01

    The complete M segment sequences of hantaviruses amplified from tissues of a patient with hantavirus pulmonary syndrome in the northeastern United States and from white-footed mice, Peromyscus leucopus, from New York were 99% identical and differed from those of Four Corners virus by 23%. The serum of this patient failed to recognize a conserved, immunodominant epitope of the Four Corners virus G1 glycoprotein. Collectively, these findings indicate that P. leucopus harbors a genetically and antigenically distinct hantavirus that causes hantavirus pulmonary syndrome. PMID:7494337

  19. Computer-assisted diagnostic tool to quantify the pulmonary veins in sickle cell associated pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Jajamovich, Guido H.; Pamulapati, Vivek; Alam, Shoaib; Mehari, Alem; Kato, Gregory J.; Wood, Bradford J.; Linguraru, Marius George

    2012-03-01

    Pulmonary hypertension is a common cause of death among patients with sickle cell disease. This study investigates the use of pulmonary vein analysis to assist the diagnosis of pulmonary hypertension non-invasively with CT-Angiography images. The characterization of the pulmonary veins from CT presents two main challenges. Firstly, the number of pulmonary veins is unknown a priori and secondly, the contrast material is degraded when reaching the pulmonary veins, making the edges of these vessels to appear faint. Each image is first denoised and a fast marching approach is used to segment the left atrium and pulmonary veins. Afterward, a geodesic active contour is employed to isolate the left atrium. A thinning technique is then used to extract the skeleton of the atrium and the veins. The locations of the pulmonary veins ostia are determined by the intersection of the skeleton and the contour of the atrium. The diameters of the pulmonary veins are measured in each vein at fixed distances from the corresponding ostium, and for each distance, the sum of the diameters of all the veins is computed. These indicators are shown to be significantly larger in sickle-cell patients with pulmonary hypertension as compared to controls (p-values < 0.01).

  20. Pulmonary function in microgravity

    NASA Technical Reports Server (NTRS)

    Guy, H. J.; Prisk, G. K.; West, J. B.

    1992-01-01

    We report the successful collection of a large quantity of human resting pulmonary function data on the SLS-1 mission. Preliminary analysis suggests that cardiac stroke volumes are high on orbit, and that an adaptive reduction takes at least several days, and in fact may still be in progress after 9 days on orbit. It also suggests that pulmonary capillary blood volumes are high, and remain high on orbit, but that the pulmonary interstitium is not significantly impacted. The data further suggest that the known large gravitational gradients of lung function have only a modest influence on single breath tests such as the SBN washout. They account for only approximately 25% of the phase III slope of nitrogen, on vital capacity SBN washouts. These gradients are only a moderate source of the cardiogenic oscillations seen in argon (bolus gas) and nitrogen (resident gas), on such tests. They may have a greater role in generating the normal CO2 oscillations, as here the phase relationship to argon and nitrogen reverses in microgravity, at least at mid exhalation in those subjects studied to date. Microgravity may become a useful tool in establishing the nature of the non-gravitational mechanisms that can now be seen to play such a large part in the generation of intra-breath gradients and oscillations of expired gas concentration. Analysis of microgravity multibreath nitrogen washouts, single breath washouts from more physiological pre-inspiratory volumes, both using our existing SLS-1 data, and data from the upcoming D-2 and SLS-2 missions, should be very fruitful in this regard.(ABSTRACT TRUNCATED AT 250 WORDS).

  1. Pulmonary Arteriovenous Malformations

    PubMed Central

    2014-01-01

    Within the past decade, pulmonary arteriovenous malformations (PAVMs) have evolved from rare curiosities to not uncommon clinical states, with the latest estimates suggesting a prevalence of ∼1 in 2,600. PAVMs provide anatomic right-to-left shunts, allowing systemic venous blood to bypass gas exchange and pulmonary capillary bed processing. Hypoxemia and enhanced ventilatory demands result, although both are usually asymptomatic. Paradoxical emboli lead to strokes and cerebral abscesses, and these commonly occur in individuals with previously undiagnosed PAVMs. PAVM hemorrhage is rare but is the main cause of maternal death in pregnancy. PAVM occlusion by embolization is the standard of care to reduce these risks. However, recent data demonstrate that currently recommended management protocols can result in levels of radiation exposure that would be classified as harmful. Recent publications also provide a better appreciation of the hematologic and cardiovascular demands required to maintain arterial oxygen content and oxygen consumption in hypoxemic patients, identify patient subgroups at higher risk of complications, and emphasize the proportion of radiologically visible PAVMs too small to treat by embolization. This review, therefore, outlines medical states that exacerbate the consequences of PAVMs. Chief among these is iron deficiency, which is commonly present due to concurrent hereditary hemorrhagic telangiectasia: iron deficiency impairs hypoxemia compensations by restricting erythropoiesis and increases the risk of ischemic strokes. Management of periodontal disease, dental interventions, pulmonary hypertension, and pregnancy also requires specific consideration in the setting of PAVMs. The review concludes by discussing to what extent previously recommended protocols may benefit from modification or revision. PMID:25420112

  2. Pulmonary microlithiasis - A case report.

    PubMed

    Mahmood, Khalid; Ubaid, Muhammad; Mahmood, Aamer

    2016-01-01

    Pulmonary alveolar microlithiasis is a rare diffuse lung disease characterized by widespread sand-like intra-alveolar calcifications (calcospherites composed of calcium and phosphorus). Around 800 cases have been reported in the literature to date. We report here a case of a 35 years old female with prolonged h/o of exertional dyspnoea and mild cough. Clinical examination was mostly normal. Her Chest X-Ray revealed bilateral multiple nodular opacities (sand storm appearance). CT Scan chest showed diffuse micronodular calcifications with septal thickening, compatible with alveolar microlithiasis. Pulmonary function tests showed moderately restrictive lung disease. Bronchoscopic alveolar lavage revealed calcospherites in the alveloli and bronchi confirming the diagnosis of pulmonary alveolar microlithiasis.

  3. Peptide-micelle hybrids containing fasudil for targeted delivery to the pulmonary arteries and arterioles to treat pulmonary arterial hypertension.

    PubMed

    Gupta, Nilesh; Ibrahim, Hany M; Ahsan, Fakhrul

    2014-11-01

    This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cell-penetrating and lung-homing peptide, conjugated polyethylene glycol-distearoyl-phosphoethanolamine micelles containing fasudil, an investigational anti-PAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotaline-induced PAH rats. CAR micelles containing fasudil had an entrapment efficiency of approximately 58%, showed controlled release of the drug, and were monodispersed with an average size of approximately 14 nm. Nuclear magnetic resonance scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by approximately 1.7-fold and extended the drug half-life by approximately fivefold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy.

  4. Implantation of a stent graft in the right pulmonary artery enables radical resection of a central endothelial sarcoma of the left pulmonary artery.

    PubMed

    Kissling, Pascal; Brosi, Philippe; Kull, Christof; Toia, Damien; Maurer, Christoph Andreas

    2013-09-01

    In a patient with a huge endothelial sarcoma of the left pulmonary artery, we report successful implantation of a stent graft in the right pulmonary artery, including the pulmonary arterial trunk. This preoperative measure enabled a safe and radical left-sided pneumonectomy, including the tumor and the central parts of the left pulmonary artery. No major blood loss occurred, and neither use of a heart-lung machine nor cardiopulmonary bypass was necessary.

  5. Cardiac septic pulmonary embolism

    PubMed Central

    Song, Xin yu; Li, Shan; Cao, Jian; Xu, Kai; Huang, Hui; Xu, Zuo jun

    2016-01-01

    Abstract Based on the source of the embolus, septic pulmonary embolism (SPE) can be classified as cardiac, peripheral endogenous, or exogenous. Cardiac SPEs are the most common. We conducted a retrospective analysis of 20 patients with cardiac SPE hospitalized between 1991 and 2013 at a Chinese tertiary referral hospital. The study included 14 males and 6 females with a median age of 38.1 years. Fever (100%), cough (95%), hemoptysis (80%), pleuritic chest pain (80%), heart murmur (80%), and moist rales (75%) were common clinical manifestations. Most patients had a predisposing condition: congenital heart disease (8 patients) and an immunocompromised state (5 patients) were the most common. Staphylococcal (8 patients) and Streptococcal species (4 patients) were the most common causative pathogens. Parenchymal opacities, nodules, cavitations, and pleural effusions were the most common manifestations observed via computed tomography (CT). All patients exhibited significant abnormalities by echocardiography, including 15 patients with right-sided vegetations and 4 with double-sided vegetations. All patients received parenteral antimicrobial therapy as an initial treatment. Fourteen patients received cardiac surgery, and all survived. Among the 6 patients who did not undergo surgery, only 1 survived. Most patients in our cardiac SPE cohort had predisposing conditions. Although most exhibited typical clinical manifestations and radiography, they were nonspecific. For suspected cases of SPE, blood culture, echocardiography, and CT pulmonary angiography (CTPA) are important measures to confirm an early diagnosis. Vigorous early therapy, including appropriate antibiotic treatment and timely cardiac surgery to eradicate the infective source, is critical. PMID:27336870

  6. DNA Damage and Pulmonary Hypertension

    PubMed Central

    Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

    2016-01-01

    Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

  7. Riociguat for the treatment of pulmonary hypertension.

    PubMed

    Hambly, Nathan; Granton, John

    2015-01-01

    Nitric oxide (NO) is a critical signaling molecule in the pulmonary vasculature. NO activates soluble guanylate cyclase (sGC) resulting in the synthesis of cyclic guanosine monophosphate (cGMP) - a key mediator of pulmonary artery vasodilatation that may also inhibit smooth muscle proliferation and platelet aggregation. Pulmonary hypertension, a serious, progressive and often fatal disease is characterized by NO-sGC-sGMP pathway dysregulation. Riociguat is a member of a novel therapeutic class known as soluble guanylate stimulators. Riociguat has a dual mode of action, acting in synergy with endogenous NO and also directly stimulating sGC independently of NO availability. Phase 3 randomized control trials have demonstrated that riociguat improves clinical, physiologic and hemodynamic parameters in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. In this review we will discuss the pharmacologic properties of riociguat and its appropriate implementation into clinical practice.

  8. [Congenital pulmonary capillary hemangiomatosis in a newborn].

    PubMed

    Sposito Cavallo, Sandra L; Macias Sobrino, Luciano A; Marenco Altamar, Luifer J; Mejía Alquichire, Andrés F

    2017-02-01

    Pulmonary capillary hemangiomatosis is a rare entity characterized by the proliferation of capillaries into alveolar walls, interlobular septa, pleura and pulmonary interstitium, without malignant characteristics, with almost constant association with pulmonary hypertension. Until now two cases of congenital presentation have been reported in the literature. This is the third case in a newborn; he has not followed the usual pattern associated with pulmonary hypertension as occurs in most patients with this pathology; the highest incidence is among 20-40 years old. We report a preterm newborn patient of 36 weeks of gestation with progressive respiratory distress requiring mechanical ventilation by constant desaturation during his clinical evolution without clinical, radiological or ultrasonographic signs of pulmonary hypertension.

  9. Diffuse persistent interstitial pulmonary emphysema treated by lobectomy.

    PubMed

    Matta, Reva; Matta, Judy; Hage, Pierre; Nassif, Yolla; Mansour, Nabil; Diab, Nabil

    2011-10-01

    Persistent interstitial pulmonary emphysema is a rare condition that occurs in preterm infants on mechanical ventilation, characterized by abnormal accumulation of air in the pulmonary interstitium, due to disruption of the basement membrane. Diffuse persistent interstitial pulmonary emphysema is observed when small cysts are noted in all lobes of the lung. The management of infants suffering from diffuse persistent interstitial pulmonary emphysema varies according to severity and stability of the patient, being either conservative treatment or aggressive surgical treatment by pneumonectomy. We report a case of an unstable patient with diffuse persistent interstitial pulmonary emphysema successfully treated by lobectomy as a form of conservative surgical approach.

  10. Pulmonary toxocariasis: a case report and literature review.

    PubMed

    Ranasuriya, G; Mian, A; Boujaoude, Z; Tsigrelis, C

    2014-06-01

    Toxocariasis is a parasitic disease caused by Toxocara canis or T. cati. We report a patient with toxocariasis who presented with dyspnea, high-grade eosinophilia, and bilateral pulmonary nodules. To further characterize the pulmonary manifestations of toxocariasis, we have reviewed 11 previously published pulmonary toxocariasis cases. The most common pulmonary symptoms in our review were cough and dyspnea, and the most common finding on chest imaging was bilateral pulmonary nodules. Risk factors for Toxocara infection primarily included exposure to dogs. Most patients received albendazole and responded well. A high index of suspicion is needed to diagnose this otherwise preventable parasitic disease.

  11. Pulmonary tissue volume in dogs during pulmonary edema.

    PubMed

    Peterson, B T; Petrini, M F; Hyde, R W; Schreiner, B F

    1978-05-01

    Pulmonary tissue volume (Vt) and pulmonary capillary blood flow (Qc) were measured in anesthetized dogs by analyzing end-expiratory concentrations of dimethyl ether (DME), acetylene (C2H2), and sulfur hexafluoride during a 30-s rebreathing maneuver. Vt was compared to the postmortem lung weight of control dogs and dogs with hemodynamic and nonhemodynamic (alloxan) pulmonary edema. Qc was compared to the cardiac output measured by dye dilution. A 100-ml increase in alveolar volume (VA) in the range of 1-2 liters resulted in a 9 +/- 3 ml increase in Vt. Vt measured at a VA of 1.9 liters measures 114 +/- 18% of the postmortem lung weight in 20 control dogs and in 6 dogs with moderate edema (lung weight < 250% of predicted). Vt measured only 53 +/- 14% of the lung weight in 11 dogs with more severe edema. DME and C2H2 gave the smae mean values of Vt, but the reproducibility of a series of 3-7 measurements was greater with DME (coefficient of variation was 5% with DME and 8% C2H2). Qc measured 96 +/ 15% of the cardiac output during the rebreathing maneuver, but the maneuver caused a 4-40% fall in the cardiac output. These data show that Vt determined by rebreathing DME is between 86% and 135% of the lung weight in dogs with pulmonary edema until the lung weight is greater than 250% of the predicted value.

  12. Ovarian angiogenesis. Phenotypic characterization of endothelial cells in a physiological model of blood vessel growth and regression.

    PubMed Central

    Augustin, H. G.; Braun, K.; Telemenakis, I.; Modlich, U.; Kuhn, W.

    1995-01-01

    Angiogenesis occurs during embryogenesis and is a down-regulated process in the healthy adult that is almost exclusively linked to pathological conditions such as tumor growth, wound healing, and inflammation. Physiological angiogenic processes in the adult are restricted to the female reproductive system where they occur cyclically during the ovarian and uterine cycle as well as during pregnancy. By systematically analyzing the phenotypic changes of endothelial cells during bovine corpus luteum (CL) formation and regression, we have established a physiological model of blood vessel growth and regression. Quantitation of vessel density, percentage of vessels with lumen, and ratio of Bandeiraea simplicifolia-I to von Willebrand Factor-positive endothelial cells were established as parameters of angiogenesis. Sprouting endothelial cells invade the growing CL and continue to grow throughout the first third of the ovarian cycle. Thereafter the mature CL is characterized by a dense network of vessels with gradually decreasing vessel density. During luteolysis and for several weeks thereafter (regressing and residual CL) all newly formed vessels regress, which is accompanied by gradual foreshortening and rounding of endothelial cells and subsequent detachment. Based on histochemical detection of nucleosomal fragmentation products physiological blood vessel regression in the cyclic CL does not appear to involve endothelial cell apoptosis. Lectin histochemical analysis revealed a distinct alteration of endothelial cell glycoconjugate expression during ovarian angiogenesis comparable with the distinct pattern of hyperglycosylation of cultured migrating endothelial cells (up-regulation of binding sites for Lycopersicon esculentum lectin, wheat germ agglutinin, neuraminidase-treated peanut agglutinin, and Ricinus communis agglutinin-I on sprouting ECs). Northern blot analysis of glycosyltransferases during the different stages of angiogenesis revealed an up-regulation of beta

  13. Pulmonary complications in patients with chronic obstructive pulmonary disease following transthoracic esophagectomy

    PubMed Central

    Jiao, Wen-Jie; Wang, Tian-You; Gong, Min; Pan, Hao; Liu, Yan-Bing; Liu, Zhi-Hua

    2006-01-01

    AIM: To investigate the incidence of various types of postoperative pulmonary complications (POPCs) and to evaluate the significance of perioperative arterial blood gases in patients with esophageal cancer accompanied with chronic obstructive pulmonary disease (COPD) after esophagectomy. MEHTODS: Three hundred and fifty-eight patients were divided into POPC group and COPD group. We performed a retrospective review of the 358 consecutive patients after esophagectomy for esophageal cancer with or without COPD to assess the possible influence of COPD on postoperative pulmonary complications. We classified COPD into four grades according to percent-predicted forced expiratory volume in 1 s (FEV1) and analyzed the incidence rate of complications among the four grades. Perioperative arterial blood gases were tested in patients with or without pulmonary complications in COPD group and compared with POPC group. RESULTS: Patients with COPD (29/86, 33.7%) had more pulmonary complications than those without COPD (36/272, 13.2%) (P < 0.001). Pneumonia (15/29, 51.7%), atelectasis (13/29, 44.8%), prolonged O2 supplement (10/29, 34.5%), and prolonged mechanical ventilation (8/29, 27.6%) were the major complications in COPD group. Moreover, patients with severe COPD (gradeIIB, FEV1 < 50% of predicted) had more POPCs than those with moderate(gradeIIA, 50%-80% of predicted) and mild (gradeI≥ 80% of predicted) COPD (P < 0.05). PaO2 was decreased and PaCO2 was increased in patients with pulmonary complications in COPD group in the first postoperative week. CONCLUSION: The criteria of COPD are the critical predictor for pulmonary complications in esophageal cancer patients undergoing esophagectomy. Severity of COPD affects the incidence rate of the pulmonary complication, and percent-predicted FEV1 is a good predictive variable for pulmonary complication in patients with COPD. Arterial blood gases are helpful in directing perioperative management. PMID:16688794

  14. Interstitial Pulmonary Edema Following Bromocarbamide Intoxication

    PubMed Central

    Sugihara, H.; Hagedorn, M.; Bōttcher, D.; Neuhof, H.; Mittermayer, Ch.

    1974-01-01

    Bromocarbamides are sleep-inducing drugs which can lead, in man, to intoxication and death due to respiratory failure. To prove whether hemodynamic factors or the changed endothelial permeability induce pulmonary edema, animal experiments were performed. The fine structural changes in pulmonary edema in rabbits were observed at 60, 90 and 120 minutes after oral administration. The major findings were a) large blebs between capillary endothelium and alveolar epithelium and b) interstitial edema of the vessel wall. The bleb contents were much less electron dense than the blood contents in the capillary. Colloidal carbon did not enter the bleb or the edematous interstitial tissue. Exogenous peroxidase uptake in pinocytotie vesicles increased in pathologic cases. The hemodynamic measurements in animal receiving artificial respiration which maintained the blood pO2 at a steady state showed similar blebs in the pulmonary vessels, indicating that anoxia is not the major cause of the vascular lesion. Moreover, pulmonary arterial pressure and pulmonary vascular resistance could be held in the normal range in artificially respirated animals under bromocarbamide intoxication. Thus, hemodynamic factors are not likely to play a pathogenetic role in bringing about pulmonary edema. The chief, early factor is the increased endothelial permeability due to increased cytoplasmic transport. From this a practical suggestion for treating patients with bromocarbamide intoxication is derived: the usual fluid replacement in shock patients should be handled with great care to avoid fluid overload of the lung. ImagesFig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:4835993

  15. Pulmonary vasculature in COPD: The silent component.

    PubMed

    Blanco, Isabel; Piccari, Lucilla; Barberà, Joan Albert

    2016-08-01

    Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that results from an inflammatory process affecting the airways and lung parenchyma. Despite major abnormalities taking place in bronchial and alveolar structures, changes in pulmonary vessels also represent an important component of the disease. Alterations in vessel structure are highly prevalent and abnormalities in their function impair gas exchange and may result in pulmonary hypertension (PH), an important complication of the disease associated with reduced survival and worse clinical course. The prevalence of PH is high in COPD, particularly in advanced stages, although it remains of mild to moderate severity in the majority of cases. Endothelial dysfunction, with imbalance between vasodilator/vasoconstrictive mediators, is a key determinant of changes taking place in pulmonary vasculature in COPD. Cigarette smoke products may perturb endothelial cells and play a critical role in initiating vascular changes. The concurrence of inflammation, hypoxia and emphysema further contributes to vascular damage and to the development of PH. The use of drugs that target endothelium-dependent signalling pathways, currently employed in pulmonary arterial hypertension, is discouraged in COPD due to the lack of efficacy observed in randomized clinical trials and because there is compelling evidence indicating that these drugs may worsen pulmonary gas exchange. The subgroup of patients with severe PH should be ideally managed in centres with expertise in both PH and chronic lung diseases because alterations of pulmonary vasculature might resemble those observed in pulmonary arterial hypertension. Because this condition entails poor prognosis, it warrants specialist treatment.

  16. Branched perfluorooctane sulfonate isomer quantification and characterization in blood serum samples by HPLC/ESI-MS(/MS).

    PubMed

    Riddell, Nicole; Arsenault, Gilles; Benskin, Jonathan P; Chittim, Brock; Martin, Jonathan W; McAlees, Alan; McCrindle, Robert

    2009-10-15

    Perfluorooctane sulfonate (PFOS) is a global contaminant and is currently among the most prominent contaminants in human blood and wildlife samples. Although "total PFOS" (SigmaPFOS) analytical methods continue to be the most commonly used for quantification, recent analytical method developments have made it possible to resolve the various isomers of PFOS by HPLC-MS/MS. Characterized technical PFOS standards (i.e., containing a mixture of PFOS isomers) are now available that enable isomer specific quantification of PFOS, however the advantages of such an analysis have notyet been examined systematically. Herein, PFOS isomers have been individually quantified for the first time in real samples and the results are compared to a traditional SigmaPFOS method; the influence of analytical standards and isomer specific electrospray and MS/ MS behavior were also investigated. The two human serum standard reference materials chosen for analysis contained dramaticallydifferent PFOS isomer profiles (approximately 30-50% total branched isomers) emphasizing that isomer patterns should not be ignored and may provide useful information on exposure sources (i.e., direct exposure to PFOS vs indirect exposure from PFOS-precursors). Depending on the sample and the particular MS/MS transition chosen for SigmaPFOS analysis (i.e., 499-->80 or 499-->99), SigmaPFOS concentrations may be over- or underestimated compared to the isomer specific analysis. Differences in the extent of in-source fragmentation and MS/MS dissociation contributed to the systematic analytical bias. It was also shown that SigmaPFOS data are prone to interlaboratory variation due to various choices of PFOS standards and instrumental conditions used. In the future, for either SigmaPFOS or isomer specific PFOS analyses, we suggest that accuracy can be maximized and interlaboratory discrepancies minimized by using a common chemically pure technical PFOS standard characterized by 19F NMR.

  17. Right heart thrombi in pulmonary embolism.

    PubMed

    Barrios, Deisy; Rosa-Salazar, Vladimir; Jiménez, David; Morillo, Raquel; Muriel, Alfonso; Del Toro, Jorge; López-Jiménez, Luciano; Farge-Bancel, Dominique; Yusen, Roger; Monreal, Manuel

    2016-11-01

    There is a lack of comprehensive data on the prevalence, predictors and prognostic significance of right heart thrombi (RHT) in pulmonary embolism.In this study of patients with pulmonary embolism from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry, we assessed the prevalence and predictors of RHT, and the association between the presence of RHT and the outcomes of all-cause mortality, pulmonary embolism-related mortality, recurrences, and major bleeding through 30 days after initiation of pulmonary embolism treatment.Of 12 441 patients with pulmonary embolism and baseline echocardiographic data, 2.6% had RHT. The following increased the risk of RHT: younger age, previous bleeding, congestive heart failure, cancer, syncope, systolic blood pressure <100 mmHg, and arterial oxyhaemoglobin saturation <90%. Patients with RHT were significantly more likely to die from any cause (adjusted OR 2.50 (95% CI 1.62-3.84); p<0.001) and from pulmonary embolism (adjusted OR 4.29 (95% CI 2.45-7.48); p<0.001) during follow-up. RHT was associated with an increased risk of recurrence during follow-up (1.8% versus 0.7%; p=0.04). Major bleeding was similar in patients with and without RHT.In patients presenting with pulmonary embolism, RHT is relatively infrequent. Patients with RHT had a worse outcome when compared with those without RHT.

  18. Pulmonary disability in former Appalachian coal miners.

    PubMed Central

    Young, R. C.; Rachal, R. E.

    1996-01-01

    A prospective case-control study was undertaken to assess respiratory disability in 133 former coal miners who were claimants for "black lung" benefits. Consecutive assignment was made to either case or control group based on their chest radiograph having shown coal workers' pneumoconiosis or no coal workers' pneumoconiosis. A respiratory occupational survey was completed with physical examination that placed special emphasis on the cardiorespiratory systems. Subjects underwent pulmonary function testing while 92 of these also received arterial blood gases to assess respiratory disability and pulmonary insufficiency. Arterial blood gases were superior to spirometry in assessment of pulmonary insufficiency/disability. Smoking interacts with coal workers' pneumoconiosis to cause pulmonary insufficiency. The most frequent spirometric pattern was obstructive. Disability was caused by occupational injuries and comorbidities, both of which occurred with greater frequency in miners with coal workers' pneumoconiosis than in controls. Pulmonary insufficiency appears to be a better discriminator than respiratory disability in coal miners, suggesting that arterial blood gases replace spirometry in their evaluation. Greater emphasis on smoking intervention among coal miners should be given. Images Figure PMID:8803434

  19. Chronic obstructive pulmonary disease.

    PubMed

    Vijayan, V K

    2013-02-01

    The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are observed in central airways, small airways and alveolar space. The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair. Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec) to FVC (forced vital capacity) ratio <0.70. COPD is characterized by an accelerated decline in FEV1. Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure), hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline. The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death) and this is essential to guide therapy. COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor. Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support. Lung volume reduction surgery and lung transplantation are advised in selected severe patients. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease guidelines

  20. [Asthma and chronic obstructive pulmonary disease overlap].

    PubMed

    Müller, Veronika; Gálffy, Gabriella; Tamási, Lilla

    2011-01-16

    Asthma bronchiale and chronic obstructive pulmonary disease are the most prevalent lung diseases characterized by inflammation of the airways. International and Hungarian guidelines provide proper definitions for clinical symptoms, diagnostics and therapy of both diseases. However, in everyday clinical practice, overlap of asthma and chronic obstructive pulmonary disease has become more frequent. As guidelines are mainly based on large, multicenter, randomized, controlled trials that exclude overlap patients, there is a lack of diagnostic and especially therapeutic strategies for these patients. This review summarizes clinical characteristics of asthma and chronic obstructive pulmonary disease overlap, and provides daily practical examples for its management.

  1. Characterization of surface interleukin-2 receptor expression on gated populations of peripheral blood mononuclear cells from manatees, Trichechus manatus latirostris.

    PubMed

    Sweat, J M; Johnson, C M; Marikar, Y; Gibbs, E P

    2005-12-15

    An in vitro system to determine surface interleukin-2 receptor (IL-2R) expression on mitogen-stimulated peripheral blood mononuclear cells (PBMC) from free-ranging manatees, Trichechus manatus latirostris was developed. Human recombinant IL-2, conjugated with a fluorescein dye was used in conjunction with flow cytometric analysis to determine changes in surface expression of IL-2R at sequential times over a 48-h period of in vitro stimulation. Surface expression of IL-2R was detected on manatee PBMC, which also cross-reacted with an anti-feline pan T-cell marker. An expression index (EI) was calculated by comparing mitogen-activated and non-activated PBMC. Based on side- and forward-scatter properties, flow cytometric analysis showed an increase in the number of larger, more granular "lymphoblasts" following concanavalin A (Con A) stimulation. The appearance of lymphoblasts was correlated with an increase in their surface expression of IL-2 receptors. Surface IL-2R expression, in Con A-stimulated PBMC, was detected at 16 h, peaked at 24-36 h, and began to decrease by 48 h. Characterization of the IL-2R expression should provide additional information on the health status of manatees, and the effect of their sub lethal exposure to brevetoxin.

  2. Pulmonary Hypertension in Sarcoidosis.

    PubMed

    Baughman, Robert P; Engel, Peter J; Nathan, Steven

    2015-12-01

    Pulmonary hypertension is a complication of sarcoidosis leading to dyspnea and associated with increased morbidity and mortality. Sarcoidosis-associated pulmonary hypertension (SAPH) can be due to several factors, including vascular involvement by the granulomatous inflammation, compression of the pulmonary arteries by adenopathy, fibrotic changes within the lung, and left ventricular diastolic dysfunction. Several case series have suggested that some patients with SAPH benefit from specific therapy for pulmonary hypertension. A randomized, placebo-controlled trial found 16 weeks' bosentan therapy to be associated with significant improvement in pulmonary artery pressure. Future studies may better define who would respond to treatment of pulmonary hypertension.

  3. [Pulmonary alveolar microlithiasis. Study of pulmonary circulation].

    PubMed

    Orea Tejeda, A; Atencio, C; Sandoval, J; Lupi Herrera, E

    1982-01-01

    Pulmonary alveolar microlithiasis is a rare disease of unknown etiology which consists of alveolar deposit of calcium microspheres. We report the procedures for the diagnosis of this disease, as well as the hemodynamic features of the pulmonary circulation. Pulmonary arterial hypertension (PAH), and cor pulmonale were documented. The active and passive factors involved in PAH are analyzed. We conclude that alveolar hypoxia and estructural vascular changes play a major role in the genesis of PAH.

  4. Pulmonary pathophysiology of pneumococcal pneumonia.

    PubMed

    Light, R B

    1999-09-01

    Respiratory failure is one of the most important causes of death in patients with acute pneumococcal pneumonia. There are two forms that may or may not coexist: ventilatory failure and hypoxemic respiratory failure. Ventilatory failure is principally caused by mechanical changes in the lungs resulting from pneumonia. Inflammatory exudate fills alveoli at slightly less than their normal functional residual capacity (FRC), causing a volume loss at FRC roughly proportional to the extent of the pulmonary infiltrate. Because this consolidated air space does not inflate easily at higher transpulmonary pressures, at higher lung volumes the volume loss is proportionally greater. This loss of volume reduces total lung compliance and increases the work of breathing. There is also evidence that the dynamic compliance of the remaining ventilated lung is reduced in pneumococcal pneumonia, possibly by reduction in surfactant activity, further increasing the work of breathing. Arterial hypoxemia early in acute pneumococcal pneumonia is principally caused by persistence of pulmonary artery blood flow to consolidated lung resulting in an intrapulmonary shunt, but also, to a varying degree, it is caused by intrapulmonary oxygen consumption by the lung during the acute phase and by ventilation-perfusion mismatch later. The persistence of pulmonary blood flow to consolidated lung appears to be caused by a relative failure of the hypoxic pulmonary vasoconstriction (HPV) mechanism during acute pneumonia, which is at least caused by endogenous vasodilator prostaglandins associated with the inflammatory process but also by other as yet undefined mechanisms. During convalescence, arterial oxygenation improves as blood flow to consolidated lung falls. The magnitude of the intrapulmonary shunt may be influenced by a number of factors that modify the distribution of pulmonary blood flow. Factors that tend to increase flow to consolidated lung and worsen shunt include endogenous vasodilator

  5. Cardiac cavernous hemangioma and multiple pulmonary cavernous hemangiomas.

    PubMed

    Yang, Lili; Dai, Jun; Xiao, Ying; Cheng, Henghui; Ruan, Qiurong

    2014-02-01

    We describe for the first time a rare coexistence of a cardiac cavernous hemangioma with multiple pulmonary cavernous hemangiomas. Computed tomography revealed bilateral pulmonary nodules, left pleural effusion, and pericardial effusion. Positron emission tomography showed a pericardial neoplasm. Pathologically, multiple large dilated vascular spaces, lined by a single layer of endothelial cells and filled with blood, were revealed in both the cardiac tumor and the pulmonary nodules. Immunohistochemical examination of the lining cells showed positivity for CD31, FLI1, FVIII, and CD34. Taken together, these findings led to the diagnosis of cardiac cavernous hemangioma and multiple pulmonary cavernous hemangiomas.

  6. Blood sugar test - blood

    MedlinePlus

    ... sugar; Blood sugar level; Fasting blood sugar; Glucose test; Diabetic screening - blood sugar test; Diabetes - blood sugar test ... The test may be done in the following ways: After you have not eaten anything for at least 8 ...

  7. Pulmonary function in advanced pulmonary hypertension.

    PubMed Central

    Burke, C M; Glanville, A R; Morris, A J; Rubin, D; Harvey, J A; Theodore, J; Robin, E D

    1987-01-01

    Pulmonary mechanical function and gas exchange were studied in 33 patients with advanced pulmonary vascular disease, resulting from primary pulmonary hypertension in 18 cases and from Eisenmenger physiology in 15 cases. Evidence of airway obstruction was found in most patients. In addition, mean total lung capacity (TLC) was only 81.5% of predicted and 27% of our subjects had values of TLC less than one standard deviation below the mean predicted value. The mean value for transfer factor (TLCO) was 71.8% of predicted and appreciable arterial hypoxaemia was present, which was disproportionate to the mild derangements in pulmonary mechanics. Patients with Eisenmenger physiology had significantly lower values of arterial oxygen tension (PaO2) (p less than 0.05) and of maximum mid expiratory flow (p less than 0.05) and significantly higher pulmonary arterial pressure (p less than 0.05) than those with primary pulmonary hypertension, but no other variables were significantly different between the two subpopulations. It is concluded that advanced pulmonary vascular disease in patients with primary pulmonary hypertension and Eisenmenger physiology is associated not only with severe hypoxaemia but also with altered pulmonary mechanical function. PMID:3433237

  8. Conservation of Battlefield Blood Supply

    DTIC Science & Technology

    1996-12-01

    the anticipated blood loss is three to eight units (1500-4000 ml; e.g. extensive corrective spinal surgery, revision of artificial total hip prostheses...measurements (systemic and pulmonic arterial systolic, diastolic and mean blood pressures, central venous and pulmonary capillary "wedge" pressures, and

  9. Evolving Concepts of Pulmonary Hypertension Secondary to Left Heart Disease.

    PubMed

    Ramu, Bhavadharini; Thenappan, Thenappan

    2016-04-01

    Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension. Although its pathophysiology remains incompletely understood, it is now well recognized that the presence of pulmonary hypertension is associated with a worse prognosis. Right ventricular failure has independent and additive prognostic value over pulmonary hypertension for adverse outcomes in left heart disease. Recently, several new terminologies have been introduced to better define and characterize the nature and severity of pulmonary hypertension. Several new treatment options including the use of pulmonary arterial hypertension specific therapies are being considered, but there is lack of evidence. Here, we review the recent advances in this field and summarize the diagnostic and therapeutic modalities of use in the management of pulmonary hypertension associated with left heart disease.

  10. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary hypertension due to lung diseases and/or hypoxia.

    PubMed

    Sakkijha, Husam; Idrees, Majdy M

    2014-07-01

    Chronic lung diseases are common causes of pulmonary hypertension. It ranks second after the left heart disease. Both obstructive and restrictive lung diseases are know to cause pulmonary hypertension. The pathophysiology of the disease is complex, and includes factors affecting the blood vessels, airways, and lung parenchyma. Hypoxia and the inhalation of toxic materials are another contributing factors. Recent guidelines have further clarified the association between pulmonary hypertension and chronic lung disease and made general guidelines concerning the diagnosis and management. In this article, we will provide a detailed revision about the new classification and give general recommendations about the management of pulmonary hypertension in chronic lung diseases.

  11. Characterization of extracellular vesicles in whole blood: Influence of pre-analytical parameters and visualization of vesicle-cell interactions using imaging flow cytometry.

    PubMed

    Fendl, Birgit; Weiss, René; Fischer, Michael B; Spittler, Andreas; Weber, Viktoria

    2016-09-09

    Extracellular vesicles are central players in intercellular communication and are released from the plasma membrane under tightly regulated conditions, depending on the physiological and pathophysiological state of the producing cell. Their heterogeneity requires a spectrum of methods for isolation and characterization, where pre-analytical parameters have profound impact on vesicle analysis, particularly in blood, since sampling, addition of anticoagulants, as well as post-sampling vesicle generation may influence the outcome. Here, we characterized microvesicles directly in whole blood using a combination of flow cytometry and imaging flow cytometry. We assessed the influence of sample agitation, anticoagulation, and temperature on post-sampling vesicle generation, and show that vesicle counts remained stable over time in samples stored without agitation. Storage with gentle rolling mimicking agitation, in contrast, resulted in strong release of platelet-derived vesicles in blood anticoagulated with citrate or heparin, whereas vesicle counts remained stable upon anticoagulation with EDTA. Using imaging flow cytometry, we could visualize microvesicles adhering to blood cells and revealed an anticoagulant-dependent increase in vesicle-cell aggregates over time. We demonstrate that vesicles adhere preferentially to monocytes and granulocytes in whole blood, while no microvesicles could be visualized on lymphocytes. Our data underscore the relevance of pre-analytical parameters in vesicle analysis and demonstrate that imaging flow cytometry is a suitable tool to study the interaction of extracellular vesicles with their target cells.

  12. Possible role of lysophosphatidic acid in rat model of hypoxic pulmonary vascular remodeling

    PubMed Central

    2014-01-01

    Abstract Pulmonary hypertension is characterized by cellular and structural changes in the vascular wall of pulmonary arteries. We hypothesized that lysophosphatidic acid (LPA), a bioactive lipid, is implicated in this vascular remodeling in a rat model of hypoxic pulmonary hypertension. Exposure of Wistar rats to 10% O2 for 3 weeks induced an increase in the mean serum levels of LPA, to 40.9 (log-detransformed standard deviations: 23.4–71.7) μM versus 21.6 (11.0–42.3) μM in a matched control animal group (P = 0.037). We also observed perivascular LPA immunohistochemical staining in lungs of hypoxic rats colocalized with the secreted lysophospholipase D autotaxin (ATX). Moreover, ATX colocalized with mast cell tryptase, suggesting implication of these cells in perivascular LPA production. Hypoxic rat lungs expressed more ATX transcripts (2.4-fold) and more transcripts of proteins implicated in cell migration: β2 integrin (1.74-fold), intracellular adhesion molecule 1 (ICAM-1; 1.84-fold), and αM integrin (2.70-fold). Serum from the hypoxic group of animals had significantly higher chemoattractant properties toward rat primary lung fibroblasts, and this increase in cell migration could be prevented by the LPA receptor 1 and 3 antagonists. LPA also increased adhesive properties of human pulmonary artery endothelial cells as well as those of human peripheral blood mononuclear cells, via the activation of LPA receptor 1 or 3 followed by the stimulation of gene expression of ICAM-1, β-1, E-selectin, and vascular cell adhesion molecule integrins. In conclusion, chronic hypoxia increases circulating and tissue levels of LPA, which might induce fibroblast migration and recruitment of mononuclear cells in pulmonary vasculature, both of which contribute to pulmonary vascular remodeling. PMID:25621161

  13. TLR9 Differentiates Rapid from Slowly Progressive Forms of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Trujillo, Glenda; Meneghin, Alessia; Flaherty, Kevin R.; Sholl, Lynette M.; Myers, Jeffrey L.; Kazerooni, Ella A.; Gross, Barry H.; Oak, Sameer R.; Coelho, Ana Lucia; Evanoff, Holly; Day, Elizabeth; Toews, Galen B.; Joshi, Amrita D.; Schaller, Matthew A.; Waters, Beatrice; Jarai, Gabor; Westwick, John; Kunkel, Steve L.; Martinez, Fernando J.; Hogaboam, Cory M.

    2011-01-01

    Idiopathic pulmonary fibrosis is a generally progressive disorder with highly heterogeneous disease progression. The most common of the idiopathic interstitial pneumonias, idiopathic pulmonary fibrosis is characterized by a steady worsening of lung function and gas exchange cause by diffuse alveolar damage and severe fibrosis. We examined clinical features of patients with idiopathic pulmonary fibrosis to classify them as exhibiting rapid or slowly progressive over the first year of follow-up. We identified differences between the two groups in order to investigate the mechanism of rapid progression. Previous work from our laboratory has demonstrated that Toll-like receptor 9, a pathogen recognition receptor, promotes myofibroblast differentiation in lung fibroblasts cultured from biopsies of patients with idiopathic pulmonary fibrosis. Therefore, we hypothesized that TLR9 functions as both a sensor of pathogenic molecules and a profibrotic signal in rapidly progressive idiopathic pulmonary fibrosis. TLR9 was present at higher concentrations in surgical lung biopsies from rapidly progressive patients than in tissue from normal controls. Fibroblasts from rapid progressors were more responsive to the TLR9 agonist, CpG, than were fibroblasts from control patients. We used a humanized SCID mouse and demonstrated that there was increased fibrosis in murine lungs receiving human lung fibroblasts from rapid progressors than in mice receiving normal fibroblasts. This fibrosis was exacerbated by intranasal CpG challenges. Furthermore, CpG induced the differentiation of blood monocytes into fibrocytes and the epithelial-to-mesenchymal transition of A549 lung epithelial cells. These data suggest that TLR9 may drive the pathogenesis of rapidly progressive idiopathic pulmonary fibrosis and is a potential indicator of this subset of the disease. PMID:21068441

  14. Pulmonary microvascular cytology in the diagnosis of lymphangitic carcinomatosis.

    PubMed

    Masson, R G; Krikorian, J; Lukl, P; Evans, G L; McGrath, J

    1989-07-13

    The diagnosis of lymphangitic spread of carcinoma in the lungs is sometimes difficult. We studied the cytologic characteristics of blood drawn through a wedged pulmonary-artery catheter from eight patients in whom lymphangitic carcinomatosis was confirmed by subsequent autopsy, lung biopsy, or clinical evaluation. The sites of the primary tumors were the prostate, breast, esophagus, and lung. Malignant cells were found in seven of the eight patients. Cytologic findings were normal in 16 of 17 patients with cancer but without pulmonary metastases and in 22 of 23 patients with nonmalignant pulmonary disorders. In a patient with cancer with tumor embolism to the lungs, the findings were positive, probably because of extensive intravascular tumor in large hepatic veins. One false positive finding occurred in a patient with extensive pulmonary infarction. Megakaryocytes, which are present in large numbers in the pulmonary capillary bed, are the hallmark of a satisfactory pulmonary vascular blood sample for pulmonary microvascular cytologic study. Familiarity with the cytologic characteristics of these cells in Papanicolaou preparations is essential to avoid mistakenly identifying them as malignant. Although transbronchial lung biopsy remains the diagnostic procedure of choice in this disorder, our findings suggest that the presence of malignant cells in pulmonary microvascular-cytology preparations in patients with cancer and unexplained dyspnea constitutes presumptive evidence of lymphangitic carcinomatosis. Pulmonary microvascular cytology may be particularly valuable when lung biopsy is refused or is thought to be too hazardous.

  15. Lung Pathology in Pediatric Pulmonary Vein Stenosis.

    PubMed

    Pogoriler, Jennifer E; Kulik, Thomas J; Casey, Alicia M; Baird, Christopher W; Mullen, Mary P; Jenkins, Kathy J; Vargas, Sara O

    2016-01-01

    Pulmonary vein stenosis is a rare progressive narrowing of the extrapulmonary pulmonary veins, presenting predominantly in infancy and virtually always lethal. It typically arises following repair of congenital heart disease, particularly anomalous pulmonary venous return. Histologic characterization of pediatric pulmonary vein stenosis, not previously well described, may provide insight into the disease pathobiology. We retrieved archival lung specimens (biopsy, explant, or autopsy) from patients with pediatric pulmonary vein stenosis. Medical records were reviewed. Microscopic examination included hematoxylin and eosin (H&E)-stained slides, and for a subset of patients, elastic, trichrome, smooth-muscle actin, and D2-40. Groups with different clinical disease features were compared using Fisher's exact test. A total of 33 patients (median age, 7 months) had available tissue and 52% had congenital heart disease; 18% were premature. Within the lungs, interlobular septal veins showed thickened muscular coats (in 58%), proliferation/tortuosity (in 6%), and fibromyxoid intimal proliferation (in 3%). Associated arterial hypertensive changes were seen in 30 (91%). The one patient with intrapulmonary venous fibromyxoid intimal proliferation was the only patient with apparent primary familial disease. Lymphangiectasia and arterial medial hypertrophy were histologic features that correlated with clinical grouping. We conclude that in pediatric pulmonary vein stenosis, intrapulmonary pulmonary veins commonly show muscular thickening, best interpreted as venous hypertensive remodeling. Fibromyxoid intimal proliferation resembling that of the extrapulmonary pulmonary veins is uncommon. Awareness of intrapulmonary features in various clinical subtypes of pulmonary vein stenosis may be diagnostically and therapeutically informative considering that current catheter-based and surgical therapy is directed at the extrapulmonary component of pulmonary vein stenosis.

  16. Sudden death due to pulmonary aspergillosis.

    PubMed

    Bhagavath, Prashantha; Rastogi, Prateek; Menezes, Ritesh G; Valiathan, Manna; Mohan Kumar, T S; Raghavendra Babu, Y P; Kanchan, Tanuj; Monteiro, Francis N P; Nayak, Vinod C

    2009-01-01

    Sudden death due to respiratory pathology is not uncommon and tuberculosis with its complications is well known to cause death. We report a case of a male, train passenger, who started coughing out blood and died on reaching the hospital. Medicolegal autopsy confirmed the sudden unexpected death to be due to pulmonary aspergillosis in the person with past medical history of tuberculosis.

  17. Pulmonary Fibrosis Foundation

    MedlinePlus

    ... for a friend. Ways to Give Announcements CHICAGO BEAR JORDAN HOWARD BRINGS HIS FIGHT TO PULMONARY FIBROSIS ... 22-year-old lead rusher for the Chicago Bears, will announce his commitment to fight pulmonary fibrosis ( ...

  18. Who Needs Pulmonary Rehabilitation?

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... other symptoms. Examples of interstitial lung diseases include sarcoidosis and idiopathic pulmonary fibrosis . Cystic fibrosis (CF). CF ...

  19. Idiopathic Pulmonary Fibrosis

    MedlinePlus

    ... the NHLBI on Twitter. What Is Idiopathic Pulmonary Fibrosis? Pulmonary fibrosis (PULL-mun-ary fi-BRO-sis) is a ... time. The formation of scar tissue is called fibrosis. As the lung tissue thickens, your lungs can' ...

  20. Types of Pulmonary Hypertension

    MedlinePlus

    ... Hypertension The World Health Organization divides pulmonary hypertension (PH) into five groups. These groups are organized based ... lungs. Group 2 Pulmonary Hypertension Group 2 includes PH with left heart disease. Conditions that affect the ...

  1. [Pulmonary arterial hypertension in adult patients with congenital heart disease].

    PubMed

    Serino, G; Giacomazzi, F

    2010-01-01

    Pulmonary Hypertension (PH) is definited by a mean pulmonary artery pressure (PAPm) >25 mmHg at rest. The Dana Point 2008 Revised Classification System represents the most recent classification system update with respect of various etiologies of PH. About 10 % of adolescents or adults with uncorrected congenital heart disease (CHD) with left-to-right shunt and high pulmonary blood flow develop Pulmonary Arterial Hypertension (PAH) . Progressive vascular remodeling and increase in pulmonary vascular resistance (PVR) may ultimately lead to reversal of the shunt (pulmonary to systemic) causing cyanosis and determining the so-called Eisenmenger Syndrome (ES). Recent advances in the early diagnosis and medical targeted treatment of adult patients with CHD-PAH and ES can improve PAP, PVR and exercise tolerance, together with NYHA Class and survival, and may potentially reverse the vascular remodeling process in selected patients.