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Sample records for cardiac lymphatic dynamics

  1. Cardiac lymphatic dynamics after ischemia and reperfusion - experimental model

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    Santos, A.C. E-mail: cristina@imagem.ibili.uc.pt; Lima, J.J.P. de; Botelho, M.F.; Pacheco, M.F.; Sousa, P.; Bernardo, J.; Ferreira, N.; Goncalves, L.; Aguiar, J.; Providencia, L.A.; Pauwels, E.K.J

    1998-10-01

    The aim of the present study was to investigate the lymphatic cardiac circulation in an experimental model of ischemia plus reperfusion in mongrel dogs (Canis familiaris L). As radiotracer we used 0.2-0.25 ml (111 MBq) of {sup 99m}Tc-Re{sub 2}S{sub 7} colloid ({+-}10 {mu}m), injected subcapsullary below the second diagonal of the descending anterior ligated coronary artery with a special needle. A {gamma}-camera/Starport + DecStation were used for data acquisition. Four experimental groups with five animals each were established: G I = controls; G II = immediately after acute myocardial infarction (AMI); G III = late infarction (5 days after AMI); G IV = ischemia (90 min) + reperfusion. Four regions of interest (ROIs) were chosen: injection area (ZA), above (ZB), near right (ZD), and far right (ZC) from ZA. Mean disappearance times in ZA and dynamic parameters in the other ROIs were determined from activity/time curves drawn in each area, using homemade software. The results obtained seem to indicate that the methodology is appropriate to a detailed study of lymphatic drainage in pathological situations in animal models.

  2. Comparative and Developmental Anatomy of Cardiac Lymphatics

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    A. Ratajska

    2014-01-01

    Full Text Available The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells.

  3. Comparative and Developmental Anatomy of Cardiac Lymphatics

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    Ratajska, A.; Gula, G.; Flaht-Zabost, A.; Czarnowska, E.; Ciszek, B.; Jankowska-Steifer, E.; Niderla-Bielinska, J.; Radomska-Lesniewska, D.

    2014-01-01

    The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting) vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells. PMID:24592145

  4. Cardiac mouse lymphatics: developmental and anatomical update.

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    Flaht-Zabost, Aleksandra; Gula, Grzegorz; Ciszek, Bogdan; Czarnowska, Elżbieta; Jankowska-Steifer, Ewa; Madej, Maria; Niderla-Bielińska, Justyna; Radomska-Leśniewska, Dorota; Ratajska, Anna

    2014-06-01

    The adult mouse heart possesses an extensive lymphatic plexus draining predominantly the subepicardium and the outer layer of the myocardial wall. However, the development of this plexus has not been entirely explored, partially because of the lack of suitable methods for its visualization as well as prolonged lymphatic vessel formation that starts prenatally and proceeds during postnatal stages. Also, neither the course nor location of collecting vessels draining lymph from the mouse heart have been precisely characterized. In this article, we report that murine cardiac lymphatic plexus development that is limited prenatally only to the subepicardial area, postnatally proceeds from the subepicardium toward the myocardial wall with the base-to-apex gradient; this plexus eventually reaches the outer half of the myocardium with a predominant location around branches of coronary arteries and veins. Based on multiple marker immunostaining, the molecular marker-phenotype of cardiac lymphatic endothelial cells can be characterized as: Prox-1(+), Lyve-1(+), VEGFR3(+), Podoplanin(+), VEGFR2(+), CD144(+), Tie2(+), CD31(+), vWF(-), CD34(-), CD133(-). There are two major collecting vessels: one draining the right and left ventricles along the left conal vein and running upwards to the left side of the pulmonary trunk and further to the nearest lymph nodes (under the aortic arch and near the trachea), and the other one with its major branch running along the left cardiac vein and further on the surface of the coronary sinus and the left atrium to paratracheal lymph nodes. The extracardiac collectors gain the smooth muscle cell layer during late postnatal stages.

  5. LYMPHATIC SYSTEM: A FORGOTTEN AREA?

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    G. P. Itkin

    2016-01-01

    Full Text Available Development of new methods of visualization of the lymphatic system and in the treatment of several pathologies associated with impaired lymph fl ow. The lymphatic system is an integral part of the circulation. One of the main functions of the lymphatic system is to transport residual interstitial fl uid from the tissue back to the venous system. Despite growing recognition of the role of the lymphatic system in many disease processes, the techniques for imaging and interventions on the lymphatic system have lagged behind the well-developed methods for imaging and interventions on the cardiovascular systems. This is primarily due to small size and variability in anatomy of the lymphatic vessels, and diffi culty of introducing contrast into lymphatic ducts. Due to lack of imaging and intervention options, the fl ow function of the lymphatic system was relatively ignored over the last few decades. Recently, there has been resurgence in the interest in the fl ow function of the interventions on the lymphatic system with the development of percutaneous minimally invasive techniques, such as thoracic duct embolization, to treat life threatening lymphatic leaks. Our group recently introduced two new methods of lymphatic imaging: intranodal lymphangiography and dynamic contrast MR lymphangiography. These methods have allowed further understanding of lymphatic anatomy, pathophysiology, lymphodynamics, as well as provided guidance for novel minimally invasive lymphatic interventions. Using new techniques, the group discovered the causes and then developed treatments for several fatal conditions effecting single ventricle patients including plastic bronchitis and protein loosing enteropathy. Treatment for other conditions has evolved as well including congenital lymphodysplasia, chylothorax, and chylous ascites. The study of the liver lymphatic system has been little explored despite its signifi cant relevance as exampled in ascites formation in

  6. Lymphatic Disorders

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    ... Overview of the Lymphatic System Swollen Lymph Nodes Lymphedema Like the venous system, the lymphatic system transports ... lymphatic system leads to an accumulation of fluid ( lymphedema ). Obstruction may result from scar tissue that develops ...

  7. Study of fluid dynamics reveals direct communications between lymphatic vessels and venous blood vessels at lymph nodes of mice.

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    Takeda, Kazu; Mori, Shiro; Kodama, Tetsuya

    2017-02-22

    Cancer cells metastasize to lymph nodes, with distant metastasis resulting in poor prognosis. The role of lymph node metastasis (LNM) in the spread of cancer to distant organs remain incompletely characterized. The visualization of flow dynamics in the lymphatic and blood vessels of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes up to 10mm in diameter, has revealed that lymph nodes have the potential to be a direct source of systemic metastasis. However, it is not known whether these fluid dynamics characteristics are universal phenomena present in other strains of laboratory mice. Here we show that the fluid dynamics observed in MXH10/Mo-lpr/lpr mice are the same as those observed in C57BL/6J, BALB/cAJcl and NOD/ShiJic-scidJcl mice. Furthermore, when fluorescent solution was injected into a tumor-bearing lymph node, the flow dynamics observed in the efferent lymphatic vessels and thoracoepigastric vein depended on the type of tumor cell. Our results indicate that fluid dynamics in the lymphatic and blood vessels of MXH10/Mo-lpr/lpr mice are generalized phenomena seen in conventional laboratory mice. We anticipate our results can facilitate studies of the progression of lymphatic metastasis to hematogenous metastasis via lymph nodes and the early diagnosis and treatment of LNM.

  8. New method of displaying of bovine cardiac lymphatic vessels%牛心淋巴管显示新方法

    Institute of Scientific and Technical Information of China (English)

    许银辉; 申彪; 周楠茜; 吴满洋; 卢帅伟; 王猛; 黄俊友; 张爱梅; 李逸

    2011-01-01

    Objective To explore a new method to display the superficial lymphatic vessels of the cattle cardia. Methods The superficial lymphatic vessels were displayed by new type of lymphatic casting agent perfusion method and acid corrosion technology. Results The superficial lymphatic vessels could be seen with naked eyes after perfusion, and there were eighteen strips of integrity lymphatic stereo cast structure and lymphatic nodes after acid corrosion. Conclusion The new perfusion method can show the distribution of lymphatic vessels very well,and the specimen can be preserved for a long-term.%目的 探索显示牛心浅表淋巴管的新方法.方法 用新型淋巴管铸型剂灌注及酸腐蚀技术显示牛心浅表淋巴管.结果 灌注后肉眼可见牛心浅表淋巴管,腐蚀后显示18条完整立体管型结构及其淋巴结.结论 该灌注法能够很好的呈现出淋巴管的外形分布,并可长期保存.

  9. Cardiac fluid dynamics anticipates heart adaptation.

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    Pedrizzetti, Gianni; Martiniello, Alfonso R; Bianchi, Valter; D'Onofrio, Antonio; Caso, Pio; Tonti, Giovanni

    2015-01-21

    Hemodynamic forces represent an epigenetic factor during heart development and are supposed to influence the pathology of the grown heart. Cardiac blood motion is characterized by a vortical dynamics, and it is common belief that the cardiac vortex has a role in disease progressions or regression. Here we provide a preliminary demonstration about the relevance of maladaptive intra-cardiac vortex dynamics in the geometrical adaptation of the dysfunctional heart. We employed an in vivo model of patients who present a stable normal heart function in virtue of the cardiac resynchronization therapy (CRT, bi-ventricular pace-maker) and who are expected to develop left ventricle remodeling if pace-maker was switched off. Intra-ventricular fluid dynamics is analyzed by echocardiography (Echo-PIV). Under normal conditions, the flow presents a longitudinal alignment of the intraventricular hemodynamic forces. When pacing is temporarily switched off, flow forces develop a misalignment hammering onto lateral walls, despite no other electro-mechanical change is noticed. Hemodynamic forces result to be the first event that evokes a physiological activity anticipating cardiac changes and could help in the prediction of longer term heart adaptations.

  10. Cardiac mitochondria exhibit dynamic functional clustering

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    Felix Tobias Kurz

    2014-09-01

    Full Text Available Multi-oscillatory behavior of mitochondrial inner membrane potential ΔΨm in self-organized cardiac mitochondrial networks can be triggered by metabolic or oxidative stress. Spatio-temporal analyses of cardiac mitochondrial networks have shown that mitochondria are heterogeneously organized in synchronously oscillating clusters in which the mean cluster frequency and size are inversely correlated, thus suggesting a modulation of cluster frequency through local inter-mitochondrial coupling. In this study, we propose a method to examine the mitochondrial network's topology through quantification of its dynamic local clustering coefficients. Individual mitochondrial ΔΨm oscillation signals were identified for each cardiac myocyte and cross-correlated with all network mitochondria using previously described methods (Kurz et al., 2010. Time-varying inter-mitochondrial connectivity, defined for mitochondria in the whole network whose signals are at least 90% correlated at any given time point, allowed considering functional local clustering coefficients. It is shown that mitochondrial clustering in isolated cardiac myocytes changes dynamically and is significantly higher than for random mitochondrial networks that are constructed using the Erdös-Rényi model based on the same sets of vertices. The network's time-averaged clustering coefficient for cardiac myocytes was found to be 0.500 ± 0.051 (N=9 versus 0.061 ± 0.020 for random networks, respectively. Our results demonstrate that cardiac mitochondria constitute a network with dynamically connected constituents whose topological organization is prone to clustering. Cluster partitioning in networks of coupled oscillators has been observed in scale-free and chaotic systems and is therefore in good agreement with previous models of cardiac mitochondrial networks (Aon et al., 2008.

  11. LYMPHATIC DEVELOPMENT

    OpenAIRE

    Butler, Matthew G; Isogai, Sumio; Weinstein, Brant M.

    2009-01-01

    The lymphatic system is essential for fluid homeostasis, immune responses, and fat absorption, and is involved in many pathological processes, including tumor metastasis and lymphedema. Despite its importance, progress in understanding the origins and early development of this system has been hampered by lack of defining molecular markers and difficulties in observing lymphatic cells in vivo and performing genetic and experimental manipulation of the lymphatic system. Recent identification of...

  12. Predicting lymphatic filariasis transmission and elimination dynamics using a multi-model ensemble framework

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    Morgan E. Smith

    2017-03-01

    Full Text Available Mathematical models of parasite transmission provide powerful tools for assessing the impacts of interventions. Owing to complexity and uncertainty, no single model may capture all features of transmission and elimination dynamics. Multi-model ensemble modelling offers a framework to help overcome biases of single models. We report on the development of a first multi-model ensemble of three lymphatic filariasis (LF models (EPIFIL, LYMFASIM, and TRANSFIL, and evaluate its predictive performance in comparison with that of the constituents using calibration and validation data from three case study sites, one each from the three major LF endemic regions: Africa, Southeast Asia and Papua New Guinea (PNG. We assessed the performance of the respective models for predicting the outcomes of annual MDA strategies for various baseline scenarios thought to exemplify the current endemic conditions in the three regions. The results show that the constructed multi-model ensemble outperformed the single models when evaluated across all sites. Single models that best fitted calibration data tended to do less well in simulating the out-of-sample, or validation, intervention data. Scenario modelling results demonstrate that the multi-model ensemble is able to compensate for variance between single models in order to produce more plausible predictions of intervention impacts. Our results highlight the value of an ensemble approach to modelling parasite control dynamics. However, its optimal use will require further methodological improvements as well as consideration of the organizational mechanisms required to ensure that modelling results and data are shared effectively between all stakeholders.

  13. Dynamic NMR cardiac imaging in a piglet

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    Doyle, M.; Rzedzian, R.; Mansfield, P. (Nottingham Univ. (UK). Dept. of Physics); Coupland, R.E. (Nottingham Univ. (UK). Queen' s Medical Centre)

    1983-12-01

    NMR echo-planar imaging (EPI) has been used in a real-time mode to visualise the thorax of a live piglet. Moving pictures are available on an immediate image display system which demonstrates dynamic cardiac function. Frame rates vary from one per cardiac cycle in a prospective stroboscopic mode with immediate visual output to a maximum of 10 frames per second yielding up to six looks in one piglet heart cycle, but using a visual playback mode. A completely new system has been used to obtain these images, features of which include a probe assembly with 22 cm access and an AP400 array processor for real-time data processing.

  14. Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels.

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    Philipp Steven

    Full Text Available BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM. Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible

  15. Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus

    NARCIS (Netherlands)

    Burger, Nicole B.; Haak, Monique C.; Kok, Evelien; de Groot, Christianne J M; Shou, Weinian; Scambler, Peter J.; Lee, Youngsook; Cho, Eunjin; Christoffels, Vincent M.; Bekker, Mireille N.

    2016-01-01

    Background In human fetuses with cardiac defects and increased nuchal translucency, abnormal ductus venosus flow velocity waveforms are observed. It is unknown whether abnormal ductus venosus flow velocity waveforms in fetuses with increased nuchal translucency are a reflection of altered cardiac fu

  16. Lymphatic Education & Research Network

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    Lymphatic Education & Research Network Donate Now Become a Supporting Member X Living with LYMPHEDEMA AND Lymphatic Disease FAQs About ... 261 Madison Avenue, New York, NY 10016 | Lymphatic Education & Research Network is a 501(c)(3) under ...

  17. Accelerating Dynamic Cardiac MR Imaging Using Structured Sparse Representation

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    Nian Cai

    2013-01-01

    Full Text Available Compressed sensing (CS has produced promising results on dynamic cardiac MR imaging by exploiting the sparsity in image series. In this paper, we propose a new method to improve the CS reconstruction for dynamic cardiac MRI based on the theory of structured sparse representation. The proposed method user the PCA subdictionaries for adaptive sparse representation and suppresses the sparse coding noise to obtain good reconstructions. An accelerated iterative shrinkage algorithm is used to solve the optimization problem and achieve a fast convergence rate. Experimental results demonstrate that the proposed method improves the reconstruction quality of dynamic cardiac cine MRI over the state-of-the-art CS method.

  18. Anatomy of the lymphatics.

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    Skandalakis, John E; Skandalakis, Lee J; Skandalakis, Panagiotis N

    2007-01-01

    The lymphatic system is perhaps the most complicated system of Homo sapiens. An introduction to the anatomy, embryology, and anomalies of the lymphatics is presented. The overall anatomy and drainage of the lymphatic vessels in outlined. The topographic anatomy, relations, and variations of the principle vessels of the lymphatic system (the right lymphatic duct, the thoracic duct, and the cisterna chyli) are presented in detail.

  19. Dynamics of wave fronts and filaments in anisotropic cardiac tissue

    CERN Document Server

    Dierckx, Hans J F M

    2015-01-01

    The heartbeat is mediated between cardiac cells by waves of electrical depolarisation. During cardiac arrhythmias, electrical activity was found to be organised in scroll waves which rotate around a dynamical filament curve. In this thesis, a curved-space approach is used to mathematically capture anisotropy of wave propagation. We derive for the first time the covariant laws of motion for traveling wave fronts and scroll wave filaments in anisotropic excitable media such as cardiac tissue. We show that locally varying anisotropy yields non-zero Riemann tensor components, which may alter the stability of scroll wave filaments. The instability of scroll wave filaments has been linked to transition from ventricular tachycardia to fibrillation.

  20. Exploring the Role of Calcium in Cardiac Cell Dynamics

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    Berger, Carolyn; Idriss, Salim; Rouze, Ned; Hall, David; Gauthier, Daniel

    2007-03-01

    Bifurcations in the electrical response of cardiac tissue can destabilize spatio-temporal waves of electrochemical activity in the heart, leading to tachycardia or even fibrillation. Therefore, it is important to understand the mechanisms that cause instabilities in cardiac tissue.Traditionally, researchers have focused on understanding how the transmembrane voltage is altered in response to an increase in pacing rate, i.e. a shorter time interval between propagating electrochemical waves. However, the dynamics of the transmembrane voltage are coupled to the activity of several ions that traverse the membrane. Therefore, to fully understand the mechanisms that drive these bifurcations, we must include an investigation of the ionic behavior. We will present our recent investigation of the role of intracellular calcium in an experimental testbed of frog ventricle. Calcium and voltage are measured simultaneously, allowing for the previous research regarding voltage to guide our understanding of the calcium dynamics.

  1. Measurement of cardiac output from dynamic pulmonary circulation time CT

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    Yee, Seonghwan, E-mail: Seonghwan.Yee@Beaumont.edu [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan 48073 (United States); Scalzetti, Ernest M. [Department of Radiology, SUNY Upstate Medical University, Syracuse, New York 13210 (United States)

    2014-06-15

    Purpose: To introduce a method of estimating cardiac output from the dynamic pulmonary circulation time CT that is primarily used to determine the optimal time window of CT pulmonary angiography (CTPA). Methods: Dynamic pulmonary circulation time CT series, acquired for eight patients, were retrospectively analyzed. The dynamic CT series was acquired, prior to the main CTPA, in cine mode (1 frame/s) for a single slice at the level of the main pulmonary artery covering the cross sections of ascending aorta (AA) and descending aorta (DA) during the infusion of iodinated contrast. The time series of contrast changes obtained for DA, which is the downstream of AA, was assumed to be related to the time series for AA by the convolution with a delay function. The delay time constant in the delay function, representing the average time interval between the cross sections of AA and DA, was determined by least square error fitting between the convoluted AA time series and the DA time series. The cardiac output was then calculated by dividing the volume of the aortic arch between the cross sections of AA and DA (estimated from the single slice CT image) by the average time interval, and multiplying the result by a correction factor. Results: The mean cardiac output value for the six patients was 5.11 (l/min) (with a standard deviation of 1.57 l/min), which is in good agreement with the literature value; the data for the other two patients were too noisy for processing. Conclusions: The dynamic single-slice pulmonary circulation time CT series also can be used to estimate cardiac output.

  2. In vivo label-free monitoring microvascular and lymphatic vessel changes and dynamics during wound healing in mouse ear pinna using optical microangiography

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    Yousefi, Siavash; Wang, Ruikang K.

    2014-02-01

    Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. In this paper, we briefly review wound healing phases that were observed by utilizing optical microangiography (OMAG) to monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic area. Also, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid.

  3. Entropy Rate Maps of Complex Excitable Dynamics in Cardiac Monolayers

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    Alexander Schlemmer

    2015-02-01

    Full Text Available The characterization of spatiotemporal complexity remains a challenging task. This holds in particular for the analysis of data from fluorescence imaging (optical mapping, which allows for the measurement of membrane potential and intracellular calcium at high spatial and temporal resolutions and, therefore, allows for an investigation of cardiac dynamics. Dominant frequency maps and the analysis of phase singularities are frequently used for this type of excitable media. These methods address some important aspects of cardiac dynamics; however, they only consider very specific properties of excitable media. To extend the scope of the analysis, we present a measure based on entropy rates for determining spatiotemporal complexity patterns of excitable media. Simulated data generated by the Aliev–Panfilov model and the cubic Barkley model are used to validate this method. Then, we apply it to optical mapping data from monolayers of cardiac cells from chicken embryos and compare our findings with dominant frequency maps and the analysis of phase singularities. The studies indicate that entropy rate maps provide additional information about local complexity, the origins of wave breakup and the development of patterns governing unstable wave propagation.

  4. Pacemaker interactions induce reentrant wave dynamics in engineered cardiac culture

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    Borek, Bartłomiej; Shajahan, T. K.; Gabriels, James; Hodge, Alex; Glass, Leon; Shrier, Alvin

    2012-09-01

    Pacemaker interactions can lead to complex wave dynamics seen in certain types of cardiac arrhythmias. We use experimental and mathematical models of pacemakers in heterogeneous excitable media to investigate how pacemaker interactions can be a mechanism for wave break and reentrant wave dynamics. Embryonic chick ventricular cells are cultured invitro so as to create a dominant central pacemaker site that entrains other pacemakers in the medium. Exposure of those cultures to a potassium channel blocker, E-4031, leads to emergence of peripheral pacemakers that compete with each other and with the central pacemaker. Waves emitted by faster pacemakers break up over the slower pacemaker to form reentrant waves. Similar dynamics are observed in a modified FitzHugh-Nagumo model of heterogeneous excitable media with two distinct sites of pacemaking. These findings elucidate a mechanism of pacemaker-induced reentry in excitable media.

  5. Lymphatic fluid: exchange mechanisms and regulation

    Science.gov (United States)

    Huxley, Virginia H; Scallan, Joshua

    2011-01-01

    Abstract Regulation of fluid and material movement between the vascular space of microvessels penetrating functioning organs and the cells therein has been studied extensively. Unanswered questions as to the regulatory mechanisms and routes remain. Significantly less is known about the lymphatic vascular system given the difficulties in seeing, no less isolating, these vessels lying deeper in these same tissues. It has become evident that the exchange microvasculature is not simply a passive biophysical barrier separating the vascular and interstitial compartments but a dynamic, multicellular structure subject to acute regulation and chronic adaptation to stimuli including inflammation, sepsis, diabetes, injury, hypoxia and exercise. Similarly lymphatic vessels range, in their simplest form, from lymphatic endothelium attached to the interstitial matrix, to endothelia and phasic lymphatic smooth muscle that act as Starling resistors. Recent work has demonstrated that among the microvascular lymphatic elements, the collecting lymphatics have barrier properties similar to venules, and thus participate in exchange. As with venules, vasoactive agents can alter both the permeability and contractile properties thereby setting up previously unanticipated gradients in the tissue space and providing potential targets for the pharmacological prevention and/or resolution of oedema. PMID:21521763

  6. Spatiotemporal control of cardiac anisotropy using dynamic nanotopographic cues.

    Science.gov (United States)

    Mengsteab, Paulos Y; Uto, Koichiro; Smith, Alec S T; Frankel, Sam; Fisher, Elliot; Nawas, Zeid; Macadangdang, Jesse; Ebara, Mitsuhiro; Kim, Deok-Ho

    2016-04-01

    Coordinated extracellular matrix spatiotemporal reorganization helps regulate cellular differentiation, maturation, and function in vivo, and is therefore vital for the correct formation, maintenance, and healing of complex anatomic structures. In order to evaluate the potential for cultured cells to respond to dynamic changes in their in vitro microenvironment, as they do in vivo, the collective behavior of primary cardiac muscle cells cultured on nanofabricated substrates with controllable anisotropic topographies was studied. A thermally induced shape memory polymer (SMP) was employed to assess the effects of a 90° transition in substrate pattern orientation on the contractile direction and structural organization of cardiomyocyte sheets. Cardiomyocyte sheets cultured on SMPs exhibited anisotropic contractions before shape transition. 48 h after heat-induced shape transition, the direction of cardiomyocyte contraction reoriented significantly and exhibited a bimodal distribution, with peaks at ∼45 and -45° (P < 0.001). Immunocytochemical analysis highlighted the significant structural changes that the cells underwent in response to the shift in underlying topography. The presented results demonstrate that initial anisotropic nanotopographic cues do not permanently determine the organizational fate or contractile properties of cardiomyocytes in culture. Given the importance of surface cues in regulating primary and stem cell development, investigation of such tunable nanotopographies may have important implications for advancing cellular maturation and performance in vitro, as well as improving our understanding of cellular development in response to dynamic biophysical cues.

  7. ENDOMETRIOSIS WITH LYMPHATIC SPREAD

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    Narmadha

    2014-10-01

    Full Text Available Pelvic endometriosis is a common gynaecologic problem. But the histogenesis of endometriosis was not so clear. Various theories have been proposed by Pathologist in the past. Here we present a case of endometriosis of fallopian tube by lymphatic spread which has been proved histopathologically

  8. Image Registration and Analysis for Quantitative Myocardial Perfusion: Application to Dynamic Circular Cardiac CT

    NARCIS (Netherlands)

    Isola, A.; Schmitt, H.; Van Stevendaal, U.; Begemann, P.G.C.; Coulon, P.; Boussel, L.; Grass, M.

    2012-01-01

    Large area detector computed tomography systems with fastrotating gantries enable volumetric dynamic cardiac perfusion studies. Prospectively ECG-triggered acquisitions limit the data acquisition to a predefined cardiac phase and thereby reduce X-ray dose andlimit motion artifacts. Even in the case

  9. Image Registration and Analysis for Quantitative Myocardial Perfusion: Application to Dynamic Circular Cardiac CT

    NARCIS (Netherlands)

    Isola, A.; Schmitt, H.; Van Stevendaal, U.; Begemann, P.G.C.; Coulon, P.; Boussel, L.; Grass, M.

    2012-01-01

    Large area detector computed tomography systems with fastrotating gantries enable volumetric dynamic cardiac perfusion studies. Prospectively ECG-triggered acquisitions limit the data acquisition to a predefined cardiac phase and thereby reduce X-ray dose andlimit motion artifacts. Even in the case

  10. Nonlinear dynamics in sudden cardiac death syndrome: heartrate oscillations and bifurcations.

    Science.gov (United States)

    Goldberger, A L; Rigney, D R; Mietus, J; Antman, E M; Greenwald, S

    1988-12-01

    Patients at high risk of sudden cardiac death show evidence of nonlinear heartrate dynamics, including abrupt spectral changes (bifurcations) and sustained low frequency (.01-.04 Hz) oscillations in heartrate.

  11. Lymphatics and lymphatic-like structures in melanoma : a pathobiological study

    NARCIS (Netherlands)

    Clarijs, Johannes Antonius Godefridus Marinus

    2003-01-01

    Solid malignant tumors can be regarded as a functional tissue in which architecture and function are maintained by a dynamic interplay between tumor cells and a microenvironment consisting of extracellular matrix (ECM) containing fibroblasts, blood and lymphatic vasculature and infiltrating and resi

  12. Lymphatics and lymphatic-like structures in melanoma : a pathobiological study

    NARCIS (Netherlands)

    Clarijs, Johannes Antonius Godefridus Marinus

    2003-01-01

    Solid malignant tumors can be regarded as a functional tissue in which architecture and function are maintained by a dynamic interplay between tumor cells and a microenvironment consisting of extracellular matrix (ECM) containing fibroblasts, blood and lymphatic vasculature and infiltrating and resi

  13. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish

    Directory of Open Access Journals (Sweden)

    Katarzyna Koltowska

    2015-12-01

    Full Text Available Lymphatic vessels arise chiefly from preexisting embryonic veins. Genetic regulators of lymphatic fate are known, but how dynamic cellular changes contribute during the acquisition of lymphatic identity is not understood. We report the visualization of zebrafish lymphatic precursor cell dynamics during fate restriction. In the cardinal vein, cellular commitment is linked with the division of bipotential Prox1-positive precursor cells, which occurs immediately prior to sprouting angiogenesis. Following precursor division, identities are established asymmetrically in daughter cells; one daughter cell becomes lymphatic and progressively upregulates Prox1, and the other downregulates Prox1 and remains in the vein. Vegfc drives cell division and Prox1 expression in lymphatic daughter cells, coupling signaling dynamics with daughter cell fate restriction and precursor division.

  14. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish

    DEFF Research Database (Denmark)

    Koltowska, Katarzyna; Lagendijk, Anne Karine; Pichol-Thievend, Cathy;

    2015-01-01

    during fate restriction. In the cardinal vein, cellular commitment is linked with the division of bipotential Prox1-positive precursor cells, which occurs immediately prior to sprouting angiogenesis. Following precursor division, identities are established asymmetrically in daughter cells; one daughter...... cell becomes lymphatic and progressively upregulates Prox1, and the other downregulates Prox1 and remains in the vein. Vegfc drives cell division and Prox1 expression in lymphatic daughter cells, coupling signaling dynamics with daughter cell fate restriction and precursor division.......Lymphatic vessels arise chiefly from preexisting embryonic veins. Genetic regulators of lymphatic fate are known, but how dynamic cellular changes contribute during the acquisition of lymphatic identity is not understood. We report the visualization of zebrafish lymphatic precursor cell dynamics...

  15. The effect of lymphatic valve morphology on fluid transport

    Science.gov (United States)

    Alexeev, Alexander; Ballard, Matthew; Nepiyushchikh, Zhanna; Dixon, Brandon

    2016-11-01

    The lymphatic vasculature is present in nearly all invertebrate tissue, and is essential in the transport of fluid and particles such as immune cells, antigens, proteins and lipids from the tissue to lymph nodes and to the venous circulation. Lymphatic vessels are made of up a series of contractile units that work together in harmony as "micro hearts" to pump fluid against a pressure gradient. Lymphatic valves are critical to this functionality, as they open and close with the oscillating pressure gradients from contractions, thus allowing flow in only one direction and leading to a net pumping effect. We use a hybrid lattice-Boltzmann lattice spring model which captures fluid-solid interactions through two-way coupling between a viscous fluid and lymphatic valves in a section of a lymphatic vessel to study the dynamics of lymphatic valves and their effect on fluid transport. Further, we investigate the effect of variations in valve geometry and material properties on fluid pumping. This work helps to increase our understanding of the mechanisms of lymphatic fluid transport, which has implications in a variety of pathologies, including cancer metastasis, autoimmunity, atherosclerosis and obesity. Support from NSF CMMI 1635133 is gratefully acknowledged.

  16. Photoacoustic lymphatic imaging with high spatial-temporal resolution

    Science.gov (United States)

    Martel, Catherine; Yao, Junjie; Huang, Chih-Hsien; Zou, Jun; Randolph, Gwendalyn J.; Wang, Lihong V.

    2014-11-01

    Despite its critical function in coordinating the egress of inflammatory and immune cells out of tissues and maintaining fluid balance, the causative role of lymphatic network dysfunction in pathological settings is still understudied. Engineered-animal models and better noninvasive high spatial-temporal resolution imaging techniques in both preclinical and clinical studies will help to improve our understanding of different lymphatic-related pathologic disorders. Our aim was to take advantage of our newly optimized noninvasive wide-field fast-scanning photoacoustic (PA) microcopy system to coordinately image the lymphatic vasculature and its flow dynamics, while maintaining high resolution and detection sensitivity. Here, by combining the optical-resolution PA microscopy with a fast-scanning water-immersible microelectromechanical system scanning mirror, we have imaged the lymph dynamics over a large field-of-view, with high spatial resolution and advanced detection sensitivity. Depending on the application, lymphatic vessels (LV) were spectrally or temporally differentiated from blood vessels. Validation experiments were performed on phantoms and in vivo to identify the LV. Lymphatic flow dynamics in nonpathological and pathological conditions were also visualized. These results indicate that our newly developed PA microscopy is a promising tool for lymphatic-related biological research.

  17. Aberrant lymphatic endothelial progenitors in lymphatic malformation development.

    Directory of Open Access Journals (Sweden)

    June K Wu

    Full Text Available Lymphatic malformations (LMs are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4, circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2, and lymphatic endothelial proteins (podoplanin, VEGFR-3. Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133- cells isolated from LM fluids. CD133- LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133- LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs.

  18. Application of the chaotic power law to the study of cardiac dynamics in patients with arrhythmias

    Directory of Open Access Journals (Sweden)

    Javier Rodríguez-Velásquez

    2014-10-01

    Full Text Available Background. An exponential law for chaotic cardiac dynamics, found previously, allows the quantification of the differences between normal cardiac dynamics and those with acute diseases, as well as the cardiac dynamics of the evolution between these states. Objective. To confirm the clinical applicability of the developed methodology through the mathematical law for cardiac dynamics in dynamics with arrhythmias. Materials and methods. 60 Holter electrocardiograms were analyzed, 10 corresponded to normal subjects, and 50 to subjects with different arrhythmias. For each Holter, an attractor was performed, and its fractal dimension and spatial occupancy were measured. A mathematical evaluation was applied in order to differentiate normal dynamics from pathological ones. Sensitivity, specificity and the Kappa coefficient were calculated. Results. The mathematical evaluation differentiated occupation spaces, normal dynamics, acute illness dynamics, and evolution between these states. The sensitivity and specificity values were 100%, and the Kappa coefficient was 1. Conclusions. The clinical applicability of the methodology for cases with arrhythmia was shown. It is also applicable for the detection of changes in dynamics that are not classified clinically as pathological.

  19. Coexisting chaotic and multi-periodic dynamics in a model of cardiac alternans

    Energy Technology Data Exchange (ETDEWEB)

    Skardal, Per Sebastian, E-mail: skardals@gmail.com [Departament d' Enginyeria Informàtica i Matemàtiques, Universitat Rovira i Virgili, 43007 Tarragona (Spain); Restrepo, Juan G., E-mail: juanga@colorado.edu [Department of Applied Mathematics, University of Colorado, Boulder, Colorado 80309 (United States)

    2014-12-15

    The spatiotemporal dynamics of cardiac tissue is an active area of research for biologists, physicists, and mathematicians. Of particular interest is the study of period-doubling bifurcations and chaos due to their link with cardiac arrhythmogenesis. In this paper, we study the spatiotemporal dynamics of a recently developed model for calcium-driven alternans in a one dimensional cable of tissue. In particular, we observe in the cable coexistence of regions with chaotic and multi-periodic dynamics over wide ranges of parameters. We study these dynamics using global and local Lyapunov exponents and spatial trajectory correlations. Interestingly, near nodes—or phase reversals—low-periodic dynamics prevail, while away from the nodes, the dynamics tend to be higher-periodic and eventually chaotic. Finally, we show that similar coexisting multi-periodic and chaotic dynamics can also be observed in a detailed ionic model.

  20. Stochastic Alternating Dynamics for Synchronous EAD-Like Beating Rhythms in Cultured Cardiac Myocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ning; ZHANG Hui-Min; LIU Zhi-Qiang; DING Xue-Li; YANG Ming-Hao; GU Hua-Guang; REN Wei

    2009-01-01

    Dissolved cardiac myocytes can couple together and generate synchronous beatings in culture. We observed a synchronized early after-depolarization(EAD)-like rhythm in cultured cardiac myocytes and reproduced the experimental observation in a network mathematical model whose dynamics are close to a Hopf bifurcation. The mechanism for this EAD-like rhythm is attributed to noised-induced stochastic alternatings between the focus and the limit cycle. These results provide novel understandings for pathological heart rhythms like the early immature beatings.

  1. Coexisting chaotic and multi-periodic dynamics in a model of cardiac alternans

    CERN Document Server

    Skardal, Per Sebastian

    2014-01-01

    The spatiotemporal dynamics of cardiac tissue is an active area of research for biologists, physicists, and mathematicians. Of particular interest is the study of period-doubling bifurcations and chaos due to their link with cardiac arrhythmogenesis. In this paper we study the spatiotemporal dynamics of a recently developed model for calcium-driven alternans in a one dimensional cable of tissue. In particular, we observe in the cable coexistence in of regions with chaotic and multi-periodic dynamics over wide ranges of parameters. We study these dynamics using global and local Lyapunov exponents and spatial trajectory correlations. Interestingly, near nodes -- or phase reversals -- low-periodic dynamics prevail, while away from the nodes the dynamics tend to be higher-periodic and eventually chaotic.

  2. 69. Impact of low frequency ultrasound and lymphatic drainage on triglycerides in chronic atherosclerotic patients

    OpenAIRE

    M. Badawy

    2016-01-01

    The aim of this study was to evaluate the effect of low frequency ultrasound plus lymphatic drainage on Blood Triglycerides in Cardiac patients (chronic coronary atherosclerosis patients, with high triglycerides and fat mass body composition). Low frequency ultrasound plus lymphatic drainage as a technique could be used as an alternative to conventional exercise and alternative to many obesity surgery as Liposuction surgery and thus provide an opportunity to improve the quality of obese cardi...

  3. Numerical Study of the Cerebro-Spinal Fluid (CSF) Dynamics Under Quasistatic Condition During a Cardiac Cycle

    Science.gov (United States)

    2001-10-25

    THE CEREBRO -SPINAL FLUID (CSF) DYNAMICS UNDER QUASI- STATIC CONDITION DURING A CARDIAC CYCLE Loïc FIN, Reinhard GREBE, Olivier BALÉDENT, Ilana...from... to) - Title and Subtitle Numerical Study of the Cerebro -Spinal Fluid (CSF) Dynamics Under Quasistatic Condition During a Cardiac Cycle

  4. Exercise training improves obesity‐related lymphatic dysfunction

    OpenAIRE

    2016-01-01

    Key points Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, imp...

  5. Dynamic real-time 4D cardiac MDCT image display using GPU-accelerated volume rendering.

    Science.gov (United States)

    Zhang, Qi; Eagleson, Roy; Peters, Terry M

    2009-09-01

    Intraoperative cardiac monitoring, accurate preoperative diagnosis, and surgical planning are important components of minimally-invasive cardiac therapy. Retrospective, electrocardiographically (ECG) gated, multidetector computed tomographical (MDCT), four-dimensional (3D + time), real-time, cardiac image visualization is an important tool for the surgeon in such procedure, particularly if the dynamic volumetric image can be registered to, and fused with the actual patient anatomy. The addition of stereoscopic imaging provides a more intuitive environment by adding binocular vision and depth cues to structures within the beating heart. In this paper, we describe the design and implementation of a comprehensive stereoscopic 4D cardiac image visualization and manipulation platform, based on the opacity density radiation model, which exploits the power of modern graphics processing units (GPUs) in the rendering pipeline. In addition, we present a new algorithm to synchronize the phases of the dynamic heart to clinical ECG signals, and to calculate and compensate for latencies in the visualization pipeline. A dynamic multiresolution display is implemented to enable the interactive selection and emphasis of volume of interest (VOI) within the entire contextual cardiac volume and to enhance performance, and a novel color and opacity adjustment algorithm is designed to increase the uniformity of the rendered multiresolution image of heart. Our system provides a visualization environment superior to noninteractive software-based implementations, but with a rendering speed that is comparable to traditional, but inferior quality, volume rendering approaches based on texture mapping. This retrospective ECG-gated dynamic cardiac display system can provide real-time feedback regarding the suspected pathology, function, and structural defects, as well as anatomical information such as chamber volume and morphology.

  6. Lymphatic Biodistribution of Polylactide Nanoparticles

    Science.gov (United States)

    Chaney, Eric J.; Tang, Li; Tong, Rong; Cheng, Jianjun; Boppart, Stephen A.

    2013-01-01

    Tumor metastases occur through both the cardiovascular and lymphatic circulations. However, the majority of nanoparticle biodistribution studies have been focused on the cardiovascular circulation. In this study, we report the formulation of Cy5-labeled polylactide (Cy5-PLA) nanoparticles with controlled size and surface features and the subsequent evaluation of their lymphatic biodistribution. Cy5-PLA nanoparticles were formulated through Cy5/(BDI)ZnN(TMS)2-mediated [(BDI) = 2-((2,6-diisopropylphenyl) amido)-4-((2,6-diisopropylphenyl)-imino)-2-pentene] ring-opening polymerization of lactide followed by nanoprecipitation. Their lymphatic biodistribution was evaluated by using whole-body fluorescence imaging of nude mice and ex vivo fluorescence imaging of the resected organs. This technique has the potential for providing optical contrast and drug delivery through the lymphatic circulation for the treatment of metastatic cancer. PMID:20487681

  7. Lymphatic Biodistribution of Polylactide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Eric J. Chaney

    2010-05-01

    Full Text Available Tumor metastases occur through both the cardiovascular and lymphatic circulations. However, the majority of nanoparticle biodistribution studies have been focused on the cardiovascular circulation. In this study, we report the formulation of Cy5-labeled polylactide (Cy5-PLA nanoparticles with controlled size and surface features and the subsequent evaluation of their lymphatic biodistribution. Cy5-PLA nanoparticles were formulated through Cy5/(BDIZnN(TMS2-mediated [(BDI = 2-((2,6-diisopropylphenyl amido-4-((2,6-diisopropylphenyl-imino-2-pentene] ring-opening polymerization of lactide followed by nanoprecipitation. Their lymphatic biodistribution was evaluated by using whole-body fluorescence imaging of nude mice and ex vivo fluorescence imaging of the resected organs. This technique has the potential for providing optical contrast and drug delivery through the lymphatic circulation for the treatment of metastatic cancer.

  8. Albendazole for lymphatic filariasis (Review)

    OpenAIRE

    Addiss, D; Gamble, C.; Garner, Paul; Gelband, H; Ejere, H.; Critchley, J.

    2009-01-01

    Background\\ud Mass treatment with albendazole co-administered with another antifilarial drug is part of a global programme to eliminate lymphatic filariasis. We sought reliable evidence of the effects of albendazole on the disease and the parasite.\\ud Objectives\\ud To summarize the effects of albendazole alone or in combination with antifilarial drugs for clinical treatment and community control of lymphatic filariasis.\\ud Search strategy\\ud We searched the Cochrane Infectious Diseases Group ...

  9. Image registration and analysis for quantitative myocardial perfusion: application to dynamic circular cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Isola, A A [Philips Research Laboratories, X-ray Imaging Systems Department, Weisshausstrasse 2, D-52066 Aachen (Germany); Schmitt, H; Van Stevendaal, U; Grass, M [Philips Research Laboratories, Sector Digital Imaging, Roentgenstrasse 24-26, D-22335 Hamburg (Germany); Begemann, P G [Department of Radiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg (Germany); Coulon, P [Philips Healthcare France, 33 rue de Verdun, F-92150 Suresnes Cedex (France); Boussel, L, E-mail: Alfonso.Isola@Philips.com [Department of Radiology, Louis Pradel Hospital, CREATIS, UMR CNRS 5515, INSERM U630, Lyon (France)

    2011-09-21

    Large area detector computed tomography systems with fast rotating gantries enable volumetric dynamic cardiac perfusion studies. Prospectively, ECG-triggered acquisitions limit the data acquisition to a predefined cardiac phase and thereby reduce x-ray dose and limit motion artefacts. Even in the case of highly accurate prospective triggering and stable heart rate, spatial misalignment of the cardiac volumes acquired and reconstructed per cardiac cycle may occur due to small motion pattern variations from cycle to cycle. These misalignments reduce the accuracy of the quantitative analysis of myocardial perfusion parameters on a per voxel basis. An image-based solution to this problem is elastic 3D image registration of dynamic volume sequences with variable contrast, as it is introduced in this contribution. After circular cone-beam CT reconstruction of cardiac volumes covering large areas of the myocardial tissue, the complete series is aligned with respect to a chosen reference volume. The results of the registration process and the perfusion analysis with and without registration are evaluated quantitatively in this paper. The spatial alignment leads to improved quantification of myocardial perfusion for three different pig data sets.

  10. Image registration and analysis for quantitative myocardial perfusion: application to dynamic circular cardiac CT

    Science.gov (United States)

    Isola, A. A.; Schmitt, H.; van Stevendaal, U.; Begemann, P. G.; Coulon, P.; Boussel, L.; Grass, M.

    2011-09-01

    Large area detector computed tomography systems with fast rotating gantries enable volumetric dynamic cardiac perfusion studies. Prospectively, ECG-triggered acquisitions limit the data acquisition to a predefined cardiac phase and thereby reduce x-ray dose and limit motion artefacts. Even in the case of highly accurate prospective triggering and stable heart rate, spatial misalignment of the cardiac volumes acquired and reconstructed per cardiac cycle may occur due to small motion pattern variations from cycle to cycle. These misalignments reduce the accuracy of the quantitative analysis of myocardial perfusion parameters on a per voxel basis. An image-based solution to this problem is elastic 3D image registration of dynamic volume sequences with variable contrast, as it is introduced in this contribution. After circular cone-beam CT reconstruction of cardiac volumes covering large areas of the myocardial tissue, the complete series is aligned with respect to a chosen reference volume. The results of the registration process and the perfusion analysis with and without registration are evaluated quantitatively in this paper. The spatial alignment leads to improved quantification of myocardial perfusion for three different pig data sets.

  11. Lymphatic Regulation of Cellular Trafficking

    Science.gov (United States)

    Jackson, David G.

    2016-01-01

    Lymphatic vessels play vital roles in immune surveillance and immune regulation by conveying antigen loaded dendritic cells, memory T cells, macrophages and neutrophils from the peripheral tissues to draining lymph nodes where they initiate as well as modify immune responses. Until relatively recently however, there was little understanding of how entry and migration through lymphatic vessels is organized or the specific molecular mechanisms that might be involved. Within the last decade, the situation has been transformed by an explosion of knowledge generated largely through the application of microscopic imaging, transgenic animals, specific markers and function blocking mAbs that is beginning to provide a rational conceptual framework. This article provides a critical review of the recent literature, highlighting seminal discoveries that have revealed the fascinating ultrastructure of leucocyte entry sites in lymphatic vessels, as well as generating controversies over the involvement of integrin adhesion, chemotactic and haptotactic mechanisms in DC entry under normal and inflamed conditions. It also discusses the major changes in lymphatic architecture that occur during inflammation and the different modes of leucocyte entry and trafficking within inflamed lymphatic vessels, as well as presenting a timely update on the likely role of hyaluronan and the major lymphatic endothelial hyaluronan receptor LYVE-1 in leucocyte transit.

  12. Slow [Na+]i dynamics impacts arrhythmogenesis and spiral wave reentry in cardiac myocyte ionic model

    Science.gov (United States)

    Krogh-Madsen, Trine; Christini, David J.

    2017-09-01

    Accumulation of intracellular Na+ is gaining recognition as an important regulator of cardiac myocyte electrophysiology. The intracellular Na+ concentration can be an important determinant of the cardiac action potential duration, can modulate the tissue-level conduction of excitation waves, and can alter vulnerability to arrhythmias. Mathematical models of cardiac electrophysiology often incorporate a dynamic intracellular Na+ concentration, which changes much more slowly than the remaining variables. We investigated the dependence of several arrhythmogenesis-related factors on [Na+]i in a mathematical model of the human atrial action potential. In cell simulations, we found that [Na+]i accumulation stabilizes the action potential duration to variations in several conductances and that the slow dynamics of [Na+]i impacts bifurcations to pro-arrhythmic afterdepolarizations, causing intermittency between different rhythms. In long-lasting tissue simulations of spiral wave reentry, [Na+]i becomes spatially heterogeneous with a decreased area around the spiral wave rotation center. This heterogeneous region forms a functional anchor, resulting in diminished meandering of the spiral wave. Our findings suggest that slow, physiological, rate-dependent variations in [Na+]i may play complex roles in cellular and tissue-level cardiac dynamics.

  13. Kalman filter techniques for accelerated Cartesian dynamic cardiac imaging.

    Science.gov (United States)

    Feng, Xue; Salerno, Michael; Kramer, Christopher M; Meyer, Craig H

    2013-05-01

    In dynamic MRI, spatial and temporal parallel imaging can be exploited to reduce scan time. Real-time reconstruction enables immediate visualization during the scan. Commonly used view-sharing techniques suffer from limited temporal resolution, and many of the more advanced reconstruction methods are either retrospective, time-consuming, or both. A Kalman filter model capable of real-time reconstruction can be used to increase the spatial and temporal resolution in dynamic MRI reconstruction. The original study describing the use of the Kalman filter in dynamic MRI was limited to non-Cartesian trajectories because of a limitation intrinsic to the dynamic model used in that study. Here the limitation is overcome, and the model is applied to the more commonly used Cartesian trajectory with fast reconstruction. Furthermore, a combination of the Kalman filter model with Cartesian parallel imaging is presented to further increase the spatial and temporal resolution and signal-to-noise ratio. Simulations and experiments were conducted to demonstrate that the Kalman filter model can increase the temporal resolution of the image series compared with view-sharing techniques and decrease the spatial aliasing compared with TGRAPPA. The method requires relatively little computation, and thus is suitable for real-time reconstruction.

  14. Mechanisms of lymphatic regeneration after tissue transfer.

    Directory of Open Access Journals (Sweden)

    Alan Yan

    Full Text Available INTRODUCTION: Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer. METHODS: Nude mice (recipients underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed. RESULTS: Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration. CONCLUSIONS: Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics

  15. Lymphatic regulation in nonmammalian vertebrates.

    Science.gov (United States)

    Hedrick, Michael S; Hillman, Stanley S; Drewes, Robert C; Withers, Philip C

    2013-08-01

    All vertebrate animals share in common the production of lymph through net capillary filtration from their closed circulatory system into their tissues. The balance of forces responsible for net capillary filtration and lymph formation is described by the Starling equation, but additional factors such as vascular and interstitial compliance, which vary markedly among vertebrates, also have a significant impact on rates of lymph formation. Why vertebrates show extreme variability in rates of lymph formation and how nonmammalian vertebrates maintain plasma volume homeostasis is unclear. This gap hampers our understanding of the evolution of the lymphatic system and its interaction with the cardiovascular system. The evolutionary origin of the vertebrate lymphatic system is not clear, but recent advances suggest common developmental factors for lymphangiogenesis in teleost fishes, amphibians, and mammals with some significant changes in the water-land transition. The lymphatic system of anuran amphibians is characterized by large lymphatic sacs and two pairs of lymph hearts that return lymph into the venous circulation but no lymph vessels per se. The lymphatic systems of reptiles and some birds have lymph hearts, and both groups have extensive lymph vessels, but their functional role in both lymph movement and plasma volume homeostasis is almost completely unknown. The purpose of this review is to present an evolutionary perspective in how different vertebrates have solved the common problem of the inevitable formation of lymph from their closed circulatory systems and to point out the many gaps in our knowledge of this evolutionary progression.

  16. Dynamic CT perfusion measurement in a cardiac phantom.

    Science.gov (United States)

    Ziemer, Benjamin P; Hubbard, Logan; Lipinski, Jerry; Molloi, Sabee

    2015-10-01

    Widespread clinical implementation of dynamic CT myocardial perfusion has been hampered by its limited accuracy and high radiation dose. The purpose of this study was to evaluate the accuracy and radiation dose reduction of a dynamic CT myocardial perfusion technique based on first pass analysis (FPA). To test the FPA technique, a pulsatile pump was used to generate known perfusion rates in a range of 0.96-2.49 mL/min/g. All the known perfusion rates were determined using an ultrasonic flow probe and the known mass of the perfusion volume. FPA and maximum slope model (MSM) perfusion rates were measured using volume scans acquired from a 320-slice CT scanner, and then compared to the known perfusion rates. The measured perfusion using FPA (P(FPA)), with two volume scans, and the maximum slope model (P(MSM)) were related to known perfusion (P(K)) by P(FPA) = 0.91P(K) + 0.06 (r = 0.98) and P(MSM) = 0.25P(K) - 0.02 (r = 0.96), respectively. The standard error of estimate for the FPA technique, using two volume scans, and the MSM was 0.14 and 0.30 mL/min/g, respectively. The estimated radiation dose required for the FPA technique with two volume scans and the MSM was 2.6 and 11.7-17.5 mSv, respectively. Therefore, the FPA technique can yield accurate perfusion measurements using as few as two volume scans, corresponding to approximately a factor of four reductions in radiation dose as compared with the currently available MSM. In conclusion, the results of the study indicate that the FPA technique can make accurate dynamic CT perfusion measurements over a range of clinically relevant perfusion rates, while substantially reducing radiation dose, as compared to currently available dynamic CT perfusion techniques.

  17. Spatiotemporal dynamics of calcium-driven cardiac alternans.

    Science.gov (United States)

    Skardal, Per Sebastian; Karma, Alain; Restrepo, Juan G

    2014-05-01

    We investigate the dynamics of spatially discordant alternans (SDA) driven by an instability of intracellular calcium cycling using both amplitude equations [P. S. Skardal, A. Karma, and J. G. Restrepo, Phys. Rev. Lett. 108, 108103 (2012)] and ionic model simulations. We focus on the common case where the bidirectional coupling of intracellular calcium concentration and membrane voltage dynamics produces calcium and voltage alternans that are temporally in phase. We find that, close to the alternans bifurcation, SDA is manifested as a smooth wavy modulation of the amplitudes of both repolarization and calcium transient (CaT) alternans, similarly to the well-studied case of voltage-driven alternans. In contrast, further away from the bifurcation, the amplitude of CaT alternans jumps discontinuously at the nodes separating out-of-phase regions, while the amplitude of repolarization alternans remains smooth. We identify universal dynamical features of SDA pattern formation and evolution in the presence of those jumps. We show that node motion of discontinuous SDA patterns is strongly hysteretic even in homogeneous tissue due to the novel phenomenon of "unidirectional pinning": node movement can only be induced towards, but not away from, the pacing site in response to a change of pacing rate or physiological parameter. In addition, we show that the wavelength of discontinuous SDA patterns scales linearly with the conduction velocity restitution length scale, in contrast to the wavelength of smooth patterns that scales sublinearly with this length scale. Those results are also shown to be robust against cell-to-cell fluctuations due to the property that unidirectional node motion collapses multiple jumps accumulating in nodal regions into a single jump. Amplitude equation predictions are in good overall agreement with ionic model simulations. Finally, we briefly discuss physiological implications of our findings. In particular, we suggest that due to the tendency of

  18. Molecular dynamics simulations of the cardiac troponin complex performed with FRET distances as restraints.

    Directory of Open Access Journals (Sweden)

    Jayant James Jayasundar

    Full Text Available Cardiac troponin (cTn is the Ca(2+-sensitive molecular switch that controls cardiac muscle activation and relaxation. However, the molecular detail of the switching mechanism and how the Ca(2+ signal received at cardiac troponin C (cTnC is communicated to cardiac troponin I (cTnI are still elusive. To unravel the structural details of troponin switching, we performed ensemble Förster resonance energy transfer (FRET measurements and molecular dynamic (MD simulations of the cardiac troponin core domain complex. The distance distributions of forty five inter-residue pairs were obtained under Ca(2+-free and saturating Ca(2+ conditions from time-resolved FRET measurements. These distances were incorporated as restraints during the MD simulations of the cardiac troponin core domain. Compared to the Ca(2+-saturated structure, the absence of regulatory Ca(2+ perturbed the cTnC N-domain hydrophobic pocket which assumed a closed conformation. This event partially unfolded the cTnI regulatory region/switch. The absence of Ca(2+, induced flexibility to the D/E linker and the cTnI inhibitory region, and rotated the cTnC N-domain with respect to rest of the troponin core domain. In the presence of saturating Ca(2+ the above said phenomenon were absent. We postulate that the secondary structure perturbations experienced by the cTnI regulatory region held within the cTnC N-domain hydrophobic pocket, coupled with the rotation of the cTnC N-domain would control the cTnI mobile domain interaction with actin. Concomitantly the rotation of the cTnC N-domain and perturbation of the D/E linker rigidity would control the cTnI inhibitory region interaction with actin to effect muscle relaxation.

  19. Stochastic heart-rate model can reveal pathologic cardiac dynamics

    Science.gov (United States)

    Kuusela, Tom

    2004-03-01

    A simple one-dimensional Langevin-type stochastic difference equation can simulate the heart-rate fluctuations in a time scale from minutes to hours. The model consists of a deterministic nonlinear part and a stochastic part typical of Gaussian noise, and both parts can be directly determined from measured heart-rate data. Data from healthy subjects typically exhibit the deterministic part with two or more stable fixed points. Studies of 15 congestive heart-failure subjects reveal that the deterministic part of pathologic heart dynamics has no clear stable fixed points. Direct simulations of the stochastic model for normal and pathologic cases can produce statistical parameters similar to those of real subjects. Results directly indicate that pathologic situations simplify the heart-rate control system.

  20. Successful treatment of plastic bronchitis by selective lymphatic embolization in a Fontan patient.

    Science.gov (United States)

    Dori, Yoav; Keller, Marc S; Rychik, Jack; Itkin, Maxim

    2014-08-01

    Plastic bronchitis is a rare and often fatal complication of single-ventricle surgical palliation after total cavopulmonary connection. Although lymphatic abnormalities have been postulated to play a role in the disease process, the etiology and pathophysiology of this complication remain incompletely understood. Here we report on the etiology of plastic bronchitis in a child with total cavopulmonary connection as demonstrated by magnetic resonance (MR) lymphangiography. We also report on a new treatment of this disease. The patient underwent noncontrast T2-weighted MR lymphatic mapping and dynamic contrast MR lymphangiography with bi-inguinal intranodal contrast injection to determine the anatomy and flow pattern of lymph in his central lymphatic system. The MRI scan demonstrated the presence of a dilated right-sided peribronchial lymphatic network supplied by retrograde lymphatic flow through a large collateral lymphatic vessel originating from the thoracic duct. After careful analysis of the MRI scans we performed selective lymphatic embolization of the pathologic lymphatic network and supplying vessel. This provided resolution of plastic bronchitis for this patient. Five months after the procedure, the patient remains asymptomatic off respiratory medications. Copyright © 2014 by the American Academy of Pediatrics.

  1. Lymphatic Filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Pedersen, Erling Møller; Rwegoshora, Rwehumbiza T.

    2010-01-01

    In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs...

  2. Lymphatic filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Derua, Yahya A.; Kisinza, William N.

    2013-01-01

    Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA...

  3. Lymphatic Filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Pedersen, Erling Møller; Rwegoshora, Rwehumbiza T.;

    2010-01-01

    In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs with t...

  4. Accelerating PS model-based dynamic cardiac MRI using compressed sensing.

    Science.gov (United States)

    Zhang, Xiaoyong; Xie, Guoxi; Shi, Caiyun; Su, Shi; Zhang, Yongqin; Liu, Xin; Qiu, Bensheng

    2016-02-01

    High spatiotemporal resolution MRI is a challenging topic in dynamic MRI field. Partial separability (PS) model has been successfully applied to dynamic cardiac MRI by exploiting data redundancy. However, the model requires substantial preprocessing data to accurately estimate the model parameters before image reconstruction. Since compressed sensing (CS) is a potential technique to accelerate MRI by reducing the number of acquired data, the combination of PS and CS, named as Stepped-SparsePS, was introduced to accelerate the preprocessing data acquisition of PS in this work. The proposed Stepped-SparsePS method sequentially reconstructs a set of aliased dynamic images in each channel based on PS model and then the final dynamic images from the aliased images using CS. The results from numerical simulations and in vivo experiments demonstrate that Stepped-SparsePS could significantly reduce data acquisition time while preserving high spatiotemporal resolution. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Fully automated segmentation of left ventricle using dual dynamic programming in cardiac cine MR images

    Science.gov (United States)

    Jiang, Luan; Ling, Shan; Li, Qiang

    2016-03-01

    Cardiovascular diseases are becoming a leading cause of death all over the world. The cardiac function could be evaluated by global and regional parameters of left ventricle (LV) of the heart. The purpose of this study is to develop and evaluate a fully automated scheme for segmentation of LV in short axis cardiac cine MR images. Our fully automated method consists of three major steps, i.e., LV localization, LV segmentation at end-diastolic phase, and LV segmentation propagation to the other phases. First, the maximum intensity projection image along the time phases of the midventricular slice, located at the center of the image, was calculated to locate the region of interest of LV. Based on the mean intensity of the roughly segmented blood pool in the midventricular slice at each phase, end-diastolic (ED) and end-systolic (ES) phases were determined. Second, the endocardial and epicardial boundaries of LV of each slice at ED phase were synchronously delineated by use of a dual dynamic programming technique. The external costs of the endocardial and epicardial boundaries were defined with the gradient values obtained from the original and enhanced images, respectively. Finally, with the advantages of the continuity of the boundaries of LV across adjacent phases, we propagated the LV segmentation from the ED phase to the other phases by use of dual dynamic programming technique. The preliminary results on 9 clinical cardiac cine MR cases show that the proposed method can obtain accurate segmentation of LV based on subjective evaluation.

  6. [Anatomy of the pelvic lymphatic system].

    Science.gov (United States)

    Wolfram-Gabel, R

    2013-10-01

    The lymphatic system of the pelvis collects the lymph of the genital and urinary organs and of the digestive tract. It is formed by lymphatic nodes and vessels situated inside the conjunctive tissue, near the organs (visceral lymphatic nodes) but especially along the external, internal and common iliac vessels (iliac lymphatic nodes). These nodes receive afferent vessels issued from the different pelvic organs. From the iliac lymphnodes arise efferent vessels running towards lymphatic collectors, situated above them, and which end in the lymphatic lombar duct. The lymphatic pathways represent the preferential way of scattering of cancerous cells. Therefore, the knowledge of the anatomy, of the situation and of the draining of the nodes is of the utmost importance in the evaluation of a cancer of a pelvic organ.

  7. Comparison study of temporal regularization methods for fully 5D reconstruction of cardiac gated dynamic SPECT

    Science.gov (United States)

    Niu, Xiaofeng; Yang, Yongyi; King, Michael A.

    2012-09-01

    Temporal regularization plays a critical role in cardiac gated dynamic SPECT reconstruction, of which the goal is to obtain an image sequence from a single acquisition which simultaneously shows both cardiac motion and tracer distribution change over the course of imaging (termed 5D). In our recent work, we explored two different approaches for temporal regularization of the dynamic activities in gated dynamic reconstruction without the use of fast camera rotation: one is the dynamic EM (dEM) approach which is imposed on the temporal trend of the time activity of each voxel, and the other is a B-spline modeling approach in which the time activity is regulated by a set of B-spline basis functions. In this work, we extend the B-spline approach to fully 5D reconstruction and conduct a thorough quantitative comparison with the dEM approach. In the evaluation of the reconstruction results, we apply a number of quantitative measures on two major aspects of the reconstructed dynamic images: (1) the accuracy of the reconstructed activity distribution in the myocardium and (2) the ability of the reconstructed dynamic activities to differentiate perfusion defects from normal myocardial wall uptake. These measures include the mean square error (MSE), bias-variance analysis, accuracy of time-activity curves (TAC), contrast-to-noise ratio of a defect, composite kinetic map of the left ventricle wall and perfusion defect detectability with channelized Hotelling observer. In experiments, we simulated cardiac gated imaging with the NURBS-based cardiac-torso phantom and Tc99m-Teboroxime as the imaging agent, where acquisition with the equivalent of only three full camera rotations was used during the imaging period. The results show that both dEM and B-spline 5D could achieve similar overall accuracy in the myocardium in terms of MSE. However, compared to dEM 5D, the B-spline approach could achieve a more accurate reconstruction of the voxel TACs; in particular, B-spline 5D could

  8. Mathematical Law for Evaluating Arrhythmic Cardiac Dynamics: Application for the Arrhythmia Diagnosis

    Directory of Open Access Journals (Sweden)

    Javier Rodríguez

    2015-09-01

    Full Text Available The development of a mathematical law for chaotic dynamical systems has allowed to develop a methodology for the mathematical evaluation of cardiac dynamics which quantifies the differen­ces between normality and disease, as well as their evolution. Material and methods: 70 Holter records, 60 with cardiac arrhythmias and 10 normal were taken. From the simulation values of consecutive heart rates, an attractor was built for each Holter. The space occupancy of each at­tractor and its fractal dimension were measured. Mathematical evaluation was applied to each Holter and then the sensitivity, specificity and Kappa coefficient of this evaluation with respect to the Gold Standard was calculated. Results: The cases conventionally diagnosed as arrhythmias presented space occupancy between 29 and 198 for Kp grid, and normal cases had higher values at 200. The sensitivity and specificity were 100 % and Kappa coefficient was 1. Conclusion: The power law quantifies differences between arrhythmias and normal dynamics, assessing the evo­lution dynamics towards normality or to disease, this was evidenced by an increase or decrease of the space occupied by the attractor.

  9. Performance comparison between static and dynamic cardiac CT on perfusion quantitation and patient classification tasks

    Science.gov (United States)

    Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R.; La Riviere, Patrick J.; Alessio, Adam M.

    2015-03-01

    Cardiac CT acquisitions for perfusion assessment can be performed in a dynamic or static mode. In this simulation study, we evaluate the relative classification and quantification performance of these modes for assessing myocardial blood flow (MBF). In the dynamic method, a series of low dose cardiac CT acquisitions yields data on contrast bolus dynamics over time; these data are fit with a model to give a quantitative MBF estimate. In the static method, a single CT acquisition is obtained, and the relative CT numbers in the myocardium are used to infer perfusion states. The static method does not directly yield a quantitative estimate of MBF, but these estimates can be roughly approximated by introducing assumed linear relationships between CT number and MBF, consistent with the ways such images are typically visually interpreted. Data obtained by either method may be used for a variety of clinical tasks, including 1) stratifying patients into differing categories of ischemia and 2) using the quantitative MBF estimate directly to evaluate ischemic disease severity. Through simulations, we evaluate the performance on each of these tasks. The dynamic method has very low bias in MBF estimates, making it particularly suitable for quantitative estimation. At matched radiation dose levels, ROC analysis demonstrated that the static method, with its high bias but generally lower variance, has superior performance in stratifying patients, especially for larger patients.

  10. OptoDyCE: Automated system for high-throughput all-optical dynamic cardiac electrophysiology

    Science.gov (United States)

    Klimas, Aleksandra; Yu, Jinzhu; Ambrosi, Christina M.; Williams, John C.; Bien, Harold; Entcheva, Emilia

    2016-02-01

    In the last two decades, drugs withdrawals from the market were due to cardiac toxicity, where unintended interactions with ion channels disrupt the heart's normal electrical function. Consequently, all new drugs must undergo preclinical testing for cardiac liability, adding to an already expensive and lengthy process. Recognition that proarrhythmic effects often result from drug action on multiple ion channels demonstrates a need for integrative and comprehensive measurements. Additionally, patient-specific therapies relying on emerging technologies employing stem-cell derived cardiomyocytes (e.g. induced pluripotent stem-cell-derived cardiomyocytes, iPSC-CMs) require better screening methods to become practical. However, a high-throughput, cost-effective approach for cellular cardiac electrophysiology has not been feasible. Optical techniques for manipulation and recording provide a contactless means of dynamic, high-throughput testing of cells and tissues. Here, we consider the requirements for all-optical electrophysiology for drug testing, and we implement and validate OptoDyCE, a fully automated system for all-optical cardiac electrophysiology. We demonstrate the high-throughput capabilities using multicellular samples in 96-well format by combining optogenetic actuation with simultaneous fast high-resolution optical sensing of voltage or intracellular calcium. The system can also be implemented using iPSC-CMs and other cell-types by delivery of optogenetic drivers, or through the modular use of dedicated light-sensitive somatic cells in conjunction with non-modified cells. OptoDyCE provides a truly modular and dynamic screening system, capable of fully-automated acquisition of high-content information integral for improved discovery and development of new drugs and biologics, as well as providing a means of better understanding of electrical disturbances in the heart.

  11. Disrupted NOS signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow.

    Science.gov (United States)

    Datar, Sanjeev A; Gong, Wenhui; He, Youping; Johengen, Michael; Kameny, Rebecca J; Raff, Gary W; Maltepe, Emin; Oishi, Peter E; Fineman, Jeffrey R

    2016-07-01

    Associated abnormalities of the lymphatic circulation are well described in congenital heart disease. However, their mechanisms remain poorly elucidated. Using a clinically relevant ovine model of a congenital cardiac defect with chronically increased pulmonary blood flow (shunt), we previously demonstrated that exposure to chronically elevated pulmonary lymph flow is associated with: 1) decreased bioavailable nitric oxide (NO) in pulmonary lymph; and 2) attenuated endothelium-dependent relaxation of thoracic duct rings, suggesting disrupted lymphatic endothelial NO signaling in shunt lambs. To further elucidate the mechanisms responsible for this altered NO signaling, primary lymphatic endothelial cells (LECs) were isolated from the efferent lymphatic of the caudal mediastinal node in 4-wk-old control and shunt lambs. We found that shunt LECs (n = 3) had decreased bioavailable NO and decreased endothelial nitric oxide synthase (eNOS) mRNA and protein expression compared with control LECs (n = 3). eNOS activity was also low in shunt LECs, but, interestingly, inducible nitric oxide synthase (iNOS) expression and activity were increased in shunt LECs, as were total cellular nitration, including eNOS-specific nitration, and accumulation of reactive oxygen species (ROS). Pharmacological inhibition of iNOS reduced ROS in shunt LECs to levels measured in control LECs. These data support the conclusion that NOS signaling is disrupted in the lymphatic endothelium of lambs exposed to chronically increased pulmonary blood and lymph flow and may contribute to decreased pulmonary lymphatic bioavailable NO.

  12. Classification of cardiac rhythm using heart rate dynamical measures: validation in MIT-BIH databases.

    Science.gov (United States)

    Carrara, Marta; Carozzi, Luca; Moss, Travis J; de Pasquale, Marco; Cerutti, Sergio; Lake, Douglas E; Moorman, J Randall; Ferrario, Manuela

    2015-01-01

    Identification of atrial fibrillation (AF) is a clinical imperative. Heartbeat interval time series are increasingly available from personal monitors, allowing new opportunity for AF diagnosis. Previously, we devised numerical algorithms for identification of normal sinus rhythm (NSR), AF, and SR with frequent ectopy using dynamical measures of heart rate. Here, we wished to validate them in the canonical MIT-BIH ECG databases. We tested algorithms on the NSR, AF and arrhythmia databases. When the databases were combined, the positive predictive value of the new algorithms exceeded 95% for NSR and AF, and was 40% for SR with ectopy. Further, dynamical measures did not distinguish atrial from ventricular ectopy. Inspection of individual 24hour records showed good correlation of observed and predicted rhythms. Heart rate dynamical measures are effective ingredients in numerical algorithms to classify cardiac rhythm from the heartbeat intervals time series alone. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Lymphatic territories (lymphosomes in a canine: an animal model for investigation of postoperative lymphatic alterations.

    Directory of Open Access Journals (Sweden)

    Hiroo Suami

    Full Text Available BACKGROUND: Lymph node dissection is often performed as a part of surgical treatment for breast cancer and malignant melanoma to prevent malignant cells from traveling via the lymphatic system. Currently little is known about postoperative lymphatic drainage pattern alterations. This knowledge may be useful for management of recurrent cancer and prevention of breast cancer related lymphedema. We mapped the complete superficial lymphatic system of a dog and used this canine model to perform preliminary studies of lymphatic architectural changes in postoperative condition. METHODS: Lymphatic territories (lymphosomes were mapped with 4 female mongrel carcasses using an indocyanine green (ICG fluorescent lymphography and a radiographic microinjection technique. Two live dogs were then subjected to unilateral lymph node dissection of lymph basins of the forelimb, and ICG lymphography and lymphangiogram were performed 6 months after the surgery to investigate lymphatic changes. Lymphatic patterns in the carcass were then compared with postoperative lymphatic patterns in the live dogs. RESULTS: Ten lymphosomes were identified, corresponding with ten lymphatic basins. Postoperative fluorescent lymphographic images and lymphangiograms in the live dogs revealed small caliber lymphatic network fulfilling gaps in the surgical area and collateral lymphatic vessels arising from the network connecting to lymph nodes in the contralateral and ipsilateral neck in one dog and the ipsilateral subclavicular vein in another dog. CONCLUSION: Our canine lymphosome map allowed us to observe lymphatic collateral formations after lymph node dissection in live dogs. This canine model may help clarify our understanding of postoperative lymphatic changes in humans in future studies.

  14. Dynamic changes in sRAGE levels and relationship with cardiac function in STEMI patients

    DEFF Research Database (Denmark)

    Jensen, Louise J N; Lindberg, Søren; Hoffmann, Søren;

    2015-01-01

    the dynamic changes in sRAGE levels during AMI and relationship with cardiac dysfunction. DESIGN AND METHODS: We prospectively included 80 patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). sRAGE concentrations were measured before p......OBJECTIVES: Soluble receptor of advanced glycation end-products (sRAGE) may be a predictive biomarker in coronary artery disease (CAD). Patients with acute myocardial infarction (AMI) have higher sRAGE levels compared to healthy subjects. Accordingly, the aim of this study was to investigate...

  15. Applications of control theory to the dynamics and propagation of cardiac action potentials.

    Science.gov (United States)

    Muñoz, Laura M; Stockton, Jonathan F; Otani, Niels F

    2010-09-01

    Sudden cardiac arrest is a widespread cause of death in the industrialized world. Most cases of sudden cardiac arrest are due to ventricular fibrillation (VF), a lethal cardiac arrhythmia. Electrophysiological abnormalities such as alternans (a beat-to-beat alternation in action potential duration) and conduction block have been suspected to contribute to the onset of VF. This study focuses on the use of control-systems techniques to analyze and design methods for suppressing these precursor factors. Control-systems tools, specifically controllability analysis and Lyapunov stability methods, were applied to a two-variable Karma model of the action-potential (AP) dynamics of a single cell, to analyze the effectiveness of strategies for suppressing AP abnormalities. State-feedback-integral (SFI) control was then applied to a Purkinje fiber simulated with the Karma model, where only one stimulating electrode was used to affect the system. SFI control converted both discordant alternans and 2:1 conduction block back toward more normal patterns, over a wider range of fiber lengths and pacing intervals compared with a Pyragas-type chaos controller. The advantages conferred by using feedback from multiple locations in the fiber, and using integral (i.e., memory) terms in the controller, are discussed.

  16. Albendazole for lymphatic filariasis (Review)

    OpenAIRE

    Addiss, D; Critchley, J.; Ejere, H.; Garner, Paul; Gelband, H; Gamble, C.

    2005-01-01

    Background\\ud Mass treatment with albendazole, co-administered with another antifilarial drug, is being promoted as part of a global programme to eliminate lymphatic filariasis.\\ud Objectives\\ud To assess the effects of albendazole on patients or populations with filarial infection, and on morbidity in patients with filarial infection; and to assess the frequency of adverse events for albendazole both given singly or in combination with another antifilarial drug (diethylcarbamazine or ivermec...

  17. Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis.

    Directory of Open Access Journals (Sweden)

    Juhyun Lee

    Full Text Available Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS and pressure gradients (∇P across the atrioventricular (AV canal. Zebrafish (Danio rerio are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP (y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV across the atrioventricular (AV canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf, simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6, whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis.

  18. Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis.

    Science.gov (United States)

    Lee, Juhyun; Moghadam, Mahdi Esmaily; Kung, Ethan; Cao, Hung; Beebe, Tyler; Miller, Yury; Roman, Beth L; Lien, Ching-Ling; Chi, Neil C; Marsden, Alison L; Hsiai, Tzung K

    2013-01-01

    Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP) (y1) transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis.

  19. Fetal cardiac cine imaging using highly accelerated dynamic MRI with retrospective motion correction and outlier rejection.

    Science.gov (United States)

    van Amerom, Joshua F P; Lloyd, David F A; Price, Anthony N; Kuklisova Murgasova, Maria; Aljabar, Paul; Malik, Shaihan J; Lohezic, Maelene; Rutherford, Mary A; Pushparajah, Kuberan; Razavi, Reza; Hajnal, Joseph V

    2017-04-03

    Development of a MRI acquisition and reconstruction strategy to depict fetal cardiac anatomy in the presence of maternal and fetal motion. The proposed strategy involves i) acquisition and reconstruction of highly accelerated dynamic MRI, followed by image-based ii) cardiac synchronization, iii) motion correction, iv) outlier rejection, and finally v) cardiac cine reconstruction. Postprocessing entirely was automated, aside from a user-defined region of interest delineating the fetal heart. The method was evaluated in 30 mid- to late gestational age singleton pregnancies scanned without maternal breath-hold. The combination of complementary acquisition/reconstruction and correction/rejection steps in the pipeline served to improve the quality of the reconstructed 2D cine images, resulting in increased visibility of small, dynamic anatomical features. Artifact-free cine images successfully were produced in 36 of 39 acquired data sets; prolonged general fetal movements precluded processing of the remaining three data sets. The proposed method shows promise as a motion-tolerant framework to enable further detail in MRI studies of the fetal heart and great vessels. Processing data in image-space allowed for spatial and temporal operations to be applied to the fetal heart in isolation, separate from extraneous changes elsewhere in the field of view. Magn Reson Med, 2017. © 2017 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. 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  20. Lymphatics and Lymphangiogenesis in the Eye

    Directory of Open Access Journals (Sweden)

    Shintaro Nakao

    2012-01-01

    Full Text Available Lymphatic is a prerequisite for the maintenance of tissue fluid balance and immunity in the body. A body of evidence also shows that lymphangiogenesis plays important roles in the pathogenesis of diseases such as tumor metastasis and inflammation. The eye was thought to lack lymphatic vessels except for the conjunctiva; however, advances in the field, including the identification of lymphatic endothelial markers (e.g., LYVE-1 or podoplanin and lymphangiogenic factors (e.g., VEGF-C, have revealed the exsitence and possible roles of lymphatics and lymphangiogenesis in the eye. Recent studies have shown that corneal limbus, ciliary body, lacrimal gland, orbital meninges, and extraocular muscles contain lymphatic vessels and that the choroid might have a lymphatic-like system. There is no known lymphatic outflow from the eye. However, several lymphatic channels including uveolymphatic pathway might serve the ocular fluid homeostasis. Furthermore, lymphangiogenesis plays important roles in pathological conditions in the eye including corneal transplant rejection and ocular tumor progression. Yet, the role of lymphangiogenesis in most eye diseases, especially inflammatory disease or edema, remains unknown. A better understanding of lymphatic and lymphangiogenesis in the eye will open new therapeutic opportunities to prevent vision loss in ocular diseases.

  1. Lymphatics and cancer : VEGF-C and nitric oxide in lymphatic function, lymphangiogenesis, and metastasis

    NARCIS (Netherlands)

    Hagendoorn, Jeroen

    2006-01-01

    The lymphatics are a primary route for cancer metastasis and lymph node metastasis is an important clinical prognostic factor. The process of lymphatic metastasis is, however, not well understood. This thesis examines the function of lymphatic vessels in relation to cancer progression and metastasis

  2. An Efficient Framework for Compressed Sensing Reconstruction of Highly Accelerated Dynamic Cardiac MRI

    Science.gov (United States)

    Ting, Samuel T.

    The research presented in this work seeks to develop, validate, and deploy practical techniques for improving diagnosis of cardiovascular disease. In the philosophy of biomedical engineering, we seek to identify an existing medical problem having significant societal and economic effects and address this problem using engineering approaches. Cardiovascular disease is the leading cause of mortality in the United States, accounting for more deaths than any other major cause of death in every year since 1900 with the exception of the year 1918. Cardiovascular disease is estimated to account for almost one-third of all deaths in the United States, with more than 2150 deaths each day, or roughly 1 death every 40 seconds. In the past several decades, a growing array of imaging modalities have proven useful in aiding the diagnosis and evaluation of cardiovascular disease, including computed tomography, single photon emission computed tomography, and echocardiography. In particular, cardiac magnetic resonance imaging is an excellent diagnostic tool that can provide within a single exam a high quality evaluation of cardiac function, blood flow, perfusion, viability, and edema without the use of ionizing radiation. The scope of this work focuses on the application of engineering techniques for improving imaging using cardiac magnetic resonance with the goal of improving the utility of this powerful imaging modality. Dynamic cine imaging, or the capturing of movies of a single slice or volume within the heart or great vessel region, is used in nearly every cardiac magnetic resonance imaging exam, and adequate evaluation of cardiac function and morphology for diagnosis and evaluation of cardiovascular disease depends heavily on both the spatial and temporal resolution as well as the image quality of the reconstruction cine images. This work focuses primarily on image reconstruction techniques utilized in cine imaging; however, the techniques discussed are also relevant to

  3. Altered lymphatic function and architecture in salt-induced hypertension assessed by near-infrared fluorescence imaging

    Science.gov (United States)

    Kwon, Sunkuk; Agollah, Germaine D.; Chan, Wenyaw; Sevick-Muraca, Eva M.

    2012-08-01

    The lymphatic system plays an important role in maintaining the fluid homeostasis between the blood vascular and interstitial tissue compartment and there is recent evidence that its transport capabilities may regulate blood pressure in salt-induced hypertension. Yet, there is little known how the lymphatic contractile function and architecture responds to dietary salt-intake. Thus, we longitudinally characterized lymphatic contractile function and vessel remodeling noninvasively using dynamic near-infrared fluorescence imaging in animal models of salt-induced hypertension. The lymphatics of mice and rats were imaged following intradermal injection of indocyanine green to the ear tip or the base of the tail before and during two weeks of either a high salt diet (HSD) or normal chow. Our noninvasive imaging data demonstrated dilated lymphatic vessels in the skin of mice and rats on a HSD as compared to their baseline levels. In addition, our dynamic imaging results showed increased lymphatic contraction frequency in HSD-fed mice and rats. Lymphatic contractile function and vessel remodeling occurs in response to salt-induced hypertension suggesting a possible role for the lymphatics in the regulation of vascular blood pressure.

  4. Lymphatic filariasis in the Philippines.

    Science.gov (United States)

    Kron, M; Walker, E; Hernandez, L; Torres, E; Libranda-Ramirez, B

    2000-08-01

    Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is endemic throughout most of the southern half of the Philippine archipelago. Economic and manpower shortages prior to 1996 made it difficult to acquire new prevalence data and vector control data concurrently from all provinces. Nevertheless, analysis of cumulative prevalence data on filariasis indicates the persistence of filariasis in each of the three major island groups - Luzon, Visayas and Mindanao - including 45 out of 77 provinces. Here, Michael Kron and colleagues summarize the prevalence data, and review host, parasite and vector characteristics relevant to the design and implementation of disease control initiatives in the Philippines planned for the year 2000.

  5. Evaluation of static and dynamic perfusion cardiac computed tomography for quantitation and classification tasks.

    Science.gov (United States)

    Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R; La Riviere, Patrick J; Alessio, Adam M

    2016-04-01

    Cardiac computed tomography (CT) acquisitions for perfusion assessment can be performed in a dynamic or static mode. Either method may be used for a variety of clinical tasks, including (1) stratifying patients into categories of ischemia and (2) using a quantitative myocardial blood flow (MBF) estimate to evaluate disease severity. In this simulation study, we compare method performance on these classification and quantification tasks for matched radiation dose levels and for different flow states, patient sizes, and injected contrast levels. Under conditions simulated, the dynamic method has low bias in MBF estimates (0 to [Formula: see text]) compared to linearly interpreted static assessment (0.45 to [Formula: see text]), making it more suitable for quantitative estimation. At matched radiation dose levels, receiver operating characteristic analysis demonstrated that the static method, with its high bias but generally lower variance, had superior performance ([Formula: see text]) in stratifying patients, especially for larger patients and lower contrast doses [area under the curve [Formula: see text] to 96 versus 0.86]. We also demonstrate that static assessment with a correctly tuned exponential relationship between the apparent CT number and MBF has superior quantification performance to static assessment with a linear relationship and to dynamic assessment. However, tuning the exponential relationship to the patient and scan characteristics will likely prove challenging. This study demonstrates that the selection and optimization of static or dynamic acquisition modes should depend on the specific clinical task.

  6. Lymphatic imaging in unsedated infants and children

    Science.gov (United States)

    Rasmussen, John C.; Balaguru, Duraisamy; Douglas, William I.; Breinholt, John P.; Greives, Matthew R.; Aldrich, Melissa B.; Sevick-Muraca, Eva M.

    2017-02-01

    Primary lymphedema and lymphatic malformations in the pediatric population remains poorly diagnosed and misunderstood due to a lack of information on the underlying anatomy and function of the lymphatic system. Diagnostics for the lymphatic vasculature are limited, consisting of lymphoscintigraphy or invasive lymphangiography, both of which require sedation that can restrict use in infants and children. As a result, therapeutic protocols for pediatric patients with lymphatic disorders remain sparse and with little evidence to support them. Because near-infrared fluorescence (NIRF) imaging enables image acquisition on the order of tenths of seconds with trace administration of fluorescent dye, sedation is not necessary. The lack of harmful radiation and radioactive contrast agents further facilitates imaging. Herein we summarize our experiences in imaging infants and children who are suspected to have disorders of the lymphatic vascular system using indocyanine green (ICG) and who have developed chylothorax following surgery for congenital heart defects. The results show both anatomical as well as functional lymphatic deficits in children with congenital disease. In the future, NIRF lymphatic imaging could provide new opportunities to tailor effective therapies and monitor responses. The opportunity to use expand NIRF imaging for pediatric diagnostics beyond the lymphatic vasculature is also afforded by the rapid acquisition following trace administration of NIRF contrast agent.

  7. Lymphatic Vascular-Based Therapy for IBD

    Science.gov (United States)

    2012-07-01

    intestine which lead to a failure in normal intestinal lymphatic patterning and may be a model of human lymphedema distichiasis. These mice are... lymphedema distichiasis (humans) is not apparent, this is not seen in this model either. There is a reported apparent greater engorgement of lymphatic

  8. Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

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    Souheil El-Chemaly

    2012-09-01

    Full Text Available The primary function of the lymphatic system is absorbing and transporting macromolecules and immune cells to the general circulation, thereby regulating fluid, nutrient absorption and immune cell trafficking. Lymphangiogenesis plays an important role in tissue inflammation and tumour cell dissemination. Lymphatic involvement is seen in lymphangioleiomyomatosis (LAM and idiopathic pulmonary fibrosis (IPF. LAM, a disease primarily affecting females, involves the lung (cystic destruction, kidney (angiomyolipoma and axial lymphatics (adenopathy and lymphangioleiomyoma. LAM occurs sporadically or in association with tuberous sclerosis complex (TSC. Cystic lung destruction results from proliferation of LAM cells, which are abnormal smooth muscle-like cells with mutations in the TSC1 or TSC2 gene. Lymphatic abnormalities arise from infiltration of LAM cells into the lymphatic wall, leading to damage or obstruction of lymphatic vessels. Benign appearing LAM cells possess metastatic properties and are found in the blood and other body fluids. IPF is a progressive lung disease resulting from fibroblast proliferation and collagen deposition. Lymphangiogenesis is associated with pulmonary destruction and disease severity. A macrophage subset isolated from IPF bronchoalveolar lavage fluid (BALF express lymphatic endothelial cell markers in vitro, in contrast to the same macrophage subset from normal BALF. Herein, we review lymphatic involvement in LAM and IPF.

  9. Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats.

    Science.gov (United States)

    Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Tugues, Sònia; Fernández-Varo, Guillermo; Held, Kara F; Soria, Guadalupe; Tudela, Raúl; Planas, Anna M; Fernández-Hernando, Carlos; Arroyo, Vicente; Jiménez, Wladimiro; Morales-Ruiz, Manuel

    2013-01-01

    The lymphatic network plays a major role in maintaining tissue fluid homoeostasis. Therefore several pathological conditions associated with oedema formation result in deficient lymphatic function. However, the role of the lymphatic system in the pathogenesis of ascites and oedema formation in cirrhosis has not been fully clarified. The aim of this study was to investigate whether the inability of the lymphatic system to drain tissue exudate contributes to the oedema observed in cirrhosis. Cirrhosis was induced in rats by CCl(4) inhalation. Lymphatic drainage was evaluated using fluorescent lymphangiography. Expression of endothelial nitric oxide synthase (eNOS) was measured in primary lymphatic endothelial cells (LyECs). Inhibition of eNOS activity in cirrhotic rats with ascites (CH) was carried out by L-N(G)-methyl-L-arginine (L-NMMA) treatment (0.5 mg/kg/day). The (CH) rats had impaired lymphatic drainage in the splanchnic and peripheral regions compared with the control (CT) rats. LyECs isolated from the CH rats showed a significant increase in eNOS and nitric oxide (NO) production. In addition, the lymphatic vessels of the CH rats showed a significant reduction in smooth muscle cell (SMC) coverage compared with the CT rats. CH rats treated with L-NMMA for 7 days showed a significant improvement in lymphatic drainage and a significant reduction in ascites volume, which were associated with increased plasma volume. This beneficial effect of L-NMMA inhibition was also associated with a significant increase in lymphatic SMC coverage. The upregulation of eNOS in the LyECs of CH rats causes long-term lymphatic remodelling, which is characterised by a loss of SMC lymphatic coverage. The amelioration of this lymphatic abnormality by chronic eNOS inhibition results in improved lymphatic drainage and reduced ascites.

  10. Cine magnetic resonance imaging for evaluation of cardiac structure and flow dynamics in congenital heart disease

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    Akagi, Teiji; Kiyomatsu, Yumi; Ohara, Nobutoshi; Takagi, Junichi; Sato, Noboru; Kato, Hirohisa (Kurume Univ., Fukuoka (Japan). School of Medicine); Eto, Takaharu

    1989-10-01

    Cine magnetic resonance imaging (Cine MRI) was performed in 20 patients aged 19 days to 13 years (mean 4.0 years), who had congenital heart disease confirmed at echocardiography or angiography. Prior to cine MRI, gated MRI was performed to evaluate for cardiac structure. Cine MRI was demonstrated by fast low fip angle shot imaging technique with a 30deg flip angle, 15 msec echo time, 30-40 msec pulse repetition time, and 128 x 128 acquisition matrix. Abnormalities of cardiac structure were extremely well defined in all patients by gated MRI. Intracardiac or intravascular blood flow were visualized in 17 (85%) of 20 patients by cine MRI. Left to right shunt flow through ventricular septal defect, atrial septal defect, and endocardial cushion defect were visualized with low signal intensity area. Low intensity jets flow through the site of re-coarctation of the aorta were also visualized. However, the good recording of cine MRI was not obtained because of artifacts in 3 of 20 patients (15%) who had severe congestive heart failure or respiratory arrhythmia. Gated MRI provides excellent visualization of fine structure, and cine MRI can provide high spatial resolution imaging of flow dynamic in a variety of congenital heart disease, noninvasively. (author).

  11. Dynamic Measurement of Hemodynamic Parameters and Cardiac Preload in Adults with Dengue: A Prospective Observational Study.

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    Vipa Thanachartwet

    Full Text Available Few previous studies have monitored hemodynamic parameters to determine the physiological process of dengue or examined inferior vena cava (IVC parameters to assess cardiac preload during the clinical phase of dengue. From January 2013 to July 2015, we prospectively studied 162 hospitalized adults with confirmed dengue viral infection using non-invasive cardiac output monitoring and bedside ultrasonography to determine changes in hemodynamic and IVC parameters and identify the types of circulatory shock that occur in patients with dengue. Of 162 patients with dengue, 17 (10.5% experienced dengue shock and 145 (89.5% did not. In patients with shock, the mean arterial pressure was significantly lower on day 6 after fever onset (P = 0.045 and the pulse pressure was significantly lower between days 4 and 7 (P50% between days 4 and 5 (P<0.05. Hypovolemic shock was observed in 9 (52.9% patients and cardiogenic shock in 8 (47.1%, with a median (interquartile range time to shock onset of 6.0 (5.0-6.5 days after fever onset, which was the median day of defervescence. Intravascular hypovolemia occurred before defervescence, whereas myocardial dysfunction occurred on the day of defervescence until 2 weeks after fever onset. Hypovolemic shock and cardiogenic shock each occurred in approximately half of the patients with dengue shock. Therefore, dynamic measures to estimate changes in hemodynamic parameters and preload should be monitored to ensure adequate fluid therapy among patients with dengue, particularly patients with dengue shock.

  12. Uncovering the dynamics of cardiac systems using stochastic pacing and frequency domain analyses.

    Science.gov (United States)

    Lemay, Mathieu; de Lange, Enno; Kucera, Jan P

    2012-01-01

    Alternans of cardiac action potential duration (APD) is a well-known arrhythmogenic mechanism which results from dynamical instabilities. The propensity to alternans is classically investigated by examining APD restitution and by deriving APD restitution slopes as predictive markers. However, experiments have shown that such markers are not always accurate for the prediction of alternans. Using a mathematical ventricular cell model known to exhibit unstable dynamics of both membrane potential and Ca²⁺ cycling, we demonstrate that an accurate marker can be obtained by pacing at cycle lengths (CLs) varying randomly around a basic CL (BCL) and by evaluating the transfer function between the time series of CLs and APDs using an autoregressive-moving-average (ARMA) model. The first pole of this transfer function corresponds to the eigenvalue (λ(alt)) of the dominant eigenmode of the cardiac system, which predicts that alternans occurs when λ(alt) ≤ -1. For different BCLs, control values of λ(alt) were obtained using eigenmode analysis and compared to the first pole of the transfer function estimated using ARMA model fitting in simulations of random pacing protocols. In all versions of the cell model, this pole provided an accurate estimation of λ(alt). Furthermore, during slow ramp decreases of BCL or simulated drug application, this approach predicted the onset of alternans by extrapolating the time course of the estimated λ(alt). In conclusion, stochastic pacing and ARMA model identification represents a novel approach to predict alternans without making any assumptions about its ionic mechanisms. It should therefore be applicable experimentally for any type of myocardial cell.

  13. Uncovering the dynamics of cardiac systems using stochastic pacing and frequency domain analyses.

    Directory of Open Access Journals (Sweden)

    Mathieu Lemay

    Full Text Available Alternans of cardiac action potential duration (APD is a well-known arrhythmogenic mechanism which results from dynamical instabilities. The propensity to alternans is classically investigated by examining APD restitution and by deriving APD restitution slopes as predictive markers. However, experiments have shown that such markers are not always accurate for the prediction of alternans. Using a mathematical ventricular cell model known to exhibit unstable dynamics of both membrane potential and Ca²⁺ cycling, we demonstrate that an accurate marker can be obtained by pacing at cycle lengths (CLs varying randomly around a basic CL (BCL and by evaluating the transfer function between the time series of CLs and APDs using an autoregressive-moving-average (ARMA model. The first pole of this transfer function corresponds to the eigenvalue (λ(alt of the dominant eigenmode of the cardiac system, which predicts that alternans occurs when λ(alt ≤ -1. For different BCLs, control values of λ(alt were obtained using eigenmode analysis and compared to the first pole of the transfer function estimated using ARMA model fitting in simulations of random pacing protocols. In all versions of the cell model, this pole provided an accurate estimation of λ(alt. Furthermore, during slow ramp decreases of BCL or simulated drug application, this approach predicted the onset of alternans by extrapolating the time course of the estimated λ(alt. In conclusion, stochastic pacing and ARMA model identification represents a novel approach to predict alternans without making any assumptions about its ionic mechanisms. It should therefore be applicable experimentally for any type of myocardial cell.

  14. Potential Effects of Heliogeophysical Activity on the Dynamics of Sudden Cardiac Death at Earth Middle Latitudes

    Science.gov (United States)

    Dimitrova, S.; Babayev, E.; Mustafa, F.

    2017-01-01

    Limited studies exist on comparing the possible effects of heliogeophysical activity (solar and geomagnetic) on the dynamics of sudden cardiac death (SCD) as a function of latitude on Earth. In this work we continue our earlier studies concerning the changing space environment and SCD dynamics at middle latitudes. The study covered 25 to 80-year old males and females, and used medical data provided by all emergency and first medical aid stations in the Grand Baku Area, Azerbaijan. Data coverage includedthe second peak of Solar Cycle 23 and its descending activity years followed by its long-lasting minimum. Gradation of geomagnetic activity into six levels was introduced to study the effect of space weather on SCD. The ANalysis Of VAriance (ANOVA) test was applied to study the significance of the geomagnetic activity effect, estimated by different geomagnetic indices, on SCD dynamics. Variations inthe number of SCDs occurring on days preceding and following the development of geomagnetic storms were also studied. Results revealed that the SCD number was largest on days of very low geomagnetic activity and on days proceeding and following geomagnetic storms with different intensities. Vulnerability for males was found to be higher around days of major and severe geomagnetic storms. Females, on the other hand, were more threatened around days of lower intensity storms. It is concluded that heliogeophysical activity could be considered as one of the regulating external/environmental factors in human homeostasis.

  15. Live dynamic OCT imaging of cardiac structure and function in mouse embryos with 43 Hz direct volumetric data acquisition

    Science.gov (United States)

    Wang, Shang; Singh, Manmohan; Lopez, Andrew L.; Wu, Chen; Raghunathan, Raksha; Schill, Alexander; Li, Jiasong; Larin, Kirill V.; Larina, Irina V.

    2016-03-01

    Efficient phenotyping of cardiac dynamics in live mouse embryos has significant implications on understanding of early mammalian heart development and congenital cardiac defects. Recent studies established optical coherence tomography (OCT) as a powerful tool for live embryonic heart imaging in various animal models. However, current four-dimensional (4D) OCT imaging of the beating embryonic heart largely relies on gated data acquisition or postacquisition synchronization, which brings errors when cardiac cycles lack perfect periodicity and is time consuming and computationally expensive. Here, we report direct 4D OCT imaging of the structure and function of cardiac dynamics in live mouse embryos achieved by employing a Fourier domain mode-locking swept laser source that enables ~1.5 MHz A-line rate. Through utilizing both forward and backward scans of a resonant mirror, we obtained a ~6.4 kHz frame rate, which allows for a direct volumetric data acquisition speed of ~43 Hz, around 20 times of the early-stage mouse embryonic heart rate. Our experiments were performed on mouse embryos at embryonic day 9.5. Time-resolved 3D cardiodynamics clearly shows the heart structure in motion. We present analysis of cardiac wall movement and its velocity from the primitive atrium and ventricle. Our results suggest that the combination of ultrahigh-speed OCT imaging with live embryo culture could be a useful embryonic heart phenotyping approach for mouse mutants modeling human congenital heart diseases.

  16. Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer.

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    Xin Ming

    Full Text Available To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT, intensity-modulated radiotherapy (IMRT, or volumetric modulated arc therapy (VMAT at our institution in the past seven years.A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated.The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2% with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance.Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin's disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy.

  17. Quantifying cardiac sympathetic and parasympathetic nervous activities using principal dynamic modes analysis of heart rate variability.

    Science.gov (United States)

    Zhong, Yuru; Jan, Kung-Ming; Ju, Ki Hwan; Chon, Ki H

    2006-09-01

    The ratio between low-frequency (LF) and high-frequency (HF) spectral power of heart rate has been used as an approximate index for determining the autonomic nervous system (ANS) balance. An accurate assessment of the ANS balance can only be achieved if clear separation of the dynamics of the sympathetic and parasympathetic nervous activities can be obtained, which is a daunting task because they are nonlinear and have overlapping dynamics. In this study, a promising nonlinear method, termed the principal dynamic mode (PDM) method, is used to separate dynamic components of the sympathetic and parasympathetic nervous activities on the basis of ECG signal, and the results are compared with the power spectral approach to assessing the ANS balance. The PDM analysis based on the 28 subjects consistently resulted in a clear separation of the two nervous systems, which have similar frequency characteristics for parasympathetic and sympathetic activities as those reported in the literature. With the application of atropine, in 13 of 15 supine subjects there was an increase in the sympathetic-to-parasympathetic ratio (SPR) due to a greater decrease of parasympathetic than sympathetic activity (P=0.003), and all 13 subjects in the upright position had a decrease in SPR due to a greater decrease of sympathetic than parasympathetic activity (Pparasympathetic and sympathetic nervous systems. The culprit is equivalent decreases in both the sympathetic and parasympathetic activities irrespective of the pharmacological blockades. These findings suggest that the PDM shows promise as a noninvasive and quantitative marker of ANS imbalance, which has been shown to be a factor in many cardiac and stress-related diseases.

  18. The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics.

    Science.gov (United States)

    Silva, Luiz Eduardo Virgilio; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens

    2017-03-01

    Analysis of heart rate variability (HRV) by nonlinear approaches has been gaining interest due to their ability to extract additional information from heart rate (HR) dynamics that are not detectable by traditional approaches. Nevertheless, the physiological interpretation of nonlinear approaches remains unclear. Therefore, we propose long-term (60 min) protocols involving selective blockade of cardiac autonomic receptors to investigate the contribution of sympathetic and parasympathetic function upon nonlinear dynamics of HRV. Conscious male Wistar rats had their electrocardiogram (ECG) recorded under three distinct conditions: basal, selective (atenolol or atropine), or combined (atenolol plus atropine) pharmacological blockade of autonomic muscarinic or β1-adrenergic receptors. Time series of RR interval were assessed by multiscale entropy (MSE) and detrended fluctuation analysis (DFA). Entropy over short (1 to 5, MSE1-5) and long (6 to 30, MSE6-30) time scales was computed, as well as DFA scaling exponents at short (αshort, 5 ≤ n ≤ 15), mid (αmid, 30 ≤ n ≤ 200), and long (αlong, 200 ≤ n ≤ 1,700) window sizes. The results show that MSE1-5 is reduced under atropine blockade and MSE6-30 is reduced under atropine, atenolol, or combined blockade. In addition, while atropine expressed its maximal effect at scale six, the effect of atenolol on MSE increased with scale. For DFA, αshort decreased during atenolol blockade, while the αmid increased under atropine blockade. Double blockade decreased αshort and increased αlong Results with surrogate data show that the dynamics during combined blockade is not random. In summary, sympathetic and vagal control differently affect entropy (MSE) and fractal properties (DFA) of HRV. These findings are important to guide future studies.NEW & NOTEWORTHY Although multiscale entropy (MSE) and detrended fluctuation analysis (DFA) are recognizably useful prognostic/diagnostic methods, their physiological

  19. FOXO3a regulates BNIP3 and modulates mitochondrial calcium, dynamics, and function in cardiac stress.

    Science.gov (United States)

    Chaanine, Antoine H; Kohlbrenner, Erik; Gamb, Scott I; Guenzel, Adam J; Klaus, Katherine; Fayyaz, Ahmed U; Nair, K Sreekumaran; Hajjar, Roger J; Redfield, Margaret M

    2016-12-01

    The forkhead box O3a (FOXO3a) transcription factor has been shown to regulate glucose metabolism, muscle atrophy, and cell death in postmitotic cells. Its role in regulation of mitochondrial and myocardial function is not well studied. Based on previous work, we hypothesized that FOXO3a, through BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3), modulates mitochondrial morphology and function in heart failure (HF). We modulated the FOXO3a-BNIP3 pathway in normal and phenylephrine (PE)-stressed adult cardiomyocytes (ACM) in vitro and developed a cardiotropic adeno-associated virus serotype 9 encoding dominant-negative FOXO3a (AAV9.dn-FX3a) for gene delivery in a rat model of HF with preserved ejection fraction (HFpEF). We found that FOXO3a upregulates BNIP3 expression in normal and PE-stressed ACM, with subsequent increases in mitochondrial Ca(2+), leading to decreased mitochondrial membrane potential, mitochondrial fragmentation, and apoptosis. Whereas dn-FX3a attenuated the increase in BNIP3 expression and its consequences in PE-stressed ACM, AAV9.dn-FX3a delivery in an experimental model of HFpEF decreased BNIP3 expression, reversed adverse left ventricular remodeling, and improved left ventricular systolic and, particularly, diastolic function, with improvements in mitochondrial structure and function. Moreover, AAV9.dn-FX3a restored phospholamban phosphorylation at S16 and enhanced dynamin-related protein 1 phosphorylation at S637. Furthermore, FOXO3a upregulates maladaptive genes involved in mitochondrial apoptosis, autophagy, and cardiac atrophy. We conclude that FOXO3a activation in cardiac stress is maladaptive, in that it modulates Ca(2+) cycling, Ca(2+) homeostasis, and mitochondrial dynamics and function. Our results suggest an important role of FOXO3a in HF, making it an attractive potential therapeutic target. Copyright © 2016 the American Physiological Society.

  20. Maximum shortening velocity of lymphatic muscle approaches that of striated muscle.

    Science.gov (United States)

    Zhang, Rongzhen; Taucer, Anne I; Gashev, Anatoliy A; Muthuchamy, Mariappan; Zawieja, David C; Davis, Michael J

    2013-11-15

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

  1. [The influence of cardiosurgical intervention type and conditions of artificial blood circulation of perioperative dynamics of cardiac biomarkers].

    Science.gov (United States)

    Dement'eva, I I; Morozov, Iu A; Charnaia, M A

    2013-01-01

    125 patients after cardiac surgery operated on with the use of artificial blood circulation (ABC) were followed-up. Blood levels of cardiac protein, binding aliphatic acids and troponin 1 and 3 days after the operation were registered. The study showed that aorta clamping more then 90 minutes and hypothermic perfusion regimen influence cardiomyocites negatively. The state of "surgical trauma" and reperfusional myocardium damage was approximately the same during aortic surgery, myocardium revascularization with the use of aortic clamping and cardioplegia, and correction of the acquired heart disease, according to the dynamics of the studied proteins in blood. The minimal blood level of cardiac protein, binding aliphatic acids after coronary by-pass surgery on the working heart witnesses about negative influence of crystalloid hypothermic cardioplegia on coronary microcirculation.

  2. In vivo determination of collecting lymphatic vessel permeability to albumin: a role for lymphatics in exchange

    Science.gov (United States)

    Scallan, Joshua P; Huxley, Virginia H

    2010-01-01

    While it is well established that the lymphatic vasculature is central to fluid and solute homeostasis, how it accomplishes this task is not well defined. To clarify the basic mechanisms underlying basal fluid and solute homeostasis, we assessed permeability to rat serum albumin () in mesenteric collecting lymphatic vessels and venules of juvenile male rats. Using the quantitative microfluorometric technique originally developed for blood capillaries, we tested the hypothesis that as a consequence of venules and collecting lymphatics sharing a common embryological origin, their would not differ significantly. Supporting our hypothesis, the median collecting lymphatic (3.5 ± 1.0 × 10−7 cm s−1, N= 22) did not differ significantly from the median venular (4.0 ± 1.0 × 10−7 cm s−1, N= 8, P= 0.61). For collecting lymphatics the diffusive permeability (Pd= 2.5 × 10−7 cm s−1) was obtained from the relationship of apparent and pressure. While the measured , Pd and estimated hydraulic conductivity of collecting lymphatics and venules were similar, the contribution of convective coupling differs as a result of the higher hydrostatic pressure experienced by venules relative to collecting lymphatics in vivo. In summary, the data demonstrate the capacity for collecting lymphatics to act as exchange vessels, able to extravasate solute and filter fluid. As a consequence these data provide experimental support for the theory that prenodal lymphatic vessels concentrate intraluminal protein. PMID:19917564

  3. Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.

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    Ioannis Kokkinopoulos

    Full Text Available In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.

  4. Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.

    Science.gov (United States)

    Kokkinopoulos, Ioannis; Ishida, Hidekazu; Saba, Rie; Ruchaya, Prashant; Cabrera, Claudia; Struebig, Monika; Barnes, Michael; Terry, Anna; Kaneko, Masahiro; Shintani, Yasunori; Coppen, Steven; Shiratori, Hidetaka; Ameen, Torath; Mein, Charles; Hamada, Hiroshi; Suzuki, Ken; Yashiro, Kenta

    2015-01-01

    In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.

  5. Cardiac parasympathetic outflow during dynamic exercise in humans estimated from power spectral analysis of P-P interval variability.

    Science.gov (United States)

    Takahashi, Makoto; Nakamoto, Tomoko; Matsukawa, Kanji; Ishii, Kei; Watanabe, Tae; Sekikawa, Kiyokazu; Hamada, Hironobu

    2016-03-01

    What is the central question of this study? Should we use the high-frequency (HF) component of P-P interval as an index of cardiac parasympathetic nerve activity during moderate exercise? What is the main finding and its importance? The HF component of P-P interval variability remained even at a heart rate of 120-140 beats min(-1) and was further reduced by atropine, indicating incomplete cardiac vagal withdrawal during moderate exercise. The HF component of R-R interval is invalid as an estimate of cardiac parasympathetic outflow during moderate exercise; instead, the HF component of P-P interval variability should be used. The high-frequency (HF) component of R-R interval variability has been widely used as an indirect estimate of cardiac parasympathetic (vagal) outflow to the sino-atrial node of the heart. However, we have recently found that the variability of the R-R interval becomes much smaller during dynamic exercise than that of the P-P interval above a heart rate (HR) of ∼100 beats min(-1). We hypothesized that cardiac parasympathetic outflow during dynamic exercise with a higher intensity may be better estimated using the HF component of P-P interval variability. To test this hypothesis, the HF components of both P-P and R-R interval variability were analysed using a Wavelet transform during dynamic exercise. Twelve subjects performed ergometer exercise to increase HR from the baseline of 69 ± 3 beats min(-1) to three different levels of 100, 120 and 140 beats min(-1). We also examined the effect of atropine sulfate on the HF components in eight of the 12 subjects during exercise at an HR of 140 beats min(-1) . The HF component of P-P interval variability was significantly greater than that of R-R interval variability during exercise, especially at the HRs of 120 and 140 beats min(-1). The HF component of P-P interval variability was more reduced by atropine than that of R-R interval variability. We conclude that cardiac parasympathetic outflow to the

  6. Heart Rate Fragmentation: A New Approach to the Analysis of Cardiac Interbeat Interval Dynamics.

    Science.gov (United States)

    Costa, Madalena D; Davis, Roger B; Goldberger, Ary L

    2017-01-01

    Background: Short-term heart rate variability (HRV) is most commonly attributed to physiologic vagal tone modulation. However, with aging and cardiovascular disease, the emergence of high short-term HRV, consistent with the breakdown of the neuroautonomic-electrophysiologic control system, may confound traditional HRV analysis. An apparent dynamical signature of such anomalous short-term HRV is frequent changes in heart rate acceleration sign, defined here as heart rate fragmentation. Objective: The aims were to: (1) introduce a set of metrics designed to probe the degree of sinus rhythm fragmentation; (2) test the hypothesis that the degree of fragmentation of heartbeat time series increases with the participants' age in a group of healthy subjects; (3) test the hypothesis that the heartbeat time series from patients with advanced coronary artery disease (CAD) are more fragmented than those from healthy subjects; and (4) compare the performance of the new fragmentation metrics with standard time and frequency domain measures of short-term HRV. Methods: We analyzed annotated, open-access Holter recordings (University of Rochester Holter Warehouse) from healthy subjects and patients with CAD using these newly introduced metrics of heart rate fragmentation, as well as standard time and frequency domain indices of short-term HRV, detrended fluctuation analysis and sample entropy. Results: The degree of fragmentation of cardiac interbeat interval time series increased significantly as a function of age in the healthy population as well as in patients with CAD. Fragmentation was higher for the patients with CAD than the healthy subjects. Heart rate fragmentation metrics outperformed traditional short-term HRV indices, as well as two widely used nonlinear measures, sample entropy and detrended fluctuation analysis short-term exponent, in distinguishing healthy subjects and patients with CAD. The same level of discrimination was obtained from the analysis of normal

  7. Real-time dynamic display of registered 4D cardiac MR and ultrasound images using a GPU

    Science.gov (United States)

    Zhang, Q.; Huang, X.; Eagleson, R.; Guiraudon, G.; Peters, T. M.

    2007-03-01

    In minimally invasive image-guided surgical interventions, different imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and real-time three-dimensional (3D) ultrasound (US), can provide complementary, multi-spectral image information. Multimodality dynamic image registration is a well-established approach that permits real-time diagnostic information to be enhanced by placing lower-quality real-time images within a high quality anatomical context. For the guidance of cardiac procedures, it would be valuable to register dynamic MRI or CT with intraoperative US. However, in practice, either the high computational cost prohibits such real-time visualization of volumetric multimodal images in a real-world medical environment, or else the resulting image quality is not satisfactory for accurate guidance during the intervention. Modern graphics processing units (GPUs) provide the programmability, parallelism and increased computational precision to begin to address this problem. In this work, we first outline our research on dynamic 3D cardiac MR and US image acquisition, real-time dual-modality registration and US tracking. Then we describe image processing and optimization techniques for 4D (3D + time) cardiac image real-time rendering. We also present our multimodality 4D medical image visualization engine, which directly runs on a GPU in real-time by exploiting the advantages of the graphics hardware. In addition, techniques such as multiple transfer functions for different imaging modalities, dynamic texture binding, advanced texture sampling and multimodality image compositing are employed to facilitate the real-time display and manipulation of the registered dual-modality dynamic 3D MR and US cardiac datasets.

  8. Advances in Lymphatic Imaging and Drug Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

    2011-09-10

    Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.

  9. Connexins in lymphatic vessel physiology and disease.

    Science.gov (United States)

    Meens, Merlijn J; Sabine, Amélie; Petrova, Tatiana V; Kwak, Brenda R

    2014-04-17

    Connexins are transmembrane proteins that form gap junction- and hemi-channels. Once inserted into the membrane, hemi-channels (connexons) allow for diffusion of ions and small molecules (Gap junction channels allow diffusion of similar molecules between the cytoplasms of adjacent cells. The expression and function of connexins in blood vessels has been intensely studied in the last few decades. In contrast, only a few studies paid attention to lymphatic vessels; convincing in vivo data with respect to expression patterns of lymphatic connexins and their functional roles have only recently begun to emerge. Interestingly, mutations in connexin genes have been linked to diseases of lymphatic vasculature, most notably primary and secondary lymphedema. This review summarizes the available data regarding lymphatic connexins. More specifically it addresses (i) early studies aimed at presence of gap junction-like structures in lymphatic vessels, (ii) more recent studies focusing on lymphatic connexins using genetically engineered mice, and (iii) results of clinical studies that have reported lymphedema-linked mutations in connexin genes. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides

    Science.gov (United States)

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-01-01

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin–angiotensin–aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nm) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P= 0.01, n= 7) and 2.7 ± 0.8-fold (P= 0.07, n= 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P= 0.005) and frequency (P= 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion. PMID:23897233

  11. Novel characterization of lymphatic valve formation during corneal inflammation.

    Directory of Open Access Journals (Sweden)

    Tan Truong

    Full Text Available Lymphatic research has progressed rapidly in recent years. Though lymphatic dysfunction has been found in a wide array of disorders from transplant rejection to cancer metastasis, to date, there is still little effective treatment for lymphatic diseases. The cornea offers an optimal site for lymphatic research due to its accessible location, transparent nature, and lymphatic-free but inducible features. However, it still remains unknown whether lymphatic valves exist in newly formed lymphatic vessels in the cornea, and how this relates to an inflammatory response. In this study, we provide the first evidence showing that lymphatic valves were formed in mouse cornea during suture-induced inflammation with the up-regulation of integrin alpha 9. The number of corneal valves increased with the progression of inflammatory lymphangiogenesis. Moreover, we have detected lymphatic valves at various developmental stages, from incomplete to more developed ones. In addition to defining the average diameter of lymphatic vessels equipped with lymphatic valves, we also report that lymphatic valves were more often located near the branching points. Taken together, these novel findings not only provide new insights into corneal lymphatic formation and maturation, but also identify a new model for future investigation on lymphatic valve formation and possibly therapeutic intervention.

  12. Musical rhythms in heart period dynamics: a cross-cultural and interdisciplinary approach to cardiac rhythms.

    Science.gov (United States)

    Bettermann, H; Amponsah, D; Cysarz, D; van Leeuwen, P

    1999-11-01

    The purpose of this study was to expand classic heart period analysis methods by techniques from ethnomusicology that explicitly take complex musical rhythm principles into consideration. The methods used are based on the theory of African music, the theory of symbolic dynamics, and combinatorial theory. Heart period tachograms from 192 24-h electrocardiograms of 96 healthy subjects were transformed into binary symbol sequences that were interpretable as elementary rhythmic (percussive) patterns, the time lines in African music. Using a hierarchical rhythm pattern scheme closely related to the Derler Rhythm Classification (from jazz theory), we calculated the predominance and stability of pattern classes. The results show that during sleep certain classes, specific to individuals, occurred in a cyclically recurrent manner and many times more often than expected. Simultaneously, other classes disappeared more or less completely. Moreover, the most frequent classes obviously originate from phase-locking processes in autonomic regulation (e.g., between respiratory and cardiac cycles). In conclusion, the new interdisciplinary method presented here demonstrates that heart period patterns, in particular those occurring during night sleep, can be interpreted as musical rhythms. This method may be of great potential use in music therapy research.

  13. Dynamic vs. fixed bag filling: impact on cardiac output rebreathing protocol.

    Science.gov (United States)

    Zavorsky, Gerald S; Beck, Kenneth C; Cass, Lauren M; Artal, Raul; Wagner, Peter D

    2010-04-15

    The purpose of this study was to compare the repeatability (2.77 multiplied by the within-subject SD)between two different rebreathing protocols on cardiac output ( ˙Q ), pulmonary diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), and pulmonary capillary blood volume (Vc). This study compared two bag volume protocols [Fixed Bag Volume (FBV) = bag volume fixed at 60% of forced vital capacity; Dynamic Bag Volume (DBV) = bag volume matched to tidal volume at each stage of exercise].Ten females (age = 27±8 yrs; ˙VO2, (peak)=2.5±0.6 L/min had measurements at rest (12%), 52%, 88%, and 100% of ˙VO2, (peak) on two study days. Neither the slope nor intercept of ˙Q vs. ˙VO2 were different between either bag volume protocols. The slope of DLCO vs. ˙Q was the same but the intercept was higher for the FBV protocol. The bag volume affected the slope and the intercept between DLNO vs. ˙Q (p DLNO (p ≤ 0.06). Measurement error was lower for Vc when using the FBV protocol (p = 0.02). Also, the pattern of bag volume used during rebreathing maneuvers affected the relation between DLNO vs. ˙Q more than it affected DLCO vs. ˙Q , or Vc vs. ˙Q. Additionally, the FBV protocol provided less measurement error for Vc compared to the DBV protocol [corrected].

  14. Nonlinear dynamics of the heartbeat II. Subharmonic bifurcations of the cardiac interbeat interval in sinus node disease

    Science.gov (United States)

    Goldberger, Ary L.; Bhargava, Valmik; West, Bruce J.; Mandell, Arnold J.

    1985-10-01

    Changing the coupling of electronic relaxation oscillators may be associated with the emergence of complex periodic behavior. The electrocardiographic record of a patient with the “sick sinus syndrome” demonstrated periodic behavior including subharmonic bifurcations in an attractor of his interbeat interval. Such nonlinear dynamics which may emerge from alterations in the coupling of oscillating pacemakers are not predicted by traditional models in cardiac electrophysiology. An understanding of the nonlinear behavior of physical and mathematical systems may generalize to pathophysiological processes.

  15. Lymphatic Vessel Function and Lymphatic Growth Factor Secretion after Microvascular Lymph Node Transfer in Lymphedema Patients

    Directory of Open Access Journals (Sweden)

    Tiina P. Viitanen, MD

    2013-05-01

    Conclusions: Reconstructing the lymphatic anatomy of the axilla with a lymph node flap may offer possibilities that other reconstructive options are lacking. However, we will need further reports and comparative studies about the clinical efficacy of this new promising technique. In addition to the transferred lymph nodes, lymphatic growth factor production may also be induced by other factors related to microvascular breast reconstruction.

  16. Superselective retrograde lymphatic duct embolization for management of postoperative lymphatic leak.

    Science.gov (United States)

    Arslan, Bülent; Masrani, Abdulrahman; Tasse, Jordan Cameron; Stenson, Kerstin; Turba, Ülkü Cenk

    2017-01-01

    Lymphatic leak is a well-documented complication following neck dissection surgeries. When conservative methods fail to control the leak, thoracic duct embolization becomes an option. Transabdominal access is the standard for this procedure; however, it is not always feasible. We discuss a technique of selective lymphatic vessel embolization utilizing retrograde transvenous access.

  17. Imaging of cardiac perfusion of free-breathing small animals using dynamic phase-correlated micro-CT

    Energy Technology Data Exchange (ETDEWEB)

    Sawall, Stefan; Kuntz, Jan; Socher, Michaela; Knaup, Michael; Hess, Andreas; Bartling, Soenke; Kachelriess, Marc [Institute of Medical Physics, Friedrich-Alexander-University (FAU) Erlangen-Nuernberg, 91052 Erlangen, Germany and Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Animal Laboratory Services Core Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Institute of Medical Physics, Friedrich-Alexander-University (FAU) Erlangen-Nuernberg, 91052 Erlangen (Germany); Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University (FAU) Erlangen-Nuernberg, 91052 Erlangen (Germany); Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Institute of Medical Physics, Friedrich-Alexander-University (FAU) Erlangen-Nuernberg, 91052 Erlangen, Germany and Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2012-12-15

    Purpose:Mouse models of cardiac diseases have proven to be a valuable tool in preclinical research. The high cardiac and respiratory rates of free breathing mice prohibit conventional in vivo cardiac perfusion studies using computed tomography even if gating methods are applied. This makes a sacrification of the animals unavoidable and only allows for the application of ex vivo methods. Methods: To overcome this issue the authors propose a low dose scan protocol and an associated reconstruction algorithm that allows for in vivo imaging of cardiac perfusion and associated processes that are retrospectively synchronized to the respiratory and cardiac motion of the animal. The scan protocol consists of repetitive injections of contrast media within several consecutive scans while the ECG, respiratory motion, and timestamp of contrast injection are recorded and synchronized to the acquired projections. The iterative reconstruction algorithm employs a six-dimensional edge-preserving filter to provide low-noise, motion artifact-free images of the animal examined using the authors' low dose scan protocol. Results: The reconstructions obtained show that the complete temporal bolus evolution can be visualized and quantified in any desired combination of cardiac and respiratory phase including reperfusion phases. The proposed reconstruction method thereby keeps the administered radiation dose at a minimum and thus reduces metabolic inference to the animal allowing for longitudinal studies. Conclusions: The authors' low dose scan protocol and phase-correlated dynamic reconstruction algorithm allow for an easy and effective way to visualize phase-correlated perfusion processes in routine laboratory studies using free-breathing mice.

  18. Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure

    KAUST Repository

    Mosqueira, Diogo

    2014-03-25

    Stem cell responsiveness to extracellular matrix (ECM) composition and mechanical cues has been the subject of a number of investigations so far, yet the molecular mechanisms underlying stem cell mechano-biology still need full clarification. Here we demonstrate that the paralog proteins YAP and TAZ exert a crucial role in adult cardiac progenitor cell mechano-sensing and fate decision. Cardiac progenitors respond to dynamic modifications in substrate rigidity and nanopattern by promptly changing YAP/TAZ intracellular localization. We identify a novel activity of YAP and TAZ in the regulation of tubulogenesis in 3D environments and highlight a role for YAP/TAZ in cardiac progenitor proliferation and differentiation. Furthermore, we show that YAP/TAZ expression is triggered in the heart cells located at the infarct border zone. Our results suggest a fundamental role for the YAP/TAZ axis in the response of resident progenitor cells to the modifications in microenvironment nanostructure and mechanics, thereby contributing to the maintenance of myocardial homeostasis in the adult heart. These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design. © 2014 American Chemical Society.

  19. Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure.

    Science.gov (United States)

    Mosqueira, Diogo; Pagliari, Stefania; Uto, Koichiro; Ebara, Mitsuhiro; Romanazzo, Sara; Escobedo-Lucea, Carmen; Nakanishi, Jun; Taniguchi, Akiyoshi; Franzese, Ornella; Di Nardo, Paolo; Goumans, Marie José; Traversa, Enrico; Pinto-do-Ó, Perpetua; Aoyagi, Takao; Forte, Giancarlo

    2014-03-25

    Stem cell responsiveness to extracellular matrix (ECM) composition and mechanical cues has been the subject of a number of investigations so far, yet the molecular mechanisms underlying stem cell mechano-biology still need full clarification. Here we demonstrate that the paralog proteins YAP and TAZ exert a crucial role in adult cardiac progenitor cell mechano-sensing and fate decision. Cardiac progenitors respond to dynamic modifications in substrate rigidity and nanopattern by promptly changing YAP/TAZ intracellular localization. We identify a novel activity of YAP and TAZ in the regulation of tubulogenesis in 3D environments and highlight a role for YAP/TAZ in cardiac progenitor proliferation and differentiation. Furthermore, we show that YAP/TAZ expression is triggered in the heart cells located at the infarct border zone. Our results suggest a fundamental role for the YAP/TAZ axis in the response of resident progenitor cells to the modifications in microenvironment nanostructure and mechanics, thereby contributing to the maintenance of myocardial homeostasis in the adult heart. These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design.

  20. Study on the Functional Dynamic Changes of Peri-Operative Cellular Immunity in Esophageal and Cardiac Cancer

    Institute of Scientific and Technical Information of China (English)

    Chen Sheng; Li Shiting; Fang Youping

    2014-01-01

    Objective: To explore the systemic and local cellular immune function of patients with esophageal carcinoma or cardiac cancer. Methods: The distribution of tumor-infiltrating lymphocyte (TIL) and cancer-associated macrophage (TAM) in local tumor tissues of 52 patients with esophageal cancer or cardiac cancer were observed by immunehistochemical method. The level of peripheral SIL-2R and TNF-α of preoperative and postoperative 1, 2, 3 weeks were detected by ELISA and ABC-ELISA methods respectively, then the acquired results were compared with 30 cases of normal control group. Results:The peritumor inifltration densities of TIL and TAM was greater than that of cancer nest stroma (P<0.05). Compared with the normal control group, the levels of sIL-2R and TNF-α increased signiifcantly (P<0.01). Immune function could be suppressed by operative wound in a short time of post-operation, whose damage severity was closely associated with tumor TNM stages. Conclusion: Patients with esophageal or cardiac cancer have cellular immune function disorders. Dynamic testing of peripheral sIL-2R and TNT-α level in patients with esophageal or cardiac cancer has positive clinical signiifcance in the evaluation of cellular immune function, tumor lesion degree and curative effect.

  1. Exercise training improves obesity‐related lymphatic dysfunction

    Science.gov (United States)

    Hespe, Geoffrey E.; Kataru, Raghu P.; Savetsky, Ira L.; García Nores, Gabriela D.; Torrisi, Jeremy S.; Nitti, Matthew D.; Gardenier, Jason C.; Zhou, Jie; Yu, Jessie Z.; Jones, Lee W.

    2016-01-01

    Key points Obesity results in perilymphatic inflammation and lymphatic dysfunction.Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells.Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Abstract Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti‐inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic

  2. Exercise training improves obesity-related lymphatic dysfunction.

    Science.gov (United States)

    Hespe, Geoffrey E; Kataru, Raghu P; Savetsky, Ira L; García Nores, Gabriela D; Torrisi, Jeremy S; Nitti, Matthew D; Gardenier, Jason C; Zhou, Jie; Yu, Jessie Z; Jones, Lee W; Mehrara, Babak J

    2016-08-01

    Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti-inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic

  3. Dynamics of the late Na(+) current during cardiac action potential and its contribution to afterdepolarizations.

    Science.gov (United States)

    Horvath, Balazs; Banyasz, Tamas; Jian, Zhong; Hegyi, Bence; Kistamas, Kornel; Nanasi, Peter P; Izu, Leighton T; Chen-Izu, Ye

    2013-11-01

    The objective of this work is to examine the contribution of late Na(+) current (INa,L) to the cardiac action potential (AP) and arrhythmogenic activities. In spite of the rapidly growing interest toward this current, there is no publication available on experimental recording of the dynamic INa,L current as it flows during AP with Ca(2+) cycling. Also unknown is how the current profile changes when the Ca(2+)-calmodulin dependent protein kinase II (CaMKII) signaling is altered, and how the current contributes to the development of arrhythmias. In this study we use an innovative AP-clamp Sequential Dissection technique to directly record the INa,L current during the AP with Ca(2+) cycling in the guinea pig ventricular myocytes. First, we found that the magnitude of INa,L measured under AP-clamp is substantially larger than earlier studies indicated. CaMKII inhibition using KN-93 significantly reduced the current. Second, we recorded INa,L together with IKs, IKr, and IK1 in the same cell to understand how these currents counterbalance to shape the AP morphology. We found that the amplitude and the total charge carried by INa,L exceed that of IKs. Third, facilitation of INa,L by Anemone toxin II prolonged APD and induced Ca(2+) oscillations that led to early and delayed afterdepolarizations and triggered APs; these arrhythmogenic activities were eliminated by buffering Ca(2+) with BAPTA. In conclusion, INa,L contributes a significantly large inward current that prolongs APD and unbalances the Ca(2+) homeostasis to cause arrhythmogenic APs.

  4. Dynamics of the Late Na+ current during cardiac action potential and its contribution to afterdepolarizations

    Science.gov (United States)

    Horvath, Balazs; Banyasz, Tamas; Jian, Zhong; Hegyi, Bence; Kistamas, Kornel; Nanasi, Peter P.; Izu, Leighton T.; Chen-Izu, Ye

    2013-01-01

    The objective of this work is to examine the contribution of late Na+ current (INa,L) to the cardiac action potential (AP) and arrhythmogenic activities. In spite of the rapidly growing interest toward this current, there is no publication available on experimental recording of the dynamic INa,L current as it flows during AP with Ca2+ cycling. Also unknown is how the current profile changes when the Ca2+-calmodulin dependent protein kinase II (CaMKII) signaling is altered, and how the current contributes to the development of arrhythmias. In this study we use an innovative AP-clamp Sequential Dissection technique to directly record the INa,L current during the AP with Ca2+ cycling in the guinea pig ventricular myocytes. First, we found that the magnitude of INa,L measured under AP-clamp is substantially larger than earlier studies indicated. CaMKII inhibition using KN-93 significantly reduced the current. Second, we recorded INa,L together with IKs, IKr, and IK1 in the same cell to understand how these currents counterbalance to shape the AP morphology. We found that the amplitude and the total charge carried by INa,L exceed that of IKs. Third, facilitation of INa,L by Anemone toxin II prolonged APD and induced Ca2+ oscillations that led to early and delayed afterdepolarizations and triggered APs; these arrhythmogenic activities were eliminated by buffering Ca2+ with BAPTA. In conclusion, INa,L contributes a significantly large inward current that prolongs APD and unbalances the Ca2+ homeostasis to cause arrhythmogenic APs. PMID:24012538

  5. Lymphatic Vascular Regeneration : The Next Step in Tissue Engineering

    NARCIS (Netherlands)

    Huethorst, Eline; Krebber, Merle M; Fledderus, Joost O; Gremmels, Hendrik; Xu, Yan Juan; Pei, Jiayi; Verhaar, Marianne C; Cheng, Caroline

    2016-01-01

    The lymphatic system plays a crucial role in interstitial fluid drainage, lipid absorption, and immunological defense. Lymphatic dysfunction results in lymphedema, fluid accumulation, and swelling of soft tissues, as well as a potentially impaired immune response. Lymphedema significantly reduces qu

  6. Quantification of the uncertainty in coronary CTA plaque measurements using dynamic cardiac phantom and 3D-printed plaque models

    Science.gov (United States)

    Richards, Taylor; Sturgeon, Gregory M.; Ramirez-Giraldo, Juan Carlos; Rubin, Geoffrey; Segars, Paul; Samei, Ehsan

    2017-03-01

    The purpose of this study was to quantify the accuracy of coronary computed tomography angiography (CTA) stenosis measurements using newly developed physical coronary plaque models attached to a base dynamic cardiac phantom (Shelley Medical DHP-01). Coronary plaque models (5 mm diameter, 50% stenosis, and 32 mm long) were designed and 3D-printed with tissue equivalent materials (calcified plaque with iodine enhanced lumen). Realistic cardiac motion was achieved by fitting known cardiac motion vectors to left ventricle volume-time curves to create synchronized heart motion profiles executed by the base cardiac phantom. Realistic coronary CTA acquisition was accomplished by synthesizing corresponding ECG waveforms for gating and reconstruction purposes. All scans were acquired using a retrospective gating technique on a dual-source CT system (Siemens SOMATOM FLASH) with 75ms temporal resolution. Multi-planar reformatted images were reconstructed along vessel centerlines and the enhanced lumens were manually segmented by 5 independent operators. On average, the stenosis measurement accuracy was 0.9% positive bias for the motion free condition (0 bpm). The measurement accuracy monotonically decreased to 18.5% negative bias at 90 bpm. Contrast-tonoise (CNR), vessel circularity, and segmentation conformity also decreased monotonically with increasing heart rate. These results demonstrate successful implementation of the base cardiac phantom with 3D-printed coronary plaque models, adjustable motion profiles, and coordinated ECG waveforms. They further show the utility of the model to ascertain metrics of coronary CT accuracy and image quality under a variety of plaque, motion, and acquisition conditions.

  7. Cardiac baroreflex function and dynamic cerebral autoregulation in elderly Masters athletes

    NARCIS (Netherlands)

    Aengevaeren, V.L.; Claassen, J.A.H.R.; Levine, B.D.; Zhang, R.

    2013-01-01

    Cerebral blood flow (CBF) is stably maintained through the combined effects of blood pressure (BP) regulation and cerebral autoregulation. Previous studies suggest that aerobic exercise training improves cardiac baroreflex function and beneficially affects BP regulation, but may negatively affect ce

  8. Force Responses and Sarcomere Dynamics of Cardiac Myofibrils Induced by Rapid Changes in [Pi].

    Science.gov (United States)

    Stehle, Robert

    2017-01-24

    The second phase of the biphasic force decay upon release of phosphate from caged phosphate was previously interpreted as a signature of kinetics of the force-generating step in the cross-bridge cycle. To test this hypothesis without using caged compounds, force responses and individual sarcomere dynamics upon rapid increases or decreases in concentration of inorganic phosphate [Pi] were investigated in calcium-activated cardiac myofibrils. Rapid increases in [Pi] induced a biphasic force decay with an initial slow decline (phase 1) and a subsequent 3-5-fold faster major decay (phase 2). Phase 2 started with the distinct elongation of a single sarcomere, the so-called sarcomere "give". "Give" then propagated from sarcomere to sarcomere along the myofibril. Propagation speed and rate constant of phase 2 (k+Pi(2)) had a similar [Pi]-dependence, indicating that the kinetics of the major force decay (phase 2) upon rapid increase in [Pi] is determined by sarcomere dynamics. In contrast, no "give" was observed during phase 1 after rapid [Pi]-increase (rate constant k+Pi(1)) and during the single-exponential force rise (rate constant k-Pi) after rapid [Pi]-decrease. The values of k+Pi(1) and k-Pi were similar to the rate constant of mechanically induced force redevelopment (kTR) and Ca(2+)-induced force development (kACT) measured at same [Pi]. These results indicate that the major phase 2 of force decay upon a Pi-jump does not reflect kinetics of the force-generating step but results from sarcomere "give". The other phases of Pi-induced force kinetics that occur in the absence of "give" yield the same information as mechanically and Ca(2+)-induced force kinetics (k+Pi(1) ∼ k-Pi ∼ kTR ∼ kACT). Model simulations indicate that Pi-induced force kinetics neither enable the separation of Pi-release from the rate-limiting transition f into force states nor differentiate whether the "force-generating step" occurs before, along, or after the Pi-release.

  9. Combined heart rate variability and dynamic measures for quantitatively characterizing the cardiac stress status during cycling exercise.

    Science.gov (United States)

    Chen, Szi-Wen; Liaw, Jiunn-Woei; Chang, Ya-Ju; Chuang, Li-Ling; Chien, Chun-Tse

    2015-08-01

    In this study, we aimed to seek for different ways of measuring cardiac stress in terms of heart rate variability (HRV) and heart rate (HR) dynamics, and to develop a novel index that can effectively summarize the information reflected by these measures to continuously and quantitatively characterize the cardiac stress status during physical exercise. Standard deviation, spectral measure of HRV as well as a nonlinear detrended fluctuation analysis (DFA) based fractal-like behavior measure of HR dynamics were all evaluated on the RR time series derived from windowed electrocardiogram (ECG) data for the subjects undergoing cycling exercise. We recruited eleven young healthy subjects in our tests. Each subject was asked to maintain a fixed speed under a constant load during the pedaling test. We obtained the running estimates of the standard deviation of the normal-to-normal interval (SDNN), the high-fidelity power spectral density (PSD) of HRV, and the DFA scaling exponent α, respectively. A trend analysis and a multivariate linear regression analysis of these measures were then performed. Numerical experimental results produced by our analyses showed that a decrease in both SDNN and α was seen during the cycling exercise, while there was no significant correlation between the standard lower frequency to higher frequency (LF-to-HF) spectral power ratio of HRV and the exercise intensity. In addition, while the SDNN and α were both negatively correlated with the Borg rating of perceived exertion (RPE) scale value, it seemed that the LF-to-HF power ratio might not have substantial impact on the Borg value, suggesting that the SDNN and α may be further used as features to detect the cardiac stress status during the physical exercise. We further approached this detection problem by applying a linear discriminant analysis (LDA) to both feature candidates for the task of cardiac stress stratification. As a result, a time-varying parameter, referred to as the cardiac

  10. Cerebral Lipiodol Embolism after Lymphatic Embolization for Plastic Bronchitis.

    Science.gov (United States)

    Kirschen, Matthew P; Dori, Yoav; Itkin, Maxim; Licht, Daniel J; Ichord, Rebecca; Vossough, Arastoo

    2016-09-01

    An adolescent with plastic bronchitis due to congenital heart disease had altered mental status after an interventional lymphatic procedure in which lipiodol contrast was used. Neuroimaging revealed cerebral lipiodol embolization due to direct shunting between lymphatic channels and pulmonary veins. Cerebral lipiodol embolization is a potential neurologic morbidity associated with interventional lymphatic procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Modelling Lymphatic Filariasis: Transmission and Control

    NARCIS (Netherlands)

    S. Swaminathan

    2004-01-01

    textabstractLymphatic filariasis (LF) is a mosquito borne parasitic disease of the tropics. Of the three species of parasites causing the disease, W. bancrofti transmitted by Culex quinquefasciatus is the most widely prevalent. Infection can lead to disabling chronic manifestations: lymphoedema, ele

  12. Lymphatic Filariasis: Transmission, Treatment and Elimination

    NARCIS (Netherlands)

    W.A. Stolk (Wilma)

    2005-01-01

    textabstractLymphatic filariasis (LF) is a mosquito-borne, tropical disease caused by filarial worms. Infection can lead to disabling chronic disease, characterized by swelling of extremities or external genitalia (lymphoedema, elephantiasis and hydrocele). Mass treatment with antifilarial drugs is

  13. Lymphatic and venous function in lipoedema.

    Science.gov (United States)

    Harwood, C A; Bull, R H; Evans, J; Mortimer, P S

    1996-01-01

    Lipoedema is a common but infrequently recognized condition causing bilateral enlargement of the legs in women. Although generally considered to be the result of an abnormal deposition of subcutaneous fat with associated oedema, the precise mechanisms responsible for oedema formation have yet to be fully established. In order to evaluate the possible role of lymphatic or venous dysfunction in the pathogenesis of lipoedema, 10 patients were investigated by photoplethysmography (venous function) and quantitative lymphoscintigraphy (lymphatic function). The results were compared with those from patients with primary lymphoedema and those from healthy volunteers. The results demonstrated minor abnormalities of venous function in only two patients. One patient had moderately impaired lymphatic function in both legs and seven patients had a marginal degree of impairment in one or both legs. However, in none of these cases did the impairment attain the low levels seen in true lymphoedema. Lipoedema appears to be a distinct clinical entity best classified as a lipodystrophy rather than a direct consequence of any primary venous or lymphatic insufficiency.

  14. Lymphatic filariasis control in Tanga Region, Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Derua, Yahya A.; Magesa, Stephen M.

    2014-01-01

    BackgroundLymphatic filariasis (LF) control started in Tanga Region of Tanzania in 2004, with annual ivermectin/albendazole mass drug administration (MDA). Since then, the current project has monitored the effect in communities and schools in rural areas of Tanga District. In 2013, after 8 rounds...

  15. Lymphatic malformations: a proposed management algorithm.

    LENUS (Irish Health Repository)

    Oosthuizen, J C

    2012-02-01

    OBJECTIVE: The aim of this study was to develop a management algorithm for cervicofacial lymphatic malformations, based on the authors\\' experience in managing these lesions as well as current literature on the subject. STUDY DESIGN AND METHODS: A retrospective medical record review of all the patients treated for lymphatic malformations at our institution during a 10-year period (1998-2008) was performed. DATA COLLECTED: age at diagnosis, location and type of lesion, radiologic investigation performed, presenting symptoms, treatment modality used, complications and results achieved. RESULTS: 14 patients were identified. Eight (57%) male and six (43%) female. There was an equal distribution between the left and right sides. The majority (71%) of cases were diagnosed within the first year of life. The majority of lesions were located in the suprahyoid region. The predominant reason for referral was an asymptomatic mass in 7 cases (50%) followed by airway compromise (36%) and dysphagia (14%). Management options employed included: observation, OK-432 injection, surgical excision and laser therapy. In 5 cases (36%) a combination of these were used. CONCLUSION: Historically surgical excision has been the management option of choice for lymphatic malformations. However due to the morbidity and high complication rate associated this is increasingly being questioned. Recent advances in sclerotherapy e.g. OK-432 injection have also shown significant promise. Based on experience in managing these lesions as well as current literature the authors of this paper have developed an algorithm for the management of cervicofacial lymphatic malformations.

  16. Lymphoscintigraphy patterns in newborns and children with congenital lymphatic dysplasia.

    Science.gov (United States)

    Bellini, C; Villa, G; Sambuceti, G; Traggiai, C; Campisi, C; Bellini, T; Morcaldi, G; Massocco, D; Bonioli, E; Boccardo, F

    2014-03-01

    We performed lymphoscintigraphy on 31 patients (newborns and children) affected by congenital lymphatic dysplasia according to our previously published protocol. Congenital lymphatic dysplasia may present with various degrees of clinical severity, ranging from nonimmune hydrops fetalis with visceral effusions to lymphedema alone. We recommend that lymphoscintigraphy should be strongly considered in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, in order to obtain a very early diagnosis and to start treatment. Lymphoscintigraphy is safe and useful in the diagnosis of lymphatic dysplasia in the newborn and children. Moreover, it is well tolerated by patients and well accepted by their parents.

  17. Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

    Science.gov (United States)

    Junqueira, Luiz Fernando, Jr.

    2008-01-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

  18. Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

    Science.gov (United States)

    Junqueira, Luiz Fernando, Jr.

    2008-01-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

  19. Scroll-wave dynamics in human cardiac tissue: lessons from a mathematical model with inhomogeneities and fiber architecture.

    Directory of Open Access Journals (Sweden)

    Rupamanjari Majumder

    Full Text Available Cardiac arrhythmias, such as ventricular tachycardia (VT and ventricular fibrillation (VF, are among the leading causes of death in the industrialized world. These are associated with the formation of spiral and scroll waves of electrical activation in cardiac tissue; single spiral and scroll waves are believed to be associated with VT whereas their turbulent analogs are associated with VF. Thus, the study of these waves is an important biophysical problem. We present a systematic study of the combined effects of muscle-fiber rotation and inhomogeneities on scroll-wave dynamics in the TNNP (ten Tusscher Noble Noble Panfilov model for human cardiac tissue. In particular, we use the three-dimensional TNNP model with fiber rotation and consider both conduction and ionic inhomogeneities. We find that, in addition to displaying a sensitive dependence on the positions, sizes, and types of inhomogeneities, scroll-wave dynamics also depends delicately upon the degree of fiber rotation. We find that the tendency of scroll waves to anchor to cylindrical conduction inhomogeneities increases with the radius of the inhomogeneity. Furthermore, the filament of the scroll wave can exhibit drift or meandering, transmural bending, twisting, and break-up. If the scroll-wave filament exhibits weak meandering, then there is a fine balance between the anchoring of this wave at the inhomogeneity and a disruption of wave-pinning by fiber rotation. If this filament displays strong meandering, then again the anchoring is suppressed by fiber rotation; also, the scroll wave can be eliminated from most of the layers only to be regenerated by a seed wave. Ionic inhomogeneities can also lead to an anchoring of the scroll wave; scroll waves can now enter the region inside an ionic inhomogeneity and can display a coexistence of spatiotemporal chaos and quasi-periodic behavior in different parts of the simulation domain. We discuss the experimental implications of our study.

  20. Symbolic dynamics of heart rate variability - a promising tool to investigate cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD)?

    Science.gov (United States)

    Tonhajzerova, Ingrid; Farsky, Ivan; Mestanik, Michal; Visnovcova, Zuzana; Mestanikova, Andrea; Hrtanek, Igor; Ondrejka, Igor

    2016-06-01

    We aimed to evaluate complex cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD) by using heart rate variability (HRV) nonlinear analysis - symbolic dynamics. We examined 29 boys with untreated ADHD and 25 healthy boys (age 8-13 years). ADHD symptoms were evaluated by ADHD-RS-IV scale. ECG was recorded in 3 positions: baseline supine position, orthostasis, and clinostasis. Symbolic dynamics indices were used for the assessment of complex cardiac sympathovagal regulation: normalised complexity index (NCI), normalised unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). The results showed that HRV complexity was significantly reduced at rest (NUPI) and during standing position (NCI, NUPI) in ADHD group compared to controls. Cardiac-linked sympathetic index 0V% was significantly higher during all posture positions and cardiovagal index 2LV% was significantly lower to standing in boys suffering from ADHD. Importantly, ADHD symptom inattention positively correlated with 0V%, and negatively correlated with NCI, NUPI. Concluding, symbolic dynamics revealed impaired complex neurocardiac control characterised by potential cardiac beta-adrenergic overactivity and vagal deficiency at rest and to posture changes in boys suffering from ADHD that is correlated with inattention. We suggest that symbolic dynamics indices could represent promising cardiac biomarkers in ADHD.

  1. Laminar flow downregulates Notch activity to promote lymphatic sprouting.

    Science.gov (United States)

    Choi, Dongwon; Park, Eunkyung; Jung, Eunson; Seong, Young Jin; Yoo, Jaehyuk; Lee, Esak; Hong, Mingu; Lee, Sunju; Ishida, Hiroaki; Burford, James; Peti-Peterdi, Janos; Adams, Ralf H; Srikanth, Sonal; Gwack, Yousang; Chen, Christopher S; Vogel, Hans J; Koh, Chester J; Wong, Alex K; Hong, Young-Kwon

    2017-04-03

    The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity. In response to flow, the plasma membrane calcium channel ORAI1 mediates calcium influx in LECs and activates calmodulin to facilitate a physical interaction between Krüppel-like factor 2 (KLF2), the major regulator of shear responses, and PROX1, the master regulator of lymphatic development. The PROX1/KLF2 complex upregulates the expression of DTX1 and DTX3L. DTX1 and DTX3L, functioning as a heterodimeric Notch E3 ligase, concertedly downregulate NOTCH1 activity and enhance lymphatic sprouting. Notably, overexpression of the calcium reporter GCaMP3 unexpectedly inhibited lymphatic sprouting, presumably by disturbing calcium signaling. Endothelial-specific knockouts of Orai1 and Klf2 also markedly impaired lymphatic sprouting. Moreover, Dtx3l loss of function led to defective lymphatic sprouting, while Dtx3l gain of function rescued impaired sprouting in Orai1 KO embryos. Together, the data reveal a molecular mechanism underlying laminar flow-induced lymphatic sprouting.

  2. Donation after cardiac death: dynamic graft reconditioning during or after ischemic preservation?

    Science.gov (United States)

    Koetting, Martina; Minor, Thomas

    2011-06-01

    The benefit of gaseous oxygenation during storage of liver grafts from donors after cardiac death should be investigated as applied either during the whole period of preservation or only for the last 2 h prior to reperfusion. Rat livers were explanted 30 min after cardiac arrest of the donor and cold-stored (CS) for 20 h. Some grafts were subjected to venous systemic oxygen persufflation (VSOP) either for 20 h or for only 2 h subsequent to 18 h of CS. Viability of the livers was assessed thereafter by warm reperfusion in vitro. Twenty hours VSOP and 18 h CS + 2 h VSOP prevented mitochondrial protein breakdown of mitochondrial heat shock protein 70 and promoted a significant and approximately twofold increase in hepatic oxygen consumption, bile production, and energetic recovery upon warm reperfusion. No differences were seen whether VSOP was performed for 20 h or for only 2 h prior to reperfusion. Both techniques significantly abrogated parenchymal enzyme loss (alanine aminotransferase, aspartate aminotransferase) upon reperfusion compared with simple 20 h CS. An increase in perfusate levels of the mitochondrial enzyme glutamate dehydrogenase was observed only in the 20 h VSOP group. In conclusion, viability of donation after cardiac death liver grafts can still be augmented, similarly to continuous aerobic storage, by only endischemic reconditioning, both protocols preventing initial mitochondrial dysfunction and subsequent tissue injury. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  3. [A study of cardiac dynamics during multistage exercise tests performed on a bycicle ergometer (author's transl)].

    Science.gov (United States)

    Gobbato, F; Fiorito, A; Cornelio, G

    1977-05-01

    The authors analysed the behaviour of the mechanical systole (electromechanical systole; tension time, left ventricular ejection time), as well as of the diastole (both cardiac and hemodynamic diastole) during exercise tests performed on a bycicle ergometer, with 40, 80, 120 watt workloads. The mechanical systole--as well as its components--duration is influenced, during exercise test, by both heart rate and stroke volume--pulse pressure being assumed as an indirect index of the latter. The study of the correlation between the two above mentioned parameters has a great importance in evaluating the cardiac pump efficiency both in health and disease. The study of the behaviour of diastole is likewise very important, as it provides useful information concerning: a) the length of the cardiac muscle post-exercise recovery phase; b) the coronary available perfusion time; c) the Windkessel (arterial bellows) emptying time. Moreover, the blood pressure fall rate in diastole is an useful indirect measure of the peripheral resistance changes during muscular work. A statistical analysis is made and the correlation coefficients and the regression equations between the various parameters are defined.

  4. Tailoring of chronic lymphatic leukemia therapy

    OpenAIRE

    Elhefni, Ashraf M

    2013-01-01

    Chronic lymphocytic leukemia (CLL) remains an incurable disease, with all patients who require therapy destined to relapse and understanding of the pathophysiology of chronic lymphocytic leukemia has advanced significantly. It is now clear that chronic lymphocytic leukemia is a relatively proliferative disorder that requires the help of its microenvironment to be maintained and to progress. The stimulation of the chronic lymphatic leukemia cell occurs in most, if not all, patients through ant...

  5. Lymphatic Filariasis Disseminating to the Upper Extremity

    Directory of Open Access Journals (Sweden)

    Catherine Maldjian

    2014-01-01

    Full Text Available Lymphatic filariasis is the most common cause of acquired lymphedema worldwide (Szuba and Rockson, 1998. It is endemic to tropical and subtropical regions, and its effects are devastating. With over 100 million infected persons, it ranks second only to leprosy as the leading cause of permanent and long-term disability. Wuchereria bancrofti is the etiologic agent in 90% of cases. There is a dearth of published MRI findings with pathologically proven active infections, making this entity even more of a diagnostic dilemma. Imaging may provide the first clue that one is dealing with a parasite and may facilitate proper treatment and containment of this disease. This is the first report of pathologic correlation with MRI findings in the extremity in active filariasis. The magnetic resonance images demonstrate an enhancing, infiltrative, mass-like appearance with partial encasement of vasculature that has not been previously described in filariasis. Low signal strands in T2-hyperintense dilated lymphatic channels are seen and may depict live adult worms. We hypothesize that the low signal strands correspond to the collagen rich acellular cuticle. This, in combination with the surrounding hyperintense T2 signal, corresponding to a dilated lymphatic channel, may provide more specific MRI findings for active nematodal infection, which can prompt early biopsy, pathological correlation, and diagnosis.

  6. Aberrant mural cell recruitment to lymphatic vessels and impaired lymphatic drainage in a murine model of pulmonary fibrosis.

    Science.gov (United States)

    Meinecke, Anna-Katharina; Nagy, Nadine; Lago, Gabriela D'Amico; Kirmse, Santina; Klose, Ralph; Schrödter, Katrin; Zimmermann, Annika; Helfrich, Iris; Rundqvist, Helene; Theegarten, Dirk; Anhenn, Olaf; Orian-Rousseau, Véronique; Johnson, Randall S; Alitalo, Kari; Fischer, Jens W; Fandrey, Joachim; Stockmann, Christian

    2012-06-14

    Pulmonary fibrosis is a progressive disease with unknown etiology that is characterized by extensive remodeling of the lung parenchyma, ultimately resulting in respiratory failure. Lymphatic vessels have been implicated with the development of pulmonary fibrosis, but the role of the lymphatic vasculature in the pathogenesis of pulmonary fibrosis remains enigmatic. Here we show in a murine model of pulmonary fibrosis that lymphatic vessels exhibit ectopic mural coverage and that this occurs early during the disease. The abnormal lymphatic vascular patterning in fibrotic lungs was driven by expression of platelet-derived growth factor B (PDGF-B) in lymphatic endothelial cells and signaling through platelet-derived growth factor receptor (PDGFR)-β in associated mural cells. Because of impaired lymphatic drainage, aberrant mural cell coverage fostered the accumulation of fibrogenic molecules and the attraction of fibroblasts to the perilymphatic space. Pharmacologic inhibition of the PDGF-B/PDGFR-β signaling axis disrupted the association of mural cells and lymphatic vessels, improved lymphatic drainage of the lung, and prevented the attraction of fibroblasts to the perilymphatic space. Our results implicate aberrant mural cell recruitment to lymphatic vessels in the pathogenesis of pulmonary fibrosis and that the drainage capacity of pulmonary lymphatics is a critical mediator of fibroproliferative changes.

  7. Site-directed spectroscopy of cardiac myosin-binding protein C reveals effects of phosphorylation on protein structural dynamics.

    Science.gov (United States)

    Colson, Brett A; Thompson, Andrew R; Espinoza-Fonseca, L Michel; Thomas, David D

    2016-03-22

    We have used the site-directed spectroscopies of time-resolved fluorescence resonance energy transfer (TR-FRET) and double electron-electron resonance (DEER), combined with complementary molecular dynamics (MD) simulations, to resolve the structure and dynamics of cardiac myosin-binding protein C (cMyBP-C), focusing on the N-terminal region. The results have implications for the role of this protein in myocardial contraction, with particular relevance to β-adrenergic signaling, heart failure, and hypertrophic cardiomyopathy. N-terminal cMyBP-C domains C0-C2 (C0C2) contain binding regions for potential interactions with both thick and thin filaments. Phosphorylation by PKA in the MyBP-C motif regulates these binding interactions. Our spectroscopic assays detect distances between pairs of site-directed probes on cMyBP-C. We engineered intramolecular pairs of labeling sites within cMyBP-C to measure, with high resolution, the distance and disorder in the protein's flexible regions using TR-FRET and DEER. Phosphorylation reduced the level of molecular disorder and the distribution of C0C2 intramolecular distances became more compact, with probes flanking either the motif between C1 and C2 or the Pro/Ala-rich linker (PAL) between C0 and C1. Further insight was obtained from microsecond MD simulations, which revealed a large structural change in the disordered motif region in which phosphorylation unmasks the surface of a series of residues on a stable α-helix within the motif with high potential as a protein-protein interaction site. These experimental and computational findings elucidate structural transitions in the flexible and dynamic portions of cMyBP-C, providing previously unidentified molecular insight into the modulatory role of this protein in cardiac muscle contractility.

  8. Effects of ovarian hormones and oral contraceptive pills on cardiac vagal withdrawal at the onset of dynamic exercise.

    Science.gov (United States)

    Teixeira, André L; Ramos, Plinio S; Vianna, Lauro C; Ricardo, Djalma R

    2015-01-01

    The purpose of this study was to investigate the effects of the ovarian hormones and the use of oral contraceptive pills (OCP) on cardiac vagal withdrawal at the onset of dynamic exercise. Thirty physically active women aged 19-32 years were divided into two groups: OCP users (n = 17) and non-OCP users (n = 13). Participants were studied randomly at three different phases of the menstrual cycle: early follicular (day 3.6 ± 1.2; range 1-5), ovulatory (day 14.3 ± 0.8; range 13-16) and midluteal (day 21.3 ± 0.8; range 20-24), according to endogenous (in non-OCP users) or exogenous (in OCP users) estradiol and progesterone variations. The cardiac vagal withdrawal was represented by the cardiac vagal index (CVI), which was obtained by the 4-s exercise test. Additionally, resting heart rate, systolic (SBP) and diastolic blood pressure (DBP) were obtained. The CVI was not significantly different between the three phases of the menstrual cycle in either the non-OCP users (early follicular: 1.58 ± 0.1; ovulatory: 1.56 ± 0.1; midluteal: 1.58 ± 0.1, P > 0.05) or OCP users (early follicular: 1.47 ± 0.1; ovulatory: 1.49 ± 0.1; midluteal: 1.47 ± 0.1, P > 0.05) (mean ± SEM). Resting cardiovascular responses were not affected by hormonal phase or OCP use, except that the SBP was higher in the OCP users than non-OCP users in all phases of the cycle (P exercise was not impacted by the menstrual cycle or OCP use in physically active women.

  9. Live imaging of newly formed lymphatic vessels in the cornea

    Institute of Scientific and Technical Information of China (English)

    Don Yuen; Xiufeng Wu; Alex C Kwan; Jeffrey LeDue; Hui Zhang; Tatiana Ecoiffier; Bronislaw Pytowski; Lu Chen

    2011-01-01

    Dear Editor,Lymphatic research denotes a field of new discovery and has experienced exponential growth in recent years [1-3].Though lymphatic dysfunction has been found in a broad spectrum of disorders from transplant rejection to cancer metastasis,to date,there is still little effective treatment for lymphatic diseases,so it is a field with urgent demand for new experimental approaches and therapeutic protocols.The cornea provides an ideal site for lymphatic research due to its accessible location,transparent nature,and alymphatic status under normal condition [2,4].Indeed,the use of this tissue for tumor angiogenesis research dates back to 1970s [5].Most recently,we have demonstrated that the cornea possesses a full range of plasticity in lymphatic formation and regression [6].An advanced technology for live imaging of lymphatic vessels in this tissue would therefore have widespread applications in biomedical research.

  10. Dynamic heart model for the mathematical cardiac torso (MCAT) phantom to represent the invariant total heart volume

    Science.gov (United States)

    Pretorius, P. H.; King, Michael A.; Tsui, Benjamin M.; LaCroix, Karen; Xia, Weishi

    1998-07-01

    This manuscript documents the alteration of the heart model of the MCAT phantom to better represent cardiac motion. The objective of the inclusion of motion was to develop a digital simulation of the heart such that the impact of cardiac motion on single photon emission computed tomography (SPECT) imaging could be assessed and methods of quantitating cardiac function could be investigated. The motion of the dynamic MCAT's heart is modeled by a 128 time frame volume curve. Eight time frames are averaged together to obtain a gated perfusion acquisition of 16 time frames and ensure motion within every time frame. The position of the MCAT heart was changed during contraction to rotate back and forth around the long axis through the center of the left ventricle (LV) using the end systolic time frame as turning point. Simple respiratory motion was also introduced by changing the orientation of the heart model in a 2 dimensional (2D) plane with every time frame. The averaging effect of respiratory motion in a specific time frame was modeled by randomly selecting multiple heart locations between two extreme orientations. Non-gated perfusion phantoms were also generated by averaging over all time frames. Maximal chamber volumes were selected to fit a profile of a normal healthy person. These volumes were changed during contraction of the ventricles such that the increase in volume in the atria compensated for the decrease in volume in the ventricles. The myocardium were modeled to represent shortening of muscle fibers during contraction with the base of the ventricles moving towards a static apex. The apical region was modeled with moderate wall thinning present while myocardial mass was conserved. To test the applicability of the dynamic heart model, myocardial wall thickening was measured using maximum counts and full width half maximum measurements, and compared with published trends. An analytical 3D projector, with attenuation and detector response included, was used

  11. Mechanisms of Beat-to-Beat Regulation of Cardiac Pacemaker Cell Function by Ca2+ Cycling Dynamics

    Science.gov (United States)

    Yaniv, Yael; Stern, Michael D.; Lakatta, Edward G.; Maltsev, Victor A.

    2013-01-01

    Whether intracellular Ca2+ cycling dynamics regulate cardiac pacemaker cell function on a beat-to-beat basis remains unknown. Here we show that under physiological conditions, application of low concentrations of caffeine (2–4 mM) to isolated single rabbit sinoatrial node cells acutely reduces their spontaneous action potential cycle length (CL) and increases Ca2+ transient amplitude for several cycles. Numerical simulations, using a modified Maltsev-Lakatta coupled-clock model, faithfully reproduced these effects, and also the effects of CL prolongation and dysrhythmic spontaneous beating (produced by cytosolic Ca2+ buffering) and an acute CL reduction (produced by flash-induced Ca2+ release from a caged Ca2+ buffer), which we had reported previously. Three contemporary numerical models (including the original Maltsev-Lakatta model) failed to reproduce the experimental results. In our proposed new model, Ca2+ releases acutely change the CL via activation of the Na+/Ca2+ exchanger current. Time-dependent CL reductions after flash-induced Ca2+ releases (the memory effect) are linked to changes in Ca2+ available for pumping into sarcoplasmic reticulum which, in turn, changes the sarcoplasmic reticulum Ca2+ load, diastolic Ca2+ releases, and Na+/Ca2+ exchanger current. These results support the idea that Ca2+ regulates CL in cardiac pacemaker cells on a beat-to-beat basis, and suggest a more realistic numerical mechanism of this regulation. PMID:24094396

  12. Mechanisms of beat-to-beat regulation of cardiac pacemaker cell function by Ca²⁺ cycling dynamics.

    Science.gov (United States)

    Yaniv, Yael; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

    2013-10-01

    Whether intracellular Ca(2+) cycling dynamics regulate cardiac pacemaker cell function on a beat-to-beat basis remains unknown. Here we show that under physiological conditions, application of low concentrations of caffeine (2-4 mM) to isolated single rabbit sinoatrial node cells acutely reduces their spontaneous action potential cycle length (CL) and increases Ca(2+) transient amplitude for several cycles. Numerical simulations, using a modified Maltsev-Lakatta coupled-clock model, faithfully reproduced these effects, and also the effects of CL prolongation and dysrhythmic spontaneous beating (produced by cytosolic Ca(2+) buffering) and an acute CL reduction (produced by flash-induced Ca(2+) release from a caged Ca(2+) buffer), which we had reported previously. Three contemporary numerical models (including the original Maltsev-Lakatta model) failed to reproduce the experimental results. In our proposed new model, Ca(2+) releases acutely change the CL via activation of the Na(+)/Ca(2+) exchanger current. Time-dependent CL reductions after flash-induced Ca(2+) releases (the memory effect) are linked to changes in Ca(2+) available for pumping into sarcoplasmic reticulum which, in turn, changes the sarcoplasmic reticulum Ca(2+) load, diastolic Ca(2+) releases, and Na(+)/Ca(2+) exchanger current. These results support the idea that Ca(2+) regulates CL in cardiac pacemaker cells on a beat-to-beat basis, and suggest a more realistic numerical mechanism of this regulation.

  13. An Improved Method for Discriminating ECG Signals using Typical Nonlinear Dynamic Parameters and Recurrence Quantification Analysis in Cardiac Disease Therapy.

    Science.gov (United States)

    Tang, M; Chang, C Q; Fung, P C W; Chau, K T; Chan, F H Y

    2005-01-01

    The discrimination of ECG signals using nonlinear dynamic parameters is of crucial importance in the cardiac disease therapy and chaos control for arrhythmia defibrillation in the cardiac system. However, the discrimination results of previous studies using features such as maximal Lyapunov exponent (λmax) and correlation dimension (D2) alone are somewhat limited in recognition rate. In this paper, improved methods for computing λmaxand D2are purposed. Another parameter from recurrence quantification analysis is incorporated to the new multi-feature Bayesian classifier with λmaxand D2so as to improve the discrimination power. Experimental results have verified the prediction using Fisher discriminant that the maximal vertical line length (Vmax) from recurrence quantification analysis is the best to distinguish different ECG classes. Experimental results using the MIT-BIH Arrhythmia Database show improved and excellent overall accuracy (96.3%), average sensitivity (96.3%) and average specificity (98.15%) for discriminating sinus, premature ventricular contraction and ventricular flutter signals.

  14. Recent advances in the research of lymphatic stomata.

    Science.gov (United States)

    Wang, Zi-Bin; Li, Meng; Li, Ji-Cheng

    2010-05-01

    Lymphatic stomata are small openings of lymphatic capillaries on the free surface of the mesothelium. The peritoneal cavity, pleural cavity, and pericardial cavity are connected with lymphatic system via these small openings, which have the function of active absorption. The ultrastructure of the lymphatic stomata and their absorption from the body cavities are important clinically, such as ascites elimination, neoplasm metastasis, and inflammatory reaction. The lymphatic stomata play an important role in the physiological and pathological conditions. Our previous study indicated for the first time that nitric oxide (NO) could regulate the opening and absorption of the lymphatic stomata. It could decrease the level of free intracellular calcium [Ca(2+)] through increasing the cyclic guanosine monophosphate (cGMP) level in the rat peritoneal mesothelial cells, thus regulating the lymphatic stomata. This process is related with the NO-cGMP-[Ca(2+)] signal pathway. In this review, we summarize the recent advances in understanding the development and the function of the lymphatic stomata. The ultrastructure and regulations of the lymphatic stomata are also discussed in this review.

  15. Teaching Cardiac Electrophysiology Modeling to Undergraduate Students: Laboratory Exercises and GPU Programming for the Study of Arrhythmias and Spiral Wave Dynamics

    Science.gov (United States)

    Bartocci, Ezio; Singh, Rupinder; von Stein, Frederick B.; Amedome, Avessie; Caceres, Alan Joseph J.; Castillo, Juan; Closser, Evan; Deards, Gabriel; Goltsev, Andriy; Ines, Roumwelle Sta.; Isbilir, Cem; Marc, Joan K.; Moore, Diquan; Pardi, Dana; Sadhu, Sandeep; Sanchez, Samuel; Sharma, Pooja; Singh, Anoopa; Rogers, Joshua; Wolinetz, Aron; Grosso-Applewhite, Terri; Zhao, Kai; Filipski, Andrew B.; Gilmour, Robert F., Jr.; Grosu, Radu; Glimm, James; Smolka, Scott A.; Cherry, Elizabeth M.; Clarke, Edmund M.; Griffeth, Nancy; Fenton, Flavio H.

    2011-01-01

    As part of a 3-wk intersession workshop funded by a National Science Foundation Expeditions in Computing award, 15 undergraduate students from the City University of New York collaborated on a study aimed at characterizing the voltage dynamics and arrhythmogenic behavior of cardiac cells for a broad range of physiologically relevant conditions…

  16. The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems.

    Science.gov (United States)

    Wu, Min; Frieboes, Hermann B; McDougall, Steven R; Chaplain, Mark A J; Cristini, Vittorio; Lowengrub, John

    2013-03-07

    The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform

  17. Monoamine Oxidases, Oxidative Stress, and Altered Mitochondrial Dynamics in Cardiac Ageing

    Directory of Open Access Journals (Sweden)

    Damien Maggiorani

    2017-01-01

    Full Text Available The advances in healthcare over the past several decades have resulted in populations now living longer. With this increase in longevity, a wider prevalence of cardiovascular diseases is more common and known to be a major factor in rising healthcare costs. A wealth of scientific evidence has implicated cell senescence as an important component in the etiology of these age-dependent pathologies. A number of studies indicate that an excess of reactive oxygen species (ROS contributes to trigger and accelerate the cardiac senescence processes, and a new role of monoamine oxidases, MAO-A and MAO-B, is emerging in this context. These mitochondrial enzymes regulate the level of catecholamines and serotonin by catalyzing their oxidative deamination in the heart. MAOs’ expression substantially increases with ageing (6-fold MAO-A in the heart and 4-fold MAO-B in neuronal tissue, and their involvement in cardiac diseases is supposedly related to the formation of ROS, via the hydrogen peroxide produced during the substrate degradation. Here, we will review the most recent advances in this field and describe why MAOs could be effective targets in order to prevent age-associated cardiovascular disease.

  18. Non-linear dynamic analysis of the cardiac rhythm during transient myocardial ischemia.

    Science.gov (United States)

    Gomis, Pedro; Caminal, Pere; Vallverdú, Montserrat; Warren, Stafford; Wagner, Galen

    2006-10-01

    Coronary artery occlusions related to myocardial ischemia drive cardiac control system reactions that may lead to heart failure. The purpose of this study was to assess the autonomic nervous system (ANS) response during prolonged percutaneous transluminal coronary angioplasty (PTCA). Continuous ECG data were acquired from 50 patients before and during PTCA, with occlusions in the left anterior descending, left circumflex or right coronary artery. Heart rate variability (HRV) was analyzed for 3-min segments of the R-R interval signal obtained from ECG data. The ANS behavior was evaluated by HRV analysis using fractal-like indices. The fractal scalar exponent alpha(1) and power-law slope beta decreased considerably during PTCA. This indicates that significant reactions of autonomic control of the heart rate occurred during coronary artery occlusions, with a reduction in complexity of the ANS.

  19. Lymphatic vascular morphogenesis in development, physiology, and disease

    NARCIS (Netherlands)

    Schulte-Merker, Stefan; Sabine, Amelie; Petrova, Tatiana V.

    2011-01-01

    The lymphatic vasculature constitutes a highly specialized part of the vascular system that is essential for the maintenance of interstitial fluid balance, uptake of dietary fat, and immune response. Recently, there has been an increased awareness of the importance of lymphatic vessels in many commo

  20. Lymphatic Function Regulates Contact Hypersensitivity Dermatitis in Obesity.

    Science.gov (United States)

    Savetsky, Ira L; Albano, Nicholas J; Cuzzone, Daniel A; Gardenier, Jason C; Torrisi, Jeremy S; García Nores, Gabriela D; Nitti, Matthew D; Hespe, Geoffrey E; Nelson, Tyler S; Kataru, Raghu P; Dixon, J Brandon; Mehrara, Babak J

    2015-11-01

    Obesity is a major risk factor for inflammatory dermatologic diseases, including atopic dermatitis and psoriasis. In addition, recent studies have shown that obesity impairs lymphatic function. As the lymphatic system is a critical regulator of inflammatory reactions, we tested the hypothesis that obesity-induced lymphatic dysfunction is a key regulator of cutaneous hypersensitivity reactions in obese mice. We found that obese mice have impaired lymphatic function, characterized by leaky capillary lymphatics and decreased collecting vessel pumping capacity. In addition, obese mice displayed heightened dermatitis responses to inflammatory skin stimuli, resulting in both higher peak inflammation and a delayed clearance of inflammatory responses. Injection of recombinant vascular endothelial growth factor-C remarkably increased lymphangiogenesis, lymphatic function, and lymphatic endothelial cell expression of chemokine (C-C motif) ligand 21, while decreasing inflammation and expression of inducible nitrous oxide synthase. These changes resulted in considerably decreased dermatitis responses in both lean and obese mice. Taken together, our findings suggest that obesity-induced changes in the lymphatic system result in an amplified and a prolonged inflammatory response.

  1. Divergence of zebrafish and mouse lymphatic cell fate specification pathways

    DEFF Research Database (Denmark)

    van Impel, Andreas; Zhao, Zhonghua; Hermkens, Dorien M A;

    2014-01-01

    . Murine Prox1-null embryos lack lymphatic structures, and sustained expression of Prox1 is indispensable for the maintenance of lymphatic cell fate even at adult stages, highlighting the unique importance of this gene for the lymphatic lineage. Whether this pre-eminent role of Prox1 within the lymphatic...... vasculature is conserved in other vertebrate classes has remained unresolved, mainly owing to the lack of availability of loss-of-function mutants. Here, we re-examine the role of Prox1a in zebrafish lymphangiogenesis. First, using a transgenic reporter line, we show that prox1a is initially expressed...... that the functionally related transcription factors Coup-TFII and Sox18 are also dispensable for lymphangiogenesis. Together, these findings suggest that lymphatic commitment in zebrafish and mice is controlled in fundamentally different ways....

  2. The Glymphatic-Lymphatic Continuum: Opportunities for Osteopathic Manipulative Medicine.

    Science.gov (United States)

    Hitscherich, Kyle; Smith, Kyle; Cuoco, Joshua A; Ruvolo, Kathryn E; Mancini, Jayme D; Leheste, Joerg R; Torres, German

    2016-03-01

    The brain has long been thought to lack a lymphatic drainage system. Recent studies, however, show the presence of a brain-wide paravascular system appropriately named the glymphatic system based on its similarity to the lymphatic system in function and its dependence on astroglial water flux. Besides the clearance of cerebrospinal fluid and interstitial fluid, the glymphatic system also facilitates the clearance of interstitial solutes such as amyloid-β and tau from the brain. As cerebrospinal fluid and interstitial fluid are cleared through the glymphatic system, eventually draining into the lymphatic vessels of the neck, this continuous fluid circuit offers a paradigm shift in osteopathic manipulative medicine. For instance, manipulation of the glymphatic-lymphatic continuum could be used to promote experimental initiatives for nonpharmacologic, noninvasive management of neurologic disorders. In the present review, the authors describe what is known about the glymphatic system and identify several osteopathic experimental strategies rooted in a mechanistic understanding of the glymphatic-lymphatic continuum.

  3. Assessment of cardiac autonomic functions by heart rate recovery, heart rate variability and QT dynamicity parameters in patients with acromegaly.

    Science.gov (United States)

    Dural, Muhammet; Kabakcı, Giray; Cınar, Neşe; Erbaş, Tomris; Canpolat, Uğur; Gürses, Kadri Murat; Tokgözoğlu, Lale; Oto, Ali; Kaya, Ergün Barış; Yorgun, Hikmet; Sahiner, Levent; Dağdelen, Selçuk; Aytemir, Kudret

    2014-04-01

    Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with

  4. Localization and proliferation of lymphatic vessels in the tympanic membrane in normal state and regeneration.

    Science.gov (United States)

    Miyashita, Takenori; Burford, James L; Hong, Young-Kwon; Gevorgyan, Haykanush; Lam, Lisa; Mori, Nozomu; Peti-Peterdi, Janos

    2013-10-25

    We clarified the localization of lymphatic vessels in the tympanic membrane and proliferation of lymphatic vessels during regeneration after perforation of the tympanic membrane by using whole-mount imaging of the tympanic membrane of Prox1 GFP mice. In the pars tensa, lymphatic vessel loops surrounded the malleus handle and annulus tympanicus. Apart from these locations, lymphatic vessel loops were not observed in the pars tensa in the normal tympanic membrane. Lymphatic vessel loops surrounding the malleus handle were connected to the lymphatic vessel loops in the pars flaccida and around the tensor tympani muscle. Many lymphatic vessel loops were detected in the pars flaccida. After perforation of the tympanic membrane, abundant lymphatic regeneration was observed in the pars tensa, and these regenerated lymphatic vessels extended from the lymphatic vessels surrounding the malleus at day 7. These results suggest that site-specific lymphatic vessels play an important role in the tympanic membrane.

  5. Inflammatory manifestations of experimental lymphatic insufficiency.

    Directory of Open Access Journals (Sweden)

    Raymond Tabibiazar

    2006-07-01

    Full Text Available BACKGROUND: Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic. METHODS AND FINDINGS: We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response. CONCLUSIONS: We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.

  6. Scholars and scientists in the history of the lymphatic system.

    Science.gov (United States)

    Natale, Gianfranco; Bocci, Guido; Ribatti, Domenico

    2017-09-01

    The discovery of the lymphatic system has a long and fascinating history. The interest in anatomy and physiology of this system paralleled that of the blood cardiocirculatory system and has been maybe obscured by the latter. Paradoxically, if the closed blood system appeared open in Galen's anatomy and physiology, and took a very long time to be correctly described in terms of pulmonary and general circulation by ibn Al-Nafis/Michael Servetus/Realdo Colombo and William Harvey, respectively, the open lymphatic system was incorrectly described as a closed circuit connected with arteries and veins. In ancient times only macroscopic components of the lymphatic system have been described, although misinterpreted, including lymph nodes and lacteals, the latter being easily identified because of their milk-like content. For about 15 centuries the dogmatic acceptance of Galen's notions did not allow a significant progress in medicine. After Vesalius' revolution in anatomical studies, new knowledge was accumulated, and the 17th century was the golden age for the investigation of the lymphatic system with several discoveries: gut lacteals (Gaspare Aselli), cloacal bursa (Hieronimus Fabricius of Acquapendente), reservoir of the chyle (Jean Pecquet), extra-intestinal lymphatic vessels (Thomas Bartholin and Olaus Rudbeck dispute), hepatic lymph circulation (Francis Glisson). In the Enlightenment century Frederik Ruysch described the function of lymphatic valves, and Paolo Mascagni provided a magnificent iconography of the lymphatic network in humans. In recent times, Leonetto Comparini realized three-dimensional reconstructions of the liver lymphatic vessels, and Kari Alitalo discovered the lymphatic growth factor/receptor system. Far from a complete understanding of its anatomy and function, the lymphatic system still needs to be profoundly examined. © 2017 Anatomical Society.

  7. Role of Hyperplasia of Gingival Lymphatics in Periodontal Inflammation.

    Science.gov (United States)

    Papadakou, P; Bletsa, A; Yassin, M A; Karlsen, T V; Wiig, H; Berggreen, E

    2017-04-01

    Lymphatic vessels are important for maintenance of tissue fluid homeostasis and afferent antigen transport. In chronic inflammation, lymphangiogenesis takes place and is characterized by lymphatic endothelial cell proliferation and lymphatic hyperplasia. Vascular endothelial growth factor C (VEGFC) is the main known lymphangiogenic growth factor, and its expression is increased in periodontitis, a common chronic infectious disease that results in tissue destruction and alveolar bone loss. The role of lymphangiogenesis during development of periodontitis is unknown. Here, we test if transgenic overexpression of epithelial VEGFC in a murine model is followed by hyperplasia of lymphatic vessels in oral mucosa and if the lymphatic drainage capacity is altered. We also test if lymphatic hyperplasia protects against periodontal disease development. Transgenic keratin 14 (K14)-VEGFC mice had significant hyperplasia of lymphatics in oral mucosa, including gingiva, without changes in blood vessel vasculature. The basal lymph flow was normal but slightly lower than in wild-type mice when oral mucosa was challenged with lipopolysaccharide from Porphyromonas gingivalis. Under normal conditions, K14-VEGFC mice exhibited an increased number of neutrophils in gingiva, demonstrated enhanced phagocyte recruitment in the cervical lymph nodes, and had more alveolar bone when compared with their wild-type littermates. After induction of periodontitis, no strain differences were observed in the periodontal tissues with respect to granulocyte recruitment, bone resorption, angiogenesis, cytokines, and bone-related protein expressions or in draining lymph node immune cell proportions and vascularization. We conclude that overexpression of VEGFC results in hyperplastic lymphatics, which do not enhance lymphatic drainage capacity but facilitate phagocyte transport to draining lymph nodes. Hyperplasia of lymphatics does not protect against development of ligature-induced periodontitis.

  8. Dynamic Action of Carotenoids in Cardioprotection and Maintenance of Cardiac Health

    Directory of Open Access Journals (Sweden)

    Dipak K. Das

    2012-04-01

    Full Text Available Oxidative stress has been considered universally and undeniably implicated in the pathogenesis of all major diseases, including those of the cardiovascular system. Oxidative stress activate transcriptional messengers, such as nuclear factor—κB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Evidence is rapidly accumulating to support the role of reactive oxygen species (ROS and reactive nitrogen species (RNS as intracellular signaling molecules. Despite this connection between oxidative stress and cardiovascular disease (CVD, there are currently no recognized therapeutic interventions to address this important unmet need. Antioxidants that provide a broad, “upstream” approach via ROS/RNS quenching or free radical chain breaking seem an appropriate therapeutic option based on epidemiologic, dietary, and in vivo animal model data. Short-term dietary intervention trials suggest that diets rich in fruit and vegetable intake lead to improvements in coronary risk factors and reduce cardiovascular mortality. Carotenoids are such abundant, plant-derived, fat-soluble pigments that functions as antioxidants. They are stored in the liver or adipose tissue, and are lipid soluble by becoming incorporated into plasma lipoprotein particles during transport. For these reasons, carotenoids may represent one plausible mechanism by which fruits and vegetables reduce the risk of chronic diseases as cardiovascular disease (CVD. This review paper outlines the role of carotenoids in maintaining cardiac health and cardioprotection mediated by several mechanisms including redox signaling.

  9. Evolution in functional complexity of heart rate dynamics: a measure of cardiac allograft adaptability.

    Science.gov (United States)

    Kresh, J Y; Izrailtyan, I

    1998-09-01

    The capacity of self-organized systems to adapt is embodied in the functional organization of intrinsic control mechanisms. Evolution in functional complexity of heart rate variability (HRV) was used as measure of the capacity of the transplanted heart to express newly emergent regulatory order. In a cross-sectional study of 100 patients after (0-10 yr) heart transplantation (HTX), heart rate dynamics were assessed using pointwise correlation dimension (PD2) analysis. A new observation is that, commencing with the acute event of allograft transplantation, the dynamics of rhythm formation proceed through complex phase transitions. At implantation, the donor heart manifested metronome-like chronotropic behavior (PD2 approximately 1.0). At 11-100 days, dimensional complexity of HRV reached a peak (PD2 approximately 2.0) associated with resurgence in the high-frequency component (0.15-0.5 Hz) of the power spectral density. Subsequent dimensional loss to PD2 approximately 1.0 at 20-30 mo after HTX was followed by a progressive near-linear gain in system complexity, reaching PD2 approximately 3.0 7-10 yr after HTX. The "dynamic reorganization" in the allograft rhythm-generating system, seen in the first 100 days, is a manifestation of the adaptive capacity of intrinsic control mechanisms. The loss of HRV 2 yr after HTX implies a withdrawal of intrinsic autonomic control and/or development of an entrained dynamic pattern characteristic of extrinsic sympathetic input. The subsequent long-term progressive rise in dimensional complexity of HRV can be attributed to the restoration of a functional order patterning parasympathetic control. The recognition that the decentralized heart can restitute the multidimensional state space of HR generator dynamics independent of external autonomic signaling may provide a new perspective on principles that constitute homeodynamic regulation.

  10. Morphogenesis, structure and properties of lymphatic vessels 

    Directory of Open Access Journals (Sweden)

    Anna Ratajska

    2012-11-01

    Full Text Available In this paper, we present literature results related to structure and various manners of lymphatic vessel formation during embryonic development and in pathological events, such as tumorigenesis, wound healing, and other diseases. The functions of the lymphatic system include the collection of fluids that enter tissues from the circulation, absorption of lipids and lipid-soluble vitamins from the intestine and their subsequent transport, participation in antigen, dendritic cell, and lymphocyte migration. The lymphatic system is also a route for tumor cell and inflammatory cell transport. Native lymphatic capillaries differ from blood capillaries by having an irregular lumen, a discontinuous basement membrane, absence of pericytes, and a strong anchorage of their endothelial cells to the extracellular matrix via microfibrils built of emilin and fibrillin. Lymphatic endothelial cells express surface antigens such as Lyve-1, podoplanin, VEGFR3 (Flk4 and transcription factor Prox-1, as well as molecules which are common for blood endothelial cells and lymphatic endothelial cells (CD31, CD34, Flk-1, Tie-1, Tie-2, neuropilin 2. Lymphatic vessel formation during embryonic development starts with the occurrence of lymphatic sacs sprouting from systemic jugular veins and/or by co-option of lymphangioblasts or hematopoietic-derived cells. It can also proceed by dedifferentiation of venous endothelial cells after their detachment from the venous system, migration to the target places within the body and assembly in the lymphatic lumen. Mechanisms of lymphatic vessel formation during embryonic development and in pathological conditions, such as tumorigenesis, wound healing, and metastasis, is regulated by a plethora of growth factors and molecules, among which the most important are VEGF-C, VEGF-D, HGF, FGF, retinoic acid, IL-3, and IL-7. Macrophages and cells bearing CD45 phenotype seem to take part in the formation of lymphatics. Macrophages might act as

  11. Rho kinase enhances contractions of rat mesenteric collecting lymphatics.

    Directory of Open Access Journals (Sweden)

    Kristine H Kurtz

    Full Text Available The mechanisms that control phasic and tonic contractions of lymphatic vessels are poorly understood. We hypothesized that rho kinase ROCK, previously shown to increase calcium (Ca2+ sensitivity in vascular smooth muscle, enhances lymphatic contractile activity in a similar fashion. Contractions of isolated rat mesenteric lymphatic vessels were observed at a luminal pressure of 2 cm H2O in a 37°C bath. The expression of ROCK in isolated rat mesenteric lymphatic vessels was assessed by Western blotting and confocal microscopy. The role of ROCK in contractile function was tested using two specific yet structurally distinct inhibitors: H1152 (0.1-10 μM and Y-27632 (0.5-50 μM. In addition, lymphatics were transfected with constitutively active (ca-ROCK protein (2 μg/ml to assess gain of contractile function. Vessel diameter and the concentration of intracellular free Ca2+ ([Ca2+]i were simultaneously measured in a subset of isolated lymphatics loaded with the Ca2+-sensing dye fura-2. The results show expression of both the ROCK1 and ROCK2 isoforms in lymphatic vessels. Inhibition of ROCK increased lymphatic end diastolic diameter and end systolic diameter in a concentration-dependent manner. Significant reductions in lymphatic tone and contraction amplitude were observed after treatment 1-10 μM H1152 or 25-50 μM Y-27632. H1152 (10 μM also significantly reduced contraction frequency. Transient increases in [Ca2+]i preceded each phasic contraction, however this pattern was disrupted by either 10 μM H1152 or 50 μM Y-27632 in the majority of lymphatics studied. The significant decrease in tone caused by H1152 or Y-27632 was not associated with a significant change in the basal [Ca2+]i between transients. Transfection with ca-ROCK protein enhanced lymphatic tone, but was not associated with a significant change in basal [Ca2+]i. Our data suggest that ROCK mediates normal tonic constriction and influences phasic contractions in lymphatics. We

  12. Periportal low-attenuation: a CT sign of lymphatic obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hoon; Kim, Chong Soo; Yang, Doo Hyun; Lee, Sang Yong; Lee, Young Whan; Chung, Gyung Ho; Han, Young Min; Sohn, Myung Hee; Choi, Ki Chul [Chonbuk National University College of Medicine, Jeonju (Korea, Republic of)

    1995-07-15

    Periportal low attenuation, defined as a low attenuation rim around the portal vein and its branches which is seen on contrast material-enhanced CT scans, has been described in a variety of conditions. We tried to document that lymphatic obstruction is one of the major cause of periportal low attenuation. We retrospectively analyzed 57 cases of periportal low attenuation of abdominal CT scans and also reviewed the surgical records in 32 cases. Lymph node enlargement in the hepatoduodenal ligament which is a main lymphatic channel from the liver were analyzed the calculated the ratio of the transeverse diameter between the inferior vena cava and the aorta at the level of right adrenal gland. After complete surgical interruption of the lymphatic drainage from the liver in a dog, follow up CT scans were obtained and correlated with pathologic findings. Fifty patients (88%) had underlying disease which could cause impairment of lymphatic drainage. Periportal low attenuation was identified in several clinical conditions, including surgical lymph node dissection, lymphadenopathy in the hepatoduodenal ligament, blunt trauma. In animal model, CT scan showed prominent periportal low attenuation at 5 days after surgery. Histologic examination revealed numerous dilated lymphatic vessels and a marked lymphedema in the connective tissues surrounding the portal vein and its major branches. One of the major cause of periportal low attenuation was impaired lymphatic drainage and periportal low attenuation corresponding to the numerous dilated lymphatic vessels and a marked lymphedema in the connective tissues surrounding the portal vein and its major branches.

  13. Itching for answers: how histamine relaxes lymphatic vessels.

    Science.gov (United States)

    Scallan, Joshua P; Davis, Michael J

    2014-10-01

    In the current issue of Microcirculation, studies by Kurtz et al. and Nizamutdinova et al. together provide new evidence supporting a role for histamine as an endothelial-derived molecule that inhibits lymphatic muscle contraction. In particular, Nizamutdinova et al. show that the effects of flow-induced shear stress on lymphatic endothelium are mediated by both nitric oxide and histamine, since only blockade of both prevents contraction strength and frequency from being altered by flow. Separately, Kurtz et al. used confocal microscopy to determine a preferential expression of histamine receptors on the lymphatic endothelium and demonstrated that histamine applied to spontaneously contracting collecting lymphatics inhibits contractions. Previous studies disagreed on whether histamine stimulates or inhibits lymphatic contractions, but also used differing concentrations, species, and preparations. Together these new reports shed light on how histamine acts within the lymphatic vasculature, but also raise important questions about the cell type on which histamine exerts its effects and the signaling pathways involved. This editorial briefly discusses the contribution of each study and its relevance to lymphatic biology.

  14. Tailoring of chronic lymphatic leukemia therapy.

    Science.gov (United States)

    Elhefni, Ashraf M

    2013-01-01

    Chronic lymphocytic leukemia (CLL) remains an incurable disease, with all patients who require therapy destined to relapse and understanding of the pathophysiology of chronic lymphocytic leukemia has advanced significantly. It is now clear that chronic lymphocytic leukemia is a relatively proliferative disorder that requires the help of its microenvironment to be maintained and to progress. The stimulation of the chronic lymphatic leukemia cell occurs in most, if not all, patients through antigen stimulation via the B cell receptors. In addition, there is now a appreciation of the role of the p53 pathway leading to chemoresistance and the elucidation of the molecular and intracellular signaling mechanisms of disease is just beginning to facilitate the development of several targeted small molecules that promise to revolutionize the treatment of Chronic lymphocytic leukemia.

  15. Low-cost microcontroller platform for studying lymphatic biomechanics in vitro.

    Science.gov (United States)

    Kornuta, Jeffrey A; Nipper, Matthew E; Dixon, J Brandon

    2013-01-04

    The pumping innate to collecting lymphatic vessels routinely exposes the endothelium to oscillatory wall shear stress and other dynamic forces. However, studying the mechanical sensitivity of the lymphatic endothelium remains a difficult task due to limitations of commercial or custom systems to apply a variety of time-varying stresses in vitro. Current biomechanical in vitro testing devices are very expensive, limited in capability, or highly complex; rendering them largely inaccessible to the endothelial cell biology community. To address these shortcomings, the authors propose a reliable, low-cost platform for augmenting the capabilities of commercially available pumps to produce a wide variety of flow rate waveforms. In particular, the Arduino Uno, a microcontroller development board, is used to provide open-loop control of a digital peristaltic pump using precisely timed serial commands. In addition, the flexibility of this platform is further demonstrated through its support of a custom-built cell-straining device capable of producing oscillatory strains with varying amplitudes and frequencies. Hence, this microcontroller development board is shown to be an inexpensive, precise, and easy-to-use tool for supplementing in vitro assays to quantify the effects of biomechanical forces on lymphatic endothelial cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Multifractal analysis of the long-range correlations in the cardiac dynamics of Drosophila melanogaster

    CERN Document Server

    Vitanov, N K; Vitanov, Nikolay K.; Yankulova, Elka D.

    2006-01-01

    Time series of heartbeat activity of humans can exhibit long-range correlations. In this paper we show that such kind of correlations can exist for the heartbeat activity of much simpler species like Drosophila melanogaster. By means of the method of multifractal detrended fluctuation analysis (MFDFA) we calculate fractal spectra $f(\\alpha)$ and $h(q)$ and investigate the correlation properties of heartbeat activity of Drosophila with genetic hearth defects for three consequent generations of species. We observe that opposite to the case of humans the time series of the heartbeat activity of healtly Drosophila do not have scaling properties. Time series from flies with genetic defects can be long-range correllated and can have multifractal properties. The fractal heartbeat dynamics of Drosophila is transferred from generation to generation.

  17. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  18. Evaluation of lymphatic regeneration in rat incisional wound healing ...

    African Journals Online (AJOL)

    Nevine M.F. El Deeb

    2014-06-20

    Jun 20, 2014 ... Abstract Objective: During the wound healing process, lymphatic regeneration in the injured skin has not .... posed of newly-formed blood vessels and fibroblasts .... age plays a role in connection with traumatic deaths due to.

  19. [Quantitative Analysis of Wall Shear Stress for Human Carotid Bifurcation at Cardiac Phases by the Use of Phase Contrast Cine Magnetic Resonance Imaging: Computational Fluid Dynamics Study].

    Science.gov (United States)

    Saho, Tatsunori; Onishi, Hideo

    2015-12-01

    Detailed strategy for regional hemodynamics is significant for knowledge of plaque development on vascular diseases such as atherosclerosis. The aim of this study was to derive relation between atherosclerosis and hemodynamics at human carotid bifurcation by the use of computational fluid dynamics (CFD), and to provide more accurate hemodynamic information. Blood velocity datasets at common carotid artery were obtained by phase-contrast cine magnetic resonance imaging (PC cine MRI). Carotid bifurcation model was computed for systolic, mid-diastolic, and end-diastolic phase. Comparison of wall shear stress (WSS) was performed for each cardiac phase. PC cine MRI provided velocity measurement for common carotid artery with various cardiac phases. The blood velocity had acute variation from 0.21 m/s to 1.07 m/s at systolic phase. The variation of WSS during cardiac phase was presented at carotid bifurcation model. High shear stress area was observed at dividing wall for all cardiac phases. The systole-diastole WSS ratio was 10.15 at internal carotid side of bifurcation. And low shear stress (cine MRI was allowed to determine an accurate analysis condition. This led to the representation of hemodynamics in vivo.

  20. Lymphatic vessel density and function in experimental bladder cancer

    Directory of Open Access Journals (Sweden)

    Maier Julie

    2007-11-01

    Full Text Available Abstract Background The lymphatics form a second circulatory system that drains the extracellular fluid and proteins from the tumor microenvironment, and provides an exclusive environment in which immune cells interact and respond to foreign antigen. Both cancer and inflammation are known to induce lymphangiogenesis. However, little is known about bladder lymphatic vessels and their involvement in cancer formation and progression. Methods A double transgenic mouse model was generated by crossing a bladder cancer-induced transgenic, in which SV40 large T antigen was under the control of uroplakin II promoter, with another transgenic mouse harboring a lacZ reporter gene under the control of an NF-κB-responsive promoter (κB-lacZ exhibiting constitutive activity of β-galactosidase in lymphatic endothelial cells. In this new mouse model (SV40-lacZ, we examined the lymphatic vessel density (LVD and function (LVF during bladder cancer progression. LVD was performed in bladder whole mounts and cross-sections by fluorescent immunohistochemistry (IHC using LYVE-1 antibody. LVF was assessed by real-time in vivo imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA-Cy5.5; Gd-Cy5.5 suitable for both magnetic resonance imaging (MRI and near infrared fluorescence (NIRF. In addition, IHC of Cy5.5 was used for time-course analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31-positive blood vessels. Results SV40-lacZ mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic

  1. A dynamic double helical band as a model for cardiac pumping

    Energy Technology Data Exchange (ETDEWEB)

    Grosberg, Anna; Gharib, Morteza [Option in Bioengineering, California Institute of Technology, 1200 E. California Blvd, M/C 205-45, Pasadena, CA 91125 (United States)], E-mail: mgharib@caltech.edu

    2009-06-01

    We address here, by means of finite-element computational modeling, two features of heart mechanics and, most importantly, their timing relationship: one of them is the ejected volume and the other is the twist of the heart. The corner stone of our approach is to take the double helical muscle fiber band as the dominant active macrostructure behind the pumping function. We show that this double helical model easily reproduces a physiological maximal ejection fraction of up to 60% without exceeding the limit on local muscle fiber contraction of 15%. Moreover, a physiological ejection fraction can be achieved independently of the excitation pattern. The left ventricular twist is also largely independent of the type of excitation. However, the physiological relationship between the ejection fraction and twist can only be reproduced with Purkinje-type excitation schemes. Our results indicate that the proper timing coordination between twist and ejection dynamics can be reproduced only if the excitation front originates in the septum region near the apex. This shows that the timing of the excitation is directly related to the productive pumping operation of the heart and illustrates the direction for possible bioinspired pump design.

  2. Dynamics of cross-bridge cycling, ATP hydrolysis, force generation, and deformation in cardiac muscle.

    Science.gov (United States)

    Tewari, Shivendra G; Bugenhagen, Scott M; Palmer, Bradley M; Beard, Daniel A

    2016-07-01

    Despite extensive study over the past six decades the coupling of chemical reaction and mechanical processes in muscle dynamics is not well understood. We lack a theoretical description of how chemical processes (metabolite binding, ATP hydrolysis) influence and are influenced by mechanical processes (deformation and force generation). To address this need, a mathematical model of the muscle cross-bridge (XB) cycle based on Huxley's sliding filament theory is developed that explicitly accounts for the chemical transformation events and the influence of strain on state transitions. The model is identified based on elastic and viscous moduli data from mouse and rat myocardial strips over a range of perturbation frequencies, and MgATP and inorganic phosphate (Pi) concentrations. Simulations of the identified model reproduce the observed effects of MgATP and MgADP on the rate of force development. Furthermore, simulations reveal that the rate of force re-development measured in slack-restretch experiments is not directly proportional to the rate of XB cycling. For these experiments, the model predicts that the observed increase in the rate of force generation with increased Pi concentration is due to inhibition of cycle turnover by Pi. Finally, the model captures the observed phenomena of force yielding suggesting that it is a result of rapid detachment of stretched attached myosin heads.

  3. Usefulness of CBCT and guidance software for percutaneous embolization of a lymphatic leakage after thyroidectomy for cancer

    Science.gov (United States)

    Ierardi, Anna Maria; Liu, Xiaoli; Wu, Che-Wei; Anuwong, Angkoon; Kim, Hoon Yub; Liu, Renbin; Lavazza, Matteo; Inversini, Davide; Coppola, Andrea; Floridi, Chiara; Boni, Luigi; Carrafiello, Gianpaolo; Dionigi, Gianlorenzo

    2016-01-01

    Lymphatic leakage can develop as an iatrogenic complication of thoracic, cardiac, and neck surgery. The management of this complication may be challenging and involves more specialists. Percutaneous, image-guided techniques may offer two advantages: mini-invasivity and ability to image and identify the anatomy and the site of the leakage. We report a case of refractory cervical chylous leakage after thyroidectomy and lymphadenectomy for cancer that was successfully treated with an ultrasound-guided intranodal lymphangiography and a percutaneous puncture of the leak performed using CBCT as imaging guidance. PMID:28149811

  4. Current and Future Lymphatic Imaging Modalities for Tumor Staging

    Directory of Open Access Journals (Sweden)

    Ghulam Murtaza

    2014-01-01

    Full Text Available Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review.

  5. Dynamic molecular imaging of cardiac innervation using a dual headpinhole SPECT system

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Jicun; Boutchko, Rostyslav; Sitek, Arkadiusz; Reutter, BryanW.; Huesman, Ronald H.; Gullberg, Grant T.

    2008-03-29

    Typically 123I-MIBG is used for the study of innervation andfunction of the sympathetic nervous system in heart failure. The protocolinvolves two studies: first a planar or SPECT scan is performed tomeasure initial uptake of the tracer, followed some 3-4 hours later byanother study measuring the wash-out of the tracer from the heart. A fastwash-out is indicative of a compromised heart. In this work, a dual headpinhole SPECT system was used for imaging the distribution and kineticsof 123I-MIBG in the myocardium of spontaneous hypertensive rats (SHR) andnormotensive Wistar Kyoto (WKY) rats. The system geometry was calibratedbased on a nonlinear point projection fitting method using a three-pointsource phantom. The angle variation effect of the parameters was modeledwith a sinusoidal function. A dynamic acquisition was performed byinjecting 123I-MIBG into rats immediately after starting the dataacquisition. The detectors rotated continuously performing a 360o dataacquisition every 90 seconds. We applied the factor analysis (FA)methodand region of interest (ROI) sampling method to obtain time activitycurves (TACs)in the blood pool and myocardium and then appliedtwo-compartment modeling to estimate the kinetic parameters. Since theinitial injection bolus is too fast for obtaining a consistenttomographic data set in the first few minutes of the study, we appliedthe FA method directly to projections during the first rotation. Then thetime active curves for blood and myocardial tissue were obtained from ROIsampling. The method was applied to determine if there were differencesin the kinetics between SHR and WKY rats and requires less time byreplacing the delayed scan at 3-4 hours after injection with a dynamicacquisition over 90 to 120 minutes. The results of a faster washout and asmaller distribution volume of 123IMIBG near the end of life in the SHRmodel of hypertrophic cardiomyopthy may be indicative of a failing heartin late stages of heart failure.

  6. Quantum dots trace lymphatic drainage from the mouse eye

    Energy Technology Data Exchange (ETDEWEB)

    Tam, Alex L C; Gupta, Neeru; Zhang Zhexue; Yuecel, Yeni H, E-mail: yucely@smh.ca [Department of Ophthalmology and Vision Sciences, University of Toronto, M5T 2S8 (Canada)

    2011-10-21

    Glaucoma is a leading cause of blindness in the world, often associated with elevated eye pressure. Currently, all glaucoma treatments aim to lower eye pressure by improving fluid exit from the eye. We recently reported the presence of lymphatics in the human eye. The lymphatic circulation is known to drain fluid from organ tissues and, as such, lymphatics may also play a role in draining fluid from the eye. We investigated whether lymphatic drainage from the eye is present in mice by visualizing the trajectory of quantum dots once injected into the eye. Whole-body hyperspectral fluorescence imaging was performed in 17 live mice. In vivo imaging was conducted prior to injection, and 5, 20, 40 and 70 min, and 2, 6 and 24 h after injection. A quantum dot signal was observed in the left neck region at 6 h after tracer injection into the eye. Examination of immunofluorescence-labelled sections using confocal microscopy showed the presence of a quantum dot signal in the left submandibular lymph node. This is the first direct evidence of lymphatic drainage from the mouse eye. The use of quantum dots to image this lymphatic pathway in vivo is a novel tool to stimulate new treatments to reduce eye pressure and prevent blindness from glaucoma.

  7. The surgical anatomy of the lymphatic system of the pancreas.

    Science.gov (United States)

    Cesmebasi, Alper; Malefant, Jason; Patel, Swetal D; Du Plessis, Maira; Renna, Sarah; Tubbs, R Shane; Loukas, Marios

    2015-05-01

    The lymphatic system of the pancreas is a complex, intricate network of lymphatic vessels and nodes responsible for the drainage of the head, neck, body, and tail of the pancreas. Its anatomical divisions and embryological development have been well described in the literature with emphasis on its clinical relevance in regards to pancreatic pathologies. A thorough knowledge and understanding of the lymphatic system surrounding the pancreas is critical for physicians in providing diagnostic and treatment strategies for patients with pancreatic cancer and pancreatitis. Pancreatic cancer has an extremely poor prognosis and is a notable cause of morbidity and mortality worldwide. Although a surgeon may try to predict the routes for metastasis for pancreatic cancer, the complexity of this system presents difficulty due to variable drainage patterns. Pancreatitis also presents as another severe disease which has been shown to have an association with the lymphatics. The aim of this article is to review the literature on the lymphatics of the pancreas, pancreatic pathologies, and the available imaging methodologies used to study the pancreatic lymphatics.

  8. Altered Pulmonary Lymphatic Development in Infants with Chronic Lung Disease

    Directory of Open Access Journals (Sweden)

    Emily M. McNellis

    2014-01-01

    Full Text Available Pulmonary lymphatic development in chronic lung disease (CLD has not been investigated, and anatomy of lymphatics in human infant lungs is not well defined. Hypothesis. Pulmonary lymphatic hypoplasia is present in CLD. Method. Autopsy lung tissues of eighteen subjects gestational ages 22 to 40 weeks with and without history of respiratory morbidity were stained with monoclonal antipodoplanin and reviewed under light microscopy. Percentage of parenchyma podoplanin stained at the acinar level was determined using computerized image analysis; 9 CLD and 4 control subjects gestational ages 27 to 36 weeks were suitable for the analysis. Results. Distinct, lymphatic-specific staining with respect to other vascular structures was appreciated in all gestations. Infants with and without respiratory morbidity had comparable lymphatic distribution which extended to the alveolar ductal level. Podoplanin staining per parenchyma was increased and statistically significant in the CLD group versus controls at the alveolar ductal level (0.06% ± 0.02% versus 0.04% ± 0.01%, 95% CI −0.04% to −0.002%, P<0.03. Conclusion. Contrary to our hypothesis, the findings show that there is an increase in alveolar lymphatics in CLD. It is suggested that the findings, by expanding current knowledge of CLD pathology, may offer insight into the development of more effective therapies to tackle CLD.

  9. Lymphatic function is required prenatally for lung inflation at birth

    Science.gov (United States)

    Jakus, Zoltán; Gleghorn, Jason P.; Enis, David R.; Sen, Aslihan; Chia, Stephanie; Liu, Xi; Rawnsley, David R.; Yang, Yiqing; Hess, Paul R.; Zou, Zhiying; Yang, Jisheng; Guttentag, Susan H.; Nelson, Celeste M.

    2014-01-01

    Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants. PMID:24733830

  10. Noninvasive real-time fluorescence imaging of the lymphatic uptake of BSA-IRDye 680 conjugate administered subcutaneously in mice.

    Science.gov (United States)

    Wu, Fang; Bhansali, Suraj G; Tamhane, Mitalee; Kumar, Rajiv; Vathy, Lisa A; Ding, Hong; Yong, Ken-Tye; Bergey, Earl J; Prasad, Paras N; Morris, Marilyn E

    2012-05-01

    The goal of our studies was to determine lymphatic uptake of bovine serum albumin (BSA) using real-time noninvasive fluorescence imaging. BSA labeled with near-infrared dye (IRDye) 680 was used as a model protein-dye conjugate. The conjugation of BSA with IRDye 680 was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Size-exclusion high-performance liquid chromatography and SDS-PAGE demonstrated that the IRDye 680-labeled BSA conjugate in the lymph node (LN) homogenate samples was stable at physiological temperature (37°C) for at least 5 days. Whole-body noninvasive optical imaging of hairless SKH-1 mice was performed after subcutaneous (s.c.) injection (dose = 0.1 mg/kg) into the front footpad. Noninvasive fluorescence imaging demonstrated that BSA-IRDye 680 conjugates were dynamically taken up by the lymphatic system, accumulated in the axillary LNs and then cleared, indicating that lymphatic transport plays a role in the absorption of BSA. Ex vivo tissue imaging of LN homogenates provided confirmatory data with respect to the uptake of fluorescent-labeled BSA determined by in vivo imaging. Noninvasive real-time imaging of LNs provides a novel tool for evaluating uptake and accumulation of fluorescent-labeled proteins by the lymphatic system after s.c. injection in a mouse model.

  11. Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish

    DEFF Research Database (Denmark)

    Dahl Ejby Jensen, Lasse; Cao, Renhai; Hedlund, Eva-Maria

    2009-01-01

    The blood and lymphatic vasculatures are structurally and functionally coupled in controlling tissue perfusion, extracellular interstitial fluids, and immune surveillance. Little is known, however, about the molecular mechanisms that underlie the regulation of bloodlymphatic vessel connections...

  12. Heart rate dynamics after exercise in cardiac patients with and without type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Antti M Kiviniemi

    2011-09-01

    Full Text Available Purpose: The incidence of cardiovascular events is higher in coronary artery disease patients with type 2 diabetes (CAD+T2D than in CAD patients without T2D. There is increasing evidence that the recovery phase after exercise is a vulnerable phase for various cardiovascular events. We hypothesized that autonomic regulation differs in CAD patients with and without T2D during post-exercise condition. Methods: A symptom-limited maximal exercise test on a bicycle ergometer was performed for 68 CAD+T2D patients (age 61 ± 5 years, 78% males, ejection fraction 67 ± 8, 100% on β-blockade and 64 CAD patients (age 62 ± 5 years, 80% males, ejection fraction 64 ± 8, 100% on β-blockade. Heart rate (HR recovery after exercise was calculated as the slope of HR during the first 60 sec after cessation of exercise (HRRslope. R-R intervals were measured before (5 min and after exercise from 3 to 8 min, both in a supine position. R-R intervals were analyzed using time and frequency methods and a detrended fluctuation method (α1. Results: BMI was 30 ± 4 vs. 27 ± 3 kg•m2 (p < 0.001; maximal exercise capacity, 6.5 ± 1.7 vs. 7.7 ± 1.9 METs (p < 0.001; maximal HR, 128 ± 19 vs. 132 ± 18 bpm (p = ns; and HRRslope, -0.53 ± 0.17 vs. -0.62 ± 0.15 beats/sec (p = 0.004, for CAD patients with and without T2D, respectively. There was no differences between the groups in HRRslope after adjustment for METs, BMI and medication (ANCOVA, p = 0.228 for T2D and e.g. p = 0.030 for METs. CAD+T2D patients had a higher HR at rest than nondiabetic patients (57 ± 10 vs. 54 ± 6 bpm, p = 0.030, but no other differences were observed in HR dynamics at rest or in post-exercise condition. Conclusion: HR recovery is delayed in CAD+T2D patients, suggesting impairment of vagal activity and/or augmented sympathetic activity after exercise. Blunted HR recovery after exercise in diabetic patients compared with nondiabetic patients is more closely related to low exercise capacity and

  13. Cardiac autonomic modulation in healthy elderly after different intensities of dynamic exercise

    Science.gov (United States)

    Droguett, Viviane Santos López; Santos, Amilton da Cruz; de Medeiros, Carlos Eduardo; Marques, Douglas Porto; do Nascimento, Leone Severino; Brasileiro-Santos, Maria do Socorro

    2015-01-01

    Purpose To investigate the heart rate (HR) and its autonomic modulation at baseline and during dynamic postexercise (PEX) with intensities of 40% and 60% of the maximum HR in healthy elderly. Methods This cross-sectional study included ten apparently healthy people who had been submitted to a protocol on a cycle ergometer for 35 minutes. Autonomic modulation was evaluated by spectral analysis of HR variability (HRV). Results A relevant increase in HR response was observed at 15 minutes postexercise with intensities of 60% and 40% of the maximum HR (10±2 bpm versus 5±1 bpm, respectively; P=0.005), and a significant reduction in HRV was also noted with 40% and 60% intensities during the rest period, and significant reduction in HRV (RR variance) was also observed in 40% and 60% intensities when compared to the baseline, as well as between the post-exercise intensities (1032±32 ms versus 905±5 ms) (P<0.001). In the HRV spectral analysis, a significant increase in the low frequency component HRV and autonomic balance at 40% of the maximum HR (68±2 normalized units [nu] versus 55±1 nu and 2.0±0.1 versus 1.2±0.1; P<0.001) and at 60% of the maximum HR (77±1 nu versus 55±1 nu and 3.2±0.1 versus 1.2±0.1 [P<0.001]) in relation to baseline was observed. A significant reduction of high frequency component at 40% and 60% intensities, however, was observed when compared to baseline (31±2 nu and 23±1 nu versus 45±1 nu, respectively; P<0.001). Moreover, significant differences were observed for the low frequency and high frequency components, as well as for the sympathovagal balance between participants who reached 40% and 60% of the maximum HR. Conclusion There was an increase in the HR, sympathetic modulation, and sympathovagal balance, as well as a reduction in vagal modulation in the elderly at both intensities of the PEX. PMID:25653509

  14. Localization and proliferation of lymphatic vessels in the tympanic membrane in normal state and regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Miyashita, Takenori, E-mail: takenori@med.kagawa-u.ac.jp [Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kagawa 761-0793 (Japan); Burford, James L. [Department of Physiology and Biophysics and Department of Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Hong, Young-Kwon [Department of Surgery and Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Gevorgyan, Haykanush; Lam, Lisa [Department of Physiology and Biophysics and Department of Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Mori, Nozomu [Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kagawa 761-0793 (Japan); Peti-Peterdi, Janos [Department of Physiology and Biophysics and Department of Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States)

    2013-10-25

    Highlights: •We newly developed the whole-mount imaging method of the tympanic membrane. •Lymphatic vessel loops were localized around the malleus handle and annulus tympanicus. •In regeneration, abundant lymphatic vessels were observed in the pars tensa. •Site-specific lymphatic vessels may play an important role in the tympanic membrane. -- Abstract: We clarified the localization of lymphatic vessels in the tympanic membrane and proliferation of lymphatic vessels during regeneration after perforation of the tympanic membrane by using whole-mount imaging of the tympanic membrane of Prox1 GFP mice. In the pars tensa, lymphatic vessel loops surrounded the malleus handle and annulus tympanicus. Apart from these locations, lymphatic vessel loops were not observed in the pars tensa in the normal tympanic membrane. Lymphatic vessel loops surrounding the malleus handle were connected to the lymphatic vessel loops in the pars flaccida and around the tensor tympani muscle. Many lymphatic vessel loops were detected in the pars flaccida. After perforation of the tympanic membrane, abundant lymphatic regeneration was observed in the pars tensa, and these regenerated lymphatic vessels extended from the lymphatic vessels surrounding the malleus at day 7. These results suggest that site-specific lymphatic vessels play an important role in the tympanic membrane.

  15. Transmission models and management of lymphatic filariasis elimination.

    Science.gov (United States)

    Michael, Edwin; Gambhir, Manoj

    2010-01-01

    The planning and evaluation of parasitic control programmes are complicated by the many interacting population dynamic and programmatic factors that determine infection trends under different control options. A key need is quantification about the status of the parasite system state at any one given timepoint and the dynamic change brought upon that state as an intervention program proceeds. Here, we focus on the control and elimination of the vector-borne disease, lymphatic filariasis, to show how mathematical models of parasite transmission can provide a quantitative framework for aiding the design of parasite elimination and monitoring programs by their ability to support (1) conducting rational analysis and definition of endpoints for different programmatic aims or objectives, including transmission endpoints for disease elimination, (2) undertaking strategic analysis to aid the optimal design of intervention programs to meet set endpoints under different endemic settings and (3) providing support for performing informed evaluations of ongoing programs, including aiding the formation of timely adaptive management strategies to correct for any observed deficiencies in program effectiveness. The results also highlight how the use of a model-based framework will be critical to addressing the impacts of ecological complexities, heterogeneities and uncertainties on effective parasite management and thereby guiding the development of strategies to resolve and overcome such real-world complexities. In particular, we underscore how this approach can provide a link between ecological science and policy by revealing novel tools and measures to appraise and enhance the biological controllability or eradicability of parasitic diseases. We conclude by emphasizing an urgent need to develop and apply flexible adaptive management frameworks informed by mathematical models that are based on learning and reducing uncertainty using monitoring data, apply phased or sequential

  16. New model of macrophage acquisition of the lymphatic endothelial phenotype.

    Directory of Open Access Journals (Sweden)

    Kelly L Hall

    Full Text Available BACKGROUND: Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency in vivo and lack of model systems allowing in-depth molecular analyses in vitro. Our goal was to establish a cell culture model to characterize inflammation-induced macrophage-to-LECP differentiation under controlled conditions. METHODOLOGY/PRINCIPAL FINDINGS: Time-course analysis of diaphragms from lipopolysaccharide (LPS-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50% incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS in vitro. Activated RAW264.7 cells co-expressed VEGF-C that induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a 68% overlap with endogenous CD11b(+/VEGFR-3(+ LECPs in the expression of lymphatic-specific genes. Moreover, when injected into LPS- but not saline-treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed diaphragm followed by integration into 18% of lymphatic vessels. CONCLUSIONS/SIGNIFICANCE: We present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the "RAW model" mimics

  17. High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

    Science.gov (United States)

    Seppälä, Miia; Pohjola, Konsta; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Renkonen, Risto; Lemström, Karl; Paavonen, Timo; Toppila-Salmi, Sanna

    2016-12-01

    Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.

  18. Structural and functional features of central nervous system lymphatic vessels.

    Science.gov (United States)

    Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

    2015-07-16

    One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

  19. Is tuberculosis a lymphatic disease with a pulmonary portal?

    Science.gov (United States)

    Behr, Marcel A; Waters, W Ray

    2014-03-01

    Tuberculosis most commonly presents as a pulmonary disease, in which infection, persistence, and induction of transmissible pathology all occur in the lungs. If viewed as a pulmonary disease, enlarged lymph nodes represent reactive adenitis, and extrapulmonary forms of tuberculosis (including lymphatic tuberculosis) are not transmissible, hence representing an evolutionary dead-end for the pathogen. In an alternative theory, Mycobacterium tuberculosis passes asymptomatically through the lungs and rapidly establishes a chronic lymphatic infection. After a period of weeks to decades secondary lung pathology develops, ultimately allowing transmission to occur. Evidence that supports this lymphatic model includes historical descriptions of human tuberculosis from the preantibiotic era, analogy with other mycobacterial infections, observations of tuberculosis in non-human hosts, and experimental models of tuberculosis disease. At a fundamental level, a lymphocentric model proposes that spread of organisms outside the lung parenchyma is essential to induce adaptive immunity, which is crucial for the generation of transmissible pathology. Furthermore, a lymphatic model could explain why the lesion associated with primary infection (Ghon focus) is anatomically separated from the most common site of reactivation disease (the apex). More practically, an alternative perspective that classes tuberculosis as a lymphatic disease might affect strategies for preclinical and clinical assessment of novel diagnostics, drugs, and vaccines.

  20. A comparison of retroperitoneoscopic and open surgical renal pedicle lymphatic disconnection for the treatment of serious filarial chyluria

    Institute of Scientific and Technical Information of China (English)

    LAN Wei-hua; JIN Feng-shuo; WANG Luo-fu; ZHU Fang-qiang

    2007-01-01

    @@ Currently the most effective clinical management for serious intractable chyluria is renal pedicle lymphatic disconnection, which generally consists of nephrolympholysis, renal hilar lymphatic vessel stripping and ureterolympholysis.

  1. Recent advances in lymphatic targeted drug deliver y system for tumor metastasis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yu Zhang; Wei-Yue Lu

    2014-01-01

    Te lymphatic system has an important defensive role in the human body. hTe metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors;the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the speciifcity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.

  2. A discrete electromechanical model for human cardiac tissue: effects of stretch-activated currents and stretch conditions on restitution properties and spiral wave dynamics.

    Directory of Open Access Journals (Sweden)

    Louis D Weise

    Full Text Available We introduce an electromechanical model for human cardiac tissue which couples a biophysical model of cardiac excitation (Tusscher, Noble, Noble, Panfilov, 2006 and tension development (adjusted Niederer, Hunter, Smith, 2006 model with a discrete elastic mass-lattice model. The equations for the excitation processes are solved with a finite difference approach, and the equations of the mass-lattice model are solved using Verlet integration. This allows the coupled problem to be solved with high numerical resolution. Passive mechanical properties of the mass-lattice model are described by a generalized Hooke's law for finite deformations (Seth material. Active mechanical contraction is initiated by changes of the intracellular calcium concentration, which is a variable of the electrical model. Mechanical deformation feeds back on the electrophysiology via stretch-activated ion channels whose conductivity is controlled by the local stretch of the medium. We apply the model to study how stretch-activated currents affect the action potential shape, restitution properties, and dynamics of spiral waves, under constant stretch, and dynamic stretch caused by active mechanical contraction. We find that stretch conditions substantially affect these properties via stretch-activated currents. In constantly stretched medium, we observe a substantial decrease in conduction velocity, and an increase of action potential duration; whereas, with dynamic stretch, action potential duration is increased only slightly, and the conduction velocity restitution curve becomes biphasic. Moreover, in constantly stretched medium, we find an increase of the core size and period of a spiral wave, but no change in rotation dynamics; in contrast, in the dynamically stretching medium, we observe spiral drift. Our results may be important to understand how altered stretch conditions affect the heart's functioning.

  3. Modelling Co-Infection with Malaria and Lymphatic Filariasis

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    Slater, Hannah C.; Gambhir, Manoj; Parham, Paul E.; Michael, Edwin

    2013-01-01

    Malaria and lymphatic filariasis (LF) continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions about optimal vector control strategies in co-endemic regions, as well as the effect of the presence of each infection on endemicity of the other; there is currently little consensus on the latter. The need for comprehensive modelling studies to address such questions is therefore significant, yet very few have been undertaken to date despite the recognised explanatory power of reliable dynamic mathematical models. Here, we develop a malaria-LF co-infection modelling framework that accounts for two key interactions between these infections, namely the increase in vector mortality as LF mosquito prevalence increases and the antagonistic Th1/Th2 immune response that occurs in co-infected hosts. We consider the crucial interplay between these interactions on the resulting endemic prevalence when introducing each infection in regions where the other is already endemic (e.g. due to regional environmental change), and the associated timescale for such changes, as well as effects on the basic reproduction number R0 of each disease. We also highlight potential perverse effects of vector controls on human infection prevalence in co-endemic regions, noting that understanding such effects is critical in designing optimal integrated control programmes. Hence, as well as highlighting where better data are required to more reliably address such questions, we provide an important framework that will form the basis of future scenario analysis tools used to plan and inform policy decisions on intervention measures in different transmission settings. PMID:23785271

  4. The Lymphatic Endothelial mCLCA1 Antibody Induces Proliferation and Growth of Lymph Node Lymphatic Sinuses.

    Directory of Open Access Journals (Sweden)

    Kimberly L Jordan-Williams

    Full Text Available Lymphocyte- and leukocyte-mediated lymph node (LN lymphatic sinus growth (lymphangiogenesis is involved in immune responses and in diseases including cancer and arthritis. We previously discovered a 10.1.1 Ab that recognizes the lymphatic endothelial cell (LEC surface protein mCLCA1, which is an interacting partner for LFA1 and Mac-1 that mediates lymphocyte adhesion to LECs. Here, we show that 10.1.1 Ab treatment specifically induces LEC proliferation, and influences migration and adhesion in vitro. Functional testing by injection of mice with 10.1.1 Ab but not control hamster Abs identified rapid induction of LN LEC proliferation and extensive lymphangiogenesis within 23 h. BrdU pulse-chase analysis demonstrated incorporation of proliferating LYVE-1-positive LEC into the growing medullary lymphatic sinuses. The 10.1.1 Ab-induced LN remodeling involved coordinate increases in LECs and also blood endothelial cells, fibroblastic reticular cells, and double negative stroma, as is observed during the LN response to inflammation. 10.1.1 Ab-induced lymphangiogenesis was restricted to LNs, as mCLCA1-expressing lymphatic vessels of the jejunum and dermis were unaffected by 23 h 10.1.1 Ab treatment. These findings demonstrate that 10.1.1 Ab rapidly and specifically induces proliferation and growth of LN lymphatic sinuses and stroma, suggesting a key role of mCLCA1 in coordinating LN remodeling during immune responses.

  5. ACKR2: An Atypical Chemokine Receptor Regulating Lymphatic Biology

    Science.gov (United States)

    Bonavita, Ornella; Mollica Poeta, Valeria; Setten, Elisa; Massara, Matteo; Bonecchi, Raffaella

    2017-01-01

    The lymphatic system plays an important role in the induction of the immune response by transporting antigens, inflammatory mediators, and leukocytes from peripheral tissues to draining lymph nodes. It is emerging that lymphatic endothelial cells (LECs) are playing an active role in this context via the expression of chemokines, inflammatory mediators promoting cell migration, and chemokine receptors. Particularly, LECs express atypical chemokine receptors (ACKRs), which are unable to promote conventional signaling and cell migration while they are involved in the regulation of chemokine availability. Here, we provide a summary of the data on the role of ACKR2 expressed by lymphatics, indicating an essential role for this ACKRs in the regulation of the inflammation and the immune response in different pathological conditions, including infection, allergy, and cancer. PMID:28123388

  6. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  7. Topography of Lymphatic Markers in Human Iris and Ciliary Body.

    Science.gov (United States)

    Kaser-Eichberger, Alexandra; Schrödl, Falk; Trost, Andrea; Strohmaier, Clemens; Bogner, Barbara; Runge, Christian; Motloch, Karolina; Bruckner, Daniela; Laimer, Martin; Schlereth, Simona L; Heindl, Ludwig M; Reitsamer, Herbert A

    2015-07-01

    Reports of lymphatics in the anterior human uvea are contradictory. This might be caused due to a certain topography, which has not been considered yet. Therefore, here we systematically analyze iris and adjacent ciliary body with immunohistochemistry by combining various lymphatic markers. Human iris and ciliary body were obtained from cornea donors and prepared for cryosectioning. Cross sections of tissue blocks at 12/3/6/9 o'clock position and at corresponding intersections (1:30/4:30/7:30/10:30) were processed for immunohistochemistry of LYVE-1, PDPN, PROX1, FOXC2, VEGFR3, and CCL21, and when necessary, these lymphatic markers were combined with CD31, α-smooth muscle-actin, CD68, and 4',6-diamidino-2 phenylindole dihydrochloride (DAPI). Double, triple, and quadruple marker combinations were documented using confocal microscopy. Numerous podoplanin+ cells were mainly located at the anterior border of the iris while LYVE-1+ cells were distributed throughout the nonpigmented part. Both cell populations were PROX1/FOXC2/CCL21/VEGFR3-. Blood vessels, iris smooth muscles, and individual cells were VEGFR3+. While PDPN+ cells were rarely detected posteriorly of the iris root, many LYVE-1+ cells were present within the ciliary body muscle and villi. Within the muscle, occasionally PDPN+ vessel-like structures were detectable, but these were never colocalized with LYVE-1. Similar vessel-like structures were VEGFR3+/PROX1-/CCL21-, but CD31+. Further, ciliary muscle fibers and ciliary epithelium were immunoreactive for VEGFR3/CCL21, but were LYVE-1/PDPN-. A certain topography of structures at the various uvea-positions investigated was not obvious. The majority of LYVE-1+ cells displayed immunoreactivity for CD68. Lymphatic vessels colocalizing for at least two lymphatic markers were not detectable. Therefore, if present, putative lymphatic channels of the anterior uvea might display a different marker panel than generally presumed.

  8. Synthesis of a novel polyamidoamine dendrimer conjugating with alkali blue as a lymphatic tracer and study on the lymphatic targeting in vivo.

    Science.gov (United States)

    Yang, Rui; Xia, Suxia; Ye, Tiantian; Yao, Jianhua; Zhang, Ruizhi; Wang, Shujun; Wang, Siling

    2016-09-01

    In this study, a novel lymphatic tracer polyamidoamin-alkali blue (PAMAM-AB) was synthesized in order to evaluate the intra-lymphatic targeting ability and lymphatic tropism of PAMAM-AB after subcutaneous administration. UV-Vis, FT-IR, NMR and HPLC characterization were performed to prove the successful synthesis of PAMAM-AB. The calculated AB payload of PAMAM-AB conjugate was seven per dendrimer molecule (27.16% by weight). Hydrolysis stability of PAMAM-AB in vitro was evaluated, which was stable in PBS and human plasma. Lymphatic tracing were studied to determine the blue-stained intensity of PAMAM-AB in right popliteral lymph nodes (PLNs), iliac lymph nodes (ILNs) and para-aortic lymph nodes (PALNs) after subcutaneous administration. The pharmacokinetics and biodistribution of PAMAM-AB in mice were investigated. PLNs, ILNs and PALNs could be obviously blue-stained within 10 min after PAMAM-AB administration, and displayed a more rapid lymphatic absorption, a higher AUC value in lymph nodes and a longer lymph nodes residence time compared with methylene blue solution (MB-S), MB water-in-oil microemulsion (MB-ME), MB multiple microemulsion (MB-MME). Enhanced lymphatic drainage from the injection site and uptake into lymph of PAMAM-AB indicated that PAMAM-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors or as a lymphatic tracer in its own right.

  9. Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis

    Directory of Open Access Journals (Sweden)

    Francesca Luisi

    2016-06-01

    Full Text Available Generalised lymphatic anomaly (GLA, also known as lymphangiomatosis, is a rare disease caused by congenital abnormalities of lymphatic development. It usually presents in childhood but can also be diagnosed in adults. GLA encompasses a wide spectrum of clinical manifestations ranging from single-organ involvement to generalised disease. Given the rarity of the disease, most of the information regarding it comes from case reports. To date, no clinical trials concerning treatment are available. This review focuses on thoracic GLA and summarises possible diagnostic and therapeutic approaches.

  10. Accelerated dynamic cardiac MRI exploiting sparse-Kalman-smoother self-calibration and reconstruction (k  -  t SPARKS).

    Science.gov (United States)

    Park, Suhyung; Park, Jaeseok

    2015-05-07

    Accelerated dynamic MRI, which exploits spatiotemporal redundancies in k  -  t space and coil dimension, has been widely used to reduce the number of signal encoding and thus increase imaging efficiency with minimal loss of image quality. Nonetheless, particularly in cardiac MRI it still suffers from artifacts and amplified noise in the presence of time-drifting coil sensitivity due to relative motion between coil and subject (e.g. free breathing). Furthermore, a substantial number of additional calibrating signals is to be acquired to warrant accurate calibration of coil sensitivity. In this work, we propose a novel, accelerated dynamic cardiac MRI with sparse-Kalman-smoother self-calibration and reconstruction (k  -  t SPARKS), which is robust to time-varying coil sensitivity even with a small number of calibrating signals. The proposed k  -  t SPARKS incorporates Kalman-smoother self-calibration in k  -  t space and sparse signal recovery in x  -   f space into a single optimization problem, leading to iterative, joint estimation of time-varying convolution kernels and missing signals in k  -  t space. In the Kalman-smoother calibration, motion-induced uncertainties over the entire time frames were included in modeling state transition while a coil-dependent noise statistic in describing measurement process. The sparse signal recovery iteratively alternates with the self-calibration to tackle the ill-conditioning problem potentially resulting from insufficient calibrating signals. Simulations and experiments were performed using both the proposed and conventional methods for comparison, revealing that the proposed k  -  t SPARKS yields higher signal-to-error ratio and superior temporal fidelity in both breath-hold and free-breathing cardiac applications over all reduction factors.

  11. In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic–hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach

    Energy Technology Data Exchange (ETDEWEB)

    Kowalski, Greg M., E-mail: greg.kowalski@deakin.edu.au [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); De Souza, David P. [Metabolomics Australia, Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Risis, Steve [Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004 (Australia); Burch, Micah L. [Brigham and Women' s Hospital, Department of Medicine, Boston, MA (United States); Hamley, Steven [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Kloehn, Joachim [Metabolomics Australia, Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Selathurai, Ahrathy [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Lee-Young, Robert S. [Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004 (Australia); Tull, Dedreia; O' Callaghan, Sean; McConville, Malcolm J. [Metabolomics Australia, Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Bruce, Clinton R. [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia)

    2015-08-07

    Rationale: Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the regulation of cardiac substrate metabolism and insulin sensitivity has largely been derived from ex vivo preparations which are not subject to the same metabolic regulation as in the intact heart in vivo. Studies are therefore required to examine in vivo cardiac glucose metabolism under physiologically relevant conditions. Objective: To determine the temporal pattern of the development of cardiac insulin resistance and to compare with dynamic approaches to interrogate cardiac glucose and intermediary metabolism in vivo. Methods and results: Studies were conducted to determine the evolution of cardiac insulin resistance in C57Bl/6 mice fed a high-fat diet (HFD) for between 1 and 16 weeks. Dynamic in vivo cardiac glucose metabolism was determined following oral administration of [U-{sup 13}C] glucose. Hearts were collected after 15 and 60 min and flux profiling was determined by measuring {sup 13}C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Cardiac insulin resistance, determined by euglycemic–hyperinsulinemic clamp, was evident after 3 weeks of HFD. Despite the presence of insulin resistance, in vivo cardiac glucose metabolism following oral glucose administration was not compromised in HFD mice. This contrasts our recent findings in skeletal muscle, where TCA cycle activity was reduced in mice fed a HFD. Similar to our report in muscle, glucose derived pyruvate entry into the TCA cycle in the heart was almost exclusively via pyruvate dehydrogenase, with pyruvate carboxylase mediated anaplerosis being negligible after oral glucose administration. Conclusions: Under experimental conditions which closely mimic the postprandial state, the insulin resistant mouse heart retains the ability to stimulate glucose metabolism. - Highlights: • Insulin clamp was used to determine the evolution of cardiac

  12. Enzyme-histochemical study on postnatal development of rat stomach lymphatic vessels.

    Science.gov (United States)

    Ji, R C; Kato, S

    1997-07-01

    Postnatal development of rat gastric lymphatics was studied by an enzyme-histochemical method to elucidate the morphological changes of lymphatics and their relationship to maturation and function, especially in the glandular portion. The significant features of 5'-Nase-positive lymphatics in distribution and structure were examined in different stages (within 24 hr, 4-21 days, and 2 months). Lymphatics in the greater curvature and anterior wall grew much slower than those in the lesser curvature and posterior wall of the stomach in newborn and infant rats. Lymphatic islands isolated from the primary lymphatic networks in the submucosa and subserosa underwent a morphological change during this early period. This is considered one of the basic steps in lymphatic development. Occurrence of lymphatic networks in the deep lamina propria indicates that development in the gastric wall is well characterized from Day 10. With further growth and modification of lymphatics, the networks in the different layers formed an extensive communication network and many lymphatic valves were found in the submucosa and subserosa. Pinocytotic vesicles, open junctions, and intraendothelial channels were frequently detected in the mucosal and submucosal lymphatic networks of the corpus-antrum and antrum-duodenum divisional zones in the adult rats. These findings suggest that developing lymphatics in the rat stomach may represent rapidly growing tissue not only with high 5'-Nase activity but also with high adaptability for future physiological demands.

  13. Sphingosine-1-phosphate in the lymphatic fluid determined by novel methods

    Directory of Open Access Journals (Sweden)

    Masayuki Nagahashi

    2016-12-01

    Conclusions: In agreement with the previous theory, our results confirm “S1P gradient” among blood, lymphatic fluid and peripheral lymphatic tissues. Convenient methods for collection and measurement of sphingolipids in lymphatic fluid are expected to provide new insights on functions of sphingolipids.

  14. Lack of functioning intratumoral lymphatics in colon and pancreas cancer tissue.

    Science.gov (United States)

    Olszewski, Waldemar L; Stanczyk, Marek; Gewartowska, Magdalena; Domaszewska-Szostek, Anna; Durlik, Marek

    2012-09-01

    There are controversial views as to whether intratumoral or peritumoral lymphatics play a dominant role in the metastatic process. Most clinical observations originate from studies of colon cancer. Colon contains mucosa and submucosa rich in lymphatics and with high lymph formation rate. This seems to be a prerequisite for easy metastasis of cancer cells to regional lymph nodes. However, there are other tissues as pancreas with a rudimentary lymphatic network where cancer metastasis formation is as intensive as in colon cancer. This contradicts the common notion that intratumor lymphatics play major role in metastases. We visualized interstitial space and lymphatics in the central and peripheral regions of colon and pancreas tumors using the color stereoscopic lymphography and simultaneously immunohistochemical performed stainings specific for lymphatic and blood endothelial cells. The density of open and compressed lymphatic and blood vessels was measured in the tumor core and edge. There were very few lymphatics in the colon and pancreas tumor core but numerous minor fluid "lakes" with no visible connection to the peritumoral lymphatics. Lining of "lakes" did not express molecular markers specific for lymphatic endothelial cells. Dense connective tissue surrounding tumor foci did not contain lymphatics. Peritumoral lymphatics were irregularly distributed in both types of tumor and only sporadically contained cells that might be tumor cells. Similar lymphoscintigraphic and histological pictures were seen in colon and pancreas cancer despite of different structure of both tissues. This suggests a uniform reaction of tissues to the growing cancer irrespective of the affected organ.

  15. Evaluation of lymphatic dysplasia in patients with congenital pleural effusion and ascites using indocyanine green lymphography.

    Science.gov (United States)

    Shibasaki, Jun; Hara, Hisako; Mihara, Makoto; Adachi, Shinya; Uchida, Yasushi; Itani, Yasufumi

    2014-05-01

    To investigate the use of indocyanine green (ICG) lymphography in the diagnosis and assessment of the severity of lymphatic dysfunction in infants and neonates with congenital lymphatic pleural effusion and ascites. We performed ICG lymphography on 10 neonates and infants with congenital lymphatic pleural effusion and ascites. After the subcutaneous injection of ICG, circumferential fluorescent images of lymphatic drainage channels in the extremities and trunk were identified using an infrared camera system. The lymphographic findings were classifiable into 2 patterns-those showing a linear lymphatic pattern, suggesting normal lymphatic flow, and those showing lymphatic channels with retrograde lymphatic flow (dermal backflow pattern), suggesting an abnormal lymphatic flow. We analyzed the severity of the ICG lymphography findings and the clinical outcomes. Based on the ICG lymphography, the severity of lymphatic dysplasia were classified into 4 categories: mild dysplasia, moderate dysplasia, severe dysplasia, and lymphatic hypoplasia. All cases diagnosed with mild (n = 3) or moderate dysplasia (n = 2) survived, and 2 of the 4 cases diagnosed with severe dysplasia died. The duration of endotracheal intubation ranged from 1 to 17 days (median, 7) in the patients with mild or moderate dysplasia and from 25 to 110 days (median, 77) in those with severe dysplasia. The ICG lymphographic findings were consistent with the clinical conditions. This imaging technique may be important to the future clinical management of lymphatic dysplasia in neonates and infants. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Estimation of the parameter covariance matrix for aone-compartment cardiac perfusion model estimated from a dynamic sequencereconstructed using map iterative reconstruction algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Gullberg, Grant T.; Huesman, Ronald H.; Reutter, Bryan W.; Qi,Jinyi; Ghosh Roy, Dilip N.

    2004-01-01

    In dynamic cardiac SPECT estimates of kinetic parameters ofa one-compartment perfusion model are usually obtained in a two stepprocess: 1) first a MAP iterative algorithm, which properly models thePoisson statistics and the physics of the data acquisition, reconstructsa sequence of dynamic reconstructions, 2) then kinetic parameters areestimated from time activity curves generated from the dynamicreconstructions. This paper provides a method for calculating thecovariance matrix of the kinetic parameters, which are determined usingweighted least squares fitting that incorporates the estimated varianceand covariance of the dynamic reconstructions. For each transaxial slicesets of sequential tomographic projections are reconstructed into asequence of transaxial reconstructions usingfor each reconstruction inthe time sequence an iterative MAP reconstruction to calculate themaximum a priori reconstructed estimate. Time-activity curves for a sumof activity in a blood region inside the left ventricle and a sum in acardiac tissue region are generated. Also, curves for the variance of thetwo estimates of the sum and for the covariance between the two ROIestimates are generated as a function of time at convergence using anexpression obtained from the fixed-point solution of the statisticalerror of the reconstruction. A one-compartment model is fit to the tissueactivity curves assuming a noisy blood input function to give weightedleast squares estimates of blood volume fraction, wash-in and wash-outrate constants specifying the kinetics of 99mTc-teboroxime for theleftventricular myocardium. Numerical methods are used to calculate thesecond derivative of the chi-square criterion to obtain estimates of thecovariance matrix for the weighted least square parameter estimates. Eventhough the method requires one matrix inverse for each time interval oftomographic acquisition, efficient estimates of the tissue kineticparameters in a dynamic cardiac SPECT study can be obtained with

  17. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

    DEFF Research Database (Denmark)

    Arngrim, N; Simonsen, L; Holst, Jens Juul

    2012-01-01

    The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after ...... online publication, 3 July 2012; doi:10.1038/ijo.2012.98....

  18. Migration and lymphatic spread of calcified paraffinomas after breast augmentation

    Energy Technology Data Exchange (ETDEWEB)

    Ooi, G.C.; Peh, W.C.G.; Ip, M. [Hong Kong Univ. (Hong Kong)

    1996-11-01

    A 62 year old Chinese woman presented 25 years after having both breasts augmented with paraffin injections. Development of paraffinomas and multiple episodes of paraffin-related mastitis eventually resulted in bilateral mastectomies. The unusual distribution of migrated calcified paraffinomas in the thoracic wall and its lymphatic system is documented on computed tomography. 12 refs., 2 figs.

  19. Imaging vasculature and lymphatic flow in mice using quantum dots

    DEFF Research Database (Denmark)

    Ballou, Byron; Ernst, Lauren A.; Andreko, Susan

    2009-01-01

    Quantum dots are ideal probes for fluorescent imaging of vascular and lymphatic tissues. On injection into appropriate sites, red- and near-infrared-emitting quantum dots provide excellent definition of vasculature, lymphoid organs, and lymph nodes draining both normal tissues and tumors. We detail...

  20. Imaging vasculature and lymphatic flow in mice using quantum dots

    DEFF Research Database (Denmark)

    Ballou, Byron; Ernst, Lauren A.; Andreko, Susan

    2009-01-01

    Quantum dots are ideal probes for fluorescent imaging of vascular and lymphatic tissues. On injection into appropriate sites, red- and near-infrared-emitting quantum dots provide excellent definition of vasculature, lymphoid organs, and lymph nodes draining both normal tissues and tumors. We deta...

  1. [Hygienic evaluation of chronic lymphatic leukemia in Bashkortostan Republic].

    Science.gov (United States)

    Bakirov, B A; Varshavskiĭ, A V; Bakirov, A B

    2009-01-01

    Prevalence of chronic lymphatic leukemia increased in Bashkortostan Republic over 1999-2008 with predominance of urban population, male patients, individuals aged 80-84. Reliable correlation was seen between pollutants releases into the ambient air and the morbidity parameters over following 5 years.

  2. [THE STRUCTURE OF LYMPHATIC CAPILLARIES OF THE CILIARY BODY OF THE HUMAN EYE].

    Science.gov (United States)

    Borodin, Yu I; Bgatova, N P; Chernykh, V V; Trunov, A N; Pozhidayeva, A A; Konenkov, V I

    2015-01-01

    Using light microscopy, immunohistochemistry and electron microscopy, the structural organization of interstitial spaces and vessels of the ciliary body of the human eye (n = 5) were studied. The ciliary body was found to contain wide interstitial spaces--tissue clefts bound by collagen fibers and fibroblasts. Organ-specific lymphatic capillaries were also demonstrated in the ciliary body. According to the present findings and the lymphatic region concept, the first 2 elements of the lymphatic region of the eye were described: tissue clefts--prelymphatics and lymphatic capillaries of the ciliary body. The third element of the lymphatic region are the lymph nodes of the head and neck.

  3. Development of polygonal-surface version of ICRP reference phantoms: Lymphatic node modeling

    Energy Technology Data Exchange (ETDEWEB)

    Thang, Ngyen Tat; Yeom, Yeon Soo; Han, Min Cheol; Kim, Chan Hyeong [Hanyang University, Seoul (Korea, Republic of)

    2014-04-15

    Among radiosensitive organs/tissues considered in ICRP Publication 103, lymphatic nodes are many small size tissues and widely distributed in the ICRP reference phantoms. It is difficult to directly convert lymphatic nodes of ICRP reference voxel phantoms to polygonal surfaces. Furthermore, in the ICRP reference phantoms lymphatic nodes were manually drawn only in six lymphatic node regions and the reference number of lymphatic nodes reported in ICRP Publication 89 was not considered. To address aforementioned limitations, the present study developed a new lymphatic node modeling method for the polygonal-surface version of ICRP reference phantoms. By using the developed method, lymphatic nodes were modelled in the preliminary version of ICRP male polygonal-surface phantom. Then, lymphatic node dose values were calculated and compared with those of the ICRP reference male voxel phantom to validate the developed modeling method. The present study developed the new lymphatic node modeling method and successfully modeled lymphatic nodes in the preliminary version of the ICRP male polygonal-surface phantom. From the results, it was demonstrated that the developed modeling method can be used to model lymphatic nodes in polygonal-surface version of ICRP reference phantoms.

  4. Mathematical models for lymphatic filariasis transmission and control: Challenges and prospects

    Directory of Open Access Journals (Sweden)

    Kaliannagounder Krishnamoorthy

    2008-02-01

    Full Text Available Abstract Background Mathematical models developed for describing the dynamics of transmission, infection, disease and control of lymphatic filariasis (LF gained momentum following the 1997 World Health Assembly resolution and the launching of the Global Programme to Eliminate Lymphatic Filariasis (GPELF in 2000. Model applications could provide valuable inputs for making decisions while implementing large scale programmes. However these models need to be evaluated at different epidemiological settings for optimization and fine-tuning with new knowledge and understanding on infection/disease dynamics. Discussion EPIFIL and LYMFASIM are the two mathematical simulation models currently available for lymphatic filariasis transmission and control. Both models have been used for prediction and evaluation of control programmes under research settings. Their widespread application in evaluating large-scale elimination programmes warrants validation of assumptions governing the dynamics of infection and disease in different epidemiological settings. Furthermore, the predictive power of the models for decision support can be enhanced by generating knowledge on some important issues that pose challenges and incorporating such knowledge into the models. We highlight factors related to the efficacy of the drugs of choice, their mode of action, and the possibility that drug resistance may develop; the role of vector-parasite combinations; the magnitude of transmission thresholds; host-parasite interactions and their effects on the dynamics of infection and immunity; parasite biology, and progression to LF-associated disease. Summary The two mathematical models developed offer potential decision making tools for transmission and control of LF. In view of the goals of the GPELF, the predictive power of these models needs to be enhanced for their wide-spread application in large scale programmes. Assimilation and translation of new information into the models is

  5. cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric Lymphatic Vessels

    Directory of Open Access Journals (Sweden)

    Lukas Stanczuk

    2015-03-01

    Full Text Available Pathological lymphatic diseases mostly affect vessels in specific tissues, yet little is known about organ-specific regulation of the lymphatic vasculature. Here, we show that the vascular endothelial growth factor receptor 3 (VEGFR-3/p110α PI3-kinase signaling pathway is selectively required for the formation of mesenteric lymphatic vasculature. Using genetic lineage tracing, we demonstrate that part of the mesenteric lymphatic vasculature develops from cKit lineage cells of hemogenic endothelial origin through a process we define as lymphvasculogenesis. This is contrary to the current dogma that all mammalian lymphatic vessels form by sprouting from veins. Our results reveal vascular-bed-specific differences in the origin and mechanisms of vessel formation, which may critically underlie organ-specific manifestation of lymphatic dysfunction in disease. The progenitor cells identified in this study may be exploited to restore lymphatic function following cancer surgery, lymphedema, or tissue trauma.

  6. Receptor mechanisms of PAF mediated lymphatic constriction in the canine forelimb

    Directory of Open Access Journals (Sweden)

    D. E. Dobbins

    1992-01-01

    Full Text Available Platelet activating factor (PAF is a potent inflammatory lipid. In this study we assessed the ability of PAF to impact lymphatic vessel function by altering prenodal lymphatic resistance. Intralymphatic PAF (7.47 × 10−6, 7.47 × 10−5 and 7.47 × 10−4 M increased lymphatic perfusion pressure at the two highest infusion rates. PAF mediated lymphatic constriction was not altered by the intra-arterial infusion of phentolamine but was blocked by the intra-arterial infusion of the PAF receptor antagonist WEB 2170. These data indicate that in addition to PAF's effects on microvascular permeability, this agent may also impact the ability of the lymphatics to transport fluid through alterations in lymphatic smooth muscle tone. PAF mediated lymphatic constriction is not mediated by α-receptors but rather through PAF receptor mediated mechanism.

  7. Dynamic interactions of an intracellular Ca2+ clock and membrane ion channel clock underlie robust initiation and regulation of cardiac pacemaker function.

    Science.gov (United States)

    Maltsev, Victor A; Lakatta, Edward G

    2008-01-15

    For almost half a century it has been thought that the initiation of each heartbeat is driven by surface membrane voltage-gated ion channels (M clocks) within sinoatrial nodal cells. It has also been assumed that pacemaker cell automaticity is initiated at the maximum diastolic potential (MDP). Recent experimental evidence based on confocal cell imaging and supported by numerical modelling, however, shows that initiation of cardiac impulse is a more complex phenomenon and involves yet another clock that resides under the sarcolemma. This clock is the sarcoplasmic reticulum (SR): it generates spontaneous, but precisely timed, rhythmic, submembrane, local Ca(2+) releases (LCR) that appear not at the MDP but during the late, diastolic depolarization (DD). The Ca(2+) clock and M clock dynamically interact, defining a novel paradigm of robust cardiac pacemaker function and regulation. Rhythmic LCRs during the late DD activate inward Na(+)/Ca(2+) exchanger currents and ignite action potentials, which in turn induceCa(2+) transients and SR depletions, resetting the Ca(2+) clock. Both basal and reserve protein kinaseA-dependent phosphorylation of Ca(2+) cycling proteins control the speed and amplitude of SR Ca(2+) cycling to regulate the beating rate by strongly coupled Ca(2+) and M clocks.

  8. Cardiac Sarcoidosis.

    Science.gov (United States)

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo

    2015-12-01

    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  9. Field programmable gate array-based real-time optical Doppler tomography system for in vivo imaging of cardiac dynamics in the chick embryo

    DEFF Research Database (Denmark)

    Thrane, Lars; Larsen, Henning Engelbrecht; Norozi, Kambiz

    2009-01-01

    We demonstrate a field programmable gate-array-based real-time optical Doppler tomography system. A complex-valued bandpass filter is used for the first time in optical coherence tomography signal processing to create the analytic signal. This method simplifies the filter design, and allows...... efficient and compact implementation by combining the conversion to an analytic signal with a pulse shaping function without the need for extra resources as compared to the Hilbert transform method. The conversion of the analytic signal to amplitude and phase is done by use of the coordinate rotation...... digital computer (CORDIC) algorithm, which is an efficient algorithm that maps well to the field programmable gate array. Flow phantom experiments, and the use of this system for in vivo imaging of cardiac dynamics in the chick embryo, are presented. We demonstrate the visualization of blood flow...

  10. Assessment of normal left atrial appendage anatomy and function over gender and ages by dynamic cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Boucebci, Samy; Velasco, Stephane; Duboe, Pier-Olivier; Tasu, Jean-Pierre [University of Poitiers, University Hospital, Department of Radiology, Poitiers (France); Pambrun, Thomas [University of Poitiers, University Hospital, Department of Cardiology, Poitiers (France); Ingrand, Pierre [University of Poitiers, University Institute of Public Health, Poitiers (France)

    2016-05-15

    The aim of this study was to evaluate variations in anatomy and function according to age and gender using cardiac computed tomography (CT) in a large prospective cohort of healthy patients. The left atrial appendage (LAA) is considered the most frequent site of intracardiac thrombus formation. However, variations in normal in vivo anatomy and function according to age and gender remain largely unknown. Three-dimensional (3D) cardiac reconstructions of the LAA were performed from CT scans of 193 consecutive patients. Parameters measured included LAA number of lobes, anatomical position of the LAA tip, angulation measured between the proximal and distal portions, minimum (iVol{sub min}) and maximum (iVol{sub max}) volumes indexed to body surface area (BSA), and ejection fraction (LAAEF). Relationship with age was assessed for each parameter. We found that men had longer and wider LAAs. The iVol{sub min} and iVol{sub max} increased by 0.23 and 0.19 ml per decade, respectively, while LAAEF decreased by 2 % per decade in both sexes. Although LAA volumes increase, LAAEF decreases with age in both sexes. (orig.)

  11. Structural Dynamics of Troponin I during Ca2+-Activation of Cardiac Thin Filaments: A Multi-Site Förster Resonance Energy Transfer Study

    Science.gov (United States)

    Wang, Hui; Chalovich, Joseph M.; Marriott, Gerard

    2012-01-01

    A multi-site, steady-state Förster resonance energy transfer (FRET) approach was used to quantify Ca2+-induced changes in proximity between donor loci on human cardiac troponin I (cTnI), and acceptor loci on human cardiac tropomyosin (cTm) and F-actin within functional thin filaments. A fluorescent donor probe was introduced to unique and key cysteine residues on the C- and N-termini of cTnI. A FRET acceptor probe was introduced to one of three sites located on the inner or outer domain of F-actin, namely Cys-374 and the phalloidin-binding site on F-actin, and Cys-190 of cTm. Unlike earlier FRET analyses of protein dynamics within the thin filament, this study considered the effects of non-random distribution of dipoles for the donor and acceptor probes. The major conclusion drawn from this study is that Ca2+ and myosin S1-binding to the thin filament results in movement of the C-terminal domain of cTnI from the outer domain of F-actin towards the inner domain, which is associated with the myosin-binding. A hinge-linkage model is used to best-describe the finding of a Ca2+-induced movement of the C-terminus of cTnI with a stationary N-terminus. This dynamic model of the activation of the thin filament is discussed in the context of other structural and biochemical studies on normal and mutant cTnI found in hypertrophic cardiomyopathies. PMID:23227172

  12. Structural dynamics of troponin I during Ca2+-activation of cardiac thin filaments: a multi-site Forster resonance energy transfer study.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available A multi-site, steady-state Förster resonance energy transfer (FRET approach was used to quantify Ca(2+-induced changes in proximity between donor loci on human cardiac troponin I (cTnI, and acceptor loci on human cardiac tropomyosin (cTm and F-actin within functional thin filaments. A fluorescent donor probe was introduced to unique and key cysteine residues on the C- and N-termini of cTnI. A FRET acceptor probe was introduced to one of three sites located on the inner or outer domain of F-actin, namely Cys-374 and the phalloidin-binding site on F-actin, and Cys-190 of cTm. Unlike earlier FRET analyses of protein dynamics within the thin filament, this study considered the effects of non-random distribution of dipoles for the donor and acceptor probes. The major conclusion drawn from this study is that Ca(2+ and myosin S1-binding to the thin filament results in movement of the C-terminal domain of cTnI from the outer domain of F-actin towards the inner domain, which is associated with the myosin-binding. A hinge-linkage model is used to best-describe the finding of a Ca(2+-induced movement of the C-terminus of cTnI with a stationary N-terminus. This dynamic model of the activation of the thin filament is discussed in the context of other structural and biochemical studies on normal and mutant cTnI found in hypertrophic cardiomyopathies.

  13. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  14. LyP-1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics

    Energy Technology Data Exchange (ETDEWEB)

    Yan Zhiqiang; Zhan Changyou; Wen Ziyi; Feng Linglin; Wang Fei; Liu Yu; Yang Xiangkun; Dong Qing; Liu Min; Lu Weiyue, E-mail: wylu@shmu.edu.cn [Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203 (China)

    2011-10-14

    Lymphatic metastasis can be greatly promoted by metastases growth and lymphangiogenesis in lymph nodes (LNs). LyP-1, a cyclic peptide, is able to specifically bind with tumor cells and tumor lymphatics in metastatic LNs. This work aimed to use LyP-1-conjugated liposomes (L-LS) loaded with doxorubicin (DOX) (L-LS/DOX) to suppress lymphatic metastasis by inhibiting both metastases and tumor lymphatics in LNs. L-LS were prepared and exhibited sizes around 90 nm and spherical morphology as characterized by transmission electron microscopy. The in vitro cellular studies showed that LyP-1 modification obviously increased liposome uptake by MDA-MB-435 tumor cells and enhanced the cytotoxicity of liposomal DOX. A popliteal and iliac LN metastases model was successfully established by subcutaneous inoculation of tumor cells to nude mice. The immunofluorescence staining analysis indicated that LyP-1 modification enabled specific binding of liposome with tumor lymphatics and enhanced the destroying effect of liposomal DOX on tumor lymphatics. The in vivo fluorescence imaging and pharmacodynamic studies showed that LyP-1 modification increased liposome uptake by metastatic LNs and that L-LS/DOX significantly decreased metastatic LN growth and LN metastasis rate. These results suggested that L-LS/DOX were an effective delivery system for suppressing lymphatic metastasis by simultaneously inhibiting LN metastases and tumor lymphatics.

  15. Pediatric lymphatic malformations: evolving understanding and therapeutic options.

    Science.gov (United States)

    Defnet, Ann M; Bagrodia, Naina; Hernandez, Sonia L; Gwilliam, Natalie; Kandel, Jessica J

    2016-05-01

    Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, along with knowledge gained from clinical practice. A patient-centered approach, ideally provided by a multidisciplinary medical and surgical team, should guide timing and modality of treatment. Current treatment options include observation, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New medical and surgical therapies are emerging, and include sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management is to support and optimize these patients' quality of life. Researchers continue to study lymphatic malformations with the goal of increasing therapeutic options and developing effective clinical pathways for these complicated lesions.

  16. Imported lymphatic filariasis in an Indian immigrant to iran.

    Directory of Open Access Journals (Sweden)

    Eshrat Beigom Kia

    2014-03-01

    Full Text Available Lymphatic filariasis (LF, a nematode disease transmitted by arthropod vectors, is repeatedly reported in immigrant population. This disease is not endemic in Iran; however, different species of mosquitoes, capable of transmission of parasite microfilaria, are distributed in the country. Hereby, incidental detection of an imported case of LF due to Wuchereria bancrofti in an Indian worker in Iran is reported. Identification of the case was performed based on morphological and morphometrical characteristics of microfilaria and PCR sequencing.

  17. Follicular thyroid carcinoma invades venous rather than lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Liu Yulin

    2010-01-01

    Full Text Available Abstract Follicular thyroid carcinoma (FTC tends to metastasize to remote organs rather than local lymph nodes. Separation of FTC from follicular thyroid adenoma (FTA relies on detection of vascular and/or capsular invasion. We investigated which vascular markers, CD31, CD34 and D2-40 (lymphatic vessel marker, can best evaluate vascular invasion and why FTC tends to metastasize via blood stream to remote organs. Thirty two FTCs and 34 FTAs were retrieved for evaluation. The average age of patients with FTA was 8 years younger than FTC (p = 0.02. The female to male ratio for follicular neoplasm was 25:8. The average size of FTC was larger than FTA (p = 0.003. Fourteen of 32 (44% FTCs showed venous invasion and none showed lymphatic invasion, with positive CD31 and CD34 staining and negative D2-40 staining of the involved vessels. The average number of involved vessels was 0.88 ± 1.29 with a range from 0 to 5, and the average diameter of involved vessels was 0.068 ± 0.027 mm. None of the 34 FTAs showed vascular invasion. CD31 staining demonstrated more specific staining of vascular endothelial cells than CD34, with less background staining. We recommended using CD31 rather than CD34 and/or D2-40 in confirming/excluding vascular invasion in difficult cases. All identified FTCs with vascular invasions showed involvement of venous channels, rather than lymphatic spaces, suggesting that FTCs prefer to metastasize via veins to distant organs, instead of lymphatic vessels to local lymph nodes, which correlates with previous clinical observations.

  18. Continuous real-time photoacoustic demodulation via field programmable gate array for dynamic imaging of zebrafish cardiac cycle.

    Science.gov (United States)

    Mattison, Scott P; Shelton, Ryan L; Maxson, Ryan T; Applegate, Brian E

    2013-01-01

    A four dimensional data set of the cardiac cycle of a zebrafish embryo was acquired using postacquisition synchronization of real time photoacoustic b-scans. Utilizing an off-axis photoacoustic microscopy (OA-PAM) setup, we have expanded upon our previous work with OA-PAM to develop a system that can sustain 100 kHz line rates while demodulating the bipolar photoacoustic signal in real-time. Real-time processing was accomplished by quadrature demodulation on a Field Programmable Gate Array (FPGA) in line with the signal digitizer. Simulated data acquisition verified the system is capable of real-time processing up to a line rate of 1 MHz. Galvanometer-scanning of the excitation laser inside the focus of the ultrasonic transducer enables real data acquisition of a 200 by 200 by 200 pixel, volumetric data set across a 2 millimeter field of view at a rate of 2.5 Hz.

  19. Effect of hepatoma H22 on lymphatic endothelium in vitro

    Institute of Scientific and Technical Information of China (English)

    Hua Yu; Hong-Zhi Zhou; Chun-Mei Wang; Xiao-Ming Gu; Bo-Rong Pan

    2004-01-01

    AIM: To determine the effect of metastatic hepatoma cells on lymphangioma-derived endothelium, and to establish in vitro model systems for assessing metastasis-related response of lymphatic endothelium.METHODS: Benign lymphangioma, induced by intraperitonea linjection of the incomplete Freund's adjuvant in BALB/c mice, was embedded in fibrin gel or digested and then cultured in the conditioned medium derived from hepatoma H22. Light and electron microscopy, and the transwell migration assay were used to determine the effect of H22 on tissue or cell culture. Expressions of Flt-4, c-Fos, proliferating cell nuclear antigen (PCNA), and inducible nitric oxide synthase (iNOS) in cultured cells, and content of nitric oxide in culture medium were also examined.RESULTS: The embedded lymphangioma pieces gave rise to array of capillaries, while separated cells from lymphangioma grew to a cobblestone-like monolayer. H22 activated growth and migration of the capillaries and cells, induced expressions of Flt-4, c-Fos, PCNA and iNOS in cultured cells, and significantly increased the content of NO in the culture medium.CONCLUSION: Lymphangioma-derived cells keep the differentiated phenotypes of lymphatic endothelium, and the models established in this study are feasible for in vitro study of metastasis-related response of lymphatic endothelium.

  20. Fluorescein sodium fluorescence microscope-integrated lymphangiography for lymphatic supermicrosurgery.

    Science.gov (United States)

    Ayestaray, Benoit; Bekara, Farid

    2015-07-01

    Microscope-integrated lymphangiography is a useful method in the field of lymphatic supermicrosurgery. Fluorescence based on indocyanine green (ICG) is the most commonly used. Fluorescein sodium is a fluorescent tracer used for retinal and neurosurgical angiography but not yet for lymphatic supermicrosurgery. In this report, we present a case in which the fluorescein sodium fluorescence microscope-integrated lymphangiography was used for assessment of lymphatic drainage pathway and patency in a patient treated for secondary lymphedema by lymphaticovenular anastomoses. Fluorescein sodium fluorescence microscope-integrated lymphangiography was evaluated in a 67-year-old female presented for a Campisi clinical stage IV lymphedema of the upper limb. Transcutaneous guidance and vascular fluorescence were assessed. A comparison with ICG fluorescence was made intraoperatively. Two lymphaticovenular anastomoses were performed and their patency were checked by lymphangiography. Transcutaneous signal was found higher with fluorescein sodium fluorescence. Intraluminal visualization was possible with fluorescein sodium coloration during lymphaticovenular anastomoses. No adverse reaction occurred. The circumferential differential reduction rate of affected limb was 8.1% 3 months after lymphaticovenular anastomoses. The use of fluorescence microscope-integrated lymphangiography with fluorescein sodium may be superior to ICG fluorescence in assistance of lymphaticovenular anastomoses. © 2015 Wiley Periodicals, Inc.

  1. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

    Science.gov (United States)

    Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

    2016-01-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

  2. Scarpa Fascia Preservation in Abdominoplasty: Does It Preserve the Lymphatics?

    Science.gov (United States)

    Tourani, Saam S; Taylor, G Ian; Ashton, Mark W

    2015-08-01

    The course of the cutaneous lymphatic collectors of the abdominal wall in relation to the Scarpa fascia is unclear in the literature. Preserving the Scarpa fascia in the lower abdomen to reduce the seroma rate following abdominoplasty has been suggested based on the assumption that the lower abdominal lymphatics run deep to this layer along their entire course. Using the previously described technique, the superficial lymphatic drainage of eight hemiabdomen specimens from four fresh human cadavers was investigated. The upper and lower abdominal collectors originated at the umbilical and midline watershed areas in a subdermal plane by the union of precollectors draining the dermis. In the lower abdomen, the depth of the collectors gradually increased in the subcutaneous fat as they coursed toward the groin. They eventually pierced the Scarpa fascia before draining into the superficial inguinal nodes located deep to this layer. The transition from the supra- to the infra-Scarpa fascia plane occurred within 2 to 3 cm of the inguinal ligament in 95 percent of the collectors. In the four cadavers studied, preserving the Scarpa fascia during abdominoplasty would not preserve the lower abdominal collectors.

  3. A critical role for lymphatic endothelial heparan sulfate in lymph node metastasis

    Directory of Open Access Journals (Sweden)

    Srinivasan R Sathish

    2010-12-01

    Full Text Available Abstract Background Lymph node metastasis constitutes a key event in tumor progression. The molecular control of this process is poorly understood. Heparan sulfate is a linear polysaccharide consisting of unique sulfate-modified disaccharide repeats that allow the glycan to bind a variety of proteins, including chemokines. While some chemokines may drive lymphatic trafficking of tumor cells, the functional and genetic importance of heparan sulfate as a possible mediator of chemokine actions in lymphatic metastasis has not been reported. Results We applied a loss-of-function genetic approach employing lymphatic endothelial conditional mutations in heparan sulfate biosynthesis to study the effects on tumor-lymphatic trafficking and lymph node metastasis. Lymphatic endothelial deficiency in N-deacetylase/N-sulfotransferase-1 (Ndst1, a key enzyme involved in sulfating nascent heparan sulfate chains, resulted in altered lymph node metastasis in tumor-bearing gene targeted mice. This occurred in mice harboring either a pan-endothelial Ndst1 mutation or an inducible lymphatic-endothelial specific mutation in Ndst1. In addition to a marked reduction in tumor metastases to the regional lymph nodes in mutant mice, specific immuno-localization of CCL21, a heparin-binding chemokine known to regulate leukocyte and possibly tumor-cell traffic, showed a marked reduction in its ability to associate with tumor cells in mutant lymph nodes. In vitro modified chemotaxis studies targeting heparan sulfate biosynthesis in lymphatic endothelial cells revealed that heparan sulfate secreted by lymphatic endothelium is required for CCL21-dependent directional migration of murine as well as human lung carcinoma cells toward the targeted lymphatic endothelium. Lymphatic heparan sulfate was also required for binding of CCL21 to its receptor CCR7 on tumor cells as well as the activation of migration signaling pathways in tumor cells exposed to lymphatic conditioned medium

  4. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations

    Directory of Open Access Journals (Sweden)

    Ali Khan A

    2013-07-01

    Full Text Available Arshad Ali Khan, Jahanzeb Mudassir, Noratiqah Mohtar, Yusrida Darwis School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia Abstract: The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects

  5. A brief perspective on the diverging theories of lymphatic targeting with colloids.

    Science.gov (United States)

    Siram, Karthik; Marslin, Gregory; Raghavan, Chellan Vijaya; Balakumar, Krishnamoorthy; Rahman, Habibur; Franklin, Gregory

    2016-01-01

    For targeted delivery of colloids to the lymphatic system, the colloids should efficiently reach and remain in the lymphatics for a considerable period of time. As per the current knowledge, diffusion and phagocytosis are the two mechanisms through which colloids reach the lymphatic system. Several parameters including particle size and charge have been shown to affect the direct uptake of colloids by the lymphatic system. Although many researchers attached ligands on the surface of colloids to promote phagocytosis-mediated lymphatic delivery, another school of thought suggests avoidance of phagocytosis by use of carriers like polyethylene glycol (PEG)ylated colloids to impart stealth attributes and evade phagocytosis. In this perspective, we weigh up the paradoxical theories and approaches available in the literature to draw conclusions on the conditions favorable for achieving efficient lymphatic targeting of colloids.

  6. Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development.

    Science.gov (United States)

    van Lessen, Max; Shibata-Germanos, Shannon; van Impel, Andreas; Hawkins, Thomas A; Rihel, Jason; Schulte-Merker, Stefan

    2017-05-12

    The lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and found loosely connected endothelial cells with lymphatic molecular signature covering parts of the brain without forming endothelial tubular structures. These brain lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose macromolecules in a selective manner, which can be blocked by injection of mannose receptor ligands. This first report on brain lymphatic endothelial cells in a vertebrate embryo identifies cells with unique features, including the uptake of macromolecules at a single cell level. Future studies will address whether this represents an uptake mechanism that is conserved in mammals and how these cells affect functions of the embryonic and adult brain.

  7. [Advances in the research of the peritoneal lymphatic stomata in human].

    Science.gov (United States)

    Li, H; Li, J

    2000-12-01

    Peritoneal lymphatic stomata are small openings of the subperitoneal lymphatic vessels on the free surface of the mesothelium. The peritoneal cavity is connected with lymphatic system via these small openings which are considered to be the main passage-way that can absorb matter from the peritoneal cavity. The lymphatic stomata are claimed to be involved in many clinic procedures, such as ascites elimination; ultrafiltration failure on the continuous ambulatory peritoneal dialysis; metastasis of tumor cells from the peritoneal cavity, and so on. It was reported that the cellular factor-NO(i.e. endothelium-derived relaxing factor, EDRF) can enhance the patency of the stomata and lymphatic absorption of the stomata by stimulating guanylate way, then increasing the concentration of the cGMP, decreasing the concentration of the [Ca2+] and as a result diastole the lymphatic stomata. Some traditional Chinese medicines, which can enhance absorption of ascites, have a regulative function on the stomata by enhancing the NO concentration.

  8. Steady-state solutions of cell volume in a cardiac myocyte model elaborated for membrane excitation, ion homeostasis and Ca2+ dynamics.

    Science.gov (United States)

    Cha, Chae Young; Noma, Akinori

    2012-08-21

    The cell volume continuously changes in response to varying physiological conditions, and mechanisms underlying volume regulation have been investigated in both experimental and theoretical studies. Here, general formulations concerning cell volume change are presented in the context of developing a comprehensive cell model which takes Ca(2+) dynamics into account. Explicit formulas for charge conservation and steady-state volumes of the cytosol and endoplasmic reticulum (ER) are derived in terms of membrane potential, amount of ions, Ca(2+)-bound buffer molecules, and initial cellular conditions. The formulations were applied to a ventricular myocyte model which has plasma-membrane Ca(2+) currents with dynamic gating mechanisms, Ca(2+)-buffering reactions with diffusive and non-diffusive buffer proteins, and Ca(2+) uptake into or release from the sarcoplasmic reticulum (SR) accompanied by compensatory cationic or anionic currents through the SR membrane. Time-dependent volume changes in cardiac myocytes induced by varying extracellular osmolarity or by action potential generation were successfully simulated by the novel formulations. Through application of bifurcation analysis, the existence and uniqueness of steady-state solutions of the cell volume were validated, and contributions of individual ion channels and transporters to the steady-state volume were systematically analyzed. The new formulas are consistent with previous fundamental theory derived from simple models of minimum compositions. The new formulations may be useful for examination of the relationship between cell function and volume change in other cell types.

  9. Cross-bridge cycling gives rise to spatiotemporal heterogeneity of dynamic subcellular mechanics in cardiac myocytes probed with atomic force microscopy.

    Science.gov (United States)

    Azeloglu, Evren U; Costa, Kevin D

    2010-03-01

    To study how the dynamic subcellular mechanical properties of the heart relate to the fundamental underlying process of actin-myosin cross-bridge cycling, we developed a novel atomic force microscope elastography technique for mapping spatiotemporal stiffness of isolated, spontaneously beating neonatal rat cardiomyocytes. Cells were indented repeatedly at a rate close but unequal to their contractile frequency. The resultant changes in pointwise apparent elastic modulus cycled at a predictable envelope frequency between a systolic value of 26.2 +/- 5.1 kPa and a diastolic value of 7.8 +/- 4.1 kPa at a representative depth of 400 nm. In cells probed along their major axis, spatiotemporal changes in systolic stiffness displayed a heterogeneous pattern, reflecting the banded sarcomeric structure of underlying myofibrils. Treatment with blebbistatin eliminated contractile activity and resulted in a uniform apparent modulus of 6.5 +/- 4.8 kPa. This study represents the first quantitative dynamic mechanical mapping of beating cardiomyocytes. The technique provides a means of probing the micromechanical effects of disease processes and pharmacological treatments on beating cardiomyocytes, providing new insights and relating subcellular cardiac structure and function.

  10. Evaluation of lymphatic regeneration in rat incisional wound healing and its use in wound age estimation

    Directory of Open Access Journals (Sweden)

    Nevine M.F. El Deeb

    2015-03-01

    Conclusion: Lymphatic elements appear transiently in the wound edge, concurrent with the appearance of blood vessels but regress earlier. Identification of lymphatic vascular channels in the region of the wound may help to estimate the wound age in the early days after the injury. At later time points in the regeneration process, it may help to recognize the injured area, being the area where the dermis and subcutaneous tissue are devoid of lymphatics.

  11. Effects of pacing site and stimulation history on alternans dynamics and the development of complex spatiotemporal patterns in cardiac tissue

    Directory of Open Access Journals (Sweden)

    Alessio eGizzi

    2013-04-01

    Full Text Available Alternans of action potential duration has been associated with T-wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i Alternans predominantly develops first on the endocardium. (ii The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicate some underlying predisposition to chaos and can help the design of new drugs and devices controlling and preventing arrhythmic events.

  12. Method for the quantitative measurement of collecting lymphatic vessel contraction in mice

    Directory of Open Access Journals (Sweden)

    Shan Liao

    2014-07-01

    Full Text Available Collecting lymphatic vessels are critical for the transport of lymph and its cellular contents to lymph nodes for both immune surveillance and the maintenance of tissue-fluid balance. Collecting lymphatic vessels drive lymph flow by autonomous contraction of smooth muscle cells that cover these vessels. Here we describe methods using intravital microscopy to image and quantify collecting lymphatic vessel contraction in mice. Our methods allow for the measurement of the strength of lymphatic contraction of an individual lymphangion in a mouse, which has not yet been demonstrated using other published methods. The ability to study murine collecting lymphatic vessel contraction—using the methods described here or other recently published techniques—allows the field to dissect the molecular mechanisms controlling lymphatic pumping under normal and pathological conditions using the wide variety of molecular tools and genetic models available in the mouse. We have used our methods to study lymphatic contraction in physiological and inflammatory conditions. The methods described here will facilitate the further study of lymphatic function in other pathological conditions that feature lymphatic complications.

  13. Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation

    Science.gov (United States)

    Arokiasamy, Samantha; Zakian, Christian; Dilliway, Jessica; Wang, Wen; Nourshargh, Sussan; Voisin, Mathieu-Benoit

    2017-01-01

    Neutrophils are recognised to play a pivotal role at the interface between innate and acquired immunities following their recruitment to inflamed tissues and lymphoid organs. While neutrophil trafficking through blood vessels has been extensively studied, the molecular mechanisms regulating their migration into the lymphatic system are still poorly understood. Here, we have analysed neutrophil-lymphatic vessel interactions in real time and in vivo using intravital confocal microscopy applied to inflamed cremaster muscles. We show that antigen sensitisation of the tissues induces a rapid but transient entry of tissue-infiltrated neutrophils into lymphatic vessels and subsequent crawling along the luminal side of the lymphatic endothelium. Interestingly, using mice deficient in both TNF receptors p55 and p75, chimeric animals and anti-TNFα antibody blockade we demonstrate that tissue-release of TNFα governs both neutrophil migration through the lymphatic endothelium and luminal crawling. Mechanistically, we show that TNFα primes directly the neutrophils to enter the lymphatic vessels in a strictly CCR7-dependent manner; and induces ICAM-1 up-regulation on lymphatic vessels, allowing neutrophils to crawl along the lumen of the lymphatic endothelium in an ICAM-1/MAC-1-dependent manner. Collectively, our findings demonstrate a new role for TNFα as a key regulator of neutrophil trafficking into and within lymphatic system in vivo. PMID:28287124

  14. Bioengineering dermo-epidermal skin grafts with blood and lymphatic capillaries.

    Science.gov (United States)

    Marino, Daniela; Luginbühl, Joachim; Scola, Simonetta; Meuli, Martin; Reichmann, Ernst

    2014-01-29

    The first bioengineered, autologous, dermo-epidermal skin grafts are presently undergoing clinical trials; hence, it is reasonable to envisage the next clinical step at the forefront of plastic and burn surgery, which is the generation of autologous skin grafts that contain vascular plexuses, preformed in vitro. As the importance of the blood, and particularly the lymphatic vascular system, is increasingly recognized, it is attractive to engineer both human blood and lymphatic vessels in one tissue or organ graft. We show here that functional lymphatic capillaries can be generated using three-dimensional hydrogels. Like normal lymphatics, these capillaries branch, form lumen, and take up fluid in vitro and in vivo after transplantation onto immunocompromised rodents. Formation of lymphatic capillaries could be modulated by both lymphangiogenic and anti-lymphangiogenic stimuli, demonstrating the potential usefulness of this system for in vitro testing. Blood and lymphatic endothelial cells never intermixed during vessel development, nor did blood and lymphatic capillaries anastomose under the described circumstances. After transplantation of the engineered grafts, the human lymphatic capillaries anastomosed to the nude rat's lymphatic plexus and supported fluid drainage. Successful preclinical results suggest that these skin grafts could be applied on patients suffering from severe skin defects.

  15. A New Technique to Map the Lymphatic Distribution and Alignment of the Penis.

    Science.gov (United States)

    Long, Liu Yan; Qiang, Pan Fu; Ling, Tao; Wei, Zhang Yan; Long, Zhang Yu; Shan, Meng; Rong, Li Shi; Li, Li Hong

    2015-08-01

    The present study was to examine the distribution of lymphatic vessels in the penis of normal adult males, which could provide an anatomical basis for improvement of incisions in penile lengthening surgery, and may also help to prevent postoperative refractory edema. Thirteen normal adult male volunteers were recruited for this study. Contrast agent was injected subcutaneously in the foreskin of the penis, and after two minutes magnetic resonance lymphangiography (MRL) was performed. The acquired magnetic resonance images were analyzed to determine the changes in the number and diameter of lymphatic vessels in different parts of the penis. Maximum intensity projections (MIP) and materializes interactive medical image control system (MIMICS) were applied to analyze the overall distribution of lymphatic vessels in the penis. Magnetic resonance imaging (MRI) showed that the lymphatic vessels were in conspicuous contrast with surrounding tissues and could be clearly identified. Penile lymphatic vessels were clearly visible in the root of the penis. At the junction of the penis and the abdominal wall, all lymphatic vessels were found to be concentrated in the dorsal part of the penis. MIP two-dimensional reconstruction showed that the overall distribution of relatively large lymphatic vessels in the dorsal and ventral parts of the penis could be seen clearly on bilateral 45° position, but not inside the abdominal wall because some of lymphatic vessels were overlapped by other tissues in the abdomen. MIMICS three-dimensional reconstruction was able to reveal the overall spatial distribution of lymphatic vessels in the penis from any angle. The reconstruction results showed that there were 1-2 main lymphatic vessels on the root of dorsal penis, which coursed along the cavernous to the first physiological curvature of the penis. Lymphatic vessels merged on both sides of the ventral penis. At the root of the penis, lymphatic vessels gradually coursed to the dorsal surface

  16. The Lymphatic Anatomy of the Lower Eyelid and Conjunctiva and Correlation with Postoperative Chemosis and Edema.

    Science.gov (United States)

    Shoukath, Sajna; Taylor, G Ian; Mendelson, Bryan C; Corlett, Russell J; Shayan, Ramin; Tourani, Saam S; Ashton, Mark W

    2017-03-01

    There are minimal data in the literature regarding the lymphatic drainage of the conjunctiva and lower eyelid and the relationship with postoperative chemosis and edema. Injection, microdissection, and histologic and radiologic studies were conducted on 12 hemifacial fresh cadaver specimens. Indocyanine green lymphography was conducted in five volunteers. Histology identified lymphatic vessels superficial and deep to the orbicularis oculi. Cadaveric dissection, injection, and radiographic studies identified interconnecting superficial and deep facial lymphatic systems and a conjunctival lymphatic network draining through the tarsal plate to the deep lymphatic system. The superficial lymphatic collectors traveled in subcutaneous fat within the lateral orbital and nasolabial fat compartments. The lateral deep lymphatic collectors traveled beneath orbicularis oculi, then through the superficial orbicularis retaining ligament, and into the sub-orbicularis oculi fat in the roof of the prezygomatic space. These vessels descended to preperiosteal fat at the level of zygomaticocutaneous ligaments to travel adjacent to the facial nerve into preauricular nodes. Indocyanine green lymphography identified correlating draining pathways laterally to the parotid nodes and medially to submandibular nodes. The authors have found that the lower eyelid and conjunctiva are drained by interconnecting superficial and deep lymphatic systems of the face. The superficial system is vulnerable to damage in incisions and dissection in the infraorbital area. The deep system is vulnerable to damage in dissection around the orbicularis retaining ligament and the zygomaticocutaneous ligaments. The authors suggest that concurrent damage to both the superficial and deep lymphatic systems, especially laterally, may be responsible for postoperative chemosis and edema.

  17. [Lymphatic system of the tongue and its role in glositis of odontogenic origin].

    Science.gov (United States)

    Chkhikvishvili, M Dzh

    2005-02-01

    In aged persons reduction of diameter of tongue lymphatic capillaries precedes thinning of the Kaarl net. In the process of tongue inflammation, lymphogenic way of inclusion in 6|6 and 8|8 teeth lower area should be stuck out with existence of alleged "Integration Centers". Lymphatic knots and lymphatic ducts are in prevailed placed in corresponding tissues of lower-chin and lower teeth. Lymphatic-muscular system and its anatomical links and age-related changeability raise the special interest during odontogenic infections with tongue inflammation.

  18. Implementation of a phase detection algorithm for dynamic cardiac computed tomography analysis based on time dependent contrast agent distribution.

    Directory of Open Access Journals (Sweden)

    Carsten Kendziorra

    Full Text Available This paper presents a phase detection algorithm for four-dimensional (4D cardiac computed tomography (CT analysis. The algorithm detects a phase, i.e. a specific three-dimensional (3D image out of several time-distributed 3D images, with high contrast in the left ventricle and low contrast in the right ventricle. The purpose is to use the automatically detected phase in an existing algorithm that automatically aligns the images along the heart axis. Decision making is based on the contrast agent distribution over time. It was implemented in KardioPerfusion--a software framework currently being developed for 4D CT myocardial perfusion analysis. Agreement of the phase detection algorithm with two reference readers was 97% (95% CI: 82-100%. Mean duration for detection was 0.020 s (95% CI: 0.018-0.022 s, which was 800 times less than the readers needed (16±7 s, p<03001. Thus, this algorithm is an accurate and fast tool that can improve work flow of clinical examinations.

  19. Cardiac cameras.

    Science.gov (United States)

    Travin, Mark I

    2011-05-01

    Cardiac imaging with radiotracers plays an important role in patient evaluation, and the development of suitable imaging instruments has been crucial. While initially performed with the rectilinear scanner that slowly transmitted, in a row-by-row fashion, cardiac count distributions onto various printing media, the Anger scintillation camera allowed electronic determination of tracer energies and of the distribution of radioactive counts in 2D space. Increased sophistication of cardiac cameras and development of powerful computers to analyze, display, and quantify data has been essential to making radionuclide cardiac imaging a key component of the cardiac work-up. Newer processing algorithms and solid state cameras, fundamentally different from the Anger camera, show promise to provide higher counting efficiency and resolution, leading to better image quality, more patient comfort and potentially lower radiation exposure. While the focus has been on myocardial perfusion imaging with single-photon emission computed tomography, increased use of positron emission tomography is broadening the field to include molecular imaging of the myocardium and of the coronary vasculature. Further advances may require integrating cardiac nuclear cameras with other imaging devices, ie, hybrid imaging cameras. The goal is to image the heart and its physiological processes as accurately as possible, to prevent and cure disease processes.

  20. Differentiation of myocardial ischemia and infarction assessed by dynamic computed tomography perfusion imaging and comparison with cardiac magnetic resonance and single-photon emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Yuki; Kido, Teruhito; Kurata, Akira; Miyagawa, Masao; Mochizuki, Teruhito [Ehime University Graduate School of Medicine, Department of Radiology, Toon, Ehime (Japan); Uetani, Teruyoshi; Kono, Tamami; Ogimoto, Akiyoshi [Ehime University Graduate School of Medicine, Department of Cardiology, Pulmonology, Hypertension and Nephrology, Toon, Ehime (Japan); Soma, Tsutomu [FUJIFILM RI Pharma Co., Ltd., QMS Group, Quality Assurance Department, Tokyo (Japan); Graduate School of Medicine, University of Tokyo, Department of Radiology, Tokyo (Japan); Murase, Kenya [Osaka University Graduate School of Medicine, Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Osaka (Japan); Iwaki, Hirotaka [Ehime University Graduate School of Medicine, Center for Clinical Research Data and Biostatistics, Toon, Ehime (Japan)

    2016-11-15

    To evaluate the feasibility of myocardial blood flow (MBF) by computed tomography from dynamic CT perfusion (CTP) for detecting myocardial ischemia and infarction assessed by cardiac magnetic resonance (CMR) or single-photon emission computed tomography (SPECT). Fifty-three patients who underwent stress dynamic CTP and either SPECT (n = 25) or CMR (n = 28) were retrospectively selected. Normal and abnormal perfused myocardium (ischemia/infarction) were assessed by SPECT/CMR using 16-segment model. Sensitivity and specificity of CT-MBF (mL/g/min) for detecting the ischemic/infarction and severe infarction were assessed. The abnormal perfused myocardium and severe infarction were seen in SPECT (n = 90 and n = 19 of 400 segments) and CMR (n = 223 and n = 36 of 448 segments). For detecting the abnormal perfused myocardium, sensitivity and specificity were 80 % (95 %CI, 71-90) and 86 % (95 %CI, 76-91) in SPECT (cut-off MBF, 1.23), and 82 % (95 %CI, 76-88) and 87 % (95 %CI, 80-92) in CMR (cut-off MBF, 1.25). For detecting severe infarction, sensitivity and specificity were 95 % (95 %CI, 52-100) and 72 % (95 %CI, 53-91) in SPECT (cut-off MBF, 0.92), and 78 % (95 %CI, 67-97) and 80 % (95 %CI, 58-86) in CMR (cut-off MBF, 0.98), respectively. Dynamic CTP has a potential to detect abnormal perfused myocardium and severe infarction assessed by SPECT/CMR using comparable cut-off MBF. (orig.)

  1. Cardiac resynchronization therapy by multipoint pacing improves response of left ventricular mechanics and fluid dynamics: a three-dimensional and particle image velocimetry echo study.

    Science.gov (United States)

    Siciliano, Mariachiara; Migliore, Federico; Badano, Luigi; Bertaglia, Emanuele; Pedrizzetti, Gianni; Cavedon, Stefano; Zorzi, Alessandro; Corrado, Domenico; Iliceto, Sabino; Muraru, Denisa

    2016-12-26

    To characterize the effect of multipoint pacing (MPP) compared to biventricular pacing (BiV) on left ventricle (LV) mechanics and intraventricular fluid dynamics by three-dimensional echocardiography (3DE) and echocardiographic particle imaging velocimetry (Echo-PIV). In 11 consecutive patients [8 men; median age 65 years (57-75)] receiving cardiac resynchronization therapy (CRT) with a quadripolar LV lead (Quartet,St.Jude Medical,Inc.), 3DE and Echo-PIV data were collected for each pacing configuration (CRT-OFF, BiV, and MPP) at follow-up after 6 months. 3DE data included LV volumes, LV ejection fraction (LVEF), strain, and systolic dyssynchrony index (SDI). Echo-PIV was used to evaluate the directional distribution of global blood flow momentum, ranging from zero, when flow force is predominantly along the base-apex direction, up to 90° when it becomes transversal. MPP resulted in significant reduction in end-diastolic and end-systolic volumes compared with both CRT-OFF (P = 0.02; P = 0.008, respectively) and BiV (P = 0.04; P = 0.03, respectively). LVEF and cardiac output were significant superior in MPP compared with CRT-OFF, but similar between MPP and BiV. Statistical significant differences when comparing global longitudinal and circumferential strain and SDI with MPP vs. CRT-OFF were observed (P = 0.008; P = 0.008; P = 0.01, respectively). There was also a trend towards improvement in strain between BiV and MPP that did not reach statistical significance. MPP reflected into a significant reduction of the deviation of global blood flow momentum compared with both CRT-OFF and BiV (P = 0.002) indicating a systematic increase of longitudinal alignment from the base-apex orientation of the haemodynamic forces. These preliminary results suggest that MPP resulted in significant improvement of LV mechanics and fluid dynamics compared with BiV. However, larger studies are needed to confirm this hypothesis. © Crown copyright 2016.

  2. Two rare human mitofusin 2 mutations alter mitochondrial dynamics and induce retinal and cardiac pathology in Drosophila.

    Directory of Open Access Journals (Sweden)

    William H Eschenbacher

    Full Text Available Mitochondrial fusion is essential to organelle homeostasis and organ health. Inexplicably, loss of function mutations of mitofusin 2 (Mfn2 specifically affect neurological tissue, causing Charcot Marie Tooth syndrome (CMT and atypical optic atrophy. As CMT-linked Mfn2 mutations are predominantly within the GTPase domain, we postulated that Mfn2 mutations in other functional domains might affect non-neurological tissues. Here, we defined in vitro and in vivo consequences of rare human mutations in the poorly characterized Mfn2 HR1 domain. Human exome sequencing data identified 4 rare non-synonymous Mfn2 HR1 domain mutations, two bioinformatically predicted as damaging. Recombinant expression of these (Mfn2 M393I and R400Q in Mfn2-null murine embryonic fibroblasts (MEFs revealed incomplete rescue of characteristic mitochondrial fragmentation, compared to wild-type human Mfn2 (hMfn2; Mfn2 400Q uniquely induced mitochondrial fragmentation in normal MEFs. To compare Mfn2 mutation effects in neurological and non-neurological tissues in vivo, hMfn2 and the two mutants were expressed in Drosophila eyes or heart tubes made deficient in endogenous fly mitofusin (dMfn through organ-specific RNAi expression. The two mutants induced similar Drosophila eye phenotypes: small eyes and an inability to rescue the eye pathology induced by suppression of dMfn. In contrast, Mfn2 400Q induced more severe cardiomyocyte mitochondrial fragmentation and cardiac phenotypes than Mfn2 393I, including heart tube dilation, depressed fractional shortening, and progressively impaired negative geotaxis. These data reveal a central functional role for Mfn2 HR1 domains, describe organ-specific effects of two Mfn2 HR1 mutations, and strongly support prospective studies of Mfn2 400Q in heritable human heart disease of unknown genetic etiology.

  3. Digging deeper into lymphatic vessel formation in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Thiry Marc

    2011-06-01

    Full Text Available Abstract Background Abnormal lymphatic vessel formation (lymphangiogenesis is associated with different pathologies such as cancer, lymphedema, psoriasis and graft rejection. Lymphatic vasculature displays distinctive features than blood vasculature, and mechanisms underlying the formation of new lymphatic vessels during physiological and pathological processes are still poorly documented. Most studies on lymphatic vessel formation are focused on organism development rather than lymphangiogenic events occurring in adults. We have here studied lymphatic vessel formation in two in vivo models of pathological lymphangiogenesis (corneal assay and lymphangioma. These data have been confronted to those generated in the recently set up in vitro model of lymphatic ring assay. Ultrastructural analyses through Transmission Electron Microscopy (TEM were performed to investigate tube morphogenesis, an important differentiating process observed during endothelial cell organization into capillary structures. Results In both in vivo models (lymphangiogenic corneal assay and lymphangioma, migrating lymphatic endothelial cells extended long processes exploring the neighboring environment and organized into cord-like structures. Signs of intense extracellular matrix remodeling were observed extracellularly and inside cytoplasmic vacuoles. The formation of intercellular spaces between endothelial cells led to tube formation. Proliferating lymphatic endothelial cells were detected both at the tips of sprouting capillaries and inside extending sprouts. The different steps of lymphangiogenesis observed in vivo are fully recapitulated in vitro, in the lymphatic ring assay and include: (1 endothelial cell alignment in cord like structure, (2 intracellular vacuole formation and (3 matrix degradation. Conclusions In this study, we are providing evidence for lymphatic vessel formation through tunneling relying on extensive matrix remodeling, migration and alignment of

  4. Spatio-temporal changes of lymphatic contractility and drainage patterns following lymphadenectomy in mice.

    Directory of Open Access Journals (Sweden)

    Sunkuk Kwon

    Full Text Available OBJECTIVE: To investigate the redirection of lymphatic drainage post-lymphadenectomy using non-invasive near-infrared fluorescence (NIRF imaging, and to subsequently assess impact on metastasis. BACKGROUND: Cancer-acquired lymphedema arises from dysfunctional fluid transport after lymphadenectomy performed for staging and to disrupt drainage pathways for regional control of disease. However, little is known about the normal regenerative processes of the lymphatics in response to lymphadenectomy and how these responses can be accelerated, delayed, or can impact metastasis. METHODS: Changes in lymphatic "pumping" function and drainage patterns were non-invasively and longitudinally imaged using NIRF lymphatic imaging after popliteal lymphadenectomy in mice. In a cohort of mice, B16F10 melanoma was inoculated on the dorsal aspect of the paw 27 days after lymphadenectomy to assess how drainage patterns affect metastasis. RESULTS: NIRF imaging demonstrates that, although lymphatic function and drainage patterns change significantly in early response to popliteal lymph node (PLN removal in mice, these changes are transient and regress dramatically due to a high regenerative capacity of the lymphatics and co-opting of collateral lymphatic pathways around the site of obstruction. Metastases followed the pattern of collateral pathways and could be detected proximal to the site of lymphadenectomy. CONCLUSIONS: Both lymphatic vessel regeneration and co-opting of contralateral vessels occur following lymphadenectomy, with contractile function restored within 13 days, providing a basis for preclinical and clinical investigations to hasten lymphatic repair and restore contractile lymphatic function after surgery to prevent cancer-acquired lymphedema. Patterns of cancer metastasis after lymphadenectomy were altered, consistent with patterns of re-directed lymphatic drainage.

  5. Predictive factors for lymph node metastasis in early gastric cancer with lymphatic invasion after endoscopic resection.

    Science.gov (United States)

    Park, Ji Won; Ahn, Sangjeong; Lee, Hyuk; Min, Byung-Hoon; Lee, Jun Haeng; Rhee, Poong-Lyul; Kim, Kyoung-Mee; Kim, Jae J

    2017-04-04

    Lymph node (LN) metastasis is found in only about 5-10% of the patients who undergo additional surgery after non-curative endoscopic resection. Lymphatic invasion after endoscopic submucosal dissection (ESD) is regarded as non-curative resection due to risk of reginal LN metastasis. This study was aimed to identify clinicopathologic predictive factors for LN metastasis in early gastric cancer (EGC) with lymphatic invasion after endoscopic resection. Among a total of 2036 patients who underwent endoscopic resection for EGC at Samsung Medical Center from April 2000 to May 2011, 146 patients were diagnosed with lymphatic invasion. And 123 patients who had gastrectomy with LN dissection due to presence of lymphatic invasion as one of the non-curative factors were included in this study. Demographics, endoscopic tumor findings, histological findings, surgical findings with pathologic reports, and follow-up data were collected from the patient's medical records. Pathological re-evaluation of resected specimens was performed. Among a total of 123 patients, LN metastases were found in seven patients (5.7%). The univariate analysis revealed that the LN metastasis was significantly more frequent in patients with certain morphology of lymphatic invasion that shows adhesion to endothelium of lymphatic tumor emboli (p = 0.016), higher number of lymphatic tumor emboli in whole section (p < 0.001) and papillary adenocarcinoma component (p = 0.024). In multivariate analysis, the number of lymphatic tumor emboli [OR 93.5, 95% CI (2.62-3330.81)] and the presence of papillary adenocarcinoma component [OR 552.5, 95% CI (1.20-254871.81)] were identified as independent predictors of LN metastasis in patients with lymphatic invasion after endoscopic resection. The number of lymphatic tumor emboli and the presence of papillary adenocarcinoma component were significant predictors for LN metastasis in patients with lymphatic invasion after endoscopic resection.

  6. Lymphatic filariasis in Brazil: epidemiological situation and outlook for elimination

    Directory of Open Access Journals (Sweden)

    Fontes Gilberto

    2012-11-01

    Full Text Available Abstract Since the World Health Assembly’s (Resolution WHA 50.29, 1997 call for the elimination of lymphatic filariasis by the year 2020, most of the endemic countries identified have established programmes to meet this objective. In 1997, a National Lymphatic Filariasis Elimination Plan was drawn up by the Ministry of Health of Brazil, creating local programs for the elimination of Bancroftian filariasis in areas with active transmission. Based on a comprehensive bibliographic search for available studies and reports of filariasis epidemiology in Brazil, current status of this parasitic infection and the outlook for its elimination in the country were analysed. From 1951 to 1958 a nationwide epidemiological study conducted in Brazil confirmed autochthonous transmission of Bancroftian filariasis in 11 cities of the country. Control measures led to a decline in parasite rates, and in the 1980s only the cities of Belém in the Amazonian region (Northern region and Recife (Northeastern region were considered to be endemic. In the 1990s, foci of active transmission of LF were also described in the cities of Maceió, Olinda, Jaboatão dos Guararapes, and Paulista, all in the Northeastern coast of Brazil. Data provide evidence for the absence of microfilaremic subjects and infected mosquitoes in Belém, Salvador and Maceió in the past few years, attesting to the effectiveness of the measures adopted in these cities. Currently, lymphatic filariasis is a public health problem in Brazil only in four cities of the metropolitan Recife region (Northeastern coast. Efforts are being concentrated in these areas, with a view to eliminating the disease in the country.

  7. A microarray analysis of two distinct lymphatic endothelial cell populations

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    Bernhard Schweighofer

    2015-06-01

    Full Text Available We have recently identified lymphatic endothelial cells (LECs to form two morphologically different populations, exhibiting significantly different surface protein expression levels of podoplanin, a major surface marker for this cell type. In vitro shockwave treatment (IVSWT of LECs resulted in enrichment of the podoplaninhigh cell population and was accompanied by markedly increased cell proliferation, as well as 2D and 3D migration. Gene expression profiles of these distinct populations were established using Affymetrix microarray analyses. Here we provide additional details about our dataset (NCBI GEO accession number GSE62510 and describe how we analyzed the data to identify differently expressed genes in these two LEC populations.

  8. Rhythmic beating of stem cell-derived cardiac cells requires dynamic coupling of electrophysiology and Ca cycling.

    Science.gov (United States)

    Zahanich, Ihor; Sirenko, Syevda G; Maltseva, Larissa A; Tarasova, Yelena S; Spurgeon, Harold A; Boheler, Kenneth R; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

    2011-01-01

    There is an intense interest in differentiating embryonic stem cells to engineer biological pacemakers as an alternative to electronic pacemakers for patients with cardiac pacemaker function deficiency. Embryonic stem cell-derived cardiocytes (ESCs), however, often exhibit dysrhythmic excitations. Using Ca(2+) imaging and patch-clamp techniques, we studied requirements for generation of spontaneous rhythmic action potentials (APs) in late-stage mouse ESCs. Sarcoplasmic reticulum (SR) of ESCs generates spontaneous, rhythmic, wavelet-like Local Ca(2+)Releases (LCRs) (inhibited by ryanodine, tetracaine, or thapsigargin). L-type Ca(2+)current (I(CaL)) induces a global Ca(2+) release (CICR), depleting the Ca(2+) content SR which resets the phases of LCR oscillators. Following a delay, SR then generates a highly synchronized spontaneous Ca(2+)release of multiple LCRs throughout the cell. The LCRs generate an inward Na(+)/Ca(2+)exchanger (NCX) current (absent in Na(+)-free solution) that ignites the next AP. Interfering with SR Ca(2+) cycling (ryanodine, caffeine, thapsigargin, cyclopiazonic acid, BAPTA-AM), NCX (Na(+)-free solution), or I(CaL) (nifedipine) results in dysrhythmic excitations or cessation of automaticity. Inhibition of cAMP/PKA signaling by a specific PKA inhibitor, PKI, decreases SR Ca(2+) loading, substantially reducing both spontaneous LCRs (number, size, and amplitude) and rhythmic AP firing. In contrast, enhancing PKA signaling by cAMP increases the LCRs (number, size, duration) and converts irregularly beating ESCs to rhythmic "pacemaker-like" cells. SR Ca(2+) loading and LCR activity could be also increased with a selective activation of SR Ca(2+) pumping by a phospholamban antibody. We conclude that SR Ca(2+) loading and spontaneous rhythmic LCRs are driven by inherent cAMP/PKA activity. I(CaL) synchronizes multiple LCR oscillators resulting in strong, partially synchronized diastolic Ca(2+) release and NCX current. Rhythmic ESC automaticity can be

  9. Dynamic muscle O2 saturation response is impaired during major non-cardiac surgery despite goal-directed haemodynamic therapy.

    Science.gov (United States)

    Feldheiser, A; Hunsicker, O; Kaufner, L; Köhler, J; Sieglitz, H; Casans Francés, R; Wernecke, K-D; Sehouli, J; Spies, C

    2016-03-01

    Near-infrared spectroscopy combined with a vascular occlusion test (VOT) could indicate an impairment of microvascular reactivity (MVR) in septic patients by detecting changes in dynamic variables of muscle O2 saturation (StO2). However, in the perioperative context the consequences of surgical trauma on dynamic variables of muscle StO2 as indicators of MVR are still unknown. This study is a sub-analysis of a randomised controlled trial in patients with metastatic primary ovarian cancer undergoing debulking surgery, during which a goal-directed haemodynamic algorithm was applied using oesophageal Doppler. During a 3 min VOT, near-infrared spectroscopy was used to assess dynamic variables arising from changes in muscle StO2. At the beginning of surgery, values of desaturation and recovery slope were comparable to values obtained in healthy volunteers. During the course of surgery, both desaturation and recovery slope showed a gradual decrease. Concomitantly, the study population underwent a transition to a surgically induced systemic inflammatory response state shown by a gradual increase in norepinephrine administration, heart rate, and Interleukin-6, with a peak immediately after the end of surgery. Higher rates of norepinephrine and a higher heart rate were related to a faster decline in StO2 during vascular occlusion. Using near-infrared spectroscopy combined with a VOT during surgery showed a gradual deterioration of MVR in patients treated with optimal haemodynamic care. The deterioration of MVR was accompanied by the transition to a surgically induced systemic inflammatory response state. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Cardiac echinococcosis

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    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  11. Immunohistochemical identification of lymphatic vessels in the periodontium of equine cheek teeth.

    Science.gov (United States)

    Staszyk, Carsten; Duesterdieck, Katja F; Gasse, Hagen; Bienert, Astrid

    2005-12-01

    Immunohistochemical detection of lymphatic capillaries was performed in the periodontium of maxillary and mandibular cheek teeth from 6 horses (aged 3-23 years). Tissue sections of the periodontium were taken at 4 different horizontal levels along the long axis of the tooth. The specimens were processed for immunoreaction with anti-Prox1, in order to distinguish lymphatic endothelium from blood vascular endothelium. Lymphatic vessels were detected in all periodontal tissues except for the dental cementum. Lymphatic capillaries were most densely distributed in the gingiva compared to other tissues of the periodontium. Lymphatic capillaries were found most consistently in samples taken from the gingival and subgingival regions in all horses examined. Within these levels, the gingiva as well as the spongiosa of the maxillary and mandibular bone had the greatest incidence of lymphatic vessels. Considering the distinct distribution of the lymphatic capillaries in the periodontium of the maxillary and mandibular cheek teeth, two complementary lymphatic drainage pathways are proposed: (1) superficial lymph drainage via the gingiva, emptying into the mandibular lymph nodes; (2) deep lymph drainage via the mandibular and maxillary spongiosa, emptying into the mandibular and retropharyngeal lymph nodes, respectively.

  12. Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity.

    Science.gov (United States)

    Wang, Yixin; Jin, Yi; Mäe, Maarja Andaloussi; Zhang, Yang; Ortsäter, Henrik; Betsholtz, Christer; Mäkinen, Taija; Jakobsson, Lars

    2017-08-29

    Tissue-fluid drains through blind-ended lymphatic capillaries, via smooth muscle cell (SMC)-covered collecting vessels into venous circulation. Both defective SMC recruitment to collecting vessels and ectopic recruitment to lymphatic capillaries are thought to contribute to vessel failure, leading to lymphedema. However, mechanisms controlling lymphatic SMC recruitment and their role in vessel maturation are unknown. Here we demonstrate that platelet-derived growth factor B (PDGFB) regulates lymphatic SMC recruitment in multiple vascular beds. PDGFB is selectively expressed by lymphatic endothelial cells (LECs) of collecting vessels. LEC-specific deletion of Pdgfb prevented SMC recruitment causing dilation and failure of pulsatile contraction of collecting vessels. However, vessel remodelling and identity were unaffected. Unexpectedly, PDGFB overexpression in LECs did not induce SMC recruitment to capillaries. This was explained by the demonstrated requirement of PDGFB extracellular matrix (ECM) retention for lymphatic SMC recruitment, and low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate a requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels and suggest an ECM-controlled checkpoint preventing SMC investment of capillaries, which is a common feature in lymphedematous skin. © 2017. Published by The Company of Biologists Ltd.

  13. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk

    NARCIS (Netherlands)

    J. Bussmann (Jeroen); F.L. Bos (Frank); A. Urasaki (Akihiro); K. Kawakami (Koichi); H.J. Duckers (Henricus); S. Schulte-Merker (Stefan)

    2010-01-01

    textabstractThe endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk

  14. An Evolutionarily Conserved Role for Polydom/Svep1 during Lymphatic Vessel Formation

    NARCIS (Netherlands)

    Karpanen, Terhi; Padberg, Yvonne; Van De Pavert, Serge A.; Dierkes, Cathrin; Morooka, Nanami; Peterson-Maduro, Josi; Van De Hoek, Glenn; Adrian, Max; Mochizuki, Naoki; Sekiguchi, Kiyotoshi; Kiefer, Friedemann; Schulte, Dörte; Schulte-Merker, Stefan

    2017-01-01

    Rationale: Lymphatic vessel formation and function constitutes a physiologically and pathophysiologically important process, but its genetic control is not well understood. Objective: Here, we identify the secreted Polydom/Svep1 protein as essential for the formation of the lymphatic vasculature. We

  15. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk

    NARCIS (Netherlands)

    Bussmann, J.; Bos, F.L.; Urasaki, A.; Kawakami, K.; Duckers, H.J.; Schulte-Merker, S.

    2010-01-01

    The endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk consisting of

  16. Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors

    Energy Technology Data Exchange (ETDEWEB)

    Ran, Sophia, E-mail: sran@siumed.edu; Montgomery, Kyle E. [Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 801 N. Rutledge, Springfield, IL 62794 (United States)

    2012-06-27

    It is widely accepted that macrophages and other inflammatory cells support tumor progression and metastasis. During early stages of neoplastic development, tumor-infiltrating macrophages (TAMs) mount an immune response against transformed cells. Frequently, however, cancer cells escape the immune surveillance, an event that is accompanied by macrophage transition from an anti-tumor to a pro-tumorigenic type. The latter is characterized by high expression of factors that activate endothelial cells, suppress immune response, degrade extracellular matrix, and promote tumor growth. Cumulatively, these products of TAMs promote tumor expansion and growth of both blood and lymphatic vessels that facilitate metastatic spread. Breast cancers and other epithelial malignancies induce the formation of new lymphatic vessels (i.e., lymphangiogenesis) that leads to lymphatic and subsequently, to distant metastasis. Both experimental and clinical studies have shown that TAMs significantly promote tumor lymphangiogenesis through paracrine and cell autonomous modes. The paracrine effect consists of the expression of a variety of pro-lymphangiogenic factors that activate the preexisting lymphatic vessels. The evidence for cell-autonomous contribution is based on the observed tumor mobilization of macrophage-derived lymphatic endothelial cell progenitors (M-LECP) that integrate into lymphatic vessels prior to sprouting. This review will summarize the current knowledge of macrophage-dependent growth of new lymphatic vessels with specific emphasis on an emerging role of macrophages as lymphatic endothelial cell progenitors (M-LECP)

  17. An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

    Science.gov (United States)

    Korsgren, Erik; Korsgren, Olle

    2016-04-01

    The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  18. IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation

    DEFF Research Database (Denmark)

    Hammer, Troels; Tritsaris, Katerina; Hübschmann, Martin V;

    2009-01-01

    IL-20 is an arteriogenic cytokine that remodels collateral networks in vivo, and plays a role in cellular organization. Here, we investigate its role in lymphangiogenesis using a lymphatic endothelial cell line, hTERT-HDLEC, which expresses the lymphatic markers LYVE-1 and podoplanin. Upon stimul...

  19. EVALUATION OF MASS DRUG ADMINISTRATION FOR ELIMINATION OF LYMPHATIC FILARIASIS IN GUNTUR DISTRICT, ANDHRA PRADESH

    OpenAIRE

    Purnamma; Neelima

    2015-01-01

    BACKGROUND : Lymphatic Filariasis (LF) is a serious Socio Economic and Public Health problem in the world. In India, it is estimated that 554.2 million populations are at risk of Lymphatic Filariasis infection, in 243 implementation units (Districts). National Health Policy, 2002 aims at elimination of transmission and prevention of disability ...

  20. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk

    NARCIS (Netherlands)

    J. Bussmann (Jeroen); F.L. Bos (Frank); A. Urasaki (Akihiro); K. Kawakami (Koichi); H.J. Duckers (Henricus); S. Schulte-Merker (Stefan)

    2010-01-01

    textabstractThe endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk co

  1. Development and validation of a custom made indocyanine green fluorescence lymphatic vessel imager

    Science.gov (United States)

    Pallotta, Olivia J.; van Zanten, Malou; McEwen, Mark; Burrow, Lynne; Beesley, Jack; Piller, Neil

    2015-06-01

    Lymphoedema is a chronic progressive condition often producing significant morbidity. An in-depth understanding of an individual's lymphatic architecture is valuable both in the understanding of underlying pathology and for targeting and tailoring treatment. Severe lower limb injuries resulting in extensive loss of soft tissue require transposition of a flap consisting of muscle and/or soft tissue to close the defect. These patients are at risk of lymphoedema and little is known about lymphatic regeneration within the flap. Indocyanine green (ICG), a water-soluble dye, has proven useful for the imaging of lymphatic vessels. When injected into superficial tissues it binds to plasma proteins in lymph. By exposing the dye to specific wavelengths of light, ICG fluoresces with near-infrared light. Skin is relatively transparent to ICG fluorescence, enabling the visualization and characterization of superficial lymphatic vessels. An ICG fluorescence lymphatic vessel imager was manufactured to excite ICG and visualize real-time fluorescence as it travels through the lymphatic vessels. Animal studies showed successful ICG excitation and detection using this imager. Clinically, the imager has assisted researchers to visualize otherwise hidden superficial lymphatic pathways in patients postflap surgery. Preliminary results suggest superficial lymphatic vessels do not redevelop in muscle flaps.

  2. Advances and challenges in predicting the impact of lymphatic filariasis elimination programmes by mathematical modelling.

    NARCIS (Netherlands)

    W.A. Stolk (Wilma); S.J. de Vlas (Sake); J.D.F. Habbema (Dik)

    2006-01-01

    textabstractMathematical simulation models for transmission and control of lymphatic filariasis are useful tools for studying the prospects of lymphatic filariasis elimination. Two simulation models are currently being used. The first, EPIFIL, is a population-based, deterministic model that simulate

  3. Erratum: PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis

    DEFF Research Database (Denmark)

    Cao, R.H.; Bjorndahl, M.A.; Religa, P.;

    2006-01-01

    This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45.......This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45....

  4. A Validation Study of Near-Infrared Fluorescence Imaging of Lymphatic Vessels in Humans

    DEFF Research Database (Denmark)

    Groenlund, Jacob Hinnerup; Telinius, Niklas; Skov, Soeren Nielsen

    2017-01-01

    BACKGROUND: Near-infrared fluorescence (NIRF) imaging is a new imaging technique that is used to visualize lymphatic vessels in humans. It has a high spatial and temporal resolution, allowing real-time visualization of lymphatic flow. METHODS AND RESULTS: The current study investigated the intra...

  5. Effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats

    Institute of Scientific and Technical Information of China (English)

    Zuoli Xia; Baoling Sun; Mingfeng Yang; Dongmei Hu; Tong Zhao; Jingzhong Niu

    2006-01-01

    BACKGROUND: It has been shown that although brain does not contain lining endothelial lymphatic vessel,it has lymphatic drain.Anterior lymphatic vessel in brain tissue plays a key role in introducing brain interstitial fluid to lymphatic system;however,the significance of lymphatic drain and the affect on cerebral edema remains unclear.OBJECTIVE: To investigate the effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats.DESIGN: Randomized controlled animal study.SETTING: Institute of Cerebral Microcirulation of Taishan Medical College and Department of Neurology of Affiliated Hospital.MATERIALS:A total of 63 healthy adult male Wistar rats weighing 300-350 g were selected in this study.Forty-seven rats were used for the morphological observation induced by lymphatic drain and randomly divided into three groups:general observation group(n=12),light microscopic observation group(n=21)and electronic microscopic observation group(n=14).The rats in each group were divided into cerebral lymphatic block subgroup and sham-operation control subgroup.Sixteen rats were divided into cerebral the effect of cerebral lymphatic block on cortical evoked potential,in which the animals were randomly divided into sham-operation group(n=6)and cerebral lymphatic block group(n=10).METHODS:The experiment was carried out in the Institute of Cerebral Microcirculation of Taishan Medical College from January to August 2003.Rats in cerebral lymphatic block group were anesthetized and separated bilateral superficial and deep cervical lymph nodes under sterile condition. Superior and inferior boarders of lymph nodes were ligated the inputting and outputting channels, respectively, and then lymph node was removed so as to establish cerebral lymphatic drain disorder models. Rats in sham-operation control group were not ligated the lymphatic vessel and removed lymph nodes.and other operations were as the same as those in cerebral lymphatic block group

  6. microRNAs in the Lymphatic Endothelium: Master Regulators of Lineage Plasticity and Inflammation

    Science.gov (United States)

    Yee, Daniel; Coles, Mark C.; Lagos, Dimitris

    2017-01-01

    microRNAs (miRNAs) are highly conserved, small non-coding RNAs that regulate gene expression at the posttranscriptional level. They have crucial roles in organismal development, homeostasis, and cellular responses to pathological stress. The lymphatic system is a large vascular network that actively regulates the immune response through antigen trafficking, cytokine secretion, and inducing peripheral tolerance. Here, we review the role of miRNAs in the lymphatic endothelium with a particular focus on their role in lymphatic endothelial cell (LEC) plasticity, inflammation, and regulatory function. We highlight the lineage plasticity of LECs during inflammation and the importance of understanding the regulatory role of miRNAs in these processes. We propose that targeting miRNA expression in lymphatic endothelium can be a novel strategy in treating human pathologies associated with lymphatic dysfunction.

  7. Computational Studies of the Effect of the S23D/S24D Troponin I Mutation on Cardiac Troponin Structural Dynamics

    Science.gov (United States)

    Cheng, Yuanhua; Lindert, Steffen; Kekenes-Huskey, Peter; Rao, Vijay S.; Solaro, R. John; Rosevear, Paul R.; Amaro, Rommie; McCulloch, Andrew D.; McCammon, J. Andrew; Regnier, Michael

    2014-01-01

    During β-adrenergic stimulation, cardiac troponin I (cTnI) is phosphorylated by protein kinase A (PKA) at sites S23/S24, located at the N-terminus of cTnI. This phosphorylation has been shown to decrease KCa and pCa50, and weaken the cTnC-cTnI (C-I) interaction. We recently reported that phosphorylation results in an increase in the rate of early, slow phase of relaxation (kREL,slow) and a decrease in its duration (tREL,slow), which speeds up the overall relaxation. However, as the N-terminus of cTnI (residues 1–40) has not been resolved in the whole cardiac troponin (cTn) structure, little is known about the molecular-level behavior within the whole cTn complex upon phosphorylation of the S23/S24 residues of cTnI that results in these changes in function. In this study, we built up the cTn complex structure (including residues cTnC 1–161, cTnI 1–172, and cTnT 236–285) with the N-terminus of cTnI. We performed molecular-dynamics (MD) simulations to elucidate the structural basis of PKA phosphorylation-induced changes in cTn structure and Ca2+ binding. We found that introducing two phosphomimic mutations into sites S23/S24 had no significant effect on the coordinating residues of Ca2+ binding site II. However, the overall fluctuation of cTn was increased and the C-I interaction was altered relative to the wild-type model. The most significant changes involved interactions with the N-terminus of cTnI. Interestingly, the phosphomimic mutations led to the formation of intrasubunit interactions between the N-terminus and the inhibitory peptide of cTnI. This may result in altered interactions with cTnC and could explain the increased rate and decreased duration of slow-phase relaxation seen in myofibrils. PMID:25296321

  8. Primary mucinous carcinoma with direct histopathologic evidence of lymphatic invasion.

    Science.gov (United States)

    Warycha, Melanie; Kamino, Hideko; Mobini, Narciss; Hale, Elizabeth K

    2006-01-01

    Primary mucinous carcinoma of the skin is a rare sweat gland neoplasm which occurs most commonly in the periorbital region. Although the tumor has a propensity for local recurrence and regional spread, distant metastases are rare. The standard treatment of primary mucinous carcinoma is wide local excision. Mohs micrographic surgery may also be utilized in cases where tissue conservation is of utmost concern. We present a case of primary mucinous carcinoma arising in the scalp, which was treated with wide local excision. A case report and literature review are presented. Histopathologic evaluation revealed a well-circumscribed neoplasm characterized by lobules and aggregates of epithelial cells embedded in abundant pools of mucin. In addition, small aggregates of neoplastic cells were found at a distance from the primary nodule, indicative of lymphatic invasion. Primary mucinous carcinoma has a high propensity for locoregional metastases and recurrence. To our knowledge, this is the first report demonstrating direct histopathologic evidence of lymphatic invasion which correlates with this tumor's biologic behavior.

  9. Direct lymphangiography as treatment option of lymphatic leakage: indications, outcomes and role in patient's management.

    Science.gov (United States)

    Gruber-Rouh, Tatjana; Naguib, Nagy N N; Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin; Tsaur, Igor; Hammersting, Renate; Wichmann, Julian L; Vogl, Thomas J; Jacobi, Volkmar

    2014-12-01

    To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10)underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31),therapeutic lymphography was still successful in 58.1% of the patients. Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Cardiac Rehabilitation

    Science.gov (United States)

    ... your risk of future heart problems, and to improve your health and quality of life. Cardiac rehabilitation programs increase ... exercise routine at home or at a local gym. You may also continue to ... health concerns. Education about nutrition, lifestyle and weight loss ...

  11. Conditional shape models for cardiac motion estimation

    DEFF Research Database (Denmark)

    Metz, Coert; Baka, Nora; Kirisli, Hortense

    2010-01-01

    We propose a conditional statistical shape model to predict patient specific cardiac motion from the 3D end-diastolic CTA scan. The model is built from 4D CTA sequences by combining atlas based segmentation and 4D registration. Cardiac motion estimation is, for example, relevant in the dynamic...

  12. A novel quantitative explanation for the autonomic modulation of cardiac pacemaker cell automaticity via a dynamic system of sarcolemmal and intracellular proteins.

    Science.gov (United States)

    Maltsev, Victor A; Lakatta, Edward G

    2010-06-01

    Classical numerical models have attributed the regulation of normal cardiac automaticity in sinoatrial node cells (SANCs) largely to G protein-coupled receptor (GPCR) modulation of sarcolemmal ion currents. More recent experimental evidence, however, has indicated that GPCR modulation of SANCs automaticity involves spontaneous, rhythmic, local Ca(2+) releases (LCRs) from the sarcoplasmic reticulum (SR). We explored the GPCR rate modulation of SANCs using a unique and novel numerical model of SANCs in which Ca(2+)-release characteristics are graded by variations in the SR Ca(2+) pumping capability, mimicking the modulation by phospholamban regulated by cAMP-mediated, PKA-activated signaling. The model faithfully predicted the entire range of physiological chronotropic modulation of SANCs by the activation of beta-adrenergic receptors or cholinergic receptors only when experimentally documented changes of sarcolemmal ion channels are combined with a simultaneous increase/decrease in SR Ca(2+) pumping capability. The novel numerical mechanism of GPCR rate modulation is based on numerous complex synergistic interactions between sarcolemmal and intracellular processes via membrane voltage and Ca(2+). Major interactions include changes of diastolic Na(+)/Ca(2+) exchanger current that couple earlier/later diastolic Ca(2+) releases (predicting the experimentally defined LCR period shift) of increased/decreased amplitude (predicting changes in LCR signal mass, i.e., the product of LCR spatial size, amplitude, and number per cycle) to the diastolic depolarization and ultimately to the spontaneous action potential firing rate. Concomitantly, larger/smaller and more/less frequent activation of L-type Ca(2+) current shifts the cellular Ca(2+) balance to support the respective Ca(2+) cycling changes. In conclusion, our model simulations corroborate recent experimental results in rabbit SANCs pointing to a new paradigm for GPCR heart rate modulation by a complex system of

  13. Invasion of lymphatic vessels into the eye after open globe injuries.

    Science.gov (United States)

    Wessel, Julia M; Hofmann-Rummelt, Carmen; Kruse, Friedrich E; Cursiefen, Claus; Heindl, Ludwig M

    2012-06-20

    We analyzed whether lymphatic vessels can be detected in eyes enucleated after an open globe injury. The presence of lymphatic vessels was analyzed immunohistochemically using podoplanin as a specific lymphatic endothelial marker in 21 globes that had been enucleated after open globe injury. The localization of pathologic lymphatic vessels (within the eye wall or inside the eye) was correlated with the mechanism of trauma, anatomic site of perforation or rupture, and time interval between trauma and enucleation. Pathologic lymphatic vessels were detected in 15 of 21 eyes (71%) enucleated after an open globe injury. In 5 globes (24%) they were found within the eye, located in retrocorneal membranes, underneath the sclera, and adjacent to uveal tissue (ciliary body, iris). No significant association was observed between the presence of pathologic lymphatic vessels and the mechanism of trauma (P = 0.598), anatomic site of perforation or rupture (P = 0.303), and time interval between trauma and enucleation (P = 0.145). The human eye can be invaded secondarily by lymphatic vessels if the eye wall is opened by trauma. This mechanism could be important for wound healing, immunologic defense against intruding microorganisms, and autoimmune reactions against intraocular antigens.

  14. Efficacy of AdipoDren® in Reducing Interleukin-1-Induced Lymphatic Endothelial Hyperpermeability.

    Science.gov (United States)

    Ciccone, Valerio; Monti, Martina; Antonini, Giulia; Mattoli, Luisa; Burico, Michela; Marini, Francesca; Maidecchi, Anna; Morbidelli, Lucia

    2016-01-01

    Lymphatic leakage can be seen as a detrimental phenomenon associated with fluid retention and deposition as well as gain of weight. Moreover, lymphatic dysfunction is associated with an inflammatory environment and can be a substrate for other health conditions. A number of treatments can ameliorate lymphatic vasculature: natural substances have been used as treatment options particularly suitable for their consolidated effectiveness and safety profile. Here we report the protective effect of AdipoDren®, an association of a series of plant-derived natural complexes, on lymphatic endothelium permeability promoted by interleukin-1 beta (IL-1β) and the associated molecular mechanisms. AdipoDren® demonstrated a protective effect on dermal lymphatic endothelial cell permeability increased by IL-1β. Reduced permeability was due to the maintenance of tight junctions and cell-cell localisation of occludin and zonula occludens-1 (ZO-1). Moreover, AdipoDren® reduced the expression of the inflammatory key element cyclooxygenase-2 (COX-2), while not altering the levels of endothelial and inducible nitric oxide synthases (eNOS and iNOS). The upregulation of antioxidant enzymatic systems (catalase and superoxide dismutase-1, SOD-1) and the downregulation of pro-oxidant markers (p22 phox subunit of NADPH oxidase) were also evident. In conclusion, AdipoDren® would be useful to ameliorate conditions of altered lymphatic vasculature and to support the physiological functionality of the lymphatic endothelium.

  15. Lymphatic dysregulation in intestinal inflammation: new insights into inflammatory bowel disease pathomechanisms.

    Science.gov (United States)

    Becker, F; Yi, P; Al-Kofahi, M; Ganta, V C; Morris, J; Alexander, J S

    2014-03-01

    Alterations in the intestinal lymphatic network are well-established features of human and experimental inflammatory bowel disease (IBD). Such lymphangiogenic expansion might enhance classic intestinal lymphatic transport, eliminating excess accumulations of fluid, inflammatory cells and mediators, and could therefore be interpreted as an 'adaptive' response to acute and chronic inflammatory processes. However, whether these new lymphatic vessels are functional, unregulated or immature (and what factors may promote 'maturation' of these vessels) is currently an area under intense investigation. It is still controversial whether impaired lymphatic function in IBD is a direct consequence of the intestinal inflammation, or a preceding lymphangitis-like event. Current research has uncovered novel regulatory factors as well as new roles for familiar signaling pathways, which appear to be linked to inflammation-induced lymphatic alterations. The current review summarizes mechanisms amplifying lymphatic dysregulation and remodeling in intestinal inflammation at the organ, cell and molecular levels and discusses the influence of lymphangiogenesis and intestinal lymphatic transport function as they relate to IBD pathophysiology.

  16. Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation.

    Science.gov (United States)

    Uhrin, Pavel; Zaujec, Jan; Breuss, Johannes M; Olcaydu, Damla; Chrenek, Peter; Stockinger, Hannes; Fuertbauer, Elke; Moser, Markus; Haiko, Paula; Fässler, Reinhard; Alitalo, Kari; Binder, Bernd R; Kerjaschki, Dontscho

    2010-05-13

    During embryonic development, lymph sacs form from the cardinal vein, and sprout centrifugally to form mature lymphatic networks. Separation of the lymphatic from the blood circulation by a hitherto unknown mechanism is essential for the homeostatic function of the lymphatic system. O-glycans on the lymphatic endothelium have recently been suggested to be required for establishment and maintenance of distinct blood and lymphatic systems, primarily by mediating proper function of podoplanin. Here, we show that this separation process critically involves platelet activation by podoplanin. We found that platelet aggregates build up in wild-type embryos at the separation zone of podoplanin(+) lymph sacs and cardinal veins, but not in podoplanin(-/-) embryos. Thus, podoplanin(-/-) mice develop a "nonseparation" phenotype, characterized by a blood-filled lymphatic network after approximately embryonic day 13.5, which, however, partially resolves in postnatal mice. The same embryonic phenotype is also induced by treatment of pregnant mice with acetyl salicylic acid, podoplanin-blocking antibodies, or by inactivation of the kindlin-3 gene required for platelet aggregation. Therefore, interaction of endothelial podoplanin of the developing lymph sac with circulating platelets from the cardinal vein is critical for separating the lymphatic from the blood vascular system.

  17. Obliteration of the lymphatic trunks draining diaphragmatic lymph causes peritoneal fluid to enter the pleural cavity.

    Science.gov (United States)

    Ohtani, Y; Ohtani, O

    1997-12-01

    Pathways of peritoneal fluids to the pleural cavity in the rat were investigated by light microscopy and transmission electron microscopy (TEM). Intraperitoneally injected India ink was demonstrated to enter the subperitoneal lymphatics through lymphatic stomata, and to drain through the subpleural collecting lymphatics, into the parasternal, paravertebral and mediastinal lymphatic trunks as well as the thoracic duct. Five to 10 min after the intraperitoneal injection of India ink, the parasternal lymphatic trunk was ligated at the third intercostal space. Thirty minutes, 1 h, or 2 h after the ligation of either the right or the left trunk, India ink was macroscopically recognized only around the ligated trunk. When the right and left trunks were simultaneously ligated, India ink leaked around both trunks. Five hours after the ligation of both trunks, a massive amount of ink was located in the interstitium of the anterior thoracic wall. TEM revealed carbon particles passing through gaps of the lymphatic endothelial cells into the interstitial space, and partly reaching the mesothelial surface lining the anterior thoracic wall. Results show that obstruction or narrowing of the lymphatic trunks draining the diaphragmatic lymph causes a hydrothorax, indicating that this is at least one mechanism causing this during continuous ambulatory peritoneal dialysis and diseases with ascites.

  18. A brief perspective on the diverging theories of lymphatic targeting with colloids

    Directory of Open Access Journals (Sweden)

    Siram K

    2016-06-01

    Full Text Available Karthik Siram,1 Gregory Marslin,2 Chellan Vijaya Raghavan,1 Krishnamoorthy Balakumar,1 Habibur Rahman,1 Gregory Franklin3 1Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, India; 2Centre for the Research and Technology of Agro-Environment and Biological Sciences, University of Minho, Braga, Portugal; 3Department of Integrative Plant Biology, Institute of Plant Genetics, Polish Academy of Sciences, Poznan, Poland Abstract: For targeted delivery of colloids to the lymphatic system, the colloids should efficiently reach and remain in the lymphatics for a considerable period of time. As per the current knowledge, diffusion and phagocytosis are the two mechanisms through which colloids reach the lymphatic system. Several parameters including particle size and charge have been shown to affect the direct uptake of colloids by the lymphatic system. Although many researchers attached ligands on the surface of colloids to promote phagocytosis-mediated lymphatic delivery, another school of thought suggests avoidance of phagocytosis by use of carriers like polyethylene glycol (PEGylated colloids to impart stealth attributes and evade phagocytosis. In this perspective, we weigh up the paradoxical theories and approaches available in the literature to draw conclusions on the conditions favorable for achieving efficient lymphatic targeting of colloids. Keywords: lymphatic targeting, colloids, PEGylation, phagocytosis

  19. In vivo visualization and quantification of collecting lymphatic vessel contractility using near-infrared imaging

    Science.gov (United States)

    Chong, Chloé; Scholkmann, Felix; Bachmann, Samia B.; Luciani, Paola; Leroux, Jean-Christophe; Detmar, Michael; Proulx, Steven T.

    2016-01-01

    Techniques to image lymphatic vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome measures for collecting lymphatic vessel function are sorely needed. In this study, we aimed to develop a method to visualize and quantify collecting lymphatic vessel function in mice, and to establish an in vivo system for evaluation of contractile agonists and antagonists using near-infrared fluorescence imaging. The flank collecting lymphatic vessel in mice was exposed using a surgical technique and a near-infrared tracer was infused into the inguinal lymph node. Collecting lymphatic vessel contractility and valve function could be easily visualized after the infusion. A diameter tracking method was established and the diameter of the vessel was found to closely correlate to near-infrared fluorescence signal. Phasic contractility measures of frequency and amplitude were established using an automated algorithm. The methods were validated by tracking the vessel response to topical application of a contractile agonist, prostaglandin F2α, and by demonstrating the potential of the technique for non-invasive evaluation of modifiers of lymphatic function. These new methods will enable high-resolution imaging and quantification of collecting lymphatic vessel function in animal models and may have future clinical applications. PMID:26960708

  20. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules.

    Science.gov (United States)

    Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge; Alitalo, Kari

    2015-06-29

    The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.

  1. Gorham-Stout disease and generalized lymphatic anomaly--clinical, radiologic, and histologic differentiation.

    Science.gov (United States)

    Lala, Shailee; Mulliken, John B; Alomari, Ahmad I; Fishman, Steven J; Kozakewich, Harry P; Chaudry, Gulraiz

    2013-07-01

    Gorham-Stout disease (GSD) is a rare vascular disorder of lymphatic origin characterized by progressive osteolysis. Generalized lymphatic anomaly (GLA) is a multisystem disorder that also commonly affects bone. We hypothesized that Gorham-Stout disease is different from other osseous lymphatic anomalies. We proposed to discriminate these entities by analyzing findings on skeletal imaging. Clinical data, imaging studies, and histopathologic findings were retrospectively reviewed in patients presenting to our Vascular Anomalies Center with lymphatic anomalies of bone. Within a cohort of 51 patients with lymphatic disorder and radiological evidence of bony involvement, two distinct categories emerged. Nineteen patients met the imaging criteria for GSD: progressive osteolysis with resorption and cortical loss. Thirty-two were categorized as GLA: Discrete radiolucencies and increasing numbers of bone affected over time, but without evidence of progressive osteolysis. The ribs were the most common site in both groups, followed by the cranium, clavicle, and cervical spine in GSD, and thoracic spine, humerus, and femur in GLA. Fewer bones were involved in GSD, with relative sparing of the appendicular skeleton. Associated infiltrative soft tissue abnormality was seen in 18 in GSD, but only six with GLA. Macrocystic lymphatic malformations were identified in 14 with GLA, but none with GSD. There are significant radiological differences between GSD and GLA, although there are some overlapping features. The major distinguishing characteristic is the progressive osteolysis seen in GSD. Findings suggestive of GLA are more extensive involvement, particularly of the appendicular skeleton, presence of discretemacrocystic lymphatic malformations and visceral organ lesions.

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

    Science.gov (United States)

    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.

  3. Podoplanin immunopositive lymphatic vessels at the implant interface in a rat model of osteoporotic fractures.

    Directory of Open Access Journals (Sweden)

    Katrin Susanne Lips

    Full Text Available Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of

  4. Length-tension relationships of small arteries, veins, and lymphatics from the rat mesenteric microcirculation.

    Science.gov (United States)

    Zhang, Rong-Zhen; Gashev, Anatoliy A; Zawieja, David C; Davis, Michael J

    2007-04-01

    The passive and active length-tension relationships of isolated rat mesenteric lymphatics ( approximately 150 microm ID), and adjacent small arteries ( approximately 240 microm) and veins ( approximately 275 microm) were compared under isometric conditions using a wire myograph. About 60% of the lymphatic vessels developed spontaneous contractions in physiological saline solution at nominal preload. To maximally activate smooth muscle, 145 mM K(+) + 5 x 10(-5) M norepinephrine was used for arteries, and 145 mM K(+) + 1 x 10(-6) M substance P was used for lymphatics and veins. In response, arteries exhibited monotonic force development to a plateau level, whereas lymphatics and veins showed biphasic force development, consisting of a transient force peak followed by partial relaxation to a plateau over approximately 5 min. The passive and the active length-tension curves were similar in shape among all three vessels. However, the maximal active tension of arteries (3.4 +/- 0.42 mN/mm) was significantly greater than peak active tension (0.59 +/- 0.04 mN/mm) or plateau tension (0.20 +/- 0.04 mN/mm) in small veins and greater than peak active tension (0.34 +/- 0.02 mN/mm) or plateau tension (0.21 +/- 0.02 mN/mm) in lymphatics. Maximal active medial wall stress was similar between lymphatics and veins but was approximately fivefold higher in small arteries. For lymphatics, the pressure calculated from the optimal preload was significantly higher than that found previously in isobaric studies of isolated lymphatics, suggesting the capacity to operate at higher than normal pressures for increased responsiveness. Our results represent the first mechanical comparisons of arterial, venous, and lymphatic vessels in the same vasculature.

  5. Stewart-Treves syndrome angiosarcoma expresses phenotypes of both blood and lymphatic capillaries

    Institute of Scientific and Technical Information of China (English)

    Marek Stanczyk; Magdalena Gewartowska; Marcin Swierkowski; Bartlomiej Grala; Marek Maruszynski

    2013-01-01

    Background The development of angiosarcoma in oedematous tissue is referred to as Stewart-Treves syndrome (STS).This rare and fatal complication is associated with chronic post mastectomy lymphoedema and radiotherapy for breast cancer.Angiosarcoma spread is facilitated by the formation of blood vessels (angiogenesis) and lymph vessels (lymphangiogenesis).In the future antiangiogenic therapy may improve the poor outcome of current treatments.There was evidence that blocking the angiogenenesis would inhibit progression of angiosarcoma.It seems reasonable to hypothesize that blocking the lymphangiogenesis may yield similar results.Although angiosarcomas commonly derive from blood vessels,in case of STS angiosarcomas chronic lymphoedema may suggest its lymphatic origin.The goal of this study was to visualize interstitial space and lymphatics in the central and peripheral regions of STS angiosarcoma.Methods On tissue samples obtained from STS angiosarcoma we have performed:first colour stereoscopic lymphography to visualise the morphology of lymphatic vessels and extracellular spaces,second immunohistochemical staining specific for lymphatic vessels endothelium (LYVE-1) and blood endothelial cells (CD31,factor Ⅷ) and prolymphangiogenic vascular endothelial growth factor (VEGF-C) for precise identification of lymphatic endothelia.STS angiosarcoma morphology was assessed by comparison of pictures obtained on lymphography,microscopy and confocal microscopy.Results STS angiosarcomas present heterogenous morphology with areas dominated by hemangiosarcoma and lymphangiosarcoma structures.STS angiosarcoma expressed phenotypes of both blood and lymphatic endothelia.LYVE-1 and VEGF-C is expressed by STS angiosarcoma and may be used to discriminate tumour differentiation.Morphology of lymphatic vessels and spaces in the tumour suggest absence of their normal lymphatic function.Conclusions Our results confirmed both hemangio-and lymphangiogenic origin of STS angiosarcoma

  6. Initial afferent lymphatic vessels controlling outbound leukocyte traffic from skin to lymph nodes.

    Directory of Open Access Journals (Sweden)

    Ignacio eMelero

    2013-12-01

    Full Text Available Tissue drains fluid and macromolecules through lymphatic vessels, which are lined by a specialized endothelium that expresses peculiar differentiation proteins, not found in blood vessels (i.e: LYVE-1, Podoplanin, PROX-1 and VEGFR-3. Lymphatic capillaries are characteristically devoid of a continuous basal membrane and are anchored to the ECM by elastic fibers that act as pulling ropes which open the vessel to avoid oedema if tissue volume increases, as it occurs upon inflammation. Lymphatic vessels are also crucial for the transit of T lymphocytes and antigen presenting cells from tissue to draining lymph nodes. Importantly, cell traffic control across lymphatic endothelium is differently regulated under resting and inflammatory conditions. Under steady-state non-inflammatory conditions, leukocytes enter into the lymphatic capillaries through basal membrane gaps (portals. This entrance is integrin-independent and seems to be mainly guided by CCL21 chemokine gradients acting on leukocytes expressing CCR7. In contrast, inflammatory processes in lymphatic capillaries involve a plethora of cytokines, chemokines, leukocyte integrins and other adhesion molecules. Importantly, under inflammation a role for integrins and their ligands becomes apparent and, as a consequence, the number of leukocytes entering the lymphatic capillaries multiplies several-fold. Enhancing transmigration of dendritic cells en route to lymph nodes is conceivably useful for vaccination and cancer immunotherapy, whereas interference with such key mechanisms may ameliorate autoimmunity or excessive inflammation. Recent findings illustrate how, transient cell-to-cell interactions between lymphatic endothelial cells and leukocytes contribute to shape the subsequent behaviour of leukocytes and condition the lymphatic vessel for subsequent trans-migratory events.

  7. Identification of lymphatics in the ciliary body of the human eye: a novel "uveolymphatic" outflow pathway.

    Science.gov (United States)

    Yücel, Yeni H; Johnston, Miles G; Ly, Tina; Patel, Manoj; Drake, Brian; Gümüş, Ersin; Fraenkl, Stephan A; Moore, Sara; Tobbia, Dalia; Armstrong, Dianna; Horvath, Eva; Gupta, Neeru

    2009-11-01

    Impaired aqueous humor flow from the eye may lead to elevated intraocular pressure and glaucoma. Drainage of aqueous fluid from the eye occurs through established routes that include conventional outflow via the trabecular meshwork, and an unconventional or uveoscleral outflow pathway involving the ciliary body. Based on the assumption that the eye lacks a lymphatic circulation, the possible role of lymphatics in the less well defined uveoscleral pathway has been largely ignored. Advances in lymphatic research have identified specific lymphatic markers such as podoplanin, a transmembrane mucin-type glycoprotein, and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). Lymphatic channels were identified in the human ciliary body using immunofluorescence with D2-40 antibody for podoplanin, and LYVE-1 antibody. In keeping with the criteria for lymphatic vessels in conjunctiva used as positive control, D2-40 and LYVE-1-positive lymphatic channels in the ciliary body had a distinct lumen, were negative for blood vessel endothelial cell marker CD34, and were surrounded by either discontinuous or no collagen IV-positive basement membrane. Cryo-immunogold electron microscopy confirmed the presence D2-40-immunoreactivity in lymphatic endothelium in the human ciliary body. Fluorescent nanospheres injected into the anterior chamber of the sheep eye were detected in LYVE-1-positive channels of the ciliary body 15, 30, and 45 min following injection. Four hours following intracameral injection, Iodine-125 radio-labeled human serum albumin injected into the sheep eye (n = 5) was drained preferentially into cervical, retropharyngeal, submandibular and preauricular lymph nodes in the head and neck region compared to reference popliteal lymph nodes (P human ciliary body, and that fluid and solutes flow at least partially through this system. The discovery of a uveolymphatic pathway in the eye is novel and highly relevant to studies of glaucoma and other eye diseases.

  8. Cardiac Calcification

    Directory of Open Access Journals (Sweden)

    Morteza Joorabian

    2011-05-01

    Full Text Available There is a spectrum of different types of cardiac"ncalcifications with the importance and significance"nof each type of cardiac calcification, especially"ncoronary artery calcification. Radiologic detection of"ncalcifications within the heart is quite common. The"namount of coronary artery calcification correlates"nwith the severity of coronary artery disease (CAD."nCalcification of the aortic or mitral valve may indicate"nhemodynamically significant valvular stenosis."nMyocardial calcification is a sign of prior infarction,"nwhile pericardial calcification is strongly associated"nwith constrictive pericarditis. A spectrum of different"ntypes of cardiac calcifications (linear, annular,"ncurvilinear,... could be seen in chest radiography and"nother imaging modalities. So a carful inspection for"ndetection and reorganization of these calcifications"nshould be necessary. Numerous modalities exist for"nidentifying coronary calcification, including plain"nradiography, fluoroscopy, intravascular ultrasound,"nMRI, echocardiography, and conventional, helical and"nelectron-beam CT (EBCT. Coronary calcifications"ndetected on EBCT or helical CT can be quantifie,"nand a total calcification score (Cardiac Calcification"nScoring may be calculated. In an asymptomatic"npopulation and/or patients with concomitant risk"nfactors like diabetes mellitus, determination of the"npresence of coronary calcifications identifies the"npatients at risk for future myocardial infarction and"ncoronary artery disease. In patients without coronary"ncalcifications, future cardiovascular events could"nbe excluded. Therefore, detecting and recognizing"ncalcification related to the heart on chest radiography"nand other imaging modalities such as fluoroscopy, CT"nand echocardiography may have important clinical"nimplications.

  9. Total lymphatic irradiation and bone marrow in human heart transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-08-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem.

  10. Dynamics of matrix-free Ca2+ in cardiac mitochondria: two components of Ca2+ uptake and role of phosphate buffering.

    Science.gov (United States)

    Wei, An-Chi; Liu, Ting; Winslow, Raimond L; O'Rourke, Brian

    2012-06-01

    Mitochondrial Ca(2+) uptake is thought to provide an important signal to increase energy production to meet demand but, in excess, can also trigger cell death. The mechanisms defining the relationship between total Ca(2+) uptake, changes in mitochondrial matrix free Ca(2+), and the activation of the mitochondrial permeability transition pore (PTP) are not well understood. We quantitatively measure changes in [Ca(2+)](out) and [Ca(2+)](mito) during Ca(2+) uptake in isolated cardiac mitochondria and identify two components of Ca(2+) influx. [Ca(2+)](mito) recordings revealed that the first, MCU(mode1), required at least 1 µM Ru360 to be completely inhibited, and responded to small Ca(2+) additions in the range of 0.1 to 2 µM with rapid and large changes in [Ca(2+)](mito). The second component, MCU(mode2), was blocked by 100 nM Ru360 and was responsible for the bulk of total Ca(2+) uptake for large Ca(2+) additions in the range of 2 to 10 µM; however, it had little effect on steady-state [Ca(2+)](mito). MCU(mode1) mediates changes in [Ca(2+)](mito) of 10s of μM, even in the presence of 100 nM Ru360, indicating that there is a finite degree of Ca(2+) buffering in the matrix associated with this pathway. In contrast, the much higher Ca(2+) loads evoked by MCU(mode2) activate a secondary dynamic Ca(2+) buffering system consistent with calcium-phosphate complex formation. Increasing P(i) potentiated [Ca(2+)](mito) increases via MCU(mode1) but suppressed [Ca(2+)](mito) changes via MCU(mode2). The results suggest that the role of MCU(mode1) might be to modulate oxidative phosphorylation in response to intracellular Ca(2+) signaling, whereas MCU(mode2) and the dynamic high-capacity Ca(2+) buffering system constitute a Ca(2+) sink function. Interestingly, the trigger for PTP activation is unlikely to be [Ca(2+)](mito) itself but rather a downstream byproduct of total mitochondrial Ca(2+) loading.

  11. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk.

    Science.gov (United States)

    Bussmann, Jeroen; Bos, Frank L; Urasaki, Akihiro; Kawakami, Koichi; Duckers, Henricus J; Schulte-Merker, Stefan

    2010-08-01

    The endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk consisting of three types of lymphatic vessels that develop in close connection with the blood vasculature. We have generated transgenic lines that allow us to distinguish between arterial, venous and lymphatic endothelial cells (LECs) within a single zebrafish embryo. We found that LECs migrate exclusively along arteries in a manner that suggests that arterial endothelial cells serve as the LEC migratory substrate. In the absence of intersegmental arteries, LEC migration in the trunk is blocked. Our data therefore demonstrate a crucial role for arteries in LEC guidance.

  12. [The interpretation of immunophenotyping results during diagnostics of lymphatic proliferative disease using immunophenotyping count].

    Science.gov (United States)

    Isaeva, N V; Zaĭtseva, G A; Zagoskina, T P

    2013-02-01

    The article considers immune phenotyping heterogeneity of chronic lymphatic leukemia detected using basic diagnostic markers ofcell. The results of analysis of immune phenotypes of 108 patients with B-cell lymphatic proliferative diseases made it possible to establish that the atypical is related most rarely to indicators of expression of monotypic immunoglobulines and CD5 and most frequently to CD23, FMC7, CD22 and CS79b. During the present observation, the immune phenotyping count made up "3" or "2"points and the atypical alternative was registered among 10% of all examined patients with chronic lymphatic leukemia. It is demonstrated that patients with chronic lymphatic leukemia and with lower immune phenotyping count are characterized by major intensity of tumor substrate.

  13. The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick [University of Oxford, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Science, Oxford (United Kingdom); Jackson, David [Weatherall Institute of Molecular Medicine, Human Immunology Unit, Oxford (United Kingdom)

    2009-12-15

    Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

  14. Near-infrared laparoscopy for real-time intra-operative arterial and lymphatic perfusion imaging.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-01

    Multimodal laparoscopic imaging systems possessing the capability for extended spectrum irradiation and visualization within a unified camera system are now available to provide enhanced intracorporeal operative anatomic and dynamic perfusion assessment and potentially augmented patient outcome. While ultraviolet-range energies have limited penetration and hence are probably more useful for endoscopic mucosal interrogation, the near-infrared (NIR) spectrum is of greater potential utility for the purposes of examining inducible fluorescence in abdominopelvic tissue that can be achieved by administration of specific tracer agents, either directly into the circulation (e.g. for anastomotic perfusion assessment at the time of stapling) or into the lymphatic system (e.g. for lymph basin road-mapping and\\/or focussed target nodal assessment). This technology is also capable of supplementing anatomic recognition of the biliary system while implantable fibres can also be inserted intraoperatively for the purpose of safeguarding vital structures such as the oesphagus and ureters especially in difficult reoperations. It is likely that this technological capability will find a clear and common indication in colorectal specialist and general surgical departments worldwide in the near future.

  15. An in Vitro Study of Breast Cancer Invasion into the Lymphatics

    Science.gov (United States)

    2006-08-01

    Lymphatic, CCL21, CCR7 , interstitial flow, chemotaxis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...funded period, we accomplished nearly all of the proposed tasks. The outcomes of this preliminary project have been presented to and received by...towards the lymphatics. Furthermore, the chemokine receptor CCR7 (receptor for CCL19 and 21), normally involved in immune cell trafficking has

  16. Longitudinal monitoring of head and neck lymphatics in response to cancer treatment

    Science.gov (United States)

    Rasmussen, John C.; Tan, I.-Chih; Naqvi, Syed; Aldrich, Melissa B.; Maus, Erik A.; Blanco, Angel I.; Karni, Ron J.; Sevick-Muraca, Eva M.

    2017-02-01

    Radiation therapy (RT) can promote anti-tumoral responses, but is also known to cause lymphatic endothelial cell apoptosis, loss of dermal lymphatics, and reduction in lymph transport to draining lymph node basins. When combined with lymph node dissection (LND), the radiogenic lymphatic disruption may possibly result in lymph stasis and dermal backflow. If not resolved, this disruption may lead to chronic inflammation, edema, fibrosis, adipose tissue deposition, and ultimately to functional deficits and disfigurement. Because the head and neck (HN) region contains 1/3 of the body's lymph nodes, lymphatic responses to cancer progression and therapy may be significant. Furthermore, it may not be surprising that lymphedema has been estimated to impact as many as 75% of HN cancer survivors three months or more after LND and RT. In this study, we used near-infrared fluorescence imaging to longitudinally assess the lymphatics of 18 patients undergoing treatment for cancer of the oral cavity, oropharynx, and/or larynx following intraoral and intradermal injections of ICG. Patients were imaged before and after surgery, before and after fractionated RT for up to 100 weeks after treatments. Patients who underwent both LND and RT developed lymphatic dermal backflow on treated sides ranging from days after the start of RT to weeks after its completion, while contralateral regions that were not associated with LND but also treated with RT, experienced no such changes in functional lymphatic anatomies. The results show for the first time, the striking reorganization of the lymphatic vasculature and may enable early diagnosis of HN lymphedema.

  17. Lymphatics of the Mediastinum, Esophagus and Lungs: Thoracic Surgeon's Point of View

    OpenAIRE

    Ciprian Bolca

    2012-01-01

    The anatomy of the thoracic lymphatic system is very complex and not completely known yet. Thoracic malignancies, especially lung and esophageal cancers, are rapidly increasing as incidence. A good knowledge of the thoracic lymphatic system is very important in staging, diagnosis and treatment of these malignancies. The complete lymphadenectomy has a crucial role in both to achieve a correct postoperative stage and a complete resection of pathologic tissue. The article is a glimpse on the lym...

  18. An inguinal mass with local vascular lesions induced by a lymphatic filaria.

    Science.gov (United States)

    Abdel-Hameed, Ahmed A; Dura, Wieslaw T; Alkhalife, Ibrahim S

    2004-08-01

    A 47-year-old Indian male presented with an inguinal mass clinically suspicious as a tumor. Histological examination of the excised mass demonstrated tissue reaction to degenerating intravascular adult filarial worms. The worms have been identified as a lymphatic filariae, most probably Wuchereria bancrofti. The case report underscores the need to maintain suspicion of genitourinary filarial lesions in non-endemic areas and describes atypical vascular lesions induced by lymphatic filariae.

  19. Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease.

    Science.gov (United States)

    Randolph, Gwendalyn J; Bala, Shashi; Rahier, Jean-François; Johnson, Michael W; Wang, Peter L; Nalbantoglu, ILKe; Dubuquoy, Laurent; Chau, Amélie; Pariente, Benjamin; Kartheuser, Alex; Zinselmeyer, Bernd H; Colombel, Jean-Frederic

    2016-12-01

    Early pathological descriptions of Crohn disease (CD) argued for a potential defect in lymph transport; however, this concept has not been thoroughly investigated. In mice, poor healing in response to infection-induced tissue damage can cause hyperpermeable lymphatic collecting vessels in mesenteric adipose tissue that impair antigen and immune cell access to mesenteric lymph nodes (LNs), which normally sustain appropriate immunity. To investigate whether analogous changes might occur in human intestinal disease, we established a three-dimensional imaging approach to characterize the lymphatic vasculature in mesenteric tissue from controls or patients with CD. In CD specimens, B-cell-rich aggregates resembling tertiary lymphoid organs (TLOs) impinged on lymphatic collecting vessels that enter and exit LNs. In areas of creeping fat, which characterizes inflammation-affected areas of the bowel in CD, we observed B cells and apparent innate lymphoid cells that had invaded the lymphatic vessel wall, suggesting these cells may be mediators of lymphatic remodeling. Although TLOs have been described in many chronic inflammatory states, their anatomical relationship to preestablished LNs has never been revealed. Our data indicate that, at least in the CD-affected mesentery, TLOs are positioned along collecting lymphatic vessels in a manner expected to affect delivery of lymph to LNs. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Lymphatic involvement in the disappearance of steroidogenic cells from the corpus luteum during luteolysis.

    Directory of Open Access Journals (Sweden)

    Hironori Abe

    Full Text Available In mammals, the corpus luteum (CL is an essential endocrine gland for the establishment and maintenance of pregnancy. If pregnancy is not established, the CL regresses and disappears rapidly from the ovary. A possible explanation for the rapid disappearance of the CL is that luteal cells are transported from the ovary via lymphatic vessels. Here, we report the presence of cells positive for 3β-hydroxysteroid dehydrogenase (3β-HSD, an enzyme involved in progesterone synthesis, in the lumen of lymphatic vessels at the regressing luteal stage and in the lymphatic fluid collected from the ovarian pedicle ipsilateral to the regressing CL. The 3β-HSD positive cells were alive and contained lipid droplets. The 3β-HSD positive cells in the lymphatic fluid were most abundant at days 22-24 after ovulation. These findings show that live steroidogenic cells are in the lymphatic vessels drained from the CL. The outflow of steroidogenic cells starts at the regressing luteal stage and continues after next ovulation. The overall findings suggest that the complete disappearance of the CL during luteolysis is involved in the outflow of luteal cells from the CL via ovarian lymphatic vessels.

  1. Olfactory route for cerebrospinal fluid drainage into the cervical lymphatic system in a rabbit experimental model

    Institute of Scientific and Technical Information of China (English)

    Haisheng Liu; Zhili Ni; Yetao Chen; Dong Wang; Yan Qi; Qiuhang Zhang; Shijie Wang

    2012-01-01

    The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil(R) (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system.

  2. Lymph node transfer and perinodal lymphatic growth factor treatment for lymphedema.

    Science.gov (United States)

    Honkonen, Krista M; Visuri, Mikko T; Tervala, Tomi V; Halonen, Paavo J; Koivisto, Mari; Lähteenvuo, Markku T; Alitalo, Kari K; Ylä-Herttuala, Seppo; Saaristo, Anne M

    2013-05-01

    Our objective was to define the optimal growth factor treatment to be used in combination with lymph node transfer to normalize lymphatic vascular anatomy. In the lymph node transfer method, lymphatic anastomoses are expected to form spontaneously. However, lymphangiogenic growth factor therapies have shown promising results in preclinical models of lymphedema. The inguinal lymphatic vasculature of pigs was surgically destroyed around the inguinal lymph node. To enhance the regrowth of the lymphatic network in the defected area, adenoviral vascular endothelial growth factor C (VEGF-C) was administered intranodally or perinodally. Control animals received injections of saline or control vector. The lymphangiogenic effect of the growth factor therapy and any potential adverse effects associated with the 2 alternative delivery routes were examined 2 months postoperatively. Both routes of growth factor administration induced robust growth of lymphatic vessels and helped to preserve the structure of the transferred lymph nodes in comparison with the controls. The lymph nodes of the control treated animals regressed in size and their nodal structure was partly replaced by fibro-fatty scar tissue. Intranodally injected adenoviral VEGF-C and adenoviral vector encoding control gene LacZ induced macrophage accumulation inside the node, whereas perinodal administration of VEGF-C did not have this adverse effect. Lymphangiogenic growth factors improve lymphatic vessel regeneration and lymph node function after lymph node transfer. The perinodal route of delivery provides a basis for future clinical trials in lymphedema patients.

  3. Slit2/Robo4 signaling modulates HIV-1 gp120-induced lymphatic hyperpermeability.

    Directory of Open Access Journals (Sweden)

    Xuefeng Zhang

    2012-01-01

    Full Text Available Dissemination of HIV in the host involves transit of the virus and virus-infected cells across the lymphatic endothelium. HIV may alter lymphatic endothelial permeability to foster dissemination, but the mechanism is largely unexplored. Using a primary human lymphatic endothelial cell model, we found that HIV-1 envelope protein gp120 induced lymphatic hyperpermeability by disturbing the normal function of Robo4, a novel regulator of endothelial permeability. HIV-1 gp120 induced fibronectin expression and integrin α₅β₁ phosphorylation, which led to the complexing of these three proteins, and their subsequent interaction with Robo4 through its fibronectin type III repeats. Moreover, pretreatment with an active N-terminus fragment of Slit2, a Robo4 agonist, protected lymphatic endothelial cells from HIV-1 gp120-induced hyperpermeability by inhibiting c-Src kinase activation. Our results indicate that targeting Slit2/Robo4 signaling may protect the integrity of the lymphatic barrier and limit the dissemination of HIV in the host.

  4. [A retrospective analysis on occult neck lymphatic metastasis in early tongue cancer].

    Science.gov (United States)

    Gong, Q L; Bian, C; Liu, H

    2016-10-07

    Objective: To investigate the number and level of occult neck lymphatic metastasis for squamous cell carcinoma of tongue in clinical stage Ⅰ/Ⅱ, and the relationship between cell differentiation and occult neck lymphatic metastasis. Methods: A total of 101 cases diagnosed preoperatively as having squamous cell carcinoma of tongue in clinical stage Ⅰ/Ⅱ (cT1/T2N0M0) between January 2005 and April 2015 were analysed retrospectively. Whether presence of occult neck lymphatic metastasis in these cases was studied. Results: Occult neck lymphatic metastases were found in 22 (21.78%) of 101 cases, 10 men and 12 women, with an age range of 22 to 83 years. There was not statistically significant association between tumor size or cell differentiation and occult neck lymphatic metastasis (P>0.05). The metastasis occurred most commonly in level Ⅱ, followed by levelsⅠ, Ⅲ and Ⅳ. There was no lymph node metastasis in Level Ⅴ. There were total 20 cases with occult neck lymphatic metastasis in at least one of levelⅠ, Ⅱ, Ⅲ(90.9%), One of these case was skipping metastasis in level Ⅲ(4.6%). Conclusion: The early tongue cancer has a high rate of occult lymph metastasis, which occurs commonly in levels Ⅱ, Ⅰ and Ⅲ, but there is not significant association between the metastasis and tumor size or cell differentiation.

  5. A case of generalized lymphatic anomaly causing skull-base leakage and bacterial meningitis.

    Science.gov (United States)

    Suga, Kenichi; Goji, Aya; Inoue, Miki; Kawahito, Masami; Taki, Masako; Mori, Kazuhiro

    2017-05-01

    Generalized lymphatic anomaly is a multifocal lymphatic malformation that affects the skin, thoracic viscera, and bones. A 3year-old Japanese boy presented with right facial palsy due to cystic tumors in the ipsilateral petrous bone. Pericardial effusion had been found incidentally and generalized lymphatic anomaly had been diagnosed by pericardial biopsy. Petrous bone tumor had been followed up without surgery. At the age of seven he presented with fever and disturbance of consciousness, and bacterial meningitis due to Streptococcus pneumoniae was diagnosed. Computed tomography and magnetic resonance imaging revealed middle skull-base leakage due to lymphatic malformation. He achieved complete recovery under intensive care with antibiotics and mechanical ventilation. One year later, he presented with multiple cystic formations in bilateral femora. At the 3-year follow-up, the patient was healthy with no recurrence of meningitis and osteolytic lesions in the femora were non-progressive. Computed tomography and magnetic resonance imaging are useful for demonstration of skull-base leakage by generalized lymphatic anomaly. We should consider generalized lymphatic anomaly among the differential diagnoses for skull-base leakage. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  6. Relationship between Lymphatic Vessel Density and Lymph Node Metastasis of Invasive Micropapillary Carcinoma of the Breast

    Institute of Scientific and Technical Information of China (English)

    Xiaojing Guo; Ling Chen; Ronggang Lang; Yu Fan; Li Fu

    2006-01-01

    OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast.METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases.RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma.CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.

  7. Molecular Modeling of Cardiac Troponin

    Science.gov (United States)

    Manning, Edward P.

    The cardiac thin filament regulates interactions of actin and myosin, the force-generating elements of muscular contraction. Over the past several decades many details have been discovered regarding the structure and function of the cardiac thin filament and its components, including cardiac troponin (cTn). My hypothesis is that signal propagation occurs between distant ends of the cardiac troponin complex through calcium-dependent alterations in the dynamics of cTn and tropomyosin (Tm). I propose a model of the thin filament that encompasses known structures of cTn, Tm and actin to gain insight into cardiac troponin's allosteric regulation of thin filament dynamics. By performing molecular dynamics simulations of cTn in conjunction with overlapping Tm in two conditions, with and without calcium bound to site II of cardiac troponin C (cTnC), I found a combination of calcium-dependent changes in secondary structure and dynamics throughout the cTn-Tm complex. I then applied this model to investigate familial hypertrophic cardiomyopathy (FHC), a disease of the sarcomere that is one of the most commonly occurring genetic causes of heart disease. Approximately 15% of known FHC-related mutations are found in cardiac troponin T (cTnT), most of which are in or flank the alpha-helical N-tail domain TNT1. TNT1 directly interacts with overlapping Tm coiled coils. Using this model I identified effects of TNT1 mutations that propagate to the cTn core where site II of cTnC, the regulatory site of calcium binding in the thin filament, is located. Specifically, I found that mutations in TNT1 alter the flexibility of TNT1 and that the flexibility of TNT1 is inversely proportional to the cooperativity of calcium activation of the thin filament. Further, I identified a pathway of propagation of structural and dynamic changes linking TNT1 to site II of cTnC. Mutation-induced changes at site II cTnC alter calcium coordination which corresponds to biophysical measurements of calcium

  8. Potential application of in vivo imaging of impaired lymphatic duct to evaluate the severity of pressure ulcer in mouse model

    Science.gov (United States)

    Kasuya, Akira; Sakabe, Jun-Ichi; Tokura, Yoshiki

    2014-02-01

    Ischemia-reperfusion (IR) injury is a cause of pressure ulcer. However, a mechanism underlying the IR injury-induced lymphatic vessel damage remains unclear. We investigated the alterations of structure and function of lymphatic ducts in a mouse cutaneous IR model. And we suggested a new method for evaluating the severity of pressure ulcer. Immunohistochemistry showed that lymphatic ducts were totally vanished by IR injury, while blood vessels were relatively preserved. The production of harmful reactive oxygen species (ROS) was increased in injured tissue. In vitro study showed a high vulnerability of lymphatic endothelial cells to ROS. Then we evaluated the impaired lymphatic drainage using an in vivo imaging system for intradermally injected indocyanine green (ICG). The dysfunction of ICG drainage positively correlated with the severity of subsequent cutaneous changes. Quantification of the lymphatic duct dysfunction by this imaging system could be a useful strategy to estimate the severity of pressure ulcer.

  9. A cautionary tale: anaphylaxis to isosulfan blue dye after 12 years and 3339 cases of lymphatic mapping.

    Science.gov (United States)

    Kaufman, Gabriel; Guth, Amber A; Pachter, H Leon; Roses, Daniel F

    2008-02-01

    Sentinel node biopsy has become the standard method for lymphatic staging in early-stage breast cancer and melanomas. The most commonly used technique uses both a radioactive tracer as well as blue dye, usually isosulfan blue. In this report, we discuss two episodes of anaphylaxis to isosulfan blue during lymphatic mapping, occurring 12 years and 3339 lymphatic mapping cases after adoption of the technique, and discuss management issues raised by these events.

  10. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  11. Near-infrared fluorescence imaging of lymphatics in head and neck lymphedema

    Science.gov (United States)

    Tan, I.-Chih; Maus, Erik A.; Rasmussen, John C.; Marshall, Milton V.; Fife, Caroline E.; Smith, Latisha A.; Sevick-Muraca, Eva M.

    2011-03-01

    Treatment of lymphatic disease is complicated and controversial, due in part to the limited understanding of the lymphatic system. Lymphedema (LE) is a frequent complication after surgical resection and radiation treatment in cancer survivors, and is especially debilitating in regions where treatment options are limited. Although some extremity LE can be effectively treated with manual lymphatic drainage (MLD) therapy or compression devices to direct proximal lymph transport, head and neck LE is more challenging, due to complicated geometry and complex lymphatic structure in head and neck region. Herein, we describe the compassionate use of an investigatory technique of near-infrared (NIR) fluorescence imaging to understand the lymphatic anatomy and function, and to help direct MLD in a patient with head and neck LE. Immediately after 9 intradermal injections of 25 μg indocyanine green each around the face and neck region, NIR fluorescence images were collected using a custom-built imaging system with diffused excitation light illumination. These images were then used to direct MLD therapy. In addition, 3-dimensional (3D) surface profilometry was used to monitor response to therapy. NIR fluorescence images of functioning lymphatic vessels and abnormal structures were obtained. Precise geometries of facial structures were obtained using 3D profilometry, and detection of small changes in edema between therapy sessions was achieved. NIR fluorescence imaging provides a mapping of lymphatic architecture to direct MLD therapy and thus improve treatment efficacy in the head and neck LE, while 3D profilometry allowed longitudinal assessment of edema to evaluate the efficacy of therapy.

  12. National mass drug administration costs for lymphatic filariasis elimination.

    Directory of Open Access Journals (Sweden)

    Ann S Goldman

    Full Text Available BACKGROUND: Because lymphatic filariasis (LF elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin, a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk. METHODOLOGY/PRINCIPAL FINDINGS: To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1 the total annual cost of the LF program, 2 the average cost per person treated, and 3 the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1 the age (newness of the MDA program, 2 the use of volunteers, and 3 the size of the population treated. Substantial contributions by governments were documented - generally 60%-90% of program operation costs, excluding costs of donated medications. CONCLUSIONS/SIGNIFICANCE: MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones.

  13. CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability.

    Science.gov (United States)

    Ivanov, Stoyan; Scallan, Joshua P; Kim, Ki-Wook; Werth, Kathrin; Johnson, Michael W; Saunders, Brian T; Wang, Peter L; Kuan, Emma L; Straub, Adam C; Ouhachi, Melissa; Weinstein, Erica G; Williams, Jesse W; Briseño, Carlos; Colonna, Marco; Isakson, Brant E; Gautier, Emmanuel L; Förster, Reinhold; Davis, Michael J; Zinselmeyer, Bernd H; Randolph, Gwendalyn J

    2016-04-01

    Lymphatic collecting vessels direct lymph into and from lymph nodes (LNs) and can become hyperpermeable as the result of a previous infection. Enhanced permeability has been implicated in compromised immunity due to reduced flow of lymph and immune cells to LNs, which are the primary site of antigen presentation to T cells. Presently, very little is known about the molecular signals that affect lymphatic collecting vessel permeability. Here, we have shown that lymphatic collecting vessel permeability is controlled by CCR7 and that the chronic hyperpermeability of collecting vessels observed in Ccr7-/- mice is followed by vessel fibrosis. Reexpression of CCR7 in DCs, however, was sufficient to reverse the development of such fibrosis. IFN regulatory factor 4-positive (IRF4+) DCs constitutively interacted with collecting lymphatics, and selective ablation of this DC subset in Cd11c-Cre Irf4fl/fl mice also rendered lymphatic collecting vessels hyperpermeable and fibrotic. Together, our data reveal that CCR7 plays multifaceted roles in regulating collecting vessel permeability and fibrosis, with one of the key players being IRF4-dependent DCs.

  14. Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake

    Directory of Open Access Journals (Sweden)

    Fang Li

    2017-05-01

    Full Text Available Huperzine A (Hup-A is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve (AUC of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (P<0.01. The absorption rate constant (Ka and the apparent permeability coefficient (Papp for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of Ka and Papp of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration (Cmax of the blocking model were significantly lower than those of the control model (P<0.05. The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.

  15. Lymphatic filariasis among the Yakurr people of Cross River State, Nigeria

    Directory of Open Access Journals (Sweden)

    Iboh Cletus I

    2012-09-01

    Full Text Available Abstract Background In order to initiate a disease elimination programme for lymphatic filariasis based on mass drug administration, a proper understanding of the geographical distribution and degree of risk is essential. Methods An investigation of lymphatic filariasis due to Wuchereria bancrofti was carried out among 785 people in four communities of Yakurr Local Government Area of Cross River State, Nigeria between March and August, 2009. Finger prick blood smear samples collected from the subjects were examined for W. bancrofti using standard parasitological protocol. The subjects were also screened for clinical manifestations of lymphatic filariasis. Results Of the 785 persons examined, 48 (6.1% were positive for microfilariae in their thick blood smear. There was a significant difference in the prevalence of lymphatic filariasis among the various age groups (P  0.05. The overall mean microfilarial density of the infected individuals was 5.6mf/50 μl. There was a significant variation (P  Conclusions The National Lymphatic Filariasis Elimination Programme should intervene by expanding the distribution of albendazole and ivermectin to all endemic areas including Yakurr Local Government Area of Cross River State, Nigeria.

  16. Heterogeneity between primary colon carcinoma and paired lymphatic and hepatic metastases.

    Science.gov (United States)

    Lan, Huanrong; Jin, Ketao; Xie, Bojian; Han, Na; Cui, Binbin; Cao, Feilin; Teng, Lisong

    2012-11-01

    Heterogeneity is one of the recognized characteristics of human tumors, and occurs on multiple levels in a wide range of tumors. A number of studies have focused on the heterogeneity found in primary tumors and related metastases with the consideration that the evaluation of metastatic rather than primary sites could be of clinical relevance. Numerous studies have demonstrated particularly high rates of heterogeneity between primary colorectal tumors and their paired lymphatic and hepatic metastases. It has also been proposed that the heterogeneity between primary colon carcinomas and their paired lymphatic and hepatic metastases may result in different responses to anticancer therapies. The heterogeneity in primary colon carcinoma and corresponding metastases by genome‑wide gene expression analysis has not been extensively studied. In the present study, we investigated the differentially expressed genes between a primary colon carcinoma specimen (obtained from a 40-year-old female colon carcinoma patient with lymphatic and hepatic metastases) and its paired lymphatic and hepatic metastases by genome-wide gene expression analysis using GeneChip HGU133Plus2.0 expression arrays. Our results demonstrate that genome-wide gene expression varies between primary colon carcinoma and its paired lymphatic and hepatic metastases.

  17. Near-infrared indocyanine dye permits real-time characterization of both venous and lymphatic circulation

    Science.gov (United States)

    Kurahashi, Toshikazu; Iwatsuki, Katsuyuki; Onishi, Tetsuro; Arai, Tetsuya; Teranishi, Katsunori; Hirata, Hitoshi

    2016-08-01

    We investigated the optical properties of a near-infrared (NIR) fluorochrome, di-β-cyclodextrin-binding indocyanine derivative (TK-1), and its pharmacokinetic differences with indocyanine green (ICG). TK-1 was designed to have hydrophilic cyclodextrin molecules and, thus, for higher water solubility and smaller particle sizes than the plasma protein-bound ICG. We compared optical properties such as the absorption and fluorescence spectra, quantum yield, and photostability between both dyes in vitro. In addition, we subcutaneously injected a 1 mM solution of TK-1 or ICG into the hind footpad of rats and observed real-time NIR fluorescence intensities in their femoral veins and accompanying lymphatics at the exposed groin site to analyze the dye pharmacokinetics. These optical experiments demonstrated that TK-1 has high water solubility, a low self-aggregation tendency, and high optical and chemical stabilities. Our in vivo imaging showed that TK-1 was transported via peripheral venous flow and lymphatic flow, whereas ICG was drained only through lymphatics. The results of this study showed that lymphatic and venous transport can be differentially regulated and is most likely influenced primarily by particle size, and that TK-1 can enable real-time NIR fluorescence imaging of whole fluids and solute movement via both microvessels and lymphatics, which conventional ICG cannot achieve.

  18. Lymphatic drainage of the liver and its implications in the management of colorectal cancer liver metastases.

    Science.gov (United States)

    Lupinacci, Renato Micelli; Paye, François; Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirolla; Herman, Paulo

    2014-12-01

    The liver is the most common site of distant metastases in patients with colorectal cancer. Surgery represents the mainstream for curative treatment of colorectal cancer liver metastases (CRCLM) with long-term survival up to 58 and 36 % at 5 and 10 years, respectively. Despite advances on diagnosis, staging and surgical strategies, 60-70 % of patients will develop recurrence of the disease even after R0 resection of CRCLM. Tumor staging, prognosis, and therapeutic approaches for cancer are most often based on the extent of involvement of regional lymph nodes (LNs) and, to a lesser extent, on the invasion of regional lymphatic vessels draining the primary tumor. For CRCLM, the presence of intra hepatic lymphatic and blood vascular dissemination has been associated with an increased risk of intra hepatic recurrence, poorer disease-free and overall survival after liver resection. Also, several studies have reviewed the role of surgery in the patient with concomitant CRCLM and liver pedicle LN metastasis. Although pedicle LN involvement is related to worst survival rates, it does not differentiate patients that will relapse from those that will not. This review aims to briefly describe the anatomy of the liver's lymphatic drainage, the incidence of intrahepatic lymphatic invasion and hilar lymph node involvement, as well as their clinical impact in CRCLM. A better understanding of the role of liver lymphatic metastasis might, in the near future, impact the strategy of systemic therapies after liver resection as for primary colorectal tumors.

  19. Prediction of melanoma metastasis by the Shields index based on lymphatic vessel density

    Directory of Open Access Journals (Sweden)

    Metcalfe Chris

    2010-05-01

    Full Text Available Abstract Background Melanoma usually presents as an initial skin lesion without evidence of metastasis. A significant proportion of patients develop subsequent local, regional or distant metastasis, sometimes many years after the initial lesion was removed. The current most effective staging method to identify early regional metastasis is sentinel lymph node biopsy (SLNB, which is invasive, not without morbidity and, while improving staging, may not improve overall survival. Lymphatic density, Breslow's thickness and the presence or absence of lymphatic invasion combined has been proposed to be a prognostic index of metastasis, by Shields et al in a patient group. Methods Here we undertook a retrospective analysis of 102 malignant melanomas from patients with more than five years follow-up to evaluate the Shields' index and compare with existing indicators. Results The Shields' index accurately predicted outcome in 90% of patients with metastases and 84% without metastases. For these, the Shields index was more predictive than thickness or lymphatic density. Alternate lymphatic measurement (hot spot analysis was also effective when combined into the Shields index in a cohort of 24 patients. Conclusions These results show the Shields index, a non-invasive analysis based on immunohistochemistry of lymphatics surrounding primary lesions that can accurately predict outcome, is a simple, useful prognostic tool in malignant melanoma.

  20. Leadership in cardiac surgery.

    Science.gov (United States)

    Rao, Christopher; Patel, Vanash; Ibrahim, Michael; Ahmed, Kamran; Wong, Kathie A; Darzi, Ara; von Segesser, Ludwig K; Athanasiou, Thanos

    2011-06-01

    Despite the efficacy of cardiac surgery, less invasive interventions with more uncertain long-term outcomes are increasingly challenging surgery as first-line treatment for several congenital, degenerative and ischemic cardiac diseases. The specialty must evolve if it is to ensure its future relevance. More importantly, it must evolve to ensure that future patients have access to treatments with proven long-term effectiveness. This cannot be achieved without dynamic leadership; however, our contention is that this is not enough. The demands of a modern surgical career and the importance of the task at hand are such that the serendipitous emergence of traditional charismatic leadership cannot be relied upon to deliver necessary change. We advocate systematic analysis and strategic leadership at a local, national and international level in four key areas: Clinical Care, Research, Education and Training, and Stakeholder Engagement. While we anticipate that exceptional individuals will continue to shape the future of our specialty, the creation of robust structures to deliver collective leadership in these key areas is of paramount importance.

  1. Mitochondrial quality control in cardiac diseases.

    Directory of Open Access Journals (Sweden)

    Juliane Campos

    2016-10-01

    Full Text Available Disruption of mitochondrial homeostasis is a hallmark of cardiac diseases. Therefore, maintenance of mitochondrial integrity through different surveillance mechanisms is critical for cardiomyocyte survival. In this review, we discuss the most recent findings on the central role of mitochondrial quality control processes including regulation of mitochondrial redox balance, aldehyde metabolism, proteostasis, dynamics and clearance in cardiac diseases, highlighting their potential as therapeutic targets.

  2. Effect of water resource development and management on lymphatic filariasis, and estimates of populations at risk.

    Science.gov (United States)

    Erlanger, Tobias E; Keiser, Jennifer; Caldas De Castro, Marcia; Bos, Robert; Singer, Burton H; Tanner, Marcel; Utzinger, Jürg

    2005-09-01

    Lymphatic filariasis (LF) is a debilitating disease overwhelmingly caused by Wuchereria bancrofti, which is transmitted by various mosquito species. Here, we present a systematic literature review with the following objectives: (i) to establish global and regional estimates of populations at risk of LF with particular consideration of water resource development projects, and (ii) to assess the effects of water resource development and management on the frequency and transmission dynamics of the disease. We estimate that globally, 2 billion people are at risk of LF. Among them, there are 394.5 million urban dwellers without access to improved sanitation and 213 million rural dwellers living in close proximity to irrigation. Environmental changes due to water resource development and management consistently led to a shift in vector species composition and generally to a strong proliferation of vector populations. For example, in World Health Organization (WHO) subregions 1 and 2, mosquito densities of the Anopheles gambiae complex and Anopheles funestus were up to 25-fold higher in irrigated areas when compared with irrigation-free sites. Although the infection prevalence of LF often increased after the implementation of a water project, there was no clear association with clinical symptoms. Concluding, there is a need to assess and quantify changes of LF transmission parameters and clinical manifestations over the entire course of water resource developments. Where resources allow, integrated vector management should complement mass drug administration, and broad-based monitoring and surveillance of the disease should become an integral part of large-scale waste management and sanitation programs, whose basic rationale lies in a systemic approach to city, district, and regional level health services and disease prevention.

  3. Relationship between cardiac rhythm disorders, serum urotensin ІІ and angiotensin ІІ levels in patients with stage ii hypertension and carotid atherosclerosis in dynamics of treatment with candesartan and lercanidipine

    Directory of Open Access Journals (Sweden)

    O. V. Demidenko,

    2016-10-01

    Full Text Available Arterial hypertension is one of the most common diseases of the cardiovascular system. Objective – to study dynamics of cardiac rhythm disorders, serum urotensin II and angiotensin II levels in patients with stage II hypertension associated with carotid atherosclerosis during treatment with candesartan and lercanidipine. Methods of the study. Under our observation there were 122 patients with stage 2 hypertension aged between 36–75 years. Average age of the patients was 51.52±1.27 years, including men – 52 (43 %, women – 70 (57 %. Cardiac arrhythmias and conduction disorders were detected by means of Holter ECG. Serum urotensin II and angiotensin II levels in the blood serum were determined by use of an immunoenzymatic method. Statistical analysis was performed by means of the Statistica® 6.0 for Windows (StatSoft Inc. software using parametric and nonparametric methods. Results. It was found that the receiving of lercanidipine and candesartan showed unidirectional positive effect on cardiac rhythm disorders in most patients with stage II hypertension. The use of candesartan statistically insignificantly increased levels of angiotensin II in patients of the first group of observation by 20.8 % compared with baseline values (p>0.05. However, as a result of candesartan treatment serum angiotensin II levels in patients with stage II hypertension without carotid atherosclerosis reliably increased by 47.1 % (p<0.05. Unlike candesartan, the use of lercanidipine leads to a statistically significant decrease in the concentration of urotensin II by 30.8 % (p<0.05 in patients with stage II hypertension associated with carotid atherosclerosis. Conclusions. Lercanidipine can be recommended as a first line antihypertensive drug in case of simultaneous hypertension and atherosclerotic lesion of brachiocephalic arteries.

  4. LYMPHATIC MAPPING AND SENTINEL LYMPH NODE BIOPSY IN THE PATIENTS WITH BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To identify the feasibility of the lymphatic mapping and sentinel node biopsy (SNB) in patients with breast cancer and to examine whether the characteristics of the sentinel lymph node (SLN) accurately predict the status of axillary node. Methods: 33 patients with breast cancer intraoperatively and postoperatively underwent a lymphatic mapping and the SNB using Patent Blue. Results: The SLNs were found in 30 of 33 patients (90.9%), the SLN accurately predicted the status of the axillary in 29 (96.7%). In one case the SLN was negative, but other axillary nodes were tumor positive. Conclusion: This study confirmed that the procedure of lymphatic mapping and SNB in the patients with breast cancer is feasibility, and that the histological characteristics of the SLN accurately predict the status of the axillary node. We believe that this technique might replace axillary lymph node dissection for breast cancer patients with negative axillae in the future.

  5. Lymphatic fat absorption varies among rats administered dairy products differing in physiochemical properties

    DEFF Research Database (Denmark)

    Fruekilde, Maj-Britt; Høy, Carl-Erik

    2004-01-01

    We examined in rats the intestinal absorption of fat from dairy products differing in physiochemical properties. Five dairy products (cream cheese, cream, sour cream, butter, and mixed butter) with minor differences in fatty acid composition were administered by gavage to rats, and lymphatic fat...... absorption was examined. Absorption was followed for 8 h after administration of 300 mg fat from the dairy products. Administration of cream and sour cream resulted in faster lymphatic fat absorption than cream cheese, butter, and mixed butter, and at 8 h the accumulated absorption of fat was significantly......, these results demonstrated different lymphatic absorption patterns of fat from dairy products differing in physiochemical properties. Because the fatty acid composition of the dairy products differed only slightly, other factors such as viscosity, type of emulsion, particle size, and likely also protein content...

  6. Physics of Cardiac Arrhythmogenesis

    Science.gov (United States)

    Karma, Alain

    2013-04-01

    A normal heartbeat is orchestrated by the stable propagation of an excitation wave that produces an orderly contraction. In contrast, wave turbulence in the ventricles, clinically known as ventricular fibrillation (VF), stops the heart from pumping and is lethal without prompt defibrillation. I review experimental, computational, and theoretical studies that have shed light on complex dynamical phenomena linked to the initiation, maintenance, and control of wave turbulence. I first discuss advances made to understand the precursor state to a reentrant arrhythmia where the refractory period of cardiac tissue becomes spatiotemporally disordered; this is known as an arrhythmogenic tissue substrate. I describe observed patterns of transmembrane voltage and intracellular calcium signaling that can contribute to this substrate, and symmetry breaking instabilities to explain their formation. I then survey mechanisms of wave turbulence and discuss novel methods that exploit electrical pacing stimuli to control precursor patterns and low-energy pulsed electric fields to control turbulence.

  7. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure......About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate...

  8. Pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis in tumor lymphangiogenesis and lymphatic metastasis.

    Science.gov (United States)

    Wang, Jingwen; Huang, Yuhong; Zhang, Jun; Wei, Yuanyi; Mahoud, Salma; Bakheet, Ahmed Musa Hago; Wang, Li; Zhou, Shuting; Tang, Jianwu

    2016-10-01

    Precondition for tumor lymphatic metastasis is that tumor cells induce formation of original and newborn lymphatic vessels and invade surrounding lymphatic vessels in tumor stroma, while some pathway-related molecules play an important role in mechanisms associated with proliferation and migration of lymphatic endothelial cells (LECs) and tumor cells. In lymphangiogenesis and lymphatic metastasis, the pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, such as Furin-like enzyme, CNTN1, Prox1, LYVE-1, Podoplanin, SOX18, SDF1 and CXCR4, are direct constitutors as a portion of VEGFC/D-VEGFR3/NRP2 axis, and their biological activities rely on this ligand-receptor system. These axis-related signal molecules could gradually produce waterfall-like cascading effects, mediate differentiation and maturation of LECs, remodel original and neonatal lymphatic vessels, as well as ultimately promote tumor cell chemotaxis, migration, invasion and metastasis to lymphoid tracts. This review summarizes the structure and function features of pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, the expression changes of these molecules in different anatomic organs or histopathologic types or development stages of various tumors, the characteristics of transduction, implementation, integration of signal networks, the interactive effects on biological behaviors between tumor cells and lymphatic endothelial cells, and their molecular mechanisms and significances in tumor lymphangiogenesis and lymphatic metastasis.

  9. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

    Directory of Open Access Journals (Sweden)

    Yoshimura Kazunori

    2010-11-01

    Full Text Available Abstract Background From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs. This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs. Methods Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control and from cirrhotic livers (LC (Child A-LC and Child C-LC. Immunohistochemical (IHC, Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels. Results Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue. Conclusion It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver.

  10. Perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in human gallbladders

    Institute of Scientific and Technical Information of China (English)

    Masayuki Nagahashi; Yoshio Shirai; Toshifumi Wakai; Jun Sakata; Yoichi Ajioka; Katsuyoshi Hatakeyama

    2007-01-01

    AIM: To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders.METHODS: Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40,which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens,nine high-power (× 200) fields with the highest lymphatic vessel density (LVD), termed "hot spots", were identified for each layer (mucosa, muscle layer, and perimuscular connective tissue). In individual hot spots,the LVD and relative lymphatic vessel area (LVA) were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses.RESULTS: In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 ± 9.2,35.4 ± 15.7, and 65.5 ± 12.2, respectively, and the LVA was 0.4 ± 0.4, 2.1 ± 1.1, and 9.4 ± 2.6, respectively.Thus, both the LVD and LVA differed significantly (P <0.001 and P < 0.001, respectively; Kruskal-Wallis test)among the individual layers of the wall of the gallbladder,with the highest LVD and LVA values in the perimuscular connective tissue. Most (98 of 108) of the hot spots within the perimuscular connective tissue were located within 500 μm of the lower border of the muscle layer.CONCLUSION: The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 (tumor invading the perimuscular connective tissue) or more advanced gallbladder carcinoma.

  11. Lymphatic drainage from the treated versus untreated prostate: feasibility of sentinel node biopsy in recurrent cancer

    Energy Technology Data Exchange (ETDEWEB)

    Vermeeren, Lenka; Valdes Olmos, Renato A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Meinhardt, Willem; Poel, Henk G. van der [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Urology, Amsterdam (Netherlands)

    2010-11-15

    The goal of this study was to establish the feasibility of sentinel node biopsy in patients with recurrent prostate cancer after initial local treatment and to compare lymphatic drainage patterns of the treated versus untreated prostate. In ten patients with a proven local recurrence after initial local treatment (four external beam radiation, four brachytherapy and two high-intensity focused ultrasound), the radiotracer ({sup 99m}Tc-nanocolloid, GE Healthcare) was injected into the prostate. Planar images after 15 min and 2 h were followed by SPECT/CT (Symbia T, Siemens) to visualize lymphatic drainage. Laparoscopic sentinel lymphadenectomy was assisted by a gamma probe (Europrobe, EuroMedical Instruments) and a portable gamma camera (Sentinella, S102, Oncovision). Sentinel node identification and lymphatic drainage patterns were compared to a consecutive series of 70 untreated prostate carcinoma patients from our institute. Lymphatic drainage was visualized in all treated patients, with a median of 3.5 sentinel nodes per patient. Most sentinel nodes were localized in the pelvic area, although the percentage of patients with a sentinel node outside the pelvic para-iliac region (para-aortic, presacral, inguinal or near the ventral abdominal wall) was high compared to the untreated patients (80 versus 34%, p = 0.01). In patients with recurrent prostate cancer, 95% of the sentinel nodes could be harvested and half of the patients had at least one positive sentinel node on pathological examination. Lymphatic mapping of the treated prostate appears feasible, although sentinel nodes are more frequently found in an aberrant location. Larger trials are needed to assess the sensitivity and therapeutic value of lymphatic mapping in recurrent prostate cancer. (orig.)

  12. Mapping the distinctive populations of lymphatic endothelial cells in different zones of human lymph nodes.

    Directory of Open Access Journals (Sweden)

    Saem Mul Park

    Full Text Available The lymphatic sinuses in human lymph nodes (LNs are crucial to LN function yet their structure remains poorly defined. Much of our current knowledge of lymphatic sinuses derives from rodent models, however human LNs differ substantially in their sinus structure, most notably due to the presence of trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic sinuses are bounded and traversed by lymphatic endothelial cells (LECs. A better understanding of LECs in human LNs is likely to improve our understanding of the regulation of cell trafficking within LNs, now an important therapeutic target, as well as disease processes that involve lymphatic sinuses. We therefore sought to map all the LECs within human LNs using multicolor immunofluorescence microscopy to visualize the distribution of a range of putative markers. PROX1 was the only marker that uniquely identified the LECs lining and traversing all the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by LECs in the paracortical and medullary sinuses in the vast majority of LNs studied, whilst the subcapsular and trabecular sinuses lacked these molecules. These data highlight the existence of at least two distinctive populations of LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not specific for LECs, and CD144 and CD31 stained both LECs and blood vascular endothelial cells (BECs; in contrast, CD59 and CD105 stained BECs but not LECs. We also showed that antigen-presenting cells (APCs in the sinuses could be clearly distinguished from LECs by their expression of CD169, and their lack of expression of PROX1 and STAB2, or endothelial markers such as CD144. However, both LECs and sinus APCs were stained with DCN46, an antibody commonly used to detect CD209.

  13. Study on the mechanism of regulation on peritoneal lymphatic stomata with Chinese herbal medicine

    Science.gov (United States)

    Ding, Shi-Ping; Li, Ji-Cheng; Xu, Jian; Mao, Lian-Gen

    2002-01-01

    AIM: To study the mechanism of Chinese herbal medicine (CHM, the prescription consists of Radix Salviae Miltiorrhizae, Radix Codonopsitis Pilosulae, Rhizoma Atractylodis Alba and Rhizoma Alismatis, Leonurus Heterophyllus Sweet, etc) on the regulation of the peritoneal lymphatic stomata and the ascites drainage. METHODS: The mouse model of live fibrosis was established with the application of intragastric installations of carbon tetrachloride once every three days; scanning electron microscope and computer image processing were used to detect the area and the distributive density of the peritoneal lymphatic stomata; and the concentrations of urinary ion and NO in the serum were analyzed in the experiment. RESULTS: Two different doses of CHM could significantly increase the area of the peritoneal lymphatic stomata, promote its distributive density and enhance the drainage of urinary ion such as sodium, potassium and chlorine. Meanwhile, the NO concentration of two different doses of CHM groups was 133.52 ± 23.57 μmol/L, and 137.2 ± 26.79 μmol/L respectively. In comparison with the control group and model groups (48.36 ± 6.83 μmol/L, and 35.22 ± 8.94 μmol/L, P lymphatic stomata and the drainage of urinary ion was altered by adding NO donor(sodium nitropurruside, SNP) or NO synthase (NOS) inhibitor (N(G)-monomethyl-L-arginine, L-NMMA) to the peritoneal cavity. CONCLUSION: There existed correlations between high NO concentration and enlargement of the peritoneal lymphatic stomata, which result in enhanced drainage of ascites. These data supported the hypothesis that Chinese herbal medicine could regulate the peritoneal lymphatic stomata by accelerating the synthesis and release of endogenous NO. PMID:11833101

  14. Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

    2017-05-22

    We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation, we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and 7 methylated DNAs from primary EOC tissues that predicted lymphatic invasion, and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (P < 0.001 and P = 0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (Log rank P value = 0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed, and also associated with survival of EOC patients.

  15. Methods for effective fluorophore injection and imaging of lymphatics in small animals

    Science.gov (United States)

    DSouza, Alisha V.; Marra, Kayla A.; Gunn, Jason R.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

    2016-03-01

    Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully perform fluorescence imaging of IRDye®680RD in the lymphatics, in a repeatable manner.

  16. Evaluation of a recombinant parasite antigen for the diagnosis of lymphatic filariasis.

    Science.gov (United States)

    Dissanayake, S; Zheng, H; Dreyer, G; Xu, M; Watawana, L; Cheng, G; Wang, S; Morin, P; Deng, B; Kurniawan, L

    1994-06-01

    We evaluated the usefulness of a recombinant parasite antigen (recSXP1) for the serologic diagnosis of lymphatic filariasis. A large proportion of sera from microfilaremic donors living in five different endemic countries (356 of 446 [80%]) contained IgG antibodies to recSXP1, as do sera from approximately 33% of amicrofilaremic patients with acute filarial disease and/or indirect evidence of active filarial infection. Exposure to filarial worms per se does not appear sufficient to elicit an anti-SXP1 antibody response. Thus, this serologic test identifies a large proportion of persons with active lymphatic filariasis among residents of endemic areas.

  17. The Role of Lymphatic Endothelial Cells in Liver Injury and Tumor Development

    Science.gov (United States)

    Lukacs-Kornek, Veronika

    2016-01-01

    Lymphatics and lymphatic endothelial cells (LECs) possess multiple immunological functions besides affecting immune cell migration, such as inhibiting T cell proliferation and antigen presentation by dendritic cells. Moreover, they control the trans-endothelial transport of multiple molecules and antigens. Emerging evidence suggest their active involvements in immunregulation, tumor, and metastases formation. In the liver, increased lymphangiogenesis, specifically at the portal area has been associated with multiple liver diseases in particular primary biliary cirrhosis, idiopathic portal hypertension, and liver malignancies. Nevertheless, the exact role and contribution of LECs to liver diseases are poorly understood. The review summarizes the current understanding of LECs in liver diseases. PMID:27965673

  18. The role of lymphatic endothelial cells in liver injury and tumor development

    Directory of Open Access Journals (Sweden)

    Veronika Lukacs-Kornek

    2016-11-01

    Full Text Available Lymphatics and lymphatic endothelial cells (LECs possess multiple immunological functions besides affecting immune cell migration such as inhibiting T cell proliferation and antigen presentation by dendritic cells. Moreover, they control the trans-endothelial transport of multiple molecules and antigens. Emerging evidence suggests their active involvements in immunoregulation, tumor and metastases formation. In the liver, increased lymphangiogenesis, specifically at the portal area has been associated with multiple liver diseases in particular primary biliary cirrhosis, idiopathic portal hypertension, and liver malignancies. Nevertheless, the exact role and contribution of LECs to liver diseases are poorly understood. The review summarizes the current understanding of LECs in liver diseases.

  19. Lymphatic recovery of exogenous oleic acid in rats on long chain or specific structured triacylglycerol diets

    DEFF Research Database (Denmark)

    Vistisen, Bodil; Mu, Huiling; Høy, Carl-Erik

    2006-01-01

    Specific structured triacylglycerols, MLM (M = medium-chain fatty acid, L = long-chain fatty acid), rapidly deliver energy and long-chain fatty acids to the body and are used for longer periods in human enteral feeding. In the present study rats were fed diets of 10 wt% MLM or LLL (L = oleic acid...... structure and composition (P = 0.07). This study demonstrated that with a diet containing specific structured triacylglycerol, the lymphatic recovery of 18:1 n-9 after a single bolus of fat was dependent on the triacylglycerol structure of the bolus. This indicates that the lymphatic recovery of long...

  20. Community-acquired adenovirus pneumonia in a patient with chronic lymphatic leukaemia.

    Science.gov (United States)

    Larsen, I K; Nielsen, H

    2005-03-01

    Described here is a severe case of community-acquired adenovirus pneumonia that occurred in a previously healthy 54-year-old male who was later determined to have stage A chronic lymphatic leukemia. The clinical presentation was consistent with that of atypical pneumonia. Testing with PCR revealed adenovirus in a bronchoalveolar lavage sample, while all other tests to determine a bacterial or virological etiology were negative. Further examination of the patient revealed the previously undiagnosed chronic lymphatic leukemia. Following treatment with human immunoglobulin and oxygen therapy with continuous positive airway pressure support the patient recovered from the pneumonia completely.

  1. What Is Cardiac Rehabilitation?

    Science.gov (United States)

    ANSWERS by heart Treatments + Tests What Is Cardiac Rehabilitation? A cardiac rehabilitation (rehab) program takes place in a hospital or ... special help in making lifestyle changes. During your rehabilitation program you’ll… • Have a medical evaluation to ...

  2. Cardiac tamponade (image)

    Science.gov (United States)

    Cardiac tamponade is a condition involving compression of the heart caused by blood or fluid accumulation in the space ... they cannot adequately fill or pump blood. Cardiac tamponade is an emergency condition that requires hospitalization.

  3. Cardiac Procedures and Surgeries

    Science.gov (United States)

    ... Procedure Learn more about cardiac medications , including dual antiplatelet therapy, that you may need to take after your ... Procedure Learn more about cardiac medications , including dual antiplatelet therapy, that you may need to take after your ...

  4. Study on intralymphatic-targeted hyaluronic acid-modified nanoliposome: influence of formulation factors on the lymphatic targeting.

    Science.gov (United States)

    Tiantian, Ye; Wenji, Zhang; Mingshuang, Sun; Rui, Yang; Shuangshuang, Song; Yuling, Mao; Jianhua, Yao; Xinggang, Yang; Shujun, Wang; Weisan, Pan

    2014-08-25

    In this study, hyaluronic acid-modified docetaxel-loaded liposomes were prepared to evaluate the lymphatic targeting after subcutaneous administration, and formulation factors affecting the lymphatic targeting were examined, including free hyaluronic acid, molecular weight, hyaluronic acid-density and particle diameter. The high molecular weight hyaluronic acid-modified docetaxel-loaded liposomes (HA-LPs) and low molecular weight hyaluronic acid-modified docetaxel-loaded liposomes (LMWHA-LPs) were prepared via electrostatic attraction. The physicochemical properties and in vitro drug release were evaluated. The lymphatic drainage and the lymph node uptake were investigated by pharmacokinetics and distribution recovery of docetaxel in lymph nodes, injection site and plasma. The lymphatic targeting ability of optimized Cy7-loaded LMWHA-LPs (LMWHA-LPs/Cy7) was evaluated by near-infrared fluorescence imaging technique. The result showed that HA-LPs and LMWHA-LPs with suitable and stable physicochemical properties could be used for in vivo lymphatic targeting studies. Hyaluronic acid-modified liposome significantly increased the docetaxel recovery in lymph nodes, and displayed higher AUC(0-24h) and longer retention time compared to unmodified liposomes in vivo. In contrast, the presence of free hyaluronic acid hindered the lymphatic drainage and increased the plasma-drug concentration. Importantly, LMWHA-modification improved lymphatic drainage and lymph node uptake of liposomes compared with HA-modification. And Lymph node uptake of LMWHA-LPs depended mainly on LMWHA-density instead of particle size. The results of in vivo imaging showed that LMWHA-LPs/Cy7 significantly located in the lymphatic system. And both DTX-loaded and Cy7-loaded LMWHA-LPs had similar and stable lymphatic target level. Our investigation showed that LMWHA-LPs were a highly promising lymphatic targeting carrier for chemotherapy drugs and diagnostic fluorescence agents.

  5. Manual lymphatic drainage for lymphedema following breast cancer treatment

    Science.gov (United States)

    Ezzo, Jeanette; Manheimer, Eric; McNeely, Margaret L; Howell, Doris M; Weiss, Robert; Johansson, Karin I; Bao, Ting; Bily, Linda; Tuppo, Catherine M; Williams, Anne F; Karadibak, Didem

    2016-01-01

    Background More than one in five patients who undergo treatment for breast cancer will develop breast cancer-related lymphedema (BCRL). BCRL can occur as a result of breast cancer surgery and/or radiation therapy. BCRL can negatively impact comfort, function, and quality of life (QoL). Manual lymphatic drainage (MLD), a type of hands-on therapy, is frequently used for BCRL and often as part of complex decongestive therapy (CDT). CDT is a fourfold conservative treatment which includes MLD, compression therapy (consisting of compression bandages, compression sleeves, or other types of compression garments), skin care, and lymph-reducing exercises (LREs). Phase 1 of CDT is to reduce swelling; Phase 2 is to maintain the reduced swelling. Objectives To assess the efficacy and safety of MLD in treating BCRL. Search methods We searched Medline, EMBASE, CENTRAL, WHO ICTRP (World Health Organization’s International Clinical Trial Registry Platform), and Cochrane Breast Cancer Group’s Specialised Register from root to 24 May 2013. No language restrictions were applied. Selection criteria We included randomized controlled trials (RCTs) or quasi-RCTs of women with BCRL. The intervention was MLD. The primary outcomes were (1) volumetric changes, (2) adverse events. Secondary outcomes were (1) function, (2) subjective sensations, (3) QoL, (4) cost of care. Data collection and analysis We collected data on three volumetric outcomes. (1) LE (lymphedema) volume was defined as the amount of excess fluid left in the arm after treatment, calculated as volume in mL of affected arm post-treatment minus unaffected arm post-treatment. (2) Volume reduction was defined as the amount of fluid reduction in mL from before to after treatment calculated as the pretreatment LE volume of the affected arm minus the post-treatment LE volume of the affected arm. (3) Per cent reduction was defined as the proportion of fluid reduced relative to the baseline excess volume, calculated as volume

  6. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    Amin, A.S.; Asghari-Roodsari, A.; Tan, H.L.

    2010-01-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I-Na) during phase 0 of the cardiac action potential. The importance of I-Na for normal cardiac electrical activity is reflected by the high incidence of

  7. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    Amin, A.S.; Asghari-Roodsari, A.; Tan, H.L.

    2010-01-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I-Na) during phase 0 of the cardiac action potential. The importance of I-Na for normal cardiac electrical activity is reflected by the high incidence of

  8. Vascular, glial, and lymphatic immune gateways of the central nervous system

    NARCIS (Netherlands)

    Engelhardt, Britta; Carare, Roxana O.; Bechmann, Ingo; Fluegel, Alexander; Laman, Jon D.; Weller, Roy O.

    2016-01-01

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. R

  9. Transport in lymphatic capillaries. I. Macroscopic measurements using residence time distribution theory.

    Science.gov (United States)

    Swartz, M A; Berk, D A; Jain, R K

    1996-01-01

    We present a novel integrative method for characterizing transport in the lymphatic capillaries in the tail of the anesthetized mouse, which is both sensitive and reproducible for quantifying uptake and flow. Interstitially injected, fluorescently labeled macromolecules were used to visualize and quantify these processes. Residence time distribution (RTD) theory was employed to measure net flow velocity in the lymphatic network as well as to provide a relative measure of lymphatic uptake of macromolecules from the interstitium. The effects of particle size and injection pressure were determined. The uptake rate was found to be independent of particle size in the range of a 6- to 18-nm radius; beyond this size, the interstitial matrix seemed to pose a greater barrier. A comparison of 10 vs. 40 cmH2O injection pressure showed a significant influence on the relative uptake rate but not on the net velocity within the network (3.3 +/- 0.8 vs. 3.8 +/- 1.0 micron/s). This suggested the presence of a systemic driving force for baseline lymph propulsion that is independent of the local pressure gradients driving the uptake. This model can be used to examine various aspects of transport physiology of the initial lymphatics.

  10. Lymph Nodes and Cancer Metastasis: New Perspectives on the Role of Intranodal Lymphatic Sinuses

    Directory of Open Access Journals (Sweden)

    Rui-Cheng Ji

    2016-12-01

    Full Text Available The lymphatic system is essential for transporting interstitial fluid, soluble antigen, and immune cells from peripheral tissues to lymph nodes (LNs. Functional integrity of LNs is dependent on intact lymphatics and effective lymph drainage. Molecular mechanisms that facilitate interactions between tumor cells and lymphatic endothelial cells (LECs during tumor progression still remain to be identified. The cellular and molecular structures of LNs are optimized to trigger a rapid and efficient immune response, and to participate in the process of tumor metastasis by stimulating lymphangiogenesis and establishing a premetastatic niche in LNs. Several molecules, e.g., S1P, CCR7-CCL19/CCL21, CXCL12/CXCR4, IL-7, IFN-γ, TGF-β, and integrin α4β1 play an important role in controlling the activity of LN stromal cells including LECs, fibroblastic reticular cells (FRCs and follicular dendritic cells (DCs. The functional stromal cells are critical for reconstruction and remodeling of the LN that creates a unique microenvironment of tumor cells and LECs for cancer metastasis. LN metastasis is a major determinant for the prognosis of most human cancers and clinical management. Ongoing work to elucidate the function and molecular regulation of LN lymphatic sinuses will provide insight into cancer development mechanisms and improve therapeutic approaches for human malignancy.

  11. Quantitative immunohistochemical assessment of blood and lymphatic microcirculation in cutaneous lichen planus lesions.

    Science.gov (United States)

    Výbohová, Desanka; Mellová, Yvetta; Adamicová, Katarína; Adamkov, Marián; Hešková, Gabriela

    2015-06-01

    Latest advances have brought to light the hypothesis that angiogenesis and lymphangiogenesis are tightly connected to some chronic inflammatory diseases. The present study focuses on immunohistochemical assessment of the quantitative changes in the blood and lymphatic microcirculatory bed in common chronic dermatosis - cutaneous lichen planus. Double immunohistochemistry with CD34 and podoplanin antibodies was used to detect blood and lymphatic endothelium, while anti-human VEGF was used for the observation of a key angiogenesis and lymphangiogenesis inducer. Morphometric analysis was performed with QuickPhoto Micro image analysis software. Results confirmed statistically significant enlargement of both the blood and lymphatic microcirculatory beds. Compared to healthy skin, cutaneous lichen planus lesions revealed 1.6 times enlarged blood microcirculatory bed and 1.8 times enlarged lymphatic microcirculatory bed. Vascular endothelial growth factor (VEGF) expression in lesional skin was significantly higher in the epidermis (19.1 times increase) than in the dermis (10.3 times increase). These findings indicate a tight association of angiogenesis and lymphangiogenesis with the pathogenesis of cutaneous lichen planus.

  12. Microcirculation-on-a-Chip: A Microfluidic Platform for Assaying Blood- and Lymphatic-Vessel Permeability.

    Directory of Open Access Journals (Sweden)

    Miwa Sato

    Full Text Available We developed a microfluidic model of microcirculation containing both blood and lymphatic vessels for examining vascular permeability. The designed microfluidic device harbors upper and lower channels that are partly aligned and are separated by a porous membrane, and on this membrane, blood vascular endothelial cells (BECs and lymphatic endothelial cells (LECs were cocultured back-to-back. At cell-cell junctions of both BECs and LECs, claudin-5 and VE-cadherin were detected. The permeability coefficient measured here was lower than the value reported for isolated mammalian venules. Moreover, our results showed that the flow culture established in the device promoted the formation of endothelial cell-cell junctions, and that treatment with histamine, an inflammation-promoting substance, induced changes in the localization of tight and adherens junction-associated proteins and an increase in vascular permeability in the microdevice. These findings indicated that both BECs and LECs appeared to retain their functions in the microfluidic coculture platform. Using this microcirculation device, the vascular damage induced by habu snake venom was successfully assayed, and the assay time was reduced from 24 h to 30 min. This is the first report of a microcirculation model in which BECs and LECs were cocultured. Because the micromodel includes lymphatic vessels in addition to blood vessels, the model can be used to evaluate both vascular permeability and lymphatic return rate.

  13. Lymphatic Fatty Acid Absorption Profile During 24 Hours After Administration of Triglycerides to Rats

    DEFF Research Database (Denmark)

    Porsgaard, Trine Charlotte; Straarup, Ellen Marie; Høy, Carl-Erik

    1999-01-01

    In this study we determined in rats the complete 24-h lymphatic fatty acid profile after administration of either rapeseedoil (RO) or rapeseed oil interesterified with 10:0 (RO/C10) with special emphasis on the transition from absorptive topostabsorptive phase. Rats were subjected to cannulation...

  14. Primary Kaposi's sarcoma in lymph nodes concurrent with chronic lymphatic leukemia.

    Science.gov (United States)

    Weshler, Z; Leviatan, A; Krasnokuki, D; Kopolovitch, J

    1979-02-01

    Both Kaposi's sarcoma and chronic lymphatic leukemia affect the lymph nodes, and not infrequently, the same patient. The authors describe the occurrence of both diseases in the same lymph node. The rarity of this finding suggests different histopathogenic origins of the two diseases.

  15. IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression

    DEFF Research Database (Denmark)

    Nielsen, Sebastian Rune; Hammer, Troels; Gibson, Josefine

    2013-01-01

    OBJECTIVE: IL-27 belongs to the IL-12 family of cytokines and is recognized for its role in Th cell differentiation and as an inhibitor of tumor-angiogenesis. The purpose of this study was to investigate the effect of IL-27 on proliferation of lymphatic endothelial cells to gain insight into the ......OBJECTIVE: IL-27 belongs to the IL-12 family of cytokines and is recognized for its role in Th cell differentiation and as an inhibitor of tumor-angiogenesis. The purpose of this study was to investigate the effect of IL-27 on proliferation of lymphatic endothelial cells to gain insight......U kits and the role of STAT1 and chemokines was determined by use of siRNA and recombinant proteins. RESULTS: Stimulation of lymphatic endothelial cell cultures with IL-27 induced JAK dependent phosphorylation of STAT1 and STAT3 and inhibited lymphatic endothelial cell proliferation and migration....... Expression of CXCL10 and CXCL11, both STAT1 target genes, were profoundly up-regulated upon IL-27 stimulation, and recombinant CXCL10 and CXCL11 inhibited FGF-2-induced proliferation in vitro. siRNA targeting of STAT1 almost completely abrogated CXCL10 and CXCL11 expression as well as the proliferative...

  16. Effect of Physical Methods of Lymphatic Drainage on Postexercise Recovery of Mixed Martial Arts Athletes.

    Science.gov (United States)

    Zebrowska, Aleksandra; Trybulski, Robert; Roczniok, Robert; Marcol, Wieslaw

    2017-08-16

    Physical methods are reported to be important for accelerating skeletal muscle regeneration, decreasing muscle soreness, and shortening of the recovery time. The aim of the study was to assess the effect of the physical methods of lymphatic drainage (PMLD) such as manual lymphatic drainage (MLD), the Bodyflow (BF) therapy, and lymphatic drainage by deep oscillation (DO) on postexercise regeneration of the forearm muscles of mixed martial arts (MMA) athletes. Eighty MMA athletes aged 27.5 ± 6.4 years were allocated to 4 groups: MLD, the BF device, DO therapy, and the control group. Blood flow velocity in the cephalic vein was measured with the ultrasound Doppler velocity meter. Maximal strength of the forearm muscles (Fmax), muscle tissue tension, pain threshold, blood lactate concentration (LA), and activity of creatine kinase were measured in all groups at rest, after the muscle fatigue test (post-ex) and then 20 minutes, 24, and 48 hours after the application of PMLD. The muscle fatigue test reduced Fmax in all subjects, but in the groups receiving MLD, DO, and BF significantly higher Fmax was observed at recovery compared with post-ex values. The application of MDL reduced the postexercise blood LA and postexercise muscle tension. The lymphatic drainage methods, whether manual or using electro-stimulation and DO, improve postexercise regeneration of the forearm muscles of MMA athletes. The methods can be an important element of therapeutic management focused on optimizing training effects and reducing the risk of injuries of the combat sports athletes.

  17. Understanding Lymphatic Drainage Pathways of the Ovaries to Predict Sites for Sentinel Nodes in Ovarian Cancer

    NARCIS (Netherlands)

    Kleppe, M.; Kraima, A.C.; Kruitwagen, R.F.P.M.; Van Gorp, T.; Smit, N.N.; Van Munsteren, J.C.; De Ruiter, M.C.

    2015-01-01

    Objective: In ovarian cancer, detection of sentinel nodes is an upcoming procedure. Perioperative determination of the patient’s sentinel node(s) might prevent a radical lymphadenectomy and associated morbidity. It is essential to understand the lymphatic drainage pathways of the ovaries, which are

  18. Study on the mechanism of regulation on peritoneal lymphatic stomata with Chinese herbal medicine

    OpenAIRE

    Ding, Shi-Ping; Li, Ji-Cheng; Xu, Jian; Mao, Lian-Gen

    2002-01-01

    AIM: To study the mechanism of Chinese herbal medicine (CHM, the prescription consists of Radix Salviae Miltiorrhizae, Radix Codonopsitis Pilosulae, Rhizoma Atractylodis Alba and Rhizoma Alismatis, Leonurus Heterophyllus Sweet, etc) on the regulation of the peritoneal lymphatic stomata and the ascites drainage.

  19. Vascular, glial, and lymphatic immune gateways of the central nervous system

    NARCIS (Netherlands)

    Engelhardt, Britta; Carare, Roxana O.; Bechmann, Ingo; Fluegel, Alexander; Laman, Jon D.; Weller, Roy O.

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system.

  20. Longitudinal evaluation of manual lymphatic drainage for the treatment of gynoid lipodystrophy*

    Science.gov (United States)

    Schonvvetter, Bianca; Soares, Juliana Laudicéia Marques; Bagatin, Ediléia

    2014-01-01

    BACKGROUND The gynoidlypodystrophy, known as cellulitis or cellulite, refers to a condition that gives the skin an undulating and uneven appearance, affecting 80-90% of women after puberty. OBJECTIVES to investigate the efficacy and safety of manual lymphatic drainage for cellulite management. METHODS this was an open, prospective, intervention study including 20 women aged from 20 to 40 years. Fourteen sessions of manual lymphatic drainage were performed once a week on lower limbs and buttocks. RESULTS Fifteen women completed the study. A significant improvement on quality of life was observed (p=0.018). A significant reduction (p=0.023), estimated at 0.3±0.8 cm, in hip circumference was found, but no difference was found in thighs circumference (p>0.05). A significant reduction elastic recuperation of skin on buttocks, which means skin elasticity worsening, was observed. All measures obtained by ultrasound images showed no changes (p>0.05). CONCLUSION manual lymphatic drainage was safe but not effective as an isolated approach for cellulite management. Further randomized, controlled or comparative studies about manual lymphatic drainage for cellulite control, as unique or combined therapeutic modality, are necessary. PMID:25184909

  1. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

    DEFF Research Database (Denmark)

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

    2013-01-01

    Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

  2. Mechanisms of edema formation in myxedema--increased protein extravasation and relatively slow lymphatic drainage

    DEFF Research Database (Denmark)

    Parving, H H; Hansen, J M; Nielsen, S L;

    1979-01-01

    of generalized edema (P less than 0.05). All variables returned to normal during l-thyroxine treatment. The extravascular accumulation of albumin, and presumably of all other plasma proteins, is important in the generalized edema typically found in myxedema. Inadequate lymphatic drainage may also explain...

  3. Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: A modelling study

    NARCIS (Netherlands)

    M.A. Irvine (Michael A.); W.A. Stolk (Wilma); Smith, M.E. (Morgan E); S.V. Subramanian; B.K. Singh (Brajendra K.); G.J. Weil (Gary); E. Michael (Edwin); T.D. Hollingsworth (T. Déirdre)

    2017-01-01

    textabstractBackground: Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen (ivermectin

  4. Lymphatic Fatty Acid Absorption Profile During 24 Hours After Administration of Triglycerides to Rats

    DEFF Research Database (Denmark)

    Porsgaard, Trine Charlotte; Straarup, Ellen Marie; Høy, Carl-Erik

    1999-01-01

    In this study we determined in rats the complete 24-h lymphatic fatty acid profile after administration of either rapeseedoil (RO) or rapeseed oil interesterified with 10:0 (RO/C10) with special emphasis on the transition from absorptive topostabsorptive phase. Rats were subjected to cannulation ...

  5. Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: A modelling study

    NARCIS (Netherlands)

    M.A. Irvine (Michael A.); W.A. Stolk (Wilma); Smith, M.E. (Morgan E); S.V. Subramanian; B.K. Singh (Brajendra K.); G.J. Weil (Gary); E. Michael (Edwin); T.D. Hollingsworth (T. Déirdre)

    2017-01-01

    textabstractBackground: Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen

  6. The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel.

    Science.gov (United States)

    Aspelund, Aleksanteri; Tammela, Tuomas; Antila, Salli; Nurmi, Harri; Leppänen, Veli-Matti; Zarkada, Georgia; Stanczuk, Lukas; Francois, Mathias; Mäkinen, Taija; Saharinen, Pipsa; Immonen, Ilkka; Alitalo, Kari

    2014-09-01

    In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment.

  7. Composition of the Extracellular Matrix of Lymphatic Novel Threadlike Structures: Is It Keratin?

    Directory of Open Access Journals (Sweden)

    Hyub Huh

    2013-01-01

    Full Text Available Background. The lumen of novel threadlike structures (NTSs is enclosed by a single layer of endothelial cells surrounded by extracellular matrix (ECM. We hypothesized that collagen may be a component of the ECM associated with lymphatic NTSs. Methods. Six female New Zealand white rabbits were anesthetized, and the NTS structures within lymphatic vessels were identified by contrast-enhanced stereomicroscopy or alcian blue staining. Isolated NTS specimens were stained with acridine orange, YOYO-1, and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI. The structural and molecular composition of the ECM was investigated using transmission electron microscopy (TEM, electrospray ionization-mass spectrometry, and proteomic analysis. Results. The lymph vessel wall was stained red by DiI, and rod-shaped nuclei were stained green by YOYO-1. The area surrounding the NTS was also stained red and contained green rod-shaped nuclei. TEM images showed that the NTS consisted of many ECM fibers and the ECM fibers appeared to be ~100 nm in diameter and had narrowly spaced striated bands. Proteomic analysis of the lymphatic NTS-associated ECM identified 4 proteins: keratin 10, cytokeratin 3, cytokeratin 12, and soluble adenylyl cyclase. Conclusion. The TEM study suggested that the lymphatic NTS-associated ECM did not contain collagen. This was confirmed by proteomic analysis, which showed that keratin was the major component of the ECM.

  8. Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance.

    Science.gov (United States)

    Mohammed, Rabab A A; Ellis, Ian O; Mahmmod, Ali M; Hawkes, E Claire; Green, Andrew R; Rakha, Emad A; Martin, Stewart G

    2011-06-01

    Basal and triple-negative breast cancer phenotypes are characterised by unfavourable biological behaviour and outcome. Although certain studies have examined their pathological and molecular profile, the vascular characteristics of lymphatic and blood vessels have not been examined. Immunohistochemical staining with podoplanin, CD34 and CD31 was used to examine lymphatic and microvessel density, as well as vascular invasion in 197 basal-like and in 99 triple-negative breast tumours and compared against 200 non-basal and 334 non-triple-negative cases. All specimens were lymph node negative. Vascular invasion was identified as blood or lymphatic vascular invasion by the differential expression of markers. All measurements were correlated with clinicopathological features and prognosis. No significant difference was detected between the basal and triple-negative groups in terms of lymphatic or microvessel density or vascular invasion. However, both the basal and the triple-negative groups showed significantly higher microvessel density than did the non-basal and non-triple-negative groups (P=0.017 and Pcontrols. Interestingly, vascular invasion, almost entirely lymphatic invasion, was detected in 27% of the basal and in 26% of the triple-negative groups with no significant difference in comparison with control groups. In both basal and triple negatives, vascular invasion was associated with poorer survival by univariate and multivariate analyses. The 20-year overall survival rate in basal-like tumours was 55% in vascular invasion-positive cases compared with 73% in vascular invasion-negative tumours (P=0.012), and 46% in triple-negative vascular invasion-positive compared with 79% in vascular invasion-negative tumours (P=0.001). Basal-like vs non-basal-like and triple-negative vs non-triple-negative tumours have similar vascular characteristics in terms of lymphatic vessel density and vascular invasion but higher microvessel density, suggesting that such groups may

  9. Mechanisms of cardiac pain.

    Science.gov (United States)

    Foreman, Robert D; Garrett, Kennon M; Blair, Robert W

    2015-04-01

    Angina pectoris is cardiac pain that typically is manifested as referred pain to the chest and upper left arm. Atypical pain to describe localization of the perception, generally experienced more by women, is referred to the back, neck, and/or jaw. This article summarizes the neurophysiological and pharmacological mechanisms for referred cardiac pain. Spinal cardiac afferent fibers mediate typical anginal pain via pathways from the spinal cord to the thalamus and ultimately cerebral cortex. Spinal neurotransmission involves substance P, glutamate, and transient receptor potential vanilloid-1 (TRPV1) receptors; release of neurokinins such as nuclear factor kappa b (NF-kb) in the spinal cord can modulate neurotransmission. Vagal cardiac afferent fibers likely mediate atypical anginal pain and contribute to cardiac ischemia without accompanying pain via relays through the nucleus of the solitary tract and the C1-C2 spinal segments. The psychological state of an individual can modulate cardiac nociception via pathways involving the amygdala. Descending pathways originating from nucleus raphe magnus and the pons also can modulate cardiac nociception. Sensory input from other visceral organs can mimic cardiac pain due to convergence of this input with cardiac input onto spinothalamic tract neurons. Reduction of converging nociceptive input from the gallbladder and gastrointestinal tract can diminish cardiac pain. Much work remains to be performed to discern the interactions among complex neural pathways that ultimately produce or do not produce the sensations associated with cardiac pain.

  10. An in situ optical imaging system for measuring lipid uptake, vessel contraction, and lymph flow in small animal lymphatic vessels

    Science.gov (United States)

    Kassis, Timothy; Weiler, Michael J.; Dixon, J. Brandon

    2012-03-01

    All dietary lipids are transported to venous circulation through the lymphatic system, yet the underlying mechanisms that regulate this process remain unclear. Understanding how the lymphatics functionally respond to changes in lipid load is important in the diagnosis and treatment of lipid and lymphatic related diseases such as obesity, hypercholesterolemia, and lymphedema. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. A custom-built optical set-up provides us with the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. This is achieved by dividing the light path into two optical bands. Utilizing high-speed and back-illuminated CCD cameras and post-acquisition image processing algorithms, we have the potential quantify correlations between vessel contraction, lymph flow and lipid concentration of mesenteric lymphatic vessels in situ. Local flow velocity is measured through lymphocyte tracking, vessel contraction through measurements of the vessel walls and lipid uptake through fluorescence intensity tracking of a fluorescent long chain fatty acid analogue, Bodipy FL C16. This system will prove to be an invaluable tool for both scientists studying lymphatic function in health and disease, and those investigating strategies for targeting the lymphatic system with orally delivered drugs.

  11. Dual-channel in-situ optical imaging system for quantifying lipid uptake and lymphatic pump function

    Science.gov (United States)

    Kassis, Timothy; Kohan, Alison B.; Weiler, Michael J.; Nipper, Matthew E.; Cornelius, Rachel; Tso, Patrick; Brandon Dixon, J.

    2012-08-01

    Nearly all dietary lipids are transported from the intestine to venous circulation through the lymphatic system, yet the mechanisms that regulate this process remain unclear. Elucidating the mechanisms involved in the functional response of lymphatics to changes in lipid load would provide valuable insight into recent implications of lymphatic dysfunction in lipid related diseases. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. The imaging platform provides the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. Utilizing post-acquisition image processing algorithms, we can quantify correlations between vessel pump function, lymph flow, and lipid concentration of mesenteric lymphatic vessels in situ. All image analysis is automated with customized LabVIEW virtual instruments; local flow is measured through lymphocyte velocity tracking, vessel contraction through measurements of the vessel wall displacement, and lipid uptake through fluorescence intensity tracking of an orally administered fluorescently labelled fatty acid analogue, BODIPY FL C16. This system will prove to be an invaluable tool for scientists studying intestinal lymphatic function in health and disease, and those investigating strategies for targeting the lymphatics with orally delivered drugs to avoid first pass metabolism.

  12. An automated method to control preload by compensation for stress relaxation in spontaneously contracting, isometric rat mesenteric lymphatics.

    Science.gov (United States)

    Davis, Michael J; Lane, Megan M; Scallan, Joshua P; Gashev, Anatoliy A; Zawieja, David C

    2007-08-01

    Our objective was to devise a system to automatically correct for stress relaxation of isometric rat mesenteric lymphatics (90-120 microm, ID). Stress relaxation is a particular problem in isometric studies of highly distensible vessels and is evident as a time-dependent, secondary decline in force after an abrupt length increase. Because the phasic contraction pattern of lymphatics is exquisitely sensitive to changes in preload, stress relaxation makes stable contraction patterns difficult to achieve and analyze. A DMT wire myograph was modified to accommodate an Inchworm piezo stack in series with a standard micrometer drive to permit automated control of vessel caliber/force. The force output of the myograph was digitized and computer algorithms were devised to servo control force by changing vessel diameter. The system was tested on passive lymphatics, passive small veins, and lymphatics exhibiting spontaneous force transients. The software was designed to temporarily disable servo control during a spontaneous force transient. For both active and passive lymphatics, stable preloads were very well maintained, indicating that the system was adequately compensating for stress relaxation. The method works well with isometric rat mesenteric lymphatics without disturbing spontaneous activity. It should be applicable to arterial, venous, and lymphatic vessels (80-500 microm in diameter) isolated from other tissues and species.

  13. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  14. The Mesenteric Lymph Duct Cannulated Rat Model: Application to the Assessment of Intestinal Lymphatic Drug Transport

    Science.gov (United States)

    Trevaskis, Natalie L.; Hu, Luojuan; Caliph, Suzanne M.; Han, Sifei; Porter, Christopher J.H.

    2015-01-01

    The intestinal lymphatic system plays key roles in fluid transport, lipid absorption and immune function. Lymph flows directly from the small intestine via a series of lymphatic vessels and nodes that converge at the superior mesenteric lymph duct. Cannulation of the mesenteric lymph duct thus enables the collection of mesenteric lymph flowing from the intestine. Mesenteric lymph consists of a cellular fraction of immune cells (99% lymphocytes), aqueous fraction (fluid, peptides and proteins such as cytokines and gut hormones) and lipoprotein fraction (lipids, lipophilic molecules and apo-proteins). The mesenteric lymph duct cannulation model can therefore be used to measure the concentration and rate of transport of a range of factors from the intestine via the lymphatic system. Changes to these factors in response to different challenges (e.g., diets, antigens, drugs) and in disease (e.g., inflammatory bowel disease, HIV, diabetes) can also be determined. An area of expanding interest is the role of lymphatic transport in the absorption of orally administered lipophilic drugs and prodrugs that associate with intestinal lipid absorption pathways. Here we describe, in detail, a mesenteric lymph duct cannulated rat model which enables evaluation of the rate and extent of lipid and drug transport via the lymphatic system for several hours following intestinal delivery. The method is easily adaptable to the measurement of other parameters in lymph. We provide detailed descriptions of the difficulties that may be encountered when establishing this complex surgical method, as well as representative data from failed and successful experiments to provide instruction on how to confirm experimental success and interpret the data obtained. PMID:25866901

  15. Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration.

    Science.gov (United States)

    Choi, Inho; Lee, Yong Suk; Chung, Hee Kyoung; Choi, Dongwon; Ecoiffier, Tatiana; Lee, Ha Neul; Kim, Kyu Eui; Lee, Sunju; Park, Eun Kyung; Maeng, Yong Sun; Kim, Nam Yun; Ladner, Robert D; Petasis, Nicos A; Koh, Chester J; Chen, Lu; Lenz, Heinz-Josef; Hong, Young-Kwon

    2013-01-01

    Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs. Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling. Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57(KIP2) by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis in vivo. Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis. Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis in vitro and in vivo with a therapeutic efficacy in post-surgical lymphedema.

  16. Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation

    DEFF Research Database (Denmark)

    Mäkikallio, T H; Høiber, S; Køber, L;

    1999-01-01

    A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR.......17, 95% confidence interval 1.96 to 5.15, p negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p

  17. Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats

    DEFF Research Database (Denmark)

    Holm, René; Porter, Christopher J H; Müllertz, Anette

    2002-01-01

    animals, and this was most pronounced for the animals dosed with the structured triglycerides. CONCLUSIONS: Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption...... in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil.......PURPOSE: To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats. METHODS: Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different...

  18. Role of RhoA in regulating the pump function of isolated lymphatics from hemorrhagic shock rats.

    Science.gov (United States)

    Si, Yong-Hua; Niu, Chun-Yu; Zhao, Zi-Gang; Zhang, Li-Min; Zhang, Yu-Ping

    2013-07-01

    The aim of this present study was to examine changes in RhoA protein levels and the role in RhoA in lymphatic contractility and reactivity after hemorrhagic shock. Levels of RhoA and phospho-RhoA in lymphatic tissue isolated from hemorrhagic shock rats were measured, and the contractility and reactivity to substance P of lymphatics isolated from control rats and rats subjected to shock 0.5 and 2 h were determined with an isolated lymphatic perfusion system at a transmural pressure of 3 cmH2O. At the same time, lymphatics isolated from rats subjected to shock 0.5 and 2 h were incubated with agonists and antagonists of RhoA/Rho kinase signaling. Contractile frequency, end-diastolic and end-systolic diameter, and passive diameter were recorded and used to calculate lymphatic tonic index, contractile amplitude, and fractional pump flow. After stimulation with a gradient of substance P, the differences between the preadministration and postadministration values of contractile frequency, contractile amplitude, tonic index, and fractional pump flow were calculated to further assess lymphatic reactivity. RhoA protein levels were significantly increased at 0.5 h after shock but decreased at 2 and 3 h after shock; p-Rho levels were initially increased after shock and subsequently decreased. The contractility and reactivity of 0.5-h-shocked lymphatics were significantly reduced by the RhoA antagonist C3 transferase and the Rho kinase antagonist Y-27632. The RhoA agonist U-46619 increased the contractility and reactivity of 2-h-shocked lymphatics, whereas Y-27632 suppressed the effect of U-46619. Okadaic acid, an inhibitor of myosin light-chain phosphatase, had no effect on the contractility of 2-h-shocked lymphatics, but improved lymphatic reactivity. These results suggest that RhoA is involved in the modulation of lymphatic pump function during hemorrhagic shock and that its effects may be mediated by Rho kinase and MLCP.

  19. Using noise to determine cardiac restitution with memory

    Science.gov (United States)

    Dai, Shu; Keener, James P.

    2012-06-01

    Variation in cardiac pacing cycles, as seen, for example, in heart rate variability, has been observed for decades. Contemporarily, various mathematical models have been constructed to investigate the electrical activity of paced cardiac cells. Yet there has not been a study of these cardiac models when there is variation in the pacing cycles such as noise. We present a method that uses the stochasticity of pacing cycles to determine approximate models of the dynamics of cardiac cells, and use these models to detect bifurcations to alternans.

  20. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  1. Relations of proliferative activities of gastric carcinoma cells to lymphatic involvement, venous invasion and prognosis

    Institute of Scientific and Technical Information of China (English)

    吴云飞; 徐惠绵; 陈峻青

    2004-01-01

    Background This study was to evaluate bivariate bromodeoxyuridine(BrdUrd)/DNA flow cytometric analysis in detection of gastric carcinoma and to study the relations of cellular BrdUrd labeling indices (LI), G2/M-phase fraction(G2/MPF) and DNA ploidy pattern to lymphatic involvement, venous invasion and prognosis.Methods Fresh tumor samples from 60 patients with gastric carcinoma were analyzed by bivariate BrdUrd/DNA flow cytometry. The results were correlated with lymphatic vessel invasion, lymphatic node metastasis, the number of matastatic lymphatic nodes, and venous invasion. Propidium iodide (PI) was used as a fluorescent probe for total cellular DNA, and a monoclonal antibody against BrdUrd was used as a probe for BrdUrd incorporated into DNA. Fluorescent-labeled goat anti-mouse antibody was used as a second antibody. S-phase fractions were measured by in vitro BrdUrd labeling, and DNA ploidy and G2/MPF were also measured. Comparison of survival was performed with the log-rank test, the Chi-square test for qualitative data, and Student's t test for quantu data. Results BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic vessel invasion than in those without invasion respectively (P<0.01); the patients who had tumors with lymphatic vessel invasion showed a significantly poor prognosis (P<0.01). Both BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic node metastasis than in those without metastasis (P<0.01). A statistical significant difference was noted in the 5-year survival rates between the patients with lymph node metastasis and those without metastasis. Compared with diploid carcinoma, the incidence of lymph node metastasis was significantly higher in aneuploid carcinoma (P<0.05), and the patients with aneuploid carcinoma showed a significantly poor prognosis (P<0.05). BrdUrd LI was significantly higher in patients with more than 5 metastatic lymph nodes than those with 1-4 metastatic lymph nodes (P<0

  2. Cardiac sodium channelopathies.

    Science.gov (United States)

    Amin, Ahmad S; Asghari-Roodsari, Alaleh; Tan, Hanno L

    2010-07-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (INa) during phase 0 of the cardiac action potential. The importance of INa for normal cardiac electrical activity is reflected by the high incidence of arrhythmias in cardiac sodium channelopathies, i.e., arrhythmogenic diseases in patients with mutations in SCN5A, the gene responsible for the pore-forming ion-conducting alpha-subunit, or in genes that encode the ancillary beta-subunits or regulatory proteins of the cardiac sodium channel. While clinical and genetic studies have laid the foundation for our understanding of cardiac sodium channelopathies by establishing links between arrhythmogenic diseases and mutations in genes that encode various subunits of the cardiac sodium channel, biophysical studies (particularly in heterologous expression systems and transgenic mouse models) have provided insights into the mechanisms by which INa dysfunction causes disease in such channelopathies. It is now recognized that mutations that increase INa delay cardiac repolarization, prolong action potential duration, and cause long QT syndrome, while mutations that reduce INa decrease cardiac excitability, reduce electrical conduction velocity, and induce Brugada syndrome, progressive cardiac conduction disease, sick sinus syndrome, or combinations thereof. Recently, mutation-induced INa dysfunction was also linked to dilated cardiomyopathy, atrial fibrillation, and sudden infant death syndrome. This review describes the structure and function of the cardiac sodium channel and its various subunits, summarizes major cardiac sodium channelopathies and the current knowledge concerning their genetic background and underlying molecular mechanisms, and discusses recent advances in the discovery of mutation-specific therapies in the management of these channelopathies.

  3. Observation of {mu}s time-scale protein dynamics in the presence of Ln{sup 3+} ions: application to the N-terminal domain of cardiac troponin C

    Energy Technology Data Exchange (ETDEWEB)

    Eichmueller, Christian [Sandoz GmbH (Austria); Skrynnikov, Nikolai R. [Purdue University, Department of Chemistry (United States)], E-mail: nikolai@purdue.edu

    2007-02-15

    The microsecond time-scale motions in the N-terminal domain of cardiac troponin C (NcTnC) loaded with lanthanide ions have been investigated by means of a {sup 1}H{sup N} off-resonance spin-lock experiment. The observed relaxation dispersion effects strongly increase along the series of NcTnC samples containing La{sup 3+}, Ce{sup 3+}, and Pr{sup 3+} ions. This rise in dispersion effects is due to modulation of long-range pseudocontact shifts by {mu}s time-scale dynamics. Specifically, the motion in the coordination sphere of the lanthanide ion (i.e. in the NcTnC EF-hand motif) causes modulation of the paramagnetic susceptibility tensor which, in turn, causes modulation of pseudocontact shifts. It is also probable that opening/closing dynamics, previously identified in Ca{sup 2+}-NcTnC, contributes to some of the observed dispersions. On the other hand, it is unlikely that monomer-dimer exchange in the solution of NcTnC is directly responsible for the dispersion effects. Finally, on-off exchange of the lanthanide ion does not seem to play any significant role. The amplification of dispersion effects by Ln{sup 3+} ions is a potentially useful tool for studies of {mu}s-ms motions in proteins. This approach makes it possible to observe the dispersions even when the local environment of the reporting spin does not change. This happens, for example, when the motion involves a 'rigid' structural unit such as individual {alpha}-helix. Even more significantly, the dispersions based on pseudocontact shifts offer better chances for structural characterization of the dynamic species. This method can be generalized for a large class of applications via the use of specially designed lanthanide-binding tags.

  4. The cardiac cycle time effect revisited: Temporal dynamics of the central-vagal modulation of heart rate in human reaction time tasks.

    NARCIS (Netherlands)

    Somsen, R.J.M.; Jennings, J.R.; van der Molen, M.W.

    2004-01-01

    Lacey and Lacey (1974) suggested that during reaction time tasks higher brain centers dynamically adjust efferent vagal nerve pulses to the sino-atrial node of the heart, inducing phase-dependent heart rate changes. Since then, animal and human neuro-physiological results have provided evidence for

  5. The cardiac cycle time effect revisited: Temporal dynamics of the central-vagal modulation of heart rate in human reaction time tasks.

    NARCIS (Netherlands)

    R.J.M. Somsen; J.R. Jennings; M.W. van der Molen

    2004-01-01

    Lacey and Lacey (1974) suggested that during reaction time tasks higher brain centers dynamically adjust efferent vagal nerve pulses to the sino-atrial node of the heart, inducing phase-dependent heart rate changes. Since then, animal and human neuro-physiological results have provided evidence for

  6. Marketing cardiac CT programs.

    Science.gov (United States)

    Scott, Jason

    2010-01-01

    There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

  7. Cardiac event monitors

    Science.gov (United States)

    ... ECG) - ambulatory; Continuous electrocardiograms (EKGs); Holter monitors; Transtelephonic event monitors ... attached. You can carry or wear a cardiac event monitor up to 30 days. You carry the ...

  8. Cardiac stem cell niches

    Directory of Open Access Journals (Sweden)

    Annarosa Leri

    2014-11-01

    Full Text Available The critical role that stem cell niches have in cardiac homeostasis and myocardial repair following injury is the focus of this review. Cardiac niches represent specialized microdomains where the quiescent and activated state of resident stem cells is regulated. Alterations in niche function with aging and cardiac diseases result in abnormal sites of cardiomyogenesis and inadequate myocyte formation. The relevance of Notch1 signaling, gap-junction formation, HIF-1α and metabolic state in the regulation of stem cell growth and differentiation within the cardiac niches are discussed.

  9. Pinolenic Acid in Structured Triacylglycerols Exhibits Superior Intestinal Lymphatic Absorption As Compared to Pinolenic Acid in Natural Pine Nut Oil.

    Science.gov (United States)

    Chung, Min-Yu; Woo, Hyunjoon; Kim, Juyeon; Kong, Daecheol; Choi, Hee-Don; Choi, In-Wook; Kim, In-Hwan; Noh, Sang K; Kim, Byung Hee

    2017-03-01

    The positional distribution pattern of fatty acids (FAs) in the triacylglycerols (TAGs) affects intestinal absorption of these FAs. The aim of this study was to compare lymphatic absorption of pinolenic acid (PLA) present in structured pinolenic TAG (SPT) where PLA was evenly distributed on the glycerol backbone, with absorption of pine nut oil (PNO) where PLA was predominantly positioned at the sn-3 position. SPT was prepared via the nonspecific lipase-catalyzed esterification of glycerol with free FA obtained from PNO. Lymphatic absorption of PLA from PNO and from SPT was compared in a rat model of lymphatic cannulation. Significantly (P PNO (26.2 ± 0.6% dose), thereby indicating that PLA present in SPT has a greater capacity for lymphatic absorption than PLA from PNO.

  10. By Different Cellular Mechanisms, Lymphatic Vessels Sprout by Endothelial Cell Recruitment Whereas Blood Vessels Grow by Vascular Expansion

    Science.gov (United States)

    Parsons-Wingerter, Patricia; McKay, Terri L.; Leontiev, Dmitry; Condrich, Terence K.; DiCorleto, Paul E.

    2005-01-01

    The development of effective vascular therapies requires the understanding of all modes of vessel formation contributing to vasculogenesis, angiogenesis (here termed hemangiogenesis) and lymphangiogenesis. We show that lymphangiogenesis proceeds by blind-ended vessel sprouting via recruitment of isolated endothelial progenitor cells to the tips of growing vessels, whereas hemangiogenesis occurs by non-sprouting vessel expansion from the capillary network, during middevelopment in the quail chorioallantoic membrane (CAM). Blood vessels expanded out of capillaries that displayed transient expression of alpha smooth muscle actin (alphaSMA), accompanied by mural recruitment of migratory progenitor cells expressing SMA. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptors VEGFR-1 and VEGFR-2, alphaSMA (expressed on CAM blood vessels but not on lymphatics), homeobox transcription factor Prox-1 (specific to CAM lymphatic endothelium), and the quail hematopoetic/vascular marker, QH-1. Expression of VEGFR-1 was highly restricted to blood vessels (primarily capillaries). VEGFR-2 was expressed intensely in isolated hematopoietic cells, lymphatic vessels and moderately in blood vessels. Prox-1 was absent from endothelial progenitor cells prior to lymphatic recruitment. Although vascular endothelial growth factor-165 (VEGF(sub 165)) is a key regulator of numerous cellular processes in hemangiogenesis and vasculogenesis, the role of VEGF(sub 165) in lymphangiogenesis is less clear. Exogenous VEGF(sub 165) increased blood vessel density without changing endogenous modes of vascular/lymphatic vessel formation or marker expression patterns. However, VEGF(sub 165) did increase the frequency of blood vascular anastomoses and strongly induced the antimaturational dissociation of lymphatics from blood vessels, with frequent formation of homogeneous lymphatic networks.

  11. Aggressive cutaneous vasculitis in a patient with chronic lymphatic leukemia following granulocyte colony stimulating factor injection: a case report

    OpenAIRE

    El Husseiny Noha M; Mattar Mervat M

    2011-01-01

    Abstract Introduction Vasculitis has been reported in a few cases of chronic lymphatic leukemia and with granulocytic colony-stimulating factor therapy. Those with granulocytic colony-stimulating factor occurred after prolonged therapy and there was a rise in total leukocyte count unlike that in our patient who received just a single injection for the first time. Case presentation We report the case of a 64-year-old Egyptian man with chronic lymphatic leukemia who developed progressive cutane...

  12. Evaluation of the influence of acquisition and reconstruction parameters for 16-row multidetector CT on coronary calcium scoring using a stationary and dynamic cardiac phantom

    Energy Technology Data Exchange (ETDEWEB)

    Begemann, Philipp G.C.; Koops, Andreas; Adam, Gerhard; Nolte-Ernsting, Claus [University Medical Center Hamburg-Eppendorf, Center of Diagnostic Imaging and Intervention, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Stevendaal, Udo van; Grass, Michael [Philips Research Laboratories Hamburg, Hamburg (Germany); Koester, Ralph [University Medical Center Hamburg-Eppendorf, Center of Cardiology and Cardiovascular Surgery, Department of Cardiology/Angiology, Hamburg (Germany); Mahnken, Andreas H. [University of Technology Aachen, University Hospital, Department of Diagnostic Radiology, Aachen (Germany)

    2007-08-15

    A calcium-scoring phantom with hydroxyapatite-filled cylindrical holes (0.5 to 4 mm) was used. High-resolution scans were performed for an accuracy baseline. The phantom was mounted to a moving heart phantom. Non-moving data with the implementation of an ECG-signal were acquired for different pitches (0.2/0.3), heart rates (60/80/95 bpm) and collimations (16 x 0.75/16 x 1.5 mm). Images were reconstructed with a cone-beam multi-cycle algorithm at a standard thickness/increment of 3 mm/1.5 mm and the thinnest possible thickness (0.8/0.4 and 2/1). Subsequently, ECG-gated moving calcium-scoring phantom data were acquired. The calcium volume and Agatston score were measured. The temporal resolution and reconstruction cycles were calculated. High-resolution scans determine the calcium volume with a high accuracy (mean overestimation, 0.8%). In the non-moving measurements, the volume underestimation ranged from about 6% (16 x 0.75 mm; 0.8/0.4 mm) to nearly 25% (16 x 1.5 mm; 3/1.5 mm). Moving scans showed increased measurement errors depending on the reconstructed RR interval, collimation, pitch, heart rate and gantry rotation time. Also, a correlation with the temporal resolution could be found. The reliability of calcium-scoring results can be improved with the use of a narrower collimation, a lower pitch and the reconstruction of thinner images, resulting in higher patient doses. The choice of the correct cardiac phase within the RR interval is essential to minimize measurement errors. (orig.)

  13. Stromal CEA immunoreactivity is correlated with lymphatic invasion of human esophageal carcinoma.

    Science.gov (United States)

    Kijima, H; Oshiba, G; Kenmochi, T; Kise, Y; Tanaka, H; Chino, O; Shimada, H; Ueyama, Y; Tanaka, M; Makuuchi, H

    2000-04-01

    Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e. modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human esophageal carcinomas. In this study, we examined CEA expression in human esophageal squamous cell carcinoma and its clinicopathological significance. CEA immunoreactivity was frequently detected in the cancer cells (cytoplasmic type; 81.1%, 43/53) as well as in the cancer stroma (stromal type; 32.1%, 17/53), regardless of the depth of tumor invasion. Lymphatic invasion of cancer cells was frequently found in the stromal CEA-positive esophageal cancer (44.4%, 16/36), compared to stromal CEA-negative cancer (5.9%, 1/17) (pCEA expression plays important roles in lymphatic invasion of human esophageal squamous cell carcinoma.

  14. Lymphatic compensation during the postoperative period after breast cancer treatment with axillary dissection

    Directory of Open Access Journals (Sweden)

    Mariana Maia Freire de Oliveira

    2015-06-01

    Full Text Available Lymphedema secondary to breast cancer causes physical and psychological morbidity and compromises quality of life. The objective of this literature review was to study lymphatic compensation after surgery for breast cancer and the factors that influence this process, with a view to understanding the etiopathogenesis of lymphedema. Articles indexed on Pubmed published from 1985 to 2012 were reviewed. According to the literature, lymphangiogenesis reduces damage to lymph vessels; there is little evidence that Vascular Endothelial Growth Factor is elevated in women with lymphedema; lymphovenous communications can be observed 60 days after surgery; women without lymphedema have acquired alternative mechanisms for removal of proteins from the interstitial space; and active exercise stimulates lymphatic and venous pumping. Health professionals should teach these patients about the risk factors for lymphedema. The effects of lymphangiogenesis, proteolysis and lymphovenous communications on development of lymphedema should be studied, since these events are intimately related.

  15. Screening differentially expressed genes in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Nan Cui; Jian-Wu Tang; Li Hou; Bo Song; Li Li; Ji-Wei Liu

    2005-01-01

    AIM: To screen genes differentially expressed in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis.METHODS: A subtracted cDNA library of mouse hepatocarcinoma cell line with high potential of lymphatic metastatic Hca-F and its synogenetic cell line Hca-P with a low metastatic potential was constructed by suppression subtracted hybridization(SSH) method. The screened clones of the subtracted library were sequenced and GeneBank homology search was performed.RESULTS: Fourteen differentially expressed cDNA fragments of Hca-F were obtained with two novel genes.CONCLUSION: SSH is a useful technique to detect differentially expressioned genes and an effective method to clone novel genes.

  16. Hematopoietic and lymphatic cancers in relatives of patients with infectious mononucleosis

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Rostgaard, Klaus; Askling, Johan;

    2002-01-01

    BACKGROUND: Young adults with a history of Epstein-Barr virus (EBV)-related infectious mononucleosis have an increased risk for Hodgkin's lymphoma. EBV is detected in Hodgkin's lymphoma Reed-Sternberg cells from some patients, but in young adult patients, it is detected at a relatively low...... the importance of socioeconomic status on the association between these diseases, we determined the risk for hematopoietic and lymphatic cancers in first-degree relatives of patients with confirmed EBV-related infectious mononucleosis. METHODS: We identified parents, siblings, and offspring of 17,045 persons...... with serologically confirmed EBV-related infectious mononucleosis. Subjects in these cohorts were linked with the population-based Danish Cancer Register to identify those developing hematopoietic/lymphatic cancers after the index patient was diagnosed with infectious mononucleosis. The relative risk for cancer...

  17. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia.

    Science.gov (United States)

    Lukacs, Viktor; Mathur, Jayanti; Mao, Rong; Bayrak-Toydemir, Pinar; Procter, Melinda; Cahalan, Stuart M; Kim, Helen J; Bandell, Michael; Longo, Nicola; Day, Ronald W; Stevenson, David A; Patapoutian, Ardem; Krock, Bryan L

    2015-09-21

    Piezo1 ion channels are mediators of mechanotransduction in several cell types including the vascular endothelium, renal tubular cells and erythrocytes. Gain-of-function mutations in PIEZO1 cause an autosomal dominant haemolytic anaemia in humans called dehydrated hereditary stomatocytosis. However, the phenotypic consequence of PIEZO1 loss of function in humans has not previously been documented. Here we discover a novel role of this channel in the lymphatic system. Through whole-exome sequencing, we identify biallelic mutations in PIEZO1 (a splicing variant leading to early truncation and a non-synonymous missense variant) in a pair of siblings affected with persistent lymphoedema caused by congenital lymphatic dysplasia. Analysis of patients' erythrocytes as well as studies in a heterologous system reveal greatly attenuated PIEZO1 function in affected alleles. Our results delineate a novel clinical category of PIEZO1-associated hereditary lymphoedema.

  18. Slit-Robo signaling mediates lymphangiogenesis and promotes tumor lymphatic metastasis.

    Science.gov (United States)

    Yang, Xiao-Mei; Han, Hai-Xiong; Sui, Fei; Dai, Yu-Min; Chen, Ming; Geng, Jian-Guo

    2010-05-28

    The Slit family of guidance cues binds to Roundabout (Robo) receptors to modulate neuronal, leukocytic, and endothelial migration. Slit-Robo signaling had been reported to function as chemoattractive signal for vascular endothelial cells during angiogenesis. In this study, we found that Robo1 was expressed in lymphatic endothelial cells to mediate the migration and tube formation of these cells upon Slit2 stimulation, which were specifically inhibited by the function-blocking antibody R5 to Slit2/Robo1 interaction. To further explore the lymphangiogenic effect and significance mediated by Slit-Robo signaling, we intercrossed Slit2 transgenic mice with a non-metastatic RIP1-Tag2 mouse tumor model, and found that transgenic overexpression of Slit2 significantly enhanced tumor lymphangiogenesis and subsequently promoted mesenteric lymph node metastasis of pancreatic islet tumors. Taken together, our findings reveal that through interacting with Robo1, Slit2 is a novel and potent lymphangiogenic factor and contributes to tumor lymphatic metastasis.

  19. The emerging story of disability associated with lymphatic filariasis: a critical review.

    Directory of Open Access Journals (Sweden)

    Lynne Michelle Zeldenryk

    2011-12-01

    Full Text Available Globally, 40 million people live with the chronic effects of lymphatic filariasis (LF, making it the second leading cause of disability in the world. Despite this, there is limited research into the experiences of people living with the disease. This review summarises the research on the experiences of people living with LF disability. The review highlights the widespread social stigma and oppressive psychological issues that face most people living with LF-related disability. Physical manifestations of LF make daily activities and participation in community life difficult. The findings confirm the need for the Global Programme to Eliminate Lymphatic Filariasis (GPELF to support morbidity management activities that address the complex biopsychosocial issues that people living with LF-related disability face.

  20. Postprandial lymphatic pump function after a high-fat meal: a characterization of contractility, flow, and viscosity.

    Science.gov (United States)

    Kassis, Timothy; Yarlagadda, Sri Charan; Kohan, Alison B; Tso, Patrick; Breedveld, Victor; Dixon, J Brandon

    2016-05-15

    Dietary lipids are transported from the intestine through contractile lymphatics. Chronic lipid loads can adversely affect lymphatic function. However, the acute lymphatic pump response in the mesentery to a postprandial lipid meal has gone unexplored. In this study, we used the rat mesenteric collecting vessel as an in vivo model to quantify the effect of lipoproteins on vessel function. Lipid load was continuously monitored by using the intensity of a fluorescent fatty-acid analog, which we infused along with a fat emulsion through a duodenal cannula. The vessel contractility was simultaneously quantified. We demonstrated for the first time that collecting lymphatic vessels respond to an acute lipid load by reducing pump function. High lipid levels decreased contraction frequency and amplitude. We also showed a strong tonic response through a reduction in the end-diastolic and systolic diameters. We further characterized the changes in flow rate and viscosity and showed that both increase postprandially. In addition, shear-mediated Ca(2+) signaling in lymphatic endothelial cells differed when cultured with lipoproteins. Together these results show that the in vivo response could be both shear and lipid mediated and provide the first evidence that high postprandial lipid has an immediate negative effect on lymphatic function even in the acute setting. Copyright © 2016 the American Physiological Society.

  1. B lymphocyte-specific c-Myc expression stimulates early and functional expansion of the vasculature and lymphatics during lymphomagenesis.

    Science.gov (United States)

    Ruddell, Alanna; Mezquita, Pau; Brandvold, Kimberly A; Farr, Andrew; Iritani, Brian M

    2003-12-01

    Expression of the c-myc proto-oncogene is deregulated in many human cancers. We examined the role of c-Myc in stimulating angiogenesis and lymphangiogenesis in a highly metastatic murine model of Burkitt's lymphoma (E micro -c-myc), where c-Myc is expressed exclusively in B lymphocytes. Immunohistochemical analysis of bone marrow and lymph nodes from young (preneoplastic) E micro -c-myc transgenic mice revealed increased growth of blood vessels, which are functional by dye flow assay. Lymphatic sinuses also increased in size and number within the lymph nodes, as demonstrated by immunostaining for with a lymphatic endothelial marker 10.1.1. The 10.1.1 antibody recognizes VEGFR-2- and VEGFR-3-positive lymphatic sinuses and vessels within lymph nodes, and also recognizes lymphatic vessels in other tissues. Subcutaneously injected dye traveled more efficiently through draining lymph nodes in E micro -c-myc mice, indicating that these hypertrophic lymphatic sinuses increase lymph flow. Purified B lymphocytes and lymphoid tissues from E micro -c-myc mice expressed increased levels of vascular endothelial growth factor (VEGF) by immunohistochemical or immunoblot assays, which could promote blood and lymphatic vessel growth through interaction with VEGFR-2, which is expressed on the endothelium of both vessel types. These results indicate that constitutive c-Myc expression stimulates angiogenesis and lymphangiogenesis, which may promote the rapid growth and metastasis of c-Myc-expressing cancer cells, respectively.

  2. Significance of periductal lymphatic and blood vascular densities in intraductal carcinoma of the breast.

    Science.gov (United States)

    El-Gohary, Yasser M; Metwally, Ghada; Saad, Reda S; Robinson, Morton J; Mesko, Thomas; Poppiti, Robert J

    2009-01-01

    We investigated the significance of periductal lymphatic and blood vascular densities in intraductal carcinomas (IDC) of the breast. Thirty five cases of pure IDC treated by partial or total mastectomy were reviewed. Seven cases with normal breast tissue and 48 cases of invasive breast carcinoma were included as controls. All cases were immunostained with D2-40 and CD31. Positively stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at 400x (=0.17 mm(2)) in the periductal areas. IDC without comedonecrosis showed a mean periductal D2-40 lymphatic microvessel density (LMD) of 5.8 +/- 5 (range 0-18), and a CD31 microvessel density (MD) of 14 +/- 8.9 (range 1-40). IDC with comedonecrosis showed periductal D2-40 LMD of 8.4 +/- 3.8 (range 4-18), and a CD31 MD of 24.3 +/- 7.6 (range 14-40). There was a significant difference between periductal D2-40 LMD and CD31 MD counts in IDC with and without comedonecrosis. There was a positive correlation of periductal D2-40 LMD and CD31 MD counts with high nuclear grade (r = 0.39 and 0.56) of IDC as well as with the presence of comedonecrosis (r = 0.49 and 0.59). Both D2-40 LMD and CD31 MD did not correlate significantly with tumor size, estrogen status, or progesterone status. As IDC with comedonecrosis and/or high nuclear grade has a worse prognosis than IDC without comedonecrosis and/or with low nuclear grade, it appears that lymphatic and blood vascular density evaluated by D2-40 and CD31, respectively, are independent prognostic indicators for patients with IDC of the breast and may be an indicator of early or unrecognized invasion or "regression."

  3. Variations in lung lymphatic drainage into the inferior tracheobronchial lymph nodes junction: Applications in lung cancer.

    Science.gov (United States)

    Ndiaye, Assane; Dimarino, Vincent; Ndiaye, Aïnina; Gaye, Magaye; Ba, Papa Salmane; Nazarian, Serge

    2016-10-01

    The group of inferior tracheobronchial lymph nodes (ITB) is a lymphatic junction through which the lymph from both lungs is carried. Lymphatic activity in this area can be used to assess the lymphatic spreading of lung cancers. Our aim was to quantify lymph drainage from the lung segments towards the ITB group and to determine the direction of the lymph flow into other mediastinal and abdominal lymph nodes. We injected dye directly into the subpleural lymphatic vessels in 100 lung segments of 25 fresh cadaver subjects; the cadavers were then dissected. Thirty-eight segments (38%) drained into the ITB group in 18 subjects. The drainage into the ITB group involved 15.6% of the upper lobe segments, 87.5% of the middle lobe segments, and 70.6% of the lower lobe segments in the right lung. On the left, 6.9% of the upper lobe segments and 83.3% of the lower lobe segments were drained into the ITB group. For three subjects, the dye did not pass beyond the ITB group. The efferent vessels of the ITB group drained towards the right paratracheal and tracheoesophageal chains in 12 subjects and through the left ascending recurrent chain in five subjects. For six subjects, the efferent channels reached the abdominal lymph nodes. A contralateral drainage involved 14 segments (36%). The size and variety of the segments that drain into the ITB group, coupled with the efferent contralateral mediastinal and abdominal pathways, account for the severity of metastasis to this area. Clin. Anat. 29:955-962, 2016. © 2016 Wiley Periodicals, Inc.

  4. Study on the mechanism of regulation on peritoneal lymphatic stomata with Chinese herbal medicine

    Institute of Scientific and Technical Information of China (English)

    Shi-Ping Ding; Ji-Cheng Li; Jian Xu; Lian-Gen Mao

    2002-01-01

    AIM: To study the mechanism of Chinese herbal medicine(CHM), the prescription consists of Radix SalviaeMiltiorrhizae , Radix Codonopsitis Pilosulae , RhizornaAtractylodis Alba and Rhizoma Alismatis, LeonurusHeterophyllus Sweet, etc ) on the regulation of theperitoneal lymphatic stomata and the ascites drainage.METHODS: The mouse model of live fibrosis wasestablished with the application of intragastric installationsof carbon tetrachloride once every three days; scanningelectron microscope and computer image processing wereused to detect the area and the distributive density of theperitoneal lymphatic stomata; and the concentrations ofurinary ion and NO in the serum were measured analyzed inthe experiment.RESULTS: Two different doses of CHM could significantlyincrease the area of the peritoneal lymphatic stomata,promote its distribution density and enhance the arainage ofurinary ion such as sodium, potassium and chlorine.Meanwhile, the NO concentration of two different doses ofCHM groups was 133.52 ± 23.57μmol/L, and 137.2 ±26.79μnol/L respectively. In comparison with the controland model groups ( 48.36 ± 6.83μmol/L, and 35.22 ±8.94μmol/L, P < 0.01 ), there existed significantly markeddifference, this made it clear that Chinese herbal medicinecould induce high endogenous NO concentration. The effectof Chinese herbal medicine on the peritoneal lymphaticstomata and the drainage of urinary ion was altered byadding NO donor (sodium nitropurruside, SNP) or NOsynthase (NOS) inhibitor (N(G)-monomethyl-L-arginine, L-NMMA) to the peritoneal cavity.CONCLUSION: There existed correlations between high NOconcentration and enlargement of the peritoneal lymphaticstomata, which result in enhanced drainage of ascites.These data supported the hypothesis that Chinese herbalmedicine could regulate the peritoneal lymphatic stomata byaccelerating the synthesis and release of endogenous NO.

  5. Genetic Fingerprint Concerned with Lymphatic Metastasis of Human Lung Squamous Cancer

    Directory of Open Access Journals (Sweden)

    Xiaolong ZHAO

    2009-09-01

    Full Text Available Background and objective With the most recent introduction of microarray technology to biology, it becomes possible to perform comprehensive analysis of gene expression in cancer cell. In this study the laser microdissection technique and cDNA microarray analysis were combined to obtain accurate molecular profiles of lymphatic metastasis in patients with lung squamous cell carcinoma. Methods Primary lung squamous cancer tissues and regional lymph nodes were obtained from 10 patients who underwent complete resection of lung cancer. According to the source of lung cancer cells, the samples were classified into three groups: the primary tumor with lymphatic metastasis (TxN+, n=5, the primary tumor without lymphatic metastasis (TxN-, n=5 and matched tumor cells from metastatic lymph nodes (N+, n=5. Total RNA was extracted from laser microdissected tumor samples. Adequate RNA starting material of mRNA from primary tumor or metastatic nodes were labeled and then hybridized into the same microarray containing 6 000 known, named human genes/ESTs. After scanning, data analysis was performed using GeneSpringTM6.2. Results A total of 37 genes were found to be able to separate TxN+ from TxN-. TxN+ have higher levels of genes concerned with structural protein, signal transducer, chaperone and enzyme. TxN- have higher levels of genes coding for cell cycle regulator, transporter, signal transducer and apoptosis regulator. Interestingly, there were no differentially expressed genes between N+ and TxN+. Conclusion The acquisition of the metastatic phenotype might occur early in the development of lung squamous cancer. We raise the hypothesis that the gene-expression signature described herein is valuable to elucidate the molecular mechanisms regarding lymphatic metastasis and to look for novel therapeutic targets.

  6. ANALYSIS OF GENES ASSOCIATED WITH LYMPHATIC METASTASIS IN PANCREATIC CARCINOMA USING cDNA MICROARRAY

    Institute of Scientific and Technical Information of China (English)

    谭志军; 胡先贵; 曹贵松; 唐岩

    2003-01-01

    Objective: To identify new markers for prediction of lymph node metastasis. Methods: cDNA probes were prepared by labeling mRNA from samples of four pancreatic carcinoma tissues with Cy5-dUTP and mRNA from adjacent normal tissues with Cy3-dUTP respectively through reverse transcription. The mixed probes of each sample were then hybridized with 4,096 cDNA arrays (4,000 unique human cDNA sequences), and the fluorescent signals were scanned by ScanArray 3000 scanner (General Scanning, Inc.). The values of Cy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated by ImaGene 3.0 software (BioDiscovery, Inc.). Genes that differentially expresses in each cancerous tissue were sought out according to the standard that the absolute value of natural logarithm of the ratio of Cy5 to Cy3 is greater than 0.69, i. e., more than 2 times change of gene expression, and the signal value of either Cy3 and Cy5 need to be greater than 600. Then, the genes differently expressed in cancer with and without lymphatic metastasis were screened out for further analysis. Results: Among 2 samples with lymphatic metastasis and 2 samples without metastasis, 56 genes, which accounted for 1.40% of genes on the microarray slides, exhibited differentially expression in cancerous tissues with lymphatic metastasis. There were 32 over-expressed genes including 11 having been registered in Genebank, and 24 under-expressed genes including 3 in Genebank. Conclusion: Microarray analysis may provide invaluable information to identify specific gene expression profile of lymphatic metastasis in pancreatic cancer.

  7. Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

    Science.gov (United States)

    Kodama, Tetsuya; Hatakeyama, Yuriko; Kato, Shigeki; Mori, Shiro

    2014-01-01

    Curing/preventing micrometastasis to lymph nodes (LNs) located outside the surgically resected area is essential for improving the morbidity and mortality associated with breast cancer and head and neck cancer. However, no lymphatic therapy system exists that can deliver drugs to LNs located outside the dissection area. Here, we demonstrate proof of concept for a drug delivery system using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs being as large as 10 mm in diameter. We report that a fluorescent solution injected into the subiliac LN (defined as the upstream LN within the dissection area) was delivered successfully to the proper axillary LN (defined as the downstream LN outside the dissection area) through the lymphatic vessels. Our results suggest that this approach could be used before surgical resection to deliver drugs to downstream LNs outside the dissection area. We anticipate that our methodology could be applied clinically, before surgical resection, to cure/prevent micrometastasis in LNs outside the dissection area, using techniques such as ultrasound-guided internal jugular vein catheterization. PMID:25657881

  8. Novel Mechanisms of Compromised Lymphatic Endothelial Cell Homeostasis in Obesity: The Role of Leptin in Lymphatic Endothelial Cell Tube Formation and Proliferation.

    Directory of Open Access Journals (Sweden)

    Akinori Sato

    Full Text Available Leptin is a hormone produced by adipose tissue that regulates various physiological processes. Recent studies have shown that the level of circulating leptin is elevated in obese patients and have suggested a relationship between obesity and postoperative lymphedema. However, the mechanisms by which postoperative lymphedema develops in obese patients and the mechanisms by which leptin regulates lymphatic endothelial cell homeostasis such as tube formation and cell proliferation remain unknown. Here we report that leptin regulates tube formation and cell proliferation in human dermal lymphatic endothelial cells (HDLECs by activation of the signal transducer and activator of transcription 3 pathway, which is downstream signaling of the leptin receptor. Additionally, we found that upregulation of suppressor of cytokine signaling 3 underlies the mechanisms by which a high dose of leptin inhibits cell proliferation and tube formation. Leptin also enhanced expression of the proinflammatory cytokine IL-6 in HDLECs. Interestingly, IL-6 rescues the compromised cell proliferation and tube formation caused by treatment with a high dose of leptin in an autocrine or paracrine manner. Taken together, our findings reveal a novel mechanism by which compromised HDLECs maintain their homeostasis during inflammation mediated by leptin and IL-6. Thus, regulating the level of leptin or IL-6 may be a viable strategy to reduce the incidence of postoperative lymphedema.

  9. Morbidity trends in Lymphatic Filariasis: Analysis from a tertiary care center in Kerala, Southern India

    Directory of Open Access Journals (Sweden)

    Sushma Krishna

    2012-03-01

    Full Text Available Lymphatic filariasis in India contributes to nearly 40% of the global endemic burden. There is paucity of data regarding the association of chronic lymphatic filariasis with diabetes, coronary heart disease and other comorbidities. Case records over a period of ten years from 2001-2010 were reviewed and 113 diagnosed chronic filariasis cases from 13 districts of the state were identified.Prevalence of each of the morbidity with age and sex association was calculated. A total of 82(72.6% of them were in the age group of 60-85 years. Hypertension was noted in 48, type II diabetes in 46 and coronary artery disease in 43. Filariasis had a significant association with type II diabetes mellitus and coronary artery disease (p value< 0.05. Secondary infection. of leg ranging from cellulitis to gangrene was seen in 33(29.2%. Lymphatic Filariasis may be linked as an inclining factor for the development of type II diabetes mellitus and coronary heart disease over 60 years. Secondary leg infections continue in diabetic patients. The immuno- modulatory mechanisms involved needs to be explored.

  10. Cryotherapy for massive vulvar lymphatic leakage complicated with lymphangiomas following gynecological cancer treatment.

    Science.gov (United States)

    Yanazume, Shintaro; Douzono, Haruhiko; Kubo, Hidemichi; Nagata, Tomomi; Douchi, Tsutomu; Kobayashi, Hiroaki

    2014-11-01

    Vulvar lymphatic leakage is a severe complication associated with gynecological cancer treatments. However, standard treatment strategies have not yet been determined. We encountered a rare case of a 76-year-old multiparous woman suffering from massive lymphatic fluid leakage from the entire vulva, and papules developed and were identified as lymphangiomas. A large amount of straw-colored discharge continued from all vulvar papules, which extended over the mons pubis. Nine years ago, the patient had undergone a radical hysterectomy with concurrent chemoradiation for uterine cervical cancer treatment. Her serum albumin level was 1.9 mg/dl, which was attributed to the loss of a large amount of lymph fluid due to leakage from the vulva. Her quality of life gradually decreased because of general fatigue and the need for frequent diaper exchanges every 2 h. The patient received a less-invasive treatment with cryotherapy using liquid nitrogen. She also received a multimodality treatment consisting of the intravenous administration of albumin, massage of the lower limbs and intensive rehabilitation. Cryotherapy was administered once a week for 3 months. Her discharge almost stopped and vulvar lymphangiomas decreased without any major complications. To the best of our knowledge, this is the first case report of massive lymphatic leakage complicated with vulvar lymphangiomas. Additionally, this case may represent the first successful treatment of vulva lymph leakage by cryotherapy without recurrence. Cryotherapy may have the potential to improve the quality of life as a less-invasive treatment for gynecological cancer survivors without serious complications.

  11. Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Irene Vergara

    2016-03-01

    Full Text Available The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx. The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%–78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50 and PLA2 activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-67Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with 67Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-67Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-67Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.

  12. Delayed wound healing due to increased interleukin-10 expression in mice with lymphatic dysfunction.

    Science.gov (United States)

    Kimura, Takayuki; Sugaya, Makoto; Blauvelt, Andrew; Okochi, Hitoshi; Sato, Shinichi

    2013-07-01

    Skin wound healing is an interactive process involving soluble mediators, ECM, resident cells, and infiltrating cells. Little is known about wound healing in the presence of lymphedema. In this study, we investigated wound healing using kCYC⁺/⁻ mice, which demonstrate severe lymphatic dysfunction. Wound healing was delayed significantly in kCYC⁺/⁻ mice when compared with WT mice. In wounded skin of kCYC⁺/⁻ mice, mast cell numbers were increased compared with WT mice, whereas macrophage numbers were decreased. Moreover, IL-10 expression by mast cells was increased, and expression of bFGF, mainly produced by macrophages, was decreased in wounded skin of kCYC⁺/⁻ mice compared with WT mice. We next crossed kCYC⁺/⁻ mice with IL-10⁻/⁻ mice, which were reported to show accelerated wound closure. In kCYC⁺/⁻ IL-10⁺/⁻ mice, time course of wound healing, numbers of macrophages, and IL-10 mRNA expression levels in wounded skin were comparable with WT IL-10⁺/⁻ mice. Similar results were obtained using a different lymphedema model, in which circumferential skin excision was performed on the tails of mice to remove the superficial lymphatics. In summary, these findings suggest that IL-10 plays an important role in delayed wound healing in the setting of lymphatic dysfunction.

  13. The discovery of lymphatic system in the seventeenth century. Part I: the early history.

    Science.gov (United States)

    Suy, Raphael; Thomis, Sarah; Fourneau, Inge

    2016-08-01

    The early history of lymphatic anatomy from Hippocrates (ca. 460-377 B.C.) to Eustachius (1510-1574). The presence of lymphatic vessels and lymph nodes was reported by ancient anatomists without any accurate knowledge of their true functions. Lymph nodes were described as spongy structures, spread over the whole body for the support of vulnerable body parts. Digestion was explained as being the resorption of clear chyle from digested food by the open endings of chyle vessels. The first insights into the place of lymphatic components within nutrition emanated from the medical school of Alexandria (fourth century B.C.) where vivisection was a common practice. Herophilus and Erasistratus described mesenteric veins full of clear liquid, air or milk. For Galen of Pergamum, (104-210) mesenteric lymph nodes also had a nutritional function. He described three different types of mesenteric vessels, namely, the arterial vessels, for the transport of spirituous blood to the intestines; the venous side branches of the portal vein, for the transport of nutritive blood from the liver to the intestines; and small vessels, from the intestines to the mesenteric lymph nodes (serous lymph vessels?). According to Galen, chyle was transported via the above-mentioned mesenteric venous vessels from the intestines to the portal vein and liver, where it was transformed into nutritive blood. This doctrine would be obliterated in the seventeenth century by the discovery of systemic circulation and of the drainage of chyle through a thoracic duct to the subclavian veins.

  14. The lymphatic phenotype in Turner syndrome: an evaluation of nineteen patients and literature review.

    Science.gov (United States)

    Atton, Giles; Gordon, Kristiana; Brice, Glen; Keeley, Vaughan; Riches, Katie; Ostergaard, Pia; Mortimer, Peter; Mansour, Sahar

    2015-12-01

    Turner syndrome is a complex disorder caused by an absent or abnormal sex chromosome. It affects 1/2000-1/3000 live-born females. Congenital lymphoedema of the hands, feet and neck region (present in over 60% of patients) is a common and key diagnostic indicator, although is poorly described in the literature. The aim of this study was to analyse the medical records of a cohort of 19 Turner syndrome patients attending three specialist primary lymphoedema clinics, to elucidate the key features of the lymphatic phenotype and provide vital insights into its diagnosis, natural history and management. The majority of patients presented at birth with four-limb lymphoedema, which often resolved in early childhood, but frequently recurred in later life. The swelling was confined to the legs and hands with no facial or genital swelling. There was only one case of suspected systemic involvement (intestinal lymphangiectasia). The lymphoscintigraphy results suggest that the lymphatic phenotype of Turner syndrome may be due to a failure of initial lymphatic (capillary) function.

  15. Surgical anatomy of the retroperitoneal spaces, Part III: Retroperitoneal blood vessels and lymphatics.

    Science.gov (United States)

    Mirilas, Petros; Skandalakis, John E

    2010-02-01

    In this article, we discuss the surgical anatomy of the blood vessels and the lymphatic vessels and lymph nodes found in the retroperitoneum. Retroperitoneal blood vessels include the aorta and all its branches--parietal and visceral--from the diaphragm to the pelvis, and the inferior vena cava and its tributaries. The retroperitoneal lymphatics form a very rich and extensive chain. As a general rule, lymphatics follow the arteries and named lymph nodes are found at the root of the arteries. Retroperitoneal nodes of the abdomen comprise the inferior diaphragmatic nodes and the lumbar nodes. The latter are classified as left lumbar (aortic), intermediate (interaorticovenous), and right lumbar (caval). These nodes surround the aorta and the inferior vena cava. Around the aorta lie the paraortic nodes, preaortic nodes (include celiac, superior mesenteric, inferior mesenteric nodes collecting lymph from the splanchna supplied by the homonymous arteries), and retroaortic nodes. Similarly, around the vena cava lie the paracaval, precaval, and retrocaval nodes. Pelvic nodes include the common iliac, external and internal iliac, obturator, and sacral nodes.

  16. Endoscopically observable white nodule caused by distal intramural lymphatic spread of rectal cancer: a case report

    Directory of Open Access Journals (Sweden)

    Tsumura Ayako

    2012-10-01

    Full Text Available Abstract This report describes a case of rectal cancer with endoscopically observable white nodules caused by distal intramural lymphatic spread. A 57-year-old female presented to our hospital with frequent diarrhea and hemorrhoids. Computed tomography showed bilateral ovarian masses and three hepatic tumors diagnosed as rectal cancer metastases, and also showed multiple lymph node involvement. The patient was preoperatively diagnosed with stage IV rectal cancer. Colonoscopy demonstrated that primary rectal cancer existed 15 cm from the anal verge and that there were multiple white small nodules on the anal side of the primary tumor extending to the dentate line. Biopsies of the white spots were performed, and they were identified as adenocarcinoma. The patient underwent Hartmann’s procedure because of the locally advanced primary tumor. The white nodules were ultimately diagnosed as being caused by intramural lymphatic spreading because lymphatic permeation was strongly positive at the surrounding area. Small white nodules near a primary rectal cancer should be suspected of being intramural spreading. Endoscopic detection of white nodules may be useful for the diagnosis of distal intramural spread.

  17. Manual lymphatic drainage therapy in patients with breast cancer related lymphoedema

    Directory of Open Access Journals (Sweden)

    Martínez Helena

    2011-03-01

    Full Text Available Abstract Background Lymphoedema is a common and troublesome condition that develops following breast cancer treatment. The aim of this study is to analyze the effectiveness of Manual Lymphatic Drainage in the treatment of postmastectomy lymphoedema in order to reduce the volume of lymphoedema and evaluate the improvement of the concomitant symptomatology. Methods A randomized, controlled clinical trial in 58 women with post-mastectomy lymphoedema. The control group includes 29 patients with standard treatment (skin care, exercise and compression measures, bandages for one month and, subsequently, compression garnments. The experimental group includes 29 patients with standard treatment plus Manual Lymphatic Drainage. The therapy will be administered daily for four weeks and the patient's condition will be assessed one, three and six months after treatment. The primary outcome parameter is volume reduction of the affected arm after treatment, expressed as a percentage. Secondary outcome parameters include: duration of lymphoedema reduction and improvement of the concomitant symptomatology (degree of pain, sensation of swelling and functional limitation in the affected extremity, subjective feeling of being physically less atractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image. Discussion The results of this study will provide information on the effectiveness of Manual Lymphatic Drainage and its impact on the quality of life and physical limitations of these patients. Trial registration ClinicalTrials (NCT: NCT01152099

  18. Global eradication of lymphatic filariasis: the value of chronic disease control in parasite elimination programmes.

    Directory of Open Access Journals (Sweden)

    Edwin Michael

    Full Text Available The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, managerial impediments to executing national control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysis of empirical community data describing the association between infection and chronic disease prevalence, mathematical modelling, and economic analyses to identify and evaluate the feasibility of setting an infection target level at which the chronic pathology attributable to lymphatic filariasis--lymphoedema of the extremities and hydroceles--becomes negligible in the face of continuing transmission as a first stage option in achieving the elimination of this parasitic disease. The results show that microfilaria prevalences below a threshold of 3.55% at a blood sampling volume of 1 ml could constitute readily achievable and sustainable targets to control lymphatic filarial disease. They also show that as a result of the high marginal cost of curing the last few individuals to achieve elimination, maximal benefits can occur at this threshold. Indeed, a key finding from our coupled economic and epidemiological analysis is that when initial uncertainty regarding eradication occurs and prospects for resolving this uncertainty over time exist, it is economically beneficial to adopt a flexible, sequential, eradication strategy based on controlling chronic disease initially.

  19. Global eradication of lymphatic filariasis: the value of chronic disease control in parasite elimination programmes.

    Science.gov (United States)

    Michael, Edwin; Malecela, Mwele N; Zervos, Mihail; Kazura, James W

    2008-08-13

    The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, managerial impediments to executing national control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysis of empirical community data describing the association between infection and chronic disease prevalence, mathematical modelling, and economic analyses to identify and evaluate the feasibility of setting an infection target level at which the chronic pathology attributable to lymphatic filariasis--lymphoedema of the extremities and hydroceles--becomes negligible in the face of continuing transmission as a first stage option in achieving the elimination of this parasitic disease. The results show that microfilaria prevalences below a threshold of 3.55% at a blood sampling volume of 1 ml could constitute readily achievable and sustainable targets to control lymphatic filarial disease. They also show that as a result of the high marginal cost of curing the last few individuals to achieve elimination, maximal benefits can occur at this threshold. Indeed, a key finding from our coupled economic and epidemiological analysis is that when initial uncertainty regarding eradication occurs and prospects for resolving this uncertainty over time exist, it is economically beneficial to adopt a flexible, sequential, eradication strategy based on controlling chronic disease initially.

  20. [Advances in cardiac pacing].

    Science.gov (United States)

    de Carranza, María-José Sancho-Tello; Fidalgo-Andrés, María Luisa; Ferrer, José Martínez; Mateas, Francisco Ruiz

    2012-01-01

    This article contains a review of the current status of remote monitoring and follow-up involving cardiac pacing devices and of the latest developments in cardiac resynchronization therapy. In addition, the most important articles published in the last year are discussed.

  1. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  2. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  3. Sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Neeraj Parakh

    2015-01-01

    Full Text Available Sudden cardiac death is one of the most common cause of mortality worldwide. Despite significant advances in the medical science, there is little improvement in the sudden cardiac death related mortality. Coronary artery disease is the most common etiology behind sudden cardiac death, in the above 40 years population. Even in the apparently healthy population, there is a small percentage of patients dying from sudden cardiac death. Given the large denominator, this small percentage contributes to the largest burden of sudden cardiac death. Identification of this at risk group among the apparently healthy individual is a great challenge for the medical fraternity. This article looks into the causes and methods of preventing SCD and at some of the Indian data. Details of Brugada syndrome, Long QT syndrome, Genetics of SCD are discussed. Recent guidelines on many of these causes are summarised.

  4. A Feasibility Study of Smartphone-Based Telesonography for Evaluating Cardiac Dynamic Function and Diagnosing Acute Appendicitis with Control of the Image Quality of the Transmitted Videos.

    Science.gov (United States)

    Kim, Changsun; Cha, Hyunmin; Kang, Bo Seung; Choi, Hyuk Joong; Lim, Tae Ho; Oh, Jaehoon

    2016-06-01

    Our aim was to prove the feasibility of the remote interpretation of real-time transmitted ultrasound videos of dynamic and static organs using a smartphone with control of the image quality given a limited internet connection speed. For this study, 100 cases of echocardiography videos (dynamic organ)-50 with an ejection fraction (EF) of ≥50 s and 50 with EF smartphone, to which the images were transmitted from the ultrasound machine. The resolution of the transmitted echocardiography videos was reduced by approximately 20 % to increase the frame rate of transmission given the limited internet speed. The differences in diagnostic performance between the two devices when evaluating left ventricular (LV) systolic function by measuring the EF and when evaluating the presence of acute appendicitis were investigated using a five-point Likert scale. The average areas under the receiver operating characteristic curves for each reviewer's interpretations using the LCD monitor and smartphone were respectively 0.968 (0.949-0.986) and 0.963 (0.945-0.982) (P = 0.548) for echocardiography and 0.972 (0.954-0.989) and 0.966 (0.947-0.984) (P = 0.175) for abdominal ultrasonography. We confirmed the feasibility of remotely interpreting ultrasound images using smartphones, specifically for evaluating LV function and diagnosing pediatric acute appendicitis; the images were transferred from the ultrasound machine using image quality-controlled telesonography.

  5. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

    Science.gov (United States)

    Debrah, Alexander Yaw; Mand, Sabine; Specht, Sabine; Marfo-Debrekyei, Yeboah; Batsa, Linda; Pfarr, Kenneth; Larbi, John; Lawson, Bernard; Taylor, Mark; Adjei, Ohene; Hoerauf, Achim

    2006-09-01

    Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS), dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(s)VEGFR-3]). Lymphedema patients were additionally monitored for stage (grade) of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with the mean stage of

  6. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

    Directory of Open Access Journals (Sweden)

    Alexander Yaw Debrah

    2006-09-01

    Full Text Available Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS, dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(sVEGFR-3]. Lymphedema patients were additionally monitored for stage (grade of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with

  7. Assessment of disease and infection of lymphatic filariasis in Northeastern Cambodia.

    Science.gov (United States)

    Leang, Rithea; Socheat, Duong; Bin, Boravong; Bunkea, Tol; Odermatt, Peter

    2004-10-01

    We assessed the filariasis disease burden in four northeastern provinces of Cambodia by using and validating a key-informant questionnaire, consisting of four questions, with pictures of patients with leg elephantiasis and hydrocoele. The questionnaire was distributed and collected through the school, health and administrative systems. Validation surveys included clinical examination, a card test for W. bancrofti (ICT Filariasis card test, AMRAD) and night blood finger prick examination of patients reported with clinical elephantiasis. Only 48.0% of questionnaires were returned. A total of 220 patients were reported, mostly from Stung Treng (36.8%) and Rattanakiri provinces (35.0%). Key-informants reported patients with lymphatic filariasis with a sensitivity of 85.7% for leg and 97.0% for scrotum morbidity, and with a specificity of 95.6%. However, substantial over-reporting resulted in very low positive predictive values for elephantiasis of 19.4% for legs and of 23.7% for the scrotum. As 97.4% of patients with clinical lymphatic filariasis were older than 40 years, the diagnostic performance of the questionnaire would be improved by restricting its use to that age group. About 0.7% of 3490 W. bancrofti card tests were positive; the prevalence was 1.94% (12/618) in Rattanakiri, 0.38% (4/1055) in Stung Treng and 0.22% (2/919) in Preah Vihear. W. bancrofti microfilaria were identified in blood from two patients in Rattanakiri (0.32%) and from one patient in Stung Treng (0.09%). Brugia malayi microfilaria were identified in blood from five patients in Rattanakiri (0.81%) only. No patients with microfilariaemia were identified in Preah Vehear. In Mondulkiri province all investigations (card test, night blood examination, clinical examination) for lymphatic filariasis were negative. Our findings confirm the usefulness of key-informant questionnaire for the identification of filariasis patients provided that high adherence can be achieved. Lymphatic filariasis

  8. Cardiac nonrigid motion analysis from image sequences

    Institute of Scientific and Technical Information of China (English)

    LIU Huafeng

    2006-01-01

    Noninvasive estimation of the soft tissue kinematics properties from medical image sequences has many important clinical and physiological implications, such as the diagnosis of heart diseases and the understanding of cardiac mechanics. In this paper, we present a biomechanics based strategy, framed as a priori constraints for the ill-posed motion recovery problema, to realize estimation of the cardiac motion and deformation parameters. By constructing the heart dynamics system equations from biomechanics principles, we use the finite element method to generate smooth estimates.of heart kinematics throughout the cardiac cycle. We present the application of the strategy to the estimation of displacements and strains from in vivo left ventricular magnetic resonance image sequence.

  9. Fractal fluctuations in cardiac time series

    Science.gov (United States)

    West, B. J.; Zhang, R.; Sanders, A. W.; Miniyar, S.; Zuckerman, J. H.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

    1999-01-01

    Human heart rate, controlled by complex feedback mechanisms, is a vital index of systematic circulation. However, it has been shown that beat-to-beat values of heart rate fluctuate continually over a wide range of time scales. Herein we use the relative dispersion, the ratio of the standard deviation to the mean, to show, by systematically aggregating the data, that the correlation in the beat-to-beat cardiac time series is a modulated inverse power law. This scaling property indicates the existence of long-time memory in the underlying cardiac control process and supports the conclusion that heart rate variability is a temporal fractal. We argue that the cardiac control system has allometric properties that enable it to respond to a dynamical environment through scaling.

  10. Scalable BDDC Algorithms for Cardiac Electromechanical Coupling

    KAUST Repository

    Pavarino, L. F.

    2017-03-17

    The spread of electrical excitation in the cardiac muscle and the subsequent contraction-relaxation process is quantitatively described by the cardiac electromechanical coupling model. The electrical model consists of the Bidomain system, which is a degenerate parabolic system of two nonlinear partial differential equations (PDEs) of reaction-diffusion type, describing the evolution in space and time of the intra- and extracellular electric potentials. The PDEs are coupled through the reaction term with a stiff system of ordinary differential equations (ODEs), the membrane model, which describes the flow of the ionic currents through the cellular membrane and the dynamics of the associated gating variables. The mechanical model consists of the quasi-static finite elasticity system, modeling the cardiac tissue as a nearly-incompressible transversely isotropic hyperelastic material, and coupled with a system of ODEs accounting for the development of biochemically generated active force.

  11. Dynamics

    CERN Document Server

    Goodman, Lawrence E

    2001-01-01

    Beginning text presents complete theoretical treatment of mechanical model systems and deals with technological applications. Topics include introduction to calculus of vectors, particle motion, dynamics of particle systems and plane rigid bodies, technical applications in plane motions, theory of mechanical vibrations, and more. Exercises and answers appear in each chapter.

  12. Cardiac tumors: echo assessment.

    Science.gov (United States)

    Mankad, Rekha; Herrmann, Joerg

    2016-12-01

    Cardiac tumors are exceedingly rare (0.001-0.03% in most autopsy series). They can be present anywhere within the heart and can be attached to any surface or be embedded in the myocardium or pericardial space. Signs and symptoms are nonspecific and highly variable related to the localization, size and composition of the cardiac mass. Echocardiography, typically performed for another indication, may be the first imaging modality alerting the clinician to the presence of a cardiac mass. Although echocardiography cannot give the histopathology, certain imaging features and adjunctive tools such as contrast imaging may aid in the differential diagnosis as do the adjunctive clinical data and the following principles: (1) thrombus or vegetations are the most likely etiology, (2) cardiac tumors are mostly secondary and (3) primary cardiac tumors are mostly benign. Although the finding of a cardiac mass on echocardiography may generate confusion, a stepwise approach may serve well practically. Herein, we will review such an approach and the role of echocardiography in the assessment of cardiac masses.

  13. Cardiac tumors: echo assessment

    Directory of Open Access Journals (Sweden)

    Rekha Mankad MD

    2016-12-01

    Full Text Available Cardiac tumors are exceedingly rare (0.001–0.03% in most autopsy series. They can be present anywhere within the heart and can be attached to any surface or be embedded in the myocardium or pericardial space. Signs and symptoms are nonspecific and highly variable related to the localization, size and composition of the cardiac mass. Echocardiography, typically performed for another indication, may be the first imaging modality alerting the clinician to the presence of a cardiac mass. Although echocardiography cannot give the histopathology, certain imaging features and adjunctive tools such as contrast imaging may aid in the differential diagnosis as do the adjunctive clinical data and the following principles: (1 thrombus or vegetations are the most likely etiology, (2 cardiac tumors are mostly secondary and (3 primary cardiac tumors are mostly benign. Although the finding of a cardiac mass on echocardiography may generate confusion, a stepwise approach may serve well practically. Herein, we will review such an approach and the role of echocardiography in the assessment of cardiac masses.

  14. Therapeutic strategy for lower limb lymphedema and lymphatic fistula after resection of a malignant tumor in the hip joint region: a case report.

    Science.gov (United States)

    Hara, H; Mihara, M; Hayashi, A; Kanemaru, M; Todokoro, T; Yamamoto, T; Iida, T; Hino, R; Koshima, I

    2014-03-01

    Lymphatic fistula complicating lymphedema is thought to occur due to communication between lymph vessels and the skin, which has yet to be shown objectively. The objective of this case report is to show the pathology and treatment using simultaneous lymphatic fistula resection and lymphatico-venous anastomosis (LVA). A 40-year-old woman underwent extended resection and total hip arthroplasty for primitive neuroectodermal tumor in the right proximal femur 23 years ago. Right lower limb lymphedema developed immediately after surgery and lymphatic fistula appeared in the posterior thigh. On ICG lymphography, lymph reflux toward the distal side dispersing in a fan-shape reticular pattern from the lymphatic fistula region was noted after intracutaneous injection of ICG into the foot. We performed simultaneous lymphatic fistula resection and of LVA. Pathological examination showed that the epidermis and stratum corneum of the healthy skin were lost in the lymphatic fistula region. Dilated lymph vessels were open in this region. The examinations provide the first objective evidence that the cause of lymphatic fistula may be lymph reflux from lymphatic stems to precollectors through lymphatic perforators.

  15. Comparison of three quality of life instruments in lymphatic filariasis: DLQI, WHODAS 2.0, and LFSQQ.

    Directory of Open Access Journals (Sweden)

    Cristina Thomas

    2014-02-01

    Full Text Available BACKGROUND: The Global Program to Eliminate Lymphatic Filariasis aims to interrupt transmission of lymphatic filariasis and manage morbidity in people currently living with the disease. A component of morbidity management is improving health-related quality of life (HRQoL in patients. Measurement of HRQoL in current management programs is varied because of the lack of a standard HRQoL tool for use in the lymphatic filariasis population. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the psychometric properties of three health status measures were compared when used in a group of lymphatic filariasis patients and healthy controls. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0, the Dermatology Life Quality Index (DLQI, and the Lymphatic Filariasis Quality of Life Questionnaire (LFSQQ were administered to 36 stage II and stage III lymphatic filariasis subjects and 36 age and sex matched controls in Kerala, India. All three tools yielded missing value rates lower than 10%, suggesting high feasibility. Highest internal consistency was seen in the LFSQQ (α = 0.97. Discriminant validity analysis demonstrated that HRQoL was significantly lower in the LF group than in controls for the WHODAS 2.0, DLQI, and LFSQQ, but total HRQoL scores did not differ between stage II and stage III lymphedema subjects. The LFSQQ total score correlated most strongly with the WHODAS 2.0 (r = 0.91, p<0.001 and DLQI (r = 0.81, p<0.001. CONCLUSIONS/SIGNIFICANCE: The WHODAS 2.0, DLQI, and LFSQQ demonstrate acceptable feasibility, internal consistency, discriminate validity, and construct validity. Based on our psychometric analyses, the LFSQQ performs the best and is recommended for use in the lymphatic filariasis population.

  16. Cardiac Tamponade Revisited

    Science.gov (United States)

    Ariyarajah, Vignendra; Spodick, David H.

    2007-01-01

    Cardiac tamponade is a life-threatening clinical syndrome that requires timely diagnosis. Herein, we present an instructive case of a patient who had cardiac tamponade. The condition went undiagnosed and resulted in the patient's death because almost all of the pathognomonic clinical findings of tamponade were unrecognized or not manifest. To better prepare health care professionals for similar challenges, we discuss the symptoms and clinical signs typical of cardiac tamponade, review the medical literature, and highlight current investigative methods that enable quick, efficient diagnosis and treatment. PMID:17948086

  17. Relationship of cardiac sympathetic nerve innervation and excitability to cardiac hypertrophy in very elderly male hypertensive patients.

    Science.gov (United States)

    Li, Shijun; Zhang, Li; Guo, Yuanyuan; Li, Xiaoying

    2013-09-01

    Our study aimed to disclose the relationship of cardiac sympathetic nerve innervation and excitability to myocardial hypertrophy in very old elderly male hypertensive patients with low serum testosterone level. A total of 80 elderly male hypertensive patients aged from 80 to 95 years were recruited. Heart rate variability is determined by 24 h dynamic electrocardiogram and heart rate variability analysis system. Cardiac function and left ventricular mass index were determined using color Doppler ultrasound. Standard deviation of all normal sinus R-R intervals over 24 h (SDNN) significantly decreased in hypertensive cardiac hypertrophy patients as compared with those without cardiac hypertrophy. SDANN and Standard deviation of the average normal sinus R-R intervals for all 5-min segment index, time-domain index reflecting sympathetic nerve tension, obviously decreased and LFnu and LFnu/HFnu, frequency-domain index representing sympathetic nerve excitability, significantly increased in hypertensive cardiac hypertrophy patients as compared with those without cardiac hypertrophy. Myocardial norepinephrine content significantly increased while tyrosine hydroxylase expression significantly lowered in hypertensive cardiac hypertrophy patients, and a negative correlation between myocardial tyrosine hydroxylase expression and myocardial norepinephrine content was present. Serum total testosterone level decreased in hypertensive cardiac hypertrophy patients and was an independent risk factor for the increase in myocardial norepinephrine content and decrease in tyrosine hydroxylase expression. These data confirm that cardiac sympathetic nerve hypoinnervation and relative increase in cardiac sympathetic nerve excitability are closely related to cardiac hypertrophy in very old hypertensive patients. A lower serum total testosterone level was the independent risk factor of cardiac sympathetic nerve hypoinnervation and relative increase in excitability in very old male

  18. Molecular Basis of Cardiac Myxomas

    Directory of Open Access Journals (Sweden)

    Pooja Singhal

    2014-01-01

    Full Text Available Cardiac tumors are rare, and of these, primary cardiac tumors are even rarer. Metastatic cardiac tumors are about 100 times more common than the primary tumors. About 90% of primary cardiac tumors are benign, and of these the most common are cardiac myxomas. Approximately 12% of primary cardiac tumors are completely asymptomatic while others present with one or more signs and symptoms of the classical triad of hemodynamic changes due to intracardiac obstruction, embolism and nonspecific constitutional symptoms. Echocardiography is highly sensitive and specific in detecting cardiac tumors. Other helpful investigations are chest X-rays, magnetic resonance imaging and computerized tomography scan. Surgical excision is the treatment of choice for primary cardiac tumors and is usually associated with a good prognosis. This review article will focus on the general features of benign cardiac tumors with an emphasis on cardiac myxomas and their molecular basis.

  19. Bronchogenic Carcinoma with Cardiac Invasion Simulating Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Anirban Das

    2016-01-01

    Full Text Available Cardiac metastases in bronchogenic carcinoma may occur due to retrograde lymphatic spread or by hematogenous dissemination of tumour cells, but direct invasion of heart by adjacent malignant lung mass is very uncommon. Pericardium is frequently involved in direct cardiac invasion by adjacent lung cancer. Pericardial effusion, pericarditis, and tamponade are common and life threatening presentation in such cases. But direct invasion of myocardium and endocardium is very uncommon. Left atrial endocardium is most commonly involved in such cases due to anatomical contiguity with pulmonary hilum through pulmonary veins, and in most cases left atrial involvement is asymptomatic. But myocardial compression and invasion by adjacent lung mass may result in myocardial ischemia and may present with retrosternal, oppressive chest pain which clinically may simulate with the acute myocardial infarction (AMI. As a result, it leads to misdiagnosis and delayed diagnosis of lung cancer. Here we report a case of non-small-cell carcinoma of right lung which was presented with asymptomatic invasion in left atrium and retrosternal chest pain simulating AMI due to myocardial compression by adjacent lung mass, in a seventy-four-year-old male smoker.

  20. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies.

    Science.gov (United States)

    Han, Sifei; Quach, Tim; Hu, Luojuan; Wahab, Anisa; Charman, William N; Stella, Valentino J; Trevaskis, Natalie L; Simpson, Jamie S; Porter, Christopher J H

    2014-03-10

    A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may enhance immunomodulatory effects. Two classes of lymph-directing prodrugs were synthesised. Alkyl chain derivatives (octyl mycophenolate, MPA-C8E; octadecyl mycophenolate, MPA-C18E; and octadecyl mycophenolamide, MPA-C18AM), to promote passive partitioning into lipids in lymphatic transport pathways, and a triglyceride mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) to facilitate metabolic integration into triglyceride deacylation-reacylation pathways. Lymphatic transport, lymphocyte uptake and plasma pharmacokinetics were assessed in mesenteric lymph and carotid artery cannulated rats following intraduodenal infusion of lipid-based formulations containing MPA or MPA prodrugs. Patterns of prodrug hydrolysis in rat digestive fluid, and cellular re-esterification in vivo, were evaluated to examine the mechanisms responsible for lymphatic transport. Poor enzyme stability and low absorption appeared to limit lymphatic transport of the alkyl derivatives, although two of the three alkyl chain prodrugs - MPA-C18AM (6-fold) and MPA-C18E (13-fold) still increased lymphatic drug transport when compared to MPA. In contrast, 2-MPA-TG markedly increased lymphatic drug transport (80-fold) and drug concentrations in lymphocytes (103-fold), and this was achieved via biochemical incorporation into triglyceride deacylation-reacylation pathways. The prodrug was hydrolysed rapidly to 2-mycophenoloyl glycerol (2-MPA-MG) in the presence of rat digestive fluid, and 2-MPA-MG was subsequently re-esterified in the enterocyte with oleic acid (most likely originating from the co-administered formulation) prior to accessing the

  1. Cardiac Tumors; Tumeurs cardiaques

    Energy Technology Data Exchange (ETDEWEB)

    Laissy, J.P.; Fernandez, P. [Centre Hospitalier Universitaire Bichat Claude Bernard, Service d' Imagerie, 76 - Rouen (France); Mousseaux, E. [Hopital Europeen Georges Pompidou (HEGP), Service de Radiologie Cardio Vasculaire et Interventionnelle, 75 - Paris (France); Dacher, J.N. [Centre Hospitalier Universitaire Charles Nicolle, 75 - Rouen (France); Crochet, D. [Centre Hospitalier Universitaire, Hopital Laennec, Centre Hemodynamique, Radiologie Thoracique et Vasculaire, 44 - Nantes (France)

    2004-04-01

    Metastases are the most frequent tumors of the heart even though they seldom are recognized. Most primary cardiac tumors are benign. The main role of imaging is to differentiate a cardiac tumor from thrombus and rare pseudo-tumors: tuberculoma, hydatid cyst. Echocardiography is the fist line imaging technique to detect cardiac tumors, but CT and MRl arc useful for further characterization and differential diagnosis. Myxoma of the left atrium is the most frequent benign cardiac tumor. It usually is pedunculated and sometimes calcified. Sarcoma is the most frequent primary malignant tumor and usually presents as a sessile infiltrative tumor. Lymphoma and metastases are usually recognized by the presence of known tumor elsewhere of by characteristic direct contiguous involvement. Diagnosing primary and secondary pericardial tumors often is difficult. Imaging is valuable for diagnosis, characterization, pre-surgical evaluation and follow-up. (author)

  2. Socially differentiated cardiac rehabilitation

    DEFF Research Database (Denmark)

    Meillier, Lucette Kirsten; Nielsen, Kirsten Melgaard; Larsen, Finn Breinholt;

    2012-01-01

    to a standard rehabilitation programme (SRP). If patients were identified as socially vulnerable, they were offered an extended version of the rehabilitation programme (ERP). Excluded patients were offered home visits by a cardiac nurse. Concordance principles were used in the individualised programme elements......%. Patients were equally distributed to the SRP and the ERP. No inequality was found in attendance and adherence among referred patients. Conclusions: It seems possible to overcome unequal referral, attendance, and adherence in cardiac rehabilitation by organisation of systematic screening and social......Aim: The comprehensive cardiac rehabilitation (CR) programme after myocardial infarction (MI) improves quality of life and results in reduced cardiac mortality and recurrence of MI. Hospitals worldwide face problems with low participation rates in rehabilitation programmes. Inequality...

  3. Transvenous Temporary Cardiac Pacing

    National Research Council Canada - National Science Library

    Emmanouil Poulidakis; Antonis S Manolis

    2014-01-01

      Transvenous temporary cardiac pacing is a rather old but still contemporary life-saving technique, with a unique value in the treatment of critically ill patients suffering from rhythm disturbances...

  4. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  5. Comparison of blood neoangiogenesis and lymphatic vascularization in colorectal adenomas from patients with and without concomitant colorectal cancer

    Directory of Open Access Journals (Sweden)

    L.R. Moreira

    2009-07-01

    Full Text Available Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis and D2-40 (marker for lymphatic endothelium. Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 µm²; P = 0.019 and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041 when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.

  6. An evidence-based analysis of epidemiologic associations between lymphatic and hematopoietic cancers and occupational exposure to gasoline.

    Science.gov (United States)

    Keenan, J J; Gaffney, S; Gross, S A; Ronk, C J; Paustenbach, D J; Galbraith, D; Kerger, B D

    2013-10-01

    The presence of benzene in motor gasoline has been a health concern for potential increased risk of acute myelogenous leukemia and perhaps other lymphatic/hematopoietic cancers for approximately 40 years. Because of the widespread and increasing use of gasoline by consumers and the high exposure potential of occupational cohorts, a thorough understanding of this issue is important. The current study utilizes an evidence-based approach to examine whether or not the available epidemiologic studies demonstrate a strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers. Among 67 epidemiologic studies initially identified, 54 were ranked according to specific criteria relating to the relevance and robustness of each study for answering the research question. The 30 highest-ranked studies were sorted into three tiers of evidence and were analyzed for strength, specificity, consistency, temporality, dose-response trends and coherence. Meta statistics were also calculated for each general and specific lymphatic/hematopoietic cancer category with adequate data. The evidence-based analysis did not confirm any strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers based on the epidemiologic studies available to date. These epidemiologic findings, combined with the evidence showing relatively low occupational benzene vapor exposures associated with gasoline formulations during the last three decades, suggest that current motor gasoline formulations are not associated with increased lymphatic/hematopoietic cancer risks related to benzene.

  7. Transcription factor COUP-TFII is indispensable for venous and lymphatic development in zebrafish and Xenopus laevis

    Energy Technology Data Exchange (ETDEWEB)

    Aranguren, Xabier L., E-mail: xabier.lopezaranguren@med.kuleuven.be [Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Beerens, Manu, E-mail: manu.beerens@med.kuleuven.be [Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Vandevelde, Wouter, E-mail: woutervandevelde@gmail.com [Vesalius Research Center, VIB, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Vesalius Research Center, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Dewerchin, Mieke, E-mail: mieke.dewerchin@vib-kuleuven.be [Vesalius Research Center, VIB, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Vesalius Research Center, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Carmeliet, Peter, E-mail: peter.carmeliet@vib-kuleuven.be [Vesalius Research Center, VIB, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Vesalius Research Center, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Luttun, Aernout, E-mail: aernout.luttun@med.kuleuven.be [Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium)

    2011-06-24

    Highlights: {yields} COUP-TFII deficiency in zebrafish affects arterio-venous EC specification. {yields} COUP-TFII is indispensable for lymphatic development in zebrafish. {yields} COUP-TFII knockdown in Xenopus disrupts lymphatic EC differentiation and migration. {yields} COUP-TFII's role in EC fate decisions is evolutionary conserved. -- Abstract: Transcription factors play a central role in cell fate determination. Gene targeting in mice revealed that Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII, also known as Nuclear Receptor 2F2 or NR2F2) induces a venous phenotype in endothelial cells (ECs). More recently, NR2F2 was shown to be required for initiating the expression of Prox1, responsible for lymphatic commitment of venous ECs. Small animal models like zebrafish embryos and Xenopus laevis tadpoles have been very useful to elucidate mechanisms of (lymph) vascular development. Therefore, the role of NR2F2 in (lymph) vascular development was studied by eliminating its expression in these models. Like in mice, absence of NR2F2 in zebrafish resulted in distinct vascular defects including loss of venous marker expression, major trunk vessel fusion and vascular leakage. Both in zebrafish and Xenopus the development of the main lymphatic structures was severely hampered. NR2F2 knockdown significantly decreased prox1 expression in zebrafish ECs and the same manipulation affected lymphatic (L)EC commitment, migration and function in Xenopus tadpoles. Therefore, the role of NR2F2 in EC fate determination is evolutionary conserved.

  8. COMPARATIVE ANALYSIS OF LYMPHATIC METASTASIS--ASSOCIATED GENES IN MOUSE HEPATOCELLULAR CARCINOMA CELL LINES WITH DIFFERENT METASTATIC POTENTIAL

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To investigate the neoplasm lymphatic metastasis-associated genes and its molecular mechanisms. Methods: 22690 mouse genome cDNA microarrays (including 14500 known genes and 4371 ESTs) were used to compare and analyze the gene expression profiles of mouse hepatocellular carcinoma cell lines Hca-F (highly lymphatic metastasis potential) and Hca-P (low potential). Results: 901 genes and 129 ESTs were up-regulated at least 2-fold in Hca-F cell. 33 genes showing significant alterations in expression were presented, including endoglin (EDG), MCAM, Cdc42ep5, F2r, D7Ertd458e, Serpin h1 (HSP47), AXL, Areg and so on. These genes have functions of angiogenesis, cell adhesion, signal transduction, cell motility, chaperone activity, protein kinase activity and receptor binding. Conclusion: cDNA microarray combined with lymphatic metastasis models might contribute new methods and clues to the neoplasm lymphatic metastasis research. Some overexpressed genes might provide novel clues to the molecular mechanisms of neoplasm lymphatic metastasis.

  9. Cardiac imaging in adults

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  10. Autonomic cardiac innervation

    OpenAIRE

    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targe...

  11. Port Access Cardiac Surgery.

    Science.gov (United States)

    Viganó, Mario; Minzioni, Gaetano; Spreafico, Patrizio; Rinaldi, Mauro; Pasquino, Stefano; Ceriana, Piero; Locatelli, Alessandro

    2000-10-01

    The port-access technique for cardiac surgery was recently developed at Stanford University in California as a less invasive method to perform some cardiac operations. The port-access system has been described in detail elsewhere. It is based on femoral arterial and venous access for cardiopulmonary bypass (CPB) and on the adoption of a specially designed triple-lumen catheter described originally by Peters, and subsequently modified and developed in the definitive configuration called the endoaortic clamp.

  12. Awareness in cardiac anesthesia.

    LENUS (Irish Health Repository)

    Serfontein, Leon

    2010-02-01

    Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

  13. Post cardiac injury syndrome

    DEFF Research Database (Denmark)

    Nielsen, S L; Nielsen, F E

    1991-01-01

    The post-pericardiotomy syndrome is a symptom complex which is similar in many respects to the post-myocardial infarction syndrome and these are summarized under the diagnosis of the Post Cardiac Injury Syndrome (PCIS). This condition, which is observed most frequently after open heart surgery, i...... on the coronary vessels, with cardiac tamponade and chronic pericardial exudate. In the lighter cases, PCIS may be treated with NSAID and, in the more severe cases, with systemic glucocorticoid which has a prompt effect....

  14. Infected cardiac hydatid cyst

    OpenAIRE

    Ceviz, M; Becit, N; Kocak, H.

    2001-01-01

    A 24 year old woman presented with chest pain and palpitation. The presence of a semisolid mass—an echinococcal cyst or tumour—in the left ventricular apex was diagnosed by echocardiography, computed tomography, and magnetic resonance imaging. The infected cyst was seen at surgery. The cyst was removed successfully by using cardiopulmonary bypass with cross clamp.


Keywords: cardiac hydatid cyst; infected cardiac hydatid cyst

  15. Cardiac applications of optogenetics.

    Science.gov (United States)

    Ambrosi, Christina M; Klimas, Aleksandra; Yu, Jinzhu; Entcheva, Emilia

    2014-08-01

    In complex multicellular systems, such as the brain or the heart, the ability to selectively perturb and observe the response of individual components at the cellular level and with millisecond resolution in time, is essential for mechanistic understanding of function. Optogenetics uses genetic encoding of light sensitivity (by the expression of microbial opsins) to provide such capabilities for manipulation, recording, and control by light with cell specificity and high spatiotemporal resolution. As an optical approach, it is inherently scalable for remote and parallel interrogation of biological function at the tissue level; with implantable miniaturized devices, the technique is uniquely suitable for in vivo tracking of function, as illustrated by numerous applications in the brain. Its expansion into the cardiac area has been slow. Here, using examples from published research and original data, we focus on optogenetics applications to cardiac electrophysiology, specifically dealing with the ability to manipulate membrane voltage by light with implications for cardiac pacing, cardioversion, cell communication, and arrhythmia research, in general. We discuss gene and cell delivery methods of inscribing light sensitivity in cardiac tissue, functionality of the light-sensitive ion channels within different types of cardiac cells, utility in probing electrical coupling between different cell types, approaches and design solutions to all-optical electrophysiology by the combination of optogenetic sensors and actuators, and specific challenges in moving towards in vivo cardiac optogenetics.

  16. Pattern of lymph node metastases of squamous cell esophageal cancer based on the anatomical lymphatic drainage system: efficacy of lymph node dissection according to tumor location

    Science.gov (United States)

    2017-01-01

    Knowing the anatomical lymphatic drainage of the esophagus is crucial to understanding the dissemination pattern of esophageal tumor. During the embryonal growth, the middle and lower part of the esophagus stretches as the lymphatic networks develop in the submucosal layer. The abundant submucosal lymphatics drain in a longitudinal fashion directly to their proximal and distal ends. The lymphatic route from the proximal esophagus through recurrent nerve nodes to supraclavicular nodes are a component of the mesentery of the proximal esophagus. The lower esophagus mostly drains its lymph into paracardial nodes related to celiac nodes through the mesentery of the distal esophagus. Lymphatic routes to mid and lower paraesophageal nodes usually originate from the intermuscular area of the muscularis propria. The lymphatic communication between the submucosa and intermuscular area is limited. The anatomical concept was confirmed clinically by a large series of single institution and the nationwide registry in Japan. The clinical data for the incidence of involved nodes verified the anatomical observations that long longitudinal extension of lymphatic drainage in the submucosa connected to the upper mediastinum lymphatics and paracardial lymphatics. The extent of dissection should be not tailored according to the anatomical distance from the tumor but according to the incidences of metastasis of each area, those were differed by tumor location. The areas for node dissection should be modified according to the tumor location. Although in patients with tumor limited to within the submucosal layer, even with tumors located in the mid- and lower esophagus, lymphatic metastasis was frequent in the upper mediastinum and perigastric area via the abundant submucosal lymphatics in a longitudinal fashion. When tumor invades or penetrates the muscle layer, the incidence of paraesophageal lymph node metastasis in the middle and lower mediastinum increases. PMID:28815068

  17. Manual lymphatic drainage and therapeutic ultrasound in liposuction and lipoabdominoplasty post-operative period

    Directory of Open Access Journals (Sweden)

    Igor F. B. Masson

    2014-01-01

    Full Text Available Background: Physiotherapy in the plastic surgery post-operative (PO is essential to provide means for an adequate and fast recovery as it restores function through the use of physiotherapeutic procedures. Aim: The aim of the following study is to verify the effects of the association between the manual lymphatic drainage and the therapeutic ultrasound on pain, oedema and the tissue fibrosis in liposuction and lipoabdominoplasty PO. Design: This is a clinical trial prospective. Materials and Methods: Eighteen women aged between 18 and 60 years participated in this study, in the late PO period following lipoabdominoplasty or liposuction in the abdomen, flanks and lower trunk, which showed tissue fibrosis of the flanks and abdomen regions. They were divided into two groups: Liposuction group and lipoabdominoplasty group. A total of twelve sessions of therapeutic ultrasound followed by the manual lymphatic drainage were performed. The patients were assessed with regard to pain, oedema and tissue fibrosis in different moments: Initial assessment, during assessment and final assessment through the application of the protocol of evaluation of cysts fibrosis levels. Statistical Analysis: The test of equality for two proportions and the confidence interval test for mean to evaluate the distribution of variables. The significance level adopted for statistical tests was 5% (P < 0.05. Results: There was a statistically significant reduction of pain, swelling and tissue fibrosis in both groups. Conclusion: the association between manual lymphatic drainage and the therapeutic ultrasound reduced the swelling and the tissue fibrosis and made pain disappear in liposuction and lipoabdominoplasty PO period.

  18. [Role of master transcriptional factor Prox-1 in lymphatic endothelial differentiation of Kaposiform hemangioendothelioma].

    Science.gov (United States)

    Ke, Z Y; Yang, S J

    2017-03-08

    Objective: To analyze the clinical and pathological features of Kaposiform hemangioendothelioma (KHE), and to investigate the role of master transcriptional factor Prox-1 in the regulation of lymphatic differentiation. Methods: Nine cases of KHE (during the period from October 2009 to June 2016) were collected with clinical and pathological data. H&E stained section review and immunohistochemietry using the Dako EnVision method were performed. Results: There were 6 female and 3 male patients with age ranging from 2 months to 8 years (median 3 years and 4 months). The patients presented with either single subcutaneous soft tissue mass, or bone tumors, with the duration of disease onset ranging from 1 month to 1 year. The sites of involvement included the skins of neck (2 cases), nose root (1 case), inguinal (1 case), thigh root (1 case), humerus (2 cases), lumbar vertebrae(1 case), and mesentery (1 case). These tumors were histologically composed of nodules of densely packed spindle or ovoid cells and deformed small blood vessels in an invasive growth pattern. The tumor cells were immunohistochemically positive for both blood vessels and lymphatic endothelial markers, including Prox-1, the master transcriptional factor, and VEGFR-3. With followed-up from 1 to 60 months (median 26 months), two patients died of the disease, while the remaining patients were alive without recurrence. Conclusions: KHE is a rare vascular tumor with at least partial lymphatic endothelial differentiation, in which Prox-1 may act as a master regulator for such differentiation. KHE is an aggressive tumor of intermediate malignant potential, with local invasion and recurrence tendency, and long term follow-up is required.

  19. The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination.

    Science.gov (United States)

    Ramachandran, Sabarinathan; Kumar, Mishra Pankaj; Rami, Reddy Maryada Venkata; Chinnaiah, Harinath Basker; Nutman, Thomas; Kaliraj, Perumal; McCarthy, James

    2004-01-01

    Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2). The stage specificity of ALT-2 gene transcription and protein synthesis was confirmed by PCR using genespecific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT-2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT-2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP-1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development.

  20. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Renata Mężyk-Kopeć

    Full Text Available Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC. When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i single-cell motility, (ii cell migration through a 3D Matrigel/collagen type I matrix, and (iii their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy.

  1. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    Science.gov (United States)

    Mężyk-Kopeć, Renata; Wyroba, Barbara; Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W; Swartz, Melody A; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy.

  2. Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice.

    Science.gov (United States)

    Wang, Wensheng; Wang, Hua; Zhou, Xichao; Li, Xing; Sun, Wen; Dellinger, Michael; Boyce, Brendan F; Xing, Lianping

    2017-01-04

    Gorham-Stout disease (GSD) is a rare bone disorder characterized by aggressive osteolysis associated with lymphatic vessel invasion within bone marrow cavities. The etiology of GSD is not known, and there is no effective therapy or animal model for the disease. Here, we investigated if lymphatic endothelial cells (LECs) affect osteoclasts (OCs) to cause a GSD osteolytic phenotype in mice. We examined the effect of a mouse LEC line on osteoclastogenesis in co-cultures. LECs significantly increased receptor activator of NF-κB ligand (RANKL)-mediated OC formation and bone resorption. LECs expressed high levels of macrophage colony-stimulating factor (M-CSF), but not RANKL, interleukin-6 (IL-6), and tumor necrosis factor (TNF). LEC-mediated OC formation and bone resorption were blocked by an M-CSF neutralizing antibody or Ki20227, an inhibitor of the M-CSF receptor, c-Fms. We injected LECs into the tibias of wild-type (WT) mice and observed massive osteolysis on X-ray and micro-CT scans. Histology showed that LEC-injected tibias had significant trabecular and cortical bone loss and increased OC numbers. M-CSF protein levels were significantly higher in serum and bone marrow plasma of mice given intra-tibial LEC injections. Immunofluorescence staining showed extensive replacement of bone and marrow by podoplanin+ LECs. Treatment of LEC-injected mice with Ki20227 significantly decreased tibial bone destruction. In addition, lymphatic vessels in a GSD bone sample were stained positively for M-CSF. Thus, LECs cause bone destruction in vivo in mice by secreting M-CSF, which promotes OC formation and activation. Blocking M-CSF signaling may represent a new therapeutic approach for treatment of patients with GSD. Furthermore, tibial injection of LECs is a useful mouse model to study GSD. © 2017 American Society for Bone and Mineral Research.

  3. Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis

    Directory of Open Access Journals (Sweden)

    Aula Ammar

    2011-01-01

    Full Text Available Background: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1 in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. Methods: 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC, CD209 (immature DC, iDC and CD68 (macrophage, M&phis;. in vitro expression of CLEVER-1 on lymphatic (LEC and blood endothelial cells (BEC was