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Sample records for intravascular neutrophil chemotactic

  1. Chemotactic Activity on Human Neutrophils to Streptococcus mutans

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    Tetiana Haniastuti

    2013-07-01

    Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

  2. Enhanced neutrophil chemotactic activity after bronchial challenge in subjects with grain dust-induced asthma.

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    Park, H S; Jung, K S

    1998-03-01

    There have been few reports suggesting involvement of neutrophils in induction of bronchoconstriction after inhalation of grain dust. To understand the role of neutrophils in pathogenesis of grain dust-induced asthma. We observed serum neutrophil chemotactic activity during grain dust-bronchoprovocation tests in six asthmatic subjects with positive bronchial challenges (group I). They were compared with those of six symptomatic subjects from the same workplace with negative bronchial challenges (group II). After grain dust inhalation, serum neutrophil chemotactic activity significantly increased at 30 minutes (P = .028), and then decreased to baseline level at 240 minutes (P = .028) in five subjects of group I having isolated early asthmatic responses. Enhanced neutrophil chemotactic activity was persistent for up to 240 minutes in one asthmatic subject having both early and late asthmatic responses. There was, however, no significant change in serum neutrophil chemotactic activity during bronchial challenges in subjects of group II. Pre-incubation of sera with anti-interleukin-8 (IL-8) antibody did not affect the neutrophil chemotactic activity results of group I subjects. These results suggest that enhanced neutrophil chemotactic activity distinct from IL-8 may contribute to significant bronchoconstriction induced by grain dust.

  3. Neutrophil chemotactic activity in bronchoalveolar lavage fluid of patients with AIDS-associated Pneumocystis carinii pneumonia

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    Benfield, T L; Kharazmi, A; Larsen, C G

    1997-01-01

    been shown to confer a poor prognosis in PCP. We therefore investigated the potential of BAL fluid from 17 patients with PCP to induce neutrophil chemotaxis. BAL fluid from patients induced considerable neutrophil chemotactic activity compared to normal controls. Elevated levels of IL-8 were detected...... in patient samples as compared to controls. A specific anti-IL-8 antibody significantly reduced chemotactic activity of patient samples by more than 50%. In conclusion, IL-8 appears to be a significant participant of neutrophil chemotaxis in AIDS-associated PCP, and may participate in the recruitment...

  4. Neutrophilic nodules in the intestinal walls of Japanese monkeys associated with the neutrophil chemotactic activity of larval extracts and secretions of Oesophagostomum aculeatum.

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    Horii, Y; Ishii, A; Owhashi, M; Miyoshi, M; Usui, M

    1985-01-01

    High neutrophil chemotactic activity was detected in the culture medium from Oesophagostomum aculeatum larvae in vitro using blind-well chambers with Millipore filters, and guinea pig leucocytes as indicator cells. Neutrophil chemotactic activity was also detected in the extract from larval worms in a dose dependent fashion. This activity was detected in the low molecular weight fractions adjacent to a sodium chloride marker by gel filtration on Sephadex G200. These results were further confirmed with monkey neutrophils. The possible role of this activity in the formation of granulomatous lesions rich in neutrophils found in O aculeatum infections in the Japanese monkey is discussed.

  5. Synergic production of neutrophil chemotactic activity by colonic epithelial cells and eosinophils.

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    Dent, Gordon; Loweth, Sam C; Hasan, Anwar Matar; Leslie, Fiona M

    2014-10-01

    The presence of eosinophils in the lumen and mucosa of the intestine is characteristic of both ulcerative colitis (UC) and Crohn's disease (CD). There is evidence of eosinophil activation in the intestine during acute inflammatory episodes of these diseases; these episodes are also characterized by an influx of neutrophils, which have the potential to cause extensive tissue damage. We undertook a study to determine whether eosinophils in contact with colonic epithelial cells produce factors that may attract neutrophils in response to immunological stimulation. Neutrophil chemotactic activity (NCA) and concentrations of three neutrophil-attracting CXC chemokines - CXCL1 (Groα), CXCL5 (Ena78) and CXCL8 (IL8) - were measured in supernatants of T84 colonic epithelial cells and blood eosinophils or eosinophil-like myeloid leukaemia cells (AML14.3D10), alone or in combination. Cells were stimulated with serum-opsonized zymosan (OZ) particles. NCA (Peosinophil co-cultures were significantly higher than in the supernatants of either cell type alone. Release of CXCL1 (Peosinophils but not higher than from OZ-stimulated epithelial cells. Eosinophils and colonic epithelial cells exhibit synergy in production of neutrophil chemoattractants in response to immunological stimulation. This may represent a mechanism for exaggerated recruitment of neutrophils to the intestine in response to acute infection in conditions that are characterized by the presence of eosinophils in the bowel. Copyright © 2014 Elsevier GmbH. All rights reserved.

  6. Enhanced basophil histamine release and neutrophil chemotactic activity predispose grain dust-induced airway obstruction.

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    Park, H; Jung, K; Kang, K; Nahm, D; Cho, S; Kim, Y

    1999-04-01

    The pathogenic mechanism of grain dust (GD)-induced occupational asthma (OA) remains unclear. To understand further the mechanism of GD-induced OA. Fifteen employees working in a same GD industry, complaining of work-related respiratory symptoms, were enrolled and were divided into two groups according to the GD-bronchoprovocation test (BPT) result: six positive responders were grouped as group III, nine negative responders as group II and five healthy controls as group I. Serum GD-specific immunoglobulin (Ig)E (sIgE), specific IgG (sIgG) and specific IgG4 (sIgG4) antibodies were detected by enzyme-linked immunosorbent assay. Basophil histamine release was measured by the autofluorometric method, and changes of serum neutrophil chemotactic activity were observed by the Boyden chamber method. For clinical parameters such as degree of airway hyperresponsiveness to methacholine, duration of respiratory symptoms, exposure duration, and prevalences of serum sIgE, sIgG and sIgG4 antibodies, there were no significant differences between group II and III (P > 0.05, respectively). Serum neutrophil chemotactic activity increased significantly at 30 min and decreased at 240 min after the GD-BPT in group III subjects (P 0.05). Basophil histamine release induced by GD was significantly higher in group III than those of group I or group II (P < 0.05, respectively), while minimal release of anti-IgG4 antibodies was noted in all three groups. These results suggest that enhanced basophil histamine release and serum neutrophil chemotactic activity might contribute to the development of GD-induced occupational asthma.

  7. Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils.

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    Cheng-Yuk Lee

    Full Text Available Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis as well as upon contact (by serum-dependent adhesion and phagocytosis. This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under identical conditions. The vigorous in vitro neutrophil response suggests that C. posadasii evades in vivo recognition by neutrophils through suppression of long-range mobilization and recruitment of the immune cells. This observation elucidates an important paradigm of the recognition of microbes, i.e., that intact immunotaxis comprises an intricate spatiotemporal hierarchy of distinct chemotactic processes. Moreover, in contrast to earlier reports, human neutrophils exhibit vigorous chemotaxis toward, and frustrated phagocytosis of, the large spherules of C. posadasii under physiological-like conditions. Finally, neutrophils from healthy donors and patients with chronic coccidioidomycosis display subtle differences in their responses to antibody-coated beads, even though the patient cells appear to interact normally with C. posadasii endospores.

  8. Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8

    International Nuclear Information System (INIS)

    Grob, P.M.; David, E.; Warren, T.C.; DeLeon, R.P.; Farina, P.R.; Homon, C.A.

    1990-01-01

    Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons

  9. Effects of Garlic Oil on the Migration of Neutrophil-Like Cell Studied by Using a Chemotactic Gradient Labchip

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    Po-Chen Shih

    2010-01-01

    Full Text Available We have designed and fabricated a novel chemotactic gradient Labchip for studying cell migration quantitatively. Owing to the great potential of garlic and its preparations in developing antiinflammatory drugs, the aim of the present study is to investigate the effect of garlic oil on the locomotion of a neutrophil-like cell by measuring the dynamic features of cell migration including migration direction, average migration speed, chemotactic index (CI, and motility index (MI with the newly designed Labchip. We found that garlic oil treatment lowered the values of CI and MI and reduced the average speed of cell migration from 13 to 8 μm/min. The results indicate that garlic oil is a potential inhibitor for neutrophil-like cell migration and chemotactic responsiveness. By comparing with the effects of nocodazole and cytochalasin B, we also suggest that the antiinflammatory activity exhibited by garlic oil was mainly through inhibiting the assembly-disassembly processes of the cytoskeleton.

  10. Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

    International Nuclear Information System (INIS)

    Yasui, K.; Yamazaki, M.; Miyagawa, Y.; Komiyama, A.; Akabane, T.

    1987-01-01

    Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine ( 3 H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder

  11. The alpha hemolysin of Escherichia Coli power the metabolism oxidative of neutrophils human beings in response to the peptide chemotactic FMLP: comparison with the ionophore of calcium A23187

    International Nuclear Information System (INIS)

    Garcia, J.

    2000-01-01

    The calcium ionophore ionomycin primes polymorphonuclear leukocytes (PMN) for increased superoxide production upon stimulation with the chemotactic peptide FMLP (Helman Finkel, T. et al J Biol Chem 1987; 262: 12589-12596) In this investigation we assessed the effect of PMN priming with either alpha hemolysin (AH) or the calcium ionophore A23187, both of which increase intracellular calcium, on the oxidative metabolism of PMN (as measured by chemiluminescence) in response to secondary stimulation with FMLP. Both A23187 and AH priming increased, the luminol-enhanced chemiluminescence in response to secondary stimulation with FMLP, indicating overstimulation of PMLP oxidative metabolism. Additional experiments using lucigenin as chemiluminescence enhancer showed that A23187, but not AH priming of PMN, increased superoxide release in a manner similar to that reported for ionomycin. These results are discussed in reference to infectious processes involving hemolytic E. coli (Author) [es

  12. The chemotactic activity of sputum from patients with bronchiectasis.

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    Mikami, M; Llewellyn-Jones, C G; Bayley, D; Hill, S L; Stockley, R A

    1998-03-01

    Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.

  13. LEGO bricks used as chemotactic chambers: evaluation by a computer-assisted image analysis technique.

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    Azzarà, A; Chimenti, M

    2004-01-01

    One of the main techniques used to explore neutrophil motility, employs micropore filters in chemotactic chambers. Many new models have been proposed, in order to perform multiple microassays in a rapid, inexpensive and reproducible way. In this work, LEGO bricks have been used as chemotactic chambers in the evaluation of neutrophil random motility and chemotaxis and compared with conventional Boyden chambers in a "time-response" experiment. Neutrophil motility throughout the filters was evaluated by means of an image-processing workstation, in which a dedicated algorithm recognizes and counts the cells in several fields and focal planes throughout the whole filter; correlates counts and depth values; performs a statistical analysis of data; calculates the true value of neutrophil migration; determines the distribution of cells; and displays the migration pattern. By this method, we found that the distances travelled by the cells in conventional chambers and in LEGO bricks were perfectly identical, both in random migration and under chemotactic conditions. Moreover, no interference with the physiological behaviour of neutrophils was detectable. In fact, the kinetics of migration was identical both in random migration (characterized by a gaussian pattern) and in chemotaxis (characterized by a typical stimulation peak, previously identified by our workstation). In conclusion, LEGO bricks are extremely precise devices. They are simple to use and allow the use of small amounts of chemoattractant solution and cell suspension, supplying by itself a triplicate test. LEGO bricks are inexpensive, fast and suitable for current diagnostic activity or for research investigations in every laboratory.

  14. Amplification of the spleen macrophage population in malaria: possible role of a factor chemotactic for blood mononuclear cells

    International Nuclear Information System (INIS)

    Wyler, D.J.; Gallin, J.I.

    1976-01-01

    The mechanism of amplification of the splenic macrophages' population was investigated using mice infected with malaria as a model of an obligate intravascular infection. It was observed that these macrophages derived from blood monocytes rather than by local proliferation in the spleen. A factor, chemotactic for blood mononuclear cells, was present in spleen cells shortly after infection and preceded detectable increases in spleen macrophage number by 48 hours. This factor, in concert with spleen derived macrophage migration inhibition factor, may be important in the amplification of splenic macrophage population in intravascular infections

  15. Assessing intravascular fluid status

    African Journals Online (AJOL)

    The assessment of intravascular fluid volume is a difficult undertaking in both the intensive care unit and theatre situation ... equally applicable to pulmonary capillary wedge pressure. .... airway pressure, the more difficult it becomes to interpret ...

  16. Disseminated intravascular coagulation (DIC)

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    ... Jr, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice . 6th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 141. Thachil J, Toh CH. Current concepts in the management of disseminated intravascular coagulation. Thromb Res . 2012;129 ...

  17. Intravascular malignant lymphomatosis

    International Nuclear Information System (INIS)

    Martin-Duverneuil, N.; Lafitte, F.; Chiras, J.; Mokhtari, K.; Behin, A.; Hoang-Xuan, K.

    2002-01-01

    Intravascular malignant lymphomatosis is a rare and probably often overlooked disease characterised by massive intravascular proliferation of lymphoid cells, usually with a poor prognosis. CT and MRI appearances are nonspecific; the most suggestive finding being both asymmetrical, bilateral, contrast enhancing high-signal areas on T2 weighting and infarct-like lesions of the cortex and basal ganglia. We report two patients with previously unreported dural and spinal cord involvement. (orig.)

  18. Intravascular malignant lymphomatosis

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    Martin-Duverneuil, N.; Lafitte, F.; Chiras, J. [Service de Neuroradiologie Charcot, Batiment Babinski, Hopital de la Salpetriere, 75013 Paris (France); Mokhtari, K. [Service de Neuropathologie, Hopital de la Salpetriere, 75013 Paris (France); Behin, A.; Hoang-Xuan, K. [Departement de Neurologie, Hopital de la Salpetriere, 75013 Paris (France)

    2002-09-01

    Intravascular malignant lymphomatosis is a rare and probably often overlooked disease characterised by massive intravascular proliferation of lymphoid cells, usually with a poor prognosis. CT and MRI appearances are nonspecific; the most suggestive finding being both asymmetrical, bilateral, contrast enhancing high-signal areas on T2 weighting and infarct-like lesions of the cortex and basal ganglia. We report two patients with previously unreported dural and spinal cord involvement. (orig.)

  19. The Vi capsular polysaccharide enables Salmonella enterica serovar typhi to evade microbe-guided neutrophil chemotaxis.

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    Tamding Wangdi

    2014-08-01

    Full Text Available Salmonella enterica serovar Typhi (S. Typhi causes typhoid fever, a disseminated infection, while the closely related pathogen S. enterica serovar Typhimurium (S. Typhimurium is associated with a localized gastroenteritis in humans. Here we investigated whether both pathogens differ in the chemotactic response they induce in neutrophils using a single-cell experimental approach. Surprisingly, neutrophils extended chemotactic pseudopodia toward Escherichia coli and S. Typhimurium, but not toward S. Typhi. Bacterial-guided chemotaxis was dependent on the presence of complement component 5a (C5a and C5a receptor (C5aR. Deletion of S. Typhi capsule biosynthesis genes markedly enhanced the chemotactic response of neutrophils in vitro. Furthermore, deletion of capsule biosynthesis genes heightened the association of S. Typhi with neutrophils in vivo through a C5aR-dependent mechanism. Collectively, these data suggest that expression of the virulence-associated (Vi capsular polysaccharide of S. Typhi obstructs bacterial-guided neutrophil chemotaxis.

  20. Intravascular pulmonary metastases

    International Nuclear Information System (INIS)

    Shepard, J.A.O.; Moore, E.H.; Templeton, P.A.; McLoud, T.C.

    1988-01-01

    The diagnosis of intravascular metastatic tumor emboli to the lungs is rarely made. The authors present a characteristic radiographic finding of intravascular lung metastases that they observed in four patients with diagnoses or right atrial myoxoma, invasive renal cell carcinoma, invasive pelvic osteosarcoma, and recurrent pelvic chondrosarcoma. Substantiation of intravascular pulmonary metastases was achieved by means of autopsy, pulmonary artery biopsy, and surgical documentation of tumor invasion of the inferior vena cava or pelvic veins. In all four cases, chest computed tomography (CT) demonstrated branching, beaded opacities extending from the hila into the periphery of the lung in the distribution of pulmonary arteries. In one case, similar findings were observed in magnetic resonance (MR) images of the chest. Follow-up studies in three cases showed progressive enlargement and varicosity of the abnormal pulmonary artery consistent with proliferation of intravascular tumor. In the case of metastatic osteosarcoma, intraluminal ossification was also observed at CT. In three of four cases, pulmonary infarction was demonstrated in the distribution of the abnormal pulmonary arteries seen at CT as small, peripheral, wedge-shaped opacities. The demonstration of progressively dilated and beaded pulmonary arteries in patients with extrathoracic malignancies is suggestive of intravascular lung metastases, particularly when accompanied by peripheral infarction

  1. Intravascular "mulberry-like" bodies

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Klebe, J G; Henriques, U V

    1988-01-01

    Intravascular "mulberry-like" bodies in a stillborn female infant with moderate maceration are reported. The histogenesis of these structures is discussed based on light-microscopic, immunohistochemical and ultrastructural findings. No demonstrable causal relation between the intravascular lesion...... and fetal death was found, the cause of death being attributed to intrauterine asphyxia. It is concluded, that intravascular "mulberry-bodies" most likely represent artifacts due to red blood cell autolysis.......Intravascular "mulberry-like" bodies in a stillborn female infant with moderate maceration are reported. The histogenesis of these structures is discussed based on light-microscopic, immunohistochemical and ultrastructural findings. No demonstrable causal relation between the intravascular lesions...

  2. Intravascular (catheter) MR imaging

    International Nuclear Information System (INIS)

    Cohen, A.M.; Hurst, G.C.; Katz, D.E.; Dverk, J.L.; Wiesen, E.J.; Czerski, L.W.; Malaya, R.; Bellon, E.M.

    1989-01-01

    Intravascular MR probes allow excellent spatial resolution and have the potential to detect arterial wall microstructure. Ultrasonic intravascular probes suggest that detailed morphologic information can assist clinical decision making. Catheter MR probes of 2--7 mm outside diameter (OD) were built of copper wire, Teflon, and parts from standard commercial catheters. The probes were connected to the surface coil receiver input of our Picker VISTA 2055HP 1.5-T imaging system. The extant (linear) body coil was used for transmit. Phantoms were constructed of coaxial glass MR tubes, filled with doped water. Watanabe rabbit aorta and human autopsy iliac artery specimens were examined within 4 hours of excision or stored by freezing. In vivo iliac arteries in dogs under general anesthesia were imaged, with percutaneous placement of the probe. Results are presented

  3. Computer-assisted image analysis assay of human neutrophil chemotaxis in vitro

    DEFF Research Database (Denmark)

    Jensen, P; Kharazmi, A

    1991-01-01

    We have developed a computer-based image analysis system to measure in-filter migration of human neutrophils in the Boyden chamber. This method is compared with the conventional manual counting techniques. Neutrophils from healthy individuals and from patients with reduced chemotactic activity were....... Another advantage of the assay is that it can be used to show the migration pattern of different populations of neutrophils from both healthy individuals and patients....

  4. Intravascular "mulberry-like" bodies

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Klebe, J G; Henriques, U V

    1988-01-01

    Intravascular "mulberry-like" bodies in a stillborn female infant with moderate maceration are reported. The histogenesis of these structures is discussed based on light-microscopic, immunohistochemical and ultrastructural findings. No demonstrable causal relation between the intravascular lesions...... and fetal death was found, the cause of death being attributed to intrauterine asphyxia. It is concluded, that intravascular "mulberry-bodies" most likely represent artifacts due to red blood cell autolysis....

  5. Inhibition of neutrophil migration by aggregated immunoglobulin attached to micropore membranes.

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    Kemp, A S; Brown, S

    1980-01-01

    The effect of substrate-bound immunoglobulin on neutrophil migration was examined. Immunoglobulin aggregates bound to micropore membranes inhibited the neutrophil response to a chemotactic stimulus. This inhibition was reversed by the presence of aggregates in suspension suggesting competition between substrate-bound and free aggregates for neutrophil surface binding sites. The immobilization of neutrophils by substrate-bound aggregated immunoglobulin suggests a mechanism for the accumulation of neutrophils at sites of immune complex deposition and tissue-bound antibodies in vivo. PMID:7380477

  6. Dynamics of the Chemotactic Boycott Effect

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    Cisneros, Luis; Wolgemuth, Charles; Tuval, Idan

    2005-03-01

    Aerobic bacteria often live in thin fluid layers on irregular surfaces, near solid-air-water contact lines where the interplay between fluid interface geometry, nutrient transport, and chemotaxis is central to the micro-ecology. To elucidate these processes, we use the simplified geometry of a sessile drop and provide direct experimental evidence for the ``chemotactic Boycott effect" in suspensions of B. subtilis: upward oxygentaxis toward the drop surface leads to accumulation of cells in a thin layer, which flows down to the contact line and produces there a persistent vortex which traps cells near the meniscus. These phenomena are explained quantitatively with a mathematical model consisting of coupled oxygen diffusion and consumption, chemotaxis, and viscous fluid dynamics; they are shown to be associated with a singularity in the chemotactic dynamics at the contact line.

  7. Generation and partial characterization of an eosinophil chemotactic cytokine produced by sensitized equine mononuclear cells stimulated with Strongylus vulgaris antigen.

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    Dennis, V A; Klei, T R; Chapman, M R

    1993-07-01

    Supernatants generated by stimulation of peripheral blood mononuclear cells (PBMC) from Strongylus vulgaris sensitized or immunized ponies were assayed in vitro for eosinophil chemotactic activity (ECA) using the filter system in blind well chambers. The supernatants from these cultures were chemotactic for eosinophils, but not for neutrophils. Supernates from cultures of unsensitized PBMC stimulated with S. vulgaris antigen were not chemotactic for eosinophils. ECA was first detected in culture supernatants after 1.5 h of incubation and was dependent on both antigen and PBMC concentrations, but independent of serum concentrations. Both female and male S. vulgaris worm antigens stimulated ECA production from sensitized PBMC. ECA was not induced by in vitro stimulation of sensitized S. vulgaris PBMC by female Strongylus edentatus worm antigen. Partial characterization of the eosinophil chemotactic cytokine showed it to be nondialyzable, greater than 8000 molecular weight (MW), and sensitive to heating (56 and 95 degrees C), trypsin, and sodium metaperiodate treatments, suggesting that the cytokine is a protein containing some essential carbohydrate moieties. The cytokine described in this paper could partially contribute to the in vivo blood and tissue eosinophilia in experimental S. vulgaris infection.

  8. Neutrophil adhesion and chemotaxis depend on substrate mechanics

    International Nuclear Information System (INIS)

    Jannat, Risat A; Hammer, Daniel A; Robbins, Gregory P; Ricart, Brendon G; Dembo, Micah

    2010-01-01

    Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K D of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against β 2 -integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

  9. Neutrophil adhesion and chemotaxis depend on substrate mechanics

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    Jannat, Risat A; Hammer, Daniel A [Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104 (United States); Robbins, Gregory P; Ricart, Brendon G [Department of Chemical and Biomolecular Engineering, University of Pennsylvania, 311A Towne Building, 220 South 33rd Street, Philadelphia, PA 19104 (United States); Dembo, Micah, E-mail: hammer@seas.upenn.ed [Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215 (United States)

    2010-05-19

    Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K{sub D} of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against {beta}{sub 2}-integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

  10. p21-Activated kinase (PAK regulates cytoskeletal reorganization and directional migration in human neutrophils.

    Directory of Open Access Journals (Sweden)

    Asako Itakura

    Full Text Available Neutrophils serve as a first line of defense in innate immunity owing in part to their ability to rapidly migrate towards chemotactic factors derived from invading pathogens. As a migratory function, neutrophil chemotaxis is regulated by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In this study, we characterized the role of p21-activated kinase (PAK downstream of Rho GTPases in cytoskeletal remodeling and chemotactic processes of human neutrophils. We found that PAK activation occurred upon stimulation of neutrophils with f-Met-Leu-Phe (fMLP, and PAK accumulated at the actin-rich leading edge of stimulated neutrophils, suggesting a role for PAK in Rac-dependent actin remodeling. Treatment with the pharmacological PAK inhibitor, PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil morphological polarization and directional migration under a gradient of fMLP, and was associated with dysregulated Ca(2+ signaling. These results suggest that PAK serves as an important effector of Rho-family GTPases in neutrophil cytoskeletal reorganization, and plays a key role in driving efficient directional migration of human neutrophils.

  11. Failure of rabbit neutrophils to secrete endogenous pyrogen when stimulated with staphylococci.

    Science.gov (United States)

    Hanson, D F; Murphy, P A; Windle, B E

    1980-06-01

    Cells obtained from acute peritoneal exudates in rabbits were separated into neutrophil and mononuclear populations by centrifugation on colloidal silica gradients. When these populations were separately incubated in tissue culture medium in the presence of opsonized Staphylococcus epidermidis, endogenous pyrogen was secreted only by the adherent cells of the mononuclear population. Pyrogen production by neutrophils could not have amounted to as much as 1% of the pyrogen produced by macrophages. When mononuclear cells were added back to purified neutrophils, no pyrogen was produced that could not be accounted for by the number of macrophages added. Rabbit blood cells were similarly fractionated on colloidal silica gradients. Again, endogenous pyrogen was made only by the adherent mononuclear population. The neutrophils isolated on these gradients appeared to be morphologically normal and were 85% viable as judged by dye exclusion. They showed normal random motility. Both blood and exudate neutrophils responded chemotactically to N-formyl Met-Leu-Phe, and blood neutrophils responded chemotactically to zymosan-activated serum. Both kinds of neutrophils phagocytosed zymosan particles and both killed opsonized S. epidermidis in a roller tube system. Both blood and exudate neutrophils showed normal superoxide production when stimulated with opsonized zymosan particles. This evidence suggests that macrophages are the only source of endogenous pyrogens, and that pyrogens secreted by cell populations that are rich in neutrophils are to be attributed to the monocytes or macrophages that they contain.

  12. Grain dust induces IL-8 production from bronchial epithelial cells: effect on neutrophil recruitment.

    Science.gov (United States)

    Park, H S; Suh, J H; Kim, S S; Kwon, O J

    2000-06-01

    There have been several investigations suggesting an involvement of activated neutrophils in the development of grain dust (GD)-induced occupational asthma. Interleukin-8 in the sputa from GD-induced asthmatic patients increased significantly after the exposure to GD. To confirm IL-8 production from bronchial epithelial cells when exposed to GD, and to evaluate the role of IL-8 on neutrophil recruitment. We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four different concentrations ranging from 1 to 200 microg/mL of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production and neutrophil chemotaxis, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant derived from subjects with GD-induced asthma exposed to 10 microg/mL of GD, and then compared with those without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. Neutrophil chemotactic activity of the culture supernatant was determined by modified Boyden chamber method. Interleukin-8 production and neutrophil chemotactic activity from bronchial epithelial cells significantly increased with additions of GD in a dose-dependent manner (P < .05, respectively), and were significantly augmented with additions of PBMC supernatant (P < .05, respectively) at each concentration. Close correlation was noted between neutrophil chemotactic activity and IL-8 level (r = 0.87, P < .05). Compared with the untreated sample, pre-treatment of anti-IL-8 antibody induced a significant suppression (up to 67.2%) of neutrophil chemotactic activity in a dose-dependent manner. These results suggest that IL-8 produced from bronchial epithelial cells may be a major cytokine, which induces neutrophil migration into the airways when exposed to GD.

  13. Dosimetry in intravascular brachytherapy

    International Nuclear Information System (INIS)

    Campos, Laelia Pumilla Botelho

    2000-03-01

    Among the cardiovascular diseases responsible for deaths in the adult population in almost all countries of the world, the most common is acute myocardial infarction, which generally occurs because of the occlusion of one or more coronary arteries. Several diagnostic techniques and therapies are being tested for the treatment of coronary artery disease. Balloon angioplasty has been a popular treatment which is less invasive than traditional surgeries involving revascularization of the myocardium, thus promising a better quality of life for patients. Unfortunately, the rate of restenosis (re-closing of the vessel) after balloon angioplasty is high (approximately 30-50% within the first year after treatment).Recently, the idea of delivering high radiation doses to coronary arteries to avoid or delay restenosis has been suggested. Known as intravascular brachytherapy, the technique has been used with several radiation sources, and researchers have obtained success in decreasing the rate of restenosis in some patient populations. In order to study the radiation dosimetry in the patient and radiological protection for the attending staff for this therapy, radiation dose distributions for monoenergetic electrons and photons (at nine discrete energies) were calculated for blood vessels of diameter 0.15, o,30 and 0.45 cm with balloon and wire sources using the radiation transport code MCNP4B. Specific calculations were carried out for several candidate radionuclides as well. Two s tent sources (metallic prosthesis that put inside of patient's artery through angioplasty) employing 32 P are also simulated. Advantages and disadvantages of the various radionuclides and source geometries are discussed. The dosimetry developed here will aid in the realization of the benefits obtained in patients for this promising new technology. (author)

  14. Chemotactic droplet swimmers in complex geometries

    Science.gov (United States)

    Jin, Chenyu; Hokmabad, Babak V.; Baldwin, Kyle A.; Maass, Corinna C.

    2018-02-01

    Chemotaxis1 and auto-chemotaxis are key mechanisms in the dynamics of micro-organisms, e.g. in the acquisition of nutrients and in the communication between individuals, influencing the collective behaviour. However, chemical signalling and the natural environment of biological swimmers are generally complex, making them hard to access analytically. We present a well-controlled, tunable artificial model to study chemotaxis and autochemotaxis in complex geometries, using microfluidic assays of self-propelling oil droplets in an aqueous surfactant solution (Herminghaus et al 2014 Soft Matter 10 7008-22 Krüger et al 2016 Phys. Rev. Lett. 117). Droplets propel via interfacial Marangoni stresses powered by micellar solubilisation. Moreover, filled micelles act as a chemical repellent by diffusive phoretic gradient forces. We have studied these chemotactic effects in a series of microfluidic geometries, as published in Jin et al (2017 Proc. Natl Acad. Sci. 114 5089-94): first, droplets are guided along the shortest path through a maze by surfactant diffusing into the maze from the exit. Second, we let auto-chemotactic droplet swimmers pass through bifurcating microfluidic channels and record anticorrelations between the branch choices of consecutive droplets. We present an analytical Langevin model matching the experimental data. In a previously unpublished experiment, pillar arrays of variable sizes and shapes provide a convex wall interacting with the swimmer and, in the case of attachment, bending its trajectory and forcing it to revert to its own trail. We observe different behaviours based on the interplay of wall curvature and negative autochemotaxis, i.e. no attachment for highly curved interfaces, stable trapping at large pillars, and a narrow transition region where negative autochemotaxis makes the swimmers detach after a single orbit.

  15. Peptide secreted by human alveolar macrophages releases neutrophil granule contents

    International Nuclear Information System (INIS)

    MacArthur, C.K.; Miller, E.J.; Cohen, A.B.

    1987-01-01

    A monoclonal antibody was developed against an 8000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose, and by autoradiography. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-γ, tumor necrosis factor, or interleukin lα or 1β. The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes

  16. Characterization of the formyl peptide chemotactic receptor appearing at the phagocytic cell surface after exposure to phorbol myristate acetate

    International Nuclear Information System (INIS)

    Gardner, J.P.; Melnick, D.A.; Malech, H.L.

    1986-01-01

    The biochemistry and subcellular source of new formyl peptide chemotactic receptor appearing at the human neutrophil and differentiated HL-60 (d-HL-60) cell surface after stimulation with phorbol myristate acetate (PMA) were examined. Formyl peptide receptor was analyzed by affinity labeling with formyl-norleu-leu-phe-norleu- [ 125 I]iodotyr-lys and ethylene glycol bis(succinimidyl succinate) followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and densitometric analysis of autoradiographs. PMA, a specific granule secretagogue, increases affinity labeling of formyl peptide receptors on the neutrophil surface by 100%, and on d-HL-60, which lack specific granule markers, by 20%. Papain treatment markedly reduces surface labeling of formyl peptide receptor in both neutrophils and d-HL-60, and results in the appearance of a lower m.w. membrane-bound receptor fragment. PMA stimulation of papain-treated cells increases uncleaved surface receptor on neutrophils by 400%, and on D-HL-60 by only 45%. This newly appearing receptor is the same apparent m.w. (55,000 to 75,000 for neutrophils; 62,000 to 80,000 for d-HL-60) and yields the same papain cleavage product as receptor on the surface of unstimulated cells. These observations suggest that specific granule membranes contain large amounts of formyl peptide receptor, which is biochemically identical to that found on the cell surface and can be mobilized to the cell surface with appropriate stimulation

  17. Intravascular bronchio-alveolar tumor

    International Nuclear Information System (INIS)

    Mata, J.M.; Caceres, J.; Prat, J.; Lopez, J.I.; Velilla, O.

    1991-01-01

    In 1975 Dail and Liebow described the clinical and pathological characteristics of a pulmonary tumor which they dominated intravascular bronchio-alveolar tumor (IVBAT). Our aim is to acquaint radiologists with the existence of this tumor by describing the radiologic findings in 2 patients with IVBAT, 1 with hepatic involvement ant the other with pulmonary osteoarthropathy. (author). 7 refs.; 2 figs

  18. A dual-docking microfluidic cell migration assay (D2-Chip) for testing neutrophil chemotaxis and the memory effect.

    Science.gov (United States)

    Yang, Ke; Wu, Jiandong; Xu, Guoqing; Xie, Dongxue; Peretz-Soroka, Hagit; Santos, Susy; Alexander, Murray; Zhu, Ling; Zhang, Michael; Liu, Yong; Lin, Francis

    2017-04-18

    Chemotaxis is a classic mechanism for guiding cell migration and an important topic in both fundamental cell biology and health sciences. Neutrophils are a widely used model to study eukaryotic cell migration and neutrophil chemotaxis itself can lead to protective or harmful immune actions to the body. While much has been learnt from past research about how neutrophils effectively navigate through a chemoattractant gradient, many interesting questions remain unclear. For example, while it is tempting to model neutrophil chemotaxis using the well-established biased random walk theory, the experimental proof was challenged by the cell's highly persistent migrating nature. A special experimental design is required to test the key predictions from the random walk model. Another question that has interested the cell migration community for decades concerns the existence of chemotactic memory and its underlying mechanism. Although chemotactic memory has been suggested in various studies, a clear quantitative experimental demonstration will improve our understanding of the migratory memory effect. Motivated by these questions, we developed a microfluidic cell migration assay (so-called dual-docking chip or D 2 -Chip) that can test both the biased random walk model and the memory effect for neutrophil chemotaxis on a single chip enabled by multi-region gradient generation and dual-region cell alignment. Our results provide experimental support for the biased random walk model and chemotactic memory for neutrophil chemotaxis. Quantitative data analyses provide new insights into neutrophil chemotaxis and memory by making connections to entropic disorder, cell morphology and oscillating migratory response.

  19. In vivo activation of equine eosinophils and neutrophils by experimental Strongylus vulgaris infections.

    Science.gov (United States)

    Dennis, V A; Klei, T R; Chapman, M R; Jeffers, G W

    1988-12-01

    Eosinophils and neutrophils from ponies with Strongylus vulgaris-induced eosinophilia (eosinophilic ponies; activated eosinophils and neutrophils) were assayed in vitro for chemotactic and chemokinetic responses to zymosan-activated serum (ZAS) using the filter system in Boyden chambers, for Fc and complement (C) receptors using the EA and EAC-rosette assays, respectively, and for phagocytic and bactericidal activities using opsonized Escherichia coli and the acridine orange method. The responses of activated eosinophils and neutrophils in the above assays were compared with those of eosinophils and neutrophils from S. vulgaris-naive ponies without eosinophilia (noneosinophilic ponies; nonactivated eosinophils and neutrophils). Differences in cell density following centrifugation in a continuous Percoll gradient were used to further characterize the heterogeneity of activated eosinophils and neutrophils. Activated and nonactivated eosinophils demonstrated similar chemotactic responses to ZAS while activated and nonactivated neutrophils demonstrated similar chemokinetic responses to ZAS. A higher percentage of activated eosinophils and neutrophils expressed Fc and C receptors compared with nonactivated cells (P less than 0.05). Generally, higher percentages of eosinophils and neutrophils expressed C than Fc receptors. However, the percentage of neutrophils with both receptors was higher than that of eosinophils. Phagocytosis and killing of E. coli by either type of eosinophil were not consistently observed. Both activated and nonactivated neutrophils phagocytized E. coli and significant differences between the two cell types were not observed. The bacterial activity, however, of activated neutrophils was significantly greater than that obtained using nonactivated neutrophils (P less than 0.05). Activated eosinophils and neutrophils were both separated into two distinct fractions based on differences in cell densities. A higher percentage of band 2 eosinophils

  20. Interleukin-8: an expanding universe beyond neutrophil chemotaxis and activation.

    Science.gov (United States)

    Mukaida, N

    2000-12-01

    Since the discovery 13 years ago of interleukin (IL)-8 as a potent neutrophil chemotactic factor, accumulating evidence has established it as a crucial mediator in neutrophil-dependent acute inflammation. Numerous observations have demonstrated that various types of cells can produce a large amount of IL-8, either in response to various stimuli or constitutively, after malignant transformation. Recent studies of IL-8-mediated signaling have revealed that IL-8 activates a wide range of signaling molecules in a coordinate manner. IL-8 has been proven to have diverse actions on various types of leukocytic and nonleukocytic cells besides neutrophils. The author reviews recent progress in IL-8 signal transduction and biological actions on nonneutrophilic leukocytes, including T lymphocytes, monocytes, and hematopoietic progenitor cells. Potential involvement of IL-8 in viral infections and tumor progression is also discussed.

  1. Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

    Science.gov (United States)

    Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

    2013-01-01

    Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

  2. 21 CFR 880.5200 - Intravascular catheter.

    Science.gov (United States)

    2010-04-01

    ... Devices § 880.5200 Intravascular catheter. (a) Identification. An intravascular catheter is a device that consists of a slender tube and any necessary connecting fittings and that is inserted into the patient's vascular system for short term use (less than 30 days) to sample blood, monitor blood pressure, or...

  3. Neutrophils at work

    DEFF Research Database (Denmark)

    Nauseef, William M; Borregaard, Niels

    2014-01-01

    In this Review we discuss data demonstrating recently recognized aspects of neutrophil homeostasis in the steady state, granulopoiesis in 'emergency' conditions and interactions of neutrophils with the adaptive immune system. We explore in vivo observations of the recruitment of neutrophils from ...

  4. Transport of Chemotactic Bacteria in Porous Media with Structured Heterogeneity

    Science.gov (United States)

    Ford, R. M.; Wang, M.; Liu, J.; Long, T.

    2008-12-01

    Chemical contaminants that become trapped in low permeability zones (e.g. clay lenses) are difficult to remediate using conventional pump-and-treat approaches. Chemotactic bacteria that are transported by groundwater through more permeable regions may migrate toward these less permeable zones in response to chemical gradients created by contaminant diffusion from the low permeability source, thereby enhancing the remediation process by directing bacteria to the contaminants they degrade. What effect does the heterogeneity associated with coarse- and fine-grained layers that are characteristic of natural groundwater environments have on the transport of microorganisms and their chemotactic response? To address this question experiments were conducted over a range of scales from a single capillary tube to a laboratory- scale column in both static and flowing systems with and without chemoattractant gradients. In static capillary assays, motile bacteria accumulated at the interface between an aqueous solution and a suspension of agarose particulates. In microfluidic devices with an array of staggered cylinders, chemotactic bacteria migrated transverse to flow in response to a chemoattractant gradient. In sand columns packed with a coarse-grained core and surrounded by a fine-grained annulus, chemotactic bacteria migrated preferentially toward a chemoattractant source along the centerline. Mathematical models and computer simulations were developed to analyze the experimental observations in terms of transport parameters from the advection- disperson-sorption equation.

  5. Modulation of neutrophil and monocyte function by recombinant human granulocyte macrophage colony-stimulating factor in patients with lymphoma

    DEFF Research Database (Denmark)

    Kharazmi, A; Nielsen, H; Hovgaard, D

    1991-01-01

    by up to 43-fold. rhGM-CSF treatment did not affect degranulation of the neutrophils as measured by release of vitamin B12 binding protein. Degree of modulation of neutrophil and monocyte function by rhGM-CSF was independent of rhGM-CSF dosages administered. These data suggest that phagocytic defence...... and chemiluminescence responses to f-Met-Leu-Phe, zymosan activated serum (ZAS) and opsonized zymosan (OZ) were determined. It was observed that chemotactic response of neutrophils to f-Met-Leu-Phe and ZAS was reduced, whereas the chemiluminescence response of both cell types to f-Met-Leu-Phe and zymosan was enhanced...

  6. Chemokine Receptor Ccr1 Drives Neutrophil-Mediated Kidney Immunopathology and Mortality in Invasive Candidiasis

    Science.gov (United States)

    Lionakis, Michail S.; Swamydas, Muthulekha; Wan, Wuzhou; Richard Lee, Chyi-Chia; Cohen, Jeffrey I.; Scheinberg, Phillip; Gao, Ji-Liang; Murphy, Philip M.

    2012-01-01

    Invasive candidiasis is the 4th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1lo to Ccr1high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1+/+ and Ccr1−/− donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ. PMID:22916017

  7. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

    Directory of Open Access Journals (Sweden)

    Michail S Lionakis

    Full Text Available Invasive candidiasis is the 4(th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo to Ccr1(high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1(+/+ and Ccr1(-/- donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.

  8. Chronic neutrophilic leukemia.

    Science.gov (United States)

    Bredeweg, Arthur; Burch, Micah; Krause, John R

    2018-01-01

    Chronic neutrophilic leukemia is a rare myeloproliferative disorder characterized by a sustained peripheral blood neutrophilia, absence of the BCR/ABL oncoprotein, bone marrow hypercellularity with less than 5% myeloblasts and normal neutrophil maturation, and no dysplasia. This leukemia has been associated with mutations in the colony-stimulating factor 3 receptor (CSF3R) that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of chronic neutrophilic leukemia. We present a case of chronic neutrophilic leukemia and discuss the criteria for diagnosis and the significance of mutations found in this leukemia.

  9. Neutrophils in critical illness.

    Science.gov (United States)

    McDonald, Braedon

    2018-03-01

    During critical illness, dramatic alterations in neutrophil biology are observed including abnormalities of granulopoeisis and lifespan, cell trafficking and antimicrobial effector functions. As a result, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. In this article, the role of neutrophils in the pathogenesis of critical illness (sepsis, trauma, burns and others) will be explored, including pathological changes to neutrophil function during critical illness and the utility of monitoring aspects of the neutrophil phenotype as biomarkers for diagnosis and prognostication. Lastly, we review findings from clinical trials of therapies that target the harmful effects of neutrophils, providing a bench-to-bedside perspective on neutrophils in critical illness.

  10. 21 CFR 870.3375 - Cardiovascular intravascular filter.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiovascular intravascular filter. 870.3375... Cardiovascular intravascular filter. (a) Identification. A cardiovascular intravascular filter is an implant that... and Revision of 2/12/90 (K90-1)” and (ii) “Guidance for Cardiovascular Intravascular Filter 510(k...

  11. New strategy for sepsis: Targeting a key role of platelet-neutrophil interaction

    Directory of Open Access Journals (Sweden)

    Xu Wang

    2014-07-01

    Full Text Available Neutrophil and platelet are essential arms of the innate immune response. In sepsis, platelet abnormal activation as well as neutrophil paralysis are well recognized. For platelet, it is characterized by the contribution to disseminated intravascular coagulation (DIC and the enhanced inflammation response. In terms of neutrophil, its dysfunction is manifested by the impaired recruitment and migration to the infectious foci, abnormal sequestration in the remote organs, and the delayed clearance. More recently, it has been apparent that together platelet-neutrophil interaction can induce a faster and harder response during sepsis. This article focuses on the activation of platelet, dysfunction of neutrophil, and the interaction between them during sepsis and profiles some of the molecular mechanisms and outcomes in these cellular dialogues, providing a novel strategy for treatment of sepsis.

  12. Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro.

    Science.gov (United States)

    Llewellyn-Jones, C G; Hill, S L; Stockley, R A

    1994-03-01

    Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil function is uncertain. Fluticasone propionate is a new topically active synthetic steroid which can be measured in body fluids and which undergoes first pass metabolism. The effects of fluticasone propionate on the function of neutrophils isolated from normal, healthy control subjects and on the chemotactic activity of sputum sol phase were assessed. Preincubation of neutrophils with fluticasone propionate reduced the chemotactic response to 10(-8) mol/l F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent manner. Furthermore, when fluticasone propionate was added to sputum from eight patients with stable chronic obstructive bronchitis the chemotactic activity of a 1:5 dilution of the sol phase fell from a mean (SE) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 11.9 (0.6) cells field at 1 mumol/l, 10 mumol/l, and 100 mumol/l, respectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells and by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1% inhibition of stimulated cells with 1 mumol/l fluticasone propionate, 24% and 18.7% inhibition respectively at 100 mumol/l fluticasone propionate. Fluticasone propionate had no effect on generation of superoxide anion by resting or stimulated cells. These results indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connective tissue.

  13. Dosimetric model for intravascular brachytherapy

    International Nuclear Information System (INIS)

    Flower, E.E.; Stroud, D.B.

    2000-01-01

    Full text: Intravascular brachytherapy has been shown to be a prophylaxis for restenosis. Adventitial macrophages, which are extremely radiosensitive, initiate neointima formation. A model of the dose levels of the treatment range is developed, assuming that the adventitia is the target tissue. If the adventitia receives a dose of less than 10 Gy, it is assumed the treatment will be ineffective. If the dose to any part of the wall is above 30 Gy, it is assumed that the treatment could be detrimental. Hence the treatment range is between 10 and 30 Gy, with 20 Gy being the optimum dosage to the adventitia. An algorithm using numerical integration of published dose kernels calculates the dose at any point surrounding a beta ( 32 P) line source of finite length. Dose profiles were obtained to demonstrate edge effects. For long lesions, the source is often stepped along the artery. Dose changes due to separation or overlapping of sources during source stepping procedures were also determined. Isodose curves were superimposed on intravascular ultrasound images to demonstrate dose levels. For an exposure time of 60 seconds with a 200mCi source, the optimum dose of 20 Gy occurs at a distance 1.94mm from the centre of the source. The upper limit of the treatment dose range (30 Gy) occurs at 1.59mm. The lower limit of the treatment dose range (10 Gy) occurs at 2.7mm. Significant perturbations to the treatment dose range can be caused by non-centering of the source, edge effects and separation or overlapping of sources in stepping procedures. Despite these concerns, many successful procedures have been reported and this implies that the model is over simplified and requires modifications. Copyright (2000) Australasian College of Physical Scientists and Engineers in Medicine

  14. Neutrophil trails guide influenza-specific CD8⁺ T cells in the airways.

    Science.gov (United States)

    Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris; Capece, Tara; Bae, Seyeon; Miller, Richard; Topham, David J; Kim, Minsoo

    2015-09-04

    During viral infections, chemokines guide activated effector T cells to infection sites. However, the cells responsible for producing these chemokines and how such chemokines recruit T cells are unknown. Here, we show that the early recruitment of neutrophils into influenza-infected trachea is essential for CD8(+) T cell-mediated immune protection in mice. We observed that migrating neutrophils leave behind long-lasting trails that are enriched in the chemokine CXCL12. Experiments with granulocyte-specific CXCL12 conditionally depleted mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8(+) T cell recruitment and effector functions. Collectively, these results suggest that neutrophils deposit long-lasting, chemokine-containing trails, which may provide both chemotactic and haptotactic cues for efficient CD8(+) T cell migration and localization in influenza-infected tissues. Copyright © 2015, American Association for the Advancement of Science.

  15. Neutrophil trails guide influenza-specific CD8+ T cells in the airways

    Science.gov (United States)

    Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris; Capece, Tara; Bae, Seyeon; Miller, Richard; Topham, David J.; Kim, Minsoo

    2016-01-01

    During viral infections, chemokines guide activated effector T cells to infection sites. However, the cells responsible for producing these chemokines and how such chemokines recruit T cells is unknown. Here, we show that the early recruitment of neutrophils into influenza-infected trachea is essential for CD8+ T cell-mediated immune protection in mice. We observed that migrating neutrophils leave behind long-lasting trails that are enriched in the chemokine CXCL12. Experiments with granulocyte-specific CXCL12 conditional knock-out mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8+ T cell recruitment and effector functions. Collectively, these results suggest neutrophils deposit long-lasting, chemokine-containing trails, which may provide both chemotactic and haptotactic cues for efficient CD8+ T cell migration and localization in influenza-infected tissues. PMID:26339033

  16. Monocyte chemotactic protein-4 (MCP-4/CCL-13) and CC ...

    African Journals Online (AJOL)

    EL-HAKIM

    chronic inflammation and local tissue eosinophilia. Atopic asthma is characterized by a 50-fold increase in the number of eosinophils relative to neutrophils in the bronchial mucosa. This is the result of the cumulative and sequential effects of variable increases in selective eosinophil versus neutrophil migration occurring at ...

  17. Hemi-Intravascular Stenting for Supermicrosurgical Anastomosis

    OpenAIRE

    Kensuke Tashiro, MD; Shuji Yamashita, MD; Mitsunaga Narushima, MD; Isao Koshima, MD; Shimpei Miyamoto, MD

    2017-01-01

    Background:. Although supermicrosurgical anastomosis is a widely known reconstructive microsurgical technique, it is difficult to perform. To expand the clinical use of supermicrosurgery, we used hemi-intravascular stenting (hemi-IVaS), which is performed by inserting an intravascular stent into one side of the vessel. We conducted lymphaticovenular anastomosis, free perforator flap transfer, and fingertip replantation with supermicrosurgical anastomosis using hemi-IVaS technique and examined...

  18. Optimal methylation noise for best chemotactic performance of E. coli

    Science.gov (United States)

    Dev, Subrata; Chatterjee, Sakuntala

    2018-03-01

    In response to a concentration gradient of chemoattractant, E. coli bacterium modulates the rotational bias of flagellar motors which control its run-and-tumble motion, to migrate towards regions of high chemoattractant concentration. Presence of stochastic noise in the biochemical pathway of the cell has important consequences on the switching mechanism of motor bias, which in turn affects the runs and tumbles of the cell in a significant way. We model the intracellular reaction network in terms of coupled time evolution of three stochastic variables—kinase activity, methylation level, and CheY-P protein level—and study the effect of methylation noise on the chemotactic performance of the cell. In presence of a spatially varying nutrient concentration profile, a good chemotactic performance allows the cell to climb up the concentration gradient quickly and localize in the nutrient-rich regions in the long time limit. Our simulations show that the best performance is obtained at an optimal noise strength. While it is expected that chemotaxis will be weaker for very large noise, it is counterintuitive that the performance worsens even when noise level falls below a certain value. We explain this striking result by detailed analysis of CheY-P protein level statistics for different noise strengths. We show that when the CheY-P level falls below a certain (noise-dependent) threshold the cell tends to move down the concentration gradient of the nutrient, which has a detrimental effect on its chemotactic response. This threshold value decreases as noise is increased, and this effect is responsible for noise-induced enhancement of chemotactic performance. In a harsh chemical environment, when the nutrient degrades with time, the amount of nutrient intercepted by the cell trajectory is an effective performance criterion. In this case also, depending on the nutrient lifetime, we find an optimum noise strength when the performance is at its best.

  19. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

    Directory of Open Access Journals (Sweden)

    Gomez-Lopez Nardhy

    2013-01-01

    Full Text Available Abstract Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD 17, 20 and 22 (term gestation. We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif ligand 2 (Ccl2 gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif ligand 1/CXCL1, and CXCL10 were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.

  20. Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

    DEFF Research Database (Denmark)

    Sørensen, A L; Hey, A S; Kharazmi, A

    1994-01-01

    In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

  1. Interventional and intravascular MR angiography

    International Nuclear Information System (INIS)

    Ladd, M.E.; Debatin, J.F.

    2000-01-01

    Magnetic resonance imaging (MRI) has a number of characteristics which make it attractive for guidance of intravascular therapeutic procedures, including high soft tissue contrast, imaging in any arbitrary oblique plane, lack of ionizing radiation, and the ability to provide functional information, such as flow velocity and volume per unit time. For MR guidance of vascular interventions to be safe, catheters and guidewires must be visualized relative to the vascular system and surrounding tissues. A number of approaches for making instruments visible in an MR environment are presented, including both passive and active techniques. Passive techniques depend on contrast agents or susceptibility artifacts, whereas active techniques, including MR tracking, MR profiling, and active field inhomogeneity, use some form of electrical coil built into the instrument. The potential for obtaining high-resolution images of the vessel wall using coils built into a catheter is also discussed. These images provide the capability to distinguish and identify various plaque components. The additional capabilities of MRI could potentially open up new applications beyond those currently performed under X-ray fluoroscopic guidance. (orig.) [de

  2. Coagulación intravascular diseminada = Disseminated intravascular coagulation

    Directory of Open Access Journals (Sweden)

    Arango Barrientos, Marcos

    2010-12-01

    Full Text Available La coagulación intravascular diseminada (CID es una entidad clínica frecuente que se presenta como fenómeno secundario a diversas enfermedades entre las cuales se destacan las infecciones graves, las neoplasias y las catástrofes obstétricas. Se caracteriza por una activación difusa y simultánea de los sistemas endógenos de la coagulación y la fibrinólisis. El depósito de pequeños trombos en la circulación conduce finalmente a disfunción orgánica múltiple y en algunos casos a la muerte. Las manifestaciones clínicas pueden incluir fenómenos trombóticos y hemorrágicos. Se ha propuesto un puntaje de fácil aplicación para simplificar el diagnóstico de la entidad. El tratamiento incluye el control específico de la causa subyacente que favorece la aparición de la CID, el soporte con hemoderivados en pacientes con manifestaciones de sangrado y la anticoagulación terapéutica en pacientes con trombosis mayores. El desarrollo de CID es un factor pronóstico adverso que aumenta significativamente la tasa de mortalidad. En este artículo de revisión se incluyen los siguientes aspectos de la CID: historia, epidemiología, clasificación, entidades asociadas, fisiopatología, clínica, diagnóstico, tratamiento y pronóstico.

  3. Dosimetry in intravascular brachytherapy; Calculos dosimetricos em braquiterapia intravascular

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Laelia Pumilla Botelho

    2000-03-01

    Among the cardiovascular diseases responsible for deaths in the adult population in almost all countries of the world, the most common is acute myocardial infarction, which generally occurs because of the occlusion of one or more coronary arteries. Several diagnostic techniques and therapies are being tested for the treatment of coronary artery disease. Balloon angioplasty has been a popular treatment which is less invasive than traditional surgeries involving revascularization of the myocardium, thus promising a better quality of life for patients. Unfortunately, the rate of restenosis (re-closing of the vessel) after balloon angioplasty is high (approximately 30-50% within the first year after treatment).Recently, the idea of delivering high radiation doses to coronary arteries to avoid or delay restenosis has been suggested. Known as intravascular brachytherapy, the technique has been used with several radiation sources, and researchers have obtained success in decreasing the rate of restenosis in some patient populations. In order to study the radiation dosimetry in the patient and radiological protection for the attending staff for this therapy, radiation dose distributions for monoenergetic electrons and photons (at nine discrete energies) were calculated for blood vessels of diameter 0.15, o,30 and 0.45 cm with balloon and wire sources using the radiation transport code MCNP4B. Specific calculations were carried out for several candidate radionuclides as well. Two s tent sources (metallic prosthesis that put inside of patient's artery through angioplasty) employing {sup 32} P are also simulated. Advantages and disadvantages of the various radionuclides and source geometries are discussed. The dosimetry developed here will aid in the realization of the benefits obtained in patients for this promising new technology. (author)

  4. Dosimetry in intravascular brachytherapy; Calculos dosimetricos em braquiterapia intravascular

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Laelia Pumilla Botelho

    2000-03-01

    Among the cardiovascular diseases responsible for deaths in the adult population in almost all countries of the world, the most common is acute myocardial infarction, which generally occurs because of the occlusion of one or more coronary arteries. Several diagnostic techniques and therapies are being tested for the treatment of coronary artery disease. Balloon angioplasty has been a popular treatment which is less invasive than traditional surgeries involving revascularization of the myocardium, thus promising a better quality of life for patients. Unfortunately, the rate of restenosis (re-closing of the vessel) after balloon angioplasty is high (approximately 30-50% within the first year after treatment).Recently, the idea of delivering high radiation doses to coronary arteries to avoid or delay restenosis has been suggested. Known as intravascular brachytherapy, the technique has been used with several radiation sources, and researchers have obtained success in decreasing the rate of restenosis in some patient populations. In order to study the radiation dosimetry in the patient and radiological protection for the attending staff for this therapy, radiation dose distributions for monoenergetic electrons and photons (at nine discrete energies) were calculated for blood vessels of diameter 0.15, o,30 and 0.45 cm with balloon and wire sources using the radiation transport code MCNP4B. Specific calculations were carried out for several candidate radionuclides as well. Two s tent sources (metallic prosthesis that put inside of patient's artery through angioplasty) employing {sup 32} P are also simulated. Advantages and disadvantages of the various radionuclides and source geometries are discussed. The dosimetry developed here will aid in the realization of the benefits obtained in patients for this promising new technology. (author)

  5. Mitochondria in neutrophil apoptosis

    NARCIS (Netherlands)

    van Raam, B. J.; Verhoeven, A. J.; Kuijpers, T. W.

    2006-01-01

    Central in the regulation of the short life span of neutrophils are their mitochondria. These organelles hardly contribute to the energy status of neutrophils but play a vital role in the apoptotic process. Not only do the mitochondria contain cytotoxic proteins that are released during apoptosis

  6. Enhancement by platelets of oxygen radical responses of human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

    1986-03-01

    When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O-/sub 2/ and H/sub 2/O/sub 2/. This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O-/sub 2/ generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O-/sub 2/ responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils.

  7. Enhancement by platelets of oxygen radical responses of human neutrophils

    International Nuclear Information System (INIS)

    McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

    1986-01-01

    When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O- 2 and H 2 O 2 . This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O- 2 generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O- 2 responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils

  8. Deficiency of the Chemotactic Factor Inactivator in Human Sera with α1-Antitrypsin Deficiency

    Science.gov (United States)

    Ward, Peter A.; Talamo, Richard C.

    1973-01-01

    As revealed by appropriate fractionation procedures, human serum deficient in α1-antitrypsin (α1-AT) is also deficient in the naturally occurring chemotactic factor inactivator. These serum donors had severe pulmonary emphysema. Serum from patients with clinically similar pulmonary disease, but with presence of α1-AT in the serum, showed no such deficiency of the chemotactic factor inactivator. When normal human serum and α1-AT-deficient human sera are chemotactically activated by incubation with immune precipitates, substantially more chemotactic activity is generated in α1-AT-deficient serum. These data indicate that in α1-AT-deficient serum there is an imbalance in the generation and control of chemotactic factors. It is suggested that the theory regarding development of pulmonary emphysema in patients lacking the α1-antitrypsin in their serum should be modified to take into account a deficiency of the chemotactic factor inactivator. PMID:4683887

  9. Urease Plays an Important Role in the Chemotactic Motility of Helicobacter pylori in a Viscous Environment

    OpenAIRE

    Nakamura, Hiroki; Yoshiyama, Hironori; Takeuchi, Hiroaki; Mizote, Tomoko; Okita, Kiwamu; Nakazawa, Teruko

    1998-01-01

    Helicobacter pylori exhibits chemotactic responses to urea, flurofamide, acetohydroxamic acid, and sodium bicarbonate. In buffer, the chemotactic activities of a urease-positive strain were higher than those of the isogenic urease-negative strain. Moreover, the chemotactic activities of the urease-positive strain were increased in a viscous solution containing 3% polyvinylpyrrolidone, whereas those of the urease-negative mutant were not. These results are in accordance with the fact that the ...

  10. Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis.

    Science.gov (United States)

    Bhuiyan, Md Saruar; Ellett, Felix; Murray, Gerald L; Kostoulias, Xenia; Cerqueira, Gustavo M; Schulze, Keith E; Mahamad Maifiah, Mohd Hafidz; Li, Jian; Creek, Darren J; Lieschke, Graham J; Peleg, Anton Y

    2016-08-23

    Innate cellular immune responses are a critical first-line defense against invading bacterial pathogens. Leukocyte migration from the bloodstream to a site of infection is mediated by chemotactic factors that are often host-derived. More recently, there has been a greater appreciation of the importance of bacterial factors driving neutrophil movement during infection. Here, we describe the development of a zebrafish infection model to study Acinetobacter baumannii pathogenesis. By using isogenic A. baumannii mutants lacking expression of virulence effector proteins, we demonstrated that bacterial drivers of disease severity are conserved between zebrafish and mammals. By using transgenic zebrafish with fluorescent phagocytes, we showed that a mutation of an established A. baumannii global virulence regulator led to marked changes in neutrophil behavior involving rapid neutrophil influx to a localized site of infection, followed by prolonged neutrophil dwelling. This neutrophilic response augmented bacterial clearance and was secondary to an impaired A. baumannii phenylacetic acid catabolism pathway, which led to accumulation of phenylacetate. Purified phenylacetate was confirmed to be a neutrophil chemoattractant. These data identify a previously unknown mechanism of bacterial-guided neutrophil chemotaxis in vivo, providing insight into the role of bacterial metabolism in host innate immune evasion. Furthermore, the work provides a potentially new therapeutic paradigm of targeting a bacterial metabolic pathway to augment host innate immune responses and attenuate disease.

  11. Novel approaches to the management of disseminated intravascular coagulation

    NARCIS (Netherlands)

    Levi, M. [=Marcel M.; de Jonge, E.; van der Poll, T.; ten Cate, H.

    2000-01-01

    Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. We addressed the issue of whether there is evidence that this fibrin deposition contributes to multiple organ

  12. Fluorescent Method for Observing Intravascular Bonghan Duct

    Directory of Open Access Journals (Sweden)

    Byung-Cheon Lee

    2005-12-01

    Full Text Available Observation of intra-vascular threadlike structures in the blood vessels of rats is reported with the images by differential interference contrast microscope, and fluorescence inverted microscope of the acridine-orange stained samples. The confocal microscope image and the hematoxylin-eosin staining revealed the distinctive pattern of nuclei distribution that clearly discerned the threadlike structure from fibrin, capillary, small venule, arteriole, or lymph vessel. Physiological function of the intra-vascular thread in connection with acupuncture is discussed. Especially, this threadlike duct can be a circulation path for herb-liquid flow, which may provide the scientific mechanism for therapeutic effect of herbal acupuncture.

  13. Global solution for a chemotactic haptotactic model of cancer invasion

    Science.gov (United States)

    Tao, Youshan; Wang, Mingjun

    2008-10-01

    This paper deals with a mathematical model of cancer invasion of tissue recently proposed by Chaplain and Lolas. The model consists of a reaction-diffusion-taxis partial differential equation (PDE) describing the evolution of tumour cell density, a reaction-diffusion PDE governing the evolution of the proteolytic enzyme concentration and an ordinary differential equation modelling the proteolysis of the extracellular matrix (ECM). In addition to random motion, the tumour cells are directed not only by haptotaxis (cellular locomotion directed in response to a concentration gradient of adhesive molecules along the ECM) but also by chemotaxis (cellular locomotion directed in response to a concentration gradient of the diffusible proteolytic enzyme). In one space dimension, the global existence and uniqueness of a classical solution to this combined chemotactic-haptotactic model is proved for any chemotactic coefficient χ > 0. In two and three space dimensions, the global existence is proved for small χ/μ (where μ is the logistic growth rate of the tumour cells). The fundamental point of proof is to raise the regularity of a solution from L1 to Lp (p > 1). Furthermore, the existence of blow-up solutions to a sub-model in two space dimensions for large χ shows, to some extent, that the condition that χ/μ is small is necessary for the global existence of a solution to the full model.

  14. Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway.

    LENUS (Irish Health Repository)

    Fanning, N F

    2012-02-03

    Iodinated contrast media (ICM) can induce apoptosis (programmed cell death) in renal, myocardial and endothelial cells. Following intravascular injection, circulating immune cells are exposed to high concentrations of ICM. As neutrophils constitutively undergo apoptosis we hypothesized that ICM may adversely affect neutrophil survival. Our aim was to investigate the effect of ICM on neutrophil apoptosis. Neutrophils were isolated from healthy subjects and cultured in vitro with ionic (diatrizoate and ioxaglate) and non-ionic (iohexol and iotrolan) ICM. The effect of ICM on neutrophil apoptosis in both unstimulated and lipopolysaccharide-stimulated neutrophils was determined by annexin V flow cytometry. The influence of physicochemical properties of the different ICM on apoptosis of neutrophils was also studied. We further investigated the effects of ICM on key intracellular signal pathways, including p38 mitogen-activated protein kinase (MAPK) by Western blotting, and mitochondrial depolarization and caspase activity by flow cytometry. Isoiodine concentrations (20 mg ml(-1)) of ionic (diatrizoate 69.6+\\/-2.9%; ioxaglate 58.9+\\/-2.0%) and non-ionic (iohexol 57.3+\\/-2.9%; iotrolan 57.1+\\/-2.6%) ICM significantly induced neutrophil apoptosis over control levels (47.7+\\/-1.4%). The apoptotic effect of ICM was influenced by their chemical structure, with ionic ICM having a more significant (p<0.01) apoptotic effect than non-ionic ICM (p<0.05). Furthermore, ICM reversed the anti-apoptotic effect of lipopolysaccharide (1000 ng ml(-1)) treated neutrophils to control levels (23.0+\\/-3.5% to 61.2+\\/-5.3%; n=4; p<0.05). These agents induce apoptosis through a p38 MAPK independent pathway that results in mitochondrial depolarization, and is dependent on caspase activation. As neutrophils play a central role in host response to infection and injury, ICM, through induction of neutrophil apoptosis, could have a significant deleterious effect on host immune defence and

  15. Quinine-induced disseminated intravascular coagulation.

    Science.gov (United States)

    Spearing, R L; Hickton, C M; Sizeland, P; Hannah, A; Bailey, R R

    Recurrent disseminated intravascular coagulation occurred in 3 women after ingestion of quinine tablets for cramp. All had circulating quinine-dependent antibodies to platelets and in 2 there was initial evidence of antibody consumption, with low titres that rose steeply over the next few days and remained high for many months.

  16. Intravascular volume after aneurysmal subarachnoid hemorrhage

    NARCIS (Netherlands)

    Hoff, R.G.

    2009-01-01

    Intravascular volume after aneurysmal subarachnoid hemorrhage A subarachnoid hemorrhage (SAH) from a ruptured cerebral aneurysm is a devastating disorder with an often poor prognosis. The occurrence of delayed cerebral ischemia (DCI) is one of the most important factors determining outcome in

  17. Disseminated Intravascular Coagulation Following Induction of ...

    African Journals Online (AJOL)

    Background: Disseminated Intravascular coagulopathy (DIC) has been reported following use of Misoprostol which is an old drug with new indications in Obstetrics and. Gynecology. Its effectiveness, low cost, stability in tropical conditions and ease of administration as well as side effects like gastrointestinal effect, uterine ...

  18. Hemi-Intravascular Stenting for Supermicrosurgical Anastomosis

    Directory of Open Access Journals (Sweden)

    Kensuke Tashiro, MD

    2017-11-01

    Conclusions:. Hemi-IVaS could be a useful alternative to conventional intravascular stenting techniques and is also effective for supermicrosurgical perforator-to-perforator anastomosis. Further studies are needed to improve the success rate and to explore its other possible utilizations in supermicrosurgery.

  19. Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

    Science.gov (United States)

    Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won

    2017-09-01

    Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

  20. Urease plays an important role in the chemotactic motility of Helicobacter pylori in a viscous environment.

    Science.gov (United States)

    Nakamura, H; Yoshiyama, H; Takeuchi, H; Mizote, T; Okita, K; Nakazawa, T

    1998-10-01

    Helicobacter pylori exhibits chemotactic responses to urea, flurofamide, acetohydroxamic acid, and sodium bicarbonate. In buffer, the chemotactic activities of a urease-positive strain were higher than those of the isogenic urease-negative strain. Moreover, the chemotactic activities of the urease-positive strain were increased in a viscous solution containing 3% polyvinylpyrrolidone, whereas those of the urease-negative mutant were not. These results are in accordance with the fact that the mutant strain did not show swarming in motility agar regardless of having flagella. Incubation of the wild-type strain with flurofamide resulted in partial inhibition of the chemotactic activities in the viscous solution. In addition, incubation with acetohydroxamic acid, a low-molecular-weight, diffusible urease inhibitor, resulted in complete loss of chemotactic activity in the viscous solution. The inhibition of the chemotactic activity by urease inhibitors paralleled the inhibition of urease. The chemotactic activity of H. pylori was also inhibited by the proton carrier carbonyl cyanide m-chlorophenylhydrazone, showing that H. pylori utilizes proton motive force for motility. These results indicate that cytoplasmic urease plays an important role in the chemotactic motility of H. pylori under a condition that mimics the ecological niche of the bacterium, the gastric mucous layer.

  1. The spectrum of neutrophilic dermatoses associated with monoclonal gammopathy: Association with IgA isotype and inflammatory profile.

    Science.gov (United States)

    Szalat, Raphael; Monsel, Gentiane; Le Goff, Wilfried; Battistella, Maxime; Bengouffa, Djaouida; Schlageter, Marie-Helene; Bouaziz, Jean-David; Arnulf, Bertrand; Vignon, Marguerite; Lesnik, Philippe; Saussine, Anne; Malphettes, Marion; Lazareth, Anne; Vignon-Pennamen, Marie-Dominique; Bagot, Martine; Brouet, Jean-Claude; Fermand, Jean-Paul; Rybojad, Michel; Asli, Bouchra

    2015-11-01

    Neutrophilic dermatoses refer to a group of cutaneous inflammatory disorders characterized by neutrophilic infiltration of the skin. Neutrophilic dermatoses have been reported in association with various conditions including autoimmune diseases, inflammatory bowel diseases, and neoplasia. In the later condition, myeloproliferative disorders and monoclonal gammopathy (monoclonal immunoglobulin [MIg]) are the most frequent. Only few data are available in case of neutrophilic dermatoses associated with MIg regarding the pathophysiology and the clinical outcome. We sought to gain further insight into clinical and biological aspects of neutrophilic dermatoses associated with MIg. We report a retrospective series of 26 patients with neutrophilic dermatoses associated with MIg focusing on clinical and biological aspects, with a study of a large panel of cytokines, chemokines, and adhesion molecules. This study reveals an association between MIg IgA isotype and neutrophilic dermatoses, and a specific inflammatory pattern including elevated interleukin 6, vascular endothelial growth factor, monocyte chemotactic protein-1, epidermal growth factor, and intercellular adhesion molecule-1. This is a retrospective study from a single institution with a limited number of participants. Our data highlight a strong association between IgA isotype and neutrophilic dermatoses, and the existence of a specific inflammatory profile involving several molecules. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Ectodomain Shedding by ADAM17: Its Role in Neutrophil Recruitment and the Impairment of This Process during Sepsis.

    Science.gov (United States)

    Mishra, Hemant K; Ma, Jing; Walcheck, Bruce

    2017-01-01

    Neutrophils are specialized at killing bacteria and are recruited from the blood in a rapid and robust manner during infection. A cascade of adhesion events direct their attachment to the vascular endothelium and migration into the underlying tissue. A disintegrin and metalloproteinase 17 (ADAM17) functions in the cell membrane of neutrophils and endothelial cells by cleaving its substrates, typically in a cis manner, at an extracellular site proximal to the cell membrane. This process is referred to as ectodomain shedding and it results in the downregulation of various adhesion molecules and receptors, and the release of immune regulating factors. ADAM17 sheddase activity is induced upon cell activation and rapidly modulates intravascular adhesion events in response to diverse environmental stimuli. During sepsis, an excessive systemic inflammatory response against infection, neutrophil migration becomes severely impaired. This involves ADAM17 as indicated by increased levels of its cleaved substrates in the blood of septic patients, and that ADAM17 inactivation improves neutrophil recruitment and bacterial clearance in animal models of sepsis. Excessive ADAM17 sheddase activity during sepsis thus appears to undermine in a direct and indirect manner the necessary balance between intravascular adhesion and de-adhesion events that regulate neutrophil migration into sites of infection. This review provides an overview of ADAM17 function and regulation and its potential contribution to neutrophil dysfunction during sepsis.

  3. Neutrophilic respiratory tract inflammation and peripheral blood neutrophilia after grain sorghum dust extract challenge.

    Science.gov (United States)

    Von Essen, S G; O'Neill, D P; McGranaghan, S; Olenchock, S A; Rennard, S I

    1995-11-01

    To determine if inhalation of grain sorghum dust in the laboratory would cause neutrophilic upper and lower respiratory tract inflammation in human volunteers, as well as systemic signs of illness. Prospective. University of Nebraska Medical Center. Thirty normal volunteers. Inhalation challenge with 20 mL of a nebulized solution of filter-sterilized grain sorghum dust extract (GSDE). One group received prednisone, 20 mg for 2 days, prior to the challenge. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 24 h after challenge, with samples collected as bronchial and alveolar fractions. Findings included visible signs of airways inflammation, quantified as the bronchitis index. The percentage of bronchial neutrophils was significantly increased in those challenged with GSDE vs the control solution, Hanks' balanced salt solution (40.3 +/- 4.5% vs 14.3 +/- 5.1%, p grain dust extract. To explain the increase in peripheral blood neutrophil counts, the capacity of the peripheral blood neutrophils to migrate in chemotaxis experiments was examined. The results demonstrate an increase in peripheral blood neutrophils and an increase in chemotactic responsiveness. Inhalation challenge with a grain dust extract causes respiratory tract inflammation and a peripheral blood neutrophilia. One reason for this may be an increase in activated peripheral blood neutrophils.

  4. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J I

    1974-01-01

    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  5. Substrate-driven chemotactic assembly in an enzyme cascade

    Science.gov (United States)

    Zhao, Xi; Palacci, Henri; Yadav, Vinita; Spiering, Michelle M.; Gilson, Michael K.; Butler, Peter J.; Hess, Henry; Benkovic, Stephen J.; Sen, Ayusman

    2018-03-01

    Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase. We show that each enzyme independently follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Furthermore, we find that the chemotactic assembly of enzymes occurs even under cytosolic crowding conditions.

  6. Mapping intravascular ultrasound controversies in interventional cardiology practice.

    Directory of Open Access Journals (Sweden)

    David Maresca

    Full Text Available Intravascular ultrasound is a catheter-based imaging modality that was developed to investigate the condition of coronary arteries and assess the vulnerability of coronary atherosclerotic plaques in particular. Since its introduction in the clinic 20 years ago, use of intravascular ultrasound innovation has been relatively limited. Intravascular ultrasound remains a niche technology; its clinical practice did not vastly expand, except in Japan, where intravascular ultrasound is an appraised tool for guiding percutaneous coronary interventions. In this qualitative research study, we follow scholarship on the sociology of innovation in exploring both the current adoption practices and perspectives on the future of intravascular ultrasound. We conducted a survey of biomedical experts with experience in the technology, the practice, and the commercialization of intravascular ultrasound. The collected information enabled us to map intravascular ultrasound controversies as well as to outline the dynamics of the international network of experts that generates intravascular ultrasound innovations and uses intravascular ultrasound technologies. While the technology is praised for its capacity to measure coronary atherosclerotic plaque morphology and is steadily used in clinical research, the lack of demonstrated benefits of intravascular ultrasound guided coronary interventions emerges as the strongest factor that prevents its expansion. Furthermore, most of the controversies identified were external to intravascular ultrasound technology itself, meaning that decision making at the industrial, financial and regulatory levels are likely to determine the future of intravascular ultrasound. In light of opinions from the responding experts', a wider adoption of intravascular ultrasound as a stand-alone imaging modality seems rather uncertain, but the appeal for this technology may be renewed by improving image quality and through combination with

  7. Techniques for Intravascular Foreign Body Retrieval

    International Nuclear Information System (INIS)

    Woodhouse, Joe B.; Uberoi, Raman

    2013-01-01

    As endovascular therapies increase in frequency, the incidence of lost or embolized foreign bodies is increasing. The presence of an intravascular foreign body (IFB) is well recognized to have the potential to cause serious complications. IFB can embolize and impact critical sites such as the heart, with subsequent significant morbidity or mortality. Intravascular foreign bodies most commonly result from embolized central line fragments, but they can originate from many sources, both iatrogenic and noniatrogenic. The percutaneous approach in removing an IFB is widely perceived as the best way to retrieve endovascular foreign bodies. This minimally invasive approach has a high success rate with a low associated morbidity, and it avoids the complications related to open surgical approaches. We examined the characteristics, causes, and incidence of endovascular embolizations and reviewed the various described techniques that have been used to facilitate subsequent explantation of such materials

  8. Intravascular photoacoustic imaging of human coronary atherosclerosis

    Science.gov (United States)

    Jansen, Krista; van der Steen, Antonius F. W.; Springeling, Geert; van Beusekom, Heleen M. M.; Oosterhuis, J. Wolter; van Soest, Gijs

    2011-03-01

    We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. We specifically imaged lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction. An integrated intravascular photoacoustics (IVPA) and ultrasound (IVUS) catheter with an outer diameter of 1.25 mm was developed. The catheter comprises an angle-polished optical fiber adjacent to a 30 MHz single-element transducer. The ultrasonic transducer was optically isolated to eliminate artifacts in the PA image. We performed measurements on a cylindrical vessel phantom and isolated point targets to demonstrate its imaging performance. Axial and lateral point spread function widths were 110 μm and 550 μm, respectively, for PA and 89 μm and 420 μm for US. We imaged two fresh human coronary arteries, showing different stages of disease, ex vivo. Specific photoacoustic imaging of lipid content, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230 nm.

  9. Fluorescent Method for Observing Intravascular Bonghan Duct

    OpenAIRE

    Byung-Cheon Lee; Ku Youn Baik; Hyeon-Min Johng; Baekkyoung Sung; Kyung Soon Soh; Dae-In Kang; Kwang-Sup Soh

    2005-01-01

    Observation of intra-vascular threadlike structures in the blood vessels of rats is reported with the images by differential interference contrast microscope, and fluorescence inverted microscope of the acridine-orange stained samples. The confocal microscope image and the hematoxylin-eosin staining revealed the distinctive pattern of nuclei distribution that clearly discerned the threadlike structure from fibrin, capillary, small venule, arteriole, or lymph vessel. Physiological function of ...

  10. Heterogeneous Intravascular Ultrasound Findings of Stent Thrombosis

    OpenAIRE

    Morofuji, Toru; Inaba, Shinji; Aisu, Hiroe; Takahashi, Kayo; Saito, Makoto; Higashi, Haruhiko; Yoshii, Toyofumi; Sumimoto, Takumi

    2017-01-01

    Objective The underlying mechanisms of stent thrombosis are not completely understood. Methods We experienced 12 definite stent thrombosis cases (1 early, 1 late, and 10 very late) at our hospital from July 2011 to April 2016 and evaluated the possible causes of stent thrombosis by intravascular ultrasound (IVUS). Results Five different potential morphological causes of stent thrombosis (neoatherosclerosis, stent malapposition, stent fracture, edge dissection, and stent underexpansion) were d...

  11. Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration.

    Science.gov (United States)

    Ye, Baixin; Xiong, Xiaoxing; Deng, Xu; Gu, Lijuan; Wang, Qiongyu; Zeng, Zhi; Gao, Xiang; Gao, Qingping; Wang, Yueying

    2017-12-01

    Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases. Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases. In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration. In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway. Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.

  12. Protectin DX, a double lipoxygenase product of DHA, inhibits both ROS production in human neutrophils and cyclooxygenase activities

    Science.gov (United States)

    Liu, Miao; Boussetta, Tarek; Makni-Maalej, Karama; Fay, Michèle; Driss, Fathi; El-Benna, Jamel; Lagarde, Michel; Guichardant, Michel

    2014-01-01

    Neutrophils play a major role in inflammation by releasing large amounts of reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and myeloperoxidase (MPO). This ROS overproduction is mediated by phosphorylation of the NOX subunits with an uncontrolled manner. Therefore, targeting neutrophil subunits would represent a promising strategy to moderate NOX activity, lower ROS, and other inflammatory agents, such as cytokines and leukotrienes, produced by neutrophils. For this purpose, we investigated the effects of protectin DX (PDX) - a docosahexaenoic acid (DHA) di-hydroxylated product which inhibits blood platelet aggregation - on neutrophil activation in vitro. We found that PDX decreases ROS production, inhibits NOX activation and MPO release from neutrophils. We also confirm, that PDX is an anti-aggregatory and anti-inflammatory agent by inhibiting both cyclooxygenase-1 and -2 (COX-1 and COX-2, E.C. 1.14.99.1) as well as COX-2 in lipopolysaccharides (LPS)-treated human neutrophils. However, PDX has no effect on the 5-lipoxygenase pathway that produces the chemotactic agent leukotriene B4 (LTB4). Taken together, our results suggest that PDX could be a protective agent against neutrophil invasion in chronic inflammatory diseases. PMID:24254970

  13. Effect of the dimetilsulfoxido in the response chemiluminescent and the consumption of oxygen of neutrophils activated human

    International Nuclear Information System (INIS)

    Garcia, J.

    2001-01-01

    Dimethylsulfoxide (DMSO), a hydroxyl radical scavenger, exerted a dose dependent inhibition on the luminol and lucigenin-enhanced chemiluminescent responses of human neutrophils activated with soluble and particulate stimulants. DMSO inhibition of the luminol chemiluminescense induced by calcium ionophore A23187 was probably due to OH scavenging, whereas inhibition of the lucigenin chemiluminescence suggested DMSO negatively affects the NADPH-dependent membrane oxidase of neutrophils. In agreement with this, DMSO moderately inhibited O2 consumption in PMN suspensions stimulated with chemotactic peptide and opsonized zymosan-induced luminol chemiluminescense was observed only when added before or in conjunction with stimulants, whereas A23187-induced chemiluminescense was inhibited by DMSO regardless of time of addition. Washing of DMSO-treated PMN resulted in increased luminol enhanced chemiluminescense in response to chemotactic peptide and opsonized zymosan. This is consistent with the idea that DMSO may be interfering with activation of the membrane subunits of the oxidase by translocation and docking of the cytoplasmic, regulatory subunits. These data imply that DMSO inhibits neutrophil chemiluminescense both by OH scavenging and interfering with oxidase activation. Key words:Dimethylsulfoxide, chemiluminescent, luminol, lucigenin,neutrophils [es

  14. Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration.

    Science.gov (United States)

    Pazos, Michael A; Pirzai, Waheed; Yonker, Lael M; Morisseau, Christophe; Gronert, Karsten; Hurley, Bryan P

    2015-02-01

    Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4). We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. The effect of interleukin-8 and granulocyte macrophage colony stimulating factor on the response of neutrophils to formyl methionyl leucyl phenylalanine.

    Science.gov (United States)

    Mikami, M; Llewellyn-Jones, C G; Stockley, R A

    1998-08-14

    Neutrophils isolated from patients with chronic bronchitis and emphysema have been shown to have enhanced responses to formyl peptides when assessed in vitro compared to age, sex matched controls. It is currently unclear whether the observed differences are due to a 'priming' effect by a second agent in vivo, or whether this is a primary difference in the neutrophils. We have studied the effects of interleukin-8, which is thought to be one of the major pro-inflammatory cytokines in chronic lung disease and granulocyte macrophage colony stimulating factor (GMCSF), in order to assess their effects on neutrophil chemotaxis and connective tissue degradation. In addition, we have assessed the effect of preincubation of these agents with neutrophils for 30 min followed by stimulation with F-Met-Leu-Phe (FMLP) to investigate any possible 'priming' effect that may be relevant to our clinical data. We report suppression of neutrophil chemotaxis to FMLP following incubation of the neutrophils with both IL-8 and GMCSF. However, we have observed an additive effect of IL-8 and FMLP for neutrophil degranulation leading to fibronectin degradation. The results suggest that IL-8 does not 'prime' neutrophils for subsequent FMLP stimulation as observed in vivo. Although the results for GMCSF were similar for the chemotactic response, the agent also had a synergistic effect on connective tissue degradation. However, it is concluded that neither agent could explain the enhanced neutrophil responses seen in our patients.

  16. In vivo study of indomethacin in bronchiectasis: effect on neutrophil function and lung secretion.

    Science.gov (United States)

    Llewellyn-Jones, C G; Johnson, M M; Mitchell, J L; Pye, A; Okafor, V C; Hill, S L; Stockley, R A

    1995-09-01

    Bronchiectasis is associated with sputum containing high levels of the proteolytic enzyme elastase, which is thought to be involved in the pathogenesis of the disease. Agents which inhibit neutrophil function and interfere with neutrophil elastase release may have a beneficial effect on the development and progression of such diseases. We have studied the effects of the nonsteroidal anti-inflammatory agent indomethacin on neutrophil function in nine patients with clinically stable bronchiectasis. All patients remained clinically stable during the study. We observed a significant reduction in peripheral neutrophil chemotaxis to 10 nmol.L-1 N-formyl-methionyl-leucyl-phenylalanine (FMLP) from a mean of 19.86 (SEM 1.35) to 8.46 (0.68) cells.field-1 after 4 weeks of therapy. There was also a significant reduction in fibronectin degradation both by resting and FMLP-stimulated neutrophils, from a mean of 1.90 (0.19) micrograms x 3 x 10(5) cells at the start of therapy to 0.87 (0.08) micrograms after 4 weeks, and from 3.17 (0.35) micrograms to 1.48 (0.05) micrograms, respectively. There was no effect on spontaneous or stimulated superoxide anion generation by neutrophils. Despite the marked changes in peripheral neutrophil function, no adverse effect was observed on viable bacterial load in the bronchial secretions. In addition, there was no difference in sputum albumin, elastase or myeloperoxidase levels, and only minor changes in the chemotactic activity of the sputum. These results suggest that nonsteroidal anti-inflammatory agents have a major effect on peripheral neutrophil function but do not appear to have an adverse effect on bacterial colonization of the airways.

  17. Sperm from sneaker male squids exhibit chemotactic swarming to CO₂.

    Science.gov (United States)

    Hirohashi, Noritaka; Alvarez, Luis; Shiba, Kogiku; Fujiwara, Eiji; Iwata, Yoko; Mohri, Tatsuma; Inaba, Kazuo; Chiba, Kazuyoshi; Ochi, Hiroe; Supuran, Claudiu T; Kotzur, Nico; Kakiuchi, Yasutaka; Kaupp, U Benjamin; Baba, Shoji A

    2013-05-06

    Behavioral traits of sperm are adapted to the reproductive strategy that each species employs. In polyandrous species, spermatozoa often form motile clusters, which might be advantageous for competing with sperm from other males. Despite this presumed advantage for reproductive success, little is known about how sperm form such functional assemblies. Previously, we reported that males of the coastal squid Loligo bleekeri produce two morphologically different euspermatozoa that are linked to distinctly different mating behaviors. Consort and sneaker males use two distinct insemination sites, one inside and one outside the female's body, respectively. Here, we show that sperm release a self-attracting molecule that causes only sneaker sperm to swarm. We identified CO2 as the sperm chemoattractant and membrane-bound flagellar carbonic anhydrase as its sensor. Downstream signaling results from the generation of extracellular H(+), intracellular acidosis, and recovery from acidosis. These signaling events elicit Ca(2+)-dependent turning behavior, resulting in chemotactic swarming. These results illuminate the bifurcating evolution of sperm underlying the distinct fertilization strategies of this species. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Monocyte chemotactic protein-3: possible involvement in apical periodontitis chemotaxis.

    Science.gov (United States)

    Dezerega, A; Osorio, C; Mardones, J; Mundi, V; Dutzan, N; Franco, M; Gamonal, J; Oyarzún, A; Overall, C M; Hernández, M

    2010-10-01

    To study the expression of monocyte chemotactic protein-3 (MCP-3, also known as chemokine CCL-7) in tissue from apical lesions (AL) and to associate MCP-3 expression with symptomatic or asymptomatic apical periodontitis. To determine the expression of MCP-3 in AL, biopsies obtained during tooth extraction procedures were fixed, subjected to routine processing and diagnosed as apical granuloma (AG) (n = 7) or radicular cyst (RC) (n = 5). As controls, apical periodontal ligament (PDL) specimens from healthy premolars extracted for orthodontics reasons were included (n = 7). All specimens were immunostained for MCP-3 and examined under a light microscope. In addition, homogenates from AL (n = 14) and healthy PDL samples (n = 7) were studied through immunowestern blot. Finally, periapical exudates samples were collected from root canals of teeth having diagnosis of symptomatic (n = 14) and asymptomatic apical periodontitis (n = 14) during routine endodontic treatments and analysed by immunowestern blot and densitometry.   MCP-3 was detected in AG and RC and localized mainly to inflammatory leucocytes, whereas no expression was observed in healthy PDLs. MCP-3 was also detected in periapical exudate, and its levels were significantly higher in symptomatic than in asymptomatic apical periodontitis. MCP-3 was expressed in AL and its levels associated with clinical symptoms. MCP-3 might play a role in disease pathogenesis, possibly by stimulating mononuclear chemotaxis. © 2010 International Endodontic Journal.

  19. Achyrocline satureioides (Lam. D.C. Hydroalcoholic Extract Inhibits Neutrophil Functions Related to Innate Host Defense

    Directory of Open Access Journals (Sweden)

    Eric Diego Barioni

    2013-01-01

    Full Text Available Achyrocline satureioides (Lam. D.C. is a herb native to South America, and its inflorescences are popularly employed to treat inflammatory diseases. Here, the effects of the in vivo actions of the hydroalcoholic extract obtained from inflorescences of A. satureioides on neutrophil trafficking into inflamed tissue were investigated. Male Wistar rats were orally treated with A. satureioides extract, and inflammation was induced one hour later by lipopolysaccharide injection into the subcutaneous tissue. The number of leukocytes and the amount of chemotactic mediators were quantified in the inflammatory exudate, and adhesion molecule and toll-like receptor 4 (TLR-4 expressions and phorbol-myristate-acetate- (PMA- stimulated oxidative burst were quantified in circulating neutrophils. Leukocyte-endothelial interactions were quantified in the mesentery tissue. Enzymes and tissue morphology of the liver and kidney were evaluated. Treatment with A. satureioides extract reduced neutrophil influx and secretion of leukotriene B4 and CINC-1 in the exudates, the number of rolling and adhered leukocytes in the mesentery postcapillary venules, neutrophil L-selectin, β2-integrin and TLR-4 expression, and oxidative burst, but did not cause an alteration in the morphology and activities of liver and kidney. Together, the data show that A. satureioides extract inhibits neutrophil functions related to the innate response and does not cause systemic toxicity.

  20. Activation and regulation of arachidonic acid release in rabbit peritoneal neutrophils

    International Nuclear Information System (INIS)

    Tao, W.

    1988-01-01

    Arachidonic acid release in rabbit neutrophils can be enhanced by the addition of chemotactic fMet-Leu-Phe, platelet-activating factor, PAF, or the calcium ionophore A23187. Over 80% of the release [ 3 H]arachidonic acid comes from phosphatidylcholine and phosphatidylinositol. The release is dose-dependent and increases with increasing concentration of the stimulus. The A23187-induced release increases with increasing time of the stimulation. [ 3 H]arachidonic acid release, but not the rise in the concentration of intracellular calcium, is inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The [ 3 H]arachidonic acid released by A23187 is potentiated while that release by fMET-Leu-Phe or PAF is inhibited in phorbol 12-myristate 13-acetate, PMA, treated rabbit neutrophils. The protein kinase C inhibitor 1-(5-isoquinoline sulfonyl)-2-methylpiperazine, H-7, has no effect on the potentiation by PMA of the A23187-induced release, it prevents the inhibition by PMA of the release produced by PAF or fMet-Leu-Phe. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. The diacylglycerol kinase inhibitor R59022 increases the level of diacylglycerol in neutrophils stimulated with fMet-Leu-Phe. Furthermore, R59022 potentiates [ 3 H] arachidonic acid release produced by fMet-Leu-Phe. This potentiation is not inhibited by H-7, in fact, it is increased in H-7-treated neutrophils

  1. A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.

    Science.gov (United States)

    Shak, S; Perez, H D; Goldstein, I M

    1983-12-25

    We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.

  2. Hemi-Intravascular Stenting for Supermicrosurgical Anastomosis

    Science.gov (United States)

    Yamashita, Shuji; Narushima, Mitsunaga; Koshima, Isao; Miyamoto, Shimpei

    2017-01-01

    Background: Although supermicrosurgical anastomosis is a widely known reconstructive microsurgical technique, it is difficult to perform. To expand the clinical use of supermicrosurgery, we used hemi-intravascular stenting (hemi-IVaS), which is performed by inserting an intravascular stent into one side of the vessel. We conducted lymphaticovenular anastomosis, free perforator flap transfer, and fingertip replantation with supermicrosurgical anastomosis using hemi-IVaS technique and examined its usefulness. Methods: Between January 2013 and February 2015, 11 anastomoses in 11 cases of lymphaticovenular anastomosis for lymphedema patients, 14 anastomoses in 7 cases of free perforator flap transfer with supermicrosurgical perforator-to-perforator anastomosis, and 9 anastomoses in 5 cases of fingertip replantation were performed using hemi-IVaS. Time required for anastomosis and complications were examined. Flap survival rate was also examined in free perforator flap transfer cases and fingertip replantation cases. Results: In all cases, anastomoses were performed without complications such as inadvertent catching of the back wall of the vessel during the procedure or the need for reanastomoses. The average time required to complete the anastomosis was 16.4 ± 3.20 minutes using the hemi IVaS technique. All flaps survived in the supermicrosurgical perforator-to-perforator anastomosis as well as fingertip replantation cases. Conclusions: Hemi-IVaS could be a useful alternative to conventional intravascular stenting techniques and is also effective for supermicrosurgical perforator-to-perforator anastomosis. Further studies are needed to improve the success rate and to explore its other possible utilizations in supermicrosurgery. PMID:29263952

  3. Intravascular imaging with a storage phosphor detector

    Energy Technology Data Exchange (ETDEWEB)

    Shikhaliev, Polad M; Petrek, Peter; Matthews, Kenneth L II; Fritz, Shannon G [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA (United States); Bujenovic, L Steven [PET Imaging Center, Our Lady of the Lake Medical Center, Baton Rouge, LA (United States); Xu Tong, E-mail: pshikhal@lsu.ed [Department of Physics, Carleton University, Ottawa (Canada)

    2010-05-21

    The aim of this study is to develop and test an intravascular positron imaging system based on a storage phosphor detector for imaging and detecting vulnerable plaques of human coronary arteries. The radiotracer F18-FDG accumulates in vulnerable plaques with inflammation of the overlying cap. The vulnerable plaques can, therefore, be imaged by recording positrons emitted from F18-FDG with a detector inserted into the artery. A prototype intravascular detector was constructed based on storage phosphor. The detector uses a flexible storage phosphor tube with 55 mm length, 2 mm diameter and 0.28 mm wall thickness. The intravascular detector is guided into the vessel using x-ray fluoroscopy and the accumulated x-ray signal must be erased prior to positron imaging. For this purpose, a light diffuser, 0.9 mm in diameter and 55 mm in length, was inserted into the detector tube. The light diffuser was connected to a laser source through a 2 m long optical fiber. The diffuser redirected the 0.38 W laser light to the inner surface of the phosphor detector to erase it. A heart phantom with 300 cm{sup 3} volume and three coronary arteries with 3.2 mm diameter and with several plaques was constructed. FDG solution with 0.5 {mu}Ci cm{sup -3} activity concentration was filled in the heart and coronary arteries. The detector was inserted in a coronary artery and the signal from the plaques and surrounding background activity was recorded for 2 min. Then the phosphor detector was extracted and read out using a storage phosphor reader. The light diffuser erased the signal resulting from fluoroscopic exposure to level below that encountered during positron imaging. Vulnerable plaques with area activities higher than 1.2 nCi mm{sup -2} were visualized by the detector. This activity is a factor of 10-20 lower than that expected in human vulnerable plaques. The detector was able to image the internal surface of the coronary vessels with 50 mm length and 360{sup 0} circumference. Spatial

  4. Elucidation of Distinct Roles of Guinea Pig CXCR1 and CXCR2 in Neutrophil Migration toward IL-8 and GROα by Specific Antibodies.

    Science.gov (United States)

    Tanaka, Kento; Yoshitomi, Tomomi; Hirahara, Kazuki

    2017-01-01

    Chemokine receptors CXCR1 and CXCR2 are conserved between guinea pigs and humans, but the distinct role of each receptor in chemotactic responses of neutrophils against chemokine ligands has not been elucidated due in part to the lack of specific inhibitors against these receptors in guinea pigs. In this study, we investigated the roles of guinea pig CXCR1 and CXCR2 on neutrophils in chemotactic responses to guinea pig interleukin (IL)-8 and growth-regulated oncogene (GRO)α by using specific inhibitory antibodies against these receptors. Neutrophil migration induced by IL-8 was partially inhibited by either anti-CXCR1 antibody or anti-CXCR2 antibody. In addition, the migration was inhibited completely when both anti-CXCR1 and anti-CXCR2 antibodies were combined. On the other hand, neutrophil migration induced by GROα was not inhibited by anti-CXCR1 antibody while inhibited profoundly by anti-CXCR2 antibody. These results indicated that CXCR1 and CXCR2 mediated migration induced by the IL-8 synergistically and only CXCR2 mediated migration induced by GROα in guinea pig neutrophils. Our findings on ligand selectivity of CXCR1 and CXCR2 in guinea pigs are consistent with those in humans.

  5. Mapping Intravascular Ultrasound Controversies in Interventional Cardiology Practice

    NARCIS (Netherlands)

    Maresca, D.; Adams, S.; Maresca, B.; Van der Steen, A.F.W.

    2014-01-01

    Intravascular ultrasound is a catheter-based imaging modality that was developed to investigate the condition of coronary arteries and assess the vulnerability of coronary atherosclerotic plaques in particular. Since its introduction in the clinic 20 years ago, use of intravascular ultrasound

  6. Blockade by fenspiride of endotoxin-induced neutrophil migration in the rat.

    Science.gov (United States)

    Cunha, F Q; Boukili, M A; da Motta, J I; Vargaftig, B B; Ferreira, S H

    1993-07-06

    Fenspiride, an antiinflammatory drug with low anti-cyclooxygenase activity, administered orally at 60-200 mg/kg inhibited neutrophil migration into peritoneal and air pouches cavities as well as exudation into peritoneal cavities induced by endotoxin but not induced by carrageenin. Up to 100 microM, fenspiride failed to inhibit the in vitro release of a neutrophil chemotactic activity by endotoxin-stimulated macrophages and the in vivo migration into the peritoneal cavities induced by the supernatant of those macrophages. The release of tumour necrosis factor by stimulated macrophages was inhibited by fenspiride in a dose-dependent manner. These results suggest that the antiinflammatory effects of fenspiride are associated with the inhibition of the tumour necrosis factor release by resident macrophages.

  7. Role of informed consent for intravascular contrast media

    International Nuclear Information System (INIS)

    Hopper, K.D.; Tyler, H.N. Jr.

    1988-01-01

    To evaluate the usefulness of different degrees of informed consent for intravascular contrast media, the authors divided 100 patients into four groups: (1) informed consent with no information on intravascular contrast media, (2) simple written informed consent that detailed common risks, (3) detailed written informed consent that detailed all known risks, and (4) MD informed consent, during which a radiologist discussed all known risks of intravascular contrast media. Physician counseling time for group 4 averaged 11.4 minutes. On a postprocedure test about the common complications and risk factors of intravascular contrast media, the average scores were: group 1, 38.4%; group 2, 68.2%; group 3, 63.2%; and group 4, 69.8%. There was no statistical difference between groups 2-4 on the postprocedure test. If informed consent is to be used prior to intravascular contrast media administration, a simple written consent detailing the common risks and risk factors appears to be the best method

  8. Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira

    Science.gov (United States)

    Scharrig, Emilia; Carestia, Agostina; Ferrer, María F.; Cédola, Maia; Pretre, Gabriela; Drut, Ricardo; Picardeau, Mathieu; Schattner, Mirta; Gómez, Ricardo M.

    2015-01-01

    NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted-mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden. PMID:26161745

  9. Neutrophil extracellular traps - the dark side of neutrophils

    DEFF Research Database (Denmark)

    Sørensen, Ole E.; Borregaard, Niels

    2016-01-01

    Neutrophil extracellular traps (NETs) were discovered as extracellular strands of decondensed DNA in complex with histones and granule proteins, which were expelled from dying neutrophils to ensnare and kill microbes. NETs are formed during infection in vivo by mechanisms different from those ori...

  10. Reconstitution of a physical complex between the N-formyl chemotactic peptide receptor and G protein. Inhibition by pertussis toxin-catalyzed ADP ribosylation.

    Science.gov (United States)

    Bommakanti, R K; Bokoch, G M; Tolley, J O; Schreiber, R E; Siemsen, D W; Klotz, K N; Jesaitis, A J

    1992-04-15

    Photoaffinity-labeled N-formyl chemotactic peptide receptors from human neutrophils solubilized in octyl glucoside exhibit two forms upon sucrose density gradient sedimentation, with apparent sedimentation coefficients of approximately 4 and 7 S. The 7 S form can be converted to the 4 S form by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) with an EC50 of approximately 20 nM, suggesting that the 7 S form may represent a physical complex of the receptor with endogenous G protein (Jesaitis, A. J., Tolley, J. O., Bokoch, G. M., and Allen, R. A. (1989) J. Cell Biol. 109, 2783-2790). To probe the nature of the 7 S form, we reconstituted the 7 S form from the 4 S form by adding purified G protein. The 4 S form, obtained by solubilizing GTP gamma S-treated neutrophil plasma membranes, was incubated with purified (greater than 95%) Gi protein from bovine brain (containing both Gi alpha 1 and Gi alpha 2) or with neutrophil G protein (Gn), and formation of the 7 S complex was analyzed on sucrose density gradients. The EC50 of 7 S complex formation induced by the two G proteins was 70 +/- 25 and 170 +/- 40 nM for Gn and Gi, respectively. No complexation was measurable when bovine transducin (Gt) was used up to 30 times the EC50 for Gn. The EC50 for Gi was the same for receptors, obtained from formyl peptide-stimulated or unstimulated cells. The addition of 10 microM GTP gamma S to the reconstituted 7 S complex caused a complete revision of the receptor to the 4 S form, and anti-Gi peptide antisera immunosedimented the 7 S form. ADP-ribosylation of Gi prevented formation of the 7 S form even at 20 times the concentration of unribosylated Gi normally used to attain 50% conversion to the 7 S form. These observations suggest that the 7 S species is a physical complex containing N-formyl chemotactic peptide receptor and G protein.

  11. Association of Canine Osteosarcoma and Monocyte Phenotype and Chemotactic Function.

    Science.gov (United States)

    Tuohy, J L; Lascelles, B D X; Griffith, E H; Fogle, J E

    2016-07-01

    Monocytes/macrophages are likely key cells in immune modulation in dogs with osteosarcoma (OSA). Increased peripheral monocyte counts are negatively correlated with shorter disease-free intervals in dogs with OSA. Understanding the monocyte/macrophage's modulatory role in dogs with OSA can direct further studies in immunotherapy development for OSA. That OSA evades the immune response by down-regulating monocyte chemokine receptor expression and migratory function, and suppresses host immune responses. Eighteen dogs with OSA that have not received definitive treatment and 14 healthy age-matched controls Clinical study-expression of peripheral blood monocyte cell surface receptors, monocyte mRNA expression and cytokine secretion, monocyte chemotaxis, and survival were compared between clinical dogs with OSA and healthy control dogs. Cell surface expression of multiple chemokine receptors is significantly down-regulated in peripheral blood monocytes of dogs with OSA. The percentage expression of CCR2 (median 58%, range 2-94%) and CXCR2 expression (median 54%, range 2-92%) was higher in control dogs compared to dogs with OSA (CCR2 median 29%, range 3-45%, P = 0.0006; CXCR2 median 23%, range 0.2-52%, P = 0.0007). Prostaglandin E2 (PGE2 ) (OSA, median 347.36 pg/mL, range 103.4-1268.5; control, 136.23 pg/mL, range 69.93-542.6, P = .04) and tumor necrosis factor-alpha (TNF-α) (P = .02) levels are increased in OSA monocyte culture supernatants compared to controls. Peripheral blood monocytes of dogs with OSA exhibit decreased chemotactic function when compared to control dogs (OSA, median 1.2 directed to random migration, range 0.8-1.25; control, 1.6, range of 0.9-1.8, P = .018). Dogs with OSA have decreased monocyte chemokine receptor expression and monocyte chemotaxis, potential mechanisms by which OSA might evade the immune response. Reversal of monocyte dysfunction using immunotherapy could improve survival in dogs with OSA. Copyright © 2016 The Authors. Journal of

  12. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo

    Science.gov (United States)

    von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A.; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T.; Wagner, Denisa D.; Mackman, Nigel; Engelmann, Bernd

    2012-01-01

    Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features. PMID:22451716

  13. Immunosenescence of Polymorphonuclear Neutrophils

    Directory of Open Access Journals (Sweden)

    Inga Wessels

    2010-01-01

    Full Text Available All immune cells are affected by aging, contributing to the high susceptibility to infections and increased mortality observed in the elderly. The effect of aging on cells of the adaptive immune system is well documented. In contrast, knowledge concerning age-related defects of polymorphonuclear neutrophils (PMN is limited. During the past decade, it has become evident that in addition to their traditional role as phagocytes, neutrophils are able to secrete a wide array of immunomodulating molecules. Their importance is underlined by the finding that genetic defects that lead to neutropenia increase susceptibility to infections. Whereas there is consistence about the constant circulating number of PMN throughout aging, the abilities of tissue infiltration, phagocytosis, and oxidative burst of PMN from aged donors are discussed controversially. Furthermore, there are numerous discrepancies between in vivo and in vitro results, as well as between results for murine and human PMN. Most of the reported functional changes can be explained by defective signaling pathways, but further research is required to get a detailed insight into the underlying molecular mechanisms. This could form the basis for drug development in order to prevent or treat age-related diseases, and thus to unburden the public health systems.

  14. Ventricular metastasis resulting in disseminated intravascular coagulation

    Directory of Open Access Journals (Sweden)

    Davis Ian D

    2005-05-01

    Full Text Available Abstract Background Disseminated Intravascular Coagulation (DIC complicates up to 7% of malignancies, the commonest solid organ association being adenocarcinoma. Transitional Cell Carcinoma (TCC has rarely been associated with DIC. Case presentation A 74-year-old woman with TCC bladder and DIC was found to have a cardiac lesion suspicious for metastatic disease. The DIC improved with infusion of plasma and administration of Vitamin K, however the cardiac lesion was deemed inoperable and chemotherapy inappropriate; given the patients functional status. We postulate that direct activation of the coagulation cascade by the intraventricular metastasis probably triggered the coagulopathy in this patient. Conclusion Cardiac metastases should be considered in cancer patients with otherwise unexplained DIC. This may influence treatment choices.

  15. Death following intravascular administration of contrast media

    International Nuclear Information System (INIS)

    Shehadi, W.H.

    1985-01-01

    Adverse reactions to intravascularly administered contrast media preceding death and the autopsy findings in 44 patients are presented. There is a wide scatter of the age distribution of fatal reactions. The highest incidence is in the 50-70 year age group. Similar observations were obtained from the 405 deaths due to contrast media reported to the Food and Drug Administration of the United States. In the same age group the number of reactions is highest, likewise the autopsy findings. The predominant autopsy findings are pulmonary edema, congestion and hemorrhage; arteriosclerosis, both general and coronary. In the younger age group the autopsy findings are limited mostly to the respiratory tract. Fatal reactions to contrast media occur often without warning and most deaths occur within 15 min to 6 hours. Reactions to contrast media occur without relation to sex or age. (orig.)

  16. CYP4F18-Deficient Neutrophils Exhibit Increased Chemotaxis to Complement Component C5a

    Directory of Open Access Journals (Sweden)

    Rachel Vaivoda

    2015-01-01

    Full Text Available CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B4 (LTB4. CYP4F18 has an unusual expression in neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wild-type and Cyp4f18 knockout neutrophils using an in vitro assay. There was no significant difference in the chemotactic response to LTB4, but the response to complement component C5a increased 1.9–2.25-fold in knockout cells compared to wild-type (P < 0.01. This increase was still observed when neutrophils were treated with inhibitors of eicosanoid synthesis. There were no changes in expression of other CYP4 enzymes in knockout neutrophils that might compensate for loss of CYP4F18 or lead to differences in activity. A mouse model of dextran sodium sulfate colitis was used to investigate the consequences of increased C5a-dependent chemotaxis in vivo, but there was no significant difference in weight loss, disease activity, or colonic tissue myeloperoxidase between wild-type and Cyp4f18 knockout mice. This study demonstrates the limitations of inferring CYP4F function based on an ability to use LTB4 as a substrate, points to expanding roles for CYP4F enzymes in immune regulation, and underscores the in vivo challenges of CYP knockout studies.

  17. Targeting neutrophilic inflammation in severe neutrophilic asthma : can we target the disease-relevant neutrophil phenotype?

    NARCIS (Netherlands)

    Bruijnzeel, Piet L B; Uddin, Mohib; Koenderman, Leo

    2015-01-01

    In severe, neutrophilic asthma, neutrophils are thought to have an important role in both the maintenance of the disease and during exacerbations. These patients often display excessive, mucosal airway inflammation with unresolving neutrophilia. Because this variant of asthma is poorly controlled by

  18. Effects of Porphyromonas gingivalis LipopolysaccharideTolerized Monocytes on Inflammatory Responses in Neutrophils.

    Directory of Open Access Journals (Sweden)

    Xiang-Qing Zhu

    Full Text Available Periodontitis is a chronic inflammatory disease induced by bacteria. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, which is termed endotoxin tolerance. The role and mechanism of lipopolysaccharide (LPS-tolerized monocytes in inflammatory responses in neutrophils are currently unclear. Here, conditioned supernatants were collected from THP-1 cells treated with or without repeated 1 μg/ml Porphyromonas gingivalis (P.gingivalis LPS. The chemotactic response of freshly isolated neutrophils recruited by supernatants was determined by a transwell migration assay, which demonstrated a reduced migration of neutrophils stimulated with supernatants from tolerized THP-1 cells in comparison to non-tolerized THP-1 cells. In addition, there was a marked increase in reactive oxygen species (ROS generation and a significant decrease in Caspase 3 activities in neutrophils treated with supernatants from THP-1 cells that were treated repeatedly with P.gingivalis LPS in comparison to single treatment. A cytokine antibody array was then used to assess cytokine expression patterns in THP-1 cells. In tolerized THP-1 cells, 43 cytokine (43/170 expression levels were decreased, including chemokine ligand 23 (CCL23 and IFN-γ, while 11 cytokine (11/170 expression levels were increased, such as death receptor 6 (DR6. Furthermore, there was decreased production of IFN-γ and epithelial neutrophil activating peptide-78 (ENA-78 in THP-1 cells after stimulation with repeated P. gingivalis LPS in comparison to single challenge, which was confirmed by ELISA. Therefore, P.gingivalis LPS- tolerized THP-1 cells were able to depress neutrophil chemotaxis and apoptosis, and contribute to respiratory burst, which might be related to the changes in cytokine expression patterns in THP-1 cells.

  19. Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus aureus clearance.

    Science.gov (United States)

    Robertson, Charles M; Perrone, Erin E; McConnell, Kevin W; Dunne, W Michael; Boody, Barrett; Brahmbhatt, Tejal; Diacovo, M Julia; Van Rooijen, Nico; Hogue, Lisa A; Cannon, Carolyn L; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2008-12-01

    Staphylococcus aureus is the most common cause of healthcare-associated pneumonia. Despite the significant morbidity and mortality associated with the disease, animal models of S. aureus pneumonia are rare. We examined the pathogenicity of four different strains of S. aureus (both methicillin-sensitive and -resistant as well as Panton-Valentine leukocidin-positive and -negative) in four strains of immunocompetent inbred and outbred mice (FVB/N, C57Bl/6, BALB/c, ND4; n = 148). The immunological basis for the development of murine S. aureus pneumonia was then determined by selectively depleting neutrophils, lymphocytes, or pulmonary macrophages prior to the onset of infection. An additional cohort of animals was rendered immunosuppressed by induction of abdominal sepsis via cecal ligation and puncture 2, 4, or 7 d prior to the onset of pneumonia. Nearly all immunocompetent mice survived, regardless of which strain of S. aureus was used or which strain of mouse was infected. Among animals with immune depletion or prior immunosuppression, survival was decreased only following neutrophil depletion (26% versus 90% alive at 7 d, P < 0.0001). Compared to immunocompetent animals, neutrophil-depleted mice with S. aureus pneumonia had delayed pulmonary bacterial clearance at 16 and 40 h but had no difference in levels of bacteremia. Neutrophil-depleted mice also had elevated levels of pulmonary monocyte chemotactic protein-1 (822 pg/mL versus 150 pg/mL, P < 0.05). In contrast, pulmonary histological appearance was similar in both groups as was dry/wet lung weight. These results suggest that neutrophils play a critical role in the host response to S. aureus pneumonia, and the survival differences observed in neutrophil-depleted mice are associated with alterations in bacterial clearance and pulmonary cytokine response.

  20. Colloidal silver nanoparticles/rhamnolipid (SNPRL) composite as novel chemotactic antibacterial agent.

    Science.gov (United States)

    Bharali, P; Saikia, J P; Paul, S; Konwar, B K

    2013-10-01

    The antibacterial activity of silver nanoparticles and rhamnolipid are well known individually. In the present research, antibacterial and chemotactic activity due to colloidal silver nanoparticles (SNP), rhamnolipid (RL) and silver nanoparticles/rhamnolipid composite (SNPRL) were evaluated using Staphylococcus aureus (MTCC3160), Escherichia coli (MTCC40), Pseudomonas aeruginosa (MTCC8163) and Bacillus subtilis (MTCC441) as test strains. Further, the SNPRL nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). The observation clearly indicates that SNPRL shows prominent antibacterial and chemotactic activity in comparison to all of its individual precursor components. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Guidelines for the diagnosis and management of disseminated intravascular coagulation

    NARCIS (Netherlands)

    Levi, M. [=Marcel M.; Toh, C. H.; Thachil, J.; Watson, H. G.

    2009-01-01

    The diagnosis of disseminated intravascular coagulation (DIC) should encompass both clinical and laboratory information. The International Society for Thrombosis and Haemostasis (ISTH) DIC scoring system provides objective measurement of DIC. Where DIC is present the scoring system correlates with

  2. Temporal cascade of inflammatory cytokines and cell-type populations in monocyte chemotactic protein-1 (MCP-1)-mediated aneurysm healing.

    Science.gov (United States)

    Hoh, Brian L; Fazal, Hanain Z; Hourani, Siham; Li, Mengchen; Lin, Li; Hosaka, Koji

    2018-03-01

    We have previously shown that monocyte chemotactic protein-1 (MCP-1) promotes aneurysm healing. To determine the temporal cascade and durability of aneurysm healing. Murine carotid aneurysms were treated with MCP-1-releasing or poly(lactic-co-glycolic) acid (PLGA)-only coils. Aneurysm healing was assessed by quantitative measurements of intraluminal tissue ingrowth on 5 μm sections by blinded observers. Aneurysm healing occurred in stages characteristic of normal wound healing. The 1st stage (day 3) was characterized by a spike in neutrophils and T cells. The 2nd stage (week 1) was characterized by an influx of macrophages and CD45+ cells significantly greater with MCP-1 than with PLGA (p<0.05). The third stage (week 2-3) was characterized by proliferation of smooth muscle cells and fibroblasts (greater with MCP-1 than with PLGA, p<0.05). The fourth stage (3-6 months) was characterized by leveling off of smooth muscle cells and fibroblasts. M1 macrophages were greater at week 1, whereas M2 macrophages were greater at weeks 2 and 3 with MCP-1 than with PLGA. Interleukin 6 was present early and increased through week 2 (p<0.05 compared with PLGA) then decreased and leveled off through 6 months. Tumour necrosis factor α was present early and remained constant through 6 months. MCP-1 and PLGA treatment had similar rates of tissue ingrowth at early time points, but MCP-1 had a significantly greater tissue ingrowth at week 3 (p<0.05), which persisted for 6 months. The sequential cascade is consistent with an inflammatory model of injury, repair, and remodeling. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Disseminated intravascular and intracardiac thrombosis after cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Deepak K Tempe

    2017-01-01

    Full Text Available Massive intracardiac and intravascular thrombosis is a rare complication following cardiopulmonary bypass (CPB. Most of the cases of the disseminated thrombosis have been reported in patients undergoing complex cardiac surgeries and those receiving antifibrinolytic agents during CPB. We report the occurrence of disseminated intravascular and intracardiac thrombosis after CPB in a patient undergoing mitral valve replacement in which no antifibrinolytic agent was used. The possible pathophysiology and management of the patient is discussed.

  4. Intravascular Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Maria S. Khan MD, FACP

    2014-03-01

    Full Text Available Case Presentation . A 69-year-old Hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7, prothrombin time (PT 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (PTT 55.6 seconds, fibrin split 10 µg/L, and lactate dehydrogenase (LDH 1231 IU/L. Except for a positive DNA test for Epstein–Barr virus (EBV infection, extensive diagnostic workup for infections, malignancy, or a neurological cause was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. The patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B-cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30, and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion . Intravascular large cell B-cell lymphoma (IVLBCL is rare form of diffuse large B-cell lymphoma and tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant, and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits, and skin findings. Bone marrow, spleen, and liver are involved in a minority of patients. Nearly all patients have elevated LDH

  5. The association of elevated reactive oxygen species levels from neutrophils with low-grade inflammation in the elderly

    Directory of Open Access Journals (Sweden)

    Suzuki Katsuhiko

    2008-10-01

    Full Text Available Abstract Background Reactive oxygen species (ROS, including free radicals, oxygen ions, and peroxides, are implicated in cell damage. The objective of this study was to investigate whether the spontaneous production of ROS from neutrophils changes with age and is associated with the conventional inflammatory markers. Results Thirty-seven elderly subjects (median age, 87, range 70–95 years and 22 young subjects (median age, 26, range 21–37 years participated in this study. Circulating levels of C-reactive protein, serum amyloid A, tumor necrosis factor-α, interleukin (IL-1, IL-6, IL-8, monocyte chemotactic protein-1, and heat shock protein (HSP70 were measured with enzyme-linked immunosorbent assays. The N-formyl-methionyl-leucyl-phenylalanine and lipopolysaccharide-stimulated ROS of neutrophils were quantified by flow cytometry. Both spontaneous ROS production and circulating levels of inflammatory markers were higher in the elderly group than in the younger group. In addition, spontaneous ROS production by neutrophils was negatively associated with HSP70 in plasma. We could not find the association between spontaneous ROS production by neutrophils and the other inflammatory markers including cytokines. Conclusion The results suggest that spontaneous ROS production from neutrophils may increase with age and represent the different aspect of age-associated immune dysregulation.

  6. Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

    LENUS (Irish Health Repository)

    Hong, Ying

    2012-01-01

    The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics.

  7. Neutrophil programming dynamics and its disease relevance.

    Science.gov (United States)

    Ran, Taojing; Geng, Shuo; Li, Liwu

    2017-11-01

    Neutrophils are traditionally considered as first responders to infection and provide antimicrobial host defense. However, recent advances indicate that neutrophils are also critically involved in the modulation of host immune environments by dynamically adopting distinct functional states. Functionally diverse neutrophil subsets are increasingly recognized as critical components mediating host pathophysiology. Despite its emerging significance, molecular mechanisms as well as functional relevance of dynamically programmed neutrophils remain to be better defined. The increasing complexity of neutrophil functions may require integrative studies that address programming dynamics of neutrophils and their pathophysiological relevance. This review aims to provide an update on the emerging topics of neutrophil programming dynamics as well as their functional relevance in diseases.

  8. Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment.

    Directory of Open Access Journals (Sweden)

    Samantha P Tull

    2009-08-01

    Full Text Available Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-alpha, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA, arachidonic acid, into the eicosanoid prostaglandin-D(2 (PGD(2 by cyclooxygenase (COX enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA, was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD(3. This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD(2 receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD(2 signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not

  9. Dihydroxyoctadecamonoenoate esters inhibit the neutrophil ...

    Indian Academy of Sciences (India)

    PRAKASH

    that observed with arachidonic acid treatment (Li et al 1996). ..... An alternative possibility is that the methyl DiHOMEs .... nitric oxide-derived reactive species in vascular cells; Circ. ... necrosis factor 1-alpha-initiated neutrophil responses and.

  10. Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3.

    Czech Academy of Sciences Publication Activity Database

    Potměšil, Petr; Holý, Antonín; Kmoníčková, Eva; Křížková, Jana; Zídek, Zdeněk

    2007-01-01

    Roč. 14, č. 1 (2007), s. 59-66 ISSN 1021-7770 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40550506 Keywords : Acyclic nucleoside phosponate * HIV * Monocyte chemotactic protein Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.024, year: 2007

  11. Expression and divalent cation binding properties of the novel chemotactic inflammatory protein psoriasin

    DEFF Research Database (Denmark)

    Vorum, H; Madsen, Peder; Rasmussen, H H

    1996-01-01

    Psoriasin is a novel chemotactic inflammatory protein that possesses weak similarity to the S100 family members of Ca(2+)-binding proteins, and that is highly up-regulated in hyperproliferative psoriatic keratinocytes. Here we have used the psoriasin cDNA to express recombinant human (rh) psorias...

  12. A quality management program in intravascular brachytherapy

    International Nuclear Information System (INIS)

    Chakri, Abderrahim; Thomadsen, Bruce

    2002-01-01

    While simple, intravascular brachytherapy (IVB) presents a considerable potential for harm to the patient. The medical physicist maintains the responsibility to minimize the likelihood of operational problems or dosimetric errors. The principals for safe operation remain the same as with any radiotherapy treatment: to deliver the correct dose, to the correct location, safety. To develop an effective and comprehensive quality management (QM) program for IVB, a physicist should utilize proven risk assessment techniques rather than simply thinking of things to check, and follow guidances such as ISO9001:2000. The proposed QM program includes the following: Procedures designed to assure the safety of the patient: Identification of the patient; tests of the integrity and patency for the delivery catheter, operation of the source train, and patency of the catheter in the treatment position; a check for recovery preparations; and verification of source recovery. Procedures to assure positional accuracy of the treatment: Verification of the positioning the catheter in the artery and of the sources in the catheter. Procedures to assure dosimetry accuracy: Acceptance testing of the device, including verification of the source strength and uniformity, and of the treatment duration tables; verification of the treatment prescription and duration for each patient; and control measures that minimize the likelihood of errors removing the source at the correct time

  13. Disseminated intravascular coagulation in solid tumors

    International Nuclear Information System (INIS)

    Terzieff, V.; Alonso, I.; Vázquez, A.

    2004-01-01

    It is estimated that 20-25% of cases of disseminated intravascular coagulation (DIC) relate to an underlying neoplasia primarily hematologic. It is estimated that about 5% of patients with solid tumors have CID clinic, although the incidence of subclinical alterations is much higher. The CID is not limited to the activation of the coagulation cascade, which leads to bleeding micro thrombosis and consumption of coagulation factors. Solid tumors are frequently associated adenocarcinomas producers mucin (especially gastric), usually in the context of a disseminated disease. The mucin may act as a promoter of the cascade, but probably it is a multi-event. High levels of TNF to produced by the tumor mass and chemotherapy-induced cell lysis have Also linked. Although the bleeding is usually oriented diagnosis, the most frequent cause of death is thrombosis. There are no specific tests for diagnosis. Elevated levels of D-dimer and products oriented fibrinogen degradation diagnosis. No reduction fibrinogen and almost always, one thrombocytopenia consumption. Treatment is complex and there is no consensus on many points. To recover the lost factors for consumption, it is recommended to use fresh frozen plasma and / or washed red blood cells. the heparin anticoagulation low dose is indicated since the disease causal can not be controlled quickly, but should not be initiated if there thrombocytopenia 50.000.El under profuse bleeding can require the use of tranexamic acid or EACA. Acute DIC, the case of our patient, is rare and very serious

  14. Rotational multispectral fluorescence lifetime imaging and intravascular ultrasound: bimodal system for intravascular applications

    Science.gov (United States)

    Ma, Dinglong; Bec, Julien; Yankelevich, Diego R.; Gorpas, Dimitris; Fatakdawala, Hussain; Marcu, Laura

    2014-01-01

    Abstract. We report the development and validation of a hybrid intravascular diagnostic system combining multispectral fluorescence lifetime imaging (FLIm) and intravascular ultrasound (IVUS) for cardiovascular imaging applications. A prototype FLIm system based on fluorescence pulse sampling technique providing information on artery biochemical composition was integrated with a commercial IVUS system providing information on artery morphology. A customized 3-Fr bimodal catheter combining a rotational side-view fiberoptic and a 40-MHz IVUS transducer was constructed for sequential helical scanning (rotation and pullback) of tubular structures. Validation of this bimodal approach was conducted in pig heart coronary arteries. Spatial resolution, fluorescence detection efficiency, pulse broadening effect, and lifetime measurement variability of the FLIm system were systematically evaluated. Current results show that this system is capable of temporarily resolving the fluorescence emission simultaneously in multiple spectral channels in a single pullback sequence. Accurate measurements of fluorescence decay characteristics from arterial segments can be obtained rapidly (e.g., 20 mm in 5 s), and accurate co-registration of fluorescence and ultrasound features can be achieved. The current finding demonstrates the compatibility of FLIm instrumentation with in vivo clinical investigations and its potential to complement conventional IVUS during catheterization procedures. PMID:24898604

  15. Intravascular brachytherapy for peripheral vascular disease

    Directory of Open Access Journals (Sweden)

    Hagen, Anja

    2008-09-01

    Full Text Available Scientific background: Percutaneous transluminal angioplasties (PTA through balloon dilatation with or without stenting, i.e. vessel expansion through balloons with or without of implantation of small tubes, called stents, are used in the treatment of peripheral artery occlusive disease (PAOD. The intravascular vessel irradiation, called intravascular brachytherapy, promises a reduction in the rate of repeated stenosis (rate of restenosis after PTA. Research questions: The evaluation addresses questions on medical efficacy, cost-effectiveness as well as ethic, social and legal implications in the use of brachytherapy in PAOD patients. Methods: A systematic literature search was conducted in August 2007 in the most important medical electronic databases for publications beginning from 2002. The medical evaluation included randomized controlled trials (RCT. The information synthesis was performed using meta-analysis. Health economic modeling was performed with clinical assumptions derived from the meta-analysis and economical assumptions derived from the German Diagnosis Related Groups (G-DRG-2007. Results: Medical evaluation: Twelve publications about seven RCT on brachytherapy vs. no brachytherapy were included in the medical evaluation. Two RCT showed a significant reduction in the rate of restenosis at six and/or twelve months for brachytherapy vs. no brachytherapy after successful balloon dilatation, the relative risk in the meta-analysis was 0.62 (95% CI: 0.46 to 0.84. At five years, time to recurrence of restenosis was significantly delayed after brachytherapy. One RCT showed a significant reduction in the rate of restenosis at six months for brachytherapy vs. no brachytherapy after PTA with optional stenting, the relative risk in the meta-analysis was 0.76 (95% CI: 0.61 to 0.95. One RCT observed a significantly higher rate of late thrombotic occlusions after brachytherapy in the subgroup of stented patients. A single RCT for brachytherapy

  16. Cytochalasin B augments diacylglycerol levels in stimulated neutrophils

    International Nuclear Information System (INIS)

    Honeycutt, P.J.; Niedel, J.

    1986-01-01

    Diacylglycerol (DG) has gained wide acceptance as an important second messenger and intracellular activator of protein kinase C, but few studies have directly measured DG levels in cells or tissues. The authors measured the mass of DG in lipid extracts from normal human neutrophils by quantitative conversion of DG to [ 32 P] phosphatidic acid using E. coli DG kinase. The chemotactic peptide N-formyl-Met-Leu-Phe (fMLP) stimulated a transient 30% rise in DG that was maximal at 30 to 45 sec and returned to the basal level of 150 picomoles/10 7 cells by one min. This initial peak was followed by a slower, more prolonged 30% increase in DG that was maximal at 20 min. Cytochalasin B (CB) augments many biological responses of neutrophils to fMLP, including superoxide production and lysosomal enzyme release. CB alone caused no change in basal DG levels, but in the presence of CB, fMLP stimulated a rapid, large, and persistent DG response. DG levels increased to 290% of basal at 5 min with a t1/2 = 45 sec. The DG response to fMLP was maximal at 5 to 10 μm CB and 1 μM fMLP. The DG response to optimal fMLP and CB concentrations was decreased 40% by an fMLP antagonist, and no response was elicited by an inactive fMLP analog and CB. Protein kinase C has been implicated in fMLP-stimulated superoxide production and lysosomal enzyme release. These data are consistent with the hypothesis that CB may effect augmentation of biological responses by increasing DG levels

  17. Fulminant intravascular lymphomatosis mimicking acute haemorrhagic leukoencephalopathy.

    Science.gov (United States)

    Marino, D; Sicurelli, F; Cerase, A; Tripodi, S; Cintorino, M; Lazzi, S; Federico, A

    2012-09-15

    Intravascular lymphomatosis (IVL) is a rare non-Hodgkin's lymphoma, usually of B cell lineage, characterized by massive angiotropic growth. The clinical presentation of IVL may include changes in mental status, non-localizing neurological deficits, seizures, fever of unknown origin and skin changes. Because of its rarity and the absence of specific diagnostic procedures except for cerebral biopsy, diagnosis is often postmortem. Brain MRI usually shows non-specific abnormalities. The purpose of this case report is to increase the knowledge of clinical and neuroimaging features of IVL by describing the findings observed in a 71-year-old patient. A 71-year-old male was admitted for right hemiparesis, acute cognitive impairment and febricula. A bone marrow biopsy resulted normal. He then developed a rapid progressive impairment of his mental status and left hemisoma motor seizures. Brain CT and MRI were interpreted as consistent with acute haemorrhagic leukoencephalopathy (AHLE), including multiple areas of restricted diffusion without gadolinium enhancement and a small focal area of gadolinium enhancement in the left temporal lobe white matter. The patient died within a few days and the autopsy led to the diagnosis of IVL. IVL may present with a variety of clinical signs and symptoms, including stroke and hemiparesis. IVL may mimic AHLE at brain MRI. However, the evidence of multiple areas of restricted diffusion without gadolinium enhancement and of a small area of gadolinium enhancement could have led to the correct diagnosis. IVL should be added to the differential diagnosis of AHLE at brain MRI. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Lactose Induces Phenotypic and Functional Changes of Neutrophils and Macrophages to Alleviate Acute Pancreatitis in Mice

    Directory of Open Access Journals (Sweden)

    Li-Long Pan

    2018-04-01

    Full Text Available Acute pancreatitis (AP is one common clinical acute abdominal disease, for which specific pharmacological or nutritional therapies remain elusive. Lactose, a macronutrient and an inducer of host innate immune responses, possesses immune modulatory functions. The current study aimed to investigate potential modulatory effects of lactose and the interplay between the nutrient and pancreatic immunity during experimentally induced AP in mice. We found that either prophylactic or therapeutic treatment of lactose time-dependently reduced the severity of AP, as evidenced by reduced pancreatic edema, serum amylase levels, and pancreatic myeloperoxidase activities, as well as by histological examination of pancreatic damage. Overall, lactose promoted a regulatory cytokine milieu in the pancreas and reduced infiltration of inflammatory neutrophils and macrophages. On acinar cells, lactose was able to suppress caerulein-induced inflammatory signaling pathways and to suppress chemoattractant tumor necrosis factor (TNF-α and monocyte chemotactic protein-1 production. Additionally, lactose acted on pancreas-infiltrated macrophages, increasing interleukin-10 and decreasing tumor necrosis factor alpha production. Notably, lactose treatment reversed AP-associated infiltration of activated neutrophils. Last, the effect of lactose on neutrophil infiltration was mimicked by a galectin-3 antagonist, suggesting a potential endogenous target of lactose. Together, the current study demonstrates an immune regulatory effect of lactose to alleviate AP and suggests its potential as a convenient, value-added therapeutic macronutrient to control AP, and lower the risk of its systemic complications.

  19. Therapeutic intervention in disseminated intravascular coagulation: have we made any progress in the last millennium?

    NARCIS (Netherlands)

    Levi, Marcel; de Jonge, Evert; van der Poll, Tom

    2002-01-01

    Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and

  20. Emergency treatment by intravascular embolization in traumatic carotid cavernous fistula

    International Nuclear Information System (INIS)

    Tang Jun; Sun Zengtao; Liu Zuoqin; Liu Yanjun; Li Fengxin

    2006-01-01

    Objective: To discuss the method of intervenfional intravascular treatment in traumatic carotid cavernous fistula (TCCF) and the significance of clinical application in emergency. Methods: In 297 eases of TCCF, 36 cases were treated by interventional intravascular embolization by detachable balloon, embolization orificium or occlusion in one side of carotid artery. In the 36 cases, serious epistaxis occurred in 22 eases, cortical vein inflow in 9 cases, intracranial hemorrhage in 3 cases, aggravation of eyesight in 3 cases, and limb dysfunction in 2 cases. Results: Fistula was successfully embolized and internal carotid artery remained patent in 19 cases. Complete embolization of orificium or internal carotid artery was achieved in 17 eases. The serious epistaxias in 22 cases and intracranial hemorrhage in 3 cases stopped. Eyesight recovered in 2 eases and improved in 1 case. Limb dysfunction improved evidently in 2 cases. Conclusion: Intravascular embolization treatment is the first therapeutic choice for TCCF, especially in emergency. It is necessary, safe and effective. (authors)

  1. Localization of monocyte chemotactic and activating factor (MCAF/MCP-1) in psoriasis

    DEFF Research Database (Denmark)

    Deleuran, M; Buhl, L; Ellingsen, T

    1996-01-01

    in the epidermal pustules in pustular psoriasis. In normals positive staining was observed in all the layers of the epidermis and in a few perivascular cells and blood vessels in the dermis. Where present in normal and diseased skin, eccrine ducts of sweat glands and sebaceous glands stained positive for MCAF......The monocyte chemotactic protein-1 (MCAF) also termed MCP-1, a strong chemotactic factor towards monocytes, is produced by several cell types present in the skin. The in situ presence of MCAF/MCP-1 protein in the skin has, however, not yet been established. Using immunohistochemical techniques we...... have investigated the distribution of MCAF in skin from patients with different types of psoriasis and normal healthy volunteers. We report the novel finding that psoriasis has strong positive immunostaining for MCAF located to all the layers of the epidermis, except the stratum granulosum, in pustular...

  2. Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria

    DEFF Research Database (Denmark)

    Nielsen, H; Kharazmi, A; Theander, T G

    1986-01-01

    tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half...... of the patients when compared with healthy control subjects. The depression was found in Plasmodium falciparum malaria as well as in P. vivax or P. ovale malaria patients. The defective responsiveness was not receptor specific, since the responses towards casein and zymosan activated serum proved to be equally...... of treatment, and nearly normalized after 7 days (87% of controls). Furthermore, monocyte phagocytic and candidacidal activities were assessed in the same patients on admission and during the follow-up. In contrast to chemotaxis, these functions were normal in all of the patients whenever measured...

  3. Neutrophils, dendritic cells and Toxoplasma.

    Science.gov (United States)

    Denkers, Eric Y; Butcher, Barbara A; Del Rio, Laura; Bennouna, Soumaya

    2004-03-09

    Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.

  4. Immune modulation by neutrophil subsets

    NARCIS (Netherlands)

    Kamp, V.M.

    2013-01-01

    We show that human neutrophils can suppress T-cell proliferation in acute systemic inflammation and thus have anti-inflammatory functions, next to their well-known pro-inflammatory functions. The suppression is mediated by ROS production and integrin MAC-1, which are also important for the

  5. Intravascular Young's modulus reconstruction using a parametric finite element model

    NARCIS (Netherlands)

    Baldewsing, R.A.; Oomens, C.W.J.; Steen, van der A.F.W.; Yuhas, D.; Schneider, S.C.

    2003-01-01

    IntraVascular UltraSound (IVUS) elastography may be used to detect vulnerable, rupture prone plaques, which are held responsible for the majority of acute coronary syndromes. IVUS elastography accomplishes this by visualising local incremental radial strain of arteries, in so-called elastograms.

  6. 21 CFR 880.5440 - Intravascular administration set.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intravascular administration set. 880.5440 Section 880.5440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use...

  7. Heartbeat OCT: In vivo intravascular megahertz-optical coherence tomography

    NARCIS (Netherlands)

    T. Wang (Tianshi); A.F.H. Pfeiffer (Andreas); E.S. Regar (Eveline); W. Wieser (Wolfgang); H.M.M. van Beusekom (Heleen); C.T. Lancée (Charles); T. Springeling (Tirza); I. Krabbendam (Ilona); A.F.W. van der Steen (Ton); R. Huber (Roman); G. van Soest (Gijs)

    2015-01-01

    textabstractCardiac motion artifacts, non-uniform rotational distortion and undersampling affect the image quality and the diagnostic impact of intravascular optical coherence tomography (IV-OCT). In this study we demonstrate how these limitations of IV-OCT can be addressed by using an imaging

  8. Mechanical scanning in intravascular ultrasound imaging: Artifacts and driving mechanisms

    NARCIS (Netherlands)

    H. ten Hoff (H.); E.J. Gussenhoven (Elma); C.M. Korbijn (Carin); F. Mastik (Frits); C.T. Lancée (Charles); N. Bom (Klaas)

    1995-01-01

    textabstractObjective: Currently, intravascular ultrasound (US) imaging catheters are developed and produced to provide a complementary diagnostic method in the treatment of blood vessel obstructive disease. Typical catheter dimensions are a diameter of 1–2.5 mm and a length of 1–1.5 m. A real-time

  9. Intravascular catheter related infections in children admitted on the ...

    African Journals Online (AJOL)

    peripheral venous intravascular catheters uncoated with no antibiotic or antiseptic, was done. Social demographic characteristics, anthropometry, clinical examination including the catheter site were determined at enrollment. The children had their blood, catheter tip and hub samples taken off for culture and sensitivity as ...

  10. Disseminated intravascular coagulation in meningococcal sepsis. Case 7

    NARCIS (Netherlands)

    Zeerleder, S.; Zürcher Zenklusen, R.; Hack, C. E.; Wuillemin, W. A.

    2003-01-01

    We report on a man (age: 49 years), who died from severe meningococcal sepsis with disseminated intravascular coagulation (DIC), multiple organ dysfunction syndrome and extended skin necrosis. We discuss in detail the pathophysiology of the activation of coagulation and fibrinolysis during sepsis.

  11. Intravascular catheter sepsis | Mer | South African Medical Journal

    African Journals Online (AJOL)

    Intravascular devices are an integral component of modern-day medical practice. They are used to administer intravenous fluids, medications, blood products and parenteral nutrition. In addition, they serve as a valuable monitor of the haemodynamic status of critically ill patients.

  12. In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model.

    Directory of Open Access Journals (Sweden)

    Koji Tanaka

    Full Text Available Neutrophil extracellular traps (NETs represent extracellular microbial trapping and killing. Recently, it has been implicated in thrombogenesis, autoimmune disease, and cancer progression. The aim of this study was to characterize NETs in various organs of a murine sepsis model in vivo and to investigate their associations with platelets, leukocytes, or vascular endothelium. NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell-free NETs were characterized as fragmented or cotton-like structures, while anchored NETs were characterized as linear, reticular, membranous, or spot-like structures. In septic mice, both anchored and cell-free NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung. The interactions of NETs with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium of arterioles and venules were observed in the microcirculation of septic mice. Microvessel occlusions which may be caused by platelet aggregates or leukocyte-platelet aggregates and heterogeneously decreased blood flow were also observed in septic mice. NETs appeared to be associated with the formation of platelet aggregates or leukocyte-platelet aggregates. These observational findings may suggest the adverse effect of intravascular NETs on the host during a sepsis.

  13. Cytoplasmic lipid bodies of human neutrophilic leukocytes

    International Nuclear Information System (INIS)

    Weller, P.F.; Ackerman, S.J.; Nicholson-Weller, A.; Dvorak, A.M.

    1989-01-01

    The morphology and function of cytoplasmic lipid bodies in human neutrophils were evaluated. By transmission electron microscopy, neutrophil lipid bodies were cytoplasmic inclusions, usually several microns in diameter, that occasionally coalesced to attain a diameter up to 7 microM. Neutrophil lipid bodies were not enveloped by membrane but were often surrounded by a more electron-dense shell at their periphery. Normal peripheral blood neutrophils contained an average of approximately one lipid body per cell. Lipid bodies appeared in greater numbers in neutrophils from inflammatory lesions. Perturbation of neutrophils during conventional methods of cell isolation and purification modestly increased lipid body numbers in neutrophils, whereas incubation of neutrophils with 1 microM oleic acid rapidly induced lipid body formation over 30 to 60 minutes. After granulocytes were incubated for 2 hours with 3H-fatty acids, including arachidonic, oleic, and palmitic acids, electron microscopic autoradiography demonstrated that lipid bodies represented the predominant intracellular sites of localization of each of the three 3H-fatty acids. There was lesser labeling noted in the perinuclear cisterna, but not in cell membranes. Virtually all of each of the three 3H-fatty acids incorporated by the neutrophils were esterified into chromatographically resolved classes of neutral lipids or phospholipids. These findings indicate that cytoplasmic lipid bodies are more prominent in neutrophils in vivo engaged in inflammatory responses and that these organelles in human neutrophils function as sites of deposition of esterified, incorporated fatty acids

  14. Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

    Science.gov (United States)

    Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

    2008-06-01

    Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

  15. Biomaterial associated impairment of local neutrophil function.

    Science.gov (United States)

    Kaplan, S S; Basford, R E; Kormos, R L; Hardesty, R L; Simmons, R L; Mora, E M; Cardona, M; Griffith, B L

    1990-01-01

    The effect of biomaterials on neutrophil function was studied in vitro to determine if these materials activated neutrophils and to determine the subsequent response of these neutrophils to further stimulation. Two biomaterials--polyurethane, a commonly used substance, and Velcro pile (used in the Jarvik 7 heart)--were evaluated. Two control substances, polyethylene and serum-coated polystyrene, were used for comparison. Neutrophil superoxide release was measured following incubation with these materials for 10, 30, and 120 min in the absence of additional stimulation and after stimulation with formylmethionylleucylphenylalanine (fMLP) or phorbol myristate acetate (PMA). The authors observed that the incubation of neutrophils on both polyurethane and Velcro resulted in substantially increased superoxide release that was greater after the 10 min than after the 30 or 120 min association. These activated neutrophils exhibited a poor additional response to fMLP but responded well to PMA. The effect of implantation of the Novacor left ventricular assist device on peripheral blood neutrophil function was also evaluated. The peripheral blood neutrophils exhibited normal superoxide release and chemotaxis. These studies suggest that biomaterials may have a profound local effect on neutrophils, which may predispose the patient to periprosthetic infection, but that the reactivity of circulating neutrophils is unimpaired.

  16. Effect of sevoflurane on human neutrophil apoptosis.

    LENUS (Irish Health Repository)

    Tyther, R

    2012-02-03

    BACKGROUND AND OBJECTIVE: Both chronic occupational exposure to volatile anaesthetic agents and acute in vitro exposure of neutrophils to isoflurane have been shown to inhibit the rate of apoptosis of human neutrophils. It is possible that inhibition of neutrophil apoptosis arises through delaying mitochondrial membrane potential collapse. We assessed mitochondrial depolarization and apoptosis in unexposed neutrophils and neutrophils exposed to sevoflurane in vivo. METHODS: A total of 20 mL venous blood was withdrawn pre- and postinduction of anaesthesia, the neutrophils isolated and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. Mitochondrial depolarization was measured using the dual emission styryl dye JC-1. RESULTS: Apoptosis was significantly inhibited in neutrophils exposed to sevoflurane in vivo at 24 (exposed: 38 (12)% versus control: 28 (11)%, P = 0.001), but not at 1 or 12 h, in culture. Mitochondrial depolarization was not delayed in neutrophils exposed to sevoflurane. CONCLUSIONS: The most important findings are that sevoflurane inhibits neutrophil apoptosis in vivo and that inhibition is not mediated primarily by an effect on mitochondrial depolarization.

  17. Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

    Science.gov (United States)

    Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

    2018-03-01

    Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

  18. Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity

    Directory of Open Access Journals (Sweden)

    Jiehao Zhou

    2010-01-01

    Full Text Available We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE. The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of bovine RPE-Choroid explants was evaluated by measuring [H] mannitol flux in a modified Ussing chamber. The expression of matrix metalloproteinase- (MMP- 9 in murine peritoneal neutrophils, and the effects of neutrophils on RPE tight-junction protein expression were assessed by confocal microscopy and western blot. Our results revealed that basolateral incubation of explants with neutrophils decreased occludin and ZO-1 expression at 1 and 3 hours and increased the permeability of bovine RPE-Choroid explants by >3-fold (P<.05. Similarly, basolateral incubation of explants with neutrophil lysate decreased ZO-1 expression at 1 and 3 hours (P<.05 and increased permeability of explants by 75%. Further, we found that neutrophils prominently express MMP-9 and that incubation of explants with neutrophils in the presence of anti-MMP-9 antibody inhibited the increase in permeability. These data suggest that neutrophil-derived MMP-9 may play an important role in disrupting the integrity of the outer blood-retina barrier.

  19. Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity.

    Science.gov (United States)

    Mori, Shogo; Williams, Howard; Cagle, Davey; Karanovich, Kristopher; Horgen, F David; Smith, Roger; Watanabe, Coran M H

    2015-10-09

    A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue.

  20. Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

    OpenAIRE

    Mori, Shogo; Williams, Howard; Cagle, Davey; Karanovich, Kristopher; Horgen, F. David; Smith, Roger; Watanabe, Coran M. H.

    2015-01-01

    A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol re...

  1. Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

    Directory of Open Access Journals (Sweden)

    Shogo Mori

    2015-10-01

    Full Text Available A new bioactive macrolactone, nuiapolide (1 was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue.

  2. Defect of netrophil chemotactic function is one of the etiology of aggressive periodontitis.

    Directory of Open Access Journals (Sweden)

    Yanti Rusyanti

    2016-06-01

    Full Text Available Characteristic of progressive destructive periodontal tissue in Aggressive Periodontitis is a features of disruption of the host-homeostasis as the results of imbalance between host response and specific bacterial pathogenic which presents at gingival sulcus. The objective of this study was to evaluate netrophil function of  Aggressive periodontitis molecularly by means of gen polimorphism of Formyl Peptide Receptor (FPR1 at the surface of netrophil cell, the level of IL-8 and netrophil chemotactic. The results of  the study  can be used as an early detection, prevention or to arrest tissue destruction and to restore a health-associated homeostasis in order to get better prognosis of Aggressive Periodontitis. The study was conducted during 20 months in Periodontic Clinic Dental Hospital, Faculty of Dentistry, Padjadjaran University, Genetica Moleculer Medical Laboratory of Research Institution Padjadjaran University Bandung. Research design used case control methode and sample selection is done in concecutive sampling of 32 aggressive periodontitis patients and 29 non aggressive periodontitis patients who were included in the inclusion criteria. Research materials were venous blood and gingival crevicular fluid. PCR-Sequensing methode was used to asses of gene FPR1 Polimorphism. ELISA methode was used to measure IL-8 level in gingival crevicular fluid, and Human CD66abce Microbead Kit by MACS Separation methode was used to asses netrophil chemotactic. Chi-square test, Fisher’s exact, unpaired t tests were employed to analyse the differences of  characteristic, allele frequencies and genotypic, bivariate analysis to analyse of risk factors and biserial point correlation to analyse correlation between risk factors. The results showed the existence of c576T>C>G gene FPR1 polymorphism 5.040 time-fold (p=0.006; OR=5.040 while the down regulation of IL-8( ≤0.064 pg/µl is 34.5 times-fold of having aggressive periodontitis (OR=34, and c576T

  3. Newer techniques for intravascular and intraoperative neurointerventional procedures

    International Nuclear Information System (INIS)

    Higashida, R.T.; Halbach, V.V.; Hieshima, G.B.; Yang, P.

    1987-01-01

    A videotape demonstrating newer techniques used in intravascular and intraoperative embolization procedures will be presented. The authors discuss the use of some of the newer embolic agents, real-time digital subtraction angiography, roadmapping techniques, and the use of microcatheters and steerable micro guide wires, which has greatly facilitated neurovascullar embolization procedures and enhanced patient safety. A number of actual intraoperative and intravascular cases will be shown demonstrating treatment of vascular malformations of the brain and spinal cord, carotid cavernous sinus fistulas, aneurysms and dural arteriovenous malformations. The indications for treatment, patient selection, technical preparation and newer methodologies and approaches to complex vascular lesions of the brain and spinal cord are discussed in detail

  4. Intravascular brachytherapy: a model for the calculation of the dose

    International Nuclear Information System (INIS)

    Pirchio, Rosana; Martin, Gabriela; Rivera, Elena; Cricco, Graciela; Cocca, Claudia; Gutierrez, Alicia; Nunez, Mariel; Bergoc, Rosa; Guzman, Luis; Belardi, Diego

    2002-01-01

    In this study we present the radiation dose distribution for a theoretical model with Montecarlo simulation, and based on an experimental model developed for the study of the prevention of restenosis post-angioplasty employing intravascular brachytherapy. In the experimental in vivo model, the atherosclerotic plaques were induced in femoral arteries of male New Zealand rabbits through surgical intervention and later administration of cholesterol enriched diet. For the intravascular irradiation we employed a 32P source contained within the balloon used for the angioplasty. The radiation dose distributions were calculated using the Monte Carlo code MCNP4B according to a segment of a simulated artery. We studied the radiation dose distribution in the axial and radial directions for different thickness of the atherosclerotic plaques. The results will be correlated with the biologic effects observed by means of histological analysis of the irradiated arteries (Au)

  5. Design of low noise transimpedance amplifier for intravascular ultrasound

    KAUST Repository

    Reda, Dina

    2009-11-01

    In this paper, we study transimpedance amplifiers for capacitive sensing applications with a focus on Intravascular Ultra Sound (IVUS). We employ RF noise cancellation technique on capacitive feedback based transimpedance amplifiers. This technique eliminates the input-referred noise of TIAs completely and enhances the dynamic range of front-end electronics. Simulation results verify the proposed technique used in two different TIA topologies employing shunt-shunt feedback. ©2009 IEEE.

  6. Asian-variant intravascular lymphoma in the African race

    Directory of Open Access Journals (Sweden)

    Holly Geyer

    2012-03-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBCL is an exceptionally rare form of non- Hodgkin lymphoma (NHL distinguished by the preferential growth of neoplastic cells within blood vessel lumen. Challenging to detect and deemed disseminated at diagnosis, this condition is characterized by a highly aggressive, inconspicuous course with a high mortality rate. We describe the case of a 48 year-old African-American female presenting with a two month history of low-grade fevers and malaise. Laboratory data was notable for anemia, thrombocytopenia, elevated liver function tests, and hematuria. An extensive workup for infectious, rheumatologic and malignant causes was negative. Her symptoms progressed and within two weeks, she was admitted for disseminated intravascular coagulation (DIC. Her course was complicated by diffuse pulmonary hemorrhage and ultimately, care was withdrawn. Autopsy identified widespread CD-20 positive intravascular large B-cell lymphoma with significant hepatosplenic involvement, characteristic of the Asian variant IVLBCL. This case uniquely highlights development of the Asian variant IVLBVL in a previously undescribed race. Identified by its intraluminal vascular growth pattern, IVLBCL generally spares lymphatic channels. Diagnosis and differentiation of this condition from other hematological malignancies via skin, visceral and bone marrow biopsy is imperative as anthracycline-containing chemotherapies may significantly improve clinical outcomes. This article outlines the common presentation, natural course, and treatment options of IVLBCL, along with the histopathology, immunohistochemistry, and chromosomal aberrations common to this condition.

  7. Renal denervation by intravascular ultrasound: Preliminary in vivo study

    Science.gov (United States)

    Sinelnikov, Yegor; McClain, Steve; Zou, Yong; Smith, David; Warnking, Reinhard

    2012-10-01

    Ultrasound denervation has recently become a subject of intense research in connection with the treatment of complex medical conditions including neurological conditions, development of pain management, reproduction of skin sensation, neuropathic pain and spasticity. The objective of this study is to investigate the use of intravascular ultrasound to produce nerve damage in renal sympathetic nerves without significant injury to the renal artery. This technique may potentially be used to treat various medical conditions, such as hypertension. The study was approved by the Institutional Animal Care and Use Committee. Ultrasound was applied to renal nerves of the swine model for histopathological evaluation. Therapeutic ultrasound energy was delivered circumferentially by an intravascular catheter maneuvered into the renal arteries. Fluoroscopic imaging was conducted pre-and post-ultrasound treatment. Animals were recovered and euthanized up to 30 hours post procedure, followed by necropsy and tissue sample collection. Histopathological examination showed evidence of extensive damage to renal nerves, characterized by nuclear pyknosis, hyalinization of stroma and multifocal hemorrhages, with little or no damage to renal arteries. This study demonstrates the feasibility of intravascular ultrasound as a minimally invasive renal denervation technique. Further studies are necessary to evaluate the long-term safety and efficacy of this technique and its related clinical significance.

  8. Neutrophil Responses to Sterile Implant Materials.

    Directory of Open Access Journals (Sweden)

    Siddharth Jhunjhunwala

    Full Text Available In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30-500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety of inflammatory cytokines and chemokines. Further, we observe that they participate in the foreign body response through the formation of neutrophil extracellular traps (NETs on implant surfaces. Our results provide new insight into neutrophil function during a foreign body response to peritoneal implants which has implications for the development of biologically compatible medical devices.

  9. Neutrophil Reverse Migration Becomes Transparent with Zebrafish

    Directory of Open Access Journals (Sweden)

    Taylor W. Starnes

    2012-01-01

    Full Text Available The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

  10. Neutrophils in Tuberculosis: Heterogeneity Shapes the Way?

    Science.gov (United States)

    2017-01-01

    Infection with M. tuberculosis remains one of the most common infections in the world. The outcome of the infection depends on host ability to mount effective protection and balance inflammatory responses. Neutrophils are innate immune cells implicated in both processes. Accordingly, during M. tuberculosis infection, they play a dual role. Particularly, they contribute to the generation of effector T cells, participate in the formation of granuloma, and are directly involved in tissue necrosis, destruction, and infection dissemination. Neutrophils have a high bactericidal potential. However, data on their ability to eliminate M. tuberculosis are controversial, and the results of neutrophil depletion experiments are not uniform. Thus, the overall roles of neutrophils during M. tuberculosis infection and factors that determine these roles are not fully understood. This review analyzes data on neutrophil defensive and pathological functions during tuberculosis and considers hypotheses explaining the dualism of neutrophils during M. tuberculosis infection and tuberculosis disease. PMID:28626346

  11. Neutrophil Extracellular Traps in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Bjerg Bennike, Tue; Carlsen, Thomas Gelsing; Ellingsen, Torkell

    2015-01-01

    microscopy and confocal microscopy. RESULTS: We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did...... not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were...... validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed. CONCLUSIONS: Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate...

  12. Chemotactic behavior of deep subsurface bacteria toward carbohydrates, amino acids and a chlorinated alkene

    Energy Technology Data Exchange (ETDEWEB)

    Lopez de Victoria, G. (Puerto Rico Univ., Rio Piedras (Puerto Rico). Dept. of Biology)

    1989-02-01

    The chemotactic behavior of deep terrestrial subsurface bacteria toward amino acids, carbohydrates and trichloroethylene was assayed using a modification of the capillary method and bacterial enumeration by acridine orange direct counts. Eleven isolates of bacteria isolated from six different geological formations were investigated. A bimodal response rather than an absolute positive or negative response was observed in most assays. Most of the isolates were positively chemotactic to low concentrations of substrates and were repelled by high concentrations of the same substrate. However, this was not the case for trichloroethylene (TCE) which was mostly an attractant and elicited the highest responses in all the isolates when compared with amino acids and carbohydrates. The movement rates of these isolates in aseptic subsurface sediments in the absence and presence of TCE were also determined using a laboratory model. All of the isolates showed distinct response range, peak, and threshold concentrations when exposed to the same substrates suggesting that they are possibly different species as has been inferred from DNA homology studies. 101 refs., 4 figs., 57 tabs.

  13. An unusual protein kinase phosphorylates the chemotactic receptor of Dictystelium discoideum

    International Nuclear Information System (INIS)

    Meier, K.; Klein, C.

    1988-01-01

    The authors report the cAMP-dependent phosphorylation of the chemotactic receptor of Dictyostelium discoideum in partially purified plasma membranes. The protein kinase responsible for receptor phosphorylation is associated with this fraction and preferentially phosphorylates the ligand-occupied form of the receptor. 8-Azido[ 32 P]cAMP labeling of the cell surface has shown that the cAMP receptor exists in two forms. A 45-kDa protein is predominant on unstimulated cells. cAMP stimulation results in an increased receptor phosphorylation such that the receptor migrates on NaDodSO 4 /PAGE as a 47-kDa protein. Phosphorylation of the chemotactic receptor is not detected in membrane preparations unless cAMP is added to the incubation mixture. Only under those conditions is the phosphorylated 47-kDa form observed. The requirement for cAMP reflects the fact that the kinase involved preferentially uses the ligand-occupied receptor as a substrate. In vitro phosphorylation of the receptor does not involve tyrosine residues. The enzyme does not appear to be a cAMP- or cGMP-dependent protein kinase nor is it sensitive to guanine nucleotides, Ca 2+ /calmodulin, Ca 2+ /phospholipid, or EGTA. Similarities with the β-adrenergic receptor protein kinase are discussed

  14. Impaired neutrophil function in intestinal lymphangiectasia.

    OpenAIRE

    Bolton, R P; Cotter, K L; Losowsky, M S

    1986-01-01

    Impaired neutrophil chemotaxis and phagocytosis were shown in three patients with intestinal lymphangiectasia. Abnormalities in cell associated and serum derived activity occurred, and possible mechanisms are suggested.

  15. Complement Activation Induces Neutrophil Adhesion and Neutrophil-Platelet Aggregate Formation on Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Magdalena Riedl

    2017-01-01

    Discussion: Therefore, our findings of (i neutrophils adhering to complement-activated endothelial cells, (ii the formation of neutrophil-platelet aggregates on endothelial cells, and (iii the ability of aHUS serum to induce similar effects identify a possible role for neutrophils in aHUS manifestation.

  16. Design, construction, and validation of a rotary multifunctional intravascular diagnostic catheter combining multispectral fluorescence lifetime imaging and intravascular ultrasound.

    Science.gov (United States)

    Bec, Julien; Xie, Hongtao; Yankelevich, Diego R; Zhou, Feifei; Sun, Yang; Ghata, Narugopal; Aldredge, Ralph; Marcu, Laura

    2012-10-01

    We report the development and validation of an intravascular rotary catheter for bimodal interrogation of arterial pathologies. This is based on a point-spectroscopy scanning time-resolved fluorescence spectroscopy technique enabling reconstruction of fluorescence lifetime images (FLIm) and providing information on arterial intima composition and intravascular ultrasound (IVUS) providing information on arterial wall morphology. The catheter design allows for independent rotation of the ultrasonic and optical channels within an 8 Fr outer diameter catheter sheath and integrates a low volume flushing channel for blood removal in the optical pathways. In the current configuration, the two channels consist of (a) a standard 3 Fr IVUS catheter with single element transducer (40 MHz) and (b) a side-viewing fiber optic (400 μm core). Experiments conducted in tissue phantoms showed the ability of the catheter to operate in an intraluminal setting and to generate coregistered FLIm and IVUS in one pull-back scan. Current results demonstrate the feasibility of the catheter for simultaneous bimodal interrogation of arterial lumen and for generation of robust fluorescence lifetime data under IVUS guidance. These results facilitate further development of a FLIm-IVUS technique for intravascular diagnosis of atherosclerotic cardiovascular diseases including vulnerable plaques.

  17. Different innate neutrophil responses in controlled and uncontrolled asthma

    NARCIS (Netherlands)

    Tang, Francesca; Foxley, Gloria; Gibson, Peter; Burgess, Janette; Baines, Katherine; Oliver, Brian

    2015-01-01

    Introduction: Respiratory viruses are a major cause of asthma exacerbations. Neutrophilic inflammation occurs during infections and is associated with difficult to treat asthma. The role of neutrophils in viral infections and whether neutrophil dysfunction contributes to exacerbation pathogenesis

  18. Oral neutrophil responses to acute prolonged exercise may not be representative of blood neutrophil responses.

    Science.gov (United States)

    Davison, Glen; Jones, Arwel Wyn

    2015-03-01

    Neutrophil numbers and function (oxidative burst) were assessed in peripheral blood and oral samples before and after prolonged exercise. Blood neutrophil count increased (∼3.5-fold, P < 0.001) and function decreased (30% ± 19% decrease, P = 0.005) postexercise. Oral neutrophil count (P = 0.392) and function (P = 0.334) were unchanged. Agreement between oral and blood neutrophil function responses to exercise was poor. These findings highlight the importance of studying neutrophils within various compartments/sample types.

  19. Neutrophil migration under normal and sepsis conditions.

    Science.gov (United States)

    Lerman, Yelena V; Kim, Minsoo

    2015-01-01

    Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host.

  20. Neutrophil heterogeneity: implications for homeostasis and pathogenesis

    NARCIS (Netherlands)

    Silvestre-Roig, Carlos; Hidalgo, Andres; Soehnlein, Oliver

    2016-01-01

    Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a

  1. Candida albicans escapes from mouse neutrophils

    DEFF Research Database (Denmark)

    Ermert, David; Niemiec, Maria J; Röhm, Marc

    2013-01-01

    is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed...

  2. Neutrophils: potential therapeutic targets in tularemia?

    Directory of Open Access Journals (Sweden)

    Lee-Ann H Allen

    2013-12-01

    Full Text Available The central role of neutrophils in innate immunity and host defense has long been recognized, and the ability of these cells to efficiently engulf and kill invading bacteria has been extensively studied, as has the role of neutrophil apoptosis in resolution of the inflammatory response. In the past few years additional immunoregulatory properties of neutrophils were discovered, and it is now clear that these cells play a much greater role in control of the immune response than was previously appreciated. In this regard, it is noteworthy that Francisella tularensis is one of relatively few pathogens that can successfully parasitize neutrophils as well as macrophages, DC and epithelial cells. Herein we will review the mechanisms used by F. tularensis to evade elimination by neutrophils. We will also reprise effects of this pathogen on neutrophil migration and lifespan as compared with other infectious and inflammatory disease states. In addition, we will discuss the evidence which suggests that neutrophils contribute to disease progression rather than effective defense during tularemia, and consider whether manipulation of neutrophil migration or turnover may be suitable adjunctive therapeutic strategies.

  3. Contribution of neutrophils to acute lung injury.

    Science.gov (United States)

    Grommes, Jochen; Soehnlein, Oliver

    2011-01-01

    Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

  4. The complex interplay between neutrophils and cancer.

    Science.gov (United States)

    Rakic, Andrea; Beaudry, Paul; Mahoney, Douglas J

    2018-03-01

    Neutrophils are the most abundant type of white blood cell, and are an essential component of the innate immune system. They characteristically arrive rapidly at sites of infection and injury, and release a variety of cytokines and toxic molecules to eliminate pathogens and elicit an acute inflammatory response. Research into the function of neutrophils in cancer suggest they have divergent roles. Indeed, while most studies have found neutrophils to be associated with cancer progression, others have also documented anticancer effects. In this review, we describe the investigations into neutrophil populations that have been implicated in promoting tumor growth and metastasis as well those demonstrating antitumor functions. The collective research suggests a complex role for neutrophils in cancer biology, which raises the prospect of their targeting for the treatment of cancer.

  5. Dynamic interactions of neutrophils and biofilms

    Directory of Open Access Journals (Sweden)

    Josefine Hirschfeld

    2014-12-01

    Full Text Available Background: The majority of microbial infections in humans are biofilm-associated and difficult to treat, as biofilms are highly resistant to antimicrobial agents and protect themselves from external threats in various ways. Biofilms are tenaciously attached to surfaces and impede the ability of host defense molecules and cells to penetrate them. On the other hand, some biofilms are beneficial for the host and contain protective microorganisms. Microbes in biofilms express pathogen-associated molecular patterns and epitopes that can be recognized by innate immune cells and opsonins, leading to activation of neutrophils and other leukocytes. Neutrophils are part of the first line of defense and have multiple antimicrobial strategies allowing them to attack pathogenic biofilms. Objective/design: In this paper, interaction modes of neutrophils with biofilms are reviewed. Antimicrobial strategies of neutrophils and the counteractions of the biofilm communities, with special attention to oral biofilms, are presented. Moreover, possible adverse effects of neutrophil activity and their biofilm-promoting side effects are discussed. Results/conclusion: Biofilms are partially, but not entirely, protected against neutrophil assault, which include the processes of phagocytosis, degranulation, and formation of neutrophil extracellular traps. However, virulence factors of microorganisms, microbial composition, and properties of the extracellular matrix determine whether a biofilm and subsequent microbial spread can be controlled by neutrophils and other host defense factors. Besides, neutrophils may inadvertently contribute to the physical and ecological stability of biofilms by promoting selection of more resistant strains. Moreover, neutrophil enzymes can degrade collagen and other proteins and, as a result, cause harm to the host tissues. These parameters could be crucial factors in the onset of periodontal inflammation and the subsequent tissue breakdown.

  6. Human neutrophils in auto-immunity.

    Science.gov (United States)

    Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique

    2016-04-01

    Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Why Have So Many Intravascular Glucose Monitoring Devices Failed?

    Science.gov (United States)

    Smith, John L; Rice, Mark J

    2015-07-01

    Secondary to the inherent limitations of both point-of-care and central laboratory glucose technologies, continuous glucose measurement has recently enjoyed a high level of investment. Because of the perceived advantages by some of measuring in the intravascular space compared to the subcutaneous tissue, a number of technologies have been developed. In this review, we evaluate nine systems that have shown promise, although only one of these has been cleared for sale in the United States. The detection methodology, regulatory status, technical issues, and company circumstance surrounding each technology are examined. © 2015 Diabetes Technology Society.

  8. Prevention of adverse reactions to intravascular contrast media

    International Nuclear Information System (INIS)

    Soyer, P.; Levesque, M.

    1990-01-01

    The exact mechanisms of adverse reactions to contrast media are still imperfectly known. However, these reactions may be classified as idiosyncratic. Non-idiosyncratic reactions can be prevented by using new, non-ionic contrast agents. Idiosyncratic reactions can be prevented by specific premedication. Patients with a history of idiosyncratic reaction may benefit from corticosteroids and antihistamines administered prophylactically. Patients who seem to be more likely than others to react to contrast media must be premedicated, the risk of reaction being identified and evaluated by questioning. It has recently been suggested that all patients about to receive an intravascular injection of contrast medium should also be premedicated [fr

  9. Protection against high intravascular pressure in giraffe legs

    DEFF Research Database (Denmark)

    Petersen, Karin K; Hørlyck, Arne; Østergaard, Kristine Hovkjær

    2013-01-01

    The high blood pressure in giraffe leg arteries renders giraffes vulnerable to edema. We investigated in 11 giraffes whether large and small arteries in the legs and the tight fascia protect leg capillaries. Ultrasound imaging of foreleg arteries in anesthetized giraffes and ex vivo examination....... All three findings can contribute to protection of the capillaries in giraffe legs from a high arterial pressure....... revealed abrupt thickening of the arterial wall and a reduction of its internal diameter just below the elbow. At and distal to this narrowing, the artery constricted spontaneously and in response to norepinephrine and intravascular pressure recordings revealed a dynamic, viscous pressure drop along...

  10. Chemotactic preferences govern competition and pattern formation in simulated two-strain microbial communities.

    Science.gov (United States)

    Centler, Florian; Thullner, Martin

    2015-01-01

    Substrate competition is a common mode of microbial interaction in natural environments. While growth properties play an important and well-studied role in competition, we here focus on the influence of motility. In a simulated two-strain community populating a homogeneous two-dimensional environment, strains competed for a common substrate and only differed in their chemotactic preference, either responding more sensitively to a chemoattractant excreted by themselves or responding more sensitively to substrate. Starting from homogeneous distributions, three possible behaviors were observed depending on the competitors' chemotactic preferences: (i) distributions remained homogeneous, (ii) patterns formed but dissolved at a later time point, resulting in a shifted community composition, and (iii) patterns emerged and led to the extinction of one strain. When patterns formed, the more aggregating strain populated the core of microbial aggregates where starving conditions prevailed, while the less aggregating strain populated the more productive zones at the fringe or outside aggregates, leading to a competitive advantage of the less aggregating strain. The presence of a competitor was found to modulate a strain's behavior, either suppressing or promoting aggregate formation. This observation provides a potential mechanism by which an aggregated lifestyle might evolve even if it is initially disadvantageous. Adverse effects can be avoided as a competitor hinders aggregate formation by a strain which has just acquired this ability. The presented results highlight both, the importance of microbial motility for competition and pattern formation, and the importance of the temporal evolution, or history, of microbial communities when trying to explain an observed distribution.

  11. Transverse Chemotactic Migration of Bacteria from High to Low Permeability Regions in a Dual Permeability Porous Microfluidic Device

    Science.gov (United States)

    Singh, R.; Olson, M. S.

    2011-12-01

    Low permeability regions sandwiched between high permeability regions such as clay lenses are difficult to treat using conventional treatment methods. Trace concentrations of contaminants such as non-aqueous phase liquids (NAPLs) remain trapped in these regions and over the time diffuse out into surrounding water thereby acting as a long term source of groundwater contamination. Bacterial chemotaxis (directed migration toward a contaminant source), may be helpful in enhancing bioremediation of such contaminated sites. This study is focused on simulating a two-dimensional dual-permeability groundwater contamination scenario using microfluidic devices and evaluating transverse chemotactic migration of bacteria from high to low permeability regions. A novel bi-layer polydimethylsiloxane (PDMS) microfluidic device was fabricated using photolithography and soft lithography techniques to simulate contamination of a dual- permeability region due to leakage from an underground storage tank into a low permeability region. This device consists of a porous channel through which a bacterial suspension (Escherchia Coli HCB33) is flown and another channel for injecting contaminant/chemo-attractant (DL-aspertic acid) into the porous channel. The pore arrangement in the porous channel contains a 2-D low permeability region surrounded by high permeability regions on both sides. Experiments were performed under chemotactic and non-chemotactic (replacing attractant with buffer solution in the non porous channel) conditions. Images were captured in transverse pore throats at cross-sections 4.9, 9.8, and 19.6 mm downstream from the attractant injection point and bacteria were enumerated in the middle of each pore throat. Bacterial chemotaxis was quantified in terms of the change in relative bacterial counts in each pore throat at cross-sections 9.8 and 19.6 mm with respect to counts at the cross-section at 4.9 mm. Under non-chemotactic conditions, relative bacterial count was observed

  12. Selected mucolytic, anti-inflammatory and cardiovascular drugs change the ability of neutrophils to form extracellular traps (NETs).

    Science.gov (United States)

    Zawrotniak, Marcin; Kozik, Andrzej; Rapala-Kozik, Maria

    2015-01-01

    Neutrophils form the first line of host defense against infections that combat pathogens using two major mechanisms, the phagocytosis or the release of neutrophil extracellular traps (NETs). The netosis (NET formation) exerts additional, unfavorable effects on the fitness of host cells and is also involved at the sites of lung infection, increasing the mucus viscosity and in the circulatory system where it can influence the intravascular clot formation. Although molecular mechanisms underlying the netosis are still incompletely understood, a role of NADPH oxidase that activates the production of reactive oxygen species (ROS) during the initiation of NETs has been well documented. Since several commonly used drugs can affects the netosis, our current study was aimed to determine the effects of selected mucolytic, anti-inflammatory and cardiovascular drugs on NET formation, with a special emphasis on ROS production and NADPH oxidase activity. The treatment of neutrophils with N-acetylcysteine, ketoprofen and ethamsylate reduced the production of ROS by these cells in a dose-dependent manner. NET formation was also modulated by selected drugs. N-acetylcysteine inhibited the netosis but in the presence of H2O2 this neutrophil ability was restored, indicating that N-acetylcysteine may influence the NET formation by modulating ROS productivity. The administration of ethamsylate led to a significant reduction in NET formation and this effect was not restored by H2O2 or S. aureus, suggesting the unexpected additional side effects of this drug. Ketoprofen seemed to promote ROS-independent NET release, simultaneously inhibiting ROS production. The results, obtained in this study strongly suggest that the therapeutic strategies applied in many neutrophil-mediated diseases should take into account the NET-associated effects.

  13. Activation of bovine neutrophils by Brucella spp.

    Science.gov (United States)

    Keleher, Lauren L; Skyberg, Jerod A

    2016-09-01

    Brucellosis is a globally important zoonotic infectious disease caused by gram negative bacteria of the genus Brucella. While many species of Brucella exist, Brucella melitensis, Brucella abortus, and Brucella suis are the most common pathogens of humans and livestock. The virulence of Brucella is largely influenced by its ability to evade host factors, including phagocytic killing mechanisms, which are critical for the host response to infection. The aim of this study was to characterize the bovine neutrophil response to virulent Brucella spp. Here, we found that virulent strains of smooth B. abortus, B. melitensis, B. suis, and virulent, rough, strains of Brucella canis possess similar abilities to resist killing by resting, or IFN-γ-activated, bovine neutrophils. Bovine neutrophils responded to infection with a time-dependent oxidative burst that varied little between Brucella spp. Inhibition of TAK1, or SYK kinase blunted the oxidative burst of neutrophils in response to Brucella infection. Interestingly, Brucella spp. did not induce robust death of bovine neutrophils. These results indicate that bovine neutrophils respond similarly to virulent Brucella spp. In addition, virulent Brucella spp., including naturally rough strains of B. canis, have a conserved ability to resist killing by bovine neutrophils. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Thyroid storm complicated by bicytopenia and disseminated intravascular coagulation.

    Science.gov (United States)

    Tokushima, Yoshinori; Sakanishi, Yuta; Nagae, Kou; Tokushima, Midori; Tago, Masaki; Tomonaga, Motosuke; Yoshioka, Tsuneaki; Hyakutake, Masaki; Sugioka, Takashi; Yamashita, Shu-ichi

    2014-07-24

    Male, 23. Thyroid storm. Delirium • diarrhea • fever • hypertension • hyperventilation • tachycardia • weight loss. -. -. Endocrinology and Metabolic. Unusual clinical course. The clinical presentation of thyroid storm includes fever, tachycardia, hypertension, and neurological abnormalities. It is a serious condition with a high mortality rate. Furthermore, some other complications affect the clinical course of thyroid storm. Although it is reported that prognosis is poor when thyroid storm is complicated by disseminated intravascular coagulation syndrome (DIC) and leukopenia, reports of such cases are rare. A 23-year-old man presented with delirium, high pyrexia, diarrhea, and weight loss of 18 kg over 2 months. According to the criteria of Burch and Wartofsky, he was diagnosed with thyroid storm on the basis of his symptom-complex and laboratory data that confirmed the presence of hyperthyroidism. Investigations also found leukopenia, thrombocytopenia, and disseminated intravascular coagulation, all of which are very rare complications of thyroid storm. We successfully treated him with combined therapy including anti-thyroid medication, despite leukopenia. Early diagnosis and treatment are essential in ensuring a good outcome for patients with this rare combination of medical problems.

  15. Intravascular photoacoustic imaging: a new tool for vulnerable plaque identification.

    Science.gov (United States)

    Jansen, Krista; van Soest, Gijs; van der Steen, Antonius F W

    2014-06-01

    The vulnerable atherosclerotic plaque is believed to be at the root of the majority of acute coronary events. Even though the exact origins of plaque vulnerability remain elusive, the thin-cap fibroatheroma, characterized by a lipid-rich necrotic core covered by a thin fibrous cap, is considered to be the most prominent type of vulnerable plaque. No clinically available imaging technique can characterize atherosclerotic lesions to the extent needed to determine plaque vulnerability prognostically. Intravascular photoacoustic imaging (IVPA) has the potential to take a significant step in that direction by imaging both plaque structure and composition. IVPA is a natural extension of intravascular ultrasound that adds tissue type specificity to the images. IVPA utilizes the optical contrast provided by the differences in the absorption spectra of plaque components to image composition. Its capability to image lipids in human coronary atherosclerosis has been shown extensively ex vivo and has recently been translated to an in vivo animal model. Other disease markers that have been successfully targeted are calcium and inflammatory markers, such as macrophages and matrix metalloproteinase; the latter two through application of exogenous contrast agents. By simultaneously displaying plaque morphology and composition, IVPA can provide a powerful prognostic marker for disease progression, and as such has the potential to transform the current practice in percutaneous coronary intervention. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  16. High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

    Science.gov (United States)

    Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

    2016-02-01

    Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

  17. Intravascular stenting (IVaS) method for fingertip replantation.

    Science.gov (United States)

    Narushima, Mitsunaga; Mihara, Makoto; Koshima, Isao; Gonda, Koichi; Takuya, Iida; Kato, Harunosuke; Nakanishi, Kenji; Yamamoto, Yusuke; Araki, Jun; Abe, Hiroaki; Mundinger, Gerhard S; Kikuchi, Kazuki; Uehara, Eri

    2009-01-01

    Remarkable progress has been made in microsurgery. However, fingertip replantation following amputation has not gained much popularity because of its technical difficulty. We have developed the intravascular stenting (IVaS) method, in which a nylon monofilament is placed inside the vessel lumen to act as a temporary stent, facilitating anastomosis completion. This report describes 7 fingertip replantations using the IVaS method. Intravascular stent size varied from 4-0 to 6-0 (0.199-0.07 mm diameter). There were no cases in which the back wall of a vessel became inadvertently caught in the anastomosis. The overall survival rate for distal digital replants was 85% (6/7 replants). It is very difficult to evenly anastomose vessels of differing diameter, especially on a supermicrosurgical scale. In this respect, the IVaS method plays a role in stably anchoring the 2 vessel ends, allowing for the even spacing of suture knots, even in vessels of different caliber. Because of its ease of use and exactitude, many surgeons may be able to use the IVaS method to reliably complete small anastomoses in fingertip replantations.

  18. An Implantable Intravascular Pressure Sensor for a Ventricular Assist Device

    Directory of Open Access Journals (Sweden)

    Luigi Brancato

    2016-08-01

    Full Text Available The aim of this study is to investigate the intravascular application of a micro-electro-mechanical system (MEMS pressure sensor to directly measure the hemodynamic characteristics of a ventricular assist device (VAD. A bio- and hemo-compatible packaging strategy is implemented, based on a ceramic thick film process. A commercial sub-millimeter piezoresistive sensor is attached to an alumina substrate, and a double coating of polydimethylsiloxane (PDMS and parylene-C is applied. The final size of the packaged device is 2.6 mm by 3.6 mm by 1.8 mm. A prototype electronic circuit for conditioning and read-out of the pressure signal is developed, satisfying the VAD-specific requirements of low power consumption (less than 14.5 mW in continuous mode and small form factor. The packaged sensor has been submitted to extensive in vitro tests. The device displayed a temperature-independent sensitivity (12 μ V/V/mmHg and good in vitro stability when exposed to the continuous flow of saline solution (less than 0.05 mmHg/day drift after 50 h. During in vivo validation, the transducer has been successfully used to record the arterial pressure waveform of a female sheep. A small, intravascular sensor to continuously register the blood pressure at the inflow and the outflow of a VAD is developed and successfully validated in vivo.

  19. Late adverse reactions to intravascular iodinated contrast media

    International Nuclear Information System (INIS)

    Webb, Judith A.W.; Stacul, Fulvio; Thomsen, Henrik S.; Morcos, Sameh K.

    2003-01-01

    Late adverse reactions to intravascular iodinated contrast media are defined as reactions occurring 1 h to 1 week after contrast medium injection. They have received increasing interest over the past decade, but their prevalence remains uncertain and their pathophysiology is not fully understood. The Contrast Media Safety Committee of the European Society of Urogenital Radiology decided to review the literature and to issue guidelines. An extensive literature search was carried out and summarized in a report. Based on the available information, simple guidelines have been drawn up. The report and guidelines were discussed at the 8th European Symposium on Urogenital Radiology in Genoa. Late adverse reactions after intravascular iodinated contrast medium include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. A significant proportion of these reactions is unrelated to the contrast medium; however, allergy-like skin reactions are well-documented side effects of contrast media with an incidence of approximately 2%. Late reactions appear to be commoner after non-ionic dimers. The majority of late skin reactions after contrast medium exposure are probably T-cell-mediated allergic reactions. Patients at increased risk of late skin reactions are those with a history of previous contrast medium reaction and those on interleukin-2 treatment. Most skin reactions are self-limiting and resolve within a week. Management is symptomatic and similar to the management of other drug-induced skin reactions. (orig.)

  20. Secretion of S100A8, S100A9, and S100A12 by Neutrophils Involves Reactive Oxygen Species and Potassium Efflux

    Directory of Open Access Journals (Sweden)

    Mélanie R. Tardif

    2015-01-01

    Full Text Available S100A8/A9 (calprotectin and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases. These cytoplasmic proteins are secreted by neutrophils at sites of inflammation via alternative secretion pathways of which little is known. This study examined the nature of the stimuli leading to S100A8/A9 and S100A12 secretion as well as the mechanism involved in this alternative secretion pathway. Chemotactic agents, cytokines, and particulate molecules were used to stimulate human neutrophils. MSU crystals, PMA, and H2O2 induced the release of S100A8, S100A9, and S100A12 homodimers, as well as S100A8/A9 heterodimer. High concentrations of S100A8/A9 and S100A12 were secreted in response to nanoparticles like MSU, silica, TiO2, fullerene, and single-wall carbon nanotubes as well as in response to microbe-derived molecules, such as zymosan or HKCA. However, neutrophils exposed to the chemotactic factors fMLP failed to secrete S100A8/A9 or S100A12. Secretion of S100A8/A9 was dependent on the production of reactive oxygen species and required K+ exchanges through the ATP-sensitive K+ channel. Altogether, these findings suggest that S100A12 and S100A8/A9 are secreted independently either via distinct mechanisms of secretion or following the activation of different signal transduction pathways.

  1. Ascorbic acid supplementation diminishes microparticle elevations and neutrophil activation following SCUBA diving.

    Science.gov (United States)

    Yang, Ming; Barak, Otto F; Dujic, Zeljko; Madden, Dennis; Bhopale, Veena M; Bhullar, Jasjeet; Thom, Stephen R

    2015-08-15

    Predicated on evidence that diving-related microparticle generation is an oxidative stress response, this study investigated the role that oxygen plays in augmenting production of annexin V-positive microparticles associated with open-water SCUBA diving and whether elevations can be abrogated by ascorbic acid. Following a cross-over study design, 14 male subjects ingested placebo and 2-3 wk later ascorbic acid (2 g) daily for 6 days prior to performing either a 47-min dive to 18 m of sea water while breathing air (∼222 kPa N2/59 kPa O2) or breathing a mixture of 60% O2/balance N2 from a tight-fitting face mask at atmospheric pressure for 47 min (∼40 kPa N2/59 kPa O2). Within 30 min after the 18-m dive in the placebo group, neutrophil activation, and platelet-neutrophil interactions occurred, and the total number of microparticles, as well as subgroups bearing CD66b, CD41, CD31, CD142 proteins or nitrotyrosine, increased approximately twofold. No significant elevations occurred among divers after ingesting ascorbic acid, nor were elevations identified in either group after breathing 60% O2. Ascorbic acid had no significant effect on post-dive intravascular bubble production quantified by transthoracic echocardiography. We conclude that high-pressure nitrogen plays a key role in neutrophil and microparticle-associated changes with diving and that responses can be abrogated by dietary ascorbic acid supplementation. Copyright © 2015 the American Physiological Society.

  2. Direct and indirect radioiodination of protein: comparative study of chemotactic peptide labeling

    International Nuclear Information System (INIS)

    Lavinas, Tatiana

    2004-01-01

    The development of simple methods for protein radioiodination have stimulated the use of radioiodinated peptides in vivo. There are two basic methods for labeling proteins with radioiodine: direct labeling, reaction of an electrophilic radioiodine with functional activated groups on protein, like the phenol ring in the tyrosine residue, and the conjugation of a previously radioiodinated molecule to the protein, referred as indirect method. The great problem related to the direct radioiodination of proteins is the in vivo dehalogenation. This problem can be minimized if a non-phenolic prosthetic group is used in the indirect radioiodination of the peptide. The ATE prosthetic group, N-succinimidyl 3-(tri-n-butylstannyl) benzoate, when radioiodinated by electrophilic iododestannilation produces N-succinimidyl 3-[ 123 l/ 131 l] iodine benzoate (SIB) that is subsequently conjugated to the protein by the acylation of the lysine group. There are many radiopharmaceuticals employed in scintigraphic images of infection and inflammation used with some limitations. These limitations stimulated the improvement of a new class of radiopharmaceuticals, the receptor-specific related labeled peptides, as the mediators of the inflammatory response, that presents high affinity by receptors expressed in the inflammation process, and fast clearance from blood and non-target tissues. One of these molecules is the synthetic chemotactic peptide fNleLFNIeYK that presents potent chemotaxis for leukocytes, with high affinity by the receptors presented in polymorphonuclear leukocytes and mononuclear phagocytes. The objective of this work included the synthesis of ATE prosthetic group and comparative radioiodination of the chemotactic peptide fNleLFNIeYK by direct and indirect methods, with radiochemical purity determination and evaluation of in vivo and in vitro stability of the compounds. This work presented an original contribution in the comparative biological distribution studies of the

  3. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... between preoperatively measured neutrophil-lymphocyte ratio (NLR) – as an inflammation ... analgesic (tenoxicam – as the first drug of choice, paracetamol, tramadol, or pethidine) usage ... fracture fixation). Age, sex, type of ...

  4. Investigation of urinary neutrophil gelatinase associated lipocalin ...

    African Journals Online (AJOL)

    Investigation of urinary neutrophil gelatinase associated lipocalin (NGAL) for early diagnosis of acute kidney ... African Journal of Urology ... Demographic and clinical data including surgical procedure were recorded in Excel and analyzed by ...

  5. Targeting Neutrophilic Inflammation using Polymersome-Mediated Cellular Delivery

    OpenAIRE

    Robertson, J.D.; Ward, J.R.; Avila-Olias, M.; Battaglia, G.; Renshaw, S.A.

    2017-01-01

    Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In ...

  6. Cryptococcus neoformans modulates extracellular killing by neutrophils

    Directory of Open Access Journals (Sweden)

    Asfia eQureshi

    2011-09-01

    Full Text Available We recently established a key role for host sphingomyelin synthase (SMS in the regulation of the killing activity of neutrophils against Cryptococcus neoformans. In this work, we studied the effect of C. neoformans on the killing activity of neutrophils and whether SMS would still be a player against C. neoformans in immunocompromised mice lacking T and NK cells (Tgε26 mice. To this end, we analyzed whether C. neoformans would have any effect on neutrophil survival and killing in vitro and in vivo. We show that unlike C. albicans, neither the presence nor the capsule size of C. neoformans cells have any effect on neutrophil viability. Interestingly, melanized C. neoformans cells totally abrogated the killing activity of neutrophils. Next, we monitored how exposure of neutrophils to C. neoformans cells would interfere with any further killing activity of the medium and found that pre-incubation with live but not heat-killed fungal cells significantly inhibits further killing activity of the medium. We next studied whether activation of SMS at the site of C. neoformans infection is dependent on T and NK cells. Using matrix-assisted laser desorption-ionization (MALDI tissue imaging in infected lung we found that similarly to previous observations in the isogenic wild type CBA/J mice, SM 16:0 levels are significantly elevated at the site of infection in mice lacking T and NK cells but only at early time points. This study highlights that C. neoformans may negatively regulate the killing activity of neutrophils and that SMS activation in neutrophils appears to be partially independent of T and/or NK cells.

  7. Neutrophil extracellular trap formation in supragingival biofilms.

    Science.gov (United States)

    Hirschfeld, Josefine; Dommisch, Henrik; Skora, Philipp; Horvath, Gabor; Latz, Eicke; Hoerauf, Achim; Waller, Tobias; Kawai, Toshihisa; Jepsen, Søren; Deschner, James; Bekeredjian-Ding, Isabelle

    2015-01-01

    Oral biofilms are the causative agents of the highly prevalent oral diseases periodontitis and caries. Additionally, the host immune response is thought to play a critical role in disease onset. Neutrophils are known to be a key host response factor to bacterial challenge on host surfaces. Release of neutrophil extracellular traps (NETs) as a novel antimicrobial defense strategy has gained increasing attention in the past years. Here, we investigated the influx of neutrophils into the dental plaque and the ability of oral bacteria to trigger intra-biofilm release of NETs and intracellular proteins. Supragingival biofilms and whole saliva were sampled from systemically healthy subjects participating in an experimental gingivitis study. Biofilms were analysed by immunofluorescence followed by confocal and fluorescence microscopy. Moreover, concentrations of cytokines and immune-associated proteins in biofilm suspensions and saliva were assessed by ELISA. Neutrophils obtained from blood were stimulated with twelve bacterial species isolated from cultured biofilms or with lipopolysaccharide to monitor NET formation. Neutrophils, NETs, neutrophil-associated proteins (myeloperoxidase, elastase-2, cathepsin G, cathelicidin LL-37), interleukin-8, interleukin-1β and tumor necrosis factor were detected within plaque samples and saliva. All tested bacterial species as well as the polymicrobial samples isolated from the plaque of each donor induced release of NETs and interleukin-8. The degree of NET formation varied among different subjects and did not correlate with plaque scores or clinical signs of local inflammation. Our findings indicate that neutrophils are attracted towards dental biofilms, in which they become incorporated and where they are stimulated by microbes to release NETs and immunostimulatory proteins. Thus, neutrophils and NETs may be involved in host biofilm control, although their specific role needs to be further elucidated. Moreover, inter

  8. Impact of maternal gestational diabetes on neutrophil functions of ...

    African Journals Online (AJOL)

    Ehab

    cell-mediated immunity and lower chemotactic activity of cord blood ... neonates born to gestational diabetic mothers on insulin during pregnancy and another 15 born to healthy ... 2) Flow cytometric assay of oxidative burst using. DHR 123:.

  9. Intravascular Ultrasound Imaging of Peripheral Arteries as an Adjunct to Balloon Angioplasty and Atherectomy

    International Nuclear Information System (INIS)

    Korogi, Yukunori; Hirai, Toshinori; Takahashi, Mutsumasa

    1996-01-01

    This article reviews many of the applications of intravascular ultrasound (US) imaging for peripheral arterial diseases. In vitro studies demonstrate an excellent correlation between ultrasound measurements of lumen and plaque crossectional area compared with histologic sections. In vivo clinical studies reveal the enhanced diagnostic capabilities of this technology compared with angiography. Intravascular US imaging can provide valuable information on the degree, eccentricity, and histologic type of stenosis before intervention, and on the morphological changes in the arterial wall and the extent of excision after intervention. Intravascular US may also serve as a superior index for gauging the diameter of balloon, stent, laser probe, and/or atherectomy catheter appropriate for a proposed intervention. Significant new insights into the mechanisms of balloon angioplasty and atherectomy have been established by intravascular US findings. Intravascular US imaging has been shown to be a more accurate method than angiography for determining the cross-sectional area of the arterial lumen, and for assessing severity of stenosis. Quantitative assessment of the luminal cross-sectional area after the balloon dilatation should be more accurate than angiography as intimal tears or dissections produced by the dilatation may not be accurately evaluated with angiography. At the present time, intravascular US is still a controversial imaging technique. Outcome studies are currently being organized to assess the clinical value and cost effectiveness of intravascular ultrasound in the context of these interventional procedures

  10. Design and implementation of an intravascular brachytherapy installation in cardiology

    International Nuclear Information System (INIS)

    Prieto, C.; Vano, E.; Fernandez, J.M.; Sabate, M.; Galvan, Y.C.

    2001-01-01

    Intravascular Brachytherapy (IVB) is a very promising technique for reducing restenosis rates. However, neither the exact absolute dose needed nor the optimal spatial and temporal distribution of dose inside the vessel wall for a successful treatment, nor the physical dosimetry of the various radioactive sources and devices for dose delivery, are well known. In this paper, an overview will be given of the design strategy, the dosimetric and radiation protection-related problems that we have met during the implementation of this technique at San Carlos hospital, adopted or foreseen solutions, and future research fields that we intend to carry out in order to reduce uncertainties and to achieve a deeper knowledge of the parameters that have an influence on the treatment. (author)

  11. Robust intravascular optical coherence elastography by line correlations

    International Nuclear Information System (INIS)

    Soest, Gijs van; Mastik, Frits; Jong, Nico de; Steen, Anton F W van der

    2007-01-01

    We present a new method for intravascular optical coherence elastography, which is robust against motion artefacts. It employs the correlation between adjacent lines, instead of subsequent frames. Pressure to deform the tissue is applied synchronously with the line scan rate of the optical coherence tomography (OCT) instrument. The viability of the method is demonstrated with a simulation study. We find that the root mean square (rms) error of the displacement estimate is 0.55 μm, and the rms error of the strain is 0.6%. It is shown that high-strain spots in the vessel wall, such as observed at the sites of vulnerable atherosclerotic lesions, can be detected with the technique

  12. Emerging Technology Update Intravascular Photoacoustic Imaging of Vulnerable Atherosclerotic Plaque.

    Science.gov (United States)

    Wu, Min; Fw van der Steen, Antonius; Regar, Evelyn; van Soest, Gijs

    2016-10-01

    The identification of vulnerable atherosclerotic plaques in the coronary arteries is emerging as an important tool for guiding atherosclerosis diagnosis and interventions. Assessment of plaque vulnerability requires knowledge of both the structure and composition of the plaque. Intravascular photoacoustic (IVPA) imaging is able to show the morphology and composition of atherosclerotic plaque. With imminent improvements in IVPA imaging, it is becoming possible to assess human coronary artery disease in vivo . Although some challenges remain, IVPA imaging is on its way to being a powerful tool for visualising coronary atherosclerotic features that have been specifically associated with plaque vulnerability and clinical syndromes, and thus such imaging might become valuable for clinical risk assessment in the catheterisation laboratory.

  13. Theoretical model of intravascular paramagnetic tracers effect on tissue relaxation

    DEFF Research Database (Denmark)

    Kjølby, Birgitte Fuglsang; Østergaard, Leif; Kiselev, Valerij G

    2006-01-01

    The concentration of MRI tracers cannot be measured directly by MRI and is commonly evaluated indirectly using their relaxation effect. This study develops a comprehensive theoretical model to describe the transverse relaxation in perfused tissue caused by intravascular tracers. The model takes...... into account a number of individual compartments. The signal dephasing is simulated in a semianalytical way by embedding Monte Carlo simulations in the framework of analytical theory. This approach yields a tool for fast, realistic simulation of the change in the transverse relaxation. The results indicate...... with bulk blood. The enhancement of relaxation in tissue is due to the contrast in magnetic susceptibility between blood vessels and parenchyma induced by the presence of paramagnetic tracer. Beyond the perfusion measurements, the results can be applied to quantitation of functional MRI and to vessel size...

  14. Evaluation of Disseminated Intravascular Coagulation in the Craniocerebral Traumas

    Directory of Open Access Journals (Sweden)

    Faruk Altinel

    2014-06-01

    Full Text Available Traumatic injury is one of the most important cause of disseminated intravascular coagulation (DIC. It occurs because of blood loss and hemodilution due to fluid resuscitation. The incidence of trauma associated DIC is mainly higher in the craniocerebral traumas. Even though craniocerebral trauma related DIC is well defined, the pathophysiology has been poorly characterized in the literature. Due to the fact that brain tissue is highly significant for procoagulant molecules, craniocerebral traumas are closely related to DIC. In the current study, 30 patients admitted to emergency room have been considered on the first and fifth day of admission to the hospital for the coagulation tests to evaluate DIC in both two groups. [Cukurova Med J 2014; 39(3.000: 488-495

  15. Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro

    Directory of Open Access Journals (Sweden)

    Alves Alessandra C

    1997-01-01

    Full Text Available In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE type III, IV and V on eosinophil chemotaxis triggered by platelet activating factor (PAF and leukotriene B4 (LTB4 in vitro. The effect of the analogues N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP and N2-2'-O- dibutyrylguanosine 3':5' cyclic monophosphate (Bt2 cyclic GMP has also been determined. The eosinophils were obtained from the peritoneal cavity of naive Wistar rats and purified in discontinuous Percoll gradients to 85-95% purity. We observed that pre-incubation of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4, in association with an increase in the intracellular levels of cyclic AMP. In contrast, neither zaprinast (type V inhibitor nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt2 cyclic AMP suppress the eosinophil chemotaxis, under conditions where Bt2 cyclic GMP was ineffective. We have concluded that inhibition of PDE IV, but not PDE III or V, was able to block the eosinophil chemotaxis in vitro, suggesting that the suppressive activity of selective PDE IV inhibitors on tissue eosinophil accumulation may, at least, be partially dependent on their ability to directly inhibit the eosinophil migration.

  16. Investigations into the design principles in the chemotactic behavior of Escherichia coli.

    Science.gov (United States)

    Kim, Tae-Hwan; Jung, Sung Hoon; Cho, Kwang-Hyun

    2008-01-01

    Inspired by the recent studies on the analysis of biased random walk behavior of Escherichia coli[Passino, K.M., 2002. Biomimicry of bacterial foraging for distributed optimization and control. IEEE Control Syst. Mag. 22 (3), 52-67; Passino, K.M., 2005. Biomimicry for Optimization, Control and Automation. Springer-Verlag, pp. 768-798; Liu, Y., Passino, K.M., 2002. Biomimicry of social foraging bacteria for distributed optimization: models, principles, and emergent behaviors. J. Optim. Theory Appl. 115 (3), 603-628], we have developed a model describing the motile behavior of E. coli by specifying some simple rules on the chemotaxis. Based on this model, we have analyzed the role of some key parameters involved in the chemotactic behavior to unravel the underlying design principles. By investigating the target tracking capability of E. coli in a maze through computer simulations, we found that E. coli clusters can be controlled as target trackers in a complex micro-scale-environment. In addition, we have explored the dynamical characteristics of this target tracking mechanism through perturbation of parameters under noisy environments. It turns out that the E. coli chemotaxis mechanism might be designed such that it is sensitive enough to efficiently track the target and also robust enough to overcome environmental noises.

  17. The actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

    Science.gov (United States)

    Westendorf, Christian; Negrete, Jose, Jr.; Bae, Albert; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

    2013-03-01

    We report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. The averaged F-actin response of many cells to a short-time pulse of cAMP is reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. We systematically exposed a large number of cells to periodic pulse trains. The results indicate a resonance peak at periodic inputs of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the actin regulatory network. To quantitatively test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and Aip1. These served as markers of the F-actin disassembly process and thus allow us to estimate the delay time. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed experimentally. Financial support by the Max-Planck Society and the DFG (SFB 937).

  18. Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques

    International Nuclear Information System (INIS)

    Jang, Moon Kyoo; Kim, Ji Young; Jeoung, Nam Ho; Kang, Mi Ae; Choi, Myung-Sook; Oh, Goo Taeg; Nam, Kyung Tak; Lee, Won-Ha; Park, Yong Bok

    2004-01-01

    Genes induced or suppressed by oxidized low-density lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using the differential display reverse transcriptase polymerase chain reaction. One of the differentially expressed (up-regulated) cDNA fragments was found to contain sequences corresponding to monocyte chemotactic protein-3 (MCP-3). The stimulatory effect of the oxLDL on the expression of MCP-3 mRNA was both time- and dose-dependent. Treatment with GF109203X and genistein, inhibitors of protein kinase C and tyrosine kinase, respectively, had no effect on the induction of MCP-3 mRNA by oxLDL, while treatment with cycloheximide inhibited the induction. The induction was reproduced by the lipid components in oxLDL such as 9-HODE and 13-HODE, which are known to activate the peroxisome proliferator-activated receptor γ (PPARγ). Introduction of an endogenous PPARγ ligand, 15d-PGJ2, in the culture of THP-1 cells resulted in the induction of MCP-3 gene expression. Furthermore, analyses of human atherosclerotic plaques revealed that the expressional pattern of MCP-3 in the regions of neointimal and necrotic core overlapped with that of PPARγ. These results suggest that oxLDL delivers its signal for MCP-3 expression via PPARγ, which may be further related to the atherogenesis

  19. Squid-derived chitin oligosaccharides are a chemotactic signal during colonization by Vibrio fischeri.

    Science.gov (United States)

    Mandel, Mark J; Schaefer, Amy L; Brennan, Caitlin A; Heath-Heckman, Elizabeth A C; Deloney-Marino, Cindy R; McFall-Ngai, Margaret J; Ruby, Edward G

    2012-07-01

    Chitin, a polymer of N-acetylglucosamine (GlcNAc), is noted as the second most abundant biopolymer in nature. Chitin serves many functions for marine bacteria in the family Vibrionaceae ("vibrios"), in some instances providing a physical attachment site, inducing natural genetic competence, and serving as an attractant for chemotaxis. The marine luminous bacterium Vibrio fischeri is the specific symbiont in the light-emitting organ of the Hawaiian bobtail squid, Euprymna scolopes. The bacterium provides the squid with luminescence that the animal uses in an antipredatory defense, while the squid supports the symbiont's nutritional requirements. V. fischeri cells are harvested from seawater during each host generation, and V. fischeri is the only species that can complete this process in nature. Furthermore, chitin is located in squid hemocytes and plays a nutritional role in the symbiosis. We demonstrate here that chitin oligosaccharides produced by the squid host serve as a chemotactic signal for colonizing bacteria. V. fischeri uses the gradient of host chitin to enter the squid light organ duct and colonize the animal. We provide evidence that chitin serves a novel function in an animal-bacterial mutualism, as an animal-produced bacterium-attracting synomone.

  20. Plant-Adapted Escherichia coli Show Increased Lettuce Colonizing Ability, Resistance to Oxidative Stress and Chemotactic Response

    Science.gov (United States)

    Dublan, Maria de los Angeles; Ortiz-Marquez, Juan Cesar Federico; Lett, Lina; Curatti, Leonardo

    2014-01-01

    Background Escherichia coli is a widespread gut commensal and often a versatile pathogen of public health concern. E. coli are also frequently found in different environments and/or alternative secondary hosts, such as plant tissues. The lifestyle of E. coli in plants is poorly understood and has potential implications for food safety. Methods/Principal Findings This work shows that a human commensal strain of E. coli K12 readily colonizes lettuce seedlings and produces large microcolony-like cell aggregates in leaves, especially in young leaves, in proximity to the vascular tissue. Our observations strongly suggest that those cell aggregates arise from multiplication of single bacterial cells that reach those spots. We showed that E. coli isolated from colonized leaves progressively colonize lettuce seedlings to higher titers, suggesting a fast adaptation process. E. coli cells isolated from leaves presented a dramatic rise in tolerance to oxidative stress and became more chemotactic responsive towards lettuce leaf extracts. Mutant strains impaired in their chemotactic response were less efficient lettuce colonizers than the chemotactic isogenic strain. However, acclimation to oxidative stress and/or minimal medium alone failed to prime E. coli cells for enhanced lettuce colonization efficiency. Conclusion/Significance These findings help to understand the physiological adaptation during the alternative lifestyle of E. coli in/on plant tissues. PMID:25313845

  1. Neutrophils in Cancer: Two Sides of the Same Coin.

    Science.gov (United States)

    Uribe-Querol, Eileen; Rosales, Carlos

    2015-01-01

    Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

  2. Neutrophils in Cancer: Two Sides of the Same Coin

    Directory of Open Access Journals (Sweden)

    Eileen Uribe-Querol

    2015-01-01

    Full Text Available Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

  3. Superoxide anion production by human neutrophils activated by Trichomonas vaginalis.

    Science.gov (United States)

    Song, Hyun-Ouk; Ryu, Jae-Sook

    2013-08-01

    Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis.

  4. Hemostasia normal y coagulación intravascular diseminada en obstetricia Normal hemostasis and disseminated intravascular clotting in Obstetrics

    Directory of Open Access Journals (Sweden)

    Danilo Nápoles Méndez

    2012-03-01

    Full Text Available En el período gravido - puerperal, la coagulación sanguínea sufre cambios que se impone conocer para interpretar correctamente esos trastornos cuando se presentan en esta etapa, teniendo en cuenta las posibles complicaciones y el peligro para la vida que pueden presentarse. El objetivo del presente artículo es proporcionar a los obstetras una revisión bibliográfica que les permita actualizarse acerca del tema y facilite su modo de actuación ante pacientes con coagulación intravascular diseminada. Se concluye que es preciso diagnosticar tempranamente el proceso en la fase bioquímica de bajo grado y aplicar en las féminas el tratamiento expedito de la enfermedad de base para eliminar las complicaciones o disminuir su ocurrenciaIn the period from pregnancy to puerperium, blood clotting suffers changes which are important to be known in order to interpret correctly those dysfunctions when they appear in this stage, keeping in mind the possible complications and the danger for life which can take place. The objective of the present work is to provide the obstetricians a literature review that allows them to be updated about the topic and facilitate their performance in case of patients with disseminated intravascular clotting. It is concluded that it is necessary to have an early diagnosis on the process during the low grade biochemical phase and to apply in these women the expedite treatment of the base disease to eliminate complications or to decrease their occurrence.

  5. Local intravascular coagulation and fibrin deposition on intestinal ischemia-reperfusion in rats

    NARCIS (Netherlands)

    Schoots, Ivo G.; Levi, Marcel; Roossink, E. H. Paulina; Bijlsma, Pieter B.; van Gulik, Thomas M.

    2003-01-01

    Background. This study investigates intravascular coagulation and thrombotic obstruction in the splanchnic vasculature after intestinal ischemia in relation to epithelial integrity and function. Methods. Intestinal ischemia was induced in rats by superior mesenteric artery occlusion for 20 or 40

  6. Intravascular radiation for restenosis prevention: could it be the holy grail?

    International Nuclear Information System (INIS)

    King, S.B.

    1996-01-01

    This brief editorial discusses the use of intravascular radiation in preventing restenosis after angioplasty in coronary interventions. Results in porcine coronary arteries and clinical applications are briefly reported. (UK)

  7. New treatment strategies for disseminated intravascular coagulation based on current understanding of the pathophysiology

    NARCIS (Netherlands)

    Levi, Marcel; de Jonge, Evert; van der Poll, Tom

    2004-01-01

    A variety of clinical conditions may cause systemic activation of coagulation, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). DIC consists of a widespread, systemic activation of coagulation, resulting in diffuse fibrin deposition in small and

  8. Neutrophil Leukocyte: Combustive Microbicidal Action and Chemiluminescence

    Directory of Open Access Journals (Sweden)

    Robert C. Allen

    2015-01-01

    Full Text Available Neutrophil leukocytes protect against a varied and complex array of microbes by providing microbicidal action that is simple, potent, and focused. Neutrophils provide such action via redox reactions that change the frontier orbitals of oxygen (O2 facilitating combustion. The spin conservation rules define the symmetry barrier that prevents direct reaction of diradical O2 with nonradical molecules, explaining why combustion is not spontaneous. In burning, the spin barrier is overcome when energy causes homolytic bond cleavage producing radicals capable of reacting with diradical O2 to yield oxygenated radical products that further participate in reactive propagation. Neutrophil mediated combustion is by a different pathway. Changing the spin quantum state of O2 removes the symmetry restriction to reaction. Electronically excited singlet molecular oxygen (O2*1 is a potent electrophilic reactant with a finite lifetime that restricts its radius of reactivity and focuses combustive action on the target microbe. The resulting exergonic dioxygenation reactions produce electronically excited carbonyls that relax by light emission, that is, chemiluminescence. This overview of neutrophil combustive microbicidal action takes the perspectives of spin conservation and bosonic-fermionic frontier orbital considerations. The necessary principles of particle physics and quantum mechanics are developed and integrated into a fundamental explanation of neutrophil microbicidal metabolism.

  9. The Incidence of Intravascular Needle Entrance during Inferior Alveolar Nerve Block Injection.

    Science.gov (United States)

    Taghavi Zenouz, Ali; Ebrahimi, Hooman; Mahdipour, Masoumeh; Pourshahidi, Sara; Amini, Parisa; Vatankhah, Mahdi

    2008-01-01

    Dentists administer thousands of local anesthetic injections every day. Injection to a highly vascular area such as pterygomandibular space during an inferior alveolar nerve block has a high risk of intravascular needle entrance. Accidental intravascular injection of local anesthetic agent with vasoconstrictor may result in cardiovascular and central nervous system toxicity, as well as tachycardia and hypertension. There are reports that indicate aspiration is not performed in every injection. The aim of the present study was to assess the incidence of intravascular needle entrance in inferior alveolar nerve block injections. Three experienced oral and maxillofacial surgeons performed 359 inferior alveolar nerve block injections using direct or indirect techniques, and reported the results of aspiration. Aspirable syringes and 27 gauge long needles were used, and the method of aspiration was similar in all cases. Data were analyzed using t-test. 15.3% of inferior alveolar nerve block injections were aspiration positive. Intravascular needle entrance was seen in 14.2% of cases using direct and 23.3% of cases using indirect block injection techniques. Of all injections, 15.8% were intravascular on the right side and 14.8% were intravascular on the left. There were no statistically significant differences between direct or indirect block injection techniques (P = 0.127) and between right and left injection sites (P = 0.778). According to our findings, the incidence of intravascular needle entrance during inferior alveolar nerve block injection was relatively high. It seems that technique and maneuver of injection have no considerable effect in incidence of intravascular needle entrance.

  10. The Incidence of Intravascular Needle Entrance during Inferior Alveolar Nerve Block Injection

    Directory of Open Access Journals (Sweden)

    Sara Pourshahidi

    2008-04-01

    Full Text Available

    Background and aims. Dentists administer thousands of local anesthetic injections every day. Injection to a highly vascular area such as pterygomandibular space during an inferior alveolar nerve block has a high risk of intravascular needle entrance. Accidental intravascular injection of local anesthetic agent with vasoconstrictor may result in cardiovascular and central nervous system toxicity, as well as tachycardia and hypertension. There are reports that indicate aspiration is not performed in every injection. The aim of the present study was to assess the incidence of intravascular needle entrance in inferior alveolar nerve block injections.

    Materials and methods. Three experienced oral and maxillofacial surgeons performed 359 inferior alveolar nerve block injections using direct or indirect techniques, and reported the results of aspiration. Aspirable syringes and 27 gauge long needles were used, and the method of aspiration was similar in all cases. Data were analyzed using t-test.

    Results. 15.3% of inferior alveolar nerve block injections were aspiration positive. Intravascular needle entrance was seen in 14.2% of cases using direct and 23.3% of cases using indirect block injection techniques. Of all injections, 15.8% were intravascular on the right side and 14.8% were intravascular on the left. There were no statistically significant differences between direct or indirect block injection techniques (P = 0.127 and between right and left injection sites (P = 0.778.

    Conclusion. According to our findings, the incidence of intravascular needle entrance during inferior alveolar nerve block injection was relatively high. It seems that technique and maneuver of injection have no considerable effect in incidence of intravascular needle entrance.

  11. Gallium SPECT detection of neoplastic intravascular obstruction of the superior vena cava

    International Nuclear Information System (INIS)

    Swayne, L.C.; Kaplan, I.L.

    1989-01-01

    A rare case of an intravascular neoplastic obstruction of the superior vena cava is discussed. The lesion was detected with gallium single photon emission computed tomography (SPECT) despite a normal appearance on a concurrent radiographic CT study. A computer-generated composite SPECT-CT image confirmed the intravascular localization of the radioisotope, and a subsequent CT-guided transthoracic needle biopsy revealed a poorly differentiated adenocarcinoma

  12. Phospholipase D catalyzes phospholipid metabolism in chemotactic peptide-stimulated HL-60 granulocytes

    International Nuclear Information System (INIS)

    Pai, J.K.; Siegel, M.I.; Egan, R.W.; Billah, M.M.

    1988-01-01

    There exists circumstantial evidence for activation of phospholipase D (PLD) in intact cells. However, because of the complexity of phospholipid remodeling processes, it is essential to distinguish PLD clearly from other phospholipases and phospholipid remodeling enzymes. Therefore, to establish unequivocally PLD activity in dimethyl sulfoxide-differentiated HL-60 granulocytes, to demonstrate the relative contribution of PLD to phospholipid turnover, and to validate the hypothesis that the formation of phosphatidylethanol is an expression of PLD-catalyzed transphosphatidylation, we have developed methodologies to label HL-60 granulocytes in 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkyl-PC) with 32P without labeling cellular ATP. These methodologies involve (a) synthesis of alkyl-lysoPC containing 32P by a combination of enzymatic and chemical procedures and (b) incubation of HL-60 granulocytes with this alkyl-[32P] lysoPC which enters the cell and becomes acylated into membrane-associated alkyl-[32P]PC. Upon stimulation of these 32P-labeled cells with the chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP), alkyl-[32P]phosphatidic acid (alkyl-[32P]PA) is formed rapidly. Because, under these conditions, cellular ATP has not been labeled with 32P, alkyl-[32P]PA must be formed via PLD-catalyzed hydrolysis of alkyl-[32P]PC at the terminal phosphodiester bond. This result conclusively demonstrates fMLP-induced activation of PLD in HL-60 granulocytes. These 32P-labeled HL-60 granulocytes have also been stimulated in the presence of ethanol to produce alkyl-[32P]phosphatidylethanol (alkyl-[32P]PEt). Formation of alkyl-[32P]PEt parallels that of alkyl-[32P]PA with respect to time course, fMLP concentration, inhibition by a specific fMLP antagonist (t-butoxycarbonyl-Met-Leu-Phe), and Ca2+ concentration

  13. Actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

    Science.gov (United States)

    Westendorf, Christian; Negrete, Jose; Bae, Albert J.; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

    2013-01-01

    The rapid reorganization of the actin cytoskeleton in response to external stimuli is an essential property of many motile eukaryotic cells. Here, we report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. When averaging the actin response of many cells to a short pulse of the chemoattractant cAMP, we observed a transient accumulation of cortical actin reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. To substantiate that an oscillatory mechanism governs the actin dynamics in these cells, we systematically exposed a large number of cells to periodic pulse trains of different frequencies. Our results indicate a resonance peak at a stimulation period of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the regulatory network of the actin system. To test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and actin-interacting protein 1, as well as knockout mutants that lack Coronin and actin-interacting protein 1. These actin-binding proteins enhance the disassembly of actin filaments and thus allow us to estimate the delay time in the regulatory feedback loop. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed in our periodic stimulation experiments. PMID:23431176

  14. Local Delivery Is Critical for Monocyte Chemotactic Protein-1 Mediated Site-Specific Murine Aneurysm Healing.

    Science.gov (United States)

    Hourani, Siham; Motwani, Kartik; Wajima, Daisuke; Fazal, Hanain; Jones, Chad H; Doré, Sylvain; Hosaka, Koji; Hoh, Brian L

    2018-01-01

    Local delivery of monocyte chemotactic protein-1 (MCP-1/CCL2) via our drug-eluting coil has been shown to promote intrasaccular aneurysm healing via an inflammatory pathway. In this study, we validate the importance of local MCP-1 in murine aneurysm healing. Whether systemic, rather than local, delivery of MCP-1 can direct site-specific aneurysm healing has significant translational implications. If systemic MCP-1 is effective, then MCP-1 could be administered as a pill rather than by endovascular procedure. Furthermore, we confirm that MCP-1 is the primary effector in our MCP-1 eluting coil-mediated murine aneurysm healing model. We compare aneurysm healing with repeated intraperitoneal MCP-1 versus vehicle injection, in animals with control poly(lactic-co-glycolic) acid (PLGA)-coated coils. We demonstrate elimination of the MCP-1-associated tissue-healing response by knockout of MCP-1 or CCR2 (MCP-1 receptor) and by selectively inhibiting MCP-1 or CCR2. Using immunofluorescent probing, we explore the cell populations found in healed aneurysm tissue following each intervention. Systemically administered MCP-1 with PLGA coil control does not produce comparable aneurysm healing, as seen with MCP-1 eluting coils. MCP-1-directed aneurysm healing is eliminated by selective inhibition of MCP-1 or CCR2 and in MCP-1-deficient or CCR2-deficient mice. No difference was detected in M2 macrophage and myofibroblast/smooth muscle cell staining with systemic MCP-1 versus vehicle in aneurysm wall, but a significant increase in these cell types was observed with MCP-1 eluting coil implant and attenuated by MCP-1/CCR2 blockade or deficiency. We show that systemic MCP-1 concurrent with PLGA-coated platinum coil implant is not sufficient to produce site-specific aneurysm healing. MCP-1 is a critical, not merely complementary, actor in the aneurysm healing pathway.

  15. Effector CD4+ T cells recognize intravascular antigen presented by patrolling monocytes.

    Science.gov (United States)

    Westhorpe, Clare L V; Norman, M Ursula; Hall, Pam; Snelgrove, Sarah L; Finsterbusch, Michaela; Li, Anqi; Lo, Camden; Tan, Zhe Hao; Li, Songhui; Nilsson, Susan K; Kitching, A Richard; Hickey, Michael J

    2018-02-21

    Although effector CD4 + T cells readily respond to antigen outside the vasculature, how they respond to intravascular antigens is unknown. Here we show the process of intravascular antigen recognition using intravital multiphoton microscopy of glomeruli. CD4 + T cells undergo intravascular migration within uninflamed glomeruli. Similarly, while MHCII is not expressed by intrinsic glomerular cells, intravascular MHCII-expressing immune cells patrol glomerular capillaries, interacting with CD4 + T cells. Following intravascular deposition of antigen in glomeruli, effector CD4 + T-cell responses, including NFAT1 nuclear translocation and decreased migration, are consistent with antigen recognition. Of the MHCII + immune cells adherent in glomerular capillaries, only monocytes are retained for prolonged durations. These cells can also induce T-cell proliferation in vitro. Moreover, monocyte depletion reduces CD4 + T-cell-dependent glomerular inflammation. These findings indicate that MHCII + monocytes patrolling the glomerular microvasculature can present intravascular antigen to CD4 + T cells within glomerular capillaries, leading to antigen-dependent inflammation.

  16. Neutrophils in Homeostasis, Immunity, and Cancer.

    Science.gov (United States)

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

    KAUST Repository

    Zhu, Jiang; Zhang, Huoming; Guo, Tiannan; Li, Wenying; Li, Huiyu; Zhu, Yi; Huang, Shiang

    2014-01-01

    Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. GROUP B STREPTOCOCCUS CIRCUMVENTS NEUTROPHILS AND NEUTROPHIL EXTRACELLULAR TRAPS DURING AMNIOTIC CAVITY INVASION AND PRETERM LABOR

    Science.gov (United States)

    Boldenow, Erica; Gendrin, Claire; Ngo, Lisa; Bierle, Craig; Vornhagen, Jay; Coleman, Michelle; Merillat, Sean; Armistead, Blair; Whidbey, Christopher; Alishetti, Varchita; Santana-Ufret, Veronica; Ogle, Jason; Gough, Michael; Srinouanprachanh, Sengkeo; MacDonald, James W; Bammler, Theo K; Bansal, Aasthaa; Liggitt, H. Denny; Rajagopal, Lakshmi; Waldorf, Kristina M Adams

    2016-01-01

    Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with the majority of early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B Streptococci (GBS) are β-hemolytic, gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases. To understand temporal events that occur during MIAC, we utilized a unique chronically catheterized nonhuman primate model that closely emulates human pregnancy. This model allows monitoring of uterine contractions, timing of MIAC and immune responses during pregnancy-associated infections. Here, we show that adverse outcomes such as preterm labor, MIAC, and fetal sepsis were observed more frequently during infection with hemolytic GBS when compared to nonhemolytic GBS. Although MIAC was associated with systematic progression in chorioamnionitis beginning with chorionic vasculitis and progressing to neutrophilic infiltration, the ability of the GBS hemolytic pigment toxin to induce neutrophil cell death and subvert killing by neutrophil extracellular traps (NETs) in placental membranes in vivo facilitated MIAC and fetal injury. Furthermore, compared to maternal neutrophils, fetal neutrophils exhibit decreased neutrophil elastase activity and impaired phagocytic functions to GBS. Collectively, our studies demonstrate how a unique bacterial hemolytic lipid toxin enables GBS to circumvent neutrophils and NETs in placental membranes to induce fetal injury and preterm labor. PMID:27819066

  19. Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

    KAUST Repository

    Zhu, Jiang

    2014-06-11

    Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. MRI phenotypes of localized intravascular coagulopathy in venous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Kevin S.H. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Dowd, Christopher F.; Hess, Christopher P. [University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Mathes, Erin F.; Frieden, Ilona J. [University of California, San Francisco, Department of Dermatology, San Francisco, CA (United States); Rosbe, Kristina W. [University of California, San Francisco, Department of Otolaryngology, San Francisco, CA (United States); Hoffman, William Y. [University of California, San Francisco, Department of Surgery, San Francisco, CA (United States)

    2015-10-15

    The incidence of localized intravascular coagulopathy (LIC) in venous malformations varies with lesion size and location, as well as the presence of palpable phleboliths. The development of LIC can cause pain and hemorrhage and can progress to disseminated intravascular coagulopathy (DIC) and thromboembolic disease resulting in death in some cases. Early recognition of LIC can relieve symptoms and prevent progression to life-threatening complications. The aim of this work was to identify MRI features of venous malformation associated with LIC. We hypothesized that venous malformations with larger capacitance, slower flow and less physiological compression (greater stasis) were more likely to be associated with LIC. In this HIPAA-compliant and IRB-approved study, we retrospectively reviewed clinical records and MRI for consecutive patients undergoing evaluation of venous malformations at our multidisciplinary Birthmarks and Vascular Anomalies Center between 2003 and 2013. Inclusion required consensus diagnosis of venous malformation and availability of laboratory data and MRI; patients on anticoagulation or those previously undergoing surgical or endovascular treatment were excluded. LIC was diagnosed when D-dimer exceeded 1,000 ng/mL and/or fibrinogen was less than 200 mg/dL. Two board-certified radiologists assessed the following MRI features for each lesion: morphology (spongiform vs. phlebectatic), presence of phleboliths, size, location (truncal vs. extremity), and tissue type(s) involved (subcutis, muscle, bone and viscera). Univariate logistic regression analyses were used to test associations between LIC and MRI findings, and stepwise regression was applied to assess the significance of the individual imaging predictors. Seventy patients, 37 with LIC, met inclusion criteria during the 10-year study period (age: 14.5 +/- 13.6 years [mean +/- standard deviation]; 30 male, 40 female). Both elevated D-dimer and low fibrinogen were associated with the presence of

  1. MRI phenotypes of localized intravascular coagulopathy in venous malformations

    International Nuclear Information System (INIS)

    Koo, Kevin S.H.; Dowd, Christopher F.; Hess, Christopher P.; Mathes, Erin F.; Frieden, Ilona J.; Rosbe, Kristina W.; Hoffman, William Y.

    2015-01-01

    The incidence of localized intravascular coagulopathy (LIC) in venous malformations varies with lesion size and location, as well as the presence of palpable phleboliths. The development of LIC can cause pain and hemorrhage and can progress to disseminated intravascular coagulopathy (DIC) and thromboembolic disease resulting in death in some cases. Early recognition of LIC can relieve symptoms and prevent progression to life-threatening complications. The aim of this work was to identify MRI features of venous malformation associated with LIC. We hypothesized that venous malformations with larger capacitance, slower flow and less physiological compression (greater stasis) were more likely to be associated with LIC. In this HIPAA-compliant and IRB-approved study, we retrospectively reviewed clinical records and MRI for consecutive patients undergoing evaluation of venous malformations at our multidisciplinary Birthmarks and Vascular Anomalies Center between 2003 and 2013. Inclusion required consensus diagnosis of venous malformation and availability of laboratory data and MRI; patients on anticoagulation or those previously undergoing surgical or endovascular treatment were excluded. LIC was diagnosed when D-dimer exceeded 1,000 ng/mL and/or fibrinogen was less than 200 mg/dL. Two board-certified radiologists assessed the following MRI features for each lesion: morphology (spongiform vs. phlebectatic), presence of phleboliths, size, location (truncal vs. extremity), and tissue type(s) involved (subcutis, muscle, bone and viscera). Univariate logistic regression analyses were used to test associations between LIC and MRI findings, and stepwise regression was applied to assess the significance of the individual imaging predictors. Seventy patients, 37 with LIC, met inclusion criteria during the 10-year study period (age: 14.5 +/- 13.6 years [mean +/- standard deviation]; 30 male, 40 female). Both elevated D-dimer and low fibrinogen were associated with the presence of

  2. Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

    Science.gov (United States)

    Kamoshida, Go; Kikuchi-Ueda, Takane; Nishida, Satoshi; Tansho-Nagakawa, Shigeru; Ubagai, Tsuneyuki; Ono, Yasuo

    2018-01-01

    Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs), has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA), and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections. PMID:29467765

  3. Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

    Directory of Open Access Journals (Sweden)

    Go Kamoshida

    2018-02-01

    Full Text Available Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs, has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA, and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections.

  4. Phenotypic Diversity and Plasticity in Circulating Neutrophil Subpopulations in Cancer

    Directory of Open Access Journals (Sweden)

    Jitka Y. Sagiv

    2015-02-01

    Full Text Available Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs. LDNs consist of both immature myeloid-derived suppressor cells (MDSCs and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.

  5. Production of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta by human polymorphonuclear neutrophils stimulated with Porphyromonas endodontalis lipopolysaccharide.

    Science.gov (United States)

    Ko, Hyun Jung; Lim, Sung Sam

    2002-11-01

    This study was undertaken to investigate the capacity of polymorphonuclear neutrophils (PMNs) to secrete Macrophage Inflammatory Protein (MIP)-1alpha and MIP-1beta after stimulation with Porphyromonas endodontalis lipopolysaccharide (LPS). Escherichia coli LPS was used as a positive control. Venous blood was collected and PMNs were isolated from healthy volunteers. Cells were cultured with various concentrations of LPS for different periods of time. Cell supernatants were assayed by enzyme-linked immunosorbent assay. The levels of chemokine secretion in PMNs stimulated with each LPS were found to be significantly higher than in the unstimulated control cells (p endodontalis LPS. These findings demonstrated that P. endodontalis LPS is capable of stimulating PMNs to produce chemotactic cytokines and suggested that PMNs stimulated with P. endodontalis LPS may play a crucial role in the inflammatory and immunopathological reactions of pulpal and periapical diseases.

  6. Renal Sympathetic Denervation System via Intraluminal Ultrasonic Ablation: Therapeutic Intravascular Ultrasound Design and Preclinical Evaluation.

    Science.gov (United States)

    Chernin, Gil; Szwarcfiter, Iris; Bausback, Yvonne; Jonas, Michael

    2017-05-01

    To assess the safety and performance of a nonfocused and nonballooned ultrasonic (US) catheter-based renal sympathetic denervation (RDN) system in normotensive swine. RDN with the therapeutic intravascular US catheter was evaluated in 3 experiments: (i) therapeutic intravascular US RDN vs a control group of untreated animals with follow-up of 30, 45, and 90 days (n = 6; n = 12 renal arteries for each group); (ii) therapeutic intravascular US RDN vs radiofrequency (RF) RDN in the contralateral artery in the same animal (n = 2; n = 4 renal arteries); and (iii) therapeutic intravascular US RDN in a recently stent-implanted renal artery (n = 2; n = 4 renal arteries). In the first experiment, therapeutic intravascular US RDN was safe, without angiographic evidence of dissection or renal artery stenosis. Neuronal tissue vacuolization, nuclei pyknosis, and perineuronal inflammation were evident after RDN, without renal artery wall damage. Norepinephrine levels were significantly lower after therapeutic intravascular US RDN after 30, 45, and 90 days compared with the control group (200.17 pg/mg ± 63.35, 184.75 pg/mg ± 44.51, and 203.43 pg/mg ± 58.54, respectively, vs 342.42 pg/mg ± 79.97). In the second experiment, deeper neuronal ablation penetrance was found with therapeutic intravascular US RDN vs RF RDN (maximal penetrance from endothelium of 7.0 mm vs 3.5 mm, respectively). There was less damage to the artery wall after therapeutic intravascular US RDN than with RF RDN, after which edema and injured endothelium were seen. In the third experiment, denervation inside the stent-implanted segments was feasible without damage to the renal artery wall or stent. The therapeutic intravascular US system performed safely and reduced norepinephrine levels. Deeper penetrance and better preservation of vessel wall were observed with therapeutic intravascular US RDN vs RF RDN. Neuronal ablations were observed in stent-implanted renal arteries. Copyright © 2017 SIR. Published

  7. Heartbeat OCT: in vivo intravascular megahertz-optical coherence tomography

    Science.gov (United States)

    Wang, Tianshi; Pfeiffer, Tom; Regar, Evelyn; Wieser, Wolfgang; van Beusekom, Heleen; Lancee, Charles T.; Springeling, Geert; Krabbendam, Ilona; van der Steen, Antonius F.W.; Huber, Robert; van Soest, Gijs

    2015-01-01

    Cardiac motion artifacts, non-uniform rotational distortion and undersampling affect the image quality and the diagnostic impact of intravascular optical coherence tomography (IV-OCT). In this study we demonstrate how these limitations of IV-OCT can be addressed by using an imaging system that we called “Heartbeat OCT”, combining a fast Fourier Domain Mode Locked laser, fast pullback, and a micromotor actuated catheter, designed to examine a coronary vessel in less than one cardiac cycle. We acquired in vivo data sets of two coronary arteries in a porcine heart with both Heartbeat OCT, working at 2.88 MHz A-line rate, 4000 frames/s and 100 mm/s pullback speed, and with a commercial system. The in vivo results show that Heartbeat OCT provides faithfully rendered, motion-artifact free, fully sampled vessel wall architecture, unlike the conventional IV-OCT data. We present the Heartbeat OCT system in full technical detail and discuss the steps needed for clinical translation of the technology. PMID:26713214

  8. A Micromotor Catheter for Intravascular Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Tianshi Wang

    2015-03-01

    Full Text Available We have developed a new form of intravascular optical coherence tomography (IV-OCT that allows the extremely fast acquisition of high-resolution images of the coronary arteries. This process leads to much better image quality by eliminating cardiac motion artefacts and undersampling. It relies on a catheter that incorporates a synchronous micromotor with a diameter of 1.0 mm and a rotational speed of up to 5600 revolutions per second, enabling an IV-OCT frame rate of 5.6 kHz. This speed is matched by a wavelength-swept laser that generates up to 2.8 million image lines per second. With this setup, our team achieved IV-OCT imaging of up to 5600 frames per second (fps in vitro and 4000 fps in vivo, deployed at a 100 mm·s−1 pullback velocity. The imaging session is triggered by the electrocardiogram of the subject, and can scan a coronary artery in the phase of the heartbeat where the heart is at rest, providing a name for this new technology: the “Heartbeat OCT.”

  9. Intravascular trans-catheter fibrinolysis in acute arterial obstructions

    International Nuclear Information System (INIS)

    Roversi, R.; Rossi, C.; Ricci, S.; Gemelli, G.; Ciliberti, M.A.

    1987-01-01

    The author's experiences is reported on intravascular fibrinolytic therapy with urokinase in acute arterial obstructions. Thirty-eight patients were treated, from 1983 to 1986, for acute thrombosis and/or thromboembolization, 22 of which developed on an atherosclerotic lesion, and 10 on a surgical stenotic by-pass graft. A complete vascular recanalization has been obtained, at the end of the procedure, in 69,4% of the cases, 77,7% had a definite final clinical improvement. The results correspond to the medium statistical of the various casistics analyzed for comparison. Surgery has been performed on 27,7% of the patients. Complication have been observed in 8% of the cases. IAF technique is of greatest value in the treatment of those lesions; better results have been obtained with intra-thrombus injection of the drug (as emphasized by many authors) in association with PTA and surgery. A close cooperation between interventional radiology, vascular surgery and angiology is therefore necessary in this field

  10. Primary intravascular large B-cell lymphoma of pituitary

    Directory of Open Access Journals (Sweden)

    K R Anila

    2012-01-01

    Full Text Available A 68-year-old retired nurse, who was a known hypertensive on medication, presented with prolonged fever of 2-month duration without any clinical evidence of infection. On examination she had altered mental status. She also had other nonspecific complaints such as sleep disturbances, loss of weight, etc. On investigation, she was found to have anemia, thrombocytopenia, raised erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and lactate dehydrogenase (LDH values. She also had electrolyte imbalance. Radiological evaluation of brain showed mass lesion in the sella turcica, suggestive of pituitary adenoma. Biochemical evaluation showed hypopituitarism. Trans-sphenoidal biopsy was done. Based on histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma (IVLBCL of pituitary was made. Our patient′s condition deteriorated rapidly and she succumbed to her illness before therapy could be initiated. We are reporting this case because of the rare subtype of large B-cell lymphoma presenting at an extremely unusual primary site.

  11. Intravascular ultrasound based dose assessment in endovascular brachytherapy

    International Nuclear Information System (INIS)

    Catalano, Gianpiero; Tamburini, Vittorio; Colombo, Antonio; Nishida, Takahiro; Parisi, Giovanni; Mazzetta, Chiara; Orecchia, Roberto

    2003-01-01

    Background: the role of endovascular brachytherapy in restenosis prevention is well documented. Dose is usually prescribed at a fixed distance from the source axis by angiographic quantification of vessel diameter. Recently, intravascular ultrasound (IVUS) was introduced in dose prescription, allowing a better evaluation of the vessel anatomy. This study retrospectively explores the difference between prescription following angiographic vessel sizing and delivered dose calculated with IVUS. Methods and results: Seventeen lesions were studied with IVUS, identifying on irradiated segment, three sections on which measuring minimal and maximal distance from the centre of IVUS catheter to the adventitia; using dedicated software, corresponding doses were calculated. The dose ranged widely, with maximal and minimal values of 71.6 and 4.9 Gy; furthermore, heterogeneity in dose among different sections was observed. In the central section, the maximal dose was 206% of the one prescribed with the QCA model at 2 mm from the source axis, while the minimal dose was 96%. In proximal and distal sections, respective values were 182, 45, 243, and 122%. Conclusions: Our analysis confirmed the dose inhomogeneity delivered with an angiographic fixed-dose prescription strategy. A dose variation was found along the irradiated segment due to the differences in vessel thickness. IVUS emerged as an important tool in endovascular brachytherapy, especially for irregular-shaped vessels

  12. Intravascular ultrasound assessed incomplete stent apposition and stent fracture in stent thrombosis after bare metal versus drug-eluting stent treatment the Nordic Intravascular Ultrasound Study (NIVUS)

    DEFF Research Database (Denmark)

    Kosonen, Petteri; Vikman, Saila; Jensen, Lisette Okkels

    2012-01-01

    This prospective multicenter registry used intravascular ultrasound (IVUS) in patients with definite stent thrombosis (ST) to compare rates of incomplete stent apposition (ISA), stent fracture and stent expansion in patients treated with drug-eluting (DES) versus bare metal (BMS) stents. ST...... is a rare, but potential life threatening event after coronary stent implantation. The etiology seems to be multifactorial....

  13. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation

    DEFF Research Database (Denmark)

    Falk, Erling

    2012-01-01

    The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving...

  14. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies : A report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation

    NARCIS (Netherlands)

    G.J. Tearney (Guillermo); E.S. Regar (Eveline); T. Akasaka (Takashi); S. Adriaenssens (Stef); P. Barlis (Peter); H.G. Bezerra (Hiram); B.E. Bouma (Brett); N. Bruining (Nico); J.-M. Cho (Jin-Man); S. Chowdhary (Saqib); M.A. Costa (Marco); R. de Silva (Ranil); J. Dijkstra (Jouke); C. di Mario (Carlo); D. Dudeck (Darius); E. Falk (Erling); M.D. Feldman (Marc); P.J. Fitzgerald (Peter); H.M. Garcia-Garcia (Hector); N. Gonzalo (Nieves); J.F. Granada (Juan); G. Guagliumi (Giulio); N.R. Holm (Niels); Y. Honda (Yasuhiro); F. Ikeno (Fumiaki); Y. Kawasaki; W. Kochman (Waclav); L. Koltowski (Lukasz); T. Kubo (Takashi); T. Kume (Teruyoshi); H. Kyono (Hiroyuki); C.C.S. Lam (Cheung Chi Simon); G. Lamouche (Guy); D.P. Lee (David); M.B. Leon (Martin); A. Maehara (Akiko); O. Manfrini (Olivia); G.S. Mintz (Gary); K. Mizuno (Kyiouchi); M-A.M. Morel (Marie-Angèle); S. Nadkarni (Seemantini); H. Okura (Hiroyuki); H. Otake (Hiromasa); A. Pietrasik (Arkadiusz); F. Prati (Francesco); L. Rber (Lorenz); M. Radu (Maria); N. Rieber (Nikolaus); M. Riga (Maria); S.M. Rollins; M. Rosenberg (Mireille); V. Sirbu (Vasile); P.W.J.C. Serruys (Patrick); K. Shimada; T. Shinke (Toshiro); J. Shite (Junya); E. Siegel (Eliot); S. Sonada (Shinjo); U. Suter (Ueli); S. Takarada (Shigeho); A. Tanaka (Atsushi); M. Terashima (Mitsuyasu); T. Troels (Thim); M. Uemura (Mayu); G.J. Ughi (Giovanni); H.M.M. van Beusekom (Heleen); A.F.W. van der Steen (Ton); G.A. van Es (Gerrit Anne); G. van Soest (Gijs); R. Virmani (Renu); S. Waxman (Sergio); N.J. Weissman (Neil); G. Weisz (Giora)

    2012-01-01

    textabstractObjectives: The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the

  15. Neutrophil beta-2 microglobulin: an inflammatory mediator

    DEFF Research Database (Denmark)

    Bjerrum, O W; Nissen, Mogens Holst; Borregaard, N

    1990-01-01

    Beta-2 microglobulin (beta 2m) constitutes the light invariant chain of HLA class I antigen, and is a constituent of mobilizable compartments of neutrophils. Two forms of beta 2m exist: native beta 2m and proteolytically modified beta 2m (Des-Lys58-beta 2m), which shows alpha mobility in crossed ...

  16. Neutrophils in atherosclerosis. A brief overview

    NARCIS (Netherlands)

    Hartwig, H.; Silvestre Roig, C.; Daemen, M.; Lutgens, E.; Soehnlein, O.

    2015-01-01

    Atherosclerosis is a chronic inflammation of the arterial wall and the continuous infiltration of leukocytes into the plaque enhances the progression of the lesion. Because of the scarce detection of neutrophils in atherosclerotic plaques compared to other immune cells, their contribution was

  17. Myeloperoxidase attracts neutrophils by physical forces

    Czech Academy of Sciences Publication Activity Database

    Klinke, A.; Nussbaum, C.; Kubala, Lukáš; Friedrichs, K.; Rudolph, T.K.; Rudolph, V.; Paust, H.-J.; Schröder, Ch.; Benten, D.; Lau, D.; Szocs, K.; Furtmüller, P.G.; Heeringa, P.; Sydow, K.; Duchstein, H.-J.; Ehmke, H.; Schumacher, U.; Meinertz, T.; Sperandio, M.; Baldus, S.

    2011-01-01

    Roč. 117, č. 4 (2011), s. 1350-1358 ISSN 0006-4971 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : myeloperoxidase * polymorphonuclear neutrophils * glycocalyx Subject RIV: BO - Biophysics Impact factor: 9.898, year: 2011

  18. Rat Neutrophil Phagocytosis Following Feed Restriction

    Czech Academy of Sciences Publication Activity Database

    Slapničková, Martina; Berger, J.

    2002-01-01

    Roč. 11, č. 3 (2002), s. 172-177 ISSN 0938-7714 Institutional research plan: CEZ:AV0Z5052915 Keywords : circulating neutrophil * diet restriction * phagocytosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.167, year: 2001

  19. Changes in Neutrophil Functions in Astronauts

    Science.gov (United States)

    Kaur, Indreshpal; Simons, Elizabeth R.; Castro, Victoria; Pierson, Duane L.

    2002-01-01

    Neutrophil functions (phagocytosis, oxidative burst, degranulation) and expression of surface markers involved in these functions were studied in 25 astronauts before and after 4 space shuttle missions. Space flight duration ranged from 5 to 11 days. Blood specimens were obtained 10 days before launch (preflight or L-10), immediately after landing (landing or R+0), and again at 3 days after landing (postflight or R+3). Blood samples were also collected from 9 healthy low-stressed subjects at 3 time points simulating a 10-day shuttle mission. The number of neutrophils increased at landing by 85 percent when compared to the preflight numbers. Neutrophil functions were studied in whole blood using flow cytometric methods. Phagocytosis of E.coli-FITC and oxidative burst capacity of the neutrophils following the 9 to 11 day missions were lower at all three sampling points than the mean values for control subjects. Phagocytosis and oxidative burst capacity of the astronauts was decreased even 10-days before space flight. Mission duration appears to be a factor in phagocytic and oxidative functions. In contrast, following the short-duration (5-days) mission, these functions were unchanged from control values. No consistent changes in degranulation were observed following either short or medium length space missions. The expression of CD16, CD32, CD11a, CD11b, CD11c, L-selectin and CD36 was measured and found to be variable. Specifically, CD16 and CD32 did not correlate with the changes in oxidative burst and phagocytosis. We can conclude from this study that the stresses associated with space flight can alter the important functions of neutrophils.

  20. Simulation of self-propelled chemotactic bacteria in a stokes flow*

    Directory of Open Access Journals (Sweden)

    Maury B.

    2010-12-01

    Full Text Available We prescrit a method to simulate the motion of self-propelled rigid particles in a twodimensional Stokesian fluid, taking into account chemotactic behaviour. Self-propulsion is modelled as a point force associated to each particle, placed at a certain distance from its gravity centre. The method for solving the fluid flow and the motion of the bacteria is based on a variational formulation on the whole domain, including fluid and particles: rigid motion is enforced by penalizing the strain rate tensor on the rigid domain, while incompressibility is treated by duality. This leads to a minimisation problem over unconstrained functional spaces which cari lie easily implemented from any finite element Stokes solver. In order to ensure robustness, a projection algorithm is used to deal with contacts between particles. The particles are meant to represent bacteria of the Escherichia coli type, which interact with their chemical environment through consumption of nutrients and orientation in some favorable direction. Our mode’ takes into account the interaction with oxygen. An advection-diffusion equation on the oxygen concentration is solved in the fluid domain, with a source term accounting for oxygen consumption by the bacteria. In addition, self-propulsion is deactivated for those particles which cannot consume enough oxygen. Finally, the mode’ includes random changes in the orientation of the individual bacteria, with a frequency that depends on the surrounding oxygen concentration, in order to favor the direction of the concentration gradient and thus to reproduce chemotactic behaviour. Numerical simulations implemented with FreeFem++ are presented. Nous présentons une méthode de simulation du mouvement de particules rigides autopropulsées dans un fluide de Stokes en dimension 2. en prenant en compte leur comportement chimiotactique. L’auto-propulsion est modélisée par une force (presque ponctuelle associée à chaque particule et plac

  1. Effect of moderate exercise on peritoneal neutrophils from juvenile rats.

    Science.gov (United States)

    Braz, Glauber Ruda; Ferreira, Diorginis Soares; Pedroza, Anderson Apolonio; da Silva, Aline Isabel; Sousa, Shirley Maria; Pithon-Curi, Tania Cristina; Lagranha, Claudia

    2015-09-01

    Previous studies showed that moderate exercise in adult rats enhances neutrophil function, although no studies were performed in juvenile rats. We evaluated the effects of moderate exercise on the neutrophil function in juvenile rats. Viability and neutrophils function were evaluated. Moderate exercise did not impair the viability and mitochondrial transmembrane potential of neutrophils, whereas there was greater reactive oxygen species production (164%; p < 0.001) and phagocytic capacity (29%; p < 0.05). Our results suggest that moderate exercise in juvenile rats improves neutrophil function, similar to adults.

  2. Imminent Cardiac Risk Assessment via Optical Intravascular Biochemical Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wetzel, D.; Wetzel, L; Wetzel, M; Lodder, R

    2009-01-01

    Heart disease is by far the biggest killer in the United States, and type II diabetes, which affects 8% of the U.S. population, is on the rise. In many cases, the acute coronary syndrome and/or sudden cardiac death occurs without warning. Atherosclerosis has known behavioral, genetic and dietary risk factors. However, our laboratory studies with animal models and human post-mortem tissue using FT-IR microspectroscopy reveal the chemical microstructure within arteries and in the arterial walls themselves. These include spectra obtained from the aortas of ApoE-/- knockout mice on sucrose and normal diets showing lipid deposition in the former case. Also pre-aneurysm chemical images of knockout mouse aorta walls, and spectra of plaque excised from a living human patient are shown for comparison. In keeping with the theme of the SPEC 2008 conference Spectroscopic Diagnosis of Disease this paper describes the background and potential value of a new catheter-based system to provide in vivo biochemical analysis of plaque in human coronary arteries. We report the following: (1) results of FT-IR microspectroscopy on animal models of vascular disease to illustrate the localized chemical distinctions between pathological and normal tissue, (2) current diagnostic techniques used for risk assessment of patients with potential unstable coronary syndromes, and (3) the advantages and limitations of each of these techniques illustrated with patent care histories, related in the first person, by the physician coauthors. Note that the physician comments clarify the contribution of each diagnostic technique to imminent cardiac risk assessment in a clinical setting, leading to the appreciation of what localized intravascular chemical analysis can contribute as an add-on diagnostic tool. The quality of medical imaging has improved dramatically since the turn of the century. Among clinical non-invasive diagnostic tools, laboratory tests of body fluids, EKG, and physical examination are

  3. Application of intravascular ultrasound in percutaneous coronary interventional therapy

    International Nuclear Information System (INIS)

    Wang Jingping; Li Bao; An Jian; Yang Bin; Wang Zhongchao; Wang Rijun; Zhang Wutang; Lei Xinyu; Wang Huixian; Lu Lifang; Gao Yongli

    2009-01-01

    Objective: To evaluate intravascular ultrasound (IVUS)in demonstrating the characteristics of coronary plaque and in implanting the coronary stent. Methods: Before stent implantation, IVUS was used to observe the plaque character/sties(soft, fibrotic, calcified or mixed) as well as the eccentric degree in 28 patients with angiographically-proved single coronary branch lesion. The minimal luminal diameter, minimal cross-sectional area and plaque area were measured. After stent deployment the above measurements were repeated, and the location, symmetrical index and expansion of the stent were observed. Results: A total of 36 stents was implanted in 28 patients with coronary disease. After the procedure the minimal luminal diameter and the minimal cross-sectional area was increased, while the plaque area was decreased. The difference between the values before and after the stent implantation was statistically significant (P<0.01). IVUS after stent deployment found that in all cases the stent had a nice location and covered the lesion completely with no interlayer at its both ends. Excellent expansion of the stent was seen in 30 cases (83.3%). Insufficient expansion occurred in 3 cases and undesirable contact of the stent to the arterial wall was found in 3 cases (16.7%). In such circumstances, one size bigger low-compliance balloon dilatation was adopted, or the original balloon was used again with higher pressure (18-22 atm), in order to expand the stent once more, and good results accord with IVUS optimal criteria were obtained. Conclusions: IVUS can clearly demonstrate the pathological features of the coronary lesions, such as plaque type, eccentric degree, luminal diameter, cross-sectional area and plaque area, which are very helpful in guiding the selection of the proper stent before the procedure, and are also very useful in evaluating the location, expansion of the stent as well as the stent-to-wall contact condition after the procedure. (authors)

  4. Intravascular papillary endothelial hyperplasia: magnetic resonance imaging of finger lesions

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Jinkyeong; Kim, Jee-Young [The Catholic University of Korea, Department of Radiology, St. Vincent' s Hospital, College of Medicine, Suwon, Gyeonggi-do (Korea, Republic of); Yoo, Changyoung [The Catholic University of Korea, Department of Hospital Pathology, St. Vincent' s Hospital, College of Medicine, Suwon, Gyeonggi-do (Korea, Republic of)

    2016-02-15

    To describe magnetic resonance imaging (MRI) features of intravascular papillary endothelial hyperplasia (IPEH), to identify findings differentiating IPEH of the finger from that of other locations, and to correlate these with pathology. Nineteen patients with 20 I.E. masses of the finger (n = 13) and other locations (n = 7) were evaluated. All patients underwent MRI, and the results were correlated with pathology. Seventeen IPEHs, including all IPEHs of the finger, were located in the subcutis, the three other lesions in the muscle layer. On T1WI, all masses were isointense or slightly hyperintense. IPEHs of the finger (n = 13) revealed focal hyperintense nodules (n = 2) or central hypointensity (n = 2) on T1WI, hypointensity with a hyperintense rim (n = 7), hyperintensity with hypointense nodules (n = 5), or isointensity with a hypointense rim (n = 1) on T2WI, and rim enhancement (n = 5), heterogeneous enhancement with nodular nonenhanced areas (n = 6), peripheral nodular enhancement (n = 1), or no enhancement (n = 1) on gadolinium-enhanced T1WI. IPEHs of other locations (n = 7) demonstrated focal hyperintense nodules (n = 5) on T1WI, hyperintensity with hypointense nodules (n = 5) or heterogeneous signal intensity (n = 2) on T2WI, and rim or rim and septal enhancement (n = 6) or peripheral nodular enhancement (n = 1). Microscopically, IPEHs were composed of thrombi that were hypointense on T2WI and papillary endothelial proliferations that showed T2 hyperintensity and enhancement. MRI of finger IPEH reveals well-demarcated subcutaneous masses with hypointensity or hypointense nodules with peripheral hyperintensity on T2WI, as well as peripheral enhancement. T1 hyperintense nodules, internal heterogeneity on T2WI, and septal enhancement are more common in IPEH of other locations. (orig.)

  5. ARCOCT: Automatic detection of lumen border in intravascular OCT images.

    Science.gov (United States)

    Cheimariotis, Grigorios-Aris; Chatzizisis, Yiannis S; Koutkias, Vassilis G; Toutouzas, Konstantinos; Giannopoulos, Andreas; Riga, Maria; Chouvarda, Ioanna; Antoniadis, Antonios P; Doulaverakis, Charalambos; Tsamboulatidis, Ioannis; Kompatsiaris, Ioannis; Giannoglou, George D; Maglaveras, Nicos

    2017-11-01

    Intravascular optical coherence tomography (OCT) is an invaluable tool for the detection of pathological features on the arterial wall and the investigation of post-stenting complications. Computational lumen border detection in OCT images is highly advantageous, since it may support rapid morphometric analysis. However, automatic detection is very challenging, since OCT images typically include various artifacts that impact image clarity, including features such as side branches and intraluminal blood presence. This paper presents ARCOCT, a segmentation method for fully-automatic detection of lumen border in OCT images. ARCOCT relies on multiple, consecutive processing steps, accounting for image preparation, contour extraction and refinement. In particular, for contour extraction ARCOCT employs the transformation of OCT images based on physical characteristics such as reflectivity and absorption of the tissue and, for contour refinement, local regression using weighted linear least squares and a 2nd degree polynomial model is employed to achieve artifact and small-branch correction as well as smoothness of the artery mesh. Our major focus was to achieve accurate contour delineation in the various types of OCT images, i.e., even in challenging cases with branches and artifacts. ARCOCT has been assessed in a dataset of 1812 images (308 from stented and 1504 from native segments) obtained from 20 patients. ARCOCT was compared against ground-truth manual segmentation performed by experts on the basis of various geometric features (e.g. area, perimeter, radius, diameter, centroid, etc.) and closed contour matching indicators (the Dice index, the Hausdorff distance and the undirected average distance), using standard statistical analysis methods. The proposed method was proven very efficient and close to the ground-truth, exhibiting non statistically-significant differences for most of the examined metrics. ARCOCT allows accurate and fully-automated lumen border

  6. Targeting Neutrophilic Inflammation Using Polymersome-Mediated Cellular Delivery.

    Science.gov (United States)

    Robertson, James D; Ward, Jon R; Avila-Olias, Milagros; Battaglia, Giuseppe; Renshaw, Stephen A

    2017-05-01

    Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In this study, we deliver therapeutic compounds to neutrophils using biocompatible, nanometer-sized synthetic vesicles, or polymersomes, which are internalized by binding to scavenger receptors and subsequently escape the early endosome through a pH-triggered disassembly mechanism. This allows polymersomes to deliver molecules into the cell cytosol of neutrophils without causing cellular activation. After optimizing polymersome size, we show that polymersomes can deliver the cyclin-dependent kinase inhibitor (R)-roscovitine into human neutrophils to promote apoptosis in vitro. Finally, using a transgenic zebrafish model, we show that encapsulated (R)-roscovitine can speed up inflammation resolution in vivo more efficiently than the free drug. These results show that polymersomes are effective intracellular carriers for drug delivery into neutrophils. This has important consequences for the study of neutrophil biology and the development of neutrophil-targeted therapeutics. Copyright © 2017 The Authors.

  7. Spontaneous neutrophil migration patterns during sepsis after major burns.

    Science.gov (United States)

    Jones, Caroline N; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Hassell, Bryan A; Warren, H Shaw; Tompkins, Ronald G; Fagan, Shawn P; Irimia, Daniel

    2014-01-01

    Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns.

  8. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2012-02-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  9. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2011-04-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  10. Evaluation of In-111 neutrophils in a model of the adult respiratory distress syndrome

    International Nuclear Information System (INIS)

    Cooper, J.A.; Solano, S.J.; Bizios, R.; Line, B.R.; Malik, A.B.

    1984-01-01

    Neutrophils (PMNs) have been implicated in the pathogenesis of the adult respiratory distress syndrome. To further define their role, the authors studied the kinetics of In-111 labeled PMNs in a sheep model of acute pulmonary vascular injury. PMNs isolated by Percoll-plasma gradient centrifugation, and labeled with 500 uCi of In-111-oxine. Following i.v. reinfusion of the labeled PMNs, lung activity was monitored with the labeled PMNs, lung activity was monitored with a gamma camera. After a two hour baseline, pulmonary vascular injury secondary to intravascular coagulation was induced by the i.v. infusion of 100 units/kg of thrombin (n=5). Pulmonary time activity curves demonstrated increases in pulmonary PMN activity averaging 14% over baseline following thrombin infusion. A portion of the uptake was transient, lasting about 20 to 30 min., but PMN activity remained above baseline for the remainder of the study. Following the infusion of gamma thrombin, a form of thrombin unable to cleave fibrinogen, increased PMN uptake was not observed. Inhibition of fibrinolysis with tranaxemic acid, reduced the PMN response to thrombin to less than a 3% increase over baseline (n=2). The findings demonstrate that PMNs are involved in acute pulmonary vascular injury, and suggest a potential role for labeled PMNs in the clinical investigation of the adult respiratory distress syndrome

  11. Disruption of a regulatory network consisting of neutrophils and platelets fosters persisting inflammation in rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Norma eMaugeri

    2016-05-01

    Full Text Available A network of cellular interactions that involve blood leukocytes and platelets maintains vessel homeostasis. It plays a critical role in the response to invading microbes by recruiting intravascular immunity and through the generation of Neutrophil Extracellular Traps (NETs and immunothrombosis. Moreover it enables immune cells to respond to remote chemoattractants by crossing the endothelial barrier and reaching sites of infection. Once the network operating under physiological conditions is disrupted, the reciprocal activation of cells in the blood and the vessel walls determines the vascular remodelling via inflammatory signals delivered to stem/progenitor cells. A deregulated leukocyte/mural cell interaction is an early critical event in the natural history of systemic inflammation. Despite intense efforts, the signals that initiate and sustain the immune-mediated vessel injury, or those that enforce the often-prolonged phases of clinical quiescence in patients with vasculitis, have only been partially elucidated. Here we discuss recent evidence that implicates the prototypic Damage-Associated Molecular Pattern/ alarmin, the High Mobility Group Box 1 (HMGB1 protein in systemic vasculitis and in the vascular inflammation associated to systemic sclerosis. HMGB1 could represent a player in the pathogenesis of rheumatic diseases and an attractive target for molecular interventions.

  12. Disruption of a Regulatory Network Consisting of Neutrophils and Platelets Fosters Persisting Inflammation in Rheumatic Diseases.

    Science.gov (United States)

    Maugeri, Norma; Rovere-Querini, Patrizia; Manfredi, Angelo A

    2016-01-01

    A network of cellular interactions that involve blood leukocytes and platelets maintains vessel homeostasis. It plays a critical role in the response to invading microbes by recruiting intravascular immunity and through the generation of neutrophil extracellular traps (NETs) and immunothrombosis. Moreover, it enables immune cells to respond to remote chemoattractants by crossing the endothelial barrier and reaching sites of infection. Once the network operating under physiological conditions is disrupted, the reciprocal activation of cells in the blood and the vessel walls determines the vascular remodeling via inflammatory signals delivered to stem/progenitor cells. A deregulated leukocyte/mural cell interaction is an early critical event in the natural history of systemic inflammation. Despite intense efforts, the signals that initiate and sustain the immune-mediated vessel injury, or those that enforce the often-prolonged phases of clinical quiescence in patients with vasculitis, have only been partially elucidated. Here, we discuss recent evidence that implicates the prototypic damage-associated molecular pattern/alarmin, the high mobility group box 1 (HMGB1) protein in systemic vasculitis and in the vascular inflammation associated with systemic sclerosis. HMGB1 could represent a player in the pathogenesis of rheumatic diseases and an attractive target for molecular interventions.

  13. Currently available methodologies for the processing of intravascular ultrasound and optical coherence tomography images.

    Science.gov (United States)

    Athanasiou, Lambros; Sakellarios, Antonis I; Bourantas, Christos V; Tsirka, Georgia; Siogkas, Panagiotis; Exarchos, Themis P; Naka, Katerina K; Michalis, Lampros K; Fotiadis, Dimitrios I

    2014-07-01

    Optical coherence tomography and intravascular ultrasound are the most widely used methodologies in clinical practice as they provide high resolution cross-sectional images that allow comprehensive visualization of the lumen and plaque morphology. Several methods have been developed in recent years to process the output of these imaging modalities, which allow fast, reliable and reproducible detection of the luminal borders and characterization of plaque composition. These methods have proven useful in the study of the atherosclerotic process as they have facilitated analysis of a vast amount of data. This review presents currently available intravascular ultrasound and optical coherence tomography processing methodologies for segmenting and characterizing the plaque area, highlighting their advantages and disadvantages, and discusses the future trends in intravascular imaging.

  14. Contribution of Neutrophils to Acute Lung Injury

    OpenAIRE

    Grommes, Jochen; Soehnlein, Oliver

    2010-01-01

    Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neut...

  15. Tumor Associated Neutrophils in Human Lung Cancer

    Science.gov (United States)

    2016-10-01

    tumor innate immune response. anti-tumor adaptive immune response, neutrophil and T cell interaction. ACCOMPLISHMENTS There were no significant...and by producing factors to recruit and acti- vate cells of the innate and adaptive immune system (Mantovani et al., 2011). Given these varying effects...vivo effects on neutro- phil activation (Figure 2, A and B) and cleavage of myeloid and lymphoid cell markers (Supplemental Figure 1, C–G). Once opti

  16. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

    2015-01-01

    Summary Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. PMID:26047922

  17. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo.

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A; Nourshargh, Sussan

    2015-06-16

    Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Perioperative Intravascular Fluid Assessment and Monitoring: A Narrative Review of Established and Emerging Techniques

    Directory of Open Access Journals (Sweden)

    Sumit Singh

    2011-01-01

    Full Text Available Accurate assessments of intravascular fluid status are an essential part of perioperative care and necessary in the management of the hemodynamically unstable patient. Goal-directed fluid management can facilitate resuscitation of the hypovolemic patient, reduce the risk of fluid overload, reduce the risk of the injudicious use of vasopressors and inotropes, and improve clinical outcomes. In this paper, we discuss the strengths and limitations of a spectrum of noninvasive and invasive techniques for assessing and monitoring intravascular volume status and fluid responsiveness in the perioperative and critically ill patient.

  19. Monooxignase ensymic system of a liver of rats exposed to intravascular laser irradiation of blood

    International Nuclear Information System (INIS)

    Ibadova, G.A.

    1997-01-01

    Experimental study of the dynamic monooxidation of liver enzymic system was carried out on rats with experimental salmonellosis and the influence of the blood intravascular laser irradiation of blood on these enzymes was revealed. It was determined that by experimental salmonellosis oppression of the MOES activity of hepatocytes occurred. The blood intravascular irradiation by He-Ne laser promotes MOES oppression in rats suffered from salmonellosis. IVLIB as well as UV-laser show pronounced effect on the enzymes detoxication protection, mobilize their resistance to endogenic intoxication under the conditions of experimental salmonellosis. (author)

  20. Use of carbon dioxide as an intravascular contrast agent: A review of current literature

    OpenAIRE

    Ali, Fahad; Mangi, Muhammad Asif; Rehman, Hiba; Kaluski, Edo

    2017-01-01

    Use of X-ray contrast allows us to differentiate between two or more adjacent structures on radiographic studies. The X-ray contrast agent can be the one with increase X-ray absorption, like iodine and a barium X-ray contrast agent or the one with decrease X-ray absorption like air and carbon dioxide contrast agent. Each contrast agent possesses different risks and benefits in various ways. Carbon dioxide as an intravascular contrast agent can be used as an alternative intravascular contrast ...

  1. Leiomyosarcoma of the Uterus with Intravascular Tumor Extension and Pulmonary Tumor Embolism

    International Nuclear Information System (INIS)

    McDonald, Douglas K.; Kalva, Sanjeeva P.; Fan, C.-M.; Vasilyev, Aleksandr

    2007-01-01

    We report the case of a 48-year-old woman presenting with recurrent uterine leiomyosarcoma (LMS) associated with right iliac vein and inferior vena cava (IVC) invasion and left lower lobe pulmonary tumor embolus. Because the prognosis and treatment differ from that of thrombotic pulmonary emboli, the differentiating imaging characteristics of intravascular tumor embolism are reviewed. To our knowledge, only two other cases of intravenous uterine leiomyosarcomatosis have been described in the existing literature, and this is the first reported case of the entity with associated intravascular tumor embolism

  2. Intravascular brachytherapy in prevention of the secondary restenosis angioplasty transluminal coronaries

    International Nuclear Information System (INIS)

    Mejia, S.

    2001-01-01

    The radiotherapy coronary intravascular has demonstrated in a convincing way in clinical and experimental studies that produces a favorable decrease of the restenosis process. There is enough evidence to define this technique as the main current therapeutic option in the handling of the reestenosis intra stent. Accumulated experience exists of up to 3 years in patient's treaties with radiation gamma and multiple studies in several centers that demonstrate similar benefits with issuing beta. The present articulates it revises a series of radiotherapy systems and makes a setting a day on the employment of the brachytherapy intravascular in cardiologic patient

  3. Intravascular ultrasound evaluation of a pseudolesion created by stent placement in the right artery.

    Science.gov (United States)

    Zientek, D M; Rodgers, G P

    1999-10-01

    The creation of a pseudolesion after guidewire placement in tortuous arterial segments is a well recognized phenomenon. Intravascular ultrasound has been useful in assessing deployment of intracoronary stents and equivocal angiographic findings. We present a case in which a pseudolesion was not observed until after placement of an intracoronary stent. Intravascular ultrasound demonstrated no dissection or significant lesion; however, there was focal calcification just distal to the stent providing a substrate for the distorted vessel architecture. The lesion resolved with removal of the guidewire.

  4. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

    Science.gov (United States)

    Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

    2014-03-01

    Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

  5. Sexy again: the renaissance of neutrophils in psoriasis.

    Science.gov (United States)

    Schön, Michael P; Broekaert, Sigrid M C; Erpenbeck, Luise

    2017-04-01

    Notwithstanding their prominent presence in psoriatic skin, the functional role of neutrophilic granulocytes still remains somewhat enigmatic. Sparked by exciting scientific discoveries regarding neutrophil functions within the last years, the interest in these short-lived cells of the innate immune system has been boosted recently. While it had been known for some time that neutrophils produce and respond to a number of inflammatory mediators, recent research has linked neutrophils with the pathogenic functions of IL-17, possibly in conjunction with the formation of NETs (neutrophil extracellular traps). Antipsoriatic therapies exert their effects, at least in part, through interference with neutrophils. Neutrophils also appear to connect psoriasis with comorbid diseases. However, directly tampering with neutrophil functions is not trivial as evinced by the failure of therapeutic approaches targeting redundantly regulated cellular communication networks. It has also become apparent that neutrophils link important pathogenic functions of the innate and the adaptive immune system and that they are intricately involved in regulatory networks underlying the pathophysiology of psoriasis. In order to advocate intensified research into the role of this interesting cell population, we here highlight some features of neutrophils and put them into perspective with our current view of the pathophysiology of psoriasis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Effect of Isolation Techniques on Viability of Bovine Blood Neutrophils

    Directory of Open Access Journals (Sweden)

    P. Sláma

    2006-01-01

    Full Text Available The effect of selected isolation methods on the viability of neutrophil granulocytes (neutrophils from the blood of healthy Holstein x Bohemian Red Pied crossbred heifers was evaluated. Two methods of neutrophil isolation were used: a neutrophil isolation on the basis of hypotonic erythrocyte lysis (in two variants: after the erythrocyte lysis proper, the cells were centrifuged at either 200 g or 1000 g, and b neutrophil isolation with FACS Lysing Solution as the lysing agent. The viability of the isolated neutrophils was evaluated on the basis of apoptosis and necrosis. The results obtained with flow cytometry (FCM suggest that, from the isolation techniques used, the method based on FACS Lysing Solution impaired the neutrophil viability least. After the application of this method, 5.36 ± 2.15% of neutrophils were apoptotic and 0.51 ± 0.12% were necrotic. In contrast, when the hypotonic erythrocyte lysis was used, the proportion of apoptotic neutrophils amounted to 42.14 ± 7.12% and 49.00 ± 14.70%, respectively, and 41.12 ± 5.55% and 36.91 ± 24.38% respectively of necrotic neutrophils (P < 0.01. This was also confirmed by the light microscopy. After the isolation with FASC Lysing Solution, 1.92 ± 1.74% of neutrophils were apoptotic and 1.05 ± 0.76% were necrotic, as distinct from after the hypotonic erythrocyte lysis where 9.43 ± 3.69% of neutrophils were apoptotic and 12.67 ± 4.74% of necrotic after centrifugation at 200 g, while 12.60 ± 4.35 were apoptotic and 14.96 ± 12.64% were necrotic after centrifugation at 1000 g. It follows from the above-mentioned data that hypotonic lysis is not a suitable method for the isolation of neutrophils, as the method itself markedly affects cell viability.

  7. Characterization of Yersinia pestis Interactions with Human Neutrophils In vitro

    Directory of Open Access Journals (Sweden)

    Sophia C. Dudte

    2017-08-01

    Full Text Available Yersinia pestis is a gram-negative, zoonotic, bacterial pathogen, and the causative agent of plague. The bubonic form of plague occurs subsequent to deposition of bacteria in the skin by the bite of an infected flea. Neutrophils are recruited to the site of infection within the first few hours and interactions between neutrophils and Y. pestis have been demonstrated in vivo. In contrast to macrophages, neutrophils have been considered non-permissive to Y. pestis intracellular survival. Several studies have shown killing of the vast majority of Y. pestis ingested by human neutrophils. However, survival of 10–15% of Y. pestis after phagocytosis by neutrophils is consistently observed. Furthermore, these surviving bacteria eventually replicate within and escape from the neutrophils. We set out to further characterize the interactions between Y. pestis and human neutrophils by (1 determining the effects of known Y. pestis virulence factors on bacterial survival after uptake by neutrophils, (2 examining the mechanisms employed by the neutrophil to kill the majority of intracellular Y. pestis, (3 determining the activation phenotype of Y. pestis-infected neutrophils, and (4 characterizing the Y. pestis-containing phagosome in neutrophils. We infected human neutrophils in vitro with Y. pestis and assayed bacterial survival and uptake. Deletion of the caf1 gene responsible for F1 capsule production resulted in significantly increased uptake of Y. pestis. Surprisingly, while the two-component regulator PhoPQ system is important for survival of Y. pestis within neutrophils, pre-induction of this system prior to infection did not increase bacterial survival. We used an IPTG-inducible mCherry construct to distinguish viable from non-viable intracellular bacteria and determined the association of the Y. pestis-containing phagosome with neutrophil NADPH-oxidase and markers of primary, secondary and tertiary granules. Additionally, we show that inhibition of

  8. Advanced Role of Neutrophils in Common Respiratory Diseases

    Directory of Open Access Journals (Sweden)

    Jinping Liu

    2017-01-01

    Full Text Available Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system. Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity. They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases. However, the pathological mechanism of neutrophils remains complex and obscure. The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD, pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed. With the development of scientific research, the involvement of neutrophils in respiratory diseases is being brought to light with emerging data on neutrophil subsets, trafficking, and cell death mechanism (e.g., NETosis, apoptosis in diseases. We reviewed all these recent studies here to provide you with the latest advances about the role of neutrophils in respiratory diseases.

  9. Localization and Functionality of the Inflammasome in Neutrophils

    DEFF Research Database (Denmark)

    Bakele, Martina; Joos, Melanie; Burdi, Sofia

    2014-01-01

    Neutrophils represent the major fraction of circulating immune cells and are rapidly recruited to sites of infection and inflammation. The inflammasome is a multiprotein complex that regulates the generation of IL-1 family proteins. The precise subcellular localization and functionality...... of the inflammasome in human neutrophils are poorly defined. Here we demonstrate that highly purified human neutrophils express key components of the NOD-like receptor family, pyrin domain containing 3 (NLRP3), and absent in melanoma 2 (AIM2) inflammasomes, particularly apoptosis-associated speck-like protein...... and released as protein, highly purified neutrophils neither expressed nor released IL-1α at baseline or upon stimulation. Upon inflammasome activation, highly purified neutrophils released substantially lower levels of IL-1β protein compared with partially purified neutrophils. Serine proteases and caspases...

  10. Diverse novel functions of neutrophils in immunity, inflammation, and beyond

    OpenAIRE

    Mocsai, A.

    2013-01-01

    Neutrophils have long been considered simple suicide killers at the bottom of the hierarchy of the immune response. That view began to change 10–20 yr ago, when the sophisticated mechanisms behind how neutrophils locate and eliminate pathogens and regulate immunity and inflammation were discovered. The last few years witnessed a new wave of discoveries about additional novel and unexpected functions of these cells. Neutrophils have been proposed to participate in protection against intracellu...

  11. Neutrophilic dermatoses in a patient with collagenous colitis

    OpenAIRE

    Didac Barco; Maria A. Barnadas; Esther Roé; Francisco J. Sancho; Elena Ricart; Agustín Alomar

    2010-01-01

    We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate...

  12. Chemotactic Activity of Cyclophilin A in the Skin Mucus of Yellow Catfish (Pelteobagrus fulvidraco) and Its Active Site for Chemotaxis

    Science.gov (United States)

    Dawar, Farman Ullah; Tu, Jiagang; Xiong, Yang; Lan, Jiangfeng; Dong, Xing Xing; Liu, Xiaoling; Khattak, Muhammad Nasir Khan; Mei, Jie; Lin, Li

    2016-01-01

    Fish skin mucus is a dynamic barrier for invading pathogens with a variety of anti-microbial enzymes, including cyclophilin A (CypA), a multi-functional protein with peptidyl-prolyl cis/trans isomerase (PPIase) activity. Beside various other immunological functions, CypA induces leucocytes migration in vitro in teleost. In the current study, we have discovered several novel immune-relevant proteins in yellow catfish skin mucus by mass spectrometry (MS). The CypA present among them was further detected by Western blot. Moreover, the CypA present in the skin mucus displayed strong chemotactic activity for yellow catfish leucocytes. Interestingly, asparagine (like arginine in mammals) at position 69 was the critical site in yellow catfish CypA involved in leucocyte attraction. These novel efforts do not only highlight the enzymatic texture of skin mucus, but signify CypA to be targeted for anti-inflammatory therapeutics. PMID:27589721

  13. Chemotactic Activity of Cyclophilin A in the Skin Mucus of Yellow Catfish (Pelteobagrus fulvidraco and Its Active Site for Chemotaxis

    Directory of Open Access Journals (Sweden)

    Farman Ullah Dawar

    2016-08-01

    Full Text Available Fish skin mucus is a dynamic barrier for invading pathogens with a variety of anti-microbial enzymes, including cyclophilin A (CypA, a multi-functional protein with peptidyl-prolyl cis/trans isomerase (PPIase activity. Beside various other immunological functions, CypA induces leucocytes migration in vitro in teleost. In the current study, we have discovered several novel immune-relevant proteins in yellow catfish skin mucus by mass spectrometry (MS. The CypA present among them was further detected by Western blot. Moreover, the CypA present in the skin mucus displayed strong chemotactic activity for yellow catfish leucocytes. Interestingly, asparagine (like arginine in mammals at position 69 was the critical site in yellow catfish CypA involved in leucocyte attraction. These novel efforts do not only highlight the enzymatic texture of skin mucus, but signify CypA to be targeted for anti-inflammatory therapeutics.

  14. Use of an Intravascular Fluorescent Continuous Glucose Sensor in ICU Patients

    NARCIS (Netherlands)

    Strasma, Paul J.; Finfer, Simon; Flower, Oliver; Hipszer, Brian; Kosiborod, Mikhail; Macken, Lewis; Sechterberger, Marjolein; van der Voort, Peter H. J.; DeVries, J. Hans; Joseph, Jeffrey I.

    2015-01-01

    Hyperglycemia and hypoglycemia are associated with adverse clinical outcomes in intensive care patients. In product development studies at 4 ICUs, the safety and performance of an intravascular continuous glucose monitoring (IV-CGM) system was evaluated in 70 postsurgical patients. The GluCath

  15. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? A prospective observational study

    DEFF Research Database (Denmark)

    Johansson, Per Ingemar; Sorensen, Anne Marie; Perner, Anders

    2011-01-01

    ABSTRACT: INTRODUCTION: It is debated whether the early trauma induced coagulopathy (TIC) in severely injured patients reflects disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, acute coagulopathy of trauma shock (ACoTS) or yet other entities. This study investigated the...

  16. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation

    NARCIS (Netherlands)

    Bakhtiari, Kamran; Meijers, Joost C. M.; de Jonge, Evert; Levi, Marcel

    2004-01-01

    Objectives: A diagnosis of disseminated intravascular coagulation (DIC) is hampered by the lack of an accurate diagnostic test. Based on the retrospective analysis of studies in patients with DIC, a scoring system (0-8 points) using simple and readily available routine laboratory tests has been

  17. Disseminated intravascular coagulation as an unusual presentation of an Epstein-Barr virus infection

    NARCIS (Netherlands)

    van Steijn, JHM; van Tol, KM; van Essen, LH; Gans, ROB

    2000-01-01

    Epstein-Barr viral (EBV)-infection usually presents as fever, sore throat, fatigue, lymphadenopathy and atypical lymphocytosis. We describe a patient with disseminated intravascular coagulation as the presenting symptom caused by a primary EBV infection. (C) 2000 Elsevier Science B.V. All rights

  18. Evidence for a novel chemotactic C1q domain-containing factor in the leech nerve cord.

    Science.gov (United States)

    Tahtouh, Muriel; Croq, Françoise; Vizioli, Jacopo; Sautiere, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Daha, Mohamed R; Pestel, Joël; Lefebvre, Christophe

    2009-02-01

    In vertebrates, central nervous system (CNS) protection is dependent on many immune cells including microglial cells. Indeed, activated microglial cells are involved in neuroinflammation mechanisms by interacting with numerous immune factors. Unlike vertebrates, some lophotrochozoan invertebrates can fully repair their CNS following injury. In the medicinal leech Hirudo medicinalis, the recruitment of microglial cells at the lesion site is essential for sprouting of injured axons. Interestingly, a new molecule homologous to vertebrate C1q was characterized in leech, named HmC1q (for H. medicinalis) and detected in neurons and glial cells. In chemotaxis assays, leech microglial cells were demonstrated to respond to human C1q. The chemotactic activity was reduced when microglia was preincubated with signaling pathway inhibitors (Pertussis Toxin or wortmannin) or anti-human gC1qR antibody suggesting the involvement of gC1qR in C1q-mediated migration in leech. Assays using cells preincubated with NO chelator (cPTIO) showed that C1q-mediated migration was associated to NO production. Of interest, by using anti-HmC1q antibodies, HmC1q released in the culture medium was shown to exhibit a similar chemotactic effect on microglial cells as human C1q. In summary, we have identified, for the first time, a molecule homologous to mammalian C1q in leech CNS. Its chemoattractant activity on microglia highlights a new investigation field leading to better understand leech CNS repair mechanisms.

  19. Neutrophils in traumatic brain injury (TBI): friend or foe?

    Science.gov (United States)

    Liu, Yang-Wuyue; Li, Song; Dai, Shuang-Shuang

    2018-05-17

    Our knowledge of the pathophysiology about traumatic brain injury (TBI) is still limited. Neutrophils, as the most abundant leukocytes in circulation and the first-line transmigrated immune cells at the sites of injury, are highly involved in the initiation, development, and recovery of TBI. Nonetheless, our understanding about neutrophils in TBI is obsolete, and mounting evidences from recent studies have challenged the conventional views. This review summarizes what is known about the relationships between neutrophils and pathophysiology of TBI. In addition, discussions are made on the complex roles as well as the controversial views of neutrophils in TBI.

  20. Hypoxia upregulates neutrophil degranulation and potential for tissue injury

    Science.gov (United States)

    Hoenderdos, Kim; Lodge, Katharine M; Hirst, Robert A; Chen, Cheng; Palazzo, Stefano G C; Emerenciana, Annette; Summers, Charlotte; Angyal, Adri; Porter, Linsey; Juss, Jatinder K; O'Callaghan, Christopher; Chilvers, Edwin R

    2016-01-01

    Background The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. Methods and results Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; both normoxic and hypoxic supernatants impaired ciliary function. Surprisingly, the hypoxic upregulation of neutrophil degranulation was not dependent on hypoxia-inducible factor (HIF), nor was it fully reversed by inhibition of phospholipase C signalling. Hypoxia augmented the resting and cytokine-stimulated phosphorylation of AKT, and inhibition of phosphoinositide 3-kinase (PI3K)γ (but not other PI3K isoforms) prevented the hypoxic upregulation of neutrophil elastase release. Conclusion Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells in a HIF-independent but PI3Kγ-dependent fashion. PMID:27581620

  1. Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+\\/-49 and 484+\\/-80 pg\\/mL, respectively; for all, presented as mean +\\/- SEM) compared with control experiments (32+\\/-4 pg\\/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome

  2. Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation.

    Science.gov (United States)

    Alemán, Omar Rafael; Mora, Nancy; Cortes-Vieyra, Ricarda; Uribe-Querol, Eileen; Rosales, Carlos

    2016-01-01

    Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

  3. Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation

    Directory of Open Access Journals (Sweden)

    Omar Rafael Alemán

    2016-01-01

    Full Text Available Neutrophils (PMN are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

  4. Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions

    NARCIS (Netherlands)

    Glogauer, Michael; Marchal, Christophe C.; Zhu, Fei; Worku, Aelaf; Clausen, Björn E.; Foerster, Irmgard; Marks, Peter; Downey, Gregory P.; Dinauer, Mary; Kwiatkowski, David J.

    2003-01-01

    Defects in myeloid cell function in Rac2 knockout mice underline the importance of this isoform in activation of NADPH oxidase and cell motility. However, the specific role of Rac1 in neutrophil function has been difficult to assess since deletion of Rac1 results in embryonic lethality in mice. To

  5. Gβ1 is required for neutrophil migration in zebrafish.

    Science.gov (United States)

    Ke, Wenfan; Ye, Ding; Mersch, Kacey; Xu, Hui; Chen, Songhai; Lin, Fang

    2017-08-01

    Signaling mediated by G protein-coupled receptors (GPCRs) is essential for the migration of cells toward chemoattractants. The recruitment of neutrophils to injured tissues in zebrafish larvae is a useful model for studying neutrophil migration and trafficking in vivo. Indeed, the study of this process led to the discovery that PI3Kγ is required for the polarity and motility of neutrophils, features that are necessary for the directed migration of these cells to wounds. However, the mechanism by which PI3Kγ is activated remains to be determined. Here we show that signaling by specifically the heterotrimeric G protein subunit Gβ1 is critical for neutrophil migration in response to wounding. In embryos treated with small-molecule inhibitors of Gβγ signaling, neutrophils failed to migrate to wound sites. Although both the Gβ1 and Gβ4 isoforms are expressed in migrating neutrophils, only deficiency for the former (morpholino-based knockdown) interfered with the directed migration of neutrophils towards wounds. The Gβ1 deficiency also impaired the ability of cells to change cell shape and reduced their general motility, defects that are similar to those in neutrophils deficient for PI3Kγ. Transplantation assays showed that the requirement for Gβ1 in neutrophil migration is cell autonomous. Finally, live imaging revealed that Gβ1 is required for polarized activation of PI3K, and for the actin dynamics that enable neutrophil migration. Collectively, our data indicate that Gβ1 signaling controls proper neutrophil migration by activating PI3K and modulating actin dynamics. Moreover, they illustrate a role for a specific Gβ isoform in chemotaxis in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Hidden truth of circulating neutrophils (polymorphonuclear neutrophil function in periodontally healthy smoker subjects

    Directory of Open Access Journals (Sweden)

    Chitra Agarwal

    2016-01-01

    Full Text Available Context: Tobacco smoking is considered to be a major risk factor associated with periodontal disease. Smoking exerts a major effect on the protective elements of the immune response, resulting in an increase in the extent and severity of periodontal destruction. Aims: The aim of the present study was to assess viability and phagocytic function of neutrophils in circulating blood of the smokers and nonsmokers who are periodontally healthy. Settings and Design: Two hundred subjects in the mean range of 20–30 years of age were included in the study population. It was a retrospective study carried out for 6 months. Materials and Methods: Two hundred subjects were divided into four groups: 50 nonsmokers, 50 light smokers (15 cigarettes/day. Full mouth plaque index, sulcus bleeding index, and probing depths were measured. Percentage viability of circulating neutrophils and average number of phagocytosed Candida albicans were recorded. Statistical Analysis Used: Means and standard deviations were calculated from data obtained within the groups. Comparison between the smokers and nonsmokers was performed by Kruskal–Wallis ANOVA analysis. Comparison between smoker groups was performed using Mann–Whitney–Wilcoxon test. Results: Percentage viability of neutrophils was significantly less in heavy smokers (66.9 ± 4.0, moderate (76.6 ± 4.2, light smokers (83.1 ± 2.5 as compared to nonsmokers (92.3 ± 2.6 (P < 0.01. The ability of neutrophils to phagocytose, i.e., mean particle number was significantly less in light smokers (3.5 ± 0.5, moderate smokers (2.3 ± 0.5, and heavy smokers (1.4 ± 0.5 compared to nonsmokers (4.9 ± 0.7 (P < 0.01 with evidence of dose-response effect. Conclusions: Smoking significantly affects neutrophils viability and phagocytic function in periodontally healthy population.

  7. Diverse novel functions of neutrophils in immunity, inflammation, and beyond.

    Science.gov (United States)

    Mócsai, Attila

    2013-07-01

    Neutrophils have long been considered simple suicide killers at the bottom of the hierarchy of the immune response. That view began to change 10-20 yr ago, when the sophisticated mechanisms behind how neutrophils locate and eliminate pathogens and regulate immunity and inflammation were discovered. The last few years witnessed a new wave of discoveries about additional novel and unexpected functions of these cells. Neutrophils have been proposed to participate in protection against intracellular pathogens such as viruses and mycobacteria. They have been shown to intimately shape the adaptive immune response at various levels, including marginal zone B cells, plasmacytoid dendritic cells and T cell populations, and even to control NK cell homeostasis. Neutrophils have been shown to mediate an alternative pathway of systemic anaphylaxis and to participate in allergic skin reactions. Finally, neutrophils were found to be involved in physiological and pathological processes beyond the immune system, such as diabetes, atherosclerosis, and thrombus formation. Many of those functions appear to be related to their unique ability to release neutrophil extracellular traps even in the absence of pathogens. This review summarizes those novel findings on versatile functions of neutrophils and how they change our view of neutrophil biology in health and disease.

  8. Regulation of calcium homeostasis in activated human neutrophils ...

    African Journals Online (AJOL)

    Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

  9. Neutrophilic dermatoses in a patient with collagenous colitis

    Directory of Open Access Journals (Sweden)

    Didac Barco

    2010-01-01

    Full Text Available We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate and Sweet’s syndrome was diagnosed. Both the neutrophilic panniculitis and the Sweet’s syndrome were accompanied by fever, malaise and diarrhea. Cutaneous and intestinal symptoms disappeared with corticoid therapy. The two types of neutrophilic dermatoses that appeared in periods of colitis activity suggest that intestinal and cutaneous manifestations may be related.

  10. Swell activated chloride channel function in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  11. Regulation of neutrophil senescence by microRNAs.

    Directory of Open Access Journals (Sweden)

    Jon R Ward

    2011-01-01

    Full Text Available Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease.

  12. Neutrophils, a candidate biomarker and target for radiation therapy?

    Science.gov (United States)

    Schernberg, Antoine; Blanchard, Pierre; Chargari, Cyrus; Deutsch, Eric

    2017-11-01

    Neutrophils are the most abundant blood-circulating white blood cells, continuously generated in the bone marrow. Growing evidence suggests they regulate the innate and adaptive immune system during tumor evolution. This review will first summarize the recent findings on neutrophils as a key player in cancer evolution, then as a potential biomarker, and finally as therapeutic targets, with respective focuses on the interplay with radiation therapy. A complex interplay: Neutrophils have been associated with tumor progression through multiple pathways. Ionizing radiation has cytotoxic effects on cancer cells, but the sensitivity to radiation therapy in vivo differ from isolated cancer cells in vitro, partially due to the tumor microenvironment. Different microenvironmental states, whether baseline or induced, can modulate or even attenuate the effects of radiation, with consequences for therapeutic efficacy. Inflammatory biomarkers: Inflammation-based scores have been widely studied as prognostic biomarkers in cancer patients. We have performed a large retrospective cohort of patients undergoing radiation therapy (1233 patients), with robust relationship between baseline blood neutrophil count and 3-year's patient's overall survival in patients with different cancer histologies. (Pearson's correlation test: p = .001, r = -.93). Therapeutic approaches: Neutrophil-targeting agents are being developed for the treatment of inflammatory and autoimmune diseases. Neutrophils either can exert antitumoral (N1 phenotype) or protumoral (N2 phenotype) activity, depending on the Tumor Micro Environment. Tumor associated N2 neutrophils are characterized by high expression of CXCR4, VEGF, and gelatinase B/MMP9. TGF-β within the tumor microenvironment induces a population of TAN with a protumor N2 phenotype. TGF-β blockade slows tumor growth through activation of CD8 + T cells, macrophages, and tumor associated neutrophils with an antitumor N1 phenotype. This supports

  13. A new method to measure necrotic core and calcium content in coronary plaques using intravascular ultrasound radiofrequency-based analysis

    NARCIS (Netherlands)

    E.S. Shin (Eun-Seok); H.M. Garcia-Garcia (Hector); P.W.J.C. Serruys (Patrick)

    2010-01-01

    textabstractAlthough previous intravascular ultrasound (IVUS) radiofrequency-based analysis data showed acceptable reproducibility for plaque composition, measurements are not easily obtained, particularly that of lumen contour, because of the limited IVUS resolution. The purpose of this study was

  14. Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions

    Directory of Open Access Journals (Sweden)

    Endalew Yizengaw

    2016-11-01

    Full Text Available Immunologically, active visceral leishmaniasis (VL is characterised by profound immunosuppression, severe systemic inflammatory responses and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the resolution of inflammation, the control of pathogen replication and the regulation of immune responses. Neutrophil functions have been investigated in human cutaneous leishmaniasis, however, their role in human visceral leishmaniasis is poorly understood.In the present study we evaluated the activation status and effector functions of neutrophils in patients with active VL and after successful anti-leishmanial treatment. Our results show that neutrophils are highly activated and have degranulated; high levels of arginase, myeloperoxidase and elastase, all contained in neutrophils’ granules, were found in the plasma of VL patients. In addition, we show that a large proportion of these cells are immature. We also analysed effector functions of neutrophils that are essential for pathogen clearance and show that neutrophils have an impaired capacity to release neutrophil extracellular traps, produce reactive oxygen species and phagocytose bacterial particles, but not Leishmania parasites.Our results suggest that impaired effector functions, increased activation and immaturity of neutrophils play a key role in the pathogenesis of VL.

  15. On the mechanism of oscillations in neutrophils

    DEFF Research Database (Denmark)

    Brasen, Jens Christian; Barington, Torben; Olsen, Lars Folke

    2010-01-01

    We have investigated the regulation of the oscillatory generation of H(2)O(2) and oscillations in shape and size in neutrophils in suspension. The oscillations are independent of cell density and hence do not represent a collective phenomena. Furthermore, the oscillations are independent...... of the external glucose concentration and the oscillations in H(2)O(2) production are 180 degrees out of phase with the oscillations in NAD(P)H. Cytochalasin B blocked the oscillations in shape and size whereas it increased the period of the oscillations in H(2)O(2) production. 1- and 2-butanol also blocked...... the oscillations in shape and size, but only 1-butanol inhibited the oscillations in H(2)O(2) production. We conjecture that the oscillations are likely to be due to feedback regulations in the signal transduction cascade involving phosphoinositide 3-kinases (PI3K). We have tested this using a simple mathematical...

  16. P-shaped Coiled Stator Ultrasound Motor for Rotating Intravascular Surgery Device

    Directory of Open Access Journals (Sweden)

    Toshinobu ABE

    2015-01-01

    Full Text Available The primary focus of this paper is the development of an ultra-miniature ultrasound motor for use in the human blood vessel. Since the size of the drive source for rotating the atherectomy device and intravascular ultrasonography system are large currently in practical use, it is installed outside the body, and the rotational power for the atherectomy device and intravascular ultrasonography system are transmitted through the long tortuous blood vessel. Such systems suffer from the problem that the rotation becomes non-uniform, and the problem that the available time is limited. We have therefore developed a P-shaped coiled stator ultrasound motor as a miniature ultrasound motor for rotating the ultrasound sensor for use in blood vessels in order to solve these problems. In this paper, we describe measurement of the torque, revolution speed, output power, efficiency, and particle motion on acoustic waveguide of the P-shaped coiled stator ultrasound motor.

  17. Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Glover, Guy W; Thomas, Richard M; Vamvakas, George

    2016-01-01

    , maintenance and rewarming phases in addition to adverse events. All-cause mortality, as well as a composite of poor neurological function or death, as evaluated by the Cerebral Performance Category and modified Rankin scale were analysed. RESULTS: For patients managed at 33 °C there was no difference between......BACKGROUND: Targeted temperature management is recommended after out-of-hospital cardiac arrest and may be achieved using a variety of cooling devices. This study was conducted to explore the performance and outcomes for intravascular versus surface devices for targeted temperature management after...... out-of-hospital cardiac arrest. METHOD: A retrospective analysis of data from the Targeted Temperature Management trial. N = 934. A total of 240 patients (26%) managed with intravascular versus 694 (74%) with surface devices. Devices were assessed for speed and precision during the induction...

  18. Transbiliary intravascular ultrasound-guided diagnostic biopsy of an inaccessible pancreatic head mass

    Directory of Open Access Journals (Sweden)

    Jeffrey Forris Beecham Chick, MD, MPH, DABR

    2017-06-01

    Full Text Available Percutaneous image-guided biopsies of pancreatic malignancies may prove challenging and nondiagnostic due to a variety of anatomic considerations. For patients with complex post-surgical anatomy, such as a Roux-en-Y gastric bypass, diagnosis via endoscopic ultrasound with fine-needle aspiration may not be possible because of an inability to reach the proximal duodenum. This report describes the first diagnostic case of transbiliary intravascular ultrasound-guided biopsy of a pancreatic head mass in a patient with prior Roux-en-Y gastric bypass for which a diagnosis could not be achieved via percutaneous and endoscopic approaches. Transbiliary intravascular ultrasound-guided biopsy resulted in a diagnosis of pancreatic adenocarcinoma, allowing the initiation of chemotherapy.

  19. Intravascular Papillary Endothelial Hyperplasia Associated with Venous Pool Arising in the Lower Lip: A Case Report

    Directory of Open Access Journals (Sweden)

    Hisanobu Yonezawa

    2009-01-01

    Full Text Available Intravascular papillary endothelial hyperplasia is a benign nonneoplastic vascular lesion that consists of endothelial cells with abundant vascular tissue with papillary proliferation. An adult female had a painless growing dark red nodule on the left side of the lower lip and often touched and gnawed at it for more than 4 years. The lesion was a tender, smooth mass approximately 1 cm in diameter without discoloration reaction. Magnetic resonance imaging of the lesion showed specific findings. She was diagnosed clinically as having mimicked hemangioma, and the lesion was totally excised under local anesthesia. Histopathological examination revealed that papillary proliferated endothelial cells with venous pool, and the lesion was diagnosed as intravascular papillary endothelial hyperplasia associated with venous pool. There has been no recurrence for more than 1 year. Despite the benign nature of this lesion, it could have been mistaken for a malignant tumor because of its clinical course and radiologic findings.

  20. Effect of catecholamines and insulin on plasma volume and intravascular mass of albumin in man

    DEFF Research Database (Denmark)

    Hilsted, J; Christensen, N J; Larsen, S

    1989-01-01

    1. The effect of intravenous catecholamine infusions and of intravenous insulin on plasma volume and intravascular mass of albumin was investigated in healthy males. 2. Physiological doses of adrenaline (0.5 microgram/min and 3 microgram/min) increased peripheral venous packed cell volume...... significantly; intravenous noradrenaline at 0.5 microgram/min had no effect on packed cell volume, whereas packed cell volume increased significantly at 3 micrograms of noradrenaline/min. No significant change in packed cell volume was found during saline infusion. 3. During adrenaline infusion at 6 micrograms...... in packed cell volume, plasma volume, intravascular mass of albumin and transcapillary escape rate of albumin during hypoglycaemia may be explained by the combined actions of adrenaline and insulin....

  1. MRI evaluation and follow-up of bone necrosis after meningococcal infection and disseminated intravascular coagulation

    International Nuclear Information System (INIS)

    Damry, N.; Schurmans, T.; Perlmutter, N.

    1993-01-01

    Disseminated intravascular coagulation (DIC) is a serious complication of meningococcal septicaemia. It often results in infarction of various tissues namely the skin, adrenal glands, kidneys, brain and, much less commonly, bones. We describe a patient who presented bone lesions after meningococcal septicaemia. In addition to plain radiography and scintigraphy the lesions were evaluated with MRI and have proved to be extensive and still progressive, approxximately 18 months after the onset of the disease. (orig.)

  2. Novel Double-Needle System That Can Prevent Intravascular Injection of Any Filler

    Directory of Open Access Journals (Sweden)

    Hsiang Huang, MD

    2017-09-01

    Full Text Available Summary:. A new type of needle system combines 2 parts, an inner needle and an outer needle. The inner needle is used for filler injection and the outer needle acts as a guiding needle that can observe blood reflow when inserting into the vessel lumen during injection process. This new needle system can be used for all kinds of filler, providing real time monitoring for physician and preventing intravascular injection of any filler.

  3. Distribution of [35S] taurine in mouse retina after intravitreal and intravascular injection

    International Nuclear Information System (INIS)

    Pourcho, R.G.

    1977-01-01

    The distribution of [ 35 S] taurine in mouse retinae was studied by autoradiographic techniques after either intravitreal or intravascular injection. The route of injection did not affect the final localization. The major sites of label accumulation were the outer nuclear layer, the inner nuclear layer, and Mueller cell processes adjacent to the vitreal surface. The distribution was consistent with the interpretation that taurine was localized within two cellular compartments of mouse retina, photoreceptor cells and Mueller cells. (author)

  4. Association of insulin resistance and coronary artery remodeling: an intravascular ultrasound study

    OpenAIRE

    Kim, Sang-Hoon; Moon, Jae-Youn; Lim, Yeong Min; Kim, Kyung Ho; Yang, Woo-In; Sung, Jung-Hoon; Yoo, Seung Min; Kim, In Jai; Lim, Sang-Wook; Cha, Dong-Hun; Cho, Seung-Yun

    2015-01-01

    Background There are few studies that investigated the correlation between insulin resistance (IR) and the coronary artery remodeling. The aim of the study is to investigate the association of IR measured by homeostasis model assessment of insulin resistance (HOMA-IR) and coronary artery remodeling evaluated by intravascular ultrasound (IVUS). Methods A total of 298 consecutive patients who received percutaneous coronary interventions under IVUS guidance were retrospectively enrolled. The val...

  5. Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

    Science.gov (United States)

    Pazos, Michael A; Lanter, Bernard B; Yonker, Lael M; Eaton, Alex D; Pirzai, Waheed; Gronert, Karsten; Bonventre, Joseph V; Hurley, Bryan P

    2017-08-01

    Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3), initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4). We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2) activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

  6. Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

    Directory of Open Access Journals (Sweden)

    Michael A Pazos

    2017-08-01

    Full Text Available Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3, initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4. We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2 activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

  7. Biomaterial-induced alterations of neutrophil superoxide production.

    Science.gov (United States)

    Kaplan, S S; Basford, R E; Mora, E; Jeong, M H; Simmons, R L

    1992-08-01

    Because periprosthetic infection remains a vexing problem for patients receiving implanted devices, we evaluated the effect of several materials on neutrophil free radical production. Human peripheral blood neutrophils were incubated with several sterile, lipopolysaccharide (LPS)-free biomaterials used in surgically implantable prosthetic devices: polyurethane, woven dacron, and velcro. Free radical formation as the superoxide (O2-) anion was evaluated by cytochrome c reduction in neutrophils that were exposed to the materials and then removed and in neutrophils allowed to remain in association with the materials. Neutrophils exposed to polyurethane or woven dacron for 30 or 60 min and then removed consistently exhibited an enhanced release of O2- after simulation via receptor engagement with formyl methionyl-leucyl-phenylalanine. Enhanced reactivity to stimulation via protein kinase C with phorbol myristate acetate, however, was not consistently observed. The cells evaluated for O2- release during continuous association with the biomaterials showed enhanced metabolic activity during short periods of association (especially with polyurethane and woven dacron). Although O2- release by neutrophils in association with these materials decreased with longer periods of incubation, it was not obliterated. These studies, therefore, show that several commonly used biomaterials activate neutrophils soon after exposure and that this activated state diminishes with prolonged exposure but nevertheless remains measurable. The diminishing level of activity with prolonged exposure, however, suggests that ultimately a depletion of reactivity may occur and may result in increased susceptibility to periprosthetic infection.

  8. Neutrophils in oral paracoccidioidomycosis and the involvement of Nrf2.

    Directory of Open Access Journals (Sweden)

    Vera Cavalcanti Araújo

    Full Text Available Neutrophils have been implicated in granuloma formation in several infectious diseases, in addition to their main phagocytic and pathogen destruction role. It has been demonstrated that Nrf2 regulates antioxidant protection in neutrophils, attenuating inflammation without compromising the hosts bacterial defense. In this study, we analyzed the presence of neutrophils in Paracoccidioides brasiliensis mycosis (PCM, as well as the immunoexpression of Nrf2. Thirty-nine cases of oral PCM were classified according to quantity of fungi and to the presence of loose or well-organized granulomas and microabscesses. An Nrf2 antibody was used for immunohistochemical analysis. The results showed that neutrophils are present in microabscesses and loose granulomas, but were absent in structured granulomas. A greater quantity of fungi was shown in cases with only loose granulomas when compared to loose and well organized granulomas. Nrf2 was observed in the nuclei of neutrophils of loose granulomas and abscesses, with its expression in loose granulomas maintained despite the additional presence of well organized granulomas in the same specimen. This study suggests that neutrophils participate in P. brasiliensis granuloma formation and that Nrf2 has a possible role in neutrophil survival, via modulation of the inflammatory response.

  9. Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions.

    Science.gov (United States)

    Balajthy, Zoltán; Csomós, Krisztián; Vámosi, György; Szántó, Attila; Lanotte, Michel; Fésüs, László

    2006-09-15

    Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2(-/-) mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2(-/-) mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.

  10. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

    Science.gov (United States)

    Knight, Jason S.; Meng, He; Coit, Patrick; Yalavarthi, Srilakshmi; Sule, Gautam; Gandhi, Alex A.; Grenn, Robert C.; Mazza, Levi F.; Ali, Ramadan A.; Renauer, Paul; Wren, Jonathan D.; Bockenstedt, Paula L.; Wang, Hui; Eitzman, Daniel T.; Sawalha, Amr H.

    2017-01-01

    Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophilsneutrophil extracellular traps (NETs), in particular — in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1–KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1–deficient mice by infusion of WT neutrophils, while an anti–PSGL-1 monoclonal antibody inhibited APS IgG–mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS. PMID:28931754

  11. Phenotypic changes in neutrophils related to anti-inflammatory therapy.

    Science.gov (United States)

    Barton, A E; Bayley, D L; Mikami, M; Llewellyn-Jones, C G; Stockley, R A

    2000-01-03

    Previous work from the group has shown that non-steroidal anti-inflammatory agents given to volunteers and patients inhibit PMN function possibly by affecting the developing neutrophil during the differentiation process. In this study indomethacin treatment in vivo reduced neutrophil chemotaxis and proteolytic degradation of fibronectin, with a maximal effect after 14 days. Stimulated neutrophil adherence to fibronectin was also reduced but this was not due to quantitative changes in beta(2) integrin expression or function. L-Selectin expression on resting and stimulated neutrophils was increased after 14 days and there was a small decrease in plasma levels of soluble L-selectin. These effects, however, could not be reproduced by treatment of neutrophils with indomethacin in vitro, suggesting they are due to effects on differentiating/maturing PMNs. In an attempt to interpret these changes, studies were performed with dexamethasone, which is known to alter neutrophil function and kinetics. Dexamethasone treatment reduced chemotaxis and increased superoxide generation after 1 day and was associated with increased expression of activated beta(2) integrins and reduced L-selectin expression on resting neutrophils. This suggests the appearance of mainly 'activated' cells as a result of demargination and indicates that the effects of indomethacin are distinctive and not related to changes in compartmentalisation.

  12. Conceptual source design and dosimetric feasibility study for intravascular treatment: a proposal for intensity modulated brachytherapy

    International Nuclear Information System (INIS)

    Kim, Si Yong; Han, Eun Young; Palta, Jatinder R.; Ha, Sung W.

    2003-01-01

    To propose a conceptual design of a novel source for intensity modulated brachytherapy. The source design incorporates both radioactive and shielding materials (stainless steel or tungsten), to provide an asymmetric dose intensity in the azimuthal direction. The intensity modulated intravascular brachytherapy was performed by combining a series of dwell positions and times, distributed along the azimuthal coordinates. Two simple designs for the beta-emitting sources, with similar physical dimensions to a 90 Sr/Y Novoste Beat-Cath source, were considered in the dosimetric feasibility study. In the first design, the radioactive and materials each occupy half of the cylinder and in the second, the radioactive material occupies only a quarter of the cylinder. The radial and azimuthal dose distributions around each source were calculated using the MCNP Monte Carlo code. The preliminary hypothetical simulation and optimization results demonstrated the 87% difference between the maximum and minimum doses to the lumen wall, due to off-centering of the radiation source, could be reduced to less than 7% by optimizing the azimuthal dwell positions and times of the partially shielded intravascular brachytherapy sources. The novel brachytherapy source design, and conceptual source delivery system, proposed in this study show promising dosimetric characteristics for the realization of intensity modulated brachytherapy in intravascular treatment. Further development of this concept will center on building a delivery system that can precisely control the angular motion of a radiation source in a small-diameter catheter

  13. Evaluation of CT virtual intravascular endoscopy in fenestrated stent grafts: a preliminary study

    International Nuclear Information System (INIS)

    Sun, Z.; Allen, Y.; Fitzsimmons, B.; Hartely, D.; Lawrence-Brown, M.

    2007-01-01

    We aim in this study to investigate the potential value of CT virtual intravascular endoscopy in patients diagnosed with abdominal aortic aneurysms undergoing fenestrated stent grafts. Both pre-and post-fenestration (within 3 months of implantation) multislice CT data were collected in eight patients and used for generation of virtual endoscopy images in our preliminary study. Variable fenestrations were deployed in 25 aortic branches with scallop fenestration implanted in six aortic ostia, large fenestration in four aortic ostia and small fenestration in 15 renal ostia, respectively. Measurements of the aortic ostia diameters both pre- and post-fenestration were successfully performed with virtual intravascular endoscopy visualization, and endovascular stents as well as their relationship to the aortic ostia were clearly demonstrated. Our results showed that there was no significant change of diameter of the aortic ostia following fenestrated stem grafts. Endovascular stents were clearly visualized on virtual endoscopy images, and no apparent deformity or malrotation was observed in this small group. Our preliminary study provides new insights into anatomic configuration/dimension of aortic ostia and endovascular stents, and virtual intravascular endoscopy could be a valuable technique to follow-up patients treated with fenestrated stent grafts. (orig.)

  14. Evaluation of CT virtual intravascular endoscopy in fenestrated stent grafts: a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Z. [Dept. of Imaging and Applied Physics, Curtin Univ. of Tech., Perth, WA (Australia); Allen, Y.; Fitzsimmons, B.; Hartely, D. [Cook R and D, WA (Australia); Lawrence-Brown, M. [Dept. of Public Health, Curtin Univ. of Tech., Perth, WA (Australia)

    2007-06-15

    We aim in this study to investigate the potential value of CT virtual intravascular endoscopy in patients diagnosed with abdominal aortic aneurysms undergoing fenestrated stent grafts. Both pre-and post-fenestration (within 3 months of implantation) multislice CT data were collected in eight patients and used for generation of virtual endoscopy images in our preliminary study. Variable fenestrations were deployed in 25 aortic branches with scallop fenestration implanted in six aortic ostia, large fenestration in four aortic ostia and small fenestration in 15 renal ostia, respectively. Measurements of the aortic ostia diameters both pre- and post-fenestration were successfully performed with virtual intravascular endoscopy visualization, and endovascular stents as well as their relationship to the aortic ostia were clearly demonstrated. Our results showed that there was no significant change of diameter of the aortic ostia following fenestrated stem grafts. Endovascular stents were clearly visualized on virtual endoscopy images, and no apparent deformity or malrotation was observed in this small group. Our preliminary study provides new insights into anatomic configuration/dimension of aortic ostia and endovascular stents, and virtual intravascular endoscopy could be a valuable technique to follow-up patients treated with fenestrated stent grafts. (orig.)

  15. Disseminated intravascular coagulation caused by moojenactivase, a procoagulant snake venom metalloprotease.

    Science.gov (United States)

    Sartim, Marco A; Cezarette, Gabriel N; Jacob-Ferreira, Anna L; Frantz, Fabiani G; Faccioli, Lucia H; Sampaio, Suely V

    2017-10-01

    Snake venom toxins that activate coagulation factors are key players in the process of venom-induced coagulopathy, and account for severe clinical manifestations. The present study applies a variety of biochemical, hematological, and histopathological approaches to broadly investigate the intravascular and systemic effects of moojenactivase (MooA), the first described PIIId subclass metalloprotease isolated from Bothrops sp. venom that activates coagulation factors. MooA induced consumption coagulopathy with high toxic potency, characterized by prolongation of prothrombin and activated partial thromboplastin time, consumption of fibrinogen and the plasma coagulation factors X and II, and thrombocytopenia. MooA promoted leukocytosis and expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-α, accompanied by tissue factor-dependent procoagulant activity in peripheral blood mononuclear cells. This metalloprotease also caused intravascular hemolysis, elevated plasma levels of creatine kinase-MB, aspartate transaminase, and urea/creatinine, and induced morphopathological alterations in erythrocytes, heart, kidney, and lungs associated with thrombosis and hemorrhage. Diagnosis of MooA-induced disseminated intravascular coagulation represents an important approach to better understand the pathophysiology of Bothrops envenomation and develop novel therapeutic strategies targeting hemostatic disturbances. Copyright © 2017. Published by Elsevier B.V.

  16. Cardiovascular disease in haemodialysis: role of the intravascular innate immune system.

    Science.gov (United States)

    Ekdahl, Kristina N; Soveri, Inga; Hilborn, Jöns; Fellström, Bengt; Nilsson, Bo

    2017-05-01

    Haemodialysis is a life-saving renal replacement modality for end-stage renal disease, but this therapy also represents a major challenge to the intravascular innate immune system, which is comprised of the complement, contact and coagulation systems. Chronic inflammation is strongly associated with cardiovascular disease (CVD) in patients on haemodialysis. Biomaterial-induced contact activation of proteins within the plasma cascade systems occurs during haemodialysis and initially leads to local generation of inflammatory mediators on the biomaterial surface. The inflammation is spread by soluble activation products and mediators that are generated during haemodialysis and transported in the extracorporeal circuit back into the patient together with activated leukocytes and platelets. The combined effect is activation of the endothelium of the cardiovascular system, which loses its anti-thrombotic and anti-inflammatory properties, leading to atherogenesis and arteriosclerosis. This concept suggests that maximum suppression of the intravascular innate immune system is needed to minimize the risk of CVD in patients on haemodialysis. A potential approach to achieve this goal is to treat patients with broad-specificity systemic drugs that target more than one of the intravascular cascade systems. Alternatively, 'stealth' biomaterials that cause minimal cascade system activation could be used in haemodialysis circuits.

  17. Intravascular pulmonary metastases from sarcoma: appearance on computed tomography in 3 cases

    International Nuclear Information System (INIS)

    Ting, P.T.; Burrowes, P.W.; Gray, R.R.

    2005-01-01

    Various common malignant neoplasms (ie, liver, kidney, stomach and breast) have been reported to embolize to the pulmonary arterial system. This uncommon occurrence can also result from metastatic sarcoma. We report 3 cases- 2 chondrosarcomas and 1 osteosarcoma-associated with intravascular motastases to the pulmonary vasculature and discuss the clinical presentation and differentiating radiologic features on computed tomography (CT). Intravascular pulmonary tumour emboli may present with nonspecific respiratory symptoms or remain completely asymptomatic, and therefore, many patients are often misdiagnosed with thromboembolic disease or undiagnosed until autopsy. Chest CTs in all our patients demonstrated a striking pattern of multifocal tubular branching beaded opacities along the pulmonary vasculature in a multilobular distribution. Our observations and a review of the literature indicate that chest CT is the most useful diagnostic tool for detecting intravascular pulmonary tumour emboli. CT can distinguish this entity from mucous plugging by demonstrating the normal adjacent bronchus. The tubular nature of these metastases distinguishes them from the more common parenchymal metastases. (author)

  18. The lateral neostriatum is necessary for compensatory ingestive behaviour after intravascular dehydration in female rats.

    Science.gov (United States)

    Lelos, M J; Harrison, D J; Rosser, A E; Dunnett, S B

    2013-12-01

    Aberrant striatal function results in an array of physiological symptoms, including impaired consummatory and regulatory behaviours, which can lead to weight loss and dehydration. It was hypothesised, therefore, that cell loss in the neostriatum may contribute to altered fluid intake by regulating physiological signals related to dehydration status. To test this theory, rats with lesions of the lateral neostriatum and sham controls underwent a series of physiological challenges, including the experimental induction of intracellular and intravascular dehydration. No baseline differences in prandial or non-prandial drinking were observed, nor were differences in locomotor activity evident between groups. Furthermore, intracellular dehydration increased water intake in lesion rats in a manner comparable to sham rats. Interestingly, a specific impairment was evident in lesion rats after subcutaneous injection of poly-ethylene glycol was used to induce intravascular dehydration, such that lesion rats failed to adapt their water intake to this physiological change. The results suggest that the striatal lesions resulted in regulatory dysfunction by impairing motivational control over compensatory ingestive behaviour after intravascular hydration, while the physiological signals related to dehydration remain intact. Loss of these cells in neurodegenerative disorders, such Huntington's disease, may contribute to regulatory changes evident in the course of the disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Conceptual source design and dosimetric feasibility study for intravascular treatment: a proposal for intensity modulated brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Si Yong; Han, Eun Young; Palta, Jatinder R. [College of Medicine, Florida Univ., Florida (United States); Ha, Sung W. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2003-06-01

    To propose a conceptual design of a novel source for intensity modulated brachytherapy. The source design incorporates both radioactive and shielding materials (stainless steel or tungsten), to provide an asymmetric dose intensity in the azimuthal direction. The intensity modulated intravascular brachytherapy was performed by combining a series of dwell positions and times, distributed along the azimuthal coordinates. Two simple designs for the beta-emitting sources, with similar physical dimensions to a {sub 90}Sr/Y Novoste Beat-Cath source, were considered in the dosimetric feasibility study. In the first design, the radioactive and materials each occupy half of the cylinder and in the second, the radioactive material occupies only a quarter of the cylinder. The radial and azimuthal dose distributions around each source were calculated using the MCNP Monte Carlo code. The preliminary hypothetical simulation and optimization results demonstrated the 87% difference between the maximum and minimum doses to the lumen wall, due to off-centering of the radiation source, could be reduced to less than 7% by optimizing the azimuthal dwell positions and times of the partially shielded intravascular brachytherapy sources. The novel brachytherapy source design, and conceptual source delivery system, proposed in this study show promising dosimetric characteristics for the realization of intensity modulated brachytherapy in intravascular treatment. Further development of this concept will center on building a delivery system that can precisely control the angular motion of a radiation source in a small-diameter catheter.

  20. Pulsed arterial spin labeling using TurboFLASH with suppression of intravascular signal.

    Science.gov (United States)

    Pell, Gaby S; Lewis, David P; Branch, Craig A

    2003-02-01

    Accurate quantification of perfusion with the ADC techniques requires the suppression of the majority of the intravascular signal. This is normally achieved with the use of diffusion gradients. The TurboFLASH sequence with its ultrashort repetition times is not readily amenable to this scheme. This report demonstrates the implementation of a modified TurboFLASH sequence for FAIR imaging. Intravascular suppression is achieved with a modified preparation period that includes a driven equilibrium Fourier transform (DEFT) combination of 90 degrees-180 degrees-90 degrees hard RF pulses subsequent to the inversion delay. These pulses rotate the perfusion-prepared magnetization into the transverse plane where it can experience the suitably placed diffusion gradients before being returned to the longitudinal direction by the second 90 degrees pulse. A value of b = 20-30 s/mm(2) was thereby found to suppress the majority of the intravascular signal. For single-slice perfusion imaging, quantification is only slightly modified. The technique can be readily extended to multislice acquisition if the evolving flow signal after the DEFT preparation is considered. An advantage of the modified preparation scheme is evident in the multislice FAIR images by the preservation of the sign of the magnetization difference. Copyright 2003 Wiley-Liss, Inc.

  1. An experimental method for detecting blood splatter from retractable phlebotomy and intravascular devices.

    Science.gov (United States)

    Haiduven, Donna; Applegarth, Shawn; Shroff, Miloni

    2009-03-01

    This study was designed to evaluate the safety of retractable intravascular devices in terms of their potential to produce blood splatter. A method for measuring this blood splatter designed by the research team was used to evaluate 3 specific intravascular devices. Scientific filters were positioned around the retraction mechanisms of the devices and weighed with an analytical scale, both before and after activation, in a simulated vein containing mock venous blood. The difference in filter mass was used as the primary unit of analysis to detect blood splatter. In addition, the filters were visually inspected for the presence or absence of blood. A paired t-test revealed significant differences in the prefilter and postfilter groups for 2 of the 3 devices tested (P blood was detected on 23% to 40% of the scientific filters for 2 of the devices. Our findings indicate a potential for bloodborne pathogen exposure with the use of intravascular devices with a retractable mechanism. This experiment may serve as a model in the design and implementation of future sharps device evaluation protocols to validate the threat of bloodborne pathogen exposure.

  2. Hydrophilic Polymer Embolism: Implications for Manufacturing, Regulation, and Postmarket Surveillance of Coated Intravascular Medical Devices.

    Science.gov (United States)

    Mehta, Rashi I; Mehta, Rupal I

    2018-03-19

    Hydrophilic polymers are ubiquitously applied as surface coatings on catheters and intravascular medical technologies. Recent clinical literature has heightened awareness on the complication of hydrophilic polymer embolism, the phenomenon wherein polymer coating layers separate from catheter and device surfaces, and may be affiliated with a range of unanticipated adverse reactions. Significant system barriers have limited and delayed reporting on this iatrogenic complication, the full effects of which remain underrecognized by healthcare providers and manufacturers of various branded devices. In 2015, the United States Food and Drug Administration acknowledged rising clinical concerns and stated that the agency would work with stakeholders to further evaluate gaps that exist in current national and international device standards for coated intravascular medical technologies. The present article reviews current knowledge on this complication as well as factors that played a role in delaying detection and dissemination of information and new knowledge once hazards and clinical risks were identified. Furthermore, organ-specific effects and adverse reaction patterns are summarized, along with implications for device manufacturing, safety assurance, and regulation. Qualitative and quantitative particulate testing are needed to optimize coated intravascular device technologies. Moreover, general enhanced processes for medical device surveillance are required for timely adverse event management and to ensure patient safety.

  3. Monocyte chemotactic protein-1 deficiency attenuates and high-fat diet exacerbates bone loss in mice with Lewis lung carcinoma.

    Science.gov (United States)

    Yan, Lin; Nielsen, Forrest H; Sundaram, Sneha; Cao, Jay

    2017-04-04

    Bone loss occurs in obesity and cancer-associated complications including wasting. This study determined whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects in male C57BL/6 mice with Lewis lung carcinoma (LLC) metastases in lungs. Compared to non-tumor-bearing mice, LLC reduced bone volume fraction, connectivity density, trabecular number, trabecular thickness and bone mineral density and increased trabecular separation in femurs. Similar changes occurred in vertebrae. The high-fat diet compared to the AIN93G diet exacerbated LLC-induced detrimental structural changes; the exacerbation was greater in femurs than in vertebrae. Mice deficient in MCP-1 compared to wild-type mice exhibited increases in bone volume fraction, connectivity density, trabecular number and decreases in trabecular separation in both femurs and vertebrae, and increases in trabecular thickness and bone mineral density and a decrease in structure model index in vertebrae. Lewis lung carcinoma significantly decreased osteocalcin but increased tartrate-resistant acid phosphatase 5b (TRAP 5b) in plasma. In LLC-bearing mice, the high-fat diet increased and MCP-1 deficiency decreased plasma TRAP 5b; neither the high-fat diet nor MCP-1 deficiency resulted in significant changes in plasma concentration of osteocalcin. In conclusion, pulmonary metastasis of LLC is accompanied by detrimental bone structural changes; MCP-1 deficiency attenuates and high-fat diet exacerbates the metastasis-associated bone wasting.

  4. Influence of prosthetic radioiodination on the chemical and biological behavior of chemotactic peptides labeled at high specific activity

    International Nuclear Information System (INIS)

    Pozzi, Oscar R.; Sajaroff, Elisa O.; Edreira, Martin M.

    2006-01-01

    The influence of radioiodination made through prosthetic group N-succinimidyl-3-[ 131 I]iodo-benzoate ([ 131 I]SIB) on the behavior of small peptides was investigated using as model the chemotactic hexapeptide Nα-for-Nle-Leu-Phe-Nle-Tyr-Lys. No carrier added labeled peptide was isolated by reverse-phase HPLC (RP-HPLC) with coupling efficiencies up to 59-75%. Biodistribution in normal and infected C57 mice showed mainly a hepatobiliary clearance, a very low thyroid uptake and the highest uptake at the infection site was within 1h of injection. Superoxide production and competitive binding assays studies in human polymorphonuclear leukocytes showed a preserved biological activity and high-affinity specific binding. However, the results indicated that the changes observed in the receptor-binding properties with an IC 50 almost twice than the unlabeled peptide and the increasing in the hepatobiliary excretion could be the consequence of the increased lipophicity observed due to the presence of the prosthetic group together with a strong influence of the radioisotope per se

  5. Influence of prosthetic radioiodination on the chemical and biological behavior of chemotactic peptides labeled at high specific activity

    Energy Technology Data Exchange (ETDEWEB)

    Pozzi, Oscar R. [National Atomic Energy Commission, Ezeiza Atomic Centre, Buenos Aires (Argentina)]. E-mail: oscar.pozzi@duke.edu; Sajaroff, Elisa O. [National Atomic Energy Commission, Ezeiza Atomic Centre, Buenos Aires (Argentina); Edreira, Martin M. [National Atomic Energy Commission, Ezeiza Atomic Centre, Buenos Aires (Argentina)

    2006-06-15

    The influence of radioiodination made through prosthetic group N-succinimidyl-3-[{sup 131}I]iodo-benzoate ([{sup 131}I]SIB) on the behavior of small peptides was investigated using as model the chemotactic hexapeptide N{alpha}-for-Nle-Leu-Phe-Nle-Tyr-Lys. No carrier added labeled peptide was isolated by reverse-phase HPLC (RP-HPLC) with coupling efficiencies up to 59-75%. Biodistribution in normal and infected C57 mice showed mainly a hepatobiliary clearance, a very low thyroid uptake and the highest uptake at the infection site was within 1h of injection. Superoxide production and competitive binding assays studies in human polymorphonuclear leukocytes showed a preserved biological activity and high-affinity specific binding. However, the results indicated that the changes observed in the receptor-binding properties with an IC{sub 50} almost twice than the unlabeled peptide and the increasing in the hepatobiliary excretion could be the consequence of the increased lipophicity observed due to the presence of the prosthetic group together with a strong influence of the radioisotope per se.

  6. Predictors of neutrophilic airway inflammation in young smokers with asthma

    DEFF Research Database (Denmark)

    Westergaard, Christian Grabow; Munck, Christian; Helby, Jens

    2014-01-01

    by a higher degree of neutrophilic inflammation than in non-smokers. A state of neutrophilic inflammation may lead to increased steroid resistance and an accelerated loss of lung function owing to tissue destruction. The aim of this study was to elucidate predictors of neutrophilic inflammation in young...... asthmatic smokers not on steroid treatment, including analysis of tobacco history and bacterial colonization. Methods: In a cross-sectional study, 52 steroid-free, current smokers with asthma were examined with induced sputum, fractional exhaled nitric oxide (FeNO), lung function, ACQ6 score, mannitol...... smokers, neutrophilia may be induced when a certain threshold of tobacco consumption is reached....

  7. Characterization of neutrophil adhesion to different titanium surfaces

    Indian Academy of Sciences (India)

    Scanning electron microscopy and flow cytometry were used to measure .... discs containing neutrophils were inverted and placed in a tube assembly that ... Representative AFM images of smooth (a) and rough (b) Ti surfaces. The arithmetic ...

  8. Neutrophil evasion strategies by Streptococcus pneumoniae and Staphylococcus aureus.

    Science.gov (United States)

    Lewis, Megan L; Surewaard, Bas G J

    2018-03-01

    Humans are well equipped to defend themselves against bacteria. The innate immune system employs diverse mechanisms to recognize, control and initiate a response that can destroy millions of different microbes. Microbes that evade the sophisticated innate immune system are able to escape detection and could become pathogens. The pathogens Streptococcus pneumoniae and Staphylococcus aureus are particularly successful due to the development of a wide variety of virulence strategies for bacterial pathogenesis and they invest significant efforts towards mechanisms that allow for neutrophil evasion. Neutrophils are a primary cellular defense and can rapidly kill invading microbes, which is an indispensable function for maintaining host health. This review compares the key features of Streptococcus pneumoniae and Staphylococcus aureus in epidemiology, with a specific focus on virulence mechanisms utilized to evade neutrophils in bacterial pathogenesis. It is important to understand the complex interactions between pathogenic bacteria and neutrophils so that we can disrupt the ability of pathogens to cause disease.

  9. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These stu......Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies....... These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function...

  10. Cryptococcal capsular glucuronoxylomannan reduces ischaemia-related neutrophil influx

    NARCIS (Netherlands)

    Ellerbroek, PM; Schoemaker, RG; van Veghel, R; Hoepelman, AIM; Coenjaerts, FEJ

    Background The capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans interferes with the chemotaxis and transendothelial migration of neutrophils. Intravenous administration of purified GXM has been shown to reduce the influx of inflammatory cells in an animal model of

  11. Effects of Acrolein on Leukotriene Biosynthesis in Human Neutrophils

    OpenAIRE

    Zemski Berry, Karin A.; Henson, Peter M.; Murphy, Robert C.

    2008-01-01

    Acrolein is a toxic, highly reactive α,β-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-LO products in addition to small amounts of COX produc...

  12. Disentangling the effects of tocilizumab on neutrophil survival and function.

    Science.gov (United States)

    Gaber, Timo; Hahne, Martin; Strehl, Cindy; Hoff, Paula; Dörffel, Yvonne; Feist, Eugen; Burmester, Gerd-Rüdiger; Buttgereit, Frank

    2016-06-01

    The synovial tissue in rheumatoid arthritis (RA) represents a hypoxic environment with up-regulated pro-inflammatory cytokines and cellular infiltrates including neutrophils. Although inhibition of the interleukin (IL)6 receptor pathway by tocilizumab is a potent treatment option for RA, it may also cause adverse effects such as an occasionally high-grade neutropenia. We analysed the impact of tocilizumab on survival, mediator secretion, oxidative burst, phagocytosis and energy availability of high-dose toll-like receptor (TLR)2/4-stimulated neutrophils (to mimic an arthritis flare) under normoxic versus hypoxic conditions. Human neutrophils were purified, pre-treated with varying doses of tocilizumab, dexamethasone or human IgG1 and high-dose-stimulated with lipopolysaccharide (LPS) alone-triggering TLR2/4-, LPS plus IL6, or left unstimulated. Cells were then incubated under normoxic (18 % O2) or hypoxic (1 % O2) conditions and subsequently analysed. Neutrophil survival and energy availability were significantly decreased by tocilizumab in a dose-dependent manner in high-dose TLR2/4-stimulated cells, but to a greater extent under normoxia as compared to hypoxia. We also found high-dose LPS-stimulated oxidative burst and phagocytosis of neutrophils to be higher under hypoxic versus normoxic conditions, but this difference was reduced by tocilizumab. Finally, we observed that tocilizumab affected neutrophil mediator secretion as a function of oxygen availability. Tocilizumab is known for both beneficial effects and a higher incidence of neutropenia when treating RA patients. Our results suggest that both effects can at least in part be explained by a reduction in neutrophil survival, a dose-dependent inhibition of hypoxia-induced NADPH oxidase-mediated oxidative burst and phagocytosis of infiltrating hypoxic neutrophils and an alteration of mediator secretion.

  13. Lipoxin A4 and lipoxin B4 stimulate the release but not the oxygenation of arachidonic acid in human neutrophils: Dissociation between lipid remodeling and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Nigam, S.; Fiore, S.; Luscinskas, F.W.; Serhan, C.N. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-06-01

    The profiles of actions of lipoxin A4 (LXA4) and lipoxin B4 (LXB4), two lipoxygenase-derived eicosanoids, were examined with human neutrophils. At nanomolar concentrations, LXA4 and LXB4 each stimulated the release of (1-14C)arachidonic acid from esterified sources in neutrophils. Lipoxin-induced release of (1-14C)arachidonic acid was both dose- and time-dependent and was comparable to that induced by the chemotactic peptide f-met-leu-phe. Time-course studies revealed that lipoxin A4 and lipoxin B4 each induced a biphasic release of (1-14C)arachidonic acid, which was evident within seconds (5-15 sec) in its initial phase and minutes (greater than 30 sec) in the second phase. In contrast, the all-trans isomers of LXA4 and LXB4 did not provoke (1-14C)AA release. Lipoxin-induced release of arachidonic acid was inhibited by prior treatment of the cells with pertussis toxin but not by its beta-oligomers, suggesting the involvement of guaninine nucleotide-binding regulatory proteins in this event. Dual radiolabeling of neutrophil phospholipid classes with (1-14C)arachidonic acid and (3H)palmitic acid showed that phosphatidylcholine was a major source of lipoxin-induced release of (1-14C)arachidonic acid. They also demonstrated that lipoxins rapidly stimulate both formation of phosphatidic acid as well as phospholipid remodeling. Although both LXA4 and LXB4 (10(-8)-10(-6) M) stimulated the release of (1-14C)arachidonic acid, neither compound evoked its oxygenation by either the 5- or 15-lipoxygenase pathways (including the formation of LTB4, 20-COOH-LTB4, 5-HETE, or 15-HETE). LXA4 and LXB4 (10(-7) M) each stimulated the elevation of cytosolic Ca2+ as monitored with Fura 2-loaded cells, albeit to a lesser extent than equimolar concentrations of FMLP. Neither lipoxin altered the binding of (3H)LTB4 to its receptor on neutrophils.

  14. Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jaehong Kim

    2016-01-01

    Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

  15. Pathophysiology of neutrophil-mediated extracellular redox reactions.

    Science.gov (United States)

    Jaganjac, Morana; Cipak, Ana; Schaur, Rudolf Joerg; Zarkovic, Neven

    2016-01-01

    Neutrophil granulocyte leukocytes (neutrophils) play fundamental role in the innate immune response. In the presence of adequate stimuli, neutrophils release excessive amount of reactive oxygen species (ROS) that may induce cell and tissue injury. Oxidative burst of neutrophils acts as a double-edged sword. It may contribute to the pathology of atherosclerosis and brain injury but is also necessary in resolving infections. Moreover, neutrophil-derived ROS may also have both a tumor promoting and tumor suppressing role. ROS have a specific activities and diffusion distance, which is related to their short lifetime. Therefore, the manner in which ROS will act depends on the cells targeted and the intra- and extracellular levels of individual ROS, which can further cause production of reactive aldehydes like 4-hydroxynonenal (HNE) that act as a second messengers of ROS. In this review we discuss the influence of neutrophil mediated extracellular redox reactions in ischemia reperfusion injury, transplant rejection and chronic diseases (atherosclerosis, inflammatory bowel diseases and cancer). At the end a brief overview of cellular mechanisms to maintain ROS homeostasis is given.

  16. Granule protein processing and regulated secretion in neutrophils

    Directory of Open Access Journals (Sweden)

    Avinash eSheshechalam

    2014-09-01

    Full Text Available Neutrophils are part of a family of granulocytes that, together with eosinophils and basophils, play an essential role in innate immunity. Neutrophils are the most abundant circulating leukocytes and are vital for rapid immune responses, being recruited to sites of injury or infection within minutes, where they can act as specialized phagocytic cells. However, another prominent function of neutrophils is the release of pro-inflammatory compounds, including cytokines, chemokines and digestive enzymes, which are stored in intracellular compartments and released through regulated exocytosis. Hence, an important feature that contributes to rapid immune responses is capacity of neutrophils to synthesize and store pre-formed pro-inflammatory mediators in specialized intracellular vesicles and thus no new synthesis is required. This review will focus on advancement in three topics relevant to neutrophil secretion. First we will examine what is known about basal level pro-inflammatory mediator synthesis, trafficking and storage in secretory compartments. Second, we will review recent advancements in the mechanisms that control vesicle mobilization and the release of pre-formed mediators. Third, we will examine the upregulation and de novo synthesis of pro-inflammatory mediators by neutrophils engaged at sites of infection.

  17. Suppressed neutrophil function in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Tanaka, Fumiko; Goto, Hiroaki; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Kajiwara, Ryosuke; Naruto, Takuya; Nishimaki, Shigeru; Yokota, Shumpei

    2009-10-01

    Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 +/- 13.2 or 70.0 +/- 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 +/- 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.

  18. An investigation on the chemotactic responses of different entomopathogenic nematode strains to mechanically damaged maize root volatile compounds.

    Science.gov (United States)

    Laznik, Z; Trdan, S

    2013-07-01

    Entomopathogenic nematodes (EPNs) respond to a variety of stimuli when foraging. In a laboratory investigation, we tested the chemotactic responses of 8 EPN strains (Steinernema and Heterorhabditis) to three mechanically damaged maize root compounds (linalool, α-caryophyllene and β-caryophyllene). We hypothesized that the EPN directional response to the tested volatile compounds would vary among the species and volatile compound and may be related to foraging strategies. The nematodes with an intermediate foraging strategy (Steinernema feltiae) proved to be less active in their movement toward volatile compounds in a comparison with the ambushers (Steinernema carpocapsae) and cruisers (Steinernema kraussei and Heterorhabditis bacteriophora); β-caryophyllene was found to be the most attractive substance in our experiment. The results of our investigation showed that the cruisers were more attracted to β-caryophyllene than the ambushers and intermediates. The foraging strategy did not affect the movement of the IJs toward the other tested volatile compounds or the control. Our results suggest that the response to different volatile cues is more a strain-specific characteristic than a different host-searching strategy. Only S. carpocapsae strain B49 displayed an attraction to linalool, whereas S. kraussei showed a retarded reaction to β-caryophyllene and α-caryophyllene in our experiment. The EPN strains showed only a weak attraction to α-caryophyllene, suggesting that this volatile compound could not have an important role in the orientation of IJs to the damaged roots of maize plants. These results expand our knowledge of volatile compounds as the cues that may be used by EPNs for finding hosts or other aspects of navigation in the soil. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  20. Age is the work of art? Impact of neutrophil and organism age on neutrophil extracellular trap formation.

    Science.gov (United States)

    Ortmann, Weronika; Kolaczkowska, Elzbieta

    2018-03-01

    Neutrophil extracellular traps or NETs are released by highly activated neutrophils in response to infectious agents, sterile inflammation, autoimmune stimuli and cancer. In the cells, the nuclear envelop disintegrates and decondensation of chromatin occurs that depends on peptidylarginine deiminase 4 (PAD4) and neutrophil elastase (NE). Subsequently, proteins from neutrophil granules (e.g., NE, lactoferrin and myeloperoxidase) and the nucleus (histones) bind to decondensed DNA and the whole structure is ejected from the cell. The DNA decorated with potent antimicrobials and proteases can act to contain dissemination of infection and in sterile inflammation NETs were shown to degrade cytokines and chemokines via serine proteases. On the other hand, overproduction of NETs, or their inadequate removal and prolonged presence in vasculature or tissues, can lead to bystander damage or even initiation of diseases. Considering the pros and cons of NET formation, it is of relevance if the stage of neutrophil maturation (immature, mature and senescent cells) affects the capacity to produce NETs as the cells of different age-related phenotypes dominate in given (pathological) conditions. Moreover, the immune system of neonates and elderly individuals is weaker than in adulthood. Is the same pattern followed when it comes to NETs? The overall importance of individual and neutrophil age on the capacity to release NETs is reviewed in detail and the significance of these facts is discussed.

  1. Slow clearance gadolinium-based extracellular and intravascular contrast media for three-dimensional MR angiography.

    Science.gov (United States)

    Bremerich, J; Colet, J M; Giovenzana, G B; Aime, S; Scheffler, K; Laurent, S; Bongartz, G; Muller, R N

    2001-04-01

    The objective of this study was to assess two new slow-clearance contrast media with extracellular and intravascular distribution for magnetic resonance angiography (MRA). Extracellular Gd-DTPA-BC(2)glucA and intravascular Gd(DO3A)(3)-lys(16) were developed within the European Biomed2 MACE Program and compared with two reference compounds, intravascular CMD-A2-Gd-DOTA and extracellular GdDOTA, in 12 rats. Pre- and post-contrast three-dimensional MR (TR/TE = 5 msec/2.2 msec; isotropic voxel size 0.86 mm(3)) was acquired for 2 hours. Signal-to-noise enhancement (DeltaSNR) was calculated. Two minutes after injection, all contrast media provided strong vascular signal enhancement. The DeltaSNR for Gd-DTPA-BC(2)glucA, Gd(DO3A)(3)-lys(16), CMD-A2-Gd-DOTA, and GdDOTA were 13.0 +/- 1.8, 25.0 +/- 3.2, 25.0 +/- 4.0, and 18.0 +/- 3.4, respectively. Gd-DTPA-BC(2)glucA, Gd(DO3A)(3)-lys(16), and CMD-A2-Gd-DOTA cleared slowly from the circulation, whereas GdDOTA cleared rapidly. Vascular DeltaSNR at 2 hours were 2.9 +/- 0.6, 25.0 +/- 3.2, 25.0 +/- 4.0, and 0.4 +/- 1.0. Gd(DO3A)(3)-lys(16) provided strong vascular and minor background enhancement, and thus may be useful for MRA or perfusion imaging. Gd-DTPA-BC(2)glucA produces persistent enhancement of extracellular water, and thus may allow quantification of extracellular distribution volume and assessment of myocardial viability.

  2. Polymer coating embolism from intravascular medical devices - a clinical literature review.

    Science.gov (United States)

    Chopra, Amitabh M; Mehta, Monik; Bismuth, Jean; Shapiro, Maksim; Fishbein, Michael C; Bridges, Alina G; Vinters, Harry V

    Over the past three decades, lubricious (hydrophobic and/or hydrophilic) polymer-coated devices have been increasingly adopted by interventional physicians and vascular surgeons to access and treat a wider range of clinical presentations. Recent clinical literature highlights the presence of polymer coating emboli within the anatomy - a result of coating separation from an intravascular device - and associates it with a range of adverse clinical sequelae. The 2015 U.S. Food and Drug Administration safety communication titled "Lubricious Coating Separation from Intravascular Medical Devices" acknowledges these concerns and concludes that it will work with stakeholders to develop nonclinical test methodologies, establish performance criteria, and identify gaps in current national and international device standards for coating integrity performance. Despite this communication and multiple case reports from interventional physicians, pathologists, dermatologists and other involved physician specialties, polymer coating embolism remains clinically underrecognized. This article consolidates the available literature on polymer coating embolism (1986-2016) and highlights the following relevant information for the physician: (a) the history and elusive nature of polymer coating embolism; (b) potential incidence rates of this phenomenon; (c) reported histologic findings and clinical effects of polymer emboli in the anatomy; (d) the importance of the collaborative clinician-pathologist partnership to report polymer embolism findings; and (e) the importance to study particulate release from intravascular devices so as to further understand and potentially evolve coated interventional technologies. Preliminary research on coatings highlights the potential of using iterations of coatings on medical devices that attain the desired therapeutic result and mitigate or eliminate particulates altogether. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Management of subarachnoid hemorrhage classified grade V. Possibility of intravascular treatment

    Energy Technology Data Exchange (ETDEWEB)

    Uzura, Masahiko; Oshima, Kousuke; Morishima, Hiroyuki; Uchida, Kazuyoshi; Watanabe, Hiroyuki; Nakamura, Homare; Tanaka, Katsuyuki; Sekino, Hiroaki; Akashi, Katsuya [St. Marianna Univ., Kawasaki, Kanagawa (Japan). School of Medicine

    2001-10-01

    Management outcomes in poor-grade patients (World Federation of Neurological Surgeons Committee on a Universal Subarachnoid Hemorrhage Grading Scale Grade V) with ruptured cerebral aneurysms have historically been unsatisfactory. In the present study, we examined the possibility of intravascular treatment for ruptured aneurysm detected by 3-Dimensional CT angiography (3D-CTA) in poor-grade SAH patients. From April 1997 to July 2000, 3D-CTA was performed on 54 of 73 patients admitted with Grade V subarachnoid hemorrhage (SAH). Excluding 3 patients who underwent emergency surgery for ruptured aneurysms and intracerebral hematomas, CT findings from the remaining 51 patients were analyzed. The study included 23 men and 28 women, ranging in age from 28 to 91 with an average age of 63.6. The patients' initial scores on the Glasgow Coma Scale upon admission were 3 in 36 patients (including 19 patients who had undergone cardio-pulmonary arrest), 4 in 11 patients, 5 in 2 patients, and 6 in 2 patients. Ruptured aneurysms responsible for SAH were clearly delineated in 41 aneurysms from 39 patients, with 32 aneurysms in the anterior circulation and 9 in the posterior circulation. Patients with Glasgow Coma Scale of 4 or higher whose score did not progressively decrease for 12 hours after symptom onset were considered for intravascular treatment. In our study, 4 of 39 patients (10.3%) met these criteria. Glasgow Outcome Scale results were good recovery in 1 case, moderate disability in 1 case, severe disability in 1 case, and death in the remaining 48 cases. These results suggest that the management course for poor-grade (WFNS Grade V) SAH patients who retain brain stem reflexes contain the following: identification of aneurysms by 3D-CTA, maintenance of adequate sedation and external drainage to treat acute hydrocephalus, continued minimum 12-hour observation, monitoring levels of consciousness where possible, and consideration of aggressive therapy including

  4. Ischemia monitoring in off-pump coronary artery bypass surgery using intravascular near-infrared spectroscopy

    Directory of Open Access Journals (Sweden)

    Zerkowski Hans-Reinhard

    2006-05-01

    Full Text Available Abstract Background In off-pump coronary artery bypass surgery, manipulations on the beating heart can lead to transient interruptions of myocardial oxygen supply, which can generate an accumulation of oxygen-dependent metabolites in coronary venous blood. The objective of this study was to evaluate the reliability of intravascular near-infrared spectroscopy as a monitoring method to detect possible ischemic events in off-pump coronary artery bypass procedures. Methods In 15 elective patients undergoing off-pump myocardial revascularization, intravascular near-infrared spectroscopic analysis of coronary venous blood was performed. NIR signals were transferred through a fiberoptic catheter for signal emission and collection. For data analysis and processing, a miniature spectrophotometer with multivariate statistical package was used. Signal acquisition and analysis were performed before and after revascularization. Spectroscopic data were compared with hemodynamic parameters, electrocardiogram, transesophageal echocardiography and laboratory findings. Results A conversion to extracorporeal circulation was not necessary. The mean number of grafts per patient was 3.1 ± 0.6. An intraoperative myocardial ischemia was not evident, as indicated by electrocardiogram and transesophageal echocardiography. Continuous spectroscopic analysis showed reproducible absorption spectra of coronary sinus blood. Due to uneventful intraoperative courses, clear ischemia-related changes could be detected in none of the patients. Conclusion Our initial results show that intravascular near-infrared spectroscopy can reliably be used for an online intraoperative ischemia monitoring in off-pump coronary artery bypass surgery. However, the method has to be further evaluated and standardized to determine the role of spectroscopy in off-pump coronary artery bypass surgery.

  5. Intravascular ultrasonic-photoacoustic (IVUP) endoscope with 2.2-mm diameter catheter for medical imaging.

    Science.gov (United States)

    Bui, Nhat Quang; Hlaing, Kyu Kyu; Nguyen, Van Phuc; Nguyen, Trung Hau; Oh, Yun-Ok; Fan, Xiao Feng; Lee, Yong Wook; Nam, Seung Yun; Kang, Hyun Wook; Oh, Junghwan

    2015-10-01

    Intravascular ultrasound (IVUS) imaging is extremely important for detection and characterization of high-risk atherosclerotic plaques as well as gastrointestinal diseases. Recently, intravascular photoacoustic (IVPA) imaging has been used to differentiate the composition of biological tissues with high optical contrast and ultrasonic resolution. The combination of these imaging techniques could provide morphological information and molecular screening to characterize abnormal tissues, which would help physicians to ensure vital therapeutic value and prognostic significance for patients before commencing therapy. In this study, integration of a high-frequency IVUS imaging catheter (45MHz, single-element, unfocused, 0.7mm in diameter) with a multi-mode optical fiber (0.6mm in core diameter, 0.22 NA), an integrated intravascular ultrasonic-photoacoustic (IVUP) imaging catheter, was developed to provide spatial and functional information on light distribution in a turbid sample. Simultaneously, IVUS imaging was co-registered to IVPA imaging to construct 3D volumetric sample images. In a phantom study, a polyvinyl alcohol (PVA) tissue-mimicking arterial vessel phantom with indocyanine green (ICG) and methylene blue (MB) inclusion was used to demonstrate the feasibility of mapping the biological dyes, which are used in cardiovascular and cancer diagnostics. For the ex vivo study, an excised sample of pig intestine with ICG was utilized to target the biomarkers present in the gastrointestinal tumors or the atherosclerotic plaques with the proposed hybrid technique. The results indicated that IVUP endoscope with the 2.2-mm diameter catheter could be a useful tool for medical imaging. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The acute neutrophil response mediated by S100 alarmins during vaginal Candida infections is independent of the Th17-pathway.

    Science.gov (United States)

    Yano, Junko; Kolls, Jay K; Happel, Kyle I; Wormley, Floyd; Wozniak, Karen L; Fidel, Paul L

    2012-01-01

    Vulvovaginal candidiasis (VVC) caused by Candida albicans affects a significant number of women during their reproductive ages. Clinical observations revealed that a robust vaginal polymorphonuclear neutrophil (PMN) migration occurs in susceptible women, promoting pathological inflammation without affecting fungal burden. Evidence to date in the mouse model suggests that a similar acute PMN migration into the vagina is mediated by chemotactic S100A8 and S100A9 alarmins produced by vaginal epithelial cells in response to Candida. Based on the putative role for the Th17 response in mucosal candidiasis as well as S100 alarmin induction, this study aimed to determine whether the Th17 pathway plays a role in the S100 alarmin-mediated acute inflammation during VVC using the experimental mouse model. For this, IL-23p19(-/-), IL-17RA(-/-) and IL-22(-/-) mice were intravaginally inoculated with Candida, and vaginal lavage fluids were evaluated for fungal burden, PMN infiltration, the presence of S100 alarmins and inflammatory cytokines and chemokines. Compared to wild-type mice, the cytokine-deficient mice showed comparative levels of vaginal fungal burden and PMN infiltration following inoculation. Likewise, inoculated mice of all strains with substantial PMN infiltration exhibited elevated levels of vaginal S100 alarmins in both vaginal epithelia and secretions in the vaginal lumen. Finally, cytokine analyses of vaginal lavage fluid from inoculated mice revealed equivalent expression profiles irrespective of the Th17 cytokine status or PMN response. These data suggest that the vaginal S100 alarmin response to Candida does not require the cells or cytokines of the Th17 lineage, and therefore, the immunopathogenic inflammatory response during VVC occurs independently of the Th17-pathway.

  7. Influence of standard and novel LTB4 analogs on human neutrophil chemotaxis measured by the multiwell cap assay.

    Science.gov (United States)

    Psychoyos, S; Uziel-Fusi, S; Bhagwat, S; Morrissey, M M

    1989-11-30

    Standard and novel LTB4 analogs were tested for neutrophil chemoattractant activity using the multiwell cap assay (Evans et al. (1986) Biosc. Rep. 6, 1041). The assay uses disposable equipment and measures chemotaxis by the number of cells able to migrate across the full thickness of cellulose nitrate filters. Under standard conditions (90 min incubation at 37 degrees C in buffer containing 2% bovine albumin), LTB4 and 6-cis-LTB1 had EC50 values of 3.5 and 15,000 nM, respectively. 20-hydroxy-LTB4 was equipotent with LTB4 and exhibited a similar biphasic chemotactic response, however, only one third of the number of cells migrated through the filter. 20-carboxy-LTB4 was inactive up to 1,000 nM. 5-desoxy-((6,7)-cis-cyclopropyl)-LTB2, (6,7)-benzo-LTB2 and 5-desoxy-(8,10)-LTB2 had EC50 values of 11,300, 50,000 and 84,000 nM, respectively. Checkerboard analysis indicated a chemokinetic component of 42% for LTB4 at a concentration causing peak chemotaxis. Reduction of albumin in the buffer to 0.5% increased the apparent potencies of LTB4 and 6-cis-LTB1 five-fold. Since LTB4 is a mediator of inflammation, various anti-inflammatory agents were tested at peak concentrations observed in vivo for in vitro inhibition of LTB4-stimulated chemotaxis in the presence of 0.5% albumin. Under the conditions of the assay, chloroquine diphosphate, dexamethasone, indomethacin, penicillamine, piroxicam and diclofenac sodium were inactive; gold sodium thiomalate was inhibitory (IC50 = 20 microM).

  8. Rash, disseminated intravascular coagulation and legionella: Episode 10 and a rewind into the past

    Directory of Open Access Journals (Sweden)

    Prashanth M. Thalanayar

    2015-01-01

    Full Text Available Legionella pneumophila is the most common cause of legionellosis and is one of the organisms causing atypical pneumonia. We report the presentation of disseminated intravascular coagulation (DIC and skin rash in a single case of severe Legionella pneumonia. The unique clinical presentation of a diffuse rash diagnosed as purpura fulminans and the unpredictable variations encountered during the diagnostic work-up of the case make this write-up crucial. This article synthesizes all reported cases of L. pneumonia associated with cutaneous manifestations as well as cases presenting with DIC. Furthermore, this manuscript illustrates the correlation between cutaneous and coagulopathic manifestations, and morbidity and mortality from L. pneumonia.

  9. Fatal Klebsiella pneumoniae meningitis and concomitant disseminated intravascular coagulation in a patient with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ho Min-Po

    2009-01-01

    Full Text Available Bacterial meningitis remains a major cause of death and long-term neurologic sequelae worldwide. We present a case of fatal Klebsiella pneumoniae meningitis and concomitant disseminated intravascular coagulation (DIC in a 72-year-old woman with diabetes mellitus (DM. Both blood and cerebrospinal fluid cultures grew Klebsiella pneumoniae . Due to advanced age, newly recognized DM, K. pneumoniae bacteremia, and DIC, the prognosis of our patient was poor. Eight hours after arrival to the emergency department, cardiopulmonary resuscitation was necessary in this patient, but she died despite an early diagnosis and appropriate antibiotic therapy.

  10. Acute kidney injury and disseminated intravascular coagulation due to mercuric chloride poisoning

    Directory of Open Access Journals (Sweden)

    J Dhanapriya

    2016-01-01

    Full Text Available Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (DIC. Renal biopsy showed acute tubular necrosis. Later, the consumed substance was proven to be mercuric chloride. His renal failure improved over time, and his creatinine normalized after 2 months.

  11. Disseminated intravascular coagulation in a patient with metastatic prostate cancer: Fatal outcome following strontium-89 therapy

    Energy Technology Data Exchange (ETDEWEB)

    Leong, C.; McKenzie, R.; Coupland, D.B. [Univ. of British Columbia, (Canada)] [and others

    1994-10-01

    A patient with metastatic prostate cancer was found to have low-grade disseminated intravascular coagulation (DIC). He had significant bone pain despite external-beam radiotherapy and was given {sup 89}Sr with subsequent thrombocytopenia and epistaxis. The patient died from generalized hemorrhage 36 days postinjection. Although it is not possible to establish a causal relationship between {sup 89}Sr and DIC, practitioners should be alert to complications associated with the primary disorder which might occur at a time to raise concern about the intervention. 8 refs., 1 tab.

  12. [Intravascular Hemolysis Caused by Stenosis of an Elephant Trunk;Report of a Case].

    Science.gov (United States)

    Takamaru, Rikako; Kawahito, Koji; Aizawa, Kei; Misawa, Yoshio

    2017-07-01

    Symptomatic intravascular hemolysis after prosthetic aortic graft replacement is rare. It is primarily attributed to mechanical injury of red blood cells caused by stenosis of the vascular graft. A 50-year-old man presented with hemolytic anemia, 5 years after total arch replacement with an elephant trunk for type A aortic dissection. The hemolysis was caused by graft stenosis of the elephant trunk. Endovascular treatment for the stenotic elephant trunk was successfully performed. The postoperative course was uneventful, and the hemolysis was resolved immediately after operation.

  13. Effects of acrolein on leukotriene biosynthesis in human neutrophils.

    Science.gov (United States)

    Berry, Karin A Zemski; Henson, Peter M; Murphy, Robert C

    2008-12-01

    Acrolein is a toxic, highly reactive alpha,beta-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-lipoxygenase (5-LO) products in addition to small amounts of cyclooxygenase (COX) products were detected using LC/MS/MS. A dose-dependent decrease in the formation of 5-LO products was observed in GM-CSF/fMLP-stimulated neutrophils when acrolein (0-50 microM) was present with almost complete inhibition at > or = 25 microM acrolein. The production of COX products was not affected by acrolein in these cells. The effect of acrolein was examined on key parts of the eicosanoid pathway, such as arachidonic acid release, intracellular calcium ion concentration, and adenosine production. In addition, the direct effect of acrolein on 5-LO enzymatic activity was probed using a recombinant enzyme. Some of these factors were affected by acrolein but did not completely explain the almost complete inhibition of 5-LO product formation in GM-CSF/fMLP-treated cells with acrolein. In addition, the effect of acrolein on different stimuli that initiate the 5-LO pathway [platelet-activating factor (PAF)/fMLP, GM-CSF/PAF, opsonized zymosan, and A23187] was examined. Acrolein had no significant effect on the leukotriene production in neutrophils stimulated with PAF/fMLP, GM-CSF/ PAF, or OPZ. Additionally, 50% inhibition of the 5-LO pathway was observed in A23187-stimulated neutrophils. Our results suggest that acrolein has a profound effect on the 5-LO pathway in neutrophils, which may have implications in disease states, such as chronic obstructive pulmonary disease and other pulmonary disease, where both activated neutrophils and acrolein are

  14. Platelet modulation of human neutrophil functions

    Energy Technology Data Exchange (ETDEWEB)

    McGarrity, S.T.; Hyers, T.M.; Webster, R.O.

    1986-03-01

    The combined presence of platelets (PLTS) and neutrophils (PMN) at inflammatory sites has led to examination of the hypothesis that interaction of these cells modulates their responses to stimuli. Gel-filtered human PLTS (GFP) were found to inhibit N-formyl-met-leu-phe (FMLP) and phorbol myristate acetate (PMA) stimulated PMN O/sub 2//sup -/ generation in a concentration-dependent fashion. The heat-stable inhibitory activity was present in the supernatants of GFP after incubation with FMLP (10/sup -7/M), thrombin (0.5 U/ml) or ADP (20 ..mu..M), suggesting a role for PLT release products. PLT lysates added to PMN produced up to 80% inhibition of O/sub 2//sup -/ generation for PMA and 40% for FMLP. Like GFP, lysates failed to scavenge O/sub 2/..pi.. produced by xanthine oxidase-hypoxanthine. The inhibitory activity could not be ascribed to serotonin or adenosine. PLT lysates failed to compete with /sup 3/H-FMLP for binding to PMN. Sephadex G-200 fractionation of PLT lysates releaved two peaks of inhibitory activity with apparent Mr > 200,000 and < 14,000 Daltons. Pretreatment of PMN with PLT lysates also results in a concentration-dependent inhibition of degranulation provoked by FMLP (2 x 10/sup -7/M) or PMA (2 ng/ml) and PMN chemotaxis to FMLP (10/sup -8/M). These studies indicate that preformed PLT mediator(s) released in response to physiological stimuli may limit tissue damage by PMN at sites of inflammation.

  15. Neutrophil labeling with [99mTc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

    International Nuclear Information System (INIS)

    Gallagher, Hayley; Ramsay, Stuart C.; Barnes, Jodie; Maggs, Jacqueline; Cassidy, Nathan; Ketheesan, Natkunam

    2006-01-01

    Introduction: [ 99m Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection

  16. Neutrophil labeling with [{sup 99m}Tc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, Hayley [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Ramsay, Stuart C. [School of Medicine, James Cook University, Townsville, Queensland (Australia) and Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia)]. E-mail: stuart.ramsey@jcu.edu.au; Barnes, Jodie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Maggs, Jacqueline [Department of Nuclear Medicine, Townsville Hospital, Townsville, Queensland 4814 (Australia); Cassidy, Nathan [Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia); Ketheesan, Natkunam [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland (Australia)

    2006-04-15

    Introduction: [{sup 99m}Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection.

  17. Intravascular Large B-Cell Lymphoma Presenting with Diffuse Gallbladder Wall Thickening: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Sayf Al-Katib

    2018-01-01

    Full Text Available Intravascular large B-cell lymphoma is a rare subtype of extranodal diffuse B-cell lymphoma characterized by proliferation of neoplastic cells within the lumen of small and medium sized vessels. Clinical and imaging findings are nebulous as the intravascular subtype of lymphoma can involve a multitude of organs. Involvement of the gallbladder is extremely uncommon, and imaging findings can be easily confused for more prevalent pathologies. We report a case of intravascular large B-cell lymphoma in an 83-year-old male and review clinical presentation and imaging findings on CT, ultrasound, hepatobiliary iminodiacetic acid (HIDA scan, and MRI. It is important for the radiologist to know about this disease as the imaging findings are atypical of other types of lymphoma, and this may lead to a delay in diagnosis and treatment.

  18. Combined hyponatremia and hypocalcemia after intravascular absorption of 1.5% glycine during operative hysteroscopy. A case report

    Directory of Open Access Journals (Sweden)

    Sherif S. Sultan

    2016-07-01

    Full Text Available Intravascular absorption of distending media may complicate operative hysteroscopy. Consequences differ according to type, amount and speed of absorption of the distending media. We report a case of intravascular absorption of more than one liter of 1.5% glycine. A 36 years old female developed metabolic acidosis, hyponatremia and hypocalcemia during operative hysteroscopy scheduled for resection of a uterine fibroid. Serum sodium reached down to 119 mmol/l and ionized calcium to 0.898 mmol/l. Serial estimations of arterial blood gases and serum electrolytes were followed. Management was successful in preventing serious side effects. Meticulous monitoring of distending media input/output balance remains the cornerstone in prevention of intravascular absorption.

  19. Effects of Hypoxia on Erythrocyte Membrane Properties—Implications for Intravascular Hemolysis and Purinergic Control of Blood Flow

    Directory of Open Access Journals (Sweden)

    Ryszard Grygorczyk

    2017-12-01

    Full Text Available Intravascular hemolysis occurs in hereditary, acquired, and iatrogenic hemolytic conditions but it could be also a normal physiological process contributing to intercellular signaling. New evidence suggests that intravascular hemolysis and the associated release of adenosine triphosphate (ATP may be an important mechanism for in vivo local purinergic signaling and blood flow regulation during exercise and hypoxia. However, the mechanisms that modulate hypoxia-induced RBC membrane fragility remain unclear. Here, we provide an overview of the role of RBC ATP release in the regulation of vascular tone and prevailing assumptions on the putative release mechanisms. We show importance of intravascular hemolysis as a source of ATP for local purinergic regulation of blood flow and discuss processes that regulate membrane propensity to rupture under stress and hypoxia.

  20. Offline fusion of co-registered intravascular ultrasound and frequency domain optical coherence tomography images for the analysis of human atherosclerotic plaques

    DEFF Research Database (Denmark)

    Räber, Lorenz; Heo, Jung Ho; Radu, Maria D

    2012-01-01

    To demonstrate the feasibility and potential usefulness of an offline fusion of matched optical coherence tomography (OCT) and intravascular ultrasound (IVUS)/virtual histology (IVUS-VH) images.......To demonstrate the feasibility and potential usefulness of an offline fusion of matched optical coherence tomography (OCT) and intravascular ultrasound (IVUS)/virtual histology (IVUS-VH) images....

  1. Comparison of utility of blood cultures from intravascular catheters and peripheral veins: a systematic review and decision analysis.

    Science.gov (United States)

    Falagas, Matthew E; Kazantzi, Maria S; Bliziotis, Ioannis A

    2008-01-01

    Blood cultures are sometimes obtained from intravascular catheters for convenience. However, there is controversy regarding this practice. The authors compared the diagnostic test characteristics of blood cultures obtained from intravascular catheters and peripheral veins. Relevant studies for inclusion in this review were identified through PubMed (January 1970-October 2005) and the Cochrane Central Register of Controlled Trials. Studies that reported clear definitions of true bacteraemia were included in the analysis. Two reviewers independently extracted the data. Six studies were included in the analysis, providing data for 2677 pairs of blood cultures obtained from an intravascular catheter and a peripheral venipuncture. A culture obtained from an intravascular catheter was found to be a diagnostic test for bacteraemia with better sensitivity (OR 1.85, 95 % CI 1.14-2.99, fixed effects model) and better negative predictive value (almost with statistical significance) (OR 1.55, 95 % CI 0.999-2.39, fixed effects model) but with less specificity (OR 0.33, 95 % CI 0.18-0.59, random effects model) and lower positive predictive value (OR 0.41, 95 % CI 0.23-0.76, random effects model) compared to a culture taken by peripheral venipuncture. In a group of 1000 patients, eight additional patients with true bacteraemia would be identified and 59 falsely diagnosed as having bacteraemia by a blood culture obtained from an intravascular catheter compared to results of the peripheral blood culture. Given the consequences of undertreating patients with bacteraemia, the authors believe that, based on the available evidence, at least one blood culture should be obtained from the intravascular catheter.

  2. Formation of neutrophil extracellular traps under low oxygen level

    Directory of Open Access Journals (Sweden)

    Katja Branitzki-Heinemann

    2016-11-01

    Full Text Available Since their discovery, neutrophil extracellular traps (NETs have been characterized as a fundamental host innate immune defense mechanism. Conversely, excessive NET release may have a variety of detrimental consequences for the host. A fine balance between NET formation and elimination is necessary to sustain a protective effect during an infectious challenge. Our own recently published data revealed that stabilization of hypoxia inducible factor 1α (HIF-1α by the iron chelating HIF-1α-agonist desferoxamine or AKB-4924 enhanced the release of phagocyte extracellular traps. Since HIF-1α is a global regulator of the cellular response to low oxygen, we hypothesized that NET formation may be similarly increased under low oxygen conditions. Hypoxia occurs in tissues during infection or inflammation, mostly due to overconsumption of oxygen by pathogens and recruited immune cells. Therefore, experiments were performed to characterize the formation of NETs under hypoxic oxygen conditions compared to normoxia. Human blood-derived neutrophils were isolated and incubated under normoxic (21% oxygen level and compared to hypoxic (1% conditions. Dissolved oxygen levels were monitored in the primary cell culture using a Fibox4-PSt3 measurement system. The formation of NETs was quantified by fluorescence microscopy in response to the known NET-inducer phorbol 12-myristate 13-acetate (PMA or S. aureus wildtype and a nuclease-deficient mutant. In contrast to our hypothesis, spontaneous NET formation of neutrophils incubated under hypoxia was distinctly reduced compared to control neutrophils incubated under normoxia. Furthermore, neutrophils incubated under hypoxia showed significantly reduced formation of NETs in response to PMA. Gene expression analysis revealed that mRNA level of hif-1α as well as hif-1α target genes was not altered. However, in good correlation to the decreased NET formation under hypoxia, the cholesterol content of the neutrophils was

  3. Combined hyponatremia and hypocalcemia after intravascular absorption of 1.5% glycine during operative hysteroscopy. A case report

    OpenAIRE

    Sherif S. Sultan

    2016-01-01

    Intravascular absorption of distending media may complicate operative hysteroscopy. Consequences differ according to type, amount and speed of absorption of the distending media. We report a case of intravascular absorption of more than one liter of 1.5% glycine. A 36 years old female developed metabolic acidosis, hyponatremia and hypocalcemia during operative hysteroscopy scheduled for resection of a uterine fibroid. Serum sodium reached down to 119 mmol/l and ionized calcium to 0.898 mmol/l...

  4. Demodex-associated bacterial proteins induce neutrophil activation.

    LENUS (Irish Health Repository)

    2012-02-01

    Background: Patients with rosacea demonstrate a higher density of Demodex mites in their skin than controls. A bacterium isolated from a Demodex mite from a patient with papulopustular rosacea (PPR) was previously shown to provoke an immune response in patients with PPR or ocular rosacea thus suggesting a possible role for bacterial proteins in the etiology of this condition. Objectives: To examine the response of neutrophils to proteins derived from a bacterium isolated from a Demodex mite. Methods: Bacterial cells were lysed and proteins were partially purified by AKTA-FPLC. Isolated neutrophils were exposed to bacterial proteins and monitored for alterations in migration, degranulation and cytokine production. Results: Neutrophils exposed to proteins from Bacillus cells demonstrated increased levels of migration and elevated release of MMP-9, an enzyme known to degrade collagen and cathelicidin, an antimicrobial peptide. In addition neutrophils exposed to the bacterial proteins demonstrated elevated rates of Il-8 and TNF-alpha production. Conclusions: Proteins produced by a bacterium isolated from a Demodex mite have the ability to increase the migration, degranulation and cytokine production abilities of neutrophils. These results suggest that bacteria may play a role in the inflammatory erythema associated with rosacea.

  5. Burn injury reduces neutrophil directional migration speed in microfluidic devices.

    Directory of Open Access Journals (Sweden)

    Kathryn L Butler

    2010-07-01

    Full Text Available Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72-120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.

  6. Increased lung neutrophil apoptosis and inflammation resolution in nonresponding pneumonia.

    Science.gov (United States)

    Moret, I; Lorenzo, M J; Sarria, B; Cases, E; Morcillo, E; Perpiñá, M; Molina, J M; Menéndez, R

    2011-11-01

    Neutrophil activation state and its relationship with an inflammatory environment in community-acquired pneumonia (CAP) remain insufficiently elucidated. We aimed to evaluate the neutrophil apoptosis and cytokine pattern in CAP patients after 72 h of treatment, and their impact on infection resolution. Apoptosis of blood and bronchoalveolar lavage (BAL) neutrophils was measured in nonresponding CAP (NCAP), in responding CAP (blood only) and in patients without infection (control). Pro-inflammatory (interleukin (IL)-6, IL-8) and anti-inflammatory (IL-10) cytokines were measured. Main outcomes were clinical stability and days of hospitalisation. Basal neutrophil apoptosis was higher in the BAL and blood of NCAP, whereas spontaneous apoptosis (after 24 h culture) was lower. Cytokines in NCAP were higher than in responding CAP and control: IL-6 was increased in BAL and blood, IL-8 in BAL and IL-10 in blood. An increased basal apoptosis (≥20%) in BAL of NCAP was associated with lower systemic IL-10 (p<0.01), earlier clinical stability (p=0.05) and shorter hospital stay (p=0.02). A significant correlation was found for systemic IL-6 and IL-10 with days to reach stability and length of stay. After 72 h of treatment, an increased basal alveolar neutrophil apoptosis might contribute to downregulation of inflammation and to faster clinical stability.

  7. CD147 and CD98 complex-mediated homotypic aggregation attenuates the CypA-induced chemotactic effect on Jurkat T cells.

    Science.gov (United States)

    Guo, Na; Zhang, Kui; Lv, Minghua; Miao, Jinlin; Chen, Zhinan; Zhu, Ping

    2015-02-01

    Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3ζ and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4(+) T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data

  8. Development of sup 1 sup 9 sup 2 Ir radiation sources for intravascular irradiation

    CERN Document Server

    Kogure, H; Iwamoto, S; Iwata, K; Kawauchi, Y; Nagata, Y; Sorita, T; Suzuki, K

    2003-01-01

    Intravascular brachytherapy is a novel therapy for preventing the restenosis of coronary artery by use of low-dose irradiation. JAERI and Kyoto University have been developing sup 1 sup 9 sup 2 Ir radiation sources by the cooperative research project entitled as 'The research on safety and effectiveness of the intravascular brachytherapy for preventing restenosis of the coronary artery disease' since 1998. The radiation source was introduced into the stenosis through a catheter (a guide-tube to insert directly into vascular) to irradiate the diseased part. Ten sup 1 sup 9 sup 2 Ir seed sources (phi 0.4 mm x 2.5 mm) were positioned between nylon spacers (phi 0.3 mm x 1.0 mm) in a flexible covering tube and the tube was plugged with a core-wire; the tube was shrunk to fix the inside materials and the size is 0.46 mm in diameter and 3 m in length. The physically optimal design was determined to insert the radiation source easily into vascular and to get the dose uniformity in the diseased part. The production me...

  9. Intrauterine intravascular transfusion for fetal haemolytic anaemia: the Western Australian experience.

    Science.gov (United States)

    Newnham, J P; Phillips, J M; Stock, R

    1992-11-16

    To report the first four years' clinical experience with fetal intravascular blood transfusion for the treatment of fetal haemolytic anaemia in Western Australia. King Edward Memorial Hospital, Perth, which is the sole tertiary level perinatal centre in Western Australia with a referral base of approximately 25,000 pregnancies each year. Transfusion was by injection of packed cells from Rh-negative donors into the fetal umbilical vein near the site of insertion into the placenta. Fetal haemoglobin levels were measured before and after each transfusion. In most cases, the fetus was paralysed by intramuscular tubocurarine. Sixty intravenous transfusions were performed in 20 pregnancies. At the time of the initial transfusion, the mean haemoglobin level was 5.8 g/dL (range, 2.5-8.5 g/dL) and six fetuses had signs of hydrops. The case survival rate was 80% and the procedure survival rate was 93%. Three of the deaths occurred in the first five cases. Caesarean section was performed during two of the procedures, one because of bleeding from the cord puncture site and one because of tamponade of the umbilical vessels. Fetal intravascular transfusion is a highly effective treatment for fetal alloimmunisation and allows pregnancies to continue to term and to be delivered vaginally. However, the procedure may be difficult and requires a team approach with ready access to fetal monitoring and emergency caesarean section. Our results suggest that increasing experience of the team is a major factor in improved outcome.

  10. Pulmonary intravascular lymphoma detected by FDG PET-CT: a case report.

    Science.gov (United States)

    Kohan, A A; Paganini, L; Biedak, P; Arma, J I; Dalurzo, M C L; Garcia-Monaco, R D

    2013-01-01

    Intravascular lymphoma is a rare subtype of extranodal Non-Hodgkin's lymphoma. Its prognosis is poor in a high percentage of cases due to its insidious appearance and low clinical suspicion. Its diagnosis is usually only reached after an autopsy. It may affect different organs as a whole or only one organ. It is extremely rare that the lung is the only damaged organ. Its diagnosis depends of the clinician's suspicion and proper evaluation with imaging studies as well as correct selection of the organ to be biopsied. When detected on time, the treatment of choice is a combination of a series of chemotherapy associated to a monoclonal antibody (anti-CD20). We present the case of a male patient who underwent a positron emission tomography-computed tomography with 2-[F-18]-fluoro-2 deoxy-D-glucose (FDG) due to symptoms suggestive of a lymphoproliferative disease with no clear structural abnormalities. The images led to a diagnosis of pulmonary intravascular large B cell lymphoma. Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

  11. Plasma volume, intravascular albumin and its transcapillary escape rate in patients with extensive skin disease

    DEFF Research Database (Denmark)

    Parving, H H; Worm, A M; Rossing, N

    1976-01-01

    Plasma volume and plasma concentration and transcapillary escape rate of albumin (TER alb), i.e. the fraction of intravascular mass of albumin that passes to the extravascular space per unit time, were determined using 125I-labelled human albumin in eight patients with extensive skin disease....... Plasma volume and plasma albumin concentration were reduced (P less than 0-05). Thus the intravascular albumin mass was moderately decreased to an average of 0-55 +/- 0-06 (s.d.) g/cm height compared with a normal mean value of 0-77 +/- 0-07 (s.d.) g/cm. This 29% decrease is statistically significant (P...... less than 0-001). The transcapillary escape rate of albumin (TER alb) was significantly elevated, mean 8-6 +/- 1-1 (s.d.) % X h-1, as compared to normal subjects, mean 5-6 +/- 1-1 (s.d.) % X h-1, (+54%, P less than 0-001). The same patients were studied again after a 1-week treatment with prednisone...

  12. Focus on the research utility of intravascular ultrasound - comparison with other invasive modalities

    Directory of Open Access Journals (Sweden)

    Hoye Angela

    2011-01-01

    Full Text Available Abstract Intravascular ultrasound (IVUS is an invasive modality which provides cross-sectional images of a coronary artery. In these images both the lumen and outer vessel wall can be identified and accurate estimations of their dimensions and of the plaque burden can be obtained. In addition, further processing of the IVUS backscatter signal helps in the characterization of the type of the plaque and thus it has been used to study the natural history of the atherosclerotic evolution. On the other hand its indigenous limitations do not allow IVUS to assess accurately stent struts coverage, existence of thrombus or exact site of plaque rupture and to identify some of the features associated with increased plaque vulnerability. In order this information to be obtained, other modalities such as optical coherence tomography, angioscopy, near infrared spectroscopy and intravascular magnetic resonance imaging have either been utilized or are under evaluation. The aim of this review article is to present the current utilities of IVUS in research and to discuss its advantages and disadvantages over the other imaging techniques.

  13. Cardiac variation of inferior vena cava: new concept in the evaluation of intravascular blood volume.

    Science.gov (United States)

    Nakamura, Kensuke; Tomida, Makoto; Ando, Takehiro; Sen, Kon; Inokuchi, Ryota; Kobayashi, Etsuko; Nakajima, Susumu; Sakuma, Ichiro; Yahagi, Naoki

    2013-07-01

    Evaluation of the intravascular blood volume is an important assessment in emergency and critical care medicine. Measurement of the inferior vena cava (IVC) respiratory variation by ultrasound echography is useful, but it entails subjective problems. We have hypothesized that IVC cardiac variation is also correlated with intravascular blood volume and analyzed it automatically using computer software of two kinds, later comparing the results. Snakes, software to track boundaries by curve line continuity, and template matching software were incorporated into a computer with an ultrasound machine to track the short-axis view of IVC automatically and analyze it with approximation by ellipse. Eight healthy volunteers with temporary mild hypovolemia underwent echography before and after passive leg raising and while wearing medical anti-shock trousers. IVC cardiac variation was visually decreased by both leg raising and medical anti-shock trousers. The collapse index (maximum - minimum/maximum) of area during three cardiac beats was decreased showing a good relationship to fluid load simulations; 0.24 ± 0.03 at baseline versus 0.11 ± 0.01 with leg raising and 0.12 ± 0.01 with medical anti-shock trousers. In conclusion, IVC cardiac variation has the potential to provide an evaluation of water volume. It presents some advantages in mechanical analysis over respiratory variation. At the very least, we need to exercise some caution with cardiac variation when evaluating respiratory variation.

  14. One-stage surgery for removal of intravascular leiomyomatosis extending to right ventricle.

    Science.gov (United States)

    Chiang, Ching-Shu; Chen, Po-Lin; Kuo, Tzu-Ting; Chen, I-Ming; Wu, Nai-Yuan; Chang, Hsiao-Huang

    2018-03-01

    Intravascular leiomyomatosis (IVL) is a rare nonmalignant tumor that can be fatal if untreated. A 49-year-old nulliparous Asian woman who underwent hysterectomy and left salpingo-oophorectomy for multiple uterine leiomyomas 18 months prior presented complaining of intermittent palpitation and chest tightness for approximately 1 month. Echocardiography revealed a large mobile tumor mass extending from the inferior vena cava (IVC) to the right atrium that partially obstructed IVC flow and tricuspid inflow. Thoracicabdominopelvic computed tomography revealed a left adnexal tumor (4.8 × 2.5 cm) causing intravascular obstruction extending from the left internal iliac vein to the IVC, right atrium, and right ventricle. IVL with right heart involvement INTERVENTIONS:: Under cardiopulmonary bypass, a one-stage surgery combining sternotomy and laparotomy was performed. The tumor was approached and extracted via sternotomy, and tumor detachment and removal of residual tumors was accomplished via laparotomy. A firm, smooth, and regularly shape tumor 15.5 × 5.5 × 2.5 in size was completely removed and histopathologically confirmed as IVL. The patient tolerated the surgical procedure well and no postoperative complication was noted. We describe a one-stage surgical approach to completely remove an IVL extending to the right ventricle.

  15. Visualization of Chronic Myocardial Infarction Using the Intravascular Contrast Agent MS-325 (Gadofosveset in Patients

    Directory of Open Access Journals (Sweden)

    Thomas Thouet

    2012-01-01

    Full Text Available Aims. The aim of this study was to evaluate the potential of visualizing chronic myocardial infarction in patients using the intravascular CA MS-325 (gadofosveset, EPIX Pharmaceuticals, Mass, USA. Methods. Nine patients were enrolled in a clinical phase II multicenter trial for MRCA and perfusion imaging using MS-325. They had objective evidence of chronic myocardial infarction as visualized by previously performed late gadolinium (Gd enhancement imaging (LGE with a conventional extracellular Gd-DTPA CA (Magnevist, Bayer Healthcare, Germany, 0.2 mmol/kg/body weight serving as reference standard. A prepulse-optimized LGE study was performed immediately and at several time points after injection of MS-325 (0.05 mmol/kg/body weight. The number and localization of segments demonstrating LGE with MS-325 as well as signal intensities were compared with the reference standard (Gd-DTPA. Results. Using MS-325, LGE could be detected at every time point in all 9 patients. The accuracy of LGE with MS-325 as compared to LGE with Gd-DTPA was highest 54±4 minutes after contrast injection, resulting in a sensitivity of 84% with a specificity of 98%. Conclusion. The intravascular CA MS-325 has the potential to visualize chronic myocardial infarction. However, in comparison with Gd-DTPA, the transmural extent and the number of segments are smaller.

  16. Radiation-induced muscositis and neutrophil granulocytes in oral mucosa; Strahleninduzierte Mukositis und neutrophile Granulozyten in der Mundschleimhaut

    Energy Technology Data Exchange (ETDEWEB)

    Schmidberger, H.; Rave-Fraenk, M.; Kim, S.; Hille, A.; Pradier, O.; Hess, C.F. [Klinik fuer Strahlentherapie und Radioonkologie, Univ. Goettingen (Germany)

    2003-10-01

    Background: Chemotherapy-induced mucositis can be related to a decrease in oral neutrophils. We tested the relationship between radiation-induced mucositis and oral neutrophil counts. Patients and Methods: Oral neutrophil counts were obtained for ten patients with head and neck cancer who received radiotherapy of the pharynx and oral cavity. Four patients received additional chemotherapy (5-FU, Mitomycin). Counts were obtained before and during treatment; four healthy volunteers were included in the study as well. For evaluation, a quantitative mouth rinse assay, including neutrophil-staining with acridin-orange, was applied. Results: We observed large inter-individual variations with respect to neutrophil counts for patients and control persons (Table 1). During treatment (irradiation or chemoirradiation), large intra-individual variations were seen additionally (Figure 1). We found a correlation between neutrophil counts and clinical reaction grade. Neutrophil counts increased with increasing mucositis (Figure 2). This increase was more pronounced for patients treated with chemoirradiation compared to radiation alone. Treatment breaks at weekends had no clear influence on neutrophil counts. Conclusions: We observed a weak correlation between neutrophil counts and clinical reaction grade. However, the variations in neutrophil counts are too large to utilize this parameter as a surrogate for clinical mucositis grading. The assumption that a decrease in oral neutrophils is associated with radiation-induced mucositis was clearly negated. (orig.) [German] Hintergrund: Die chemotherapieinduzierte Mukositis kann mit einer Verarmung der Mundschleimhaut an neutrophilen Granulozyten vergesellschaftet sein. Wir ueberprueften den Zusammenhang zwischen der radiogenen Mukositis und der Anzahl neutrophiler Granulozyten. Patienten und Methoden: Bei zehn Patienten mit Tumoren der Kopf-Hals-Region, die sich einer Strahlentherapie unterzogen, wurde die Anzahl enoraler neutrophiler

  17. Doxycycline induced photodamage to human neutrophils and tryptophan

    International Nuclear Information System (INIS)

    Sandberg, S.; Glette, J.; Hopen, G.; Solberg, C.O.

    1984-01-01

    Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 μM doxycycline. At increasing light fluence the locomotion, chemiluminescence and glucose oxidation (by the hexose monophosphate shunt) of the neutrophils steadily decreased. The photodamage increased with increasing preincubation temperature and time and was enhanced in D 2 O, reduced in azide and abolished in anaerobiosis. Superoxide dismutase, catalase or mannitol did not influence the photodamage. Photooxidation of tryptophan in the presence of doxycycline was increased 9-10-fold in D 2 O and nearly abolished in the presence of 0.25 mM NaN 3 , indicating that singlet oxygen is the most important reactive oxygen species in the doxycycline-induced photodamage. The results may explain some of the features of tetracycline-induced photosensitivity and why other authors have obtained diverging results when studying the influence of tetracyclines on neutrophil functions. (author)

  18. Accelerated apoptosis of neutrophils in familial Mediterranean fever

    DEFF Research Database (Denmark)

    Manukyan, Gayane; Aminov, Rustam; Hakobyan, Gagik

    2015-01-01

    The causative mutations for familial Mediterranean fever (FMF) are located in the MEFV gene, which encodes pyrin. Pyrin modulates the susceptibility to apoptosis via its PYD domain, but how the mutated versions of pyrin affect apoptotic processes are poorly understood. Spontaneous and induced rates...... of systemic neutrophil apoptosis as well as the levels of proteins involved in apoptosis were investigated ex vivo in patients with FMF using flow cytometry and RT-qPCR. The freshly collected neutrophils from the patients in FMF remission displayed a significantly larger number of cells spontaneously entering...... apoptosis compared to control (6.27 ± 2.14 vs. 1.69 ± 0.18%). This elevated ratio was retained after 24 h incubation of neutrophils in the growth medium (32.4 ± 7.41 vs. 7.65 ± 1.32%). Correspondingly, the mRNA level for caspase-3 was also significantly increased under these conditions. In response...

  19. Neutrophilic dermatosis resembling pyoderma gangrenosum in a dog with polyarthritis.

    Science.gov (United States)

    Bardagí, M; Lloret, A; Fondati, A; Ferrer, L

    2007-04-01

    This report describes a case of neutrophilic dermatosis in a dog, with a number of clinical and pathological similarities to human pyoderma gangrenosum. A seven-year-old, female German shepherd dog with a history of non-erosive idiopathic polyarthritis was presented with severe facial swelling, bilateral erosivoulcerative lesions on the muzzle and multiple, eroded, dermal-subcutaneous nodules on the cranial trunk. Histopathological examination of skin biopsies revealed a necrotising neutrophilic dermatitis. No infectious agents could be detected using specific stains, immunohistochemistry, serology and bacterial aerobic, anaerobic or fungal cultures. A sterile neutrophilic dermatosis resembling human pyoderma gangrenosum was presumptively diagnosed, and the patient showed an excellent response to treatment with prednisone and ciclosporin.

  20. Localized Subcutaneous Acute Febrile Neutrophilic Dermatosis in a Dog

    Directory of Open Access Journals (Sweden)

    Karolin Schoellhorn

    2012-01-01

    Full Text Available A two-year-old spayed female mixed-breed dog was presented with a five-day history of hemorrhagic gastroenteritis and fever. On physical examination, the dog was lethargic and clinically dehydrated. The skin of the entire ventral abdomen extending to both flanks was erythematous, swollen and painful on palpation. Histopathological examination of skin biopsies revealed a severe diffuse neutrophilic dermatitis and panniculitis, resembling the subcutaneous form of Sweet’s syndrome in humans. A large part of the skin lesion developed full-thickness necrosis. After intensive care, three surgical wound debridements and wound adaptations, the wound healed by secondary intention within ten weeks. In the absence of infection of the skin or neoplasia, a diagnosis of neutrophilic dermatosis and panniculitis, resembling the subcutaneous form of acute febrile neutrophilic dermatosis, was made.

  1. Spontaneous neutrophil activation in HTLV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Jaqueline B. Guerreiro

    Full Text Available Human T cell lymphotropic Virus type-1 (HTLV-1 induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy; 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS-stimulated neutrophil activity (reduction of NBT to formazan. The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001 in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24% and 17±4.8% respectively (p< 0.001, while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20%. Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

  2. Intravascular ultrasound assessment of minimumlumen area and intimal hyperplasia in in-stent restenosis after drug-eluting or bare-metal stent implantation. The Nordic Intravascular Ultrasound Study (NIVUS)

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Vikman, Saila; Antonsen, Lisbeth

    2017-01-01

    presenting with a DES or bare-metal stent (BMS) in-stent restenosis. Methods: The ``Nordic Intravascular Ultrasound Study (NIVUS)'' study was conducted in Nordic and Baltic countries as a prospective multicenter registry. Two hundred nine patients (DES n = 121 and BMS n = 88) with instent restenosis were...

  3. Intravascular Ultrasound

    Science.gov (United States)

    ... Rounds Seminar Series & Daily Conferences Fellowships and Residencies School of Perfusion Technology Education Resources Library & Learning Resource Center CME Resources THI Journal THI Cardiac Society Register for the Cardiac Society ...

  4. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

    Directory of Open Access Journals (Sweden)

    Alexander D Malkin

    2015-10-01

    Full Text Available Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8, a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5

  5. The emerging role of neutrophils in thrombosis – The journey of TF through NETs

    Directory of Open Access Journals (Sweden)

    Konstantinos eKambas

    2012-12-01

    Full Text Available The production of TF by neutrophils and their contribution in thrombosis was until recently a matter of scientific debate. Experimental data suggested the de novo TF production by neutrophils under inflammatory stimuli, while others proposed that these cells acquired microparticle-derived TF. Recent experimental evidence revealed the critical role of neutrophils in thrombotic events. Neutrophil derived TF has been implicated in this process in several human and animal models. Additionally, neutrophil extracellular trap (NET release has emerged as a major contributor in neutrophil-driven thrombogenicity in disease models including sepsis, deep venous thrombosis and malignancy. It is suggested that NETs provide the scaffold for fibrin deposition and platelet entrapment and subsequent activation. The recently reported autophagy-dependent extracellular delivery of TF in NETs further supports the involvement of neutrophils in thrombosis. Herein, we seek to review novel data regarding the role of neutrophils in thrombosis, emphasizing the implication of TF and NETs.

  6. CXCR2 mediates NADPH oxidase-independent neutrophil extracellular trap formation in cystic fibrosis airway inflammation

    NARCIS (Netherlands)

    Marcos, Veronica; Zhou, Zhe; Yildirim, Ali Onder; Bohla, Alexander; Hector, Andreas; Vitkov, Ljubomir; Wiedenbauer, Eva-Maria; Krautgartner, Wolf Dietrich; Stoiber, Walter; Belohradsky, Bernd H.; Rieber, Nikolaus; Kormann, Michael; Koller, Barbara; Roscher, Adelbert; Roos, Dirk; Griese, Matthias; Eickelberg, Oliver; Döring, Gerd; Mall, Marcus A.; Hartl, Dominik

    2010-01-01

    Upon activation, neutrophils release DNA fibers decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). Although NETs are bactericidal and contribute to innate host defense, excessive NET formation has been linked to the pathogenesis of autoinflammatory diseases.

  7. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Marcussen, Niels

    2009-01-01

    : The intratumoral neutrophils ranged from zero to 289 cells/mm(2) tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX

  8. Functional characterization of mitochondria in neutrophils: a role restricted to apoptosis

    NARCIS (Netherlands)

    Maianski, N. A.; Geissler, J.; Srinivasula, S. M.; Alnemri, E. S.; Roos, D.; Kuijpers, T. W.

    2004-01-01

    Mitochondria are known to combine life-supporting functions with participation in apoptosis by controlling caspase activity. Here, we report that in human blood neutrophils the mitochondria are different, because they preserve mainly death-mediating abilities. Neutrophil mitochondria hardly

  9. Increased neutrophil priming and sensitization before commencing cardiopulmonary bypass in cardiac surgical patients

    NARCIS (Netherlands)

    Gu, YJ; Schoen, P; Tigchelaar, [No Value; Loef, BG; Ebels, T; Rankin, AJ; van Oeveren, W

    2002-01-01

    Background. Neutrophil activation is implicated in postoperative complications in patients having cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to determine the temporal fluctuations in the primability of neutrophils in the preoperative, intraoperative, and postoperative

  10. Multicenter assessment of the reproducibility of volumetric radiofrequency-based intravascular ultrasound measurements in coronary lesions that were consecutively stented

    NARCIS (Netherlands)

    Huisman, Jeroen; Egede, R.; Rdzanek, A.; Böse, D.; Erbel, R.; van der Palen, Jacobus Adrianus Maria; von Birgelen, Clemens

    2012-01-01

    To assess in a multicenter design the between-center reproducibility of volumetric virtual histology intravascular ultrasound (VH-IVUS) measurements with a semi-automated, computer-assisted contour detection system in coronary lesions that were consecutively stented. To evaluate the reproducibility

  11. Direct sGC activation bypasses no scavenging reactions of intravascular free oxy-hemoglobin and limits vasoconstriction

    NARCIS (Netherlands)

    N.J.H. Raat (Nicolaas); D.M. Tabima (D. Marcela); P. Specht (Patricia); J. Tejero (Jesús); M.P. Champion (Michael); D.B. Kim-Shapiro (Daniel); J.G. Baust (John ); E.G. Mik (Egbert); M. Hildesheim (Mariana); J.-P. Stasch (Johannes-Peter); E.-M. Becker (Eva-Maria); H. Truebel (Hubert); M.T. Gladwin (Mark)

    2013-01-01

    textabstractAims: Hemoglobin-based oxygen carriers (HBOC) provide a potential alternative to red blood cell (RBC) transfusion. Their clinical application has been limited by adverse effects, in large part thought to be mediated by the intravascular scavenging of the vasodilator nitric oxide (NO) by

  12. Soluble CD40 ligand stimulates CD40-dependent activation of the β2 integrin Mac-1 and protein kinase C zeda (PKCζ in neutrophils: implications for neutrophil-platelet interactions and neutrophil oxidative burst.

    Directory of Open Access Journals (Sweden)

    Rong Jin

    Full Text Available Recent work has revealed an essential involvement of soluble CD40L (sCD40L in inflammation and vascular disease. Activated platelets are the major source of sCD40L, which has been implicated in platelet and leukocyte activation, although its exact functional impact on leukocyte-platelet interactions and the underlying mechanisms remain undefined. We aimed to determine the impact and the mechanisms of sCD40L on neutrophils. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte recruitment to the sites of injury. Our data show that CD40L contributes to neutrophil firm adhesion to and transmigration across activated surface-adherent platelets, possibly through two potential mechanisms. One involves the direct interaction of ligand-receptor (CD40L-CD40, i.e., platelet surface CD40L interaction with neutrophil CD40; another involves an indirect mechanism, i.e. soluble CD40L stimulates activation of the leukocyte-specific β2 integrin Mac-1 in neutrophils and thereby further promotes neutrophil adhesion and migration. Activation of the integrin Mac-1 is known to be critical for mediating neutrophil adhesion and migration. sCD40L activated Mac-1 in neutrophils and enhanced neutrophil-platelet interactions in wild-type neutrophils, but failed to elicit such responses in CD40-deficient neutrophils. Furthermore, our data show that the protein kinase C zeta (PKCζ is critically required for sCD40L-induced Mac-1 activation and neutrophil adhesive function. sCD40L strongly stimulated the focal clustering of Mac-1 (CD11b and the colocalization of Mac-1 with PKCζ in wild-type neutrophils, but had minimal effect in CD40-deficient neutrophils. Blocking PKCζ completely inhibited sCD40L-induced neutrophil firm adhesion. Moreover, sCD40L strongly stimulates neutrophil oxidative burst via CD40-dependent activation of PI3K/NF-KB, but independent of Mac-1 and PKCζ. These findings may contribute to a better

  13. File list: His.Bld.10.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: His.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: His.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: His.Bld.20.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Unc.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  19. File list: ALL.Bld.20.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Unc.Bld.05.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: His.Bld.10.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.AllAg.Neutrophils mm9 Histone Blood Neutrophils SRX760584,SRX760583,SRX7...60581,SRX760582,SRX760580 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.10.AllAg.Neutrophils.bed ...

  2. File list: Unc.Bld.10.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.Neutrophils hg19 Unclassified Blood Neutrophils SRX956552,SRX95654...9,SRX956546 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.10.AllAg.Neutrophils.bed ...

  3. File list: His.Bld.05.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Neutrophils hg19 Histone Blood Neutrophils SRX956551,SRX956548,SRX...956545,SRX956544,SRX956550,SRX956547 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.05.AllAg.Neutrophils.bed ...

  4. File list: His.Bld.05.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: ALL.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Neutrophils mm9 All antigens Blood Neutrophils SRX760581,SRX760584...,SRX760583,SRX760580,SRX801903,SRX760582 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.50.AllAg.Neutrophils.bed ...

  6. Neutrophil CD64 has a high negative predictive value for exclusion ...

    African Journals Online (AJOL)

    [13] Multiple studies agree that neutrophil CD64 has high diagnostic speci city and sensitivity.[13,18-20] In the light of the above information, we prospectively evaluated the usefulness of neutrophil CD64 expression in diagnosing neonatal infection. e main objective of the study was quantitation of neutrophil. CD64 by ow ...

  7. Evidence for a self-enforcing inflammation in neutrophil-mediated chronic diseases

    NARCIS (Netherlands)

    Overbeek, S.A.

    2011-01-01

    In summary, this thesis provides evidence for the self-sustaining role of neutrophils in the inflammatory state in the pathogenesis of COPD and CD. In active disease, neutrophils release proteolytic enzymes that breakdown collagen. One of the collagen fragments can be neutrophilic chemoattractant

  8. File list: His.Bld.20.AllAg.Neutrophils [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.Neutrophils hg19 Histone Blood Neutrophils SRX956551,SRX956548,SRX...956545,SRX956544,SRX956547,SRX956550 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.20.AllAg.Neutrophils.bed ...

  9. Neutrophil extracellular traps in the host defense against sepsis induced by Burkholderia pseudomallei (melioidosis)

    NARCIS (Netherlands)

    de Jong, Hanna K.; Koh, Gavin C. K. W.; Achouiti, Ahmed; van der Meer, Anne J.; Bulder, Ingrid; Stephan, Femke; Roelofs, Joris J. T. H.; Day, Nick P. J.; Peacock, Sharon J.; Zeerleder, Sacha; Wiersinga, W. Joost

    2014-01-01

    Neutrophil extracellular traps (NETs) are a central player in the host response to bacteria: neutrophils release extracellular DNA (nucleosomes) and neutrophil elastase to entrap and kill bacteria. We studied the role of NETs in Burkholderia pseudomallei infection (melioidosis), an important cause

  10. On the pharmacology of oxidative burst of neutrophils

    Czech Academy of Sciences Publication Activity Database

    Nosáľ, R.; Drábiková, K.; Harmatha, Juraj; Jančinová, V.; Mačičková, T.; Pečivová, J.; Perečko, T.

    2011-01-01

    Roč. 4, č. 2 (2011), A51-A51 ISSN 1337-6853. [TOXCON 2011. Interdisciplinary Toxicology Conference /16./. 17.05.2011-20.05.2011, Praha] Institutional research plan: CEZ:AV0Z40550506 Keywords : N-feruloyl- serotonin * oxidative burst * inhibition of neutrophil activation Subject RIV: CC - Organic Chemistry

  11. Flavonoids inhibit the respiratory burst of neutrophils in mammals

    Czech Academy of Sciences Publication Activity Database

    Číž, Milan; Denev, P.; Kratchanova, M.; Vašíček, Ondřej; Ambrožová, Gabriela; Lojek, Antonín

    2012-01-01

    Roč. 2012, č. 2012 (2012), ID 181295 ISSN 1942-0900 R&D Projects: GA ČR(CZ) GA524/08/1753 Institutional research plan: CEZ:AV0Z50040702 Keywords : flavonoids * neutrophils * respiratory burst Subject RIV: BO - Biophysics Impact factor: 3.393, year: 2012

  12. Activity of neutrophil elastase reflects the progression of acute pancreatitis

    DEFF Research Database (Denmark)

    Novovic, Srdan; Andersen, Anders M; Nord, Magnus

    2013-01-01

    Abstract Objective. Neutrophil elastase (NE) concentration is associated with progression of acute pancreatitis (AP), but measuring total NE concentration includes biologically inactive NE. This study aims to investigate the relationship between NE activity and the aetiology and severity of AP...... was associated with predicted severity of AP and AP-associated respiratory failure. Specific NE inhibitors may have therapeutic potential in acute pancreatitis....

  13. Neutrophil superoxide-anion generating capacity in chronic smoking ...

    Indian Academy of Sciences (India)

    We investigated whether long-term -tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 ± 21 pack years of smoking) to treatment with placebo ( = 64) or -tocopherol (400 IU dL--tocopherol daily, ...

  14. Platelet indices and neutrophil to lymphocyte ratio in adults with ...

    African Journals Online (AJOL)

    Background: A study was performed in adults with acute appendicitis and matched controls to assess the utility of the platelet indices and neutrophil to lymphocyte ratio, as a diagnostic adjunct. Methods: Data were retrospectively collected from a complete blood count test of 155 adult patients (72 men and 83 women) with ...

  15. Semi-Automatic Rating Method for Neutrophil Alkaline Phosphatase Activity.

    Science.gov (United States)

    Sugano, Kanae; Hashi, Kotomi; Goto, Misaki; Nishi, Kiyotaka; Maeda, Rie; Kono, Keigo; Yamamoto, Mai; Okada, Kazunori; Kaga, Sanae; Miwa, Keiko; Mikami, Taisei; Masauzi, Nobuo

    2017-01-01

    The neutrophil alkaline phosphatase (NAP) score is a valuable test for the diagnosis of myeloproliferative neoplasms, but it has still manually rated. Therefore, we developed a semi-automatic rating method using Photoshop ® and Image-J, called NAP-PS-IJ. Neutrophil alkaline phosphatase staining was conducted with Tomonaga's method to films of peripheral blood taken from three healthy volunteers. At least 30 neutrophils with NAP scores from 0 to 5+ were observed and taken their images. From which the outer part of neutrophil was removed away with Image-J. These were binarized with two different procedures (P1 and P2) using Photoshop ® . NAP-positive area (NAP-PA) and granule (NAP-PGC) were measured and counted with Image-J. The NAP-PA in images binarized with P1 significantly (P < 0.05) differed between images with NAP scores from 0 to 3+ (group 1) and those from 4+ to 5+ (group 2). The original images in group 1 were binarized with P2. NAP-PGC of them significantly (P < 0.05) differed among all four NAP score groups. The mean NAP-PGC with NAP-PS-IJ indicated a good correlation (r = 0.92, P < 0.001) to results by human examiners. The sensitivity and specificity of NAP-PS-IJ were 60% and 92%, which might be considered as a prototypic method for the full-automatic rating NAP score. © 2016 Wiley Periodicals, Inc.

  16. Yersinia pestis targets neutrophils via complement receptor 3

    Science.gov (United States)

    Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.

    2015-01-01

    Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection. PMID:25359083

  17. Circulating neutrophil transcriptome may reveal intracranial aneurysm signature.

    Directory of Open Access Journals (Sweden)

    Vincent M Tutino

    Full Text Available Unruptured intracranial aneurysms (IAs are typically asymptomatic and undetected except for incidental discovery on imaging. Blood-based diagnostic biomarkers could lead to improvements in IA management. This exploratory study examined circulating neutrophils to determine whether they carry RNA expression signatures of IAs.Blood samples were collected from patients receiving cerebral angiography. Eleven samples were collected from patients with IAs and 11 from patients without IAs as controls. Samples from the two groups were paired based on demographics and comorbidities. RNA was extracted from isolated neutrophils and subjected to next-generation RNA sequencing to obtain differential expressions for identification of an IA-associated signature. Bioinformatics analyses, including gene set enrichment analysis and Ingenuity Pathway Analysis, were used to investigate the biological function of all differentially expressed transcripts.Transcriptome profiling identified 258 differentially expressed transcripts in patients with and without IAs. Expression differences were consistent with peripheral neutrophil activation. An IA-associated RNA expression signature was identified in 82 transcripts (p<0.05, fold-change ≥2. This signature was able to separate patients with and without IAs on hierarchical clustering. Furthermore, in an independent, unpaired, replication cohort of patients with IAs (n = 5 and controls (n = 5, the 82 transcripts separated 9 of 10 patients into their respective groups.Preliminary findings show that RNA expression from circulating neutrophils carries an IA-associated signature. These findings highlight a potential to use predictive biomarkers from peripheral blood samples to identify patients with IAs.

  18. Modulation of neutrophil oxidative burst via histamine receptors

    Czech Academy of Sciences Publication Activity Database

    Číž, Milan; Lojek, Antonín

    2013-01-01

    Roč. 170, č. 1 (2013), s. 17-22 ISSN 0007-1188 R&D Projects: GA MŠk(CZ) LD11010 Institutional support: RVO:68081707 Keywords : neutrophil * oxidative burst * reactive oxygen species Subject RIV: BO - Biophysics Impact factor: 4.990, year: 2013

  19. (neutrophil) Activity, Chronic Gastritis, Gastric Atrophy And Intestinal ...

    African Journals Online (AJOL)

    Incidental (early gastric) cancer was found in 3%, dysplasia in 2% and reactive gastropathy in 7% of the cases. A statistically significant relationship was found between Helicobacter pylori colonization intensity and the degrees of neutrophil activity, chronic inflammation and intestinal metaplasia. Conclusion: We concluded ...

  20. On the Pharmacology of Oxidative Burst of Human Neutrophils

    Czech Academy of Sciences Publication Activity Database

    Nosáľ, R.; Drábiková, K.; Jančinová, V.; Mačičková, T.; Pečivová, J.; Perečko, T.; Harmatha, Juraj; Šmidrkal, J.

    2015-01-01

    Roč. 64, Suppl 4 (2015), S445-S452 ISSN 0862-8408 Institutional support: RVO:61388963 Keywords : human neutrophils * oxidative burst * chemiluminescence * protein kinase C * apoptosis Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.643, year: 2015 http://www.biomed.cas.cz/physiolres/pdf/64/64_S445.pdf

  1. ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils

    DEFF Research Database (Denmark)

    Roychaudhuri, Robin; Hergrueter, Anja H; Polverino, Francesca

    2014-01-01

    A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by monocytes and macrophages. In this study, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein...

  2. Nucleases from Prevotella intermedia can degrade neutrophil extracellular traps.

    Science.gov (United States)

    Doke, M; Fukamachi, H; Morisaki, H; Arimoto, T; Kataoka, H; Kuwata, H

    2017-08-01

    Periodontitis is an inflammatory disease caused by periodontal bacteria in subgingival plaque. These bacteria are able to colonize the periodontal region by evading the host immune response. Neutrophils, the host's first line of defense against infection, use various strategies to kill invading pathogens, including neutrophil extracellular traps (NETs). These are extracellular net-like fibers comprising DNA and antimicrobial components such as histones, LL-37, defensins, myeloperoxidase, and neutrophil elastase from neutrophils that disarm and kill bacteria extracellularly. Bacterial nuclease degrades the NETs to escape NET killing. It has now been shown that extracellular nucleases enable bacteria to evade this host antimicrobial mechanism, leading to increased pathogenicity. Here, we compared the DNA degradation activity of major Gram-negative periodontopathogenic bacteria, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We found that Pr. intermedia showed the highest DNA degradation activity. A genome search of Pr. intermedia revealed the presence of two genes, nucA and nucD, putatively encoding secreted nucleases, although their enzymatic and biological activities are unknown. We cloned nucA- and nucD-encoding nucleases from Pr. intermedia ATCC 25611 and characterized their gene products. Recombinant NucA and NucD digested DNA and RNA, which required both Mg 2+ and Ca 2+ for optimal activity. In addition, NucA and NucD were able to degrade the DNA matrix comprising NETs. © 2016 The Authors Molecular Oral Microbiology Published by John Wiley & Sons Ltd.

  3. Neutrophil elastase-mediated increase in airway temperature during inflammation

    DEFF Research Database (Denmark)

    Schmidt, Annika; Belaaouaj, Azzaq; Bissinger, Rosi

    2014-01-01

    in the exhaled air of cystic fibrosis (CF) patients. To further test our hypothesis, a pouch inflammatory model using neutrophil elastase-deficient mice was employed. Next, the impact of temperature changes on the dominant CF pathogen Pseudomonas aeruginosa growth was tested by plating method and RNAseq. Results...

  4. Neutrophil extracellular traps in patients with pulmonary tuberculosis

    NARCIS (Netherlands)

    van der Meer, Anne Jan; Zeerleder, Sacha; Blok, Dana C.; Kager, Liesbeth M.; Lede, Ivar O.; Rahman, Wahid; Afroz, Rumana; Ghose, Aniruddha; Visser, Caroline E.; Zahed, Abu Shahed Md; Husain, Md Anwar; Alam, Khan Mashrequl; Barua, Pravat Chandra; Hassan, Mahtabuddin; Tayab, Md Abu; Dondorp, Arjen M.; van der Poll, Tom

    2017-01-01

    Tuberculosis is a devastating infectious disease causing many deaths worldwide. Recent investigations have implicated neutrophil extracellular traps (NETs) in the host response to tuberculosis. The aim of the current study was to obtain evidence for NETs release in the circulation during human

  5. Increased neutrophil expression of pattern recognition receptors during COPD exacerbations

    NARCIS (Netherlands)

    Pouwels, Simon D.; Van Geffen, Wouter H.; Jonker, Marnix R.; Kerstjens, Huib A. M.; Nawijn, Martijn C.; Heijink, Irene H.

    Previously, we observed increased serum levels of damage-associated molecular patterns (DAMPs) during COPD exacerbations. Here, gene expression of DAMP receptors was measured in peripheral blood neutrophils of COPD patients during stable disease and severe acute exacerbation. The expression of

  6. The strength of integrin binding between neutrophils and endothelial cells

    Czech Academy of Sciences Publication Activity Database

    Labrador, V.; Říha, Pavel; Muller, S.; Dumas, D.; Wang, X.; Stoltz, J. F.

    2003-01-01

    Roč. 32, č. 8 (2003), s. 684-688 ISSN 0175-7571 R&D Projects: GA ČR GA305/01/1605 Institutional research plan: CEZ:AV0Z2060917 Keywords : endothelium * integrins * neutrophil adhesion * scanning microscopy Subject RIV: BO - Biophysics Impact factor: 1.769, year: 2003

  7. Pharmacological intervention with oxidative burst in human neutrophils

    Czech Academy of Sciences Publication Activity Database

    Nosál, R.; Drábiková, K.; Jančinová, V.; Mačičková, T.; Pečivová, J.; Perečko, T.; Harmatha, Juraj

    2017-01-01

    Roč. 10, č. 2 (2017), s. 56-60 ISSN 1337-6853 Institutional support: RVO:61388963 Keywords : human neutrophils * oxidative burst * tharapeutical drugs * natural antioxidants Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy https://www.degruyter.com/downloadpdf/j/intox.2017.10.issue-2/intox-2017-0009/intox-2017-0009.pdf

  8. Circulating neutrophil transcriptome may reveal intracranial aneurysm signature

    Science.gov (United States)

    Tutino, Vincent M.; Poppenberg, Kerry E.; Jiang, Kaiyu; Jarvis, James N.; Sun, Yijun; Sonig, Ashish; Siddiqui, Adnan H.; Snyder, Kenneth V.; Levy, Elad I.; Kolega, John

    2018-01-01

    Background Unruptured intracranial aneurysms (IAs) are typically asymptomatic and undetected except for incidental discovery on imaging. Blood-based diagnostic biomarkers could lead to improvements in IA management. This exploratory study examined circulating neutrophils to determine whether they carry RNA expression signatures of IAs. Methods Blood samples were collected from patients receiving cerebral angiography. Eleven samples were collected from patients with IAs and 11 from patients without IAs as controls. Samples from the two groups were paired based on demographics and comorbidities. RNA was extracted from isolated neutrophils and subjected to next-generation RNA sequencing to obtain differential expressions for identification of an IA-associated signature. Bioinformatics analyses, including gene set enrichment analysis and Ingenuity Pathway Analysis, were used to investigate the biological function of all differentially expressed transcripts. Results Transcriptome profiling identified 258 differentially expressed transcripts in patients with and without IAs. Expression differences were consistent with peripheral neutrophil activation. An IA-associated RNA expression signature was identified in 82 transcripts (pIAs on hierarchical clustering. Furthermore, in an independent, unpaired, replication cohort of patients with IAs (n = 5) and controls (n = 5), the 82 transcripts separated 9 of 10 patients into their respective groups. Conclusion Preliminary findings show that RNA expression from circulating neutrophils carries an IA-associated signature. These findings highlight a potential to use predictive biomarkers from peripheral blood samples to identify patients with IAs. PMID:29342213

  9. Changes in neutrophil count, creatine kinases and muscle soreness ...

    African Journals Online (AJOL)

    Objective. A primary objective was to examine circulating neutrophil count after repeated bouts of downhill running. An additional aim was to determine creatine kinase (CK) levels during the initial 12 hours, after repeated DHRs. Design. Eleven healthy, untrained Caucasian males performed 2 x 60 min bouts of DHR ...

  10. Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Elham Vali Khojeini

    2014-01-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

  11. Application of Gafchromic registered film in the dosimetry of an intravascular brachytherapy source

    International Nuclear Information System (INIS)

    Song Haijun; Roa, D. Eduardo; Yue Ning; D'Errico, Francesco; Chen Zhe; Nath, Ravinder

    2006-01-01

    The methodology of brachytherapy source dosimetry with Gafchromic registered MD 55-2 film (ISP Technologies, Inc.) is examined with an emphasis on the nonlinearity of the optical density-dose relation within the dynamic dose range, the radial distance-dependent measurement uncertainty, and the format of data presentation. The specific source chosen for this study was a Checkmate trade mark sign (Cordis Corporation) intravascular brachytherapy system. The two-dimensional dose distribution around the source was characterized by a comprehensive analysis of measurement uncertainties. A comparative analysis of the dosimetric data from the vendor and from the scientific literature showed a substantial consistency of the information available for the Checkmate trade mark sign source. Our two-dimensional dosimetric data for the Checkmate trade mark sign source trains is presented in the form of measured along and away dose tables

  12. Intravascular Papillary Endothelial Hyperplasia (Masson’s Tumor) of the Radial Artery: A Case Report

    International Nuclear Information System (INIS)

    Stark, Christopher; Olsen, Daniel; Morris, Christopher; Bertges, Daniel; Najarian, Kenneth

    2016-01-01

    Intravascular papillary endothelial hyperplasia (IPEH), often referred to as Masson’s tumor, is a benign non-neoplastic vascular lesion of the skin and subcutaneous tissues. Although it is rare, knowledge of the existence of IPEH is important as it can mimic other benign and malignant tumors, most notably angiosarcoma. IPEH remains an incompletely understood entity; however, most consider it to be the result of reactive endothelial proliferation following thrombus formation within a vessel, vascular malformation, or adjacent to a vessel. In this article, we report a case of IPEH arising within an arteriovenous malformation of the radial artery and present accompanying multimodality imaging and pathology figures. We will also describe the clinical presentation, pathophysiology, histology, imaging features, and management of IPEH.

  13. Intravascular large B-cell lymphoma presenting with anasarca-type edema and acute renal failure.

    Science.gov (United States)

    Bilgili, Serap Gunes; Yılmaz, Deniz; Soyoral, Yasemin Usul; Karadag, Ayse Serap; Bayram, Irfan

    2013-09-01

    Intravascular lymphoma (IVL) is a rare extra nodal subtype (usually of B-cell origin) presenting with infiltration of large neoplastic lymphocytes into lumina of blood vessels, leading to vascular occlusion. The early diagnosis is very crucial, however it is usually diagnosed postmortem investigation in most of the cases. A 56-year-old female presented with elevated creatinine level, and anasarca-type edema that superimposed with hard, indurated, erythematous plaques extending to inguinal region, abdomen, anterior aspect of chest, and face. B-cell IVL was confirmed with skin biopsy. The patient had some degree of clinical improvement following chemotherapy. B-cell IVL presenting with anasarca edema was not previously reported in the literature. Even if its rarity, IVL should be considered in the differential diagnosis of renal failure with anasarca edema.

  14. A state-of-the-art review on segmentation algorithms in intravascular ultrasound (IVUS) images.

    Science.gov (United States)

    Katouzian, Amin; Angelini, Elsa D; Carlier, Stéphane G; Suri, Jasjit S; Navab, Nassir; Laine, Andrew F

    2012-09-01

    Over the past two decades, intravascular ultrasound (IVUS) image segmentation has remained a challenge for researchers while the use of this imaging modality is rapidly growing in catheterization procedures and in research studies. IVUS provides cross-sectional grayscale images of the arterial wall and the extent of atherosclerotic plaques with high spatial resolution in real time. In this paper, we review recently developed image processing methods for the detection of media-adventitia and luminal borders in IVUS images acquired with different transducers operating at frequencies ranging from 20 to 45 MHz. We discuss methodological challenges, lack of diversity in reported datasets, and weaknesses of quantification metrics that make IVUS segmentation still an open problem despite all efforts. In conclusion, we call for a common reference database, validation metrics, and ground-truth definition with which new and existing algorithms could be benchmarked.

  15. Intravascular Papillary Endothelial Hyperplasia (Masson’s Tumor) of the Radial Artery: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Stark, Christopher, E-mail: Christopher.stark@uvmhealth.org [University of Vermont Medical Center, Department of Radiology (United States); Olsen, Daniel [Mayo Clinic, Department of Pathology (United States); Morris, Christopher [University of Vermont Medical Center, Department of Radiology (United States); Bertges, Daniel [University of Vermont Medical Center, Department of Surgery (United States); Najarian, Kenneth [University of Vermont Medical Center, Department of Radiology (United States)

    2016-11-15

    Intravascular papillary endothelial hyperplasia (IPEH), often referred to as Masson’s tumor, is a benign non-neoplastic vascular lesion of the skin and subcutaneous tissues. Although it is rare, knowledge of the existence of IPEH is important as it can mimic other benign and malignant tumors, most notably angiosarcoma. IPEH remains an incompletely understood entity; however, most consider it to be the result of reactive endothelial proliferation following thrombus formation within a vessel, vascular malformation, or adjacent to a vessel. In this article, we report a case of IPEH arising within an arteriovenous malformation of the radial artery and present accompanying multimodality imaging and pathology figures. We will also describe the clinical presentation, pathophysiology, histology, imaging features, and management of IPEH.

  16. The role of the adventitia in the arterial response to angioplasty: the effect of intravascular radiation

    International Nuclear Information System (INIS)

    Wilcox, Josiah N.; Waksman, Ron; King, Spencer B.; Scott, Neal A.

    1996-01-01

    Purpose: In the current series of experiments we have characterized cell proliferation leading to vascular lesion formation in a porcine model for post-angioplasty restenosis and examined the mechanism of action of intravascular beta irradiation in the prevention of lesion formation in this model. Methods and Materials: Juvenile male pigs were subjected to balloon overstretch injury of the left anterior descending and circumflex coronary arteries using clinical angioplasty catheters. Proliferating cells were labelled by injections of 50 mg/kg of bromo-deoxyuridine (BrDU) 24, 16 and 8 hrs prior to sacrifice and were detected by immunohistochemistry using a specific antibody to BrDU. In some cases, BrDU was given as a pulse 3 days after angioplasty and the animals sacrificed on day 14 to follow the migration of the cells which had proliferated earlier. Characterization of the proliferating cells was performed by immunohistochemistry using antibodies to specific cytoskeletal proteins specific for smooth muscle cells and myofibroblasts. Some vessels were treated at the time of angioplasty with 14 or 28 Gy (to a depth of 2 mm) intravascular irradiation using a flexible catheter with a pure beta emitter 90 SR/Y and the effect on cell proliferation and terminal transferase-mediated UTP nick-end labelling (TUNEL) examined 3 or 7 days later. Results: The first major site of cell proliferation between 2-3 days after angioplasty is the adventitia and not the medial wall. Seven days after angioplasty cell proliferation is predominant in the neointima and is reduced in the media and adventitia. Differential staining with antibodies directed against smooth muscle alpha actin and other cytoskeletal proteins indicates that the proliferating adventitial cells are myofibroblasts. Pulse label studies with BrDU indicates that the proliferating adventitial myofibroblasts migrate into the neointima and contribute to the mass of the restenosis lesion. Fourteen days after angioplasty the

  17. Specific features of red blood cell morphology in hemolytic disease neonates undergoing intrauterine intravascular blood transfusion

    Directory of Open Access Journals (Sweden)

    A. V. Ivanova

    2016-01-01

    Full Text Available The paper presents data on the characteristics of red blood cell morphology in infants who have undergone intrauterine intravascular blood transfusion for hemolytic disease of the fetus. The infants are shown to have a reduction in the mean volume of red blood cells and in their mean level of hemoglobin, a decrease in the fraction of fetal hemoglobin and an increase in oxygen tension at half saturation. The above morphological characteristics of red blood cells remain decreased during the neonatal period after exchange transfusion or others, as clinically indicated, which seems to suggest that the compensatory-adaptive mechanisms to regulate hematopoiesis are exhausted and a donor’s red blood cells continue to be predominant.

  18. Histopathological approach for diagnosis of intravascular leiomyosarcoma of the femoral vein

    Directory of Open Access Journals (Sweden)

    Gaurav Singal

    2016-04-01

    Full Text Available Malignant tumors arising from venous walls in the lower extremities are uncommon and intravascular leiomyosarcoma represents only a small proportion and rare of soft tissue leiomyosarcoma. All publications in the literature are of small clinical series or case reports. We present a case of primary leiomyosarcoma of the femoral vein in a 40 year old man; which is a rare lesion with less than 40 cases reported. The patient presented with swelling and localized leg pain. The diagnosis was made histopathologically, the tumor was resected, vascular reconstruction was performed, and for postoperative radiation therapy and chemotherapy patient was referred to the oncologist. Primary leiomyosarcoma of a major peripheral artery is extremely rare, and this report share the clinical presentation, histopathological findings, treatment, and prognosis in these patients

  19. Splenic angiomyxoma with intravascular tumor embolus in a dog: a case report.

    Science.gov (United States)

    Lee, Eun-Mi; Kim, Ah-Young; Lee, Eun-Joo; Park, Jin-Kyu; Kim, Tae-Hwan; Park, Se-Il; Jeong, Kyu-Shik

    2016-07-01

    A 13-year-old castrated male Yorkshire terrier dog had a soft splenic mass, which measured 11 cm in the greatest diameter. Microscopically, the parenchyma of the spleen was completely replaced by myxoid substances. Numerous spindle and stellate cells were loosely arranged in the myxoid stroma, and variable vessels of variable sizes were observed in a loose matrix with poorly defined margins. Immunohistochemical analysis showed that tumor cells were positive for desmin and alpha-SMA, but negative for S-100. Interestingly, intravascular tumor embolus with positive α-SMA expression was observed. This case is meaningful, because angiomyxoma, a rare tumor of dogs, occurs in the spleen. Even in human cases, splenic angiomyxoma was not reported.

  20. Intravascular ultrasound assessment of remodelling and reference segment plaque burden in type-2 diabetic patients

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Thayssen, Per; Mintz, Gary S

    2007-01-01

    AIMS: Intravascular ultrasound (IVUS) assesses arterial remodelling by comparing the lesion external elastic membrane (EEM) with the reference segments; however, reference segments are rarely disease-free. The aim was to assess lesion and reference segment remodelling and plaque burden in patients...... with type-2 diabetes mellitus. METHODS AND RESULTS: We used pre-intervention IVUS to study 62 de novo lesions in 43 patients with type-2 diabetes mellitus. The lesion site was the image slice with the smallest lumen cross-sectional area (CSA). The proximal and distal reference segments were the most normal...... size [slope = -0.12 (95% CI -0.17 to -0.07); P type-2 diabetes mellitus. CONCLUSION: Lesions in type-2 diabetic patients are different from previous reports in non-diabetics. Lesions in type-2 diabetics are characterized by a large reference segment plaque burden...

  1. Early Blood Transfusion and Resolution of Disseminated Intravascular Coagulation Associated with Massive Subgaleal Hemorrhage.

    Science.gov (United States)

    Modanlou, Houchang; Hutson, Shandee; Merritt, Allan Thurman

    2016-01-01

    A male infant delivered to a primipara woman following vacuum applications. He was vigorous at birth, with small caput and scalp bruising. His head was enlarging; he became pale with respiratory distress. Subgaleal hemorrhage (SGH) was suspected. His hematocrit was noted to be 26.2 percent prior to transfusion of O, Rh-negative blood (40 mL/kg). Moderate disseminated intravascular coagulation (DIC) was noted at 12 hours of age. Posttransfusion of fresh frozen plasma (FFP), his condition became stable, and DIC gradually resolved. Head magnetic resonance imaging did not show intracranial hemorrhage. Although one episode of seizures was noted, electroencephalogram was normal. With the application of obstetric vacuum, we recommend that the neonatal health care professionals frequently evaluate the infant's condition. In light of developing fluctuant subgaleal fluid associated with pallor, anemia, metabolic acidosis, and respiratory distress, immediate blood transfusion is warranted. In the presence of DIC, transfusion of FFP is beneficial.

  2. Catheter design optimization for practical intravascular photoacoustic imaging (IVPA) of vulnerable plaques

    Science.gov (United States)

    Iskander-Rizk, Sophinese; Wu, Min; Springeling, Geert; Mastik, Frits; Beurskens, Robert H. S. H.; van der Steen, Antonius F. W.; van Soest, Gijs

    2018-02-01

    Intravascular photoacoustic/ultrasound imaging (IVPA/US) can image the structure and composition of atherosclerotic lesions identifying lipid-rich plaques ex vivo and in vivo. In the literature, multiple IVPA/US catheter designs were presented and validated both in ex-vivo models and preclinical in-vivo situations. Since the catheter is a critical component of the imaging system, we discuss here a catheter design oriented to imaging plaque in a realistic and translatable setting. We present a catheter optimized for light delivery, manageable flush parameters and robustness with reduced mechanical damage risks at the laser/catheter joint interface. We also show capability of imaging within sheath and in water medium.

  3. An automated approach for segmentation of intravascular ultrasound images based on parametric active contour models

    International Nuclear Information System (INIS)

    Vard, Alireza; Jamshidi, Kamal; Movahhedinia, Naser

    2012-01-01

    This paper presents a fully automated approach to detect the intima and media-adventitia borders in intravascular ultrasound images based on parametric active contour models. To detect the intima border, we compute a new image feature applying a combination of short-term autocorrelations calculated for the contour pixels. These feature values are employed to define an energy function of the active contour called normalized cumulative short-term autocorrelation. Exploiting this energy function, the intima border is separated accurately from the blood region contaminated by high speckle noise. To extract media-adventitia boundary, we define a new form of energy function based on edge, texture and spring forces for the active contour. Utilizing this active contour, the media-adventitia border is identified correctly even in presence of branch openings and calcifications. Experimental results indicate accuracy of the proposed methods. In addition, statistical analysis demonstrates high conformity between manual tracing and the results obtained by the proposed approaches.

  4. Comparison of angiography and intravascular ultrasound before and after balloon angioplasty of the femoropopliteal artery

    International Nuclear Information System (INIS)

    Lankeren, Winnifred van; Gussenhoven, Elma J.; Pieterman, Herman; Sambeek, Marc R. H. M. van; Lugt, Aad van der

    1998-01-01

    Purpose: To compare angiographic and intravascular ultrasound (IVUS) data before and after balloon angioplasty (PTA) of the femoropopliteal artery.Methods: Qualitative and quantitative analyses were performed on corresponding angiographic and IVUS levels obtained from 135 patients.Results: IVUS detected more lesions, calcified lesions, and vascular damage than angiography. Sensitivity of angiography was good for the presence of a lesion (84%), moderate for eccentric lesions (53%) and for vascular damage (52%), and poor for calcified lesions (30%). The increase in angiographic diameter stenosis was associated with a decrease in lumen area and increase in percentage area stenosis on IVUS.Conclusions: Angiography is less sensitive than IVUS for detecting lesion eccentricity, calcified lesions, and vascular damage. Presence of a lesion and amount of plaque were underestimated angiographically. Only before PTA was good agreement found between angiographic diameter stenosis and lumen size on IVUS.

  5. Perspectives on Imaging the Left Main Coronary Artery Using Intravascular Ultrasound and Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Harry C Lowe

    2015-01-01

    Full Text Available Percutaneous Coronary Intervention (PCI for significant left main coronary artery (LMCA stenosis is increasingly being viewed as a viable alternative to Coronary Artery Bypass Grafting (CABG (1. This is leading to an expectation of increasing numbers of such procedures, with a consequent focus on both the ability to image both lesion severity, and assess more accurately the results of PCI. While there have been advances in physiologic assessment of left main severity using fractional flow reserve (FFR, imaging of the LMCA using Intravascular Ultrasound (IVUS and more recently Optical Coherence Tomography (OCT has the specific advantage of being able to provide detailed anatomical information both pre and post PCI, such that it is timely to review briefly the current status of these two imaging technologies in the context of LMCA intervention.

  6. Intravascular forward-looking ultrasound transducers for microbubble-mediated sonothrombolysis.

    Science.gov (United States)

    Kim, Jinwook; Lindsey, Brooks D; Chang, Wei-Yi; Dai, Xuming; Stavas, Joseph M; Dayton, Paul A; Jiang, Xiaoning

    2017-06-14

    Effective removal or dissolution of large blood clots remains a challenge in clinical treatment of acute thrombo-occlusive diseases. Here we report the development of an intravascular microbubble-mediated sonothrombolysis device for improving thrombolytic rate and thus minimizing the required dose of thrombolytic drugs. We hypothesize that a sub-megahertz, forward-looking ultrasound transducer with an integrated microbubble injection tube is more advantageous for efficient thrombolysis by enhancing cavitation-induced microstreaming than the conventional high-frequency, side-looking, catheter-mounted transducers. We developed custom miniaturized transducers and demonstrated that these transducers are able to generate sufficient pressure to induce cavitation of lipid-shelled microbubble contrast agents. Our technology demonstrates a thrombolysis rate of 0.7 ± 0.15 percent mass loss/min in vitro without any use of thrombolytic drugs.

  7. Neuroendocrine and renal effects of intravascular volume expansion in compensated heart failure

    DEFF Research Database (Denmark)

    Gabrielsen, A; Bie, P; Holstein-Rathlou, N H

    2001-01-01

    To examine if the neuroendocrine link between volume sensing and renal function is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 +/- 0.03 (mean +/- SE)] we tested the hypothesis that intravascular and central blood volume expansion by 3 h of water immersion (WI) elicits...... sustained angiotensin-converting enzyme inhibitor therapy, n = 9) absolute and fractional sodium excretion increased (P Renal free water clearance increased during WI in control subjects but not in HF......, albeit plasma vasopressin concentrations were similar in the two groups. In conclusion, the neuroendocrine link between volume sensing and renal sodium excretion is preserved in compensated HF. The natriuresis of WI is, however, modulated by the prevailing ANG II and Aldo concentrations. In contrast...

  8. The cerebral intravascular enhancement sign is not specific: a contrast-enhanced MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Bakshi, R.; Kinkel, W.R.; Bates, V.E.; Mechtler, L.L.; Kinkel, P.R. [Lucy Dent Imaging Center, University at Buffalo, NY (United States)

    1999-02-01

    The intravascular enhancement (IVE) sign, also known as the ``arterial enhancement sign``, is an abnormal finding in the brain on contrast-enhanced MRI studies. IVE has been described in arterial cerebrovascular disorders, most commonly in acute or subacute arterial ischemic infarcts. However, the specificity of this sign has not been established. We describe four patients with disorders other than arterial strokes in whom gadolinium-enhanced high-field (1.5 T) MRI suggested IVE. The conditions were herpes simplex viral encephalitis, idiopathic cerebellitis, pneumococcal meningitis, and superior sagittal sinus thrombosis with venous infarction. IVE in these cases may be due to multiple factors, including arterial, venous, perivascular, and leptomeningeal or sulcal contrast medium accumulation. Our observations suggest that arterial ischemia, previously described as the cardinal cause of IVE, probably does not explain all instances, and urge caution in interpreting this sign as a specific MRI manifestation of acute arterial infarction or ischemia. (orig.) With 4 figs., 1 tab., 44 refs.

  9. Intravascular papillary endothelial hyperplasia of the extremities: MR imaging findings with pathologic correlation

    International Nuclear Information System (INIS)

    Lee, Sang Hoon; Suh, Jin-Suck; Lim, Byung Il; Yang, Woo Ick; Shin, Kyoo-Ho

    2004-01-01

    We report the MRI findings of three cases of intravascular papillary endothelial hyperplasia (IPEH) of the extremities with correlation of the pathologic findings. The IPEH is a non-neoplastic reactive lesion within the vessels and is commonly associated with thrombi. Signal intensity of the IPEH is complex due to the thrombi and the PEH itself. The thrombi are characterized by a slightly hyperintense signal on T1- and T2-weighted images compared with that of muscle when it comes at the medium stage of hemorrhage. Papillary endothelial hyperplastic tissue appears either as iso- or hyperintense to the muscle on T2- and T1-weighted images and shows variable enhancement on Gd-DTPA-enhanced images. (orig.)

  10. Establishment of virtual three-dimensional model for intravascular interventional devices and its clinical value

    International Nuclear Information System (INIS)

    Wei Xin; Zhong Liming; Xie Xiaodong; Wang Chaohua; You Jian; Hu Hong; Hu Kongqiong; Zhao Xiaowei

    2012-01-01

    Objective: To explore virtual three-dimensional (3D) model for intravascular interventional devices,the method of preoperative simulation and its value in clinical work. Methods: The virtual models including catheter, guide wire, stent and coil were established by using the 3D moulding software of 3D Studio MAX R3. The interventional preoperative simulation was performed on personal computer including 21 patients of cerebral aneurysm embolization (anterior communicating artery 5, posterior communicating artery 10,middle cerebral artery 3, internal carotid artery 2, and vertebral artery 1), during interventional procedures, the surgeon relied on the simulation results for plastic micro-guide wire, catheter and the release of micro-coils and stents. Results: (1) All the virtual instruments and real instruments had similar shape,the overall tine for constructing virtual model was about 20 hours. The preoperative simulation took 50 to 80 minutes. (2) The simulation result of catheter insertion in the 18 cases had relevant value to guide micro-catheter, molding micro-guide wire tip, and shortened the operating time. For embolization, the simulation results of filling coil and releasing stent were similar to surgical results in 76% of the patients (16/21). (3)For teaching and training, 93% (38/41) of doctors in training believed that preoperative simulation facilitated the understanding of surgery. Conclusions: The method of virtual model of intravascular interventional devices was reliable. The preoperative simulation results could be used to guide practical clinical operation with relatively high degree of similarity, and could play a role in promoting researches on interventional virtual operations. (authors)

  11. Intravascular large B-cell lymphoma of the kidney: A case report

    Directory of Open Access Journals (Sweden)

    Jia Nan

    2011-09-01

    Full Text Available Abstract We report a 41-year-old Chinese woman with intravascular large B-cell lymphoma diagnosed by percutaneous renal biopsy. The patient was admitted to Nanfang Hospital of Southern Medical University, Guangzhou, China with complaints of high spiking fever for a month and bilateral lower limb fatigue with difficulty ambulating for the past 5 months. She had renal dysfunction with a total urinary protein of 5.61 g/dL (56.1 g/L, serum albumin of 2.89 g/dL (28.9 g/L, urea nitrogen of 2.24 mg/dL (1.6 mmol/L, and serum creatinine of 0.54 mg/dL (48 μmol/L. Bone marrow biopsy revealed myeloproliferative disorder without abnormal myeloid or lymphocytic proliferation. Positron Emission Tomography-Computed Tomography (PET-CT showed marked bilateral swelling and enlargement of the renal parenchyma with splenic enlargement and involvement of multiple vertebrae. Percutaneous renal biopsy showed island-like accumulations of medium to large lymphoid cells in many areas of the interstitium, with round vesicular nuclei containing distinct basophilic nucleoli. Immunohistochemical analysis together with other supportive investigation confirmed the diagnosis of intravascular large B-cell lymphoma. Ten days later, she was started on chemotherapy with CHOP (cyclophosphamide, doxorubicin, leurocristime and prednisone for a week. Palliative radiotherapy DT 40Gy/20F with other supportive treatment was provided for metastatic foci in the medullary cavity of the sternum, T1-T7. The patient regained muscle strength in both lower limbs and was able to walk again after three weeks. The patient was discharged after hepatic and renal function and proteinuria values had returned to normal. Follow-up data shows the patient to be alive nine months after discharge.

  12. Prediction of postpercutaneous coronary intervention myocardial infarction: insights from intravascular imaging, coronary flow, and biomarker evaluation.

    Science.gov (United States)

    Hoole, Stephen P; Hernández-Sánchez, Jules; Brown, Adam J; Giblett, Joel P; Bennett, Martin R; West, Nick E J

    2018-05-01

    Percutaneous coronary intervention-induced myocardial infarction (PMI) has prognostic significance. Identifying patients at high risk for PMI is desirable as it may alter strategy and facilitate early preventative therapy. We therefore sought to establish whether preprocedural demographic, interventional (plaque characteristics and coronary microcirculatory function), and inflammatory, endothelial damage, and platelet-derived biomarker data could predict the risk of PMI. We performed target vessel pressure wire to assess fractional flow reserve, index of microcirculatory resistance (IMR) and coronary flow reserve, plaque characterization by virtual histology intravascular ultrasound, and assayed peripheral biomarkers before uncomplicated PCI in 88 patients. We then analyzed post-PCI cardiac troponin level to adjudicate PMI based on the third universal definition of myocardial infarction. Overall incidence of PMI was 27%. Women [10/15 (66%) vs. 14/73 (19%), PPMI. Preprocedural coronary flow reserve was lower in individuals with a subsequent PMI (1.8±1.2 vs. 2.1±1.3. P=0.03), and patients with higher pre-PCI IMR were more likely to sustain PMI [IMR>22: 10/23 (44%) vs. ≤22: 14/65 (22%), P=0.04], although neither was predictive after multivariate analysis. Plaque characterization by virtual histology intravascular ultrasound did not discriminate those at risk of PMI. However, peripheral venous interleukin (IL)-18 and IL-8 levels were independently negatively and positively associated with PMI, respectively. Women and those with low BMI, particularly when associated with high IL-8 and low IL-18 levels, appear to be at increased risk of PMI.

  13. The effects of serial intravascular transfusions in ascitic/hydropic RhD-alloimmunized fetuses.

    Science.gov (United States)

    Craparo, F J; Bonati, F; Gementi, P; Nicolini, U

    2005-02-01

    To evaluate the effects of serial intravascular transfusions on RhD-alloimmunized fetuses with ascites/hydrops at the time of the first transfusion by measuring multiple hematological/biochemical blood variables. Thirty-one singleton pregnancies were referred for management of RhD alloimmunization. Seven fetuses had hydrops on presentation and were transfused immediately. The remainder underwent weekly ultrasound examinations, and fetal blood sampling and transfusion were performed on development of ascites. In the 104 samples collected overall from the 31 fetuses, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase (PCHE), creatine kinase, triglycerides and cholesterol were measured and compared with a reference range for non-anemic fetuses. The median gestational age at first transfusion was 26 (range, 18-34) weeks. There were three fetal losses after the first transfusion, two of which were due to procedure-related complications; one further loss occurred. At the first transfusion fetal hematocrit, pO2, total protein, PCHE, creatinine and urea concentrations were significantly decreased compared to reference data, while total and direct bilirubin, AST, ALT, amylase, triglyceride and uric acid concentrations were increased. In all surviving fetuses ascites/hydrops had disappeared by the second transfusion. Fetal pO2, total protein, AST, ALT and PCHE concentrations had normalized by the third transfusion. Correction of fetal anemia did not affect the other variables. RhD-alloimmunized fetuses with ascites/hydrops at the time of the first transfusion had a survival rate of 87%. Alterations of several biochemical fetal blood indices are present at the first sampling/transfusion, but most variables normalize with intravascular transfusions. Copyright 2005 ISUOG.

  14. Evaluation of cerebral intravascular blood flow by time density curve study of intravenous digital subtraction angiography

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    Imamura, Toru; Kogure, Kyuya (Tohoku Univ., Sendai (Japan). School of Medicine); Sekine, Teiko; Satoh, Kei; Endoh, Minoru; Tsuburaya, Kenji; Hoshi, Akihiko

    1992-01-01

    Time density curve (TDC) can be reconstructed from the data of intravenous digital subtraction angiography (IVDSA). We evaluated peak time (PT) and modal transit time (MOTT) of the TDC as the probable indicator of cerebral intravascular blood flow. Cerebral IVDSA and single photon emission CT (SPECT) were performed on 12 patients with ischemic cerebrovascular disease, which consisted of 3 internal carotid artery (ICA) occlusions, one middle cerebral artery (MCA) occlusion, one anterior cerebral artery (ACA) branch occlusion and 7 lacunar infarctions. We classified former 4 patients as occlusion group and latter 8 as reference group. In 3 patients (2 ICA and one MCA occlusions), SPECT study revealed definite hypoaccumulation in the MCA territory of occlusive side. Two regions of interest (ROI) were placed on the territories of right and left middle cerebral arteries in the frontal view of cerebral IVDSA. Digital data processor fitted {gamma} curve to the TDC of each ROI, and calculated PT and MOTT. The absolute lateralities of PT and MOTT of MCA territory was significantly (p<0.05) larger in occlusion group than reference group. Patients with hypoaccumulation in SPECT had significantly (p<0.02) larger laterality of MOTT than patients with isoaccumulation. One ICA occluded patient without hypoaccumulation in corresponding MCA territory had relatively small laterality of MOTT similar to the patients of ACA branch occlusion and lacunar infarction. These results suggest that PT and MOTT are possible to detect the laterality of the intravascular blood flow in MCA territories caused by major artery occlusion. Cerebral TDC study of IVDSA may be useful in some clinical therapeutic situations such as hemodilution or intra-arterial thrombolysis, and worth further clinical evaluation. (author).

  15. Ensemble models of neutrophil trafficking in severe sepsis.

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    Sang Ok Song

    Full Text Available A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about 18% of the treated population that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental

  16. d(− Lactic Acid-Induced Adhesion of Bovine Neutrophils onto Endothelial Cells Is Dependent on Neutrophils Extracellular Traps Formation and CD11b Expression

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    Pablo Alarcón

    2017-08-01

    Full Text Available Bovine ruminal acidosis is of economic importance as it contributes to reduced milk and meat production. This phenomenon is mainly attributed to an overload of highly fermentable carbohydrate, resulting in increased d(− lactic acid levels in serum and plasma. Ruminal acidosis correlates with elevated acute phase proteins in blood, along with neutrophil activation and infiltration into various tissues leading to laminitis and aseptic polysynovitis. Previous studies in bovine neutrophils indicated that d(− lactic acid decreased expression of L-selectin and increased expression of CD11b to concentrations higher than 6 mM, suggesting a potential role in neutrophil adhesion onto endothelia. The two aims of this study were to evaluate whether d(− lactic acid influenced neutrophil and endothelial adhesion and to trigger neutrophil extracellular trap (NET production (NETosis in exposed neutrophils. Exposure of bovine neutrophils to 5 mM d(− lactic acid elevated NET release compared to unstimulated neutrophil negative controls. Moreover, this NET contains CD11b and histone H4 citrullinated, the latter was dependent on PAD4 activation, a critical enzyme in DNA decondensation and NETosis. Furthermore, NET formation was dependent on d(− lactic acid plasma membrane transport through monocarboxylate transporter 1 (MCT1. d(− lactic acid enhanced neutrophil adhesion onto endothelial sheets as demonstrated by in vitro neutrophil adhesion assays under continuous physiological flow conditions, indicating that cell adhesion was a NET- and a CD11b/ICAM-1-dependent process. Finally, d(− lactic acid was demonstrated for the first time to trigger NETosis in a PAD4- and MCT1-dependent manner. Thus, d(− lactic acid-mediated neutrophil activation may contribute to neutrophil-derived pro-inflammatory processes, such as aseptic laminitis and/or polysynovitis in animals suffering acute ruminal acidosis.

  17. Interval and continuous exercise regimens suppress neutrophil-derived microparticle formation and neutrophil-promoted thrombin generation under hypoxic stress.

    Science.gov (United States)

    Chen, Yi-Ching; Ho, Ching-Wen; Tsai, Hsing-Hua; Wang, Jong-Shyan

    2015-04-01

    Acute hypoxic exposure increases vascular thrombotic risk. The release of procoagulant-rich microparticles from neutrophils accelerates the pathogenesis of inflammatory thrombosis. The present study explicates the manner in which interval and continuous exercise regimens affect neutrophil-derived microparticle (NDMP) formation and neutrophil/NDMP-mediated thrombin generation (TG) under hypoxic condition. A total of 60 sedentary males were randomized to perform either aerobic interval training [AIT; 3-min intervals at 40% and 80% V̇O2max (maximal O2 consumption)] or moderate continuous training (MCT; sustained 60% V̇O2max) for 30 min/day, 5 days/week for 5 weeks, or to a control (CTL) group who did not receive any form of training. At rest and immediately after hypoxic exercise test (HE, 100 W under 12% O2 for 30 min), the NDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. Before the intervention, HE (i) elevated coagulant factor VIII/fibrinogen concentrations and shortened activated partial thromboplastin time (aPTT), (ii) increased total and tissue factor (TF)-rich/phosphatidylserine (PS)-exposed NDMP counts and (iii) enhanced the peak height and rate of TG promoted by neutrophils/NDMPs. Following the 5-week intervention, AIT exhibited higher enhancement of V̇O2max than did MCT. Notably, both MCT and AIT attenuated the extents of HE-induced coagulant factor VIII/fibrinogen elevations and aPTT shortening. Furthermore, the two exercise regimens significantly decreased TF-rich/PS-exposed NDMP formation and depressed neutrophil/NDMP-mediated dynamic TG at rest and following HE. Hence, we conclude that AIT is superior to MCT for enhancing aerobic capacity. Moreover, either AIT or MCT effectively ameliorates neutrophil/NDMP-promoted TG by down-regulating expression of procoagulant factors during HE, which may reduce thrombotic risk evoked by hypoxia. Moreover, either AIT or MCT effectively ameliorates neutrophil

  18. A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8.

    Science.gov (United States)

    Kamoshida, Go; Tansho-Nagakawa, Shigeru; Kikuchi-Ueda, Takane; Nakano, Ryuichi; Hikosaka, Kenji; Nishida, Satoshi; Ubagai, Tsuneyuki; Higashi, Shouichi; Ono, Yasuo

    2016-12-01

    Hospital-acquired infections as a result of Acinetobacter baumannii have become problematic because of high rates of drug resistance. Although neutrophils play a critical role in early protection against bacterial infection, their interactions with A. baumannii remain largely unknown. To elucidate the interactions between A. baumannii and human neutrophils, we cocultured these cells and analyzed them by microscopy and flow cytometry. We found that A. baumannii adhered to neutrophils. We next examined neutrophil and A. baumannii infiltration into Matrigel basement membranes by an in vitro transmigration assay. Neutrophils were activated by A. baumannii, and invasion was enhanced. More interestingly, A. baumannii was transported together by infiltrating neutrophils. Furthermore, we observed by live cell imaging that A. baumannii and neutrophils moved together. In addition, A. baumannii-activated neutrophils showed increased IL-8 production. The transport of A. baumannii was suppressed by inhibiting neutrophil infiltration by blocking the effect of IL-8. A. baumannii appears to use neutrophils for transport by activating these cells via IL-8. In this study, we revealed a novel bacterial transport mechanism that A. baumannii exploits human neutrophils by adhering to and inducing IL-8 release for bacterial portage. This mechanism might be a new treatment target. © Society for Leukocyte Biology.

  19. G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling

    Science.gov (United States)

    Bajrami, Besnik; Zhu, Haiyan; Zhang, Yu C.

    2016-01-01

    Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. PMID:27551153

  20. [Optimal intravascular brachytherapy: safety and radiation protection, reliability and precision guaranteed by guidelines, recommendations and regulatory requirements].

    Science.gov (United States)

    Quast, Ulrich; Kaulich, Theodor W; Lorenz, Joachim

    2002-02-01

    The success of intravascular brachytherapy relies entirely on the interdisciplinary approach. Interventional cardiologists, radiation oncologists and medical physicists must form a team from day 1. All members of the team need special knowledge and regular training in the field of vascular radiation therapy. Optimization of intravascular brachytherapy requires the use of standardized methods of dose specification, recording and reporting. This also implies using standardized methods of source calibration in terms of absorbed dose to water and having methods for simple internal control of the dosimetric quantities of new or replaced sources. Guidance is offered by international recommendations (AAPM TG 60, DGMP Report 16, NCS and EVA GEC-ESTRO). LEGAL REQUIREMENTS FOR RADIATION PROTECTION--WHAT'S NEW?: In Europe, new legal requirements on radiation protection issues have to be fulfilled. For Germany, the revised "Strahlenschutzverordnung" has been released recently. Nearly all organizational and medical processes are affected. For intravascular brachytherapy, several changes of requirements have to be considered. However, to follow these requirements does not cause serious problems. DGMP REPORT 16: GUIDELINES FOR MEDICAL PHYSICAL ASPECTS OF INTRAVASCULAR BRACHYTHERAPY: Evaluation of clinical results by comparison of intravascular brachytherapy treatment parameters is possible only if the prescribed dose and the applied dose distribution are reported clearly, completely and uniformly. The DGMP guidelines thus recommend to prescribe the dose to water at the system related reference point PRef at 2 mm radial distance for intracoronary application (and at 5 mm for peripheral vessels). The mean dose at 1 mm tissue depth (respectively at 2 mm) should be reported in addition. To safely define the planning target volume from the injured length, safety margins of at least 5 mm (10 mm) have to be taken into account on both ends. Safety margins have also to be considered for

  1. Autophagy Mediates Interleukin-1β Secretion in Human Neutrophils

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    Leonardo Iula

    2018-02-01

    Full Text Available Interleukin-1β (IL-1β, a major pro-inflammatory cytokine, is a leaderless cytosolic protein whose secretion does not follow the classical endoplasmic reticulum-to-Golgi pathway, and for which a canonical mechanism of secretion remains to be established. Neutrophils are essential players against bacterial and fungi infections. These cells are rapidly and massively recruited from the circulation into infected tissues and, beyond of displaying an impressive arsenal of toxic weapons effective to kill pathogens, are also an important source of IL-1β in infectious conditions. Here, we analyzed if an unconventional secretory autophagy mechanism is involved in the exportation of IL-1β by these cells. Our findings indicated that inhibition of autophagy with 3-methyladenine and Wortmannin markedly reduced IL-1β secretion induced by LPS + ATP, as did the disruption of the autophagic flux with Bafilomycin A1 and E64d. These compounds did not noticeable affect neutrophil viability ruling out that the effects on IL-1β secretion were due to cell death. Furthermore, VPS34IN-1, a specific autophagy inhibitor, was still able to reduce IL-1β secretion when added after it was synthesized. Moreover, siRNA-mediated knockdown of ATG5 markedly reduced IL-1β secretion in neutrophil-differentiated PLB985 cells. Upon LPS + ATP stimulation, IL-1β was incorporated to an autophagic compartment, as was revealed by its colocalization with LC3B by confocal microscopy. Overlapping of IL-1β-LC3B in a vesicular compartment peaked before IL-1β increased in culture supernatants. On the other hand, stimulation of autophagy by cell starvation augmented the colocalization of IL-1β and LC3B and then promoted neutrophil IL-1β secretion. In addition, specific ELISAs indicated that although both IL-1β and pro-IL-1β are released to culture supernatants upon neutrophil stimulation, autophagy only promotes IL-1β secretion. Furthermore, the serine proteases inhibitor

  2. Reduction of exit-site infections of tunnelled intravascular catheters among neutropenic patients by sustained-release chlorhexidine dressings: results from a prospective randomized controlled trial.

    Science.gov (United States)

    Chambers, S T; Sanders, J; Patton, W N; Ganly, P; Birch, M; Crump, J A; Spearing, R L

    2005-09-01

    Exit-site and tunnel infections of tunnelled central intravascular catheters are a frequent source of morbidity among neutropenic patients and may necessitate catheter removal. They require antimicrobial therapy that increases healthcare costs and is associated with adverse drug reactions. A prospective randomized clinical trial was conducted among adult patients undergoing chemotherapy in a haematology unit. Tunnelled intravascular catheters were randomized to receive the control of a standard dressing regimen as recommended by the British Committee for Standards in Haematology, or to receive the intervention of a sustained-release chlorhexidine dressing. Follow-up data were available in 112 of 114 tunnelled intravascular catheters which were randomized. Exit-site or combined exit-site/tunnel infections occurred in 23 (43%) of 54 catheters in the control group, and five (9%) of 58 catheters in the intervention group [odds ratio (OR) for intervention group compared with control group =0.13, 95% confidence intervals (CI) 0.04-0.37, P<0.001]. More tunnelled intravascular catheters were prematurely removed from the control group than the intervention group for documented infections [20/54 (37%) vs 6/58 (10%), OR=0.20, 95%CI 0.53-0.07]. However, there was no difference in the numbers of tunnelled intravascular catheters removed for all proven and suspected intravascular catheter-related infections [21/54 (39%) vs 19/58 (33%)], or in the time to removal of catheters for any reason other than death or end of treatment for underlying disease. Thus chlorhexidine dressings reduced the incidence of exit-site/tunnel infections of indwelling tunnelled intravascular catheters without prolonging catheter survival in neutropenic patients, and could be considered as part of the routine management of indwelling tunnelled intravascular catheters among neutropenic patients.

  3. Head to head comparison of optical coherence tomography, intravascular ultrasound echogenicity and virtual histology for the detection of changes in polymeric struts over time

    DEFF Research Database (Denmark)

    Brugaletta, Salvatore; Gomez-Lara, Josep; Bruining, Nico

    2012-01-01

    To analyse and to compare the changes in the various optical coherence tomography (OCT), echogenicity and intravascular ultrasound virtual histology (VH) of the everolimus-eluting bioresorbable scaffold (ABSORB) degradation parameters during the first 12 months after ABSORB implantation. In the A......To analyse and to compare the changes in the various optical coherence tomography (OCT), echogenicity and intravascular ultrasound virtual histology (VH) of the everolimus-eluting bioresorbable scaffold (ABSORB) degradation parameters during the first 12 months after ABSORB implantation...

  4. Neutrophil extracellular traps: double-edged swords of innate immunity.

    Science.gov (United States)

    Kaplan, Mariana J; Radic, Marko

    2012-09-15

    Spectacular images of neutrophils ejecting nuclear chromatin and bactericidal proteins, in response to microbes, were first reported in 2004. As externalized chromatin could entangle bacteria, these structures were named neutrophil extracellular traps (NETs). Subsequent studies identified microorganisms and sterile conditions that stimulate NETs, as well as additional cell types that release extracellular chromatin. The release of NETs is the most dramatic stage in a cell death process called NETosis. Experimental evidence suggests that NETs participate in pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. Exaggerated NETosis or diminished NET clearance likely increases risk of autoreactivity to NET components. The biological significance of NETs is just beginning to be explored. A more complete integration of NETosis within immunology and pathophysiology will require better understanding of NET properties associated with specific disease states and microbial infections. This may lead to the identification of important therapeutic targets.

  5. Neutrophils and Granulocytic MDSC: The Janus God of Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Serena Zilio

    2016-09-01

    Full Text Available Neutrophils are the most abundant circulating blood cell type in humans, and are the first white blood cells recruited at the inflammation site where they orchestrate the initial immune response. Although their presence at the tumor site was recognized in the 1970s, until recently these cells have been neglected and considered to play just a neutral role in tumor progression. Indeed, in recent years neutrophils have been recognized to play a dual role in tumor development by either assisting the growth, angiogenesis, invasion, and metastasis or by exerting tumoricidal action directly via the secretion of antitumoral compounds, or indirectly via the orchestration of antitumor immunity. Understanding the biology of these cells and influencing their polarization in the tumor micro- and macro-environment may be the key for the development of new therapeutic strategies, which may finally hold the promise of an effective immunotherapy for cancer.

  6. 3D dosimetry study of 188Re liquid balloon for intravascular brachytherapy using BANG polymer gel dosemeters

    International Nuclear Information System (INIS)

    Wuu, S.; Schiff, P.B.; Maryanski, M.; Liu, T.; Borzillary, S.; Weinberger, J.

    2002-01-01

    It has been suggested that the combination of intravascular brachytherapy and coronary stent implantation may result in further reduction of restenosis after percutaneous balloon angioplasty. The use of an angioplasty balloon filled with a P 188 Re liquid beta source for intravascular brachytherapy provides the advantage of accurate source positioning and uniform dose distribution to the coronary vessel wall. The effect of source edge and stent on the dose distribution of the target tissue may be clinically important. In BANG gels, the absorbed radiation produces free-radical chain polymerisation of acrylic monomers that are initially dissolved in the gel. The number of polymer particles is proportional to the absorbed dose. In this study, 3D dose distributions are presented for 188 Re balloons, with and without stents, using a prototype He-Ne laser CT scanner and the proprietary BANG polymer gel dosemeters. (author)

  7. High glucose impairs superoxide production from isolated blood neutrophils

    DEFF Research Database (Denmark)

    Perner, A; Nielsen, S E; Rask-Madsen, J

    2003-01-01

    Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study...... measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils....

  8. Association of microparticles and neutrophil activation with decompression sickness.

    Science.gov (United States)

    Thom, Stephen R; Bennett, Michael; Banham, Neil D; Chin, Walter; Blake, Denise F; Rosen, Anders; Pollock, Neal W; Madden, Dennis; Barak, Otto; Marroni, Alessandro; Balestra, Costantino; Germonpre, Peter; Pieri, Massimo; Cialoni, Danilo; Le, Phi-Nga Jeannie; Logue, Christopher; Lambert, David; Hardy, Kevin R; Sward, Douglas; Yang, Ming; Bhopale, Veena B; Dujic, Zeljko

    2015-09-01

    Decompression sickness (DCS) is a systemic disorder, assumed due to gas bubbles, but additional factors are likely to play a role. Circulating microparticles (MPs)--vesicular structures with diameters of 0.1-1.0 μm--have been implicated, but data in human divers have been lacking. We hypothesized that the number of blood-borne, Annexin V-positive MPs and neutrophil activation, assessed as surface MPO staining, would differ between self-contained underwater breathing-apparatus divers suffering from DCS vs. asymptomatic divers. Blood was analyzed from 280 divers who had been exposed to maximum depths from 7 to 105 meters; 185 were control/asymptomatic divers, and 90 were diagnosed with DCS. Elevations of MPs and neutrophil activation occurred in all divers but normalized within 24 h in those who were asymptomatic. MPs, bearing the following proteins: CD66b, CD41, CD31, CD142, CD235, and von Willebrand factor, were between 2.4- and 11.7-fold higher in blood from divers with DCS vs. asymptomatic divers, matched for time of sample acquisition, maximum diving depth, and breathing gas. Multiple logistic regression analysis documented significant associations (P < 0.001) between DCS and MPs and for neutrophil MPO staining. Effect estimates were not altered by gender, body mass index, use of nonsteroidal anti-inflammatory agents, or emergency oxygen treatment and were modestly influenced by divers' age, choice of breathing gas during diving, maximum diving depth, and whether repetitive diving had been performed. There were no significant associations between DCS and number of MPs without surface proteins listed above. We conclude that MP production and neutrophil activation exhibit strong associations with DCS. Copyright © 2015 the American Physiological Society.

  9. Neutrophil extracellular traps promote deep vein thrombosis in mice

    Science.gov (United States)

    Brill, A.; Fuchs, T.A.; Savchenko, A.S.; Thomas, G.M.; Martinod, K.; De Meyer, S.F.; Bhandari, A.A.; Wagner, D.D.

    2011-01-01

    Summary Background Upon activation, neutrophils can release nuclear material known as neutrophil extracellular traps (NETs), which were initially described as a part of antimicrobial defense. Extracellular chromatin was recently reported to be pro-thrombotic in vitro and to accumulate in plasma and thrombi of baboons with experimental deep vein thrombosis (DVT). Objective To explore the source and role of extracellular chromatin in DVT. Methods We used an established murine model of DVT induced by flow restriction (stenosis) in the inferior vena cava (IVC). Results We demonstrate that the levels of extracellular DNA increase in plasma after 6 h IVC stenosis, compared to sham-operated mice. Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated histone H3 (CitH3), an element of NETs’ structure, was present only in the red part of thrombi and was frequently associated with the Gr-1 antigen. Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated mixture of calf thymus histones increased plasma VWF and promoted DVT early after stenosis application. Conclusions Extracellular chromatin, likely originating from neutrophils, is a structural part of a venous thrombus and both the DNA scaffold and histones appear to contribute to the pathogenesis of DVT in mice. NETs may provide new targets for DVT drug development. PMID:22044575

  10. Distinct neutrophil subpopulations phenotype by flow cytometry in myelodysplastic syndromes.

    Science.gov (United States)

    Vikentiou, Myrofora; Psarra, Katerina; Kapsimali, Violetta; Liapis, Konstantinos; Michael, Michalis; Tsionos, Konstantinos; Lianidou, Evi; Papasteriades, Chryssa

    2009-03-01

    The cardinal feature of myelodysplastic syndromes (MDS) is dysplasia involving one or more myeloid cell lineages. In the present study, we used 4-color flow cytometric analysis to investigate dysgranulopoiesis in bone marrow specimens from 65 patients with MDS. The antigen expression patterns of total neutrophil granulocytes (TNG) and of the two distinct neutrophil granulocytic subpopulations (NGSs), NGS-1 (dimmer CD45 expression) and NGS-2 (stronger CD45 expression) identified on the side scatter (SS) vs. CD45-intensity plot, were studied. The neutrophil granulocytes from patients with MDS showed characteristic antigen expression aberrancies which were more pronounced in NGS-2 subpopulation. Studying separately the NGS-2 subpopulation with the CD16/MPO/LF combination, the low CD16(+)/MPO(+) and low CD16(+)/LF(+) percentages seemed to discriminate between lower-risk and higher-risk patients with MDS in most occasions. Furthermore, a detailed assessment of the NGS-1 and NGS-2 immunophenotypic patterns revealed early dysplastic changes, not otherwise observed by standard TNG analysis, especially in cases of lower-risk MDS.

  11. Elevated Neutrophil Lymphocyte Ratio in Recurrent Optic Neuritis

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    Hande Guclu

    2015-01-01

    Full Text Available Purpose. To demonstrate the relation between optic neuritis (ON and systemic inflammation markers as neutrophil lymphocyte ratio (N/L ratio, platelet count, mean platelet volume (MPV, and red cell distribution width (RDW and furthermore to evaluate the utilization of these markers to predict the frequency of the ON episodes. Methods. Forty-two patients with acute ON and forty healthy subjects were enrolled into the study. The medical records were reviewed for age, sex, hemoglobin (Hb, Haematocrit (Htc, RDW, platelet count, MPV, white blood cell count (WBC, neutrophil and lymphocyte count, and neutrophil lymphocyte ratio (N/L ratio. Results. The mean N/L ratio, platelet counts, and RDW were significantly higher in ON group (p=0.000, p=0.048, and p=0.002. There was a significant relation between N/L ratio and number of episodes (r=0.492, p=0.001. There was a statistically significant difference for MPV between one episode group and recurrent ON group (p=0.035. Conclusions. Simple and inexpensive laboratory methods could help us show systemic inflammation and monitor ON patients. Higher N/L ratio can be a useful marker for predicting recurrent attacks.

  12. Ascorbic acid transport and accumulation in human neutrophils

    International Nuclear Information System (INIS)

    Washko, P.; Rotrosen, D.; Levine, M.

    1989-01-01

    The transport, accumulation, and distribution of ascorbic acid were investigated in isolated human neutrophils utilizing a new ascorbic acid assay, which combined the techniques of high performance liquid chromatography and coulometric electrochemical detection. Freshly isolated human neutrophils contained 1.0-1.4 mM ascorbic acid, which was localized greater than or equal to 94% to the cytosol, was not protein bound, and was present only as ascorbic acid and not as dehydroascorbic acid. Upon addition of ascorbic acid to the extracellular medium in physiologic amounts, ascorbic acid was accumulated in neutrophils in millimolar concentrations. Accumulation was mediated by a high affinity and a low affinity transporter; both transporters were responsible for maintenance of concentration gradients as large as 50-fold. The high affinity transporter had an apparent Km of 2-5 microns by Lineweaver-Burk and Eadie-Hofstee analyses, and the low affinity transporter had an apparent Km of 6-7 mM by similar analyses. Each transporter was saturable and temperature dependent. In normal human blood the high affinity transporter should be saturated, whereas the low affinity transporter should be in its linear phase of uptake

  13. Flavonoids Inhibit the Respiratory Burst of Neutrophils in Mammals

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    Milan Ciz

    2012-01-01

    Full Text Available Neutrophils represent the front-line defence cells in protecting organisms against infection and play an irreplaceable role in the proper performance of the immune system. As early as within the first minutes of stimulation, neutrophilic NADPH oxidase is activated, and cells release large quantities of highly toxic reactive oxygen species (ROS. These oxidants can be highly toxic not only for infectious agents but also for neighboring host tissues. Since flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of ROS production. The present paper summarizes contemporary knowledge on the effects of various flavonoids on the respiratory burst of mammalian neutrophils. It can be summarized that the inhibitory effects of flavonoids on the respiratory burst of phagocytes are mediated via inhibition of enzymes involved in cell signaling as well as via modulation of redox status. However, the effects of flavonoids are even more complex, and several sites of action, depending upon the flavonoid structure and way of application, are included.

  14. Association between neutrophil/lymphocyte ratio and coronary collateral circulation

    Directory of Open Access Journals (Sweden)

    Mustafa Oylumlu

    2012-03-01

    Full Text Available Objectives: To investigate relation between neutrophil/lymphocyte ratio and coronary collateral flow.Material and methods: Eighty-two patients admittedDicle University Medical Faculty Hospital Cardiology Departmentwith diagnosis of coronary artery disease anddetected significant stenosis or occlusion at least one ofthe coronary arteries, were included to study. Age, sex,presence of diabetes mellitus and hypertension, acute/stable coronary disease, body mass index, neutrophil/lymphocyte ratio, white blood count, Rentrop scores andnumber of diseased vessel were recorded.Results: Well-developed coronary collateral circulationwas found in 33 of the patients. Forty-nine patients hadpoor coronary collateral circulation. Mean age, sex, bodymass index, presence of diabetes mellitus and hypertensionwere similar in two groups. Mean neutrophil/lymphocyteratio was lower in well-developed coronary collateralcirculation group than poor coronary collateral circulationgroup, but there was no significant differences (2.78 vs2.89, p=0.12.Conclusions: There was no association between neutron/hil lymphocyte ratio and coronary collateral circulationaccording to our data. J Clin Exp Invest 2012; 3(1:29-32

  15. Specific features of a neonatal period in infants following intrauterine intravascular blood transfusion for fetal hemolytic disease

    Directory of Open Access Journals (Sweden)

    A. V. Ivanova

    2015-01-01

    Full Text Available The paper gives data on the characteristics of a neonatal period in infants following intrauterine blood transfusion for Rh-induced fetal hemolytic disease. It is shown that the early diagnosis and detection of the signs of fetal hemolytic disease, and intrauterine intravascular blood transfusion may prolong pregnancy, ensure the birth of a baby with normal anthropometric indicators, optimize his/her neonatal period and prognosis of severe hemolytic disease in the fetus and newborn.

  16. Lumen and calcium characteristics within calcified coronary lesions. Comparison of computed tomography coronary angiography versus intravascular ultrasound

    OpenAIRE

    Noll, Dariusz; Kruk, Mariusz; Pręgowski, Jerzy; Kaczmarska, Edyta; Kryczka, Karolina; Pracoń, Radosław; Skwarek, Mirosław; Dzielińska, Zofia; Petryka, Joanna; Śpiewak, Mateusz; Lubiszewska, Barbara; Norwa-Otto, Bożena; Opolski, Maksymilian; Witkowski, Adam; Demkow, Marcin

    2013-01-01

    Introduction Computed tomography coronary angiography (CTCA) is a diagnostic method used for exclusion of coronary artery disease. However, lower accuracy of CTCA in assessment of calcified lesions is a significant factor impeding applicability of CTCA for assessment of coronary atherosclerosis. Aim To provide insight into lumen and calcium characteristics assessed with CTCA, we compared these parameters to the reference of intravascular ultrasound (IVUS). Material and methods Two hundred and...

  17. Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death

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    Hiroto Kambara

    2018-03-01

    Full Text Available Summary: Gasdermin D (GSDMD is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, which established GSDMD as a negative regulator of innate immunity. In contrast to its activation in macrophages, in which activated inflammatory caspases cleave GSDMD to produce an N-terminal fragment (GSDMD-cNT to trigger pyroptosis, GSDMD cleavage and activation in neutrophils was caspase independent. It was mediated by a neutrophil-specific serine protease, neutrophil elastase (ELANE, released from cytoplasmic granules into the cytosol in aging neutrophils. ELANE-mediated GSDMD cleavage was upstream of the caspase cleavage site and produced a fully active ELANE-derived NT fragment (GSDMD-eNT that induced lytic cell death as efficiently as GSDMD-cNT. Thus, GSDMD is pleiotropic, exerting both pro- and anti-inflammatory effects that make it a potential target for antibacterial and anti-inflammatory therapies. : Kambara et al. find that GSDMD deficiency augments host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, establishing GSDMD as a negative regulator of innate immunity. GSDMD cleavage and activation in neutrophils is mediated by ELANE, released from cytoplasmic granules into the cytosol in aging neutrophils. Keywords: GSDMD, neutrophil death, neutrophil elastase, innate immunity, host defense

  18. Regulation of apoptosis and priming of neutrophil oxidative burst by diisopropyl fluorophosphate

    Directory of Open Access Journals (Sweden)

    Tsang Jennifer LY

    2010-07-01

    Full Text Available Abstract Background Diisopropyl fluorophosphate (DFP is a serine protease inhibitor that is widely used as an inhibitor of endogenous proteases in in vitro neutrophil studies. Its effects on neutrophil function are unclear. We sought to determine the biological effects of DFP on human neutrophil apoptosis and oxidative burst. Methods We isolated neutrophils from healthy volunteers, incubated them with DFP (2.5 mM, and evaluated neutrophil elastase (NE activity, neutrophil degranulation, apoptosis as reflected in hypodiploid DNA formation and exteriorization of phosphatidylserine (PS, processing and activity of caspases-3 and -8, oxidative burst activity and hydrogen peroxide release. Results Consistent with its activity as a serine protease inhibitor, DFP significantly inhibited NE activity but not the degranulation of azurophilic granules. DFP inhibited constitutive neutrophil apoptosis as reflected in DNA fragmentation, and the processing and activity of caspases-3 and -8. DFP also inhibited priming of neutrophils for oxidative burst activity and hydrogen peroxide release. However, DFP enhanced the exteriorization of PS in a dose-dependent manner. Conclusion We conclude that DFP exerts significant effects on neutrophil inflammatory function that may confound the interpretation of studies that use it for its antiprotease activity. We further conclude that endogenous proteases play a role in the biology of constitutive neutrophil apoptosis.

  19. Dose-volume histograms based on serial intravascular ultrasound: a calculation model for radioactive stents

    International Nuclear Information System (INIS)

    Kirisits, Christian; Wexberg, Paul; Gottsauner-Wolf, Michael; Pokrajac, Boris; Ortmann, Elisabeth; Aiginger, Hannes; Glogar, Dietmar; Poetter, Richard

    2001-01-01

    Background and purpose: Radioactive stents are under investigation for reduction of coronary restenosis. However, the actual dose delivered to specific parts of the coronary artery wall based on the individual vessel anatomy has not been determined so far. Dose-volume histograms (DVHs) permit an estimation of the actual dose absorbed by the target volume. We present a method to calculate DVHs based on intravascular ultrasound (IVUS) measurements to determine the dose distribution within the vessel wall. Materials and methods: Ten patients were studied by intravascular ultrasound after radioactive stenting (BX Stent, P-32, 15-mm length) to obtain tomographic cross-sections of the treated segments. We developed a computer algorithm using the actual dose distribution of the stent to calculate differential and cumulative DVHs. The minimal target dose, the mean target dose, the minimal doses delivered to 10 and 90% of the adventitia (DV10, DV90), and the percentage of volume receiving a reference dose at 0.5 mm from the stent surface cumulated over 28 days were derived from the DVH plots. Results were expressed as mean±SD. Results: The mean activity of the stents was 438±140 kBq at implantation. The mean reference dose was 111±35 Gy, whereas the calculated mean target dose within the adventitia along the stent was 68±20 Gy. On average, DV90 and DV10 were 33±9 Gy and 117±41 Gy, respectively. Expanding the target volume to include 2.5-mm-long segments at the proximal and distal ends of the stent, the calculated mean target dose decreased to 55±17 Gy, and DV 90 and DV 10 were 6.4±2.4 Gy and 107±36 Gy, respectively. Conclusions: The assessment of DVHs seems in principle to be a valuable tool for both prospective and retrospective analysis of dose-distribution of radioactive stents. It may provide the basis to adapt treatment planning in coronary brachytherapy to the common standards of radiotherapy

  20. Intravascular enhancement with identical iodine delivery rate using different iodine contrast media in a circulation phantom.

    Science.gov (United States)

    Mihl, Casper; Wildberger, Joachim E; Jurencak, Tomas; Yanniello, Michael J; Nijssen, Estelle C; Kalafut, John F; Nalbantov, Georgi; Mühlenbruch, Georg; Behrendt, Florian F; Das, Marco

    2013-11-01

    Both iodine delivery rate (IDR) and iodine concentration are decisive factors for vascular enhancement in computed tomographic angiography. It is unclear, however, whether the use of high-iodine concentration contrast media is beneficial to lower iodine concentrations when IDR is kept identical. This study evaluates the effect of using different iodine concentrations on intravascular attenuation in a circulation phantom while maintaining a constant IDR. A circulation phantom with a low-pressure venous compartment and a high-pressure arterial compartment simulating physiological circulation parameters was used (heart rate, 60 beats per minute; stroke volume, 60 mL; blood pressure, 120/80 mm Hg). Maintaining a constant IDR (2.0 g/s) and a constant total iodine load (20 g), prewarmed (37°C) contrast media with differing iodine concentrations (240-400 mg/mL) were injected into the phantom using a double-headed power injector. Serial computed tomographic scans at the level of the ascending aorta (AA), the descending aorta (DA), and the left main coronary artery (LM) were obtained. Total amount of contrast volume (milliliters), iodine delivery (grams of iodine), peak flow rate (milliliter per second), and intravascular pressure (pounds per square inch) were monitored using a dedicated data acquisition program. Attenuation values in the AA, the DA, and the LM were constantly measured (Hounsfield unit [HU]). In addition, time-enhancement curves, aortic peak enhancement, and time to peak were determined. All contrast injection protocols resulted in similar attenuation values: the AA (516 [11] to 531 [37] HU), the DA (514 [17] to 531 [32] HU), and the LM (490 [10] to 507 [17] HU). No significant differences were found between the AA, the DA, and the LM for either peak enhancement (all P > 0.05) or mean time to peak (AA, 19.4 [0.58] to 20.1 [1.05] seconds; DA, 21.1 [1.0] to 21.4 [1.15] seconds; LM, 19.8 [0.58] to 20.1 [1.05] seconds). This phantom study demonstrates that