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Sample records for perfused term human

  1. Long-term three-dimensional perfusion culture of human adult bone marrow mononuclear cells in bioreactors.

    PubMed

    Schmelzer, Eva; Finoli, Anthony; Nettleship, Ian; Gerlach, Jörg C

    2015-04-01

    The construction and long-term maintenance of three-dimensional in vitro bone marrow models is of great interest but still quite challenging. Here we describe the use of a multi-compartment hollow-fiber membrane based three-dimensional perfusion bioreactor for long-term culture of whole human bone marrow mononuclear cells. We also investigated bioreactors with incorporated open-porous foamed hydroxyapatite scaffolds, mimicking the in vivo bone matrix. Cells in bioreactors with and without scaffolds were cultured to 6 weeks and compared to Petri dish controls. Cells were analyzed for gene expression, surface markers by flow cytometry, metabolic activity, hematopoietic potential, viability, and attachment by immunocytochemistry. Cells in bioreactors were metabolic active during long-term culture. The percentages of hematopoietic stem cell and mature endothelial cell fractions were maintained in bioreactors. The expression of most of the analyzed genes stabilized and increased after long-term culture of 6 weeks. Compared to Petri dish culture controls, bioreactor perfusion culture improved in both the short and long-term, the colony formation unit capacity of hematopoietic progenitors. Cells attached to the ample surface area provided by hydroxyapatite scaffolds. The implementation of a hydroxyapatite scaffold did not influence colony formation capacity, percentages of cell type specific fractions, gene expression, cell viability or metabolic turnover when compared to control cells cultured in bioreactors without scaffolds. In conclusion, three-dimensional perfusion bioreactor culture enables long-term maintenance of primary human bone marrow cells, with hydroxyapatite scaffolds providing an in vivo-like scaffold for three-dimensional culture.

  2. Periodic "flow-stop" perfusion microchannel bioreactors for mammalian and human embryonic stem cell long-term culture.

    PubMed

    Korin, Natanel; Bransky, Avishay; Dinnar, Uri; Levenberg, Shulamit

    2009-02-01

    The present study examines the use of automated periodic "flow-stop" perfusion systems for long-term culture of mammalian cells in a microchannel bioreactor. The method is used to culture Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) for long periods of time (>7 d) in a microchannel (height 100 mum). Design parameters, mass transport and shear stress issues are theoretically examined via numerical simulations. Cell growth and morphology are experimentally monitored and an enhanced growth rate was measured compared to constant perfusion micro-reactors and to traditional culture in Petri dishes. Moreover, we demonstrate the use of the method to co-culture undifferentiated colonies of human Embryonic Stem Cells (hESC) on HFF feeder cells in microchannels. The successful hESC-HFF co-culture in the microbioreactor is achieved due to two vital characteristics of the developed method-short temporal exposure to flow followed by long static incubation periods. The short pulsed exposure to shear enables shear sensitive cells (e.g., hESC) to withstand the medium renewal flow. The long static incubation period may enable secreted factors (e.g., feeder cells secreted factors) to accumulate locally. Thus the developed method may be suitable for long-term culture of sensitive multi-cellular complexes in microsystems.

  3. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  4. Transplacental transfer of nitrosodimethylamine in perfused human placenta.

    PubMed

    Annola, K; Heikkinen, A T; Partanen, H; Woodhouse, H; Segerbäck, D; Vähäkangas, K

    2009-03-01

    Nitrosodimethylamine (NDMA) is a carcinogenic compound present in tobacco smoke and food such as cured meat, smoked fish and beer. The O(6)-methylguanine formed in human cord blood in mothers highly exposed to such products implicates NDMA exposure of the fetus. Dual recirculating human placental perfusion was used to get direct evidence of the transplacental transfer of NDMA and DNA adduct formation in perfused human placenta. Eleven placentas from normal full-term pregnancies were collected immediately after delivery and an isolated lobule was perfused with 1 or 5 microM of (14)C-NDMA with a reference substance, antipyrine (0.1mg/ml) added to the maternal circulation. Perfusate samples were collected from both maternal and fetal circulations every half an hour for the first two hours and once per hour from thereon. NDMA was analyzed by scintillation counting and antipyrine by high performance liquid chromatography. The transfer of NDMA was comparable to that of antipyrine and probably occurred through passive diffusion, with the concentrations in maternal and fetal sides equilibrating in 2-3h. No indication of any effect by efflux transporters on NDMA kinetics was noticed in the experiments utilizing Caco-2 or MDCK- MDCKII-MDR1 cell culture monolayer in a transwell system, either. Furthermore, no NDMA-DNA-adducts were found after the perfusions and no DNA-binding of NDMA was seen in in vitro incubations with human placental microsomes from 8 additional placentas. Thus, our study demonstrates that the human fetus can be exposed to NDMA from the maternal circulation. According to this study and the literature, NDMA is not metabolized in full-term human placenta from healthy non-smoking, non-drinking mothers. It remains to be studied whether NDMA concentrations high enough to evoke fetal toxicity can be obtained from dietary sources.

  5. ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta

    SciTech Connect

    Myllynen, Paeivi Kummu, Maria; Kangas, Tiina; Ilves, Mika; Immonen, Elina; Rysae, Jaana; Pirilae, Rauna; Lastumaeki, Anni; Vaehaekangas, Kirsi H.

    2008-10-15

    We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of {sup 14}C-PhIP (2 {mu}M) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72 {+-} 0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of {sup 14}C-PhIP from maternal to fetal circulation (FM ratio 0.90 {+-} 0.08 at 6 h, p < 0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75 {+-} 0.10, p = 0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of {sup 14}C-PhIP (R = - 0.81, p < 0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: - 0.11, p = 0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of {sup 14}C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarinoma cells.

  6. Ventilation-perfusion matching in long-term microgravity

    NASA Technical Reports Server (NTRS)

    Verbandt, Y.; Wantier, M.; Prisk, G. K.; Paiva, M.; West, J. B. (Principal Investigator)

    2000-01-01

    We studied the ventilation-perfusion matching pattern in normal gravity (1 G) and short- and long-duration microgravity (microG) using the cardiogenic oscillations in the sulfur hexaflouride (SF(6)) and CO(2) concentration signals during the phase III portion of vital capacity single-breath washout experiments. The signal power of the cardiogenic concentration variations was assessed by spectral analysis, and the phase angle between the oscillations of the two simultaneously expired gases was obtained through cross-correlation. For CO(2), a significant reduction of cardiogenic power was observed in microG, with respect to 1 G, but the reduction was smaller and more variable in the case of SF(6). A shift from an in-phase condition in 1 G to an out-of-phase condition was found for both short- and long-duration microG. We conclude that, although the distribution of ventilation and perfusion becomes more homogeneous in microG, significant inhomogeneities persist and that areas of high perfusion become associated with areas of relatively lower ventilation. In addition, these modifications seem to remain constant during long-term exposure to microG.

  7. The culture of human embryonic stem cells in microchannel perfusion bioreactors

    NASA Astrophysics Data System (ADS)

    Korin, Natanel; Bransky, Avishay; Dinnar, Uri; Levenberg, Shulamit

    2007-12-01

    The culture of human Embryonic Stem (ES) cells in microchannel bioreactors can be highly beneficial for ES cell biology studies and ES tissue engineering applications. In the present study we examine the use of Human Foreskin Fibroblasts (HFF) cells as feeder cells for human ES culture in a microchannel perfusion bioreactor. PDMS microchannels (depth:130 micron) were fabricated using conventional soft-lithography techniques. The channels were sterilized, coated with a human fibronectin solution and seeded with cells. Following a period of static incubation, culture medium was perfused through the channels at various flow rates and cell growth was monitored throughout the culture process. Mass transport and fluid mechanics models were used to evaluate the culture conditions (shear stress, oxygen levels within the micro-bioreactor as a function of the medium flow rate. The conditions for successful long-term culture (>7 days) of HFF under flow were established. Experiments with human embryonic stem cells cultured in microchannels show that the conditions essential to co-culture human ES cell on HFF cells under perfusion differ from the conditions necessary for HFF cell culture. Human ES cells were found to be highly sensitive to flow and culture conditions and did not grow under flow rates which were suitable for HFF long-term culture. Successful culture of undifferentiated human ES cell colonies in a perfusion micro-bioreactor is a basic step towards utilizing microfluidic techniques to explore stem cell biology.

  8. Skin blood perfusion and oxygenation colour affect perceived human health.

    PubMed

    Stephen, Ian D; Coetzee, Vinet; Law Smith, Miriam; Perrett, David I

    2009-01-01

    Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.

  9. A microfluidically perfused three dimensional human liver model.

    PubMed

    Rennert, Knut; Steinborn, Sandra; Gröger, Marko; Ungerböck, Birgit; Jank, Anne-Marie; Ehgartner, Josef; Nietzsche, Sandor; Dinger, Julia; Kiehntopf, Michael; Funke, Harald; Peters, Frank T; Lupp, Amelie; Gärtner, Claudia; Mayr, Torsten; Bauer, Michael; Huber, Otmar; Mosig, Alexander S

    2015-12-01

    Within the liver, non-parenchymal cells (NPCs) are critically involved in the regulation of hepatocyte polarization and maintenance of metabolic function. We here report the establishment of a liver organoid that integrates NPCs in a vascular layer composed of endothelial cells and tissue macrophages and a hepatic layer comprising stellate cells co-cultured with hepatocytes. The three-dimensional liver organoid is embedded in a microfluidically perfused biochip that enables sufficient nutrition supply and resembles morphological aspects of the human liver sinusoid. It utilizes a suspended membrane as a cell substrate mimicking the space of Disse. Luminescence-based sensor spots were integrated into the chip to allow online measurement of cellular oxygen consumption. Application of microfluidic flow induces defined expression of ZO-1, transferrin, ASGPR-1 along with an increased expression of MRP-2 transporter protein within the liver organoids. Moreover, perfusion was accompanied by an increased hepatobiliary secretion of 5(6)-carboxy-2',7'-dichlorofluorescein and an enhanced formation of hepatocyte microvilli. From this we conclude that the perfused liver organoid shares relevant morphological and functional characteristics with the human liver and represents a new in vitro research tool to study human hepatocellular physiology at the cellular level under conditions close to the physiological situation.

  10. Transport of benzo[alpha]pyrene in the dually perfused human placenta perfusion model: effect of albumin in the perfusion medium.

    PubMed

    Mathiesen, Line; Rytting, Erik; Mose, Tina; Knudsen, Lisbeth E

    2009-09-01

    Transport of benzo[alpha]pyrene (BaP) across the placenta was examined because it is a ubiquitous and highly carcinogenic substance found in tobacco smoke, polluted air and certain foods. Foetal exposure to this substance is highly relevant but is difficult to estimate. The human placenta is unique compared to other species; since it is available without major ethical obstacles, we have used the human placenta perfusion model to study transport from mother to foetus. Placentas were donated after births at Rigshospitalet in Copenhagen from pregnant mothers who signed an informed consent. BaP is lipophilic and studies using cell culture medium in 6-hr placenta perfusions showed minimal transport through the placenta. To increase the solubility of BaP in perfusion medium and to increase physiological relevance, perfusions were also performed with albumin added to the perfusion medium [2 and 30 mg/ml bovine serum albumin (BSA) and 30 mg/ml human serum albumin (HSA)]. The addition of albumin resulted in increased transfer of BaP from maternal to foetal reservoirs. The transfer was even higher in the presence of an HSA formulation containing acetyltryptophanate and caprylate, resulting in a foetal-maternal concentration (FM) ratio of 0.71 +/- 0.10 after 3 hr and 0.78 +/- 0.11 after 6 hr, whereas the FM ratio in perfusions without albumin was only 0.05 +/- 0.03 after 6 hr of perfusion. Less BaP accumulated in placental tissue in perfusions with added albumin. This shows that transplacental transport of the pro-carcinogenic substance BaP occurs, and emphasizes the importance of adding physiological concentrations of albumin when studying the transport of lipophilic substances.

  11. The isolated perfused human skin flap model: A missing link in skin penetration studies?

    PubMed

    Ternullo, Selenia; de Weerd, Louis; Flaten, Gøril Eide; Holsæter, Ann Mari; Škalko-Basnet, Nataša

    2017-01-01

    Development of effective (trans)dermal drug delivery systems requires reliable skin models to evaluate skin drug penetration. The isolated perfused human skin flap remains metabolically active tissue for up to 6h during in vitro perfusion. We introduce the isolated perfused human skin flap as a close-to-in vivo skin penetration model. To validate the model's ability to evaluate skin drug penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine) fluorescence marker were applied. The skin flaps were perfused with modified Krebs-Henseleit buffer (pH7.4). Infrared technology was used to monitor perfusion and to select a well-perfused skin area for administration of the markers. Flap perfusion and physiological parameters were maintained constant during the 6h experiments and the amount of markers in the perfusate was determined. Calcein was detected in the perfusate, whereas rhodamine was not detectable. Confocal images of skin cross-sections shoved that calcein was uniformly distributed through the skin, whereas rhodamine accumulated in the stratum corneum. For comparison, the penetration of both markers was evaluated on ex vivo human skin, pig skin and cellophane membrane. The proposed perfused flap model enabled us to distinguish between the penetrations of the two markers and could be a promising close-to-in vivo tool in skin penetration studies and optimization of formulations destined for skin administration.

  12. Ex vivo normothermic machine perfusion and viability testing of discarded human donor livers.

    PubMed

    op den Dries, S; Karimian, N; Sutton, M E; Westerkamp, A C; Nijsten, M W N; Gouw, A S H; Wiersema-Buist, J; Lisman, T; Leuvenink, H G D; Porte, R J

    2013-05-01

    In contrast to traditional static cold preservation of donor livers, normothermic machine perfusion may reduce preservation injury, improve graft viability and potentially allows ex vivo assessment of graft viability before transplantation. We have studied the feasibility of normothermic machine perfusion in four discarded human donor livers. Normothermic machine perfusion consisted of pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion for 6 h. Two hollow fiber membrane oxygenators provided oxygenation of the perfusion fluid. Biochemical markers in the perfusion fluid reflected minimal hepatic injury and improving function. Lactate levels decreased to normal values, reflecting active metabolism by the liver (mean lactate 10.0 ± 2.3 mmol/L at 30 min to 2.3 ± 1.2 mmol/L at 6 h). Bile production was observed throughout the 6 h perfusion period (mean rate 8.16 ± 0.65 g/h after the first hour). Histological examination before and after 6 h of perfusion showed well-preserved liver morphology without signs of additional hepatocellular ischemia, biliary injury or sinusoidal damage. In conclusion, this study shows that normothermic machine perfusion of human donor livers is technically feasible. It allows assessment of graft viability before transplantation, which opens new avenues for organ selection, therapeutic interventions and preconditioning.

  13. Placental Transfer of Darunavir in an Ex Vivo Human Cotyledon Perfusion Model

    PubMed Central

    Duro, Dominique; Belissa, Emilie; Peytavin, Gilles

    2014-01-01

    Placental transfer of the HIV protease inhibitor darunavir was investigated in 5 term human cotyledons perfused with darunavir (1,000 ng/ml) in the maternal to fetal direction. The mean (± the standard deviation [SD]) fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 30 to 90 min) was 15.0% ± 2.1%, and the mean (±SD) clearance index (darunavir FTR/antipyrine FTR) was 40.3% ± 5.8%. This shows that darunavir crosses the placenta at a relatively low rate, resulting in fetal exposure. PMID:24982090

  14. Long-term measurement of renal cortical and medullary tissue oxygenation and perfusion in unanesthetized sheep.

    PubMed

    Calzavacca, Paolo; Evans, Roger G; Bailey, Michael; Lankadeva, Yugeesh R; Bellomo, Rinaldo; May, Clive N

    2015-05-15

    The role of renal cortical and medullary hypoxia in the development of acute kidney injury is controversial, partly due to a lack of techniques for the long-term measurement of intrarenal oxygenation and perfusion in conscious animals. We have, therefore, developed a methodology to chronically implant combination probes to chronically measure renal cortical and medullary tissue perfusion and oxygen tension (tPO2) in conscious sheep and evaluated their responsiveness and reliability. A transit-time flow probe and a vascular occluder were surgically implanted on the left renal artery. At the same operation, dual fiber-optic probes, comprising a fluorescence optode to measure tPO2 and a laser-Doppler probe to assess tissue perfusion, were inserted into the renal cortex and medulla. In recovered conscious sheep (n = 8) breathing room air, mean 24-h cortical and medullary tPO2 were similar (31.4 ± 0.6 and 29.7 ± 0.7 mmHg, respectively). In the renal cortex and medulla, a 20% reduction in renal blood flow (RBF) decreased perfusion (14.6 ± 8.6 and 41.2 ± 8.5%, respectively) and oxygenation (48.1 ± 8.5 and 72.4 ± 8.5%, respectively), with greater decreases during a 50% reduction in RBF. At autopsy, minimal fibrosis was observed around the probes. In summary, we have developed a technique to chronically implant fiber-optic probes in the renal cortex and medulla for recording tissue perfusion and oxygenation over many days. In normal resting conscious sheep, cortical and medullary tPO2 were similar. The responses to and recovery from renal artery occlusion, together with the consistent measurements over a 24-h period, demonstrate the responsiveness and stability of the probes.

  15. Kinetic assessment of manganese using magnetic resonance imaging in the dually perfused human placenta in vitro

    SciTech Connect

    Miller, R.K.; Mattison, D.R.; Panigel, M.; Ceckler, T.; Bryant, R.; Thomford, P.

    1987-10-01

    The transfer and distribution of paramagnetic manganese was investigated in the dually perfused human placenta in vitro (using 10, 20, 100 ..mu..M Mn with and without /sup 54/Mn) using magnetic resonance imaging (MRI) and conventional radiochemical techniques. The human placenta concentrated /sup 54/Mn rapidly during the first 15 min of perfusion and by 4 hr was four times greater than the concentrations of Mn in the maternal perfusate, while the concentration of Mn in the fetal perfusate was 25% of the maternal perfusate levels. Within placentae, 45% of the /sup 54/Mn was free in the 100,000g supernatant, with 45% in the 1000g pellet. The magnetic field dependence of proton nuclear spin-lattice relaxation time (T/sub 1/) in placental tissue supports this Mn binding. Mn primarily affected the MRI partial saturation rather than spin-echo images of the human placenta, which provided for the separation of perfusate contributions from those produced by Mn. The washout of the Mn from the placenta was slow compared with its uptake, as determined by MRI. Thus, Mn was concentrated by the human placenta, but transfer of Mn across the placenta was limited in either direction. These studies also illustrate the opportunity for studies of human placental function using magnetic resonance imaging as a noninvasive biomarker.

  16. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

    PubMed Central

    Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

    2016-01-01

    Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

  17. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro.

    PubMed

    Killian, Nathaniel J; Vernekar, Varadraj N; Potter, Steve M; Vukasinovic, Jelena

    2016-01-01

    Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations.

  18. Procedure for Human Saphenous Veins Ex Vivo Perfusion and External Reinforcement

    PubMed Central

    Berard, Xavier; Alonso, Florian; Haefliger, Jacques-Antoine

    2014-01-01

    The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal hyperplasia (IH) that eventually leads to vessel occlusion and graft failure. Mechanical forces, particularly low shear stress and high wall tension, are thought to initiate and to sustain these cellular and molecular changes, but their exact contribution remains to be unraveled. To selectively evaluate the role of pressure and shear stress on the biology of IH, an ex vivo perfusion system (EVPS) was created to perfuse segments of human saphenous veins under arterial regimen (high shear stress and high pressure). Further technical innovations allowed the simultaneous perfusion of two segments from the same vein, one reinforced with an external mesh. Veins were harvested using a no-touch technique and immediately transferred to the laboratory for assembly in the EVPS. One segment of the freshly isolated vein was not perfused (control, day 0). The two others segments were perfused for up to 7 days, one being completely sheltered with a 4 mm (diameter) external mesh. The pressure, flow velocity, and pulse rate were continuously monitored and adjusted to mimic the hemodynamic conditions prevailing in the femoral artery. Upon completion of the perfusion, veins were dismounted and used for histological and molecular analysis. Under ex vivo conditions, high pressure perfusion (arterial, mean = 100 mm Hg) is sufficient to generate IH and remodeling of human veins. These alterations are reduced in the presence of an external polyester mesh. PMID:25350681

  19. Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus.

    PubMed

    Viggiano, A; Manara, R; Conforti, R; Paccone, A; Secondulfo, C; Lorusso, L; Sbordone, L; Di Salle, F; Monda, M; Tedeschi, G; Esposito, F

    2015-12-17

    Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing.

  20. Regional pulmonary perfusion following human heart-lung transplantation

    SciTech Connect

    Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. )

    1989-08-01

    Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

  1. Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.

    PubMed

    Sutton, Michael E; op den Dries, Sanna; Karimian, Negin; Weeder, Pepijn D; de Boer, Marieke T; Wiersema-Buist, Janneke; Gouw, Annette S H; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

    2014-01-01

    Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37 °C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥ 30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.

  2. Integrated microdevice for long-term automated perfusion culture without shear stress and real-time electrochemical monitoring of cells.

    PubMed

    Li, Lin-Mei; Wang, Wei; Zhang, Shu-Hui; Chen, Shi-Jing; Guo, Shi-Shang; Français, Olivier; Cheng, Jie-Ke; Huang, Wei-Hua

    2011-12-15

    Electrochemical techniques based on ultramicroelectrodes (UMEs) play a significant role in real-time monitoring of chemical messengers' release from single cells. Conversely, precise monitoring of cells in vitro strongly depends on the adequate construction of cellular physiological microenvironment. In this paper, we developed a multilayer microdevice which integrated high aspect ratio poly(dimethylsiloxane) (PDMS) microfluidic device for long-term automated perfusion culture of cells without shear stress and an independently addressable microelectrodes array (IAMEA) for electrochemical monitoring of the cultured cells in real time. Novel design using high aspect ratio between circular "moat" and ring-shaped micropillar array surrounding cell culture chamber combined with automated "circular-centre" and "bottom-up" perfusion model successfully provided continuous fresh medium and a stable and uniform microenvironment for cells. Two weeks automated culture of human umbilical endothelial cell line (ECV304) and neuronal differentiation of rat pheochromocytoma (PC12) cells have been realized using this device. Furthermore, the quantal release of dopamine from individual PC12 cells during their culture or propagation process was amperometrically monitored in real time. The multifunctional microdevice developed in this paper integrated cellular microenvironment construction and real-time monitoring of cells during their physiological process, and would possibly provide a versatile platform for cell-based biomedical analysis.

  3. Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model

    PubMed Central

    Grafmüller, Stefanie; Manser, Pius; Krug, Harald F.; Wick, Peter; von Mandach, Ursula

    2013-01-01

    Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ 1. Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 2 and continuously modified by Schneider et al. in 1972 3, can serve as an excellent model to study the transfer of xenobiotics or particles. Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results. The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data. PMID:23851364

  4. Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model.

    PubMed

    Grafmüller, Stefanie; Manser, Pius; Krug, Harald F; Wick, Peter; von Mandach, Ursula

    2013-06-18

    Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ (1). Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 (2) and continuously modified by Schneider et al. in 1972 (3), can serve as an excellent model to study the transfer of xenobiotics or particles. Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results. The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data.

  5. Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation.

    PubMed

    Bruinsma, B G; Yeh, H; Ozer, S; Martins, P N; Farmer, A; Wu, W; Saeidi, N; Op den Dries, S; Berendsen, T A; Smith, R N; Markmann, J F; Porte, R J; Yarmush, M L; Uygun, K; Izamis, M-L

    2014-06-01

    To reduce widespread shortages, attempts are made to use more marginal livers for transplantation. Many of these grafts are discarded for fear of inferior survival rates or biliary complications. Recent advances in organ preservation have shown that ex vivo subnormothermic machine perfusion has the potential to improve preservation and recover marginal livers pretransplantation. To determine the feasibility in human livers, we assessed the effect of 3 h of oxygenated subnormothermic machine perfusion (21°C) on seven livers discarded for transplantation. Biochemical and microscopic assessment revealed minimal injury sustained during perfusion. Improved oxygen uptake (1.30 [1.11-1.94] to 6.74 [4.15-8.16] mL O2 /min kg liver), lactate levels (4.04 [3.70-5.99] to 2.29 [1.20-3.43] mmol/L) and adenosine triphosphate content (45.0 [70.6-87.5] pmol/mg preperfusion to 167.5 [151.5-237.2] pmol/mg after perfusion) were observed. Liver function, reflected by urea, albumin and bile production, was seen during perfusion. Bile production increased and the composition of bile (bile salts/phospholipid ratio, pH and bicarbonate concentration) became more favorable. In conclusion, ex vivo subnormothermic machine perfusion effectively maintains liver function with minimal injury and sustains or improves various hepatobiliary parameters postischemia.

  6. In vitro studies of ferric carboxymaltose on placental permeability using the dual perfusion model of human placenta.

    PubMed

    Malek, Antoine

    2010-01-01

    An in vitro perfusion model of human placenta was used to study the transplacental passage of iron applied in the form of the drug compound ferric carboxymaltose (FCM) which had been radio-labelled with 59Fe. In four placental perfusion experiments, two simulated circuits for the maternal and fetal sides of the placenta were set up with two experimental phases each lasting 3 h. FCM was added to the maternal circuit at the beginning of each phase to a final iron concentration of 11 mM, which is at least 10 times higher than the maximal predicted level in blood after an administration of 200 mg iron as FCM. The effects of adding transferrin at a physiological concentration of 1.67 mg/ ml were also tested. The concentration profiles of 59Fe showed a 10% decrease within the first 30 min of perfusion on the maternal side. Thereafter the radioactivity levels remained unchanged. The addition of transferrin had no effect on the tissue uptake of 59Fe-FCM. No transferred iron radioactivity could be detected in the fetal circuit. Despite a loss of approximately 10% of the radio-labelled iron observed on the maternal side, only 0.5-2% of the radioactivity was detected in the placental tissue after perfusion. No free iron could be detected at the end of perfusion on the maternal side using ultrafiltration or acid precipitation methods. In addition, the production of transferrin receptor remained unchanged, with similar concentrations in placental tissue before and after perfusion. No effects of FCM on placental viability were observed in terms of energy metabolism (glucose consumption and lactate production), hormone release or placental permeability (assessed by the transfer rates of creatinine and antipyrine). However, two additional observations were made: firstly, a significant reduction in the rate of cell death compared to control conditions was observed in the presence of FCM; secondly, the integrity of the fetal capillary system was improved on the fetal side of the

  7. A 4D CT digital phantom of an individual human brain for perfusion analysis

    PubMed Central

    Brune, Christoph; van Ginneken, Bram; Prokop, Mathias

    2016-01-01

    Brain perfusion is of key importance to assess brain function. Modern CT scanners can acquire perfusion maps of the cerebral parenchyma in vivo at submillimeter resolution. These perfusion maps give insights into the hemodynamics of the cerebral parenchyma and are critical for example for treatment decisions in acute stroke. However, the relations between acquisition parameters, tissue attenuation curves, and perfusion values are still poorly understood and cannot be unraveled by studies involving humans because of ethical concerns. We present a 4D CT digital phantom specific for an individual human brain to analyze these relations in a bottom-up fashion. Validation of the signal and noise components was based on 1,000 phantom simulations of 20 patient imaging data. This framework was applied to quantitatively assess the relation between radiation dose and perfusion values, and to quantify the signal-to-noise ratios of penumbra regions with decreasing sizes in white and gray matter. This is the first 4D CT digital phantom that enables to address clinical questions without having to expose the patient to additional radiation dose. PMID:27917312

  8. An integrated environmental perfusion chamber and heating system for long-term, high resolution imaging of living cells.

    PubMed

    Hing, W A; Poole, C A; Jensen, C G; Watson, M

    2000-08-01

    This communication presents the design and application of an integrated environmental perfusion chamber and stage heating blanket suitable for time-lapse video microscopy of living cells. The system consists of two independently regulated components: a perfusion chamber suitable for the maintenance of cell viability and the variable delivery of environmental factors, and a separate heating blanket to control the temperature of the microscope stage and limit thermal conduction from the perfusion chamber. Two contrasting experiments are presented to demonstrate the versatility of the system. One long-term sequence illustrates the behaviour of cells exposed to ceramic fibres. The other shows the shrinking response of cultured articular cartilage chondrons under dynamic hyper-osmotic conditions designed to simulate joint loading. The chamber is simple in design, economical to produce and permits long-term examination of dynamic cellular behaviour while satisfying the fundamental requirements for the maintenance of environmental factors that influence cell viability.

  9. A New Apparatus and Surgical Technique for the Dual Perfusion of Human Tumor Xenografts in Situ in Nude Rats

    PubMed Central

    Dauchy, Robert T; Dauchy, Erin M; Mao, Lulu; Belancio, Victoria P; Hill, Steven M; Blask, David E

    2012-01-01

    We present a new perfusion system and surgical technique for simultaneous perfusion of 2 tissue-isolated human cancer xenografts in nude rats by using donor blood that preserves a continuous flow. Adult, athymic nude rats (Hsd:RH-Foxn1rnu) were implanted with HeLa human cervical or HT29 colon adenocarcinomas and grown as tissue-isolated xenografts. When tumors reached an estimated weight of 5 to 6 g, rats were prepared for perfusion with donor blood and arteriovenous measurements. The surgical procedure required approximately 20 min to complete for each tumor, and tumors were perfused for a period of 150 min. Results showed that tumor venous blood flow, glucose uptake, lactic acid release, O2 uptake and CO2 production, uptake of total fatty acid and linoleic acid and conversion to the mitogen 13-HODE, cAMP levels, and activation of several marker kinases were all well within the normal physiologic, metabolic, and signaling parameters characteristic of individually perfused xenografts. This new perfusion system and technique reduced procedure time by more than 50%. These findings demonstrate that 2 human tumors can be perfused simultaneously in situ or ex vivo by using either rodent or human blood and suggest that the system may also be adapted for use in the dual perfusion of other organs. Advantages of this dual perfusion technique include decreased anesthesia time, decreased surgical manipulation, and increased efficiency, thereby potentially reducing the numbers of laboratory animals required for scientific investigations. PMID:22546915

  10. Human cortical perfusion and the arterial pulse: a near-infrared spectroscopy study

    PubMed Central

    Kwan, Hon C; Cheng, Anita; Liu, Ruth; Borrett, Donald S

    2004-01-01

    Background The pulsatile nature of the arterial pulse induces a pulsatile perfusion pattern which can be observed in human cerebral cortex with non-invasive near-infrared spectroscopy. The present study attempts to establish a quantitative relation between these two events, even in situations of very weak signal-to-noise ratio in the cortical perfusion signal. The arterial pulse pattern was extracted from the left middle finger by means of plethesmographic techniques. Changes in cortical perfusion were detected with a continuous-wave reflectance spectrophotometer on the scalp overlying the left prefrontal cortex. Cross-correlation analysis was performed to provide evidence for a causal relation between the arterial pulse and relative changes in cortical total hemoglobin. In addition, the determination of the statistical significance of this relation was established by the use of phase-randomized surrogates. Results The results showed statistically significant cross correlation between the arterial and perfusion signals. Conclusions The approach designed in the present study can be utilized for a quantitative and continuous assessment of the perfusion states of the cerebral cortex in experimental and clinical settings even in situations of extremely low signal-to-noise ratio. PMID:15113424

  11. Teratoma formation of human embryonic stem cells in three-dimensional perfusion culture bioreactors.

    PubMed

    Stachelscheid, H; Wulf-Goldenberg, A; Eckert, K; Jensen, J; Edsbagge, J; Björquist, P; Rivero, M; Strehl, R; Jozefczuk, J; Prigione, A; Adjaye, J; Urbaniak, T; Bussmann, P; Zeilinger, K; Gerlach, J C

    2013-09-01

    Teratoma formation in mice is today the most stringent test for pluripotency that is available for human pluripotent cells, as chimera formation and tetraploid complementation cannot be performed with human cells. The teratoma assay could also be applied for assessing the safety of human pluripotent cell-derived cell populations intended for therapeutic applications. In our study we examined the spontaneous differentiation behaviour of human embryonic stem cells (hESCs) in a perfused 3D multi-compartment bioreactor system and compared it with differentiation of hESCs and human induced pluripotent cells (hiPSCs) cultured in vitro as embryoid bodies and in vivo in an experimental mouse model of teratoma formation. Results from biochemical, histological/immunohistological and ultrastuctural analyses revealed that hESCs cultured in bioreactors formed tissue-like structures containing derivatives of all three germ layers. Comparison with embryoid bodies and the teratomas revealed a high degree of similarity of the tissues formed in the bioreactor to these in the teratomas at the histological as well as transcriptional level, as detected by comparative whole-genome RNA expression profiling. The 3D culture system represents a novel in vitro model that permits stable long-term cultivation, spontaneous multi-lineage differentiation and tissue formation of pluripotent cells that is comparable to in vivo differentiation. Such a model is of interest, e.g. for the development of novel cell differentiation strategies. In addition, the 3D in vitro model could be used for teratoma studies and pluripotency assays in a fully defined, controlled environment, alternatively to in vivo mouse models.

  12. An Optical Oxygen Sensor for Long-Term Continuous Monitoring of Dissolved Oxygen in Perfused Bioreactors

    NASA Technical Reports Server (NTRS)

    Gao, F. G.; Jeevarajan, A. S.; Anderson, M. M.

    2002-01-01

    For long-term growth of man1ITlalian cells in perfused bioreactors, it is essential to monitor the concentration of dissolved oxygen (DO) present in the culture medium to quantitate and control level of DO. Continuous measurement of the amount of DO in the cell culture medium in-line under sterile conditions in NASA's perfused bioreactor requires that the oxygen sensor provide increased sensitivity and be sterilizable and nontoxic. Additionally, long-term cell culture experiments require that the calibration be maintained several weeks or months. Although there are a number of sensors for dissolved oxygen on the market and under development elsewhere, very few meet these stringent conditions. An optical oxygen sensor (BOXY) based on dynamic fluorescent quenching and a pulsed blue LED light source was developed in our laboratory to address these requirements. Tris( 4,7 -diphenyl-l, 1 O-phenanthroline )ruthenium(II) chloride is employed as the fluorescent dye indicator. The sensing element consists of a glass capillary (OD 4.0 mm; ID 2.0 mm) coated internally with a thin layer of the fluorescent dye in silicone matrix and overlayed with a black shielding layer. Irradiation of the sensing element with blue light (blue LED with emission maximum at 475 nm) generates a red fluorescence centered at 626 nm. The fluorescence intensity is correlated to the concentration of DO present in the culture medium, following the modified non-linear Stern-Volmer equation. By using a pulsed irradiating light source, the problem of dye-bleaching, which is often encountered in long-term continuous measurements of tIns type, 'is minimized. To date we achieved sensor resolution of 0.3 mmHg at 50 mmHg p02, and 0.6 mmHg at 100 mmHg p02, with a response time of about one minute. Calibration was accomplished in sterile phosphate-buffered saline with a blood-gas analyzer (BGA) measurement as reference. Stand-alone software was also developed to control the sensor and bioreactor as well as to

  13. Blood temperature and perfusion to exercising and non‐exercising human limbs

    PubMed Central

    Calbet, José A. L.; Boushel, Robert; Helge, Jørn W.; Søndergaard, Hans; Munch‐Andersen, Thor; van Hall, Gerrit; Mortensen, Stefan P.; Secher, Niels H.

    2015-01-01

    New Findings What is the central question of this study? Temperature‐sensitive mechanisms are thought to contribute to blood‐flow regulation, but the relationship between exercising and non‐exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non‐exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature‐ and metabolism‐sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature‐sensitive mechanisms may contribute to blood‐flow regulation, but the influence of temperature on perfusion to exercising and non‐exercising human limbs is not established. Blood temperature (T B), blood flow and oxygen uptake (V˙O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher T B and limb V˙O2. Leg and arm vascular conductance during exercise compared with rest was related closely to T B (r 2 = 0.91; P < 0.05), plasma ATP (r 2 = 0.94; P < 0.05) and limb V˙O2 (r 2 = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in T B and limb V˙O2, whereas ABF, arm T B and V˙O2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in V˙O2. In 12 trained males, increases in femoral T B and LBF during incremental leg exercise were mirrored by similar pulmonary artery T B and cardiac output dynamics, suggesting that processes in active limbs dominate central

  14. Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Shansky, J.; Perrone, C.; Vandenburgh, H. H.

    1998-01-01

    Three-dimensional skeletal muscle organ-like structures (organoids) formed in tissue culture by fusion of proliferating myoblasts into parallel networks of long, unbranched myofibers provide an in vivo-like model for examining the effects of growth factors, tension, and space flight on muscle cell growth and metabolism. To determine the feasibility of maintaining either avian or mammalian muscle organoids in a commercial perfusion bioreactor system, we measured metabolism, protein turnover. and autocrine/paracrine growth factor release rates. Medium glucose was metabolized at a constant rate in both low-serum- and serum-free media for up to 30 d. Total organoid noncollagenous protein and DNA content decreased approximately 22-28% (P < 0.05) over a 13-d period. Total protein synthesis rates could be determined accurately in the bioreactors for up to 30 h and total protein degradation rates could be measured for up to 3 wk. Special fixation and storage conditions necessary for space flight studies were validated as part of the studies. For example, the anabolic autocrine/paracrine skeletal muscle growth factors prostaglandin F2alpha (PGF2alpha) and insulin-like growth factor-1 (IGF-1) could be measured accurately in collected media fractions, even after storage at 37 degrees C for up to 10 d. In contrast, creatine kinase activity (a marker of cell damage) in collected media fractions was unreliable. These results provide initial benchmarks for long-term ex vivo studies of tissue-engineered skeletal muscle.

  15. Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

    SciTech Connect

    Myllynen, Paeivi . E-mail: paivi.k.myllynen@oulu.fi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-09-01

    Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placental transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure.

  16. Matching of postcontraction perfusion to oxygen consumption across submaximal contraction intensities in exercising humans

    PubMed Central

    Elder, Christopher P.; Donahue, Manus J.; Damon, Bruce M.

    2015-01-01

    Studying the magnitude and kinetics of blood flow, oxygen extraction, and oxygen consumption at exercise onset and during the recovery from exercise can lead to insights into both the normal control of metabolism and blood flow and the disturbances to these processes in metabolic and cardiovascular diseases. The purpose of this study was to examine the on- and off-kinetics for oxygen delivery, extraction, and consumption as functions of submaximal contraction intensity. Eight healthy subjects performed four 1-min isometric dorsiflexion contractions, with two at 20% MVC and two at 40% MVC. During one contraction at each intensity, relative perfusion changes were measured by using arterial spin labeling, and the deoxyhemoglobin percentage (%HHb) was estimated using the spin- and gradient-echo sequence and a previously published empirical calibration. For the whole group, the mean perfusion did not increase during contraction. The %HHb increased from ∼28 to 38% during contractions of each intensity, with kinetics well described by an exponential function and mean response times (MRTs) of 22.7 and 21.6 s for 20 and 40% MVC, respectively. Following contraction, perfusion increased ∼2.5-fold. The %HHb, oxygen consumption, and perfusion returned to precontraction levels with MRTs of 27.5, 46.4, and 50.0 s, respectively (20% MVC), and 29.2, 75.3, and 86.0 s, respectively (40% MVC). These data demonstrate in human subjects the varied recovery rates of perfusion and oxygen consumption, along with the similar rates of %HHb recovery, across these exercise intensities. PMID:26066829

  17. Matching of postcontraction perfusion to oxygen consumption across submaximal contraction intensities in exercising humans.

    PubMed

    Buck, Amanda K W; Elder, Christopher P; Donahue, Manus J; Damon, Bruce M

    2015-08-01

    Studying the magnitude and kinetics of blood flow, oxygen extraction, and oxygen consumption at exercise onset and during the recovery from exercise can lead to insights into both the normal control of metabolism and blood flow and the disturbances to these processes in metabolic and cardiovascular diseases. The purpose of this study was to examine the on- and off-kinetics for oxygen delivery, extraction, and consumption as functions of submaximal contraction intensity. Eight healthy subjects performed four 1-min isometric dorsiflexion contractions, with two at 20% MVC and two at 40% MVC. During one contraction at each intensity, relative perfusion changes were measured by using arterial spin labeling, and the deoxyhemoglobin percentage (%HHb) was estimated using the spin- and gradient-echo sequence and a previously published empirical calibration. For the whole group, the mean perfusion did not increase during contraction. The %HHb increased from ∼28 to 38% during contractions of each intensity, with kinetics well described by an exponential function and mean response times (MRTs) of 22.7 and 21.6 s for 20 and 40% MVC, respectively. Following contraction, perfusion increased ∼2.5-fold. The %HHb, oxygen consumption, and perfusion returned to precontraction levels with MRTs of 27.5, 46.4, and 50.0 s, respectively (20% MVC), and 29.2, 75.3, and 86.0 s, respectively (40% MVC). These data demonstrate in human subjects the varied recovery rates of perfusion and oxygen consumption, along with the similar rates of %HHb recovery, across these exercise intensities.

  18. Cultivation of human bone-like tissue from pluripotent stem cell-derived osteogenic progenitors in perfusion bioreactors.

    PubMed

    de Peppo, Giuseppe Maria; Vunjak-Novakovic, Gordana; Marolt, Darja

    2014-01-01

    Human pluripotent stem cells represent an unlimited source of skeletal tissue progenitors for studies of bone biology, pathogenesis, and the development of new approaches for bone reconstruction and therapies. In order to construct in vitro models of bone tissue development and to grow functional, clinical-size bone substitutes for transplantation, cell cultivation in three-dimensional environments composed of porous osteoconductive scaffolds and dynamic culture systems-bioreactors-has been studied. Here, we describe a stepwise procedure for the induction of human embryonic and induced pluripotent stem cells (collectively termed PSCs) into mesenchymal-like progenitors, and their subsequent cultivation on decellularized bovine bone scaffolds in perfusion bioreactors, to support the development of viable, stable bone-like tissue in defined geometries.

  19. Human immunodeficiency virus-infected subjects have no altered myocardial perfusion.

    PubMed

    Catzin-Kuhlmann, Andres; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Colín-Ramírez, Eloisa; Asz, Daniel; Aguirre, Víctor H; Herrera, Luis E; Valles, Victoria; Aguilar-Salinas, Carlos A; Sierra, Juan; Calva, Juan J

    2007-10-31

    We assessed myocardial perfusion (blinded interpretation of a single-photon emission computed tomography) and known risk factors for atherosclerosis in 105 randomly selected human immunodeficiency virus (HIV)-infected patients in a clinic in Mexico City and in a community sample of 105 age and gender-matched infection-free subjects. An abnormal scan was obtained in 4.8% of the infected and in 7.6% of the non-infected subjects. Severity of scintigraphic abnormalities was similar in both groups. In these Mexican HIV-infected patients, despite a long time of infection and of exposure to combined antiretroviral therapy and to other classical risk factors for atherosclerosis, there was no evidence of increased risk for abnormal myocardial perfusion. Dissimilar magnitude in the hazard of coronary heart disease may occur among infected populations with different frequencies of traditional predisposing factors for cardiovascular illness.

  20. Long-term outdoor cultivation by perfusing spent medium for biodiesel production from Chlorella minutissima.

    PubMed

    Oh, Sung Ho; Kwon, Min Chul; Choi, Woon Yong; Seo, Yong Chang; Kim, Ga Bin; Kang, Do Hyung; Lee, Shin Young; Lee, Hyeon Yong

    2010-08-01

    A unique perfusion process was developed to maintain high concentrations of marine alga, Chlorella minutissima. This method is based on recycling cells by continuous feeding with warm spent sea water from nuclear power plants, which has very similar properties as sea water. A temperature of at least 30 degrees C in a 200 L photo-bioreactor was maintained in this system by perfusion of the thermal plume for 80 days in the coldest season. The maximum cell concentration and total lipid content was 8.3 g-dry wt./L and 23.2 %, w/w, respectively, under mixotrophic conditions. Lipid production was found to be due to a partially or non-growth related process, which implies that large amounts of biomass are needed for a high accumulation of lipids within the cells. At perfusion rates greater than 1.5 L/h, the temperature of the medium inside the reactor was around 30 degrees C, which was optimal for cell growth. For this system, a perfusion rate of 2.8 L/h was determined to be optimal for maintaining rapid cell growth and lipid production during outdoor cultivation. It was absolutely necessary to maintain the appropriate perfusion rate so that the medium temperature was optimal for cell growth. In addition, the lipids produced using this process were shown to be feasible for biodiesel production since the lipid composition of C. minutissima grown under these conditions consisted of 17 % (w/w) of C(16) and 47% (w/w) of C(18). The combined results of this study clearly demonstrated that the discharged energy of the thermal plume could be reused to cultivate marine alga by maintaining a relatively constant temperature in an outdoor photo-bioreactor without the need for supplying any extra energy, which could allow for cheap production of biodiesel from waste energy.

  1. Validation of minimally invasive measurement of myocardial perfusion using electron beam computed tomography and application in human volunteers

    PubMed Central

    Bell, M; Lerman, L; Rumberger, J

    1999-01-01

    OBJECTIVES—To measure myocardial perfusion using an estimate of intramyocardial vascular volume obtained by electron beam computed tomography (EBCT) in an animal model; to assess the feasibility and validity of measuring regional myocardial perfusion in human volunteers using the techniques developed and validated in the animal studies.
METHODS—Measurements of myocardial perfusion with EBCT employing intravenous contrast injections were compared with radioactive microsphere measurements (flow 57 to 346 ml/100 g/min) in seven closed chest dogs. Fourteen human volunteers then underwent EBCT scans using intravenous contrast injections.
RESULTS—Mean (SEM) global intramyocardial vascular volume by EBCT was 7.6 (1.1)%. The correlation between global EBCT (y) and microsphere (x) perfusion was y = 0.59x + 15.56 (r = 0.86) before, and y = 0.72x + 6.06 (r = 0.88) after correcting for intramyocardial vascular volume. Regional perfusion correlation was y = 0.75x + 23.84 (r = 0.82). Corresponding improvements in agreement between the two techniques were also seen using Bland-Altman plots. In the human subjects, mean resting global myocardial flow was 98 (6) ml/100 g/min, with homogeneous flow across all regions. In 10 of these subjects, perfusion was studied during coronary vasodilatation using intravenous adenosine. Global flow increased from 93 (5) ml/100 g/min at rest to 250 (19) ml/100 g/min during adenosine (p < 0.001), with an average perfusion reserve ratio of 2.8 (0.2). Similar changes in regional perfusion were observed and were uniform throughout all regions, with a mean regional perfusion reserve ratio of 2.8 (0.3).
CONCLUSIONS—Accounting for intramyocardial vascular volume improves the accuracy of EBCT measurements of myocardial perfusion when using intravenous contrast injections. The feasibility of providing accurate measurements of global and regional myocardial perfusion and perfusion reserve in people using this

  2. Active skin perfusion and thermoregulatory response in the hand following nerve injury and repair in human upper extremities.

    PubMed

    Deng, Aidong; Liu, Dan; Gu, Chen; Gu, Xiaosong; Gu, Jianhui; Hu, Wen

    2016-01-01

    Cutaneous vasoconstriction/vasodilatation occurs in response to whole body and local cooling/heating, and the vasomotor activities play a pivotal role in thermal control of the human body. The mechanisms underlying regulation of skin blood flow involve both neurogenic and humeral/local chemical influence, contributing to the initial response to thermal stimuli and the prolonged phase of response, respectively. Previous studies have suggested the impairment of cutaneous thermal regulation after nerve injury. However, the evidence regarding how the skin perfusion and thermoregulatory response evolve after nerve injury and repair remains limited. Here we observed, by utilizing laser-Doppler perfusion imaging, baseline skin perfusion and perfusion change in response to thermal stimuli after median and ulnar nerve injury, and the results showed that baseline perfusion in autonomous skin area profoundly decreased and active rewarming after clod stress dramatically diminished before sensory recovery of the skin became detectable. In addition, baseline cutaneous perfusion was recovered as the skin regained touch sensation, and exhibited positive correlation to touch sensibility of the skin. These data indicate that both active perfusion and thermoregulatory response of the skin are markedly compromised during skin denervation and can be recovered by re-innervation. This suggests the importance of timely repair of injured nerve, especially in the practice of replantation.

  3. Intravital lectin perfusion analysis of vascular permeability in human micro- and macro- blood vessels.

    PubMed

    Debbage, P L; Sölder, E; Seidl, S; Hutzler, P; Hugl, B; Ofner, D; Kreczy, A

    2001-10-01

    We previously applied intravital lectin perfusion in mouse models to elucidate mechanisms underlying vascular permeability. The present work transfers this technique to human models, analysing vascular permeability in macro- and microvessels. Human vascular endothelial surface carbohydrate biochemistry differs significantly from its murine counterpart, lacking alpha-galactosyl epitopes and expressing the L-fucose moiety in the glycocalyx; the poly-N-lactosamine glycan backbone is common to all mammals. We examined extensively lectin binding specificities in sections and in vivo, and then applied the poly-N-lactosamine-specific lectin LEA and the L-fucose-specific lectin UEA-I in human intravital perfusions. Transendothelial transport differed in macrovessels and microvessels. In microvessels of adult human fat tissue, rectal wall and rectal carcinomas, slow transendothelial transport by vesicles was followed by significant retention at the subendothelial basement membrane; paracellular passage was not observed. Passage time exceeded 1 h. Thus we found barrier mechanisms resembling those we described previously in murine tissues. In both adult and fetal macrovessels, the vena saphena magna and the umbilical vein, respectively, rapid passage across the endothelial lining was observed, the tracer localising completely in the subendothelial tissues within 15 min; vesicular transport was more rapid than in microvessels, and retention at the subendothelial basement membrane briefer.

  4. Three-dimensional perfusion cultivation of human cardiac-derived progenitors facilitates their expansion while maintaining progenitor state.

    PubMed

    Kryukov, Olga; Ruvinov, Emil; Cohen, Smadar

    2014-11-01

    The therapeutic application of autologous cardiac-derived progenitor cells (CPCs) requires a large cell quantity generated under defined conditions. Herein, we investigated the applicability of a three-dimensional (3D) perfusion cultivation system to facilitate the expansion of CPCs harvested from human heart biopsies and characterized by a relatively high percentage of c-kit(+) cells. The cells were seeded in macroporous alginate scaffolds and after cultivation for 7 days under static conditions, some of the constructs were transferred into a perfusion bioreactor, which was operated for an additional 14 days. A robust and highly reproducible human CPC (hCPC) expansion of more than seven-fold was achieved under the 3D perfusion culture conditions, while under static conditions, the expansion of CPCs was limited only to the first 7 days, after which it leveled-off. On day 21 of perfusion cultivation, the expanded cells exhibited a higher expression level of the progenitor marker c-kit, suggesting that the c-kit-positive CPCs are the main cell population undergoing proliferation. The profile of the spontaneous differentiation in the perfused construct was different from that in the static cultivated constructs; genes typical for cardiac and endothelial cell lineages were more widely expressed in the perfused constructs. By contrast, the differentiation to osteogenic (Von Kossa staining and alkaline phosphatase activity) and adipogenic (Oil Red staining) lineages was reduced in the perfused constructs compared with static cultivated constructs. Collectively, our results indicate that 3D perfusion cultivation mode is an appropriate system for robust expansion of human CPCs while maintaining their progenitor state and differentiation potential into the cardiovascular cell lineages.

  5. In vivo confocal Raman spectroscopy study of the vitamin A derivative perfusion through human skin

    NASA Astrophysics Data System (ADS)

    dos Santos, Laurita; Téllez Soto, Claudio A.; Favero, Priscila P.; Martin, Airton A.

    2016-03-01

    In vivo confocal Raman spectroscopy is a powerful non-invasive technique able to analyse the skin constituents. This technique was applied to transdermal perfusion studies of the vitamin A derivative in human skin. The composition of the stratum corneum (lipid bilayer) is decisive for the affinity and transport of the vitamin through skin. The vitamin A is significantly absorbed by human skin when applied with water in oil emulsion or hydro-alcoholic gel. The purpose of this study is to elucidate the behaviour of vitamin A derivative into human skin without the presence of enhancers. The results showed that the intensity band of the derivative (around 1600 cm-1), which represents the -C=O vibrational mode, was detected in different stratum corneum depths (up to 20 μm). This Raman peak of vitamin A derivative has non-coincident band with the Raman spectra of the skin epidermis, demonstrating that compound penetrated in forearm skin.

  6. Evolution and resolution of human brain perfusion responses to the stress of induced hypoglycemia.

    PubMed

    Teh, Ming Ming; Dunn, Joel T; Choudhary, Pratik; Samarasinghe, Yohan; Macdonald, Ian; O'Doherty, Michael; Marsden, Paul; Reed, Laurence J; Amiel, Stephanie A

    2010-11-01

    The relationship between the human brain response to acute stress and subjective, behavioural and physiological responses is poorly understood. We have examined the human cerebral response to the intense interoceptive stressor of hypoglycemia, controlling plasma glucose at either normal fasting concentrations (5 mmol/l, n=7) or at hypoglycemia (2.7 mmol/l, n=10) for 1 h in healthy volunteers. Hypoglycemia was associated with symptomatic responses, counterregulatory neuroendocrine responses and a sequential pattern of brain regional engagement, mapped as changes in relative cerebral perfusion using [(15)O]-H(2)O water positron emission tomography. The early cerebral response comprised activation bilaterally in anterior cingulate cortex (ACC) and thalamic pulvinar, with deactivation in posterior parahippocampal gyrus. Later responses (>20 min) engaged bilateral anterior insula, ventral striatum and pituitary. Following resolution of hypoglycemia, the majority of responses returned to baseline, save persistent engagement of the ACC and sustained elevation of growth hormone and cortisol. Catecholamine responses correlated with increased perfusion in pulvinar and medial thalamus, ACC and pituitary, while growth hormone and cortisol responses showed no correlation with thalamic activation but did show additional correlation with the hypothalamus and ventral striatum bilaterally. These data demonstrate complex dynamic responses to the stressor of hypoglycemia that would be expected to drive physiological and behavioural changes to remedy the state. Further, these data show that sustained stress and its aftermath engage distinct sets of brain regions, providing a neural substrate for adaptive or 'allostasic' responses to stressors.

  7. Induced Human Decidual NK-Like Cells Improve Utero-Placental Perfusion in Mice

    PubMed Central

    Pernicone, Elizabeth; Korkes, Henri A.; Burke, Suzanne D.; Rajakumar, Augustine; Thadhani, Ravi I.; Roberts, Drucilla J.; Bhasin, Manoj; Karumanchi, S. Ananth

    2016-01-01

    Decidual NK (dNK) cells, a distinct type of NK cell, are thought to regulate uterine spiral artery remodeling, a process that allows for increased blood delivery to the fetal-placental unit. Impairment of uterine spiral artery remodeling is associated with decreased placental perfusion, increased uterine artery resistance, and obstetric complications such as preeclampsia and intrauterine growth restriction. Ex vivo manipulation of human peripheral blood NK (pNK) cells by a combination of hypoxia, TGFß-1 and 5-aza-2’-deoxycytidine yields cells with phenotypic and in vitro functional similarities to dNK cells, called idNK cells. Here, gene expression profiling shows that CD56Bright idNK cells derived ex vivo from human pNK cells, and to a lesser extent CD56Dim idNK cells, are enriched in the gene expression signature that distinguishes dNK cells from pNK cells. When injected into immunocompromised pregnant mice with elevated uterine artery resistance, idNK cells homed to the uterus and reduced the uterine artery resistance index, suggesting improved placental perfusion. PMID:27736914

  8. Tolerance of human placental tissue to severe hypoxia and its relevance for dual ex vivo perfusion.

    PubMed

    Schneider, H

    2009-03-01

    In the dual ex vivo perfusion of an isolated human placental cotyledon it takes on average 20-30 min to set up stable perfusion circuits for the maternal and fetal vascular compartments. In vivo placental tissue of all species maintains a highly active metabolism and it continues to puzzle investigators how this tissue can survive 30 min of ischemia with more or less complete anoxia following expulsion of the organ from the uterus and do so without severe damage. There seem to be parallels between "depressed metabolism" seen in the fetus and the immature neonate in the peripartum period and survival strategies described in mammals with increased tolerance of severe hypoxia like hibernators in the state of torpor or deep sea diving turtles. Increased tolerance of hypoxia in both is explained by "partial metabolic arrest" in the sense of a temporary suspension of Kleiber's rule. Furthermore the fetus can react to major changes in surrounding oxygen tension by decreasing or increasing the rate of specific basal metabolism, providing protection against severe hypoxia as well as oxidative stress. There is some evidence that adaptive mechanisms allowing increased tolerance of severe hypoxia in the fetus or immature neonate can also be found in placental tissue, of which at least the villous portion is of fetal origin. A better understanding of the molecular details of reprogramming of fetal and placental tissues in late pregnancy may be of clinical relevance for an improved risk assessment of the individual fetus during the critical transition from intrauterine life to the outside and for the development of potential prophylactic measures against severe ante- or intrapartum hypoxia. Responses of the tissue to reperfusion deserve intensive study, since they may provide a rational basis for preventive measures against reperfusion injury and related oxidative stress. Modification of the handling of placental tissue during postpartum ischemia, and adaptation of the

  9. Optical coherence tomography microangiography for monitoring the response of vascular perfusion to external pressure on human skin tissue

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Wang, Hequn; Wang, Ruikang K.

    2014-05-01

    Characterization of the relationship between external pressure and blood flow is important in the examination of pressure-induced disturbance in tissue microcirculation. Optical coherence tomography (OCT)-based microangiography is a promising imaging technique, capable of providing the noninvasive extraction of functional vessels within the skin tissue with capillary-scale resolution. Here, we present a feasibility study of OCT microangiography (OMAG) to evaluate changes in blood perfusion in response to externally applied pressure on human skin tissue in vivo. External force is loaded normal to the tissue surface at the nailfold region of a healthy human volunteer. An incremental force is applied step by step and then followed by an immediate release. Skin perfusion events including baseline are continuously imaged by OMAG, allowing for visualization and quantification of the capillary perfusion in the nailfold tissue. The tissue strain maps are simultaneously evaluated through the available OCT structural images to assess the relationship of the microcirculation response to the applied pressure. The results indicate that the perfusion progressively decreases with the constant increase of pressure. Reactive hyperemia occurs right after the removal of the pressure. The perfusion returns to the baseline level after a few minutes. These findings suggest that OMAG may have great potential for quantitatively assessing tissue microcirculation in the locally pressed tissue in vivo.

  10. Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass.

    PubMed

    Râdegran, G; Blomstrand, E; Saltin, B

    1999-12-01

    The knee extensor exercise model was specifically developed to enable in vivo estimates of peak muscle blood flow and O(2) uptake in humans. The original finding, using thermodilution measurements to measure blood flow in relation to muscle mass [P. Andersen and B. Saltin. J. Physiol. (Lond.) 366: 233-249, 1985], was questioned, however, as the measurements were two- to threefold higher than those previously obtained with the (133)Xe clearance and the plethysmography technique. As thermodilution measurements have now been confirmed by other methods and independent research groups, we aimed to address the impact of muscle mass estimates on the peak values of muscle perfusion and O(2) uptake. In the present study, knee extensor volume was determined from multiple measurements with computer tomography along the full length of the muscle. In nine healthy humans, quadriceps muscle volume was 2.36 +/- 0.17 (range 1. 31-3.27) liters, corresponding to 2.48 +/- 0.18 (range 1.37-3.43) kg. Anthropometry overestimated the muscle volume by approximately 21-46%, depending on whether quadriceps muscle length was estimated from the patella to either the pubic bone, inguinal ligament, or spina iliaca anterior superior. One-legged, dynamic knee extensor exercise up to peak effort of 67 +/- 7 (range 55-100) W rendered peak values for leg blood flow (thermodilution) of 5.99 +/- 0.66 (range 4.15-9.52) l/min and leg O(2) uptake of 856 +/- 109 (range 590-1,521) ml/min. Muscle perfusion and O(2) uptake reached peak values of 246 +/- 24 (range 149-373) and 35.2 +/- 3.7 (range 22.6-59. 6) ml. min(-1). 100 g muscle(-1), respectively. These peak values are approximately 19-33% larger than those attained by applying anthropometric muscle mass estimates. In conclusion, the present findings emphasize that peak perfusion and O(2) uptake in human skeletal muscle may be up to approximately 30% higher than previous anthropometric-based estimates that use equivalent techniques for blood flow

  11. A proposed study on the transplacental transport of parabens in the human placental perfusion model.

    PubMed

    Mathiesen, Line; Zuri, Giuseppina; Andersen, Maria H; Knudsen, Lisbeth E

    2013-12-01

    Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim to determine the transport kinetics of these parabens across the human placenta, and to investigate placental metabolism, including differences in transport due to molecular characteristics. This will facilitate assessment of the risks associated with the use of paraben-containing products during pregnancy.

  12. Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation.

    PubMed

    Lofthouse, E M; Perazzolo, S; Brooks, S; Crocker, I P; Glazier, J D; Johnstone, E D; Panitchob, N; Sibley, C P; Widdows, K L; Sengers, B G; Lewis, R M

    2016-02-01

    Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [(14)C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [(14)C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [(14)C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [(14)C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [(14)C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer.

  13. Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease

    PubMed Central

    Kostrzewski, Tomasz; Cornforth, Terri; Snow, Sophie A; Ouro-Gnao, Larissa; Rowe, Cliff; Large, Emma M; Hughes, David J

    2017-01-01

    AIM To develop a human in vitro model of non-alcoholic fatty liver disease (NAFLD), utilising primary hepatocytes cultured in a three-dimensional (3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids (FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factor-binding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantly reduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known anti-steatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium. CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. PMID:28127194

  14. Thermal behavior of human eye in relation with change in blood perfusion, porosity, evaporation and ambient temperature.

    PubMed

    Rafiq, Aasma; Khanday, M A

    2016-12-01

    Extreme environmental and physiological conditions present challenges for thermal processes in body tissues including multi-layered human eye. A mathematical model has been formulated in this direction to study the thermal behavior of the human eye in relation with the change in blood perfusion, porosity, evaporation and environmental temperatures. In this study, a comprehensive thermal analysis has been performed on the multi-layered eye using Pennes' bio-heat equation with appropriate boundary and interface conditions. The variational finite element method and MATLAB software were used for the solution purpose and simulation of the results. The thermoregulatory effect due to blood perfusion rate, porosity, ambient temperature and evaporation at various regions of human eye was illustrated mathematically and graphically. The main applications of this model are associated with the medical sciences while performing laser therapy and other thermoregulatory investigation on human eye.

  15. Quantification of perfusion modes in terms of surplus hemodynamic energy levels in a simulated pediatric CPB model.

    PubMed

    Undar, Akif; Ji, Bingyang; Lukic, Branka; Zapanta, Conrad M; Kunselman, Allen R; Reibson, John D; Weiss, William J; Rosenberg, Gerson; Myers, John L

    2006-01-01

    The objective of this investigation was to compare pulsatile versus nonpulsatile perfusion modes in terms of surplus hemodynamic energy (SHE) levels during cardiopulmonary bypass (CPB) in a simulated neonatal model. The extracorporeal circuit consisted of a Jostra HL-20 heart-lung machine (for both pulsatile and nonpulsatile modes of perfusion), a Capiox Baby RX hollow-fiber membrane oxygenator, a Capiox pediatric arterial filter, 5 feet of arterial tubing and 6 feet of venous tubing with a quarter-inch diameter. The circuit was primed with a lactated Ringers solution. The systemic resistance of a pseudo-patient (mean weight, 3 kg) was simulated by placing a clamp at the end of the arterial line. The pseudo-patient was subjected to five pump flow rates in the 400 to 800 ml/min range. During pulsatile perfusion, the pump rate was kept constant at 120 bpm. Pressure waveforms were recorded at the preoxygenator, postoxygenator, and preaortic cannula sites. SHE was calculated by use of the following formula {SHE (ergs/cm) = 1,332 [((integral fpdt) / (integral fdt)) - Mean Arterial Pressure]} (f = pump flow and p = pressure). A total of 60 experiments were performed (n = 6 for nonpulsatile and n = 6 for pulsatile) at each of the five flow rates. A linear mixed-effects model, which accounts for the correlation among repeated measurements, was fit to the data to assess differences in SHE between flows, pumps, and sites. The Tukey multiple comparison procedure was used to adjust p values for post hoc pairwise comparisons. With a pump flow rate of 400 ml/min, pulsatile flow generated significantly higher surplus hemodynamic energy levels at the preoxygenator site (23,421 +/- 2,068 ergs/cm vs. 4,154 +/- 331 ergs/cm, p < 0.0001), the postoxygenator site (18,784 +/- 1,557 ergs/cm vs. 3,383 +/- 317 ergs/cm, p < 0.0001), and the precannula site (6,324 +/- 772 ergs/cm vs. 1,320 +/- 91 ergs/cm, p < 0.0001), compared with the nonpulsatile group. Pulsatile flow produced higher SHE

  16. External-to-Internal Iliac Stent-Graft: Medium-Term Patency Following Exclusion of a Retrogradely Perfused Common Iliac Aneurysm

    SciTech Connect

    Nicholls, Marcus John; McPherson, Simon

    2010-08-15

    Following complicated aortic aneurysm surgery a complete left iliac occlusion resulted in buttock claudication. A retrogradely perfused right common iliac aneurysm expanded. Exclusion was by external-to-internal iliac stent-graft. No deterioration in claudication occurred with medium-term stent-graft patency.

  17. Ketogenesis evaluation in perfused liver of diabetic rats submitted to short-term insulin-induced hypoglycemia.

    PubMed

    Barrena, Helenton Cristhian; Gazola, Vilma Aparecida Ferreira Godoi; Furlan, Maria Montserrat Diaz Pedrosa; Garcia, Rosângela Fernandes; de Souza, Helenir Medri; Bazotte, Roberto Barbosa

    2009-08-01

    Ketogenesis, inferred by the production of acetoacetate plus ss-hydroxybutyrate, in isolated perfused livers from 24-h fasted diabetic rats submitted to short-term insulin-induced hypoglycemia (IIH) was investigated. For this purpose, alloxan-diabetic rats that received intraperitoneal regular insulin (IIH group) or saline (COG group) injection were compared. An additional group of diabetic rats which received oral glucose (gavage) (100 mg kg(-1)) 15 min after insulin administration (IIH + glucose group) was included. The studies were performed 30 min after insulin (1.0 U kg(-1)) or saline injection. The ketogenesis before octanoate infusion was diminished (p < 0.05) in livers from rats which received insulin (COG vs. IIH group) or insulin plus glucose (COG vs. IIH + glucose group). However, the liver ketogenic capacity during the infusion of octanoate (0.3 mM) was maintained (COG vs. IIH group and COG vs. IIH + glucose group). In addition, the blood concentration of ketone bodies was not influenced by the administration of insulin or insulin plus glucose. Taken together, the results showed that inspite the fact that insulin and glucose inhibits ketogenesis, livers from diabetic rats submitted to short-term IIH which received insulin or insulin plus glucose showed maintained capacity to produce acetoacetate and ss-hydroxybutyrate from octanoate.

  18. Safety and Feasibility of High-pressure Transvenous Limb Perfusion With 0.9% Saline in Human Muscular Dystrophy

    PubMed Central

    Fan, Zheng; Kocis, Keith; Valley, Robert; Howard, James F; Chopra, Manisha; An, Hongyu; Lin, Weili; Muenzer, Joseph; Powers, William

    2012-01-01

    We evaluated safety and feasibility of the transvenous limb perfusion gene delivery method in muscular dystrophy. A dose escalation study of single limb perfusion with 0.9% saline starting with 5% of limb volume was carried out in adults with muscular dystrophies under intravenous analgesia/anesthesia. Cardiac, vascular, renal, muscle, and nerve functions were monitored. A tourniquet was placed above the knee with inflated pressure of 310 mm Hg. Infusion was carried out with a clinically approved infuser via an intravenous catheter inserted in the saphenous vein with a goal infusion rate of 80 ml/minute. Infusion volume was escalated stepwise to 20% limb volume in seven subjects. No subject complained of any post procedure pain other than due to needle punctures. Safety warning boundaries were exceeded only for transient depression of limb tissue oximetry and transient elevation of muscle compartment pressures; these were not associated with nerve, muscle, or vascular damage. Muscle magnetic resonant imaging (MRI) demonstrated fluid accumulation in muscles of the perfused lower extremity. High-pressure retrograde transvenous limb perfusion with saline up to 20% of limb volume at above infusion parameters is safe and feasible in adult human muscular dystrophy. This study will serve as a basis for future gene transfer clinical trials. PMID:21772257

  19. Pancreatic Ductal Perfusion at Organ Procurement Enhances Islet Yield in Human Islet Isolation

    PubMed Central

    Shimoda, Masayuki; Kanak, Mazhar A.; Shahbazov, Rauf; Kunnathodi, Faisal; Lawrence, Michael C.; Naziruddin, Bashoo; Levy, Marlon F.

    2015-01-01

    Objective Pancreas preservation is a major factor influencing the results of islet cell transplantation. This study evaluated the effects of two different solutions for pancreatic ductal perfusion (PDP) at organ procurement. Methods Eighteen human pancreases were assigned to three groups: non-PDP (control), PDP with ET-Kyoto solution, and PDP with cold storage/purification stock solution. Pancreatic islets were isolated according to the modified Ricordi method. Results No significant differences in donor characteristics, including cold ischemia time, were observed between the three groups. All islet isolations in the PDP groups had >400,000 IEQ in total islet yield post-purification, a significant increase when compared with the control (P = 0.04 and <0.01). The islet quality assessments—including an in vivo diabetic nude mice assay and the response of high-mobility group box protein 1 to cytokine stimulation—also showed no significant differences. The proportion of TUNEL-positive cells showing apoptosis in islets in the PDP groups was significantly lower than in the control group (P < 0.05). Conclusion Both ET-Kyoto solution and cold storage/purification stock solution are suitable for PDP and consistently resulted in isolation success. Further studies with a larger number of pancreas donors should be done to compare the effects of the PDP solutions. PMID:25058879

  20. Isolated total lung perfusion as a means to deliver organ-specific chemotherapy: long-term studies in animals

    SciTech Connect

    Johnston, M.R.; Christensen, C.W.; Minchin, R.F.; Rickaby, D.A.; Linehan, J.H.; Schuller, H.M.; Boyd, M.R.; Dawson, C.A.

    1985-07-01

    The objectives of this study were to develop a surgical procedure that would allow for bilateral isolated lung perfusion in vivo as a means of delivering organ-specific chemotherapy and to evaluate the influence of the procedure on certain pulmonary physiologic parameters. The sterile surgical procedure that was carried out in dogs involved the setting up of two separate perfusion circuits. Once standard systemic cardiopulmonary bypass was established, a second circuit was devised to perfuse the lungs by placing an inflow cannula into the main pulmonary artery and collecting venous effluent in the left atrium. Cross-contamination between perfusion circuits was determined in acute studies with labeled plasma protein or red blood cells and was found to be in an acceptable range if the aorta was cross-clamped and the heart arrested. Only about 0.4 ml/min of pulmonary perfusate leaked into the systemic circulation, indicating that systemic toxicity should not be a major concern when chemotherapy agents are added to the pulmonary perfusate. Chronic studies demonstrated that hemodynamic parameters, lung water, pulmonary endothelial serotonin extraction, and histologic findings all showed minimal changes after 50 minutes of isolated lung perfusion. Five days after perfusion, lung dynamic compliance and peak serotonin extraction showed significant decreases. However, all of the measured parameters had returned toward baseline levels by the end of the 8-week postoperative study period. The procedure offers significant advantages over the previously described single lung perfusion and may provide a method of delivering immediate high-concentration adjuvant chemotherapy to coincide with resection of primary or metastatic lung tumors.

  1. [ARTCEREB irrigation and perfusion solution for cerebrospinal surgery: pharmacological assessment using human astrocytes exposed to test solutions].

    PubMed

    Nishimura, Masuhiro; Doi, Kazuhisa; Enomoto, Riyo; Lee, Eibai; Naito, Shinsaku; Yamauchi, Aiko

    2009-09-01

    ARTCEREB irrigation and perfusion solution (Artcereb) is a preparation intended for the irrigation and perfusion of the cerebral ventricles, and it is therefore important to evaluate the effects of Artcereb on brain cells. In vitro assessment of the effects of Artcereb in cell cultures of human fetal astrocytes was conducted in comparison with normal saline and lactated Ringer's solution. The effects of exposure to Artcereb were evaluated based on microscopic images of the mitochondria stained with rhodamine 123. The effects of exposure to Artcereb on cell function were also evaluated by quantitative analysis of mitochondrial activity based on rhodamine 123 and (3)H-thymidine incorporation. Morphological changes in nuclear structure were also evaluated. The results of the present study showed that cell function in cell cultures of human astrocytes was relatively unaffected by exposure to Artcereb as compared with normal saline or lactated Ringer's solution, suggesting that Artcereb has less effect on brain cells than normal saline or lactated Ringer's solution when used for the irrigation or perfusion of the cerebral ventricles.

  2. A Perfusion-based Human Cadaveric Model for Management of Carotid Artery Injury during Endoscopic Endonasal Skull Base Surgery

    PubMed Central

    Pham, Martin; Kale, Aydemir; Marquez, Yvette; Winer, Jesse; Lee, Brian; Harris, Brianna; Minnetti, Michael; Carey, Joseph; Giannotta, Steven; Zada, Gabriel

    2014-01-01

    Objective To create and develop a reproducible and realistic training environment to prepare residents and trainees for arterial catastrophes during endoscopic endonasal surgery. Design An artificial blood substitute was perfused at systolic blood pressures in eight fresh human cadavers to mimic intraoperative scenarios. Setting The USC Keck School of Medicine Fresh Tissue Dissection Laboratory was used as the training site. Participants Trainees were USC neurosurgery residents and junior faculty. Main Outcome A 5-point questionnaire was used to assess pre- and posttraining confidence scores. Results High-pressure extravasation at normal arterial blood pressure mimicked real intraoperative internal carotid artery (ICA) injury. Residents developed psychomotor skills required to achieve hemostasis using suction, cottonoids, and muscle grafts. Questionnaire responses from all trainees reported a realistic experience enhanced by the addition of the perfusion model. Conclusions The addition of an arterial perfusion system to fresh tissue cadavers is among the most realistic training models available. This enables the simulation of rare intraoperative scenarios such as ICA injury. Strategies for rapid hemostasis and implementation of techniques including endoscope manipulation, suction, and packing can all be rehearsed via this novel paradigm. PMID:25301092

  3. Human periosteal-derived cell expansion in a perfusion bioreactor system: proliferation, differentiation and extracellular matrix formation.

    PubMed

    Sonnaert, M; Papantoniou, I; Bloemen, V; Kerckhofs, G; Luyten, F P; Schrooten, J

    2017-02-01

    Perfusion bioreactor systems have shown to be a valuable tool for the in vitro development of three-dimensional (3D) cell-carrier constructs. Their use for cell expansion, however, has been much less explored. Since maintenance of the initial cell phenotype is essential in this process, it is imperative to obtain insight into the bioreactor-related variables determining cell fate. Therefore, this study investigated the influence of fluid flow-induced shear stress on the proliferation, differentiation and matrix deposition of human periosteal-derived cells in the absence of additional differentiation-inducing stimuli; 120 000 cells were seeded on additive manufactured 3D Ti6Al4V scaffolds and cultured for up to 28 days at different flow rates in the range 0.04-6 ml/min. DNA measurements showed, on average, a three-fold increase in cell content for all perfused conditions in comparison to static controls, whereas the magnitude of the flow rate did not have an influence. Contrast-enhanced nanofocus X-ray computed tomography showed substantial formation of an engineered neotissue in all perfused conditions, resulting in a filling (up to 70%) of the total internal void volume, and no flow rate-dependent differences were observed. The expression of key osteogenic markers, such as RunX2, OCN, OPN and Col1, did not show any significant changes in comparison to static controls after 28 days of culture, with the exception of OSX at high flow rates. We therefore concluded that, in the absence of additional osteogenic stimuli, the investigated perfusion conditions increased cell proliferation but did not significantly enhance osteogenic differentiation, thus allowing for this process to be used for cell expansion. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Incubator-independent cell-culture perfusion platform for continuous long-term microelectrode array electrophysiology and time-lapse imaging

    PubMed Central

    Saalfrank, Dirk; Konduri, Anil Krishna; Latifi, Shahrzad; Habibey, Rouhollah; Golabchi, Asiyeh; Martiniuc, Aurel Vasile; Knoll, Alois; Ingebrandt, Sven; Blau, Axel

    2015-01-01

    Most in vitro electrophysiology studies extract information and draw conclusions from representative, temporally limited snapshot experiments. This approach bears the risk of missing decisive moments that may make a difference in our understanding of physiological events. This feasibility study presents a simple benchtop cell-culture perfusion system adapted to commercial microelectrode arrays (MEAs), multichannel electrophysiology equipment and common inverted microscopy stages for simultaneous and uninterrupted extracellular electrophysiology and time-lapse imaging at ambient CO2 levels. The concept relies on a transparent, replica-casted polydimethylsiloxane perfusion cap, gravity- or syringe-pump-driven perfusion and preconditioning of pH-buffered serum-free cell-culture medium to ambient CO2 levels at physiological temperatures. The low-cost microfluidic in vitro enabling platform, which allows us to image cultures immediately after cell plating, is easy to reproduce and is adaptable to the geometries of different cell-culture containers. It permits the continuous and simultaneous multimodal long-term acquisition or manipulation of optical and electrophysiological parameter sets, thereby considerably widening the range of experimental possibilities. Two exemplary proof-of-concept long-term MEA studies on hippocampal networks illustrate system performance. Continuous extracellular recordings over a period of up to 70 days revealed details on both sudden and gradual neural activity changes in maturing cell ensembles with large intra-day fluctuations. Correlated time-lapse imaging unveiled rather static macroscopic network architectures with previously unreported local morphological oscillations on the timescale of minutes. PMID:26543581

  5. Bidirectional Transfer Study of Polystyrene Nanoparticles across the Placental Barrier in an ex Vivo Human Placental Perfusion Model

    PubMed Central

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Diener, Pierre-André; Maeder-Althaus, Xenia; Maurizi, Lionel; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula

    2015-01-01

    Background Nanoparticle exposure in utero might not be a major concern yet, but it could become more important with the increasing application of nanomaterials in consumer and medical products. Several epidemiologic and in vitro studies have shown that nanoparticles can have potential toxic effects. However, nanoparticles also offer the opportunity to develop new therapeutic strategies to treat specifically either the pregnant mother or the fetus. Previous studies mainly addressed whether nanoparticles are able to cross the placental barrier. However, the transport mechanisms underlying nanoparticle translocation across the placenta are still unknown. Objectives In this study we examined which transport mechanisms underlie the placental transfer of nanoparticles. Methods We used the ex vivo human placental perfusion model to analyze the bidirectional transfer of plain and carboxylate modified polystyrene particles in a size range between 50 and 300 nm. Results We observed that the transport of polystyrene particles in the fetal to maternal direction was significantly higher than for the maternal to fetal direction. Regardless of their ability to cross the placental barrier and the direction of perfusion, all polystyrene particles accumulated in the syncytiotrophoblast of the placental tissue. Conclusions Our results indicate that the syncytiotrophoblast is the key player in regulating nanoparticle transport across the human placenta. The main mechanism underlying this translocation is not based on passive diffusion, but is likely to involve an active, energy-dependent transport pathway. These findings will be important for reproductive toxicology as well as for pharmaceutical engineering of new drug carriers. Citation Grafmueller S, Manser P, Diener L, Diener PA, Maeder-Althaus X, Maurizi L, Jochum W, Krug HF, Buerki-Thurnherr T, von Mandach U, Wick P. 2015. Bidirectional transfer study of polystyrene nanoparticles across the placental barrier in an ex vivo human

  6. Morphological behaviour and metabolic capacity of cryopreserved human primary hepatocytes cultivated in a perfused multiwell device.

    PubMed

    Vivares, Aurelie; Salle-Lefort, Sandrine; Arabeyre-Fabre, Catherine; Ngo, Robert; Penarier, Geraldine; Bremond, Michele; Moliner, Patricia; Gallas, Jean-François; Fabre, Gerard; Klieber, Sylvie

    2015-01-01

    1. The quantitative prediction of the pharmacokinetic parameters of a drug from data obtained using human in vitro systems remains a significant challenge i.e. prediction of metabolic clearance in humans and estimation of the relative contribution of enzymes involved in the clearance. This has become particularly problematic for low turnover compounds. 2. Having human hepatocytes with stable cellular function over several days that adequately mimic the complexity of the physiological environment would be a major advance. Thus, we evaluated human hepatocytes, maintained in culture during 7 days in the microfluidic LiverChip™ system, in terms of morphological appearance, relative mRNA expression of phase I and II enzymes and transporters as a function of time, and metabolic capacity using probe substrates. 3. The results showed that mRNA levels of the major genes for enzymes involved in drug metabolism were well-maintained over a 7-day period of culture. Furthermore, after 4 days of culture, in the Liverchip™ device, human hepatocytes exhibited higher or similar CYPs activities compared to 1 day of culture in 2D-static conditions. 4. The functional data were supported by light/electron microscopies and immunohistochemistry showing viable tissue structure and well-differentiated human hepatocytes: presence of cell junctions, glycogen storage, and bile canaliculi.

  7. Do perfume additives termed human pheromones warrant being termed pheromones?

    PubMed

    Winman, Anders

    2004-09-30

    Two studies of the effects of perfume additives, termed human pheromones by the authors, have conveyed the message that these substances can promote an increase in human sociosexual behaviour [Physiol. Behav. 75 (2003) R1; Arch. Sex. Behav. 27 (1998) R2]. The present paper presents an extended analysis of this data. It is shown that in neither study is there a statistically significant increase in any of the sociosexual behaviours for the experimental groups. In the control groups of both studies, there are, however, moderate but statistically significant decreases in the corresponding behaviour. Most notably, there is no support in data for the claim that the substances increase the attractiveness of the wearers of the substances to the other sex. It is concluded that more research using matched homogenous groups of participants is needed.

  8. Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts

    NASA Astrophysics Data System (ADS)

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Maurizi, Lionel; Diener, Pierre-André; Hofmann, Heinrich; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula; Wick, Peter

    2015-08-01

    Nanotechnology is a rapidly expanding and highly promising new technology with many different fields of application. Consequently, the investigation of engineered nanoparticles in biological systems is steadily increasing. Questions about the safety of such engineered nanoparticles are very important and the most critical subject with regard to the penetration of biological barriers allowing particle distribution throughout the human body. Such translocation studies are technically challenging and many issues have to be considered to obtain meaningful and comparable results. Here we report on the transfer of polystyrene nanoparticles across the human placenta using an ex vivo human placenta perfusion model. We provide an overview of several challenges that can potentially occur in any translocation study in relation to particle size distribution, functionalization and stability of labels. In conclusion, a careful assessment of nanoparticle properties in a physiologically relevant milieu is as challenging and important as the actual study of nanoparticle-cell interactions itself.

  9. Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts

    PubMed Central

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Maurizi, Lionel; Diener, Pierre-André; Hofmann, Heinrich; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula; Wick, Peter

    2015-01-01

    Nanotechnology is a rapidly expanding and highly promising new technology with many different fields of application. Consequently, the investigation of engineered nanoparticles in biological systems is steadily increasing. Questions about the safety of such engineered nanoparticles are very important and the most critical subject with regard to the penetration of biological barriers allowing particle distribution throughout the human body. Such translocation studies are technically challenging and many issues have to be considered to obtain meaningful and comparable results. Here we report on the transfer of polystyrene nanoparticles across the human placenta using an ex vivo human placenta perfusion model. We provide an overview of several challenges that can potentially occur in any translocation study in relation to particle size distribution, functionalization and stability of labels. In conclusion, a careful assessment of nanoparticle properties in a physiologically relevant milieu is as challenging and important as the actual study of nanoparticle–cell interactions itself. PMID:27877820

  10. Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts.

    PubMed

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Maurizi, Lionel; Diener, Pierre-André; Hofmann, Heinrich; Jochum, Wolfram; Krug, Harald F; Buerki-Thurnherr, Tina; von Mandach, Ursula; Wick, Peter

    2015-08-01

    Nanotechnology is a rapidly expanding and highly promising new technology with many different fields of application. Consequently, the investigation of engineered nanoparticles in biological systems is steadily increasing. Questions about the safety of such engineered nanoparticles are very important and the most critical subject with regard to the penetration of biological barriers allowing particle distribution throughout the human body. Such translocation studies are technically challenging and many issues have to be considered to obtain meaningful and comparable results. Here we report on the transfer of polystyrene nanoparticles across the human placenta using an ex vivo human placenta perfusion model. We provide an overview of several challenges that can potentially occur in any translocation study in relation to particle size distribution, functionalization and stability of labels. In conclusion, a careful assessment of nanoparticle properties in a physiologically relevant milieu is as challenging and important as the actual study of nanoparticle-cell interactions itself.

  11. Step-by-step protocol to perfuse and dissect the mouse parotid gland and isolation of high-quality RNA from murine and human parotid tissue.

    PubMed

    Watermann, Christoph; Valerius, Klaus Peter; Wagner, Steffen; Wittekindt, Claus; Klussmann, Jens Peter; Baumgart-Vogt, Eveline; Karnati, Srikanth

    2016-04-01

    Macroscopic identification and surgical removal of the mouse parotid gland is demanding because of its anatomic location and size. Moreover, the mouse parotid gland contains high concentrations of RNases, making it difficult to isolate high-quality RNA. So far, appropriate methods for optimal perfusion-fixation and dissection of mouse parotid glands, as well as the isolation of high quality RNA from this tissue, are not available. Here we present a simple, optimized, step-by-step surgical method to perfuse and isolate murine parotid glands. We also compared two common RNA extraction methods (RNeasy Mini Kit versus TRIzol) for their yields of high-quality, intact RNA from human and murine parotid gland tissues that were either snap-frozen or immersed in RNAlater stabilization solution. Mouse parotid tissue that was perfused and immersed in RNAlater and human samples immersed in RNAlater exhibited the best RNA quality, independent of the isolation method.

  12. Bidirectional placental transfer of Bisphenol A and its main metabolite, Bisphenol A-Glucuronide, in the isolated perfused human placenta.

    PubMed

    Corbel, T; Gayrard, V; Puel, S; Lacroix, M Z; Berrebi, A; Gil, S; Viguié, C; Toutain, P-L; Picard-Hagen, N

    2014-08-01

    The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G.

  13. Effects of long chain fatty acids on solute absorption: perfusion studies in the human jejunum.

    PubMed Central

    Ammon, H V; Thomas, P J; Phillips, S F

    1977-01-01

    Perfusion studies were performed in healthy volunteers to test the hypothesis that net fluid secretion induced by fatty acids is accompanied by parallel reduction in solute transport. Ricinoleic acid provoked a marked net secretion of fluid and concomitantly inhibited the absorption of all solutes tested; these included glucose, xylose, L-leucine, L-lysine, Folic acid, and 2-mono-olein. Oleic acid also reduced net fluid and solute transport, but was less potent in reducing solute absorption than was ricinoleic acid. When fluid secretion was induced osmotically with mannitol, glucose and xylose absorption was not affected. The mechanism for this generalised effect of fatty acids on solute absorption is uncertain, possibly nonspecific, and might be related to mucosal damage and altered mucosal permeability induced by these agents. PMID:590838

  14. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans.

    PubMed

    Seifert, Thomas; Fisher, James P; Young, Colin N; Hartwich, Doreen; Ogoh, Shigehiko; Raven, Peter B; Fadel, Paul J; Secher, Niels H

    2010-10-01

    Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral metabolism (from arterial and internal jugular venous O(2), glucose and lactate differences), as well as the middle cerebral artery mean blood velocity (MCA V(mean); transcranial Doppler ultrasound) during a sustained static handgrip contraction at 40% of maximal voluntary contraction (n = 9) and the MCA V(mean) during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from approximately 60 to approximately 110 beats min(-1) (P < 0.01) and cardiac output by approximately 40% (P < 0.05), but did not affect mean arterial pressure. The central cardiovascular responses to exercise with glycopyrrolate were similar to the control responses, except that cardiac output did not increase during static handgrip with glycopyrrolate. Glycopyrrolate did not significantly affect cerebral metabolism during static handgrip, but a parallel increase in MCA V(mean) (approximately 16%; P < 0.01) and CBF (approximately 12%; P < 0.01) during static handgrip, as well as the increase in MCA V(mean) during cycling (approximately 15%; P < 0.01), were abolished by glycopyrrolate (P < 0.05). Thus, during both cycling and static handgrip, a cholinergic receptor mechanism is important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen.

  15. Autophagy in term normal human placentas.

    PubMed

    Signorelli, P; Avagliano, L; Virgili, E; Gagliostro, V; Doi, P; Braidotti, P; Bulfamante, G P; Ghidoni, R; Marconi, A M

    2011-06-01

    Autophagy is an inducible catabolic process that responds to environment and is essential for cell survival during stress, starvation and hypoxia. Its function in the human placenta it is not yet understood. We collected 14 placentas: 7 at vaginal delivery and 7 at elective caesarean section after uneventful term pregnancies. The presence of autophagy was assessed in different placental areas by immunoblotting, immunohistochemistry and electron microscopy. We found that autophagy is significantly higher in placentas obtained from cesarean section than in those from vaginal delivery. Moreover there is a significant inverse relationship between autophagy and umbilical arterial glucose concentration.

  16. Circadian Kisspeptin expression in human term placenta.

    PubMed

    de Pedro, M A; Morán, J; Díaz, I; Murias, L; Fernández-Plaza, C; González, C; Díaz, E

    2015-11-01

    Kisspeptin is an essential gatekeeper of reproductive function. During pregnancy high circulating levels of kisspeptin have been described, however the clear role of this neuropeptide in pregnancy remains unknown. We tested the existence of rhythmic kisspeptin expression in human full-term placenta from healthy pregnant women at six different time points during the day. The data obtained by Western blotting were fitted to a mathematical model (Fourier series), demonstrating, for the first time, the existence of a circadian rhythm in placental kisspeptin expression.

  17. Human Behaviour in Long-Term Missions

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  18. Acute effects of ethanol on the transfer of nicotine and two dietary carcinogens in human placental perfusion.

    PubMed

    Veid, Jenni; Karttunen, Vesa; Myöhänen, Kirsi; Myllynen, Päivi; Auriola, Seppo; Halonen, Toivo; Vähäkangas, Kirsi

    2011-09-10

    Many mothers use, against instructions, alcohol during pregnancy. Simultaneously mothers are exposed to a wide range of other environmental chemicals. These chemicals may also harm the developing fetus, because almost all toxic compounds can go through human placenta. Toxicokinetic effects of ethanol on the transfer of other environmental compounds through human placenta have not been studied before. It is known that ethanol has lytic properties and increases the permeability and fluidity of cell membranes. We studied the effects of ethanol on the transfer of three different environmental toxins: nicotine, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) and NDMA (N-nitrosodimethylamine) in placental perfusion. We tested in human breast cancer adenocarcinoma cell line MCF-7 whether ethanol affects ABCG2/BCRP, which is also the major transporter in human placenta. We found that the transfer of ethanol is comparable to that of antipyrine, which points to passive diffusion as the transfer mechanism. Unexpectedly, ethanol had no statistically significant effect on the transfer of the other studied compounds. Neither did ethanol inhibit the function of ABCG2/BCRP. These experiments represent only the effects of acute exposure to ethanol and chronic exposure remains to be studied.

  19. Ex vivo lung perfusion.

    PubMed

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

  20. Renal perfusion scintiscan

    MedlinePlus

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  1. Bonded Cumomer Analysis of Human Melanoma Metabolism Monitored by 13C NMR Spectroscopy of Perfused Tumor Cells*

    PubMed Central

    Shestov, Alexander A.; Mancuso, Anthony; Lee, Seung-Cheol; Guo, Lili; Nelson, David S.; Roman, Jeffrey C.; Henry, Pierre-Gilles; Leeper, Dennis B.; Blair, Ian A.; Glickson, Jerry D.

    2016-01-01

    A network model for the determination of tumor metabolic fluxes from 13C NMR kinetic isotopomer data has been developed and validated with perfused human DB-1 melanoma cells carrying the BRAF V600E mutation, which promotes oxidative metabolism. The model generated in the bonded cumomer formalism describes key pathways of tumor intermediary metabolism and yields dynamic curves for positional isotopic enrichment and spin-spin multiplets. Cells attached to microcarrier beads were perfused with 26 mm [1,6-13C2]glucose under normoxic conditions at 37 °C and monitored by 13C NMR spectroscopy. Excellent agreement between model-predicted and experimentally measured values of the rates of oxygen and glucose consumption, lactate production, and glutamate pool size validated the model. ATP production by glycolytic and oxidative metabolism were compared under hyperglycemic normoxic conditions; 51% of the energy came from oxidative phosphorylation and 49% came from glycolysis. Even though the rate of glutamine uptake was ∼50% of the tricarboxylic acid cycle flux, the rate of ATP production from glutamine was essentially zero (no glutaminolysis). De novo fatty acid production was ∼6% of the tricarboxylic acid cycle flux. The oxidative pentose phosphate pathway flux was 3.6% of glycolysis, and three non-oxidative pentose phosphate pathway exchange fluxes were calculated. Mass spectrometry was then used to compare fluxes through various pathways under hyperglycemic (26 mm) and euglycemic (5 mm) conditions. Under euglycemic conditions glutamine uptake doubled, but ATP production from glutamine did not significantly change. A new parameter measuring the Warburg effect (the ratio of lactate production flux to pyruvate influx through the mitochondrial pyruvate carrier) was calculated to be 21, close to upper limit of oxidative metabolism. PMID:26703469

  2. Temperature-dependent release of ATP from human erythrocytes: mechanism for the control of local tissue perfusion

    PubMed Central

    Kalsi, Kameljit K; González-Alonso, José

    2012-01-01

    Human limb muscle and skin blood flow increases significantly with elevations in temperature, possibly through physiological processes that involve temperature-sensitive regulatory mechanisms. Here we tested the hypothesis that the release of the vasodilator ATP from human erythrocytes is sensitive to physiological increases in temperature both in vitro and in vivo, and examined potential channel/transporters involved. To investigate the source of ATP release, whole blood, red blood cells (RBCs), plasma and serum were heated in vitro to 33, 36, 39 and 42°C. In vitro heating augmented plasma or ‘bathing solution’ ATP in whole blood and RBC samples, but not in either isolated plasma or serum samples. Heat-induced ATP release was blocked by niflumic acid and glibenclamide, but was not affected by inhibitors of nucleoside transport or anion exchange. Heating blood to 42°C enhanced (P < 0.05) membrane protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR) in RBCs. In a parallel in vivo study in humans exposed to whole-body heating at rest and during exercise, increases in muscle temperature from 35 to 40°C correlated strongly with elevations in arterial plasma ATP (r2 = 0.91; P = 0.0001), but not with femoral venous plasma ATP (r2 = 0.61; P = 0.14). In vitro, however, the increase in ATP release from RBCs was similar in arterial and venous samples heated to 39°C. Our findings demonstrate that erythrocyte ATP release is sensitive to physiological increases in temperature, possibly via activation of CFTR-like channels, and suggest that temperature-dependent release of ATP from erythrocytes might be an important mechanism regulating human limb muscle and skin perfusion in conditions that alter blood and tissue temperature. PMID:22227202

  3. Temperature-dependent release of ATP from human erythrocytes: mechanism for the control of local tissue perfusion.

    PubMed

    Kalsi, Kameljit K; González-Alonso, José

    2012-03-01

    Human limb muscle and skin blood flow increases significantly with elevations in temperature, possibly through physiological processes that involve temperature-sensitive regulatory mechanisms. Here we tested the hypothesis that the release of the vasodilator ATP from human erythrocytes is sensitive to physiological increases in temperature both in vitro and in vivo, and examined potential channel/transporters involved. To investigate the source of ATP release, whole blood, red blood cells (RBCs), plasma and serum were heated in vitro to 33, 36, 39 and 42°C. In vitro heating augmented plasma or 'bathing solution' ATP in whole blood and RBC samples, but not in either isolated plasma or serum samples. Heat-induced ATP release was blocked by niflumic acid and glibenclamide, but was not affected by inhibitors of nucleoside transport or anion exchange. Heating blood to 42°C enhanced (P < 0.05) membrane protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR) in RBCs. In a parallel in vivo study in humans exposed to whole-body heating at rest and during exercise, increases in muscle temperature from 35 to 40°C correlated strongly with elevations in arterial plasma ATP (r(2) = 0.91; P = 0.0001), but not with femoral venous plasma ATP (r(2) = 0.61; P = 0.14). In vitro, however, the increase in ATP release from RBCs was similar in arterial and venous samples heated to 39°C. Our findings demonstrate that erythrocyte ATP release is sensitive to physiological increases in temperature, possibly via activation of CFTR-like channels, and suggest that temperature-dependent release of ATP from erythrocytes might be an important mechanism regulating human limb muscle and skin perfusion in conditions that alter blood and tissue temperature.

  4. Interstitial Perfusion Culture with Specific Soluble Factors Inhibits Type I Collagen Production from Human Osteoarthritic Chondrocytes in Clinical-Grade Collagen Sponges

    PubMed Central

    Talò, Giuseppe; Lovati, Arianna B.; Pasdeloup, Marielle; Riboldi, Stefania A.; Moretti, Matteo; Mallein-Gerin, Frédéric

    2016-01-01

    Articular cartilage has poor healing ability and cartilage injuries often evolve to osteoarthritis. Cell-based strategies aiming to engineer cartilaginous tissue through the combination of biocompatible scaffolds and articular chondrocytes represent an alternative to standard surgical techniques. In this context, perfusion bioreactors have been introduced to enhance cellular access to oxygen and nutrients, hence overcoming the limitations of static culture and improving matrix deposition. Here, we combined an optimized cocktail of soluble factors, the BIT (BMP-2, Insulin, Thyroxin), and clinical-grade collagen sponges with a bidirectional perfusion bioreactor, namely the oscillating perfusion bioreactor (OPB), to engineer in vitro articular cartilage by human articular chondrocytes (HACs) obtained from osteoarthritic patients. After amplification, HACs were seeded and cultivated in collagen sponges either in static or dynamic conditions. Chondrocyte phenotype and the nature of the matrix synthesized by HACs were assessed using western blotting and immunohistochemistry analyses. Finally, the stability of the cartilaginous tissue produced by HACs was evaluated in vivo by subcutaneous implantation in nude mice. Our results showed that perfusion improved the distribution and quality of cartilaginous matrix deposited within the sponges, compared to static conditions. Specifically, dynamic culture in the OPB, in combination with the BIT cocktail, resulted in the homogeneous production of extracellular matrix rich in type II collagen. Remarkably, the production of type I collagen, a marker of fibrous tissues, was also inhibited, indicating that the association of the OPB with the BIT cocktail limits fibrocartilage formation, favoring the reconstruction of hyaline cartilage. PMID:27584727

  5. In vivo (31)P magnetic resonance spectroscopy and morphometric analysis of the perfused vascular architecture of human glioma xenografts in nude mice.

    PubMed Central

    van der Sanden, B. P.; Rijken, P. F.; Heerschap, A.; Bernsen, H. J.; van der Kogel, A. J.

    1997-01-01

    The relationship between the bioenergetic status of human glioma xenografts in nude mice and morphometric parameters of the perfused vascular architecture was studied using (31)P magnetic resonance spectroscopy (MRS), fluorescence microscopy and two-dimensional digital image analysis. Two tumour lines with a different vascular architecture were used for this study. Intervascular distances and non-perfused area fractions varied greatly between tumours of the same line and tumours of different lines. The inorganic phosphate-nucleoside triphosphate (P(i)/NTP) ratio increased rapidly as mean intervascular distances increased from 100 microm to 300 microm. Two morphometric parameters - the percentage of intervascular distances larger than 200 microm (ivd200) and the non-perfused area fraction at a distance larger than 100 microm from a nearest perfused vessel (area100), - were deduced from these experiments and related to the P(i)/NTP ratio of the whole tumour. It is assumed that an aerobic to anaerobic transition influences the bioenergetic status, i.e. the P(i)/NTP ratio increased linearly with the percentage of ivd200 and the area100. PMID:9166934

  6. IFPA Meeting 2013 Workshop Report III: maternal placental immunological interactions, novel determinants of trophoblast cell fate, dual ex vivo perfusion of the human placenta.

    PubMed

    Abumaree, M H; Brownbill, P; Burton, G; Castillo, C; Chamley, L; Croy, B A; Drewlo, S; Dunk, C; Girard, S; Hansson, S; Jones, S; Jurisicova, A; Lewis, R; Letarte, M; Parast, M; Pehrson, C; Rappolee, D; Schneider, H; Tannetta, D; Varmuza, S; Wadsack, C; Wallace, A E; Zenerino, C; Lash, G E

    2014-02-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2013 there were twelve themed workshops, three of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of placental function, cell turnover and immunology: 1) immunology; 2) novel determinants of placental cell fate; 3) dual perfusion of human placental tissue.

  7. Studying Closed Hydrodynamic Models of “In Vivo” DNA Perfusion in Pig Liver for Gene Therapy Translation to Humans

    PubMed Central

    Sendra, Luis; Miguel, Antonio; Pérez-Enguix, Daniel; Montalvá, Eva; García-Gimeno, María Adelaida; Noguera, Inmaculada; Díaz, Ana; Pérez, Judith; Sanz, Pascual; López-Andújar, Rafael; Martí-Bonmatí, Luis; Aliño, Salvador F.

    2016-01-01

    Introduction Expressing exogenous genes after naked DNA delivery into hepatocytes might achieve sustained and high expression of human proteins. Tail vein DNA injection is an efficient procedure for gene transfer in murine liver. Hydrodynamic procedures in large animals require organ targeting, and improve with liver vascular exclusion. In the present study, two closed liver hydrofection models employing the human alpha-1-antitrypsin (hAAT) gene are compared to reference standards in order to evaluate their potential clinical interest. Material and Methods A solution of naked DNA bearing the hAAT gene was retrogradely injected in 7 pig livers using two different closed perfusion procedures: an endovascular catheterization-mediated procedure (n = 3) with infrahepatic inferior vena cava and portal vein blockage; and a surgery-mediated procedure (n = 4) with completely sealed liver. Gene transfer was performed through the suprahepatic inferior cava vein in the endovascular procedure and through the infrahepatic inferior vena cava in the surgical procedure. The efficiency of the procedures was evaluated 14 days after hydrofection by quantifying the hAAT protein copies per cell in tissue and in plasma. For comparison, samples from mice (n = 7) successfully hydrofected with hAAT and healthy human liver segments (n = 4) were evaluated. Results Gene decoding occurs efficiently using both procedures, with liver vascular arrest improving its efficiency. The surgically closed procedure (sealed organ) reached higher tissue protein levels (4x10^5- copies/cell) than the endovascular procedure, though the levels were lower than in human liver (5x10^6- copies/cell) and hydrofected mouse liver (10^6- copies/cell). However, protein levels in plasma were lower (p<0.001) than the reference standards in all cases. Conclusion Hydrofection of hAAT DNA to “in vivo” isolated pig liver mediates highly efficient gene delivery and protein expression in tissue. Both endovascular and

  8. Metabolite Profiling and Pharmacokinetic Evaluation of Hydrocortisone in a Perfused Three-Dimensional Human Liver Bioreactor

    PubMed Central

    Sarkar, Ujjal; Rivera-Burgos, Dinelia; Large, Emma M.; Hughes, David J.; Ravindra, Kodihalli C.; Dyer, Rachel L.; Ebrahimkhani, Mohammad R.; Griffith, Linda G.

    2015-01-01

    Endotoxin lipopolysaccharide (LPS) is known to cause liver injury primarily involving inflammatory cells such as Kupffer cells, but few in vitro culture models are applicable for investigation of inflammatory effects on drug metabolism. We have developed a three-dimensional human microphysiological hepatocyte–Kupffer cell coculture system and evaluated the anti-inflammatory effect of glucocorticoids on liver cultures. LPS was introduced to the cultures to elicit an inflammatory response and was assessed by the release of proinflammatory cytokines, interleukin 6 and tumor necrosis factor α. A sensitive and specific reversed-phase–ultra high-performance liquid chromatography–quadrupole time of flight–mass spectrometry method was used to evaluate hydrocortisone disappearance and metabolism at near physiologic levels. For this, the systems were dosed with 100 nM hydrocortisone and circulated for 2 days; hydrocortisone was depleted to approximately 30 nM, with first-order kinetics. Phase I metabolites, including tetrahydrocortisone and dihydrocortisol, accounted for 8–10% of the loss, and 45–52% consisted of phase II metabolites, including glucuronides of tetrahydrocortisol and tetrahydrocortisone. Pharmacokinetic parameters, i.e., half-life, rate of elimination, clearance, and area under the curve, were 23.03 hours, 0.03 hour−1, 6.6 × 10−5 l⋅hour−1, and 1.03 (mg/l)*h, respectively. The ability of the bioreactor to predict the in vivo clearance of hydrocortisone was characterized, and the obtained intrinsic clearance values correlated with human data. This system offers a physiologically relevant tool for investigating hepatic function in an inflamed liver. PMID:25926431

  9. Quantitative Assessment of Population Variability in Hepatic Drug Metabolism Using a Perfused Three-Dimensional Human Liver Microphysiological System

    PubMed Central

    Tsamandouras, N.; Kostrzewski, T.; Stokes, C. L.; Griffith, L. G.; Hughes, D. J.

    2017-01-01

    In this work, we first describe the population variability in hepatic drug metabolism using cryopreserved hepatocytes from five different donors cultured in a perfused three-dimensional human liver microphysiological system, and then show how the resulting data can be integrated with a modeling and simulation framework to accomplish in vitro–in vivo translation. For each donor, metabolic depletion profiles of six compounds (phenacetin, diclofenac, lidocaine, ibuprofen, propranolol, and prednisolone) were measured, along with metabolite formation, mRNA levels of 90 metabolism-related genes, and markers of functional viability [lactate dehydrogenase (LDH) release, albumin, and urea production]. Drug depletion data were analyzed with mixed-effects modeling. Substantial interdonor variability was observed with respect to gene expression levels, drug metabolism, and other measured hepatocyte functions. Specifically, interdonor variability in intrinsic metabolic clearance ranged from 24.1% for phenacetin to 66.8% for propranolol (expressed as coefficient of variation). Albumin, urea, LDH, and cytochrome P450 mRNA levels were identified as significant predictors of in vitro metabolic clearance. Predicted clearance values from the liver microphysiological system were correlated with the observed in vivo values. A population physiologically based pharmacokinetic model was developed for lidocaine to illustrate the translation of the in vitro output to the observed pharmacokinetic variability in vivo. Stochastic simulations with this model successfully predicted the observed clinical concentration-time profiles and the associated population variability. This is the first study of population variability in drug metabolism in the context of a microphysiological system and has important implications for the use of these systems during the drug development process. PMID:27760784

  10. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor

    PubMed Central

    Freyer, Nora; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Schrade, Petra; Bachmann, Sebastian; Damm, Georg; Seehofer, Daniel; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

    2016-01-01

    Abstract The hepatic differentiation of human induced pluripotent stem cells (hiPSC) holds great potential for application in regenerative medicine, pharmacological drug screening, and toxicity testing. However, full maturation of hiPSC into functional hepatocytes has not yet been achieved. In this study, we investigated the potential of a dynamic three-dimensional (3D) hollow fiber membrane bioreactor technology to improve the hepatic differentiation of hiPSC in comparison to static two-dimensional (2D) cultures. A total of 100 × 106 hiPSC were seeded into each 3D bioreactor (n = 3). Differentiation into definitive endoderm (DE) was induced by adding activin A, Wnt3a, and sodium butyrate to the culture medium. For further maturation, hepatocyte growth factor and oncostatin M were added. The same differentiation protocol was applied to hiPSC maintained in 2D cultures. Secretion of alpha-fetoprotein (AFP), a marker for DE, was significantly (p < 0.05) higher in 2D cultures, while secretion of albumin, a typical characteristic for mature hepatocytes, was higher after hepatic differentiation of hiPSC in 3D bioreactors. Functional analysis of multiple cytochrome P450 (CYP) isoenzymes showed activity of CYP1A2, CYP2B6, and CYP3A4 in both groups, although at a lower level compared to primary human hepatocytes (PHH). CYP2B6 activities were significantly (p < 0.05) higher in 3D bioreactors compared with 2D cultures, which is in line with results from gene expression. Immunofluorescence staining showed that the majority of cells was positive for albumin, cytokeratin 18 (CK18), and hepatocyte nuclear factor 4-alpha (HNF4A) at the end of the differentiation process. In addition, cytokeratin 19 (CK19) staining revealed the formation of bile duct-like structures in 3D bioreactors similar to native liver tissue. The results indicate a better maturation of hiPSC in the 3D bioreactor system compared to 2D cultures and emphasize the potential of dynamic 3D culture

  11. Characterization of technetium-99m-L,L-ECD for brain perfusion imaging, Part 2: Biodistribution and brain imaging in humans.

    PubMed

    Léveillé, J; Demonceau, G; De Roo, M; Rigo, P; Taillefer, R; Morgan, R A; Kupranick, D; Walovitch, R C

    1989-11-01

    The safety, biodistribution and kinetics of a new perfusion imaging agent [99mTc-L,L]-ethyl cysteinate dimer (ECD) was evaluated in normal volunteers. Technetium-99m-L,L-ECD is a neutral, lipophilic complex, which is radiochemically pure and stable. Twelve healthy adults were injected with 25-30 mCi of 99mTc-L,L-ECD and imaged periodically for up to 24 hr. Planar imaging showed rapid brain uptake with a peak concentration of 4.9% injected dose and very slow brain washout (approximately 6% per hour during the first 6 hr). Repeat or dynamic tomographic imaging of the brain using either a rotating gamma camera or a multidetector system was performed up to 6 hr postinjection. The distribution of 99mTc-L,L-ECD in the brain did not change and was similar to the pattern seen with other perfusion agents. Background facial areas and lungs cleared rapidly. Peak blood activity was below 10% injected dose at all times and 99mTc-L,L-ECD cleared rapidly through the kidneys. Vital signs, blood and urine chemistries were normal in all volunteers and no adverse reactions were noted. These results suggest that 99mTc-L,L-ECD should be useful for routine assessment of cerebral perfusion in humans.

  12. Association of frontal gray matter volume and cerebral perfusion in heroin addiction: a multimodal neuroimaging study.

    PubMed

    Denier, Niklaus; Schmidt, André; Gerber, Hana; Schmid, Otto; Riecher-Rössler, Anita; Wiesbeck, Gerhard A; Huber, Christian G; Lang, Undine E; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan

    2013-01-01

    Structure and function are closely related in the healthy human brain. In patients with chronic heroin exposure, brain imaging studies have identified long-lasting changes in gray matter (GM) volume. More recently, we showed that acute application of heroin in dependent patients results in hypoperfusion of fronto-temporal areas compared with the placebo condition. However, the relationship between structural and cerebral blood flow (CBF) changes in heroin addiction has not yet been investigated. Moreover, it is not known whether there is any interaction between the chronic structural changes and the short and long-term effects on perfusion caused by heroin. Using a double-blind, within-subject design, heroin or placebo (saline) was administered to 14 heroin-dependent patients from a stable heroin-assisted treatment program, in order to observe acute short-term effects. Arterial spin labeling (ASL) was used to calculate perfusion quantification maps in both treatment conditions, while Voxel-Based Morphometry (VBM) was conducted to calculate regional GM density. VBM and ASL data were used to calculate homologous correlation fields by Biological Parametric Mapping (BPM) and a whole-brain Pearson r correlation. We correlated each perfusion condition (heroin and placebo) separately with a VBM sample that was identical for the two treatment conditions. It was assumed that heroin-associated perfusion is manifested in short-term effects, while placebo-associated perfusion is more related to long-term effects. In order to restrict our analyses to fronto-temporal regions, we used an explicit mask for our analyses. Correlation analyses revealed a significant positive correlation in frontal areas between GM and both perfusion conditions (heroin and placebo). Heroin-associated perfusion was also negatively correlated with GM in the inferior temporal gyrus on both hemispheres. These findings indicate that, in heroin-dependent patients, low GM volume is positively associated with

  13. Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

    PubMed Central

    Hoven-Gondrie, Miriam L.; Thijssens, Katja M. J.; Van den Dungen, Jan J. A. M.; Loonstra, Jan; van Ginkel, Robert J.

    2007-01-01

    Background Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated. Methods Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up. Results Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17–159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50–1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91–1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1–23.9 vs. median, 7.35; range, 4.8–21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0–21.4 vs. median, 10.95; range, 8.0–32.6; P < .0005). In patients with follow-up of >5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011). Conclusions ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity. PMID:17457649

  14. Non-contrast-enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRI.

    PubMed

    Bauman, Grzegorz; Puderbach, Michael; Deimling, Michael; Jellus, Vladimir; Chefd'hotel, Christophe; Dinkel, Julien; Hintze, Christian; Kauczor, Hans-Ulrich; Schad, Lothar R

    2009-09-01

    Assessment of regional lung perfusion and ventilation has significant clinical value for the diagnosis and follow-up of pulmonary diseases. In this work a new method of non-contrast-enhanced functional lung MRI (not dependent on intravenous or inhalative contrast agents) is proposed. A two-dimensional (2D) true fast imaging with steady precession (TrueFISP) pulse sequence (TR/TE = 1.9 ms/0.8 ms, acquisition time [TA] = 112 ms/image) was implemented on a 1.5T whole-body MR scanner. The imaging protocol comprised sets of 198 lung images acquired with an imaging rate of 3.33 images/s in coronal and sagittal view. No electrocardiogram (ECG) or respiratory triggering was used. A nonrigid image registration algorithm was applied to compensate for respiratory motion. Rapid data acquisition allowed observing intensity changes in corresponding lung areas with respect to the cardiac and respiratory frequencies. After a Fourier analysis along the time domain, two spectral lines corresponding to both frequencies were used to calculate the perfusion- and ventilation-weighted images. The described method was applied in preliminary studies on volunteers and patients showing clinical relevance to obtain non-contrast-enhanced perfusion and ventilation data.

  15. Role of hypothermic machine perfusion in liver transplantation.

    PubMed

    Schlegel, Andrea; Dutkowski, Philipp

    2015-06-01

    Machine liver perfusion has significantly evolved during the last ten years to optimize extended criteria liver grafts and to address the worldwide organ shortage. This review gives an overview on available ex vivo and in vivo data on hypothermic machine liver perfusion. We discuss also possible protective pathways and show most recent clinical applications of hypothermic machine liver perfusion in human.

  16. The human milk oligosaccharide 2'-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine.

    PubMed

    Good, Misty; Sodhi, Chhinder P; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B; Martin, Laura Y; Prindle, Thomas; Nino, Diego F; Zhou, Qinjie; Ma, Congrong; Ozolek, John A; Buck, Rachael H; Goehring, Karen C; Hackam, David J

    2016-10-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2'FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2'FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2'FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2'FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2'FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2'FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.

  17. Creation of an ensemble of simulated cardiac cases and a human observer study: tools for the development of numerical observers for SPECT myocardial perfusion imaging

    NASA Astrophysics Data System (ADS)

    O'Connor, J. Michael; Pretorius, P. Hendrik; Gifford, Howard C.; Licho, Robert; Joffe, Samuel; McGuiness, Matthew; Mehurg, Shannon; Zacharias, Michael; Brankov, Jovan G.

    2012-02-01

    Our previous Single Photon Emission Computed Tomography (SPECT) myocardial perfusion imaging (MPI) research explored the utility of numerical observers. We recently created two hundred and eighty simulated SPECT cardiac cases using Dynamic MCAT (DMCAT) and SIMIND Monte Carlo tools. All simulated cases were then processed with two reconstruction methods: iterative ordered subset expectation maximization (OSEM) and filtered back-projection (FBP). Observer study sets were assembled for both OSEM and FBP methods. Five physicians performed an observer study on one hundred and seventy-nine images from the simulated cases. The observer task was to indicate detection of any myocardial perfusion defect using the American Society of Nuclear Cardiology (ASNC) 17-segment cardiac model and the ASNC five-scale rating guidelines. Human observer Receiver Operating Characteristic (ROC) studies established the guidelines for the subsequent evaluation of numerical model observer (NO) performance. Several NOs were formulated and their performance was compared with the human observer performance. One type of NO was based on evaluation of a cardiac polar map that had been pre-processed using a gradient-magnitude watershed segmentation algorithm. The second type of NO was also based on analysis of a cardiac polar map but with use of a priori calculated average image derived from an ensemble of normal cases.

  18. Quantification of absolute myocardial perfusion at rest and during exercise with positron emission tomography after human cardiac transplantation

    SciTech Connect

    Krivokapich, J.; Stevenson, L.W.; Kobashigawa, J.; Huang, S.C.; Schelbert, H.R. )

    1991-08-01

    The maximal exercise capacity of cardiac transplant recipients is reduced compared with that of normal subjects. To determine if this reduced exercise capacity is related to inadequate myocardial perfusion during exercise, myocardial perfusion was measured noninvasively with use of positron emission tomography and nitrogen (N)-13 ammonia. Twelve transplant recipients with no angiographic evidence of accelerated coronary atherosclerosis were studied. Serial N-13 ammonia imaging was performed at rest and during supine bicycle exercise. The results were compared with those from 10 normal volunteers with a low probability of having cardiac disease. A two-compartment kinetic model for estimating myocardial perfusion was applied to the data. Transplant recipients achieved a significant lower exercise work load than did the volunteers (42 {plus minus} 16 vs. 128 {plus minus} 22 W), but a higher venous lactate concentration (31.3 {plus minus} 14.9 vs. 13.7 {plus minus} 4.1 mg/100 ml). Despite the difference in exercise work load, there was no significant difference in the cardiac work achieved by transplant recipients and normal subjects as evidenced by similar rate-pressure products of 24,000 {plus minus} 3,400 versus 21,300 {plus minus} 2,800 betas/min per mm Hg, respectively. In addition, myocardial blood flow during exercise was not significantly different between the two groups (1.70 {plus minus} 0.60 vs. 1.56 {plus minus} 0.71 ml/min per g, respectively). This study demonstrates that the myocardial flow response to the physiologic stress of exercise is appropriate in transplant recipients and does not appear to explain the decreased exercise capacity in these patients.

  19. Tubular perfusion system culture of human mesenchymal stem cells on poly-l-lactic acid scaffolds produced using a supercritical carbon dioxide-assisted process

    PubMed Central

    Pisanti, Paola; Yeatts, Andrew B.; Cardea, Stefano; Fisher, John P.; Reverchon, Ernesto

    2012-01-01

    In vitro human mesenchymal stem cell (hMSC) proliferation and differentiation is dependent on scaffold design parameters and specific culture conditions. In this study, we investigate how scaffold microstructure influences hMSC behavior in a perfusion bioreactor system. Poly-l-lactic acid (PLLA) scaffolds are fabricated using supercritical carbon dioxide (SC-CO2) gel drying. This production method results in scaffolds fabricated with nanostructure. To introduce a microporous structure, porogen leaching was used in addition to this technique to produce scaffolds of average pore size of 100, 250, and 500 µm. These scaffolds were then cultured in static culture in well plates or dynamic culture in the tubular perfusion system (TPS) bioreactor. Results indicated that hMSCs were able to attach and maintain viability on all scaffolds with higher proliferation in the 250 µm and 500 µm pore sizes of bioreactor cultured scaffolds and 100 µm pore size of statically cultured scaffolds. Osteoblastic differentiation was enhanced in TPS culture as compared to static culture with the highest alkaline phosphatase expression observed in the 250 µm pore size group. Bone morphogenetic protein-2 was also analyzed and expression levels were highest in the 250 µm and 500 µm pore size bioreactor cultured samples. These results demonstrate cellular response to pore size as well as the ability of dynamic culture to enhance these effects. PMID:22528808

  20. Kidneys From α1,3-Galactosyltransferase Knockout/Human Heme Oxygenase-1/Human A20 Transgenic Pigs Are Protected From Rejection During Ex Vivo Perfusion With Human Blood

    PubMed Central

    Ahrens, Hellen E.; Petersen, Björn; Ramackers, Wolf; Petkov, Stoyan; Herrmann, Doris; Hauschild-Quintern, Janet; Lucas-Hahn, Andrea; Hassel, Petra; Ziegler, Maren; Baars, Wiebke; Bergmann, Sabine; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2015-01-01

    Background Multiple modifications of the porcine genome are required to prevent rejection after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout of the α1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase-1 and A20, and investigated their xenoprotective properties. Methods The GGTA1-KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1 gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and sequencing. The biological function of the genetic modifications was tested in a 51Chromium release assay and by ex vivo kidney perfusions with human blood. Results Disruption of the GGTA1 gene by deletion of few basepairs was demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA expression was confirmed by quantitative reverse-transcription polymerase chain reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum experimental time of 240 minutes without symptoms of rejection. Conclusions Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and could serve as a background for further genetic modifications toward the production of a donor pig that is clinically relevant for xenotransplantation. PMID:27500225

  1. Effects of KATP channel openers diazoxide and pinacidil in coronary-perfused atria and ventricles from failing and non-failing human hearts

    PubMed Central

    Fedorov, Vadim V.; Glukhov, Alexey V.; Ambrosi, Christina M.; Kostecki, Geran; Chang, Roger; Janks, Deborah; Schuessler, Richard B.; Moazami, Nader; Nichols, Colin G.; Efimov, Igor R.

    2011-01-01

    INTRODUCTION This study compared the effects of ATP-regulated potassium channel (KATP) openers, diazoxide and pinacidil, on diseased and normal human atria and ventricles. METHODS We optically mapped the endocardium of coronary-perfused right (n=11) or left (n=2) posterior atrial-ventricular free wall preparations from human hearts with congestive heart failure (CHF, n=8) and non-failing human hearts without (NF, n=3) or with (INF, n=2) infarction. We also analyzed the mRNA expression of the KATP targets Kir6.1, Kir6.2, SUR1, and SUR2 in the left atria and ventricles of NF (n=8) and CHF (n=4) hearts. RESULTS In both CHF and INF hearts, diazoxide significantly decreased action potential durations (APDs) in atria (by −21±3% and −27±13%, p<0.01) and ventricles (by −28±7% and −28±4%, p<0.01). Diazoxide did not change APD (0±5%) in NF atria. Pinacidil significantly decreased APDs in both atria (−46 to - 80%, p<0.01) and ventricles (−65 to −93%, p<0.01) in all hearts studied. The effect of pinacidil on APD was significantly higher than that of diazoxide in both atria and ventricles of all groups (p<0.05). During pinacidil perfusion, burst pacing induced flutter/fibrillation in all atrial and ventricular preparations with dominant frequencies of 14.4±6.1 Hz and 17.5 ±5.1 Hz, respectively. Glibenclamide (10 μM) terminated these arrhythmias and restored APDs to control values. Relative mRNA expression levels of KATP targets were correlated to functional observations. CONCLUSION Remodeling in response to CHF and/or previous infarct potentiated diazoxide-induced APD shortening. The activation of atrial and ventricular KATP channels enhances arrhythmogenicity, suggesting that such activation may contribute to reentrant arrhythmias in ischemic hearts. PMID:21586291

  2. Morpheus - Hypometabolic Stasis in Humans for Long term Space Flight

    NASA Astrophysics Data System (ADS)

    Ayre, M.; Zancanaro, C.; Malatesta, M.

    An overview of the application of hypometabolic stasis (HS) to humans for long-term space flight is presented. In the first section, the paper begins with a discussion of why HS in humans would be, from a resource-driven perspective, desirable during long-term space flight. The second section then reviews mammalian hibernation, covering behavioural, physiological and genetic strategies. The third part presents a general review of the effects on human physiology of the space environment, and the overlapping areas between the likely physiological effects of human-hibernation and the space environment are briefly discussed. In the fourth section, possible hibernation strategies for humans are considered, including pharmacological, genetic and environ- mental tactics. The fifth section briefly discusses the impact of human hibernation at a system level, particularly with regards to life support. The report finishes by concluding that the achievement of the goal of human hibernation on the Earth will probably take decades of research. Hibernation in space, with the concomitant increases in the complexity of the problem caused by the space environment, will be substantially more difficult to achieve. But, if realised, it will be of significant benefit to the extension of human presence in space.

  3. Multiphoton imaging reveals that nanosecond pulsed electric fields collapse tumor and normal vascular perfusion in human glioblastoma xenografts

    PubMed Central

    Bardet, Sylvia M.; Carr, Lynn; Soueid, Malak; Arnaud-Cormos, Delia; Leveque, Philippe; O’Connor, Rodney P.

    2016-01-01

    Despite the biomedical advances of the last century, many cancers including glioblastoma are still resistant to existing therapies leaving patients with poor prognoses. Nanosecond pulsed electric fields (nsPEF) are a promising technology for the treatment of cancer that have thus far been evaluated in vitro and in superficial malignancies. In this paper, we develop a tumor organoid model of glioblastoma and apply intravital multiphoton microscopy to assess their response to nsPEFs. We demonstrate for the first time that a single 10 ns, high voltage electric pulse (35–45 kV/cm), collapses the perfusion of neovasculature, and also alters the diameter of capillaries and larger vessels in normal tissue. These results contribute to the fundamental understanding of nsPEF effects in complex tissue environments, and confirm the potential of nsPEFs to disrupt the microenvironment of solid tumors such as glioblastoma. PMID:27698479

  4. Noninvasive estimation of oxygen consumption in human calf muscle through combined NMR measurements of ASL perfusion and T₂ oxymetry.

    PubMed

    Decorte, Nicolas; Buehler, Tania; Caldas de Almeida Araujo, Ericky; Vignaud, Alexandre; Carlier, Pierre G

    2014-01-01

    The objective of this work was to demonstrate the feasibility of measuring muscle O2 consumption (V˙O2) noninvasively with a combination of functional nuclear magnetic resonance (NMR) imaging methods, and to verify that changes in muscle V˙O2 can be detected with a temporal resolution compatible with physiological investigation and patient ease. T2-based oxymetry of arterial and venous blood was combined with the arterial-spin labeling (ASL)-based determination of muscle perfusion. These measurements were performed on 8 healthy volunteers under normoxic and hypoxic conditions in order to assess the sensitivity of measurements over a range of saturation values. Blood samples were drawn simultaneously and used to titrate blood T2 measurements versus hemoglobin O2 saturation (%HbO2) in vitro. The in vitro calibration curve of blood T2 fitted very well with the %HbO2 (r(2): 0.95). The in vivo venous T2 measurements agreed well with the in vitro measurements (intraclass correlation coefficient 0.82, 95% confidence interval 0.61-0.91). Oxygen extraction at rest decreased in the calf muscles subjected to hypoxia (p = 0.031). The combination of unaltered muscle perfusion and pinched arteriovenous O2 difference (p = 0.038) pointed towards a reduced calf muscle V˙O2 during transient hypoxia (p = 0.018). The results of this pilot study confirmed that muscle O2 extraction and V˙O2 can be estimated noninvasively using a combination of functional NMR techniques. Further studies are needed to confirm the usefulness in a larger sample of volunteers and patients.

  5. The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine

    PubMed Central

    Good, Misty; Sodhi, Chhinder P.; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B.; Martin, Laura Y.; Prindle, Thomas; Nino, Diego F.; Zhou, Qinjie; Ma, Congrong; Ozolek, John A.; Buck, Rachael H.; Goehring, Karen C.; Hackam, David J.

    2016-01-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2′-fucosyllactose (2′FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2′FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2′FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2′FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2′FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2′FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2′FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC. PMID:27609061

  6. Steroid hormone effects on intercellular communication between term pregnant human myometrial cells before labor.

    PubMed

    Ciray, H N; Bäckström, T; Ulmsten, U; Roomans, G M

    1996-08-01

    The appearance of gap junctions (GJs) between myometrial smooth muscle cells is one of the major events associated with the onset of labor. We have employed dye-coupling and electrical-current injection techniques to study the mechanisms by which steroid hormones regulate GJs in term pregnant myometrium of women before labor. Progesterone (P4) did not alter the input resistance (Ro) of the tissues when added to Tyrode's solution, which was used as control treatment. Octanol, the putative gap junctional uncoupling agent, increased the Ro of the cells compared to the control and P4-treated groups. The membrane potential (Em) did not differ between these groups. However, when P4 was applied after the tissue was perfused with estradiol (E2), the results changed dramatically: the Em hyperpolarized, and the Ro increased. Octanol increased the Ro in E2-treated tissues, but did not affect the Em. Consecutive application of E2, octanol, E2, and P4 resulted in rapid changes in the Ro of the cells. Dye-coupling was mostly detected between cells from controls and E2-treated tissues. These results indicate that P4 exerts its effects in the presence of E2 and that P4 has rapid effects on the intercellular communication between human myometrial cells.

  7. Perfusion decellularization of whole organs.

    PubMed

    Guyette, Jacques P; Gilpin, Sarah E; Charest, Jonathan M; Tapias, Luis F; Ren, Xi; Ott, Harald C

    2014-01-01

    The native extracellular matrix (ECM) outlines the architecture of organs and tissues. It provides a unique niche of composition and form, which serves as a foundational scaffold that supports organ-specific cell types and enables normal organ function. Here we describe a standard process for pressure-controlled perfusion decellularization of whole organs for generating acellular 3D scaffolds with preserved ECM protein content, architecture and perfusable vascular conduits. By applying antegrade perfusion of detergents and subsequent washes to arterial vasculature at low physiological pressures, successful decellularization of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using appropriate modifications, pressure-controlled perfusion decellularization can be achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to clinically relevant models (porcine and human organs, 12-14 d). Combining the unique structural and biochemical properties of native acellular scaffolds with subsequent recellularization techniques offers a novel platform for organ engineering and regeneration, for experimentation ex vivo and potential clinical application in vivo.

  8. Evaluation of efficacy and safety for recombinant human adenovirus-p53 in the control of the malignant pleural effusions via thoracic perfusion

    PubMed Central

    Biaoxue, Rong; Hui, Pan; Wenlong, Gao; Shuanying, Yang

    2016-01-01

    A certain number of studies have showed that p53 gene transfer has an anti-tumor activity in vitro and in vivo. This study was to evaluate the efficacy and safety of thoracic perfusion of recombinant human adenovirus p53 (rAd-p53, Gendicine) for controlling malignant pleural effusion (MPE). We searched for the relevant studies from the database of MEDLINE, Web of Science, EMBASE, Cochrance Library and CNKI to collect the trials concerning the efficacy and safety of rAd-p53 to treat MPE. Fourteen randomised controlled trials (RCTs) with 879 patients were involved in this analysis. The rAd-p53 combined with chemotherapeutic agents significantly improved the overall response rate (ORR) (P < 0.001; odds ratio = 3.73) and disease control rate (DCR) (P < 0.001; odds ratio = 2.32) of patients with MPE as well as the quality of life (QOL) of patients (P < 0.001; odds ratio = 4.27), compared with that of chemotherapeutic agents alone. In addition, the participation of rAd-p53 did not have an obvious impact on the most of incidence of adverse reactions (AEs) (P < 0.05) except the fever (P < 0.001). However, the fever was self-limited and could be tolerated well. The application of rAd-p53 through thoracic perfusion for treating MPE had a better efficacy and safety, which could be a potential choice for controlling MPE. PMID:27976709

  9. In anesthetized pigs human chorionic gonadotropin increases myocardial perfusion and function through a β-adrenergic-related pathway and nitric oxide.

    PubMed

    Grossini, Elena; Surico, Daniela; Mary, David A S G; Molinari, Claudio; Surico, Nicola; Vacca, Giovanni

    2013-08-15

    Human chorionic gonadotropin (hCG) is not only responsible for numerous pregnancy-related processes, but can affect the cardiovascular system as well. So far, however, information about any direct effect elicited by hCG on cardiac function, perfusion, and the mechanisms involved has remained scarce. Therefore, the present study aimed to determine the primary in vivo effect of hCG on cardiac contractility and coronary blood flow and the involvement of autonomic nervous system and nitric oxide (NO). Moreover, in coronary endothelial cells (CEC), the intracellular pathways involved in the effects of hCG on NO release were also examined. In 25 anesthetized pigs, intracoronary 500 mU/ml hCG infusion at constant heart rate and aortic blood pressure increased coronary blood flow, maximum rate of change of left ventricular systolic pressure, segmental shortening, cardiac output, and coronary NO release (P < 0.0001). These hemodynamic responses were graded in a further five pigs. Moreover, while blockade of muscarinic cholinoceptors (n = 5) and of α-adrenoceptors (n = 5) did not abolish the observed responses, β1-adrenoceptors blocker (n = 5) prevented the effects of hCG on cardiac function. In addition, β2-adrenoceptors (n = 5) and NO synthase inhibition (n = 5) abolished the coronary response and the effect of hCG on NO release. In CEC, hCG induced the phosphorylation of endothelial NO synthase through cAMP/PKA signaling and ERK1/2, Akt, p38 MAPK involvement, which were activated as downstream effectors of β2-adrenoceptor stimulation. In conclusion, in anesthetized pigs, hCG primarily increased cardiac function and perfusion through the involvement of β-adrenoceptors and NO release. Moreover, cAMP/PKA-dependent kinases phosphorylation was found to play a role in eliciting the observed NO production in CEC.

  10. The evolution of human cells in terms of protein innovation.

    PubMed

    Sardar, Adam J; Oates, Matt E; Fang, Hai; Forrest, Alistair R R; Kawaji, Hideya; Gough, Julian; Rackham, Owen J L

    2014-06-01

    Humans are composed of hundreds of cell types. As the genomic DNA of each somatic cell is identical, cell type is determined by what is expressed and when. Until recently, little has been reported about the determinants of human cell identity, particularly from the joint perspective of gene evolution and expression. Here, we chart the evolutionary past of all documented human cell types via the collective histories of proteins, the principal product of gene expression. FANTOM5 data provide cell-type-specific digital expression of human protein-coding genes and the SUPERFAMILY resource is used to provide protein domain annotation. The evolutionary epoch in which each protein was created is inferred by comparison with domain annotation of all other completely sequenced genomes. Studying the distribution across epochs of genes expressed in each cell type reveals insights into human cellular evolution in terms of protein innovation. For each cell type, its history of protein innovation is charted based on the genes it expresses. Combining the histories of all cell types enables us to create a timeline of cell evolution. This timeline identifies the possibility that our common ancestor Coelomata (cavity-forming animals) provided the innovation required for the innate immune system, whereas cells which now form the brain of human have followed a trajectory of continually accumulating novel proteins since Opisthokonta (boundary of animals and fungi). We conclude that exaptation of existing domain architectures into new contexts is the dominant source of cell-type-specific domain architectures.

  11. Human cervicovaginal fluid biomarkers to predict term and preterm labor

    PubMed Central

    Heng, Yujing J.; Liong, Stella; Permezel, Michael; Rice, Gregory E.; Di Quinzio, Megan K. W.; Georgiou, Harry M.

    2015-01-01

    Preterm birth (PTB; birth before 37 completed weeks of gestation) remains the major cause of neonatal morbidity and mortality. The current generation of biomarkers predictive of PTB have limited utility. In pregnancy, the human cervicovaginal fluid (CVF) proteome is a reflection of the local biochemical milieu and is influenced by the physical changes occurring in the vagina, cervix and adjacent overlying fetal membranes. Term and preterm labor (PTL) share common pathways of cervical ripening, myometrial activation and fetal membranes rupture leading to birth. We therefore hypothesize that CVF biomarkers predictive of labor may be similar in both the term and preterm labor setting. In this review, we summarize some of the existing published literature as well as our team's breadth of work utilizing the CVF for the discovery and validation of putative CVF biomarkers predictive of human labor. Our team established an efficient method for collecting serial CVF samples for optimal 2-dimensional gel electrophoresis resolution and analysis. We first embarked on CVF biomarker discovery for the prediction of spontaneous onset of term labor using 2D-electrophoresis and solution array multiple analyte profiling. 2D-electrophoretic analyses were subsequently performed on CVF samples associated with PTB. Several proteins have been successfully validated and demonstrate that these biomarkers are associated with term and PTL and may be predictive of both term and PTL. In addition, the measurement of these putative biomarkers was found to be robust to the influences of vaginal microflora and/or semen. The future development of a multiple biomarker bed-side test would help improve the prediction of PTB and the clinical management of patients. PMID:26029118

  12. A Long-term Co-perfused Disseminated Tuberculosis-3D Liver Hollow Fiber Model for Both Drug Efficacy and Hepatotoxicity in Babies

    PubMed Central

    Srivastava, Shashikant; Pasipanodya, Jotam G.; Ramachandran, Geetha; Deshpande, Devyani; Shuford, Stephen; Crosswell, Howland E.; Cirrincione, Kayle N.; Sherman, Carleton M.; Swaminathan, Soumya; Gumbo, Tawanda

    2016-01-01

    Treatment of disseminated tuberculosis in children ≤ 6 years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose–response studies in children. We designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for efficacy and toxicity. We utilized pediatric pharmacokinetics of pyrazinamide and acetaminophen to determine dose-dependent pyrazinamide efficacy and hepatotoxicity. Acetaminophen concentrations that cause hepatotoxicity in children led to elevated liver function tests, while 100 mg/kg pyrazinamide did not. Surprisingly, pyrazinamide did not kill intracellular Mycobacterium tuberculosis up to fourfold the standard dose as monotherapy or as combination therapy, despite achieving high intracellular concentrations. Host-pathogen RNA-sequencing revealed lack of a pyrazinamide exposure transcript signature in intracellular bacteria or of phagolysosome acidification on pH imaging. Artificial intelligence algorithms confirmed that pyrazinamide was not predictive of good clinical outcomes in children ≤ 6 years who had extrapulmonary tuberculosis. Thus, adding a drug that works inside macrophages could benefit children with disseminated tuberculosis. Our in vitro model can be used to identify such new regimens that could accelerate cure while minimizing toxicity. PMID:27211555

  13. A Long-term Co-perfused Disseminated Tuberculosis-3D Liver Hollow Fiber Model for Both Drug Efficacy and Hepatotoxicity in Babies.

    PubMed

    Srivastava, Shashikant; Pasipanodya, Jotam G; Ramachandran, Geetha; Deshpande, Devyani; Shuford, Stephen; Crosswell, Howland E; Cirrincione, Kayle N; Sherman, Carleton M; Swaminathan, Soumya; Gumbo, Tawanda

    2016-04-01

    Treatment of disseminated tuberculosis in children≤6years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose-response studies in children. We designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for efficacy and toxicity. We utilized pediatric pharmacokinetics of pyrazinamide and acetaminophen to determine dose-dependent pyrazinamide efficacy and hepatotoxicity. Acetaminophen concentrations that cause hepatotoxicity in children led to elevated liver function tests, while 100mg/kg pyrazinamide did not. Surprisingly, pyrazinamide did not kill intracellular Mycobacterium tuberculosis up to fourfold the standard dose as monotherapy or as combination therapy, despite achieving high intracellular concentrations. Host-pathogen RNA-sequencing revealed lack of a pyrazinamide exposure transcript signature in intracellular bacteria or of phagolysosome acidification on pH imaging. Artificial intelligence algorithms confirmed that pyrazinamide was not predictive of good clinical outcomes in children≤6years who had extrapulmonary tuberculosis. Thus, adding a drug that works inside macrophages could benefit children with disseminated tuberculosis. Our in vitro model can be used to identify such new regimens that could accelerate cure while minimizing toxicity.

  14. Abdominal perfusion computed tomography.

    PubMed

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-02-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis.

  15. Abdominal Perfusion Computed Tomography

    PubMed Central

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M. Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-01-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis. PMID:25610249

  16. Short-term and long-term plasticity interaction in human primary motor cortex.

    PubMed

    Iezzi, Ennio; Suppa, Antonio; Conte, Antonella; Li Voti, Pietro; Bologna, Matteo; Berardelli, Alfredo

    2011-05-01

    Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1.

  17. Lipopolysaccharide induces the expression of interleukin-1alpha distinctly in different compartments of term and preterm human placentae.

    PubMed

    Huleihel, Mahmoud; Amash, Alaa; Sapir, Olga; Maor, Ester; Levy, Sharon; Katz, Miriam; Dukler, Doron; Myatt, Lesly; Holcberg, Gershon

    2004-01-01

    The aim of the study was to investigate the stimulatory effect of lipopolysaccharide (LPS) on IL-lalpha production in different compartments of term and preterm placental tissues. Homogenates from amnion, chorion, and from fetal (subchorionic placental tissues, maternal decidua, and mid-placental tissue before and after perfusion of isolated placental cotyledons of 5 term placentas and 4 placentas obtained after preterm birth (28-34 W of gestation) were examined. Isolated placental cotyledons were dually perfused LPS (100 ng/kg perfused placental tissue) was perfused into the maternal side during 10 hours. Homogenates of the samples were examined by ELISA for IL-1alpha levels, and paraffin sections of the samples were stained by immunohistochemical staining, to characterize the cellular origin of placental IL-1alpha. Paired t test and ANOVA determined statistical significance. In the homogenates, there was a tendency towards higher IL-lalpha levels in all preterm placental compartments as compared to the term compartments before perfusion. A significant increase was observed only in the chorion compartment (p = 0.035). LPS had significantly increased IL-la levels only in the decidua compartment of term placentas as compared to other placental compartments (p = 0.0004), and had decreased IL-1alpha levels in the mid-placenta (p = 0.034). In preterm placentas, addition of LPS did not affect the expression levels of IL-1alpha in either fetal or maternal compartments as determined by ELISA and immunohistochemical staining. IL-la levels in the chorion compartment of preterm placenta were significantly higher as compared to term placenta. LPS affects placental tissues of term and preterm placentas differently. Also, in the term placentas, LPS affected the different compartments differently. Thus, IL-1alpha may have a key role (as a autocrine/paracrine factor) in the regulation of normal and pathological pregnancy and parturition.

  18. Hepatic Differentiation and Maturation of Human Embryonic Stem Cells Cultured in a Perfused Three-Dimensional Bioreactor

    PubMed Central

    Synnergren, Jane; Jensen, Janne; Björquist, Petter; Ingelman-Sundberg, Magnus

    2013-01-01

    Drug-induced liver injury is a serious and frequently occurring adverse drug reaction in the clinics and is hard to predict during preclinical studies. Today, primary hepatocytes are the most frequently used cell model for drug discovery and prediction of toxicity. However, their use is marred by high donor variability regarding drug metabolism and toxicity, and instable expression levels of liver-specific genes such as cytochromes P450. An in vitro model system based on human embryonic stem cells (hESC), with their unique properties of pluripotency and self-renewal, has potential to provide a stable and unlimited supply of human hepatocytes. Much effort has been made to direct hESC toward the hepatic lineage, mostly using 2-dimensional (2D) cultures. Although the results are encouraging, these cells lack important functionality. Here, we investigate if hepatic differentiation of hESC can be improved by using a 3-dimensional (3D) bioreactor system. Human ESCs were differentiated toward the hepatic lineage using the same cells in either the 3D or 2D system. A global transcriptional analysis identified important differences between the 2 differentiation regimes, and we identified 10 pathways, highly related to liver functions, which were significantly upregulated in cells differentiated in the bioreactor compared to 2D control cultures. The enhanced hepatic differentiation observed in the bioreactor system was also supported by immunocytochemistry. Taken together, our results suggest that hepatic differentiation of hESC is improved when using this 3D bioreactor technology as compared to 2D culture systems. PMID:22970843

  19. In Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System.

    PubMed

    Knöspel, Fanny; Jacobs, Frank; Freyer, Nora; Damm, Georg; De Bondt, An; van den Wyngaert, Ilse; Snoeys, Jan; Monshouwer, Mario; Richter, Marco; Strahl, Nadja; Seehofer, Daniel; Zeilinger, Katrin

    2016-04-16

    Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR)), while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR) metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro.

  20. In Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System

    PubMed Central

    Knöspel, Fanny; Jacobs, Frank; Freyer, Nora; Damm, Georg; De Bondt, An; van den Wyngaert, Ilse; Snoeys, Jan; Monshouwer, Mario; Richter, Marco; Strahl, Nadja; Seehofer, Daniel; Zeilinger, Katrin

    2016-01-01

    Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR)), while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR) metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro. PMID:27092500

  1. ARISTOLOCHIC ACID I METABOLISM IN THE ISOLATED PERFUSED RAT KIDNEY

    PubMed Central

    Priestap, Horacio A.; Torres, M. Cecilia; Rieger, Robert A.; Dickman, Kathleen G.; Freshwater, Tomoko; Taft, David R.; Barbieri, Manuel A.; Iden, Charles R.

    2012-01-01

    Aristolochic acids are natural nitro-compounds found globally in the plant genus Aristolochia that have been implicated in the severe illness in humans termed aristolochic acid nephropathy (AAN). Aristolochic acids undergo nitroreduction, among other metabolic reactions, and active intermediates arise that are carcinogenic. Previous experiments with rats showed that aristolochic acid I (AA-I), after oral administration or injection, is subjected to detoxication reactions to give aristolochic acid Ia, aristolactam Ia, aristolactam I and their glucuronide and sulfate conjugates that can be found in urine and faeces. Results obtained with whole rats do not clearly define the role of liver and kidney in such metabolic transformation. In this study, in order to determine the specific role of the kidney on the renal disposition of AA-I and to study the biotransformations suffered by AA-I in this organ, isolated kidneys of rats were perfused with AA-I. AA-I and metabolite concentrations were determined in perfusates and urines using HPLC procedures. The isolated perfused rat kidney model showed that AA-I distributes rapidly and extensively in kidney tissues by uptake from the peritubular capillaries and the tubules. It was also established that the kidney is able to metabolize AA-I into aristolochic acid Ia, aristolochic acid Ia O-sulfate, aristolactam Ia, aristolactam I and aristolactam Ia O-glucuronide. Rapid demethylation and sulfation of AA-I in the kidney generate aristolochic acid Ia and its sulfate conjugate that are voided to the urine. Reduction reactions to give the aristolactam metabolites occur to a slower rate. Renal clearances showed that filtered AA-I is reabsorbed at the tubules whereas the metabolites are secreted. The unconjugated metabolites produced in the renal tissues are transported to both urine and perfusate whereas the conjugated metabolites are almost exclusively secreted to the urine. PMID:22118289

  2. Human short-term spatial memory: precision predicts capacity.

    PubMed

    Banta Lavenex, Pamela; Boujon, Valérie; Ndarugendamwo, Angélique; Lavenex, Pierre

    2015-03-01

    Here, we aimed to determine the capacity of human short-term memory for allocentric spatial information in a real-world setting. Young adults were tested on their ability to learn, on a trial-unique basis, and remember over a 1-min interval the location(s) of 1, 3, 5, or 7 illuminating pads, among 23 pads distributed in a 4m×4m arena surrounded by curtains on three sides. Participants had to walk to and touch the pads with their foot to illuminate the goal locations. In contrast to the predictions from classical slot models of working memory capacity limited to a fixed number of items, i.e., Miller's magical number 7 or Cowan's magical number 4, we found that the number of visited locations to find the goals was consistently about 1.6 times the number of goals, whereas the number of correct choices before erring and the number of errorless trials varied with memory load even when memory load was below the hypothetical memory capacity. In contrast to resource models of visual working memory, we found no evidence that memory resources were evenly distributed among unlimited numbers of items to be remembered. Instead, we found that memory for even one individual location was imprecise, and that memory performance for one location could be used to predict memory performance for multiple locations. Our findings are consistent with a theoretical model suggesting that the precision of the memory for individual locations might determine the capacity of human short-term memory for spatial information.

  3. Short-term effects of recombinant human growth hormone and feeding on gluconeogenesis in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    After a short-term fast, lactating women have increased rates of glucose production but not gluconeogenesis (GNG) despite relative hypoinsulinemia. We explored the effects of non-insulin-dependent increase in glucose utilization and recombinant human growth hormone (rhGH) on glucose production, glyc...

  4. Task-based evaluation of a 4D MAP-RBI-EM image reconstruction method for gated myocardial perfusion SPECT using a human observer study

    NASA Astrophysics Data System (ADS)

    Lee, Taek-Soo; Higuchi, Takahiro; Lautamäki, Riikka; Bengel, Frank M.; Tsui, Benjamin M. W.

    2015-09-01

    We evaluated the performance of a new 4D image reconstruction method for improved 4D gated myocardial perfusion (MP) SPECT using a task-based human observer study. We used a realistic 4D NURBS-based Cardiac-Torso (NCAT) phantom that models cardiac beating motion. Half of the population was normal; the other half had a regional hypokinetic wall motion abnormality. Noise-free and noisy projection data with 16 gates/cardiac cycle were generated using an analytical projector that included the effects of attenuation, collimator-detector response, and scatter (ADS), and were reconstructed using the 3D FBP without and 3D OS-EM with ADS corrections followed by different cut-off frequencies of a 4D linear post-filter. A 4D iterative maximum a posteriori rescaled-block (MAP-RBI)-EM image reconstruction method with ADS corrections was also used to reconstruct the projection data using various values of the weighting factor for its prior. The trade-offs between bias and noise were represented by the normalized mean squared error (NMSE) and averaged normalized standard deviation (NSDav), respectively. They were used to select reasonable ranges of the reconstructed images for use in a human observer study. The observers were trained with the simulated cine images and were instructed to rate their confidence on the absence or presence of a motion defect on a continuous scale. We then applied receiver operating characteristic (ROC) analysis and used the area under the ROC curve (AUC) index. The results showed that significant differences in detection performance among the different NMSE-NSDav combinations were found and the optimal trade-off from optimized reconstruction parameters corresponded to a maximum AUC value. The 4D MAP-RBI-EM with ADS correction, which had the best trade-off among the tested reconstruction methods, also had the highest AUC value, resulting in significantly better human observer detection performance when detecting regional myocardial wall motion

  5. Task-Based Evaluation of a 4D MAP-RBI-EM Image Reconstruction Method for Gated Myocardial Perfusion SPECT using a Human Observer Study

    PubMed Central

    Lee, Taek-Soo; Higuchi, Takahiro; Lautamäki, Riikka; Bengel, Frank M.; Tsui, Benjamin M. W.

    2015-01-01

    We evaluated the performance of a new 4D image reconstruction method for improved 4D gated myocardial perfusion (MP) SPECT using a task-based human observer study. We used a realistic 4D NURBS-based Cardiac-Torso (NCAT) phantom that models cardiac beating motion. Half of the population was normal; the other half had a regional hypokinetic wall motion abnormality. Noise-free and noisy projection data with 16 gates/cardiac cycle were generated using an analytical projector that included the effects of attenuation, collimator-detector response, and scatter (ADS), and were reconstructed using the 3D FBP without and 3D OS-EM with ADS corrections followed by different cut-off frequencies of a 4D linear post-filter. A 4D iterative maximum a posteriori rescaled-block (MAP-RBI)-EM image reconstruction method with ADS corrections was also used to reconstruct the projection data using various values of the weighting factor for its prior. The trade-offs between bias and noise were represented by the normalized mean squared error (NMSE) and averaged normalized standard deviation (NSDav), respectively. They were used to select reasonable ranges of the reconstructed images for use in a human observer study. The observers were trained with the simulated cine images and were instructed to rate their confidence on the absence or presence of a motion defect on a continuous scale. We then applied receiver operating characteristic (ROC) analysis and used the area under the ROC curve (AUC) index. The results showed that significant differences in detection performance among the different NMSE-NSDav combinations were found and the optimal trade-off from optimized reconstruction parameters corresponded to a maximum AUC value. The 4D MAP-RBI-EM with ADS correction, which had the best trade-off among the tested reconstruction methods, also had the highest AUC value, resulting in significantly better human observer detection performance when detecting regional myocardial wall motion

  6. Quantitative myocardial perfusion SPECT.

    PubMed

    Tsui, B M; Frey, E C; LaCroix, K J; Lalush, D S; McCartney, W H; King, M A; Gullberg, G T

    1998-01-01

    In recent years, there has been much interest in the clinical application of attenuation compensation to myocardial perfusion single photon emission computed tomography (SPECT) with the promise that accurate quantitative images can be obtained to improve clinical diagnoses. The different attenuation compensation methods that are available create confusion and some misconceptions. Also, attenuation-compensated images reveal other image-degrading effects including collimator-detector blurring and scatter that are not apparent in uncompensated images. This article presents basic concepts of the major factors that degrade the quality and quantitative accuracy of myocardial perfusion SPECT images, and includes a discussion of the various image reconstruction and compensation methods and misconceptions and pitfalls in implementation. The differences between the various compensation methods and their performance are demonstrated. Particular emphasis is directed to an approach that promises to provide quantitative myocardial perfusion SPECT images by accurately compensating for the 3-dimensional (3-D) attenuation, collimator-detector response, and scatter effects. With advances in the computer hardware and optimized implementation techniques, quantitatively accurate and high-quality myocardial perfusion SPECT images can be obtained in clinically acceptable processing time. Examples from simulation, phantom, and patient studies are used to demonstrate the various aspects of the investigation. We conclude that quantitative myocardial perfusion SPECT, which holds great promise to improve clinical diagnosis, is an achievable goal in the near future.

  7. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  8. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  9. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  10. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  11. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  12. Cardiac tissue engineering using perfusion bioreactor systems

    PubMed Central

    Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana

    2009-01-01

    This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955

  13. Assessment of a new cell culture perfusion apparatus for in vitro chronic toxicity testing. Part 1: technical description.

    PubMed

    Koppelstaetter, Christian; Jennings, Paul; Ryan, Michael P; Morin, Jean-Paul; Hartung, Thomas; Pfaller, Walter

    2004-01-01

    In vitro models for chronic toxicity, defined as a recurring exposure to compounds over a prolonged period of time, are still underrepresented in drug evaluation processes. The classical approach to cell culture is not readily suitable to long term repetitive applications. Therefore, we assessed the use of a commercially available perfusion cell culture apparatus in its applicability to chronic renal toxicity testing and describe the technical aspects of adopting the perfusion cell culture system to our purposes. It was apparent that there is a subtle dynamic difference between human renal proximal tubular cells cultured under perfusion and static conditions as illustrated by the accumulation of lactate dehydrogenase (LDH) and the secondary metabolism of resazurin to hydroresorufin, which occurred only under static conditions. The major achievement was the standardisation of the handling of this system with regard to cell cultivation, pH regulation, temperature regulation, and reproducibility of common toxicity endpoints.

  14. [Portable peristaltic perfusion pumps].

    PubMed

    Magallón Pedrera, I; Soto Torres, I

    1999-11-01

    Portable peristaltic perfusion pumps allow one to administer pharmaceuticals in hospitals as well as in primary health care centers and furthermore these pumps present multiple advantages for patients and their families since they make it possible to carry out treatment in a patient's home while at the same time lowering the costs involved. The authors analyze the most out standing aspects of portable peristaltic perfusion pumps along with their characteristics, installation, programming, and how to turn them on; in addition, the authors list the maintenance care which these pumps require.

  15. High-Pressure Transvenous Perfusion of the Upper Extremity in Human Muscular Dystrophy: A Safety Study with 0.9% Saline

    PubMed Central

    Fan, Zheng; Kocis, Keith; Valley, Robert; Howard, James F.; Chopra, Manisha; Chen, Yasheng; An, Hongyu; Lin, Weili; Muenzer, Joseph; Powers, William

    2015-01-01

    We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity. PMID:25953425

  16. High-Pressure Transvenous Perfusion of the Upper Extremity in Human Muscular Dystrophy: A Safety Study with 0.9% Saline.

    PubMed

    Fan, Zheng; Kocis, Keith; Valley, Robert; Howard, James F; Chopra, Manisha; Chen, Yasheng; An, Hongyu; Lin, Weili; Muenzer, Joseph; Powers, William

    2015-09-01

    We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity.

  17. Short-term effect of antibiotics on human gut microbiota.

    PubMed

    Panda, Suchita; El khader, Ismail; Casellas, Francesc; López Vivancos, Josefa; García Cors, Montserrat; Santiago, Alba; Cuenca, Silvia; Guarner, Francisco; Manichanh, Chaysavanh

    2014-01-01

    From birth onwards, the human gut microbiota rapidly increases in diversity and reaches an adult-like stage at three years of age. After this age, the composition may fluctuate in response to external factors such as antibiotics. Previous studies have shown that resilience is not complete months after cessation of the antibiotic intake. However, little is known about the short-term effects of antibiotic intake on the gut microbial community. Here we examined the load and composition of the fecal microbiota immediately after treatment in 21 patients, who received broad-spectrum antibiotics such as fluoroquinolones and β-lactams. A fecal sample was collected from all participants before treatment and one week after for microbial load and community composition analyses by quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively. Fluoroquinolones and β-lactams significantly decreased microbial diversity by 25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at the phylum level, these antibiotics increased the Bacteroidetes/Firmicutes ratio (p = 0.0007, FDR = 0.002). At the species level, our findings unexpectedly revealed that both antibiotic types increased the proportion of several unknown taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p = 0.0003, FDR<0.016). Furthermore, the average microbial load was affected by the treatment. Indeed, the β-lactams increased it significantly by two-fold (p = 0.04). The maintenance of or possible increase detected in microbial load and the selection of Gram-negative over Gram-positive bacteria breaks the idea generally held about the effect of broad-spectrum antibiotics on gut microbiota.

  18. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung

    PubMed Central

    Sá, Rui Carlos; Theilmann, Rebecca J.; Buxton, Richard B.; Prisk, G. Kim; Hopkins, Susan R.

    2013-01-01

    The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (V̇a/Q̇) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional V̇a/Q̇ ratio, the gravitational gradients in proton density, ventilation, perfusion, and V̇a/Q̇ ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min−1·ml−1) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min−1·ml−1) images to obtain regional V̇a/Q̇ ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (−0.17 ± 0.10 ml·min−1·ml−1·cm−1 supine, −0.040 ± 0.03 prone ml·min−1·ml−1·cm−1, P = 0.02) as was the slope of the perfusion-height relationship (−0.14 ± 0.05 ml·min−1·ml−1·cm−1 supine, −0.08 ± 0.09 prone ml·min−1·ml−1·cm−1, P = 0.02). There was a significant gravitational gradient in V̇a/Q̇ ratio in both postures (P < 0.05) that was less in prone (0.09 ± 0.08 cm−1 supine, 0.04 ± 0.03 cm−1 prone, P = 0.04). The gravitational gradients in ventilation, perfusion, and regional V̇a/Q̇ ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of

  19. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung.

    PubMed

    Henderson, A Cortney; Sá, Rui Carlos; Theilmann, Rebecca J; Buxton, Richard B; Prisk, G Kim; Hopkins, Susan R

    2013-08-01

    The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (Va/Q) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional Va/Q ratio, the gravitational gradients in proton density, ventilation, perfusion, and Va/Q ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min(-1)·ml(-1)) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min(-1)·ml(-1)) images to obtain regional Va/Q ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (-0.17 ± 0.10 ml·min(-1)·ml(-1)·cm(-1) supine, -0.040 ± 0.03 prone ml·min(-1)·ml(-1)·cm(-1), P = 0.02) as was the slope of the perfusion-height relationship (-0.14 ± 0.05 ml·min(-1)·ml(-1)·cm(-1) supine, -0.08 ± 0.09 prone ml·min(-1)·ml(-1)·cm(-1), P = 0.02). There was a significant gravitational gradient in Va/Q ratio in both postures (P < 0.05) that was less in prone (0.09 ± 0.08 cm(-1) supine, 0.04 ± 0.03 cm(-1) prone, P = 0.04). The gravitational gradients in ventilation, perfusion, and regional Va/Q ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of gravity on Va/Q matching.

  20. Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis

    SciTech Connect

    Kahan, A.; Devaux, J.Y.; Amor, B.; Menkes, C.J.; Weber, S.; Nitenberg, A.; Venot, A.; Guerin, F.; Degeorges, M.; Roucayrol, J.C.

    1986-05-29

    Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined.

  1. Free flap rescue using an extracorporeal perfusion device.

    PubMed

    Fichter, Andreas M; Ritschl, Lucas M; Rau, Andrea; Schwarzer, Claudia; von Bomhard, Achim; Wagenpfeil, Stefan; Wolff, Klaus-Dietrich; Mücke, Thomas

    2016-12-01

    The warm ischaemia time of microvascular free flaps is limited. Incalculable events, such as lack of adequate recipient vessels or intraoperative medical emergencies, can lead to prolonged ischaemia and potentially to flap loss. In this study, critically perfused ischaemic or congested flaps were temporarily perfused with an extracorporeal perfusion system until anastomosis could be commenced. Temporary extracorporeal perfusion was performed in 8 radial forearm flaps for 147 ± 52 (range 77-237) minutes. Flap perfusion was assessed using Indocyanine Green fluorescence angiography and combined laser Doppler flowmetry and remission spectroscopy. Results were compared with those of 30 patients who underwent conventional reconstruction with radial forearm flaps. Flap survival, flap microcirculation, postoperative complications, and hospital stay did not differ between groups. We report successful free flap transfer after short-term extracorporeal perfusion for up to 4 h in 8 patient cases. Temporary extracorporeal free flap perfusion reduces the warm ischaemia time in emergency situations and can help to prevent flap failure in critically perfused or congested flaps. The trial is registered with ClinicalTrials.gov, number NCT02449525.

  2. Contactless mapping of rhythmical phenomena in tissue perfusion using PPGI

    NASA Astrophysics Data System (ADS)

    Huelsbusch, Markus; Blazek, Vladimir

    2002-04-01

    This paper presents the experimental setup and preliminary results of a near infrared CCD camera based Photoplethysmography Imaging (PPGI) system, which has been shown to be suitable for contactless and spatially resolved assessment of rhythmical blood volume changes in the skin. To visualize the complex rhythmical patterns in the dermal perfusion the Wavelet Transform is utilized. It is able to jointly assess time and frequency behavior of signals and thus allows to analyze instationary oscillations and variabilities in the different human rhythmics. The presented system is expected to provide new insights into the functional sequences of physiological tissue perfusion as well as of the perfusion status in ulcer formation and wound healing.

  3. A long term model of circulation. [human body

    NASA Technical Reports Server (NTRS)

    White, R. J.

    1974-01-01

    A quantitative approach to modeling human physiological function, with a view toward ultimate application to long duration space flight experiments, was undertaken. Data was obtained on the effect of weightlessness on certain aspects of human physiological function during 1-3 month periods. Modifications in the Guyton model are reviewed. Design considerations for bilateral interface models are discussed. Construction of a functioning whole body model was studied, as well as the testing of the model versus available data.

  4. Neutrophil gelatinase-associated lipocalin, a new biomarker candidate in perfusate of machine-perfused kidneys: a porcine pilot experiment.

    PubMed

    Jochmans, I; Monbaliu, D; Pirenne, J

    2011-11-01

    The enduring kidney graft shortage has led to the increasing use of expanded-criteria donors as well as kidneys donated after cardiac death, triggering the revival of machine perfusion preservation. Indeed, machine perfusion not only preserves these kidneys better than static cold storage, but also has the potential to evaluate them. The presence of certain biomarkers, among them aspartate aminotransferase (AST) and heart-type fatty acid binding protein (H-FABP), has been demonstrated in the perfusate of human kidneys, making them potentially useful as biomarkers of graft quality. Neutrophil gelatinase-associated lipocalin (NGAL) which is believed to be released upon renal tubular cell injury is another biomarker candidate. However, because it is also released from neutrophils, it is currently unclear whether NGAL is a direct or indirect, inflammatory-mediated marker of kidney injury. To resolve this issue we established a pilot experiment to study the concentrations of AST, H-FABP, and NGAL in the perfusates of 6 porcine kidneys that were exposed to incremental periods of warm ischemia before machine perfusion for 22 hours. An ex vivo porcine model was chosen because preclinical large animal work remains necessary to refine machine perfusion technology and because the presence of these markers in perfusates of porcine kidneys had not been shown previously. All 3 biomarkers were detectable in the cold acellular perfusate; their release seemed to be proportionate to the degree of warm injury, albeit that this must be confirmed in a larger sample. In conclusion, NGAL is directly released by ischemically damaged kidneys, independent of neutrophil activation. In addition to NGAL, the determination of AST and H-FABP in perfusates of machine-perfused porcine kidneys is also feasible. Determination of these markers may be added to the arsenal of research tools for preclinical preservation research.

  5. Immunoglobulin M-enriched human intravenous immunoglobulins reduce leukocyte-endothelial cell interactions and attenuate microvascular perfusion failure in normotensive endotoxemia.

    PubMed

    Hoffman, Johannes N; Fertmann, Jan M; Vollmar, Brigitte; Laschke, Matthias W; Jauch, Karl W; Menger, Michael D

    2008-01-01

    Clinical studies indicate potential differences in the efficacy of immunoglobulin (Ig) preparations in patients with sepsis. A recent meta-analysis showed improved survival rates with IgM-enriched Igs. It was the objective of the present study to characterize microcirculatory actions of different clinically used Ig preparations in a rodent endotoxin model by intravital microscopy. Male Syrian golden hamsters 6 to 8 weeks old with a body weight of 60 to 80 g were investigated by intravital fluorescence microscopy. Endotoxemia was induced by administration of 2 mg/kg (i.v.) endotoxin (LPS, Escherichia coli). Two different Ig preparations containing IgM, IgA, and IgG (intravenous IgM group; n = 6; 5 mL Pentaglobin/kg body weight, i.v.) or exclusively IgG (intravenous IgG group; n = 5; 5 mL Flebogamma/kg body weight, i.v.) were applied 5 min before LPS. Saline-treated endotoxemic animals served as controls (control; n = 8). In controls, LPS induced massive leukocyte-endothelial cell interactions, pronounced microvascular leakage, a decrease of systemic platelet count, and distinct capillary perfusion failure (P < 0.05). Both intravenous IgM and IgG reduced venular leakage (P< 0.05) and ameliorated the decrease in platelet count (P < 0.05). Of interest, intravenous IgM was capable of significantly (P< 0.05) reducing leukocyte adhesion in venules. This was associated with normalization of capillary perfusion at 24 h of endotoxemia, whereas intravenous IgG could not prevent LPS-mediated microvascular perfusion failure. We demonstrate that IgM-enriched Igs are superior to IgG alone in attenuating LPS-induced leukocytic inflammation and microcirculatory dysfunction. Our findings can explain better efficacy of IgM-enriched Igs in patients with severe sepsis.

  6. Human sperm chromosomes. Long-term effect of cancer treatment

    SciTech Connect

    Genesca, A.; Caballin, M.R.; Miro, R.; Benet, J.; Bonfill, X.; Egozcue, J. )

    1990-06-01

    The long-term cytogenetic effect of radio- or chemotherapy or both on male germ cells was evaluated by study of the chromosomal abnormalities in spermatozoa of four men treated for cancer 5-18 years earlier. The cytogenetic analysis of 422 sperm metaphases showed no differences in the aneuploidy rate. The incidence of structural chromosome aberrations was 14.0%, however, which is much higher than in controls. Thus, the high incidence of structurally aberrant spermatozoa observed in our long-term study indicates that antitumoral treatments affect stem-cell spermatogonia and that aberrant cells can survive germinal selection and produce abnormal spermatozoa.

  7. Low dose CT perfusion using k-means clustering

    NASA Astrophysics Data System (ADS)

    Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

    2016-03-01

    We aim at improving low dose CT perfusion functional parameters maps and CT images quality, preserving quantitative information. In a dynamic CT perfusion dataset, each voxel is measured T times, where T is the number of acquired time points. In this sense, we can think about a voxel as a point in a T-dimensional space, where the coordinates of the voxels would be the values of its time attenuation curve (TAC). Starting from this idea, a k-means algorithm was designed to group voxels in K classes. A modified guided time-intensity profile similarity (gTIPS) filter was implemented and applied only for those voxels belonging to the same class. The approach was tested on a digital brain perfusion phantom as well as on clinical brain and body perfusion datasets, and compared to the original TIPS implementation. The TIPS filter showed the highest CNR improvement, but lowest spatial resolution. gTIPS proved to have the best combination of spatial resolution and CNR improvement for CT images, while k-gTIPS was superior to both gTIPS and TIPS in terms of perfusion maps image quality. We demonstrate k-means clustering analysis can be applied to denoise dynamic CT perfusion data and to improve functional maps. Beside the promising results, this approach has the major benefit of being independent from the perfusion model employed for functional parameters calculation. No similar approaches were found in literature.

  8. Space Resource Utilization: Near-Term Missions and Long-Term Plans for Human Exploration

    NASA Technical Reports Server (NTRS)

    Sanders, Gerald B.

    2015-01-01

    NASA's Human Exploration Plans: A primary goal of all major space faring nations is to explore space: from the Earth with telescopes, with robotic probes and space telescopes, and with humans. For the US National Aeronautics and Space Administration (NASA), this pursuit is captured in three important strategic goals: 1. Ascertain the content, origin, and evolution of the solar system and the potential for life elsewhere, 2. Extend and sustain human activities across the solar system (especially the surface of Mars), and 3. Create innovative new space technologies for exploration, science, and economic future. While specific missions and destinations are still being discussed as to what comes first, it is imperative for NASA that it foster the development and implementation of new technologies and approaches that make space exploration affordable and sustainable. Critical to achieving affordable and sustainable human exploration beyond low Earth orbit (LEO) is the development of technologies and systems to identify, extract, and use resources in space instead of bringing everything from Earth. To reduce the development and implementation costs for space resource utilization, often called In Situ Resource Utilization (ISRU), it is imperative to work with terrestrial mining companies to spin-in/spin-off technologies and capabilities, and space mining companies to expand our economy beyond Earth orbit. In the last two years, NASA has focused on developing and implementing a sustainable human space exploration program with the ultimate goal of exploring the surface of Mars with humans. The plan involves developing technology and capability building blocks critical for sustained exploration starting with the Space Launch System (SLS) and Orion crew spacecraft and utilizing the International Space Station as a springboard into the solar system. The evolvable plan develops and expands human exploration in phases starting with missions that are reliant on Earth, to

  9. Space Resource Utilization: Near-Term Missions and Long-Term Plans for Human Exploration

    NASA Technical Reports Server (NTRS)

    Sanders, Gerald B.

    2015-01-01

    A primary goal of all major space faring nations is to explore space: from the Earth with telescopes, with robotic probes and space telescopes, and with humans. For the US National Aeronautics and Space Administration (NASA), this pursuit is captured in three important strategic goals: 1. Ascertain the content, origin, and evolution of the solar system and the potential for life elsewhere, 2. Extend and sustain human activities across the solar system (especially the surface of Mars), and 3. Create innovative new space technologies for exploration, science, and economic future. While specific missions and destinations are still being discussed as to what comes first, it is imperative for NASA that it foster the development and implementation of new technologies and approaches that make space exploration affordable and sustainable. Critical to achieving affordable and sustainable human exploration beyond low Earth orbit (LEO) is the development of technologies and systems to identify, extract, and use resources in space instead of bringing everything from Earth. To reduce the development and implementation costs for space resource utilization, often called In Situ Resource Utilization (ISRU), it is imperative to work with terrestrial mining companies to spin-in/spin-off technologies and capabilities, and space mining companies to expand our economy beyond Earth orbit. In the last two years, NASA has focused on developing and implementing a sustainable human space exploration program with the ultimate goal of exploring the surface of Mars with humans. The plan involves developing technology and capability building blocks critical for sustained exploration starting with the Space Launch System (SLS) and Orion crew spacecraft and utilizing the International Space Station as a springboard into the solar system. The evolvable plan develops and expands human exploration in phases starting with missions that are reliant on Earth, to performing ever more challenging and

  10. Long-term population cycles in human societies.

    PubMed

    Turchin, Peter

    2009-04-01

    Human population dynamics are usually conceptualized as either boundless growth or growth to an equilibrium. The implicit assumption underlying these paradigms is that any feedback processes regulating population density, if they exist, operate on a fast-time-scale, and therefore we do not expect to observe population oscillations in human population numbers. This review asks, are population processes in historical and prehistorical human populations characterized by second-order feedback loops, that is, regulation involving lags? If yes, then the implications for forecasting future population change are obvious--what may appear as inexplicable, exogenously driven reverses in population trends may actually be a result of feedbacks operating with substantial time lags. This survey of a variety of historical and archeological data indicates that slow oscillations in population numbers, with periods of roughly two to three centuries, are observed in a number of world regions and historical periods. Next, a potential explanation for this pattern, the demographic-structural theory, is discussed. Finally, the implications of these results for global population forecasts is discussed.

  11. Human Endothelial Cells: Use of Heparin in Cloning and Long-Term Serial Cultivation

    NASA Astrophysics Data System (ADS)

    Thornton, Susan C.; Mueller, Stephen N.; Levine, Elliot M.

    1983-11-01

    Endothelial cells from human blood vessels were cultured in vitro, with doubling times of 17 to 21 hours for 42 to 79 population doublings. Cloned human endothelial cell strains were established for the first time and had similar proliferative capacities. This vigorous cell growth was achieved by addition of heparin to culture medium containing reduced concentrations of endothelial cell growth factor. The routine cloning and long-term culture of human endothelial cells will facilitate studying the human endothelium in vitro.

  12. Harmonic analysis of perfusion pumps.

    PubMed

    Dougherty, F Carroll; Donovan, F M; Townsley, Mary I

    2003-12-01

    The controversy over the use of nonpulsatile versus pulsatile pumps for maintenance of normal organ function during ex vivo perfusion has continued for many years, but resolution has been limited by lack of a congruent mathematical definition of pulsatility. We hypothesized that the waveform frequency and amplitude, as well as the underlying mean distending pressure are all key parameters controlling vascular function. Using discrete Fourier Analysis, our data demonstrate the complexity of the pulmonary arterial pressure waveform in vivo and the failure of commonly available perfusion pumps to mimic in vivo dynamics. In addition, our data show that the key harmonic signatures are intrinsic to the perfusion pumps, are similar for flow and pressure waveforms, and are unchanged by characteristics of the downstream perfusion circuit or perfusate viscosity.

  13. A compact instrument to measure perfusion of vasculature in transplanted maxillofacial free flaps

    NASA Astrophysics Data System (ADS)

    Kolodziejski, Noah J.; Stapels, Christopher J.; McAdams, Daniel R.; Fernandez, Daniel E.; Podolsky, Matthew J.; Farkas, Dana; Ward, Brent B.; Vartarian, Mark; Feinberg, Stephen E.; Lee, Seung Yup; Parikh, Urmi; Mycek, Mary-Ann; Christian, James F.

    2016-03-01

    The vascularization and resulting perfusion of transferred tissues are critical to the success of grafts in buried free flap transplantations. To enable long-term clinical monitoring of grafted tissue perfusion during neovascularization and endothelialization, we are developing an implantable instrument for the continuous monitoring of perfusion using diffuse correlation spectroscopy (DCS), and augmented with diffuse reflectance spectroscopy (DRS). This work discusses instrument construction, integration, and preliminary results using a porcine graft model.

  14. Interactions between human immunodeficiency virus type 1 and human cytomegalovirus in human term syncytiotrophoblast cells coinfected with both viruses.

    PubMed Central

    Tóth, F D; Mosborg-Petersen, P; Kiss, J; Aboagye-Mathiesen, G; Hager, H; Juhl, C B; Gergely, L; Zdravkovic, M; Aranyosi, J; Lampé, L

    1995-01-01

    Human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1) may interact in the pathogenesis of AIDS. The placental syncytiotrophoblast layer serves as the first line of defense of the fetus against viruses. We analyzed the patterns of replication of HIV-1 and HCMV in singly an dually infected human term syncytiotrophoblast cells cultured in vitro. Syncytiotrophoblast cells exhibited restricted permissiveness for HIV-1, while HCMV replication was restricted at the level of immediate-early and early gene products in the singly infected cells. We found that the syncytiotrophoblasts as an overlapping cell population could be coinfected with HIV-1 and HCMV. HIV-1 replication was markedly upregulated by previous or simultaneous infection of the cells with HCMV, whereas prior HIV-1 infection of the cells converted HCMV infection from a nonpermissive to a permissive one. No simultaneous enhancement of HCMV and HIV-1 expression was observed in the dually infected cell cultures. Major immediate-early proteins of HCMV were necessary for enhancement of HIV-1 replication, and interleukin-6 production induced by HCMV and further increased by replicating HIV-1 synergized with these proteins to produce this effect. Permissive replication cycle of HCMV was induced by the HIV-1 tat gene product. We were unable to detect HIV-1 (HCMV) or HCMV (HIV-1) pseudotypes in supernatant fluids from dually infected cell cultures. Our results suggest that interactions between HIV-1 and HCMV in coinfected syncytiotrophoblast cells may contribute to the transplacental transmission of both viruses. PMID:7884869

  15. Ex vivo lung perfusion

    PubMed Central

    Machuca, Tiago N.

    2014-01-01

    Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972

  16. In-vivo Stretch of Term Human Fetal Membranes

    PubMed Central

    Joyce, EM; Diaz, P; Tamarkin, S; Moore, R; Strohl, A; Stetzer, B; Kumar, D; Sacks, MS; Moore, JJ

    2015-01-01

    Introduction Fetal membranes (FM) usually fail prior to delivery during term labor, but occasionally fail at preterm gestation, precipitating preterm birth. To understand the FM biomechanical properties underlying these events, study of the baseline in-vivo stretch experienced by the FM is required. This study's objective was to utilize high resolution MRI imaging to determine in-vivo FM stretch. Methods Eight pregnant women (38.4±0.4wks) underwent abdominal-pelvic MRI prior to (2.88±0.83d) caesarean delivery. Software was utilized to determine the total FM in-vivo surface area (SA) and that of its components: placental disc and reflected FM. At delivery, the SA of the disc and FM in the relaxed state were measured. In-vivo (stretched) to delivered SA ratios were calculated. FM fragments were then biaxially stretched to determine the force required to re-stretch the FM back to in-vivo SA. Results Total FM SA, in-vivo vs delivered, was 2135.51±108.47 cm2 vs 842.59±35.86 cm2; reflected FM was 1778.42±107.39 cm2 vs 545.41±22.90 cm2, and disc was 357.10±28.08 cm2 vs 297.18±22.14 cm2. The ratio (in-vivo to in-vitro SA) of reflected FM was 3.26±0.11 and disc was 1.22±0.10. Reflected FM re-stretched to in-vivo SA generated a tension of 72.26N/m, corresponding to approximate pressure of 15.4mmHg. FM rupture occurred at 295.08 ± 31.73N/m corresponding to approximate pressure of 34mmHg. Physiological SA was 70% of that at rupture. Discussion FM are significantly distended in-vivo. FM collagen fibers were rapidly recruited once loaded and functioned near the failure state during in-vitro testing, suggesting that, in-vivo, minimal additional (beyond physiological) stretch may facilitate rapid, catastrophic failure. PMID:26907383

  17. Cerebral-Body Perfusion Model

    DTIC Science & Technology

    1990-07-01

    compared to the 0.5g curve) fall in flow. Fig. 9b, showing the 5g case, strongly suggests a possible, so-called, " luxury perfusion ", in which natural...as the luxury perfusion situation which bypasses the flow with the nutrients it carries (through newly opened collaterals) and result in a "blackout...89-0054 CEREBRAL-BODY PERFUSION MODEL S. Sorek’, J. Bear2, and M., Feinsod3 in Collaboration with K. Allen4, L. Bunt5 and S. Ben-IHaiM6 July 1990

  18. [Effect of eleutherococcus on short-term memory and visual perception in healthy humans].

    PubMed

    Arushanian, E B; Baĭda, O A; Mastiagin, S S; Popova, A P; Shikina, I B

    2003-01-01

    Acute administration of a liquid eleutherococcus extract significantly improves short-term memory in healthy humans. The expression of this action depends on the daytime and psychophysiological peculiarities of the volunteers. Administration of the preparation also changes light perception by increasing retinal sensitivity. This effect was more pronounced in humans with weak type of high nervous activity in evening hours.

  19. Quantitative measurement of tissue perfusion and diffusion in vivo.

    PubMed

    Chenevert, T L; Pipe, J G; Williams, D M; Brunberg, J A

    1991-01-01

    Magnetic resonance imaging techniques designed for sensitivity to microscopic motions of water diffusion and blood flow in the capillary network are also exceptionally sensitive to bulk motion properties of the tissue, which may lead to contrast artifact and large quantitative errors. The magnitude of bulk motion error that exists in human brain perfusion/diffusion imaging and the inability of cardiac gating to adequately control this motion are demonstrated by direct measurement of phase stability of voxels localized in the brain. Two methods are introduced to reduce bulk motion phase error. The first, a postprocessing phase correction algorithm, reduces coarse phase error but is inadequate by itself for quantitative perfusion/diffusion MRI. The second method employs orthogonal slice selection gradients to define a column of tissue in the object, from which echoes may be combined in a phase-insensitive manner to measure more reliably the targeted signal attenuation. Applying this acquisition technique and a simplistic model of perfusion and diffusion signal attenuations yields an estimated perfusion fraction of 3.4 +/- 1.1% and diffusion coefficient of 1.1 +/- 0.2 x 10(-5) cm2/s in the white matter of one normal volunteer. Successful separation of perfusion and diffusion effects by this technique is supported in a dynamic study of calf muscle. Periods of normal blood flow, low flow, and reactive hyperemia are clearly distinguished in the quantitative perfusion results, whereas measured diffusion remained nearly constant.

  20. Engineering of functional, perfusable 3D microvascular networks on a chip.

    PubMed

    Kim, Sudong; Lee, Hyunjae; Chung, Minhwan; Jeon, Noo Li

    2013-04-21

    Generating perfusable 3D microvessels in vitro is an important goal for tissue engineering, as well as for reliable modelling of blood vessel function. To date, in vitro blood vessel models have not been able to accurately reproduce the dynamics and responses of endothelial cells to grow perfusable and functional 3D vascular networks. Here we describe a microfluidic-based platform whereby we model natural cellular programs found during normal development and angiogenesis to form perfusable networks of intact 3D microvessels as well as tumor vasculatures based on the spatially controlled co-culture of endothelial cells with stromal fibroblasts, pericytes or cancer cells. The microvessels possess the characteristic morphological and biochemical markers of in vivo blood vessels, and exhibit strong barrier function and long-term stability. An open, unobstructed microvasculature allows the delivery of nutrients, chemical compounds, biomolecules and cell suspensions, as well as flow-induced mechanical stimuli into the luminal space of the endothelium, and exhibits faithful responses to physiological shear stress as demonstrated by cytoskeleton rearrangement and increased nitric oxide synthesis. This simple and versatile platform provides a wide range of applications in vascular physiology studies as well as in developing vascularized organ-on-a-chip and human disease models for pharmaceutical screening.

  1. Pulmonary ventilation/perfusion scan

    MedlinePlus

    ... JavaScript. A pulmonary ventilation/perfusion scan involves two nuclear scan tests to measure breathing (ventilation) and circulation ( ... In: Mettler FA, Guiberteau MJ, eds. Essentials of Nuclear Medicine Imaging . 6th ed. Philadelphia, PA: Elsevier Saunders; ...

  2. Maximizing kidneys for transplantation using machine perfusion: from the past to the future

    PubMed Central

    Hameed, Ahmer M.; Pleass, Henry C.; Wong, Germaine; Hawthorne, Wayne J.

    2016-01-01

    Abstract Background: The two main options for renal allograft preservation are static cold storage (CS) and machine perfusion (MP). There has been considerably increased interest in MP preservation of kidneys, however conflicting evidence regarding its efficacy and associated costs have impacted its scale of clinical uptake. Additionally, there is no clear consensus regarding oxygenation, and hypo- or normothermia, in conjunction with MP, and its mechanisms of action are also debated. The primary aims of this article were to elucidate the benefits of MP preservation with and without oxygenation, and/or under normothermic conditions, when compared with CS prior to deceased donor kidney transplantation. Methods: Clinical (observational studies and prospective trials) and animal (experimental) articles exploring the use of renal MP were assessed (EMBASE, Medline, and Cochrane databases). Meta-analyses were conducted for the comparisons between hypothermic MP (hypothermic machine perfusion [HMP]) and CS (human studies) and normothermic MP (warm (normothermic) perfusion [WP]) compared with CS or HMP (animal studies). The primary outcome was allograft function. Secondary outcomes included graft and patient survival, acute rejection and parameters of tubular, glomerular and endothelial function. Subgroup analyses were conducted in expanded criteria (ECD) and donation after circulatory (DCD) death donors. Results: A total of 101 studies (63 human and 38 animal) were included. There was a lower rate of delayed graft function in recipients with HMP donor grafts compared with CS kidneys (RR 0.77; 95% CI 0.69–0.87). Primary nonfunction (PNF) was reduced in ECD kidneys preserved by HMP (RR 0.28; 95% CI 0.09–0.89). Renal function in animal studies was significantly better in WP kidneys compared with both HMP (standardized mean difference [SMD] of peak creatinine 1.66; 95% CI 3.19 to 0.14) and CS (SMD of peak creatinine 1.72; 95% CI 3.09 to 0.34). MP improves renal

  3. CAD of myocardial perfusion

    NASA Astrophysics Data System (ADS)

    Storm, Corstiaan J.; Slump, Cornelis H.

    2007-03-01

    Our purpose is in the automated evaluation of the physiological relevance of lesions in coronary angiograms. We aim to extract as much as possible quantitative information about the physiological condition of the heart from standard angiographic image sequences. Coronary angiography is still the gold standard for evaluating and diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. The dimensions of the stenosis can be assessed nowadays successfully with image processing based Quantitative Coronary Angiography (QCA) techniques. Our purpose is to assess the clinical relevance of the pertinent stenosis. We therefore analyze the myocardial perfusion as revealed in standard angiographic image sequences. In a Region-of-Interest (ROI) on the angiogram (without an overlaying major blood vessel) the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In order to minimize motion artifacts we select based on the recorded ECG signal end-diastolic images in both a basal and a hyperemic run in the same projection to position the ROI. We present the development of the algorithms together with results of a small study of 20 patients which have been catheterized following the standard protocol.

  4. The prion gene is associated with human long-term memory.

    PubMed

    Papassotiropoulos, Andreas; Wollmer, M Axel; Aguzzi, Adriano; Hock, Christoph; Nitsch, Roger M; de Quervain, Dominique J-F

    2005-08-01

    Human cognitive processes are highly variable across individuals and are influenced by both genetic and environmental factors. Although genetic variations affect short-term memory in humans, it is unknown whether genetic variability has also an impact on long-term memory. Because prion-like conformational changes may be involved in the induction of long-lasting synaptic plasticity, we examined the impact of single-nucleotide polymorphisms (SNPs) of the prion protein gene (PRNP) on long-term memory in healthy young humans. SNPs in the genomic region of PRNP were associated with better long-term memory performance in two independent populations with different educational background. Among the examined PRNP SNPs, the common Met129Val polymorphism yielded the highest effect size. Twenty-four hours after a word list-learning task, carriers of either the 129MM or the 129MV genotype recalled 17% more information than 129VV carriers, but short-term memory was unaffected. These results suggest a role for the prion protein in the formation of long-term memory in humans.

  5. Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

    PubMed Central

    Giannì, Maria Lorella; Consonni, Dario; Liotto, Nadia; Roggero, Paola; Morlacchi, Laura; Piemontese, Pasqua; Menis, Camilla; Mosca, Fabio

    2016-01-01

    (1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = −47.9, 95% confidence interval (CI) = −95.7; −0.18; p = 0.049; β = −89.6, 95% CI = −131.5; −47.7; p < 0.0001; β = −104.1, 95% CI = −151.4; −56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants. PMID:27782098

  6. Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

    PubMed

    Giannì, Maria Lorella; Consonni, Dario; Liotto, Nadia; Roggero, Paola; Morlacchi, Laura; Piemontese, Pasqua; Menis, Camilla; Mosca, Fabio

    2016-10-23

    (1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = -47.9, 95% confidence interval (CI) = -95.7; -0.18; p = 0.049; β = -89.6, 95% CI = -131.5; -47.7; p < 0.0001; β = -104.1, 95% CI = -151.4; -56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants.

  7. Brain luxury perfusion during cardiopulmonary bypass in humans. A study of the cerebral blood flow response to changes in CO2, O2, and blood pressure.

    PubMed

    Henriksen, L

    1986-06-01

    CBF and related parameters were studied in 68 patients before, during, and following cardiopulmonary bypass. CBF was measured using the intraarterial 133Xe injection method. The extracorporeal circuit was nonpulsatile with a bubble oxygenator administering 3-5% CO2 in the main group of hypercapnic patients (n = 59) and no CO2 in a second group of hypocapnic patients. In the hypercapnic patients, marked changes in CBF occurred during bypass. Evidence was found of a brain luxury perfusion that could not be related to the effect of CO2 per se. Mean CBF was 29 ml/100 g/min just before bypass, 49 ml/100 g/min at steady-state hypothermia (27 degrees C), reached a maximum of 73 ml/100 g/min during the rewarming phase (32 degrees C), fell to 56 ml/100 g/min at steady-state normothermic bypass (37 degrees C), and was 48 ml/100 g/min shortly after bypass was stopped. Addition of CO2 evoked systemic vasodilation with low blood pressure and a rebound hyperemia. The hypocapnic group responded more physiologically to the induced changes in hematocrit (Htc) and temperature, CBF being 25, 23, 25, 34, and 35 ml/100 g/min, respectively, during the five corresponding periods. Carbon dioxide was an important regulator of CBF during all phases of cardiac surgery, the responsiveness of CBF being approximately 4% for each 1-mm Hg change of PaCO2. The level of MABP was important for the CO2 response. At low blood pressure states, the CBF responsiveness to changes in PaCO2 was almost abolished. An optimal level of PaCO2 during hypothermic bypass of approximately 25 mm Hg (at actual temperature) is recommended. A normal autoregulatory response of CBF to changes in blood pressure was found during and following bypass. The lower limit of autoregulation was at pressure levels of approximately 50-60 mm Hg. CBF autoregulation was almost abolished at PaCO2 levels of greater than 50 mm Hg. The degree of hemodilution neither affected the CO2 response nor impaired CBF autoregulation, although, as

  8. Supercooling enables long-term transplantation survival following 4 days of liver preservation.

    PubMed

    Berendsen, Tim A; Bruinsma, Bote G; Puts, Catheleyne F; Saeidi, Nima; Usta, O Berk; Uygun, Basak E; Izamis, Maria-Louisa; Toner, Mehmet; Yarmush, Martin L; Uygun, Korkut

    2014-07-01

    The realization of long-term human organ preservation will have groundbreaking effects on the current practice of transplantation. Herein we present a new technique based on subzero nonfreezing preservation and extracorporeal machine perfusion that allows transplantation of rat livers preserved for up to four days, thereby tripling the viable preservation duration.

  9. Short-term fasting alters cytochrome P450-mediated drug metabolism in humans.

    PubMed

    Lammers, Laureen A; Achterbergh, Roos; de Vries, Emmely M; van Nierop, F Samuel; Klümpen, Heinz-Josef; Soeters, Maarten R; Boelen, Anita; Romijn, Johannes A; Mathôt, Ron A A

    2015-06-01

    Experimental studies indicate that short-term fasting alters drug metabolism. However, the effects of short-term fasting on drug metabolism in humans need further investigation. Therefore, the aim of this study was to evaluate the effects of short-term fasting (36 h) on P450-mediated drug metabolism. In a randomized crossover study design, nine healthy subjects ingested a cocktail consisting of five P450-specific probe drugs [caffeine (CYP1A2), S-warfarin (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6), and midazolam (CYP3A4)] on two occasions (control study after an overnight fast and after 36 h of fasting). Blood samples were drawn for pharmacokinetic analysis using nonlinear mixed effects modeling. In addition, we studied in Wistar rats the effects of short-term fasting on hepatic mRNA expression of P450 isoforms corresponding with the five studied P450 enzymes in humans. In the healthy subjects, short-term fasting increased oral caffeine clearance by 20% (P = 0.03) and decreased oral S-warfarin clearance by 25% (P < 0.001). In rats, short-term fasting increased mRNA expression of the orthologs of human CYP1A2, CYP2C19, CYP2D6, and CYP3A4 (P < 0.05), and decreased the mRNA expression of the ortholog of CYP2C9 (P < 0.001) compared with the postabsorptive state. These results demonstrate that short-term fasting alters cytochrome P450-mediated drug metabolism in a nonuniform pattern. Therefore, short-term fasting is another factor affecting cytochrome P450-mediated drug metabolism in humans.

  10. Differential Gene Expression Profiling of Enriched Human Spermatogonia after Short- and Long-Term Culture

    PubMed Central

    Conrad, Sabine; Azizi, Hossein; Hatami, Maryam; Kubista, Mikael; Bonin, Michael; Hennenlotter, Jörg; Renninger, Markus; Skutella, Thomas

    2014-01-01

    This study aimed to provide a molecular signature for enriched adult human stem/progenitor spermatogonia during short-term (<2 weeks) and long-term culture (up to more than 14 months) in comparison to human testicular fibroblasts and human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic activated cell sorting and collagen−/laminin+ matrix binding from primary testis cultures obtained from ten adult men. For transcriptomic analysis, single spermatogonia-like cells were collected based on their morphology and dimensions using a micromanipulation system from the enriched germ cell cultures. Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed populations of cells were distinct at the molecular level. The germ- and pluripotency-associated genes and genes of differentiation/spermatogenesis pathway were highly expressed in enriched short-term cultured spermatogonia. After long-term culture, a proportion of cells retained and aggravated the “spermatogonial” gene expression profile with the expression of germ and pluripotency-associated genes, while in the majority of long-term cultured cells this molecular profile, typical for the differentiation pathway, was reduced and more genes related to the extracellular matrix production and attachment were expressed. The approach we provide here to study the molecular status of in vitro cultured spermatogonia may be important to optimize the culture conditions and to evaluate the germ cell plasticity in the future. PMID:24738045

  11. Long-term culture and functional characterization of follicular cells from adult normal human thyroids.

    PubMed Central

    Curcio, F; Ambesi-Impiombato, F S; Perrella, G; Coon, H G

    1994-01-01

    We have obtained long-term cultures of differentiated proliferating follicular cells from normal adult human thyroid glands. In vitro growth of such human cells has been sustained by a modified F-12 medium, supplemented with bovine hypothalamus and pituitary extracts and no added thyrotropin. Cultures have been expanded, cloned, frozen, successfully retrieved, and characterized. Functional characterization of these cells shows constitutive thyroglobulin production and release and thyrotropin-dependent adenosine 3',5'-cyclic monophosphate production, the latter apparently not associated with significant increases in DNA synthesis or cell proliferation. Genetic characterization of these cells by chromosome counting showed the normal diploid chromosome number. The ability to cultivate differentiated human thyroid follicular cells in long-term culture opens possibilities for investigating the transduction pathways of thyrotropin stimulation in normal and pathological human tissues, developing clinically relevant in vitro assays, and considering cellular and molecular therapies. Images PMID:8090760

  12. Long term and large-scale cultivation of human hepatoma Hep G2 cells in hollow fiber bioreactor. Cultivation of human hepatoma Hep G2 in hollow fiber bioreactor.

    PubMed

    Liu, J J; Chen, B S; Tsai, T F; Wu, Y J; Pang, V F; Hsieh, A; Hsieh, J H; Chang, T H

    1991-02-01

    Long-term and large scale cultivation of an anchorage-dependent cell line using an industrial scale hollow fiber perfusion bioreactor is described. Hep G2 cells (a human hepatoma cell line) were cultivated in an Acusyst-P (Endotronic) with a total fiber surface area of 7.2 m2 6 x 1.2m2) to produce Hep G2 crude conditioned medium (CCM). Pretreatment of the cellulose acetate hollow fibers with collagen enhances the attachment of the anchorage-dependent cells. We have succeeded in growing the Hep G2 cells in an antibiotics- and serum-free IMDM medium, supplemented with 50 micrograms/ml of Hep G2 CCM protein at inoculation. The Hep G2 cells replicate and secrete CCM protein in quantities comparable to those produced in DMEM containing 10% fetal calf serum (FCS). The highest CCM protein productivity during the 80-day cultivation was 1.1 g/day with a total of 30 g of protein accumulated. Hep G2 CCM (20-40 micrograms protein/ml) was comparable to or even better than 10% FCS in supporting the growth of Molt-4 (a human T leukemia cell line) and FO (a mouse myeloma cell line) cells in vitro. The availability of this large amount of Hep G2 CCM will aid the further purification and characterization of growth factor(s) which could be used as serum substituents.

  13. Modelling of temperature and perfusion during scalp cooling.

    PubMed

    Janssen, F E M; Van Leeuwen, G M J; Van Steenhoven, A A

    2005-09-07

    Hair loss is a feared side effect of chemotherapy treatment. It may be prevented by cooling the scalp during administration of cytostatics. The supposed mechanism is that by cooling the scalp, both temperature and perfusion are diminished, affecting drug supply and drug uptake in the hair follicle. However, the effect of scalp cooling varies strongly. To gain more insight into the effect of cooling, a computer model has been developed that describes heat transfer in the human head during scalp cooling. Of main interest in this study are the mutual influences of scalp temperature and perfusion during cooling. Results of the standard head model show that the temperature of the scalp skin is reduced from 34.4 degrees C to 18.3 degrees C, reducing tissue blood flow to 25%. Based upon variations in both thermal properties and head anatomies found in the literature, a parameter study was performed. The results of this parameter study show that the most important parameters affecting both temperature and perfusion are the perfusion coefficient Q10 and the thermal resistances of both the fat and the hair layer. The variations in the parameter study led to skin temperature ranging from 10.1 degrees C to 21.8 degrees C, which in turn reduced relative perfusion to 13% and 33%, respectively.

  14. Modelling of temperature and perfusion during scalp cooling

    NASA Astrophysics Data System (ADS)

    Janssen, F. E. M.; Van Leeuwen, G. M. J.; Van Steenhoven, A. A.

    2005-09-01

    Hair loss is a feared side effect of chemotherapy treatment. It may be prevented by cooling the scalp during administration of cytostatics. The supposed mechanism is that by cooling the scalp, both temperature and perfusion are diminished, affecting drug supply and drug uptake in the hair follicle. However, the effect of scalp cooling varies strongly. To gain more insight into the effect of cooling, a computer model has been developed that describes heat transfer in the human head during scalp cooling. Of main interest in this study are the mutual influences of scalp temperature and perfusion during cooling. Results of the standard head model show that the temperature of the scalp skin is reduced from 34.4 °C to 18.3 °C, reducing tissue blood flow to 25%. Based upon variations in both thermal properties and head anatomies found in the literature, a parameter study was performed. The results of this parameter study show that the most important parameters affecting both temperature and perfusion are the perfusion coefficient Q10 and the thermal resistances of both the fat and the hair layer. The variations in the parameter study led to skin temperature ranging from 10.1 °C to 21.8 °C, which in turn reduced relative perfusion to 13% and 33%, respectively.

  15. Civil Conflict and Human Capital Accumulation: The Long-Term Effects of Political Violence in Peru

    ERIC Educational Resources Information Center

    Leon, Gianmarco

    2012-01-01

    This paper provides empirical evidence of the persistent effect of exposure to political violence on human capital accumulation. I exploit the variation in conflict location and birth cohorts to identify the long- and short-term effects of the civil war on educational attainment. Conditional on being exposed to violence, the average person…

  16. Citizenship, Nationalism, Human Rights and Democracy: A Tangling of Terms in the Kuwaiti Curriculum

    ERIC Educational Resources Information Center

    Al-Nakib, Rania

    2011-01-01

    Background: Citizenship, nationalism, human rights and democracy are four terms and concepts that are inextricably linked. In Kuwait, the status of citizen is based on nationality, gender and age, with women, children, naturalised citizens, expatriates and "bidoon" (stateless people) denied many freedoms, rights and services. Citizenship…

  17. Reframing Photographic Research Methods in Human Geography: A Long-Term Reflection

    ERIC Educational Resources Information Center

    Hall, Tim

    2015-01-01

    This paper offers a long-term reflection on the introduction of a photographic research project into a third-year undergraduate Human Geography module. The findings indicate that, whilst the students valued the project, it did impact on their overall performance, their evaluation of the module and the ways in which they spoke about it. The paper…

  18. Short-Term Plasticity of the Visuomotor Map during Grasping Movements in Humans

    ERIC Educational Resources Information Center

    Safstrom, Daniel; Edin, Benoni B.

    2005-01-01

    During visually guided grasping movements, visual information is transformed into motor commands. This transformation is known as the "visuomotor map." To investigate limitations in the short-term plasticity of the visuomotor map in normal humans, we studied the maximum grip aperture (MGA) during the reaching phase while subjects grasped objects…

  19. Long term effects of Climate change on Human adaptation in Middle Gila River Valley

    NASA Astrophysics Data System (ADS)

    Zhu, Tianduowa; Ertsen, Maurits

    2013-04-01

    Climate change has been one of key concerning factors for the origin and evolution of hydraulic engineering projects. The study of ancient irrigation systems in the context of long-term climate change enables us to improve the understanding on the response of human beings to variations on their environment. And niche construction starts to be used to explain the development of early small-scale irrigation canals in a view of biological evolution. Therefore, the study of early irrigation canals within a frame of long-term timescale may help to explore the roles of niche construction theory on canals' operation and further expansion. In this paper, the Hohokam canals in the middle Gila River of Southwest America are used as case study, in order to explore the influences of climate change on human behavior. A prehistoric large-scale irrigation network, the Hohokam irrigation system was composed of interconnected sections organized by local independent communities, rather than under the supervision of a central government. This common operation for water distribution without centralization provides us with the opportunity to focus on the relationship between humans and their environment. The aim of this paper is to model the process of human adaptation to their environment, including water flows, crops production and canal maintenance in long term, with the assistance of archaeological surveys and reconstructed climatological data. The results provide us with an insight on how the variation of the configuration of the canals is clearly conditioned by the interaction and adaptation of human settlements. This evolution can be explained by the combination of human food needs to the restrictions of the changing climate given by water availability. The balance of human demand and water availability guides the direction of human dynamics.

  20. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours.

    PubMed

    Becker, Simon; Steinmeyer, Jasmin; Avsar, Murat; Höffler, Klaus; Salman, Jawad; Haverich, Axel; Warnecke, Gregor; Ochs, Matthias; Schnapper, Anke

    2016-01-01

    Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition.

  1. Viable neurons with luxury perfusion in hydrocephalus.

    PubMed

    Wong, C Y; Luciano, M G; MacIntyre, W J; Brunken, R C; Hahn, J F; Go, R T

    1997-09-01

    A woman with hydrocephalus due to aqueductal stenosis had functional imaging of cerebral perfusion and metabolism to demonstrate the effects of endoscopic third ventriculostomy--a new form of internal surgical shunting. Technetium-99m-ECD SPECT and 18F-FDG PET showed regional luxury perfusion at the left frontal region. Three months after a successful third ventriculostomy, a repeated imaging of cerebral perfusion and metabolism showed resolution of luxury perfusion and global improvement of both perfusion and metabolism. This concurred with postoperative clinical improvement. The paired imaging of cerebral perfusion and metabolism provides more information than just imaging perfusion or metabolism. Thus, the detection of perfusion and metabolism mismatch may open a new window of opportunity for surgical intervention.

  2. PHENOstruct: Prediction of human phenotype ontology terms using heterogeneous data sources

    PubMed Central

    Kahanda, Indika; Funk, Christopher; Verspoor, Karin; Ben-Hur, Asa

    2015-01-01

    The human phenotype ontology (HPO) was recently developed as a standardized vocabulary for describing the phenotype abnormalities associated with human diseases. At present, only a small fraction of human protein coding genes have HPO annotations. But, researchers believe that a large portion of currently unannotated genes are related to disease phenotypes. Therefore, it is important to predict gene-HPO term associations using accurate computational methods. In this work we demonstrate the performance advantage of the structured SVM approach which was shown to be highly effective for Gene Ontology term prediction in comparison to several baseline methods. Furthermore, we highlight a collection of informative data sources suitable for the problem of predicting gene-HPO associations, including large scale literature mining data. PMID:26834980

  3. [Short-term memory characteristics of vibration intensity tactile perception on human wrist].

    PubMed

    Hao, Fei; Chen, Li-Juan; Lu, Wei; Song, Ai-Guo

    2014-12-25

    In this study, a recall experiment and a recognition experiment were designed to assess the human wrist's short-term memory characteristics of tactile perception on vibration intensity, by using a novel homemade vibrotactile display device based on the spatiotemporal combination vibration of multiple micro vibration motors as a test device. Based on the obtained experimental data, the short-term memory span, recognition accuracy and reaction time of vibration intensity were analyzed. From the experimental results, some important conclusions can be made: (1) The average short-term memory span of tactile perception on vibration intensity is 3 ± 1 items; (2) The greater difference between two adjacent discrete intensities of vibrotactile stimulation is defined, the better average short-term memory span human wrist gets; (3) There is an obvious difference of the average short-term memory span on vibration intensity between the male and female; (4) The mechanism of information extraction in short-term memory of vibrotactile display is to traverse the scanning process by comparison; (5) The recognition accuracy and reaction time performance of vibrotactile display compares unfavourably with that of visual and auditory. The results from this study are important for designing vibrotactile display coding scheme.

  4. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome

    SciTech Connect

    Jakobsson, H.; Jernberg, C.; Andersson, A.F.; Sjolund-Karlsson, M.; Jansson, J.K.; Engstrand, L.

    2010-01-15

    Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance.

  5. Construction and validation of a microprocessor controlled extracorporal circuit in rats for the optimization of isolated limb perfusion.

    PubMed

    Gürtler, Ulrich; Fuchs, Peter; Stangelmayer, Achim; Bernhardt, Günther; Buschauer, Armin; Spruss, Thilo

    2004-12-01

    Although a few experimental approaches to isolated limb perfusion (ILP) are described in the literature, none of these animal models mimics the clinical perfusion techniques adequately to improve the technique of ILP on the basis of valid preclinical data. Therefore, we developed an ILP setup in rats allowing online monitoring of essential perfusion parameters such as temperature (in perfusate, various tissues, and rectum), pH (perfusate), perfusion pressure, and O(2) concentration (in perfusate, tissue), by a tailor-made data acquisition system. This setup permits close supervision of vital parameters during ILP. Various interdependencies, concerning the flow rate and the pressure of perfusate as well as tissue oxygenation were registered. For the measurement of pO(2) values in the perfusate and in different regions of the perfused hind limb, a novel type of microoptode based on quenching of a fluorescent dye was devised. Stable normothermic (37 degrees C) perfusion conditions were maintained at a constant perfusion pressure in the range of 40-60 mm Hg by administration of the spasmo lytic moxaverine (0.5 mg/mL of perfusate as initial dose) at a perfusate flow rate of 0.5 mL/min for 60 min. At the end of an ILP, there were no signs of tissue damage, neither concerning laboratory data (K(+), myoglobin, creatine kinase, lactic dehydrogenase) nor histopathological criteria. The reported ILP model is not only well suited to investigate the effects of hyperthermia but also to assess the efficacy of new antineoplastic approaches, when nude rats, bearing human tumours in the hind limbs, are used.

  6. Continuous monitoring of cortical perfusion by laser Doppler flowmetry in ventilated patients with head injury.

    PubMed Central

    Kirkpatrick, P J; Smielewski, P; Czosnyka, M; Pickard, J D

    1994-01-01

    A method for monitoring cortical perfusion by laser Doppler flowmetry (LDF) in the neurointensive care unit is described. Out of 22 patients with head injuries, reliable and long term recordings were obtained in 16. Laser Doppler flowmetry registered changes in cortical microcirculatory flow in response to spontaneous waves of raised intracranial pressure, and to therapeutic manoeuvres that altered the cerebral perfusion pressure. Comparisons of variations in flux signal with cerebral perfusion pressure provided an indication of the autoregulatory state of the cortical microcirculation, and analysis of raw LDF data demonstrated an autoregulatory breakpoint of cerebral perfusion pressure of 58 mm Hg, below which cortical perfusion failed. Although middle cerebral artery flow velocities were generally tightly coupled with LDF signal changes, episodes of uncoupling were seen. The potential uses and limitations of LDF in the neurointensive care setting are discussed. Images PMID:7964816

  7. Effect of long-term fluoxetine treatment on the human serotonin transporter in Caco-2 cells.

    PubMed

    Iceta, Ruth; Mesonero, José E; Alcalde, Ana I

    2007-03-27

    Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) broadly used in the treatment of human mood disorders and gastrointestinal diseases involving the serotoninergic system. The effectiveness of this therapy depends on repeated long-term treatment. Most of the long-term studies in vivo of SSRI effects on serotoninergic activity have focused on their effects on autoreceptors or postsynaptic receptors. The chronic effect of SSRIs on the activity of the serotonin transporter (SERT) has been less studied and the results have been contradictory. The aim of this study was to determine the specific effect of long-term fluoxetine treatment on human serotonin transporter (hSERT) in vitro, by using the human enterocyte-like cell line Caco-2. Results show that fluoxetine diminished the 5-HT uptake in a concentration-dependent way and that this effect was reversible. Fluoxetine affected mainly the hSERT transport rate by reducing the availability of the transporter in the membrane with no significant alteration of either the total hSERT protein content or the hSERT mRNA level. These results suggest that the effect of fluoxetine on the expression of hSERT is post-translational and has shown itself to be independent of PKC and PKA activity. This study may be useful to clarify the effect of the long-term fluoxetine therapy in both gastrointestinal and central nervous system disorders.

  8. Extraction of DNA from human embryos after long-term preservation in formalin and Bouin's solutions.

    PubMed

    Nagai, Momoko; Minegishi, Katsura; Komada, Munekazu; Tsuchiya, Maiko; Kameda, Tomomi; Yamada, Shigehito

    2016-05-01

    The "Kyoto Collection of Human Embryos" at Kyoto University was begun in 1961. Although morphological analyses of samples in the Kyoto Collection have been performed, these embryos have been considered difficult to genetically analyze because they have been preserved in formalin or Bouin's solution for 20-50 years. Owing to the recent advances in molecular biology, it has become possible to extract DNA from long-term fixed tissues. The purpose of this study was to extract DNA from wet preparations of human embryo samples after long-term preservation in fixing solution. We optimized the DNA extraction protocol to be suitable for tissues that have been damaged by long-term fixation, including DNA-protein crosslinking damage. Diluting Li2 CO3 with 70% ethanol effectively removed picric acid from samples fixed in Bouin's solution. Additionally, 20.0 mg/mL proteinase was valuable to lyse the long-term fixed samples. The extracted DNA was checked with PCR amplification using several sets of primers and sequence analysis. The PCR products included at least 295- and 838-bp amplicons. These results show that the extracted DNA is applicable for genetic analyses, and indicate that old embryos in the Kyoto Collection should be made available for future studies. The protocol described in this study can successfully extract DNA from old specimens and, with improvements, should be applicable in research aiming to understand the molecular mechanisms of human congenital anomalies.

  9. Localized Spatio-Temporal Constraints for Accelerated CMR Perfusion

    PubMed Central

    Akçakaya, Mehmet; Basha, Tamer A.; Pflugi, Silvio; Foppa, Murilo; Kissinger, Kraig V.; Hauser, Thomas H.; Nezafat, Reza

    2013-01-01

    Purpose To develop and evaluate an image reconstruction technique for cardiac MRI (CMR)perfusion that utilizes localized spatio-temporal constraints. Methods CMR perfusion plays an important role in detecting myocardial ischemia in patients with coronary artery disease. Breath-hold k-t based image acceleration techniques are typically used in CMR perfusion for superior spatial/temporal resolution, and improved coverage. In this study, we propose a novel compressed sensing based image reconstruction technique for CMR perfusion, with applicability to free-breathing examinations. This technique uses local spatio-temporal constraints by regularizing image patches across a small number of dynamics. The technique is compared to conventional dynamic-by-dynamic reconstruction, and sparsity regularization using a temporal principal-component (pc) basis, as well as zerofilled data in multi-slice 2D and 3D CMR perfusion. Qualitative image scores are used (1=poor, 4=excellent) to evaluate the technique in 3D perfusion in 10 patients and 5 healthy subjects. On 4 healthy subjects, the proposed technique was also compared to a breath-hold multi-slice 2D acquisition with parallel imaging in terms of signal intensity curves. Results The proposed technique results in images that are superior in terms of spatial and temporal blurring compared to the other techniques, even in free-breathing datasets. The image scores indicate a significant improvement compared to other techniques in 3D perfusion (2.8±0.5 vs. 2.3±0.5 for x-pc regularization, 1.7±0.5 for dynamic-by-dynamic, 1.1±0.2 for zerofilled). Signal intensity curves indicate similar dynamics of uptake between the proposed method with a 3D acquisition and the breath-hold multi-slice 2D acquisition with parallel imaging. Conclusion The proposed reconstruction utilizes sparsity regularization based on localized information in both spatial and temporal domains for highly-accelerated CMR perfusion with potential utility in free

  10. Impaired Tissue Oxygenation in Metabolic Syndrome Requires Increased Microvascular Perfusion Heterogeneity.

    PubMed

    Mason McClatchey, P; Wu, Fan; Olfert, I Mark; Ellis, Christopher G; Goldman, Daniel; Reusch, Jane E B; Frisbee, Jefferson C

    2017-02-01

    Metabolic syndrome (MS) in obese Zucker rats (OZR) is associated with impaired skeletal muscle performance and blunted hyperemia. Studies suggest that reduced O2 diffusion capacity is required to explain compromised muscle performance and that heterogeneous microvascular perfusion distribution is critical. We modeled tissue oxygenation during muscle contraction in control and OZR skeletal muscle using physiologically realistic relationships. Using a network model of Krogh cylinders with increasing perfusion asymmetry and increased plasma skimming, we predict increased perfusion heterogeneity and decreased muscle oxygenation in OZR, with partial recovery following therapy. Notably, increasing O2 delivery had less impact on VO2 than equivalent decreases in O2 delivery, providing a mechanism for previous empirical work associating perfusion heterogeneity and impaired O2 extraction. We demonstrate that increased skeletal muscle perfusion asymmetry is a defining characteristic of MS and must be considered to effectively model and understand blood-tissue O2 exchange in this model of human disease.

  11. A recapitulative three-dimensional model of breast carcinoma requires perfusion for multi-week growth

    PubMed Central

    Goliwas, Kayla F; Marshall, Lauren E; Ransaw, Evette L; Berry, Joel L; Frost, Andra R

    2016-01-01

    Breast carcinomas are complex, three-dimensional tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix. In vitro models that more faithfully recapitulate this dimensionality and stromal microenvironment should more accurately elucidate the processes driving carcinogenesis, tumor progression, and therapeutic response. Herein, novel in vitro breast carcinoma surrogates, distinguished by a relevant dimensionality and stromal microenvironment, are described and characterized. A perfusion bioreactor system was used to deliver medium to surrogates containing engineered microchannels and the effects of perfusion, medium composition, and the method of cell incorporation and density of initial cell seeding on the growth and morphology of surrogates were assessed. Perfused surrogates demonstrated significantly greater cell density and proliferation and were more histologically recapitulative of human breast carcinoma than surrogates maintained without perfusion. Although other parameters of the surrogate system, such as medium composition and cell seeding density, affected cell growth, perfusion was the most influential parameter. PMID:27516850

  12. Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes

    PubMed Central

    Abeles, Shira R.; Ly, Melissa; Santiago-Rodriguez, Tasha M.; Pride, David T.

    2015-01-01

    Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances. PMID:26309137

  13. Peptidome analysis of human skim milk in term and preterm milk

    SciTech Connect

    Wan, Jun; Cui, Xian-wei; Zhang, Jun; Fu, Zi-yi; Guo, Xi-rong; Sun, Li-Zhou; Ji, Chen-bo

    2013-08-16

    Highlights: •A method was developed for preparation of peptide extracts from human milk. •Analysis of the extracts by LC–MS/MS resulted in the detection of 1000–3000 peptide-like features. •419 Peptides were identified by LC–MS/MS from 34 proteins. •Isotope dimethyl labeling analysis revealed 41 peptides differentially expressed. -- Abstract: The abundant proteins in human milk have been well characterized and are known to provide nutritional, protective, and developmental advantages to both term and preterm infants. Due to the difficulties associated with detection technology of the peptides, the expression of the peptides present in human milk is not known widely. In recent years, peptidome analysis has received increasing attention. In this report, the analysis of endogenous peptides in human milk was done by mass spectrometry. A method was also developed by our researchers, which can be used in the extraction of peptide from human milk. Analysis of the extracts by LC–MS/MS resulted in the detection of 1000–3000 Da peptide-like features. Out of these, 419 peptides were identified by MS/MS. The identified peptides were found to originate from 34 proteins, of which several have been reported. Analysis of the peptides’ cleavage sites showed that the peptides are cleaved with regulations. This may reflect the protease activity and distribution in human body, and also represent the biological state of the tissue and provide a fresh source for biomarker discovery. Isotope dimethyl labeling analysis was also used to test the effects of premature delivery on milk protein composition in this study. Differences in peptides expression between breast milk in term milk (38–41 weeks gestation) and preterm milk (28–32 weeks gestation) were investigated in this study. 41 Peptides in these two groups were found expressed differently. 23 Peptides were present at higher levels in preterm milk, and 18 were present at higher levels in term milk.

  14. Hyperaemic changes in forearm skin perfusion and RBC concentration after increasing occlusion times.

    PubMed

    Farnebo, Simon; Thorfinn, Johan; Henricson, Joakim; Tesselaar, Erik

    2010-12-01

    Tissue occlusion and the hyperaemic response upon reperfusion can be used as a tool to assess microvascular function in various vascular diseases. Currently, laser Doppler flowmetry (LDF) is applied most often to measure hyperaemic responses. In this study, we have applied tissue viability imaging (TiVi) and LDF to measure the change in red blood cell concentration and perfusion in the skin after occlusions of the forearm with increasing duration. We have found that there is a strong correlation between the changes in perfusion and red blood cell (RBC) concentration during post-occlusive hyperaemia (perfusion: r=0.80; RBC concentration: r=0.94). This correlation increases with longer occlusion durations (1, 5 and 10min). Furthermore, for both perfusion and RBC concentration, the maximum responses (perfusion: r(2)=0.59; RBC concentration: r(2)=0.78) and the recovery times (perfusion: r(2)=0.62; RBC concentration: r(2)=0.91) increase linearly with the duration of the occlusion. Maximum responses and recovery times were more reproducible for RBC concentration (as measured with TiVi) than for perfusion (as measured with LDF). These results show that perfusion and RBC concentration are related during post-occlusive hyperaemia and that TiVi can be used as a tool in the assessment of hyperaemic responses that has advantages in terms of reproducibility, sensitivity and ease of use.

  15. Thallium-201 myocardial perfusion imaging in myocarditis

    SciTech Connect

    Tamaki, N.; Yonekura, Y.; Kadota, K.; Kambara, H.; Torizuka, K.

    1985-08-01

    TI-201 myocardial perfusion imaging was performed in six patients with clinically documented myocarditis. Each case manifested electrocardiographic abnormalities with elevation of serum cardiac enzymes and no significant stenosis of the coronary arteries observed on angiogram. Resting TI-201 images were visually assessed by three observers. Focal perfusion defects were observed in three cases (50%), among which two showed multiple perfusion defects. Emission computed tomography using TI-201 clearly delineated multifocal lesions in the first case. On the other hand, no significant perfusion defects were noted in the remaining three cases. Thus, myocarditis should be considered as one of the disease entities that may produce perfusion defects on TI-201 myocardial imaging.

  16. Evaluation of Feline Renal Perfusion with Contrast-Enhanced Ultrasonography and Scintigraphy

    PubMed Central

    Vanderperren, Katrien; Bosmans, Tim; Dobbeleir, André; Duchateau, Luc; Hesta, Myriam; Lybaert, Lien; Peremans, Kathelijne; Vandermeulen, Eva; Saunders, Jimmy

    2016-01-01

    Contrast-enhanced ultrasound (CEUS) is an emerging technique to evaluate tissue perfusion. Promising results have been obtained in the evaluation of renal perfusion in health and disease, both in human and veterinary medicine. Renal scintigraphy using 99mTc-Mercaptoacetyltriglycine (MAG3) is another non-invasive technique that can be used to evaluate renal perfusion. However, no data are available on the ability of CEUS or 99mTc- MAG3 scintigraphy to detect small changes in renal perfusion in cats. Therefore, both techniques were applied in a normal feline population to evaluate detection possibilities of perfusion changes by angiotensin II (AT II). Contrast-enhanced ultrasound using a bolus injection of commercially available contrast agent and renal scintigraphy using 99mTc-MAG3 were performed in 11 healthy cats after infusion of 0,9% NaCl (control) and AT II. Angiotensin II induced changes were noticed on several CEUS parameters. Mean peak enhancement, wash-in perfusion index and wash-out rate for the entire kidney decreased significantly after AT II infusion. Moreover, a tendency towards a lower wash-in area-under-the curve was present. Renal scintigraphy could not detect perfusion changes induced by AT II. This study shows that CEUS is able to detect changes in feline renal perfusion induced by AT II infusion. PMID:27736928

  17. Human Land-Use Practices Lead to Global Long-Term Increases in Photosynthetic Capacity

    NASA Technical Reports Server (NTRS)

    Mueller, Thomas; Tucker, Compton J.; Dressler, Gunnar; Pinzon, Jorge E.; Leimgruber, Peter; Dubayah, Ralph O.; Hurtt, George C.; Boehning-Gaese, Katrin; Fagan, William F.

    2014-01-01

    Long-term trends in photosynthetic capacity measured with the satellite-derived Normalized Difference Vegetation Index (NDVI) are usually associated with climate change. Human impacts on the global land surface are typically not accounted for. Here, we provide the first global analysis quantifying the effect of the earth's human footprint on NDVI trends. Globally, more than 20% of the variability in NDVI trends was explained by anthropogenic factors such as land use, nitrogen fertilization, and irrigation. Intensely used land classes, such as villages, showed the greatest rates of increase in NDVI, more than twice than those of forests. These findings reveal that factors beyond climate influence global long-term trends in NDVI and suggest that global climate change models and analyses of primary productivity should incorporate land use effects.

  18. Short-Term Analysis of Human Dental Pulps After Direct Capping with Portland Cement

    PubMed Central

    Barbosa, Antonio Vinicius Holanda; Sampaio, Gerhilde Callou; Gomes, Fábio Almeida; de Oliveira, Daniel Pinto; de Albuquerque, Diana Santana; Sobral, Ana Paula Veras

    2009-01-01

    This study evaluated the short-term response of human pulp tissue when directly capped with Portland cement. In this series of cases, twenty human third molars that were scheduled for extraction were used. After cavity preparation, pulp exposure was achieved and Portland cement pulp capping was performed. Teeth were extracted after 1, 7, 14 and 21 days following treatment and prepared for histological examination and bacterial detection. Each group had 5 teeth. The results were descriptively analysed. Dentin bridge formation was seen in two teeth with some distance from the material interface (14 and 21 days). Soft inflammatory responses were observed in most of the cases. Bacteria were not disclosed in any specimen. PC exhibited some features of biocompatibility and capability of inducing mineral pulp response in short-term evaluation. The results suggested that PC has a potential to be used as a less expensive pulp capping material in comparison to other pulp capping materials. PMID:19444341

  19. Short-term analysis of human dental pulps after direct capping with portland cement.

    PubMed

    Barbosa, Antonio Vinicius Holanda; Sampaio, Gerhilde Callou; Gomes, Fábio Almeida; de Oliveira, Daniel Pinto; de Albuquerque, Diana Santana; Sobral, Ana Paula Veras

    2009-03-17

    This study evaluated the short-term response of human pulp tissue when directly capped with Portland cement. In this series of cases, twenty human third molars that were scheduled for extraction were used. After cavity preparation, pulp exposure was achieved and Portland cement pulp capping was performed. Teeth were extracted after 1, 7, 14 and 21 days following treatment and prepared for histological examination and bacterial detection. Each group had 5 teeth. The results were descriptively analysed. Dentin bridge formation was seen in two teeth with some distance from the material interface (14 and 21 days). Soft inflammatory responses were observed in most of the cases. Bacteria were not disclosed in any specimen. PC exhibited some features of biocompatibility and capability of inducing mineral pulp response in short-term evaluation. The results suggested that PC has a potential to be used as a less expensive pulp capping material in comparison to other pulp capping materials.

  20. Does machine perfusion decrease ischemia reperfusion injury?

    PubMed

    Bon, D; Delpech, P-O; Chatauret, N; Hauet, T; Badet, L; Barrou, B

    2014-06-01

    In 1990's, use of machine perfusion for organ preservation has been abandoned because of improvement of preservation solutions, efficient without perfusion, easy to use and cheaper. Since the last 15 years, a renewed interest for machine perfusion emerged based on studies performed on preclinical model and seems to make consensus in case of expanded criteria donors or deceased after cardiac death donations. We present relevant studies highlighted the efficiency of preservation with hypothermic machine perfusion compared to static cold storage. Machines for organ preservation being in constant evolution, we also summarized recent developments included direct oxygenation of the perfusat. Machine perfusion technology also enables organ reconditioning during the last hours of preservation through a short period of perfusion on hypothermia, subnormothermia or normothermia. We present significant or low advantages for machine perfusion against ischemia reperfusion injuries regarding at least one primary parameter: risk of DFG, organ function or graft survival.

  1. Short-term memory traces for action bias in human reinforcement learning.

    PubMed

    Bogacz, Rafal; McClure, Samuel M; Li, Jian; Cohen, Jonathan D; Montague, P Read

    2007-06-11

    Recent experimental and theoretical work on reinforcement learning has shed light on the neural bases of learning from rewards and punishments. One fundamental problem in reinforcement learning is the credit assignment problem, or how to properly assign credit to actions that lead to reward or punishment following a delay. Temporal difference learning solves this problem, but its efficiency can be significantly improved by the addition of eligibility traces (ET). In essence, ETs function as decaying memories of previous choices that are used to scale synaptic weight changes. It has been shown in theoretical studies that ETs spanning a number of actions may improve the performance of reinforcement learning. However, it remains an open question whether including ETs that persist over sequences of actions allows reinforcement learning models to better fit empirical data regarding the behaviors of humans and other animals. Here, we report an experiment in which human subjects performed a sequential economic decision game in which the long-term optimal strategy differed from the strategy that leads to the greatest short-term return. We demonstrate that human subjects' performance in the task is significantly affected by the time between choices in a surprising and seemingly counterintuitive way. However, this behavior is naturally explained by a temporal difference learning model which includes ETs persisting across actions. Furthermore, we review recent findings that suggest that short-term synaptic plasticity in dopamine neurons may provide a realistic biophysical mechanism for producing ETs that persist on a timescale consistent with behavioral observations.

  2. Neural mechanisms of short-term plasticity in the human visual system.

    PubMed

    Parks, Nathan A; Corballis, Paul M

    2012-12-01

    Following circumscribed retinal damage, extensive reorganization of topographically organized visual cortical areas has been demonstrated in several species of mammals (including humans). Although reorganization is often studied over extended time scales, neural response properties change within seconds of retinal deafferentation. Understanding the mechanisms underlying these short-term effects is essential for developing a complete picture of representational plasticity. One approach to the study of short-term plasticity has been to use an artificial scotoma, a stimulus-induced analog of a retinal scotoma, as a model. Here, we use event-related potentials in an artificial scotoma paradigm to examine 2 aspects of short-term plasticity in the human visual system. First, we investigated the changes within visual representations temporarily deprived of patterned visual input by probing the inner boundaries of an artificial scotoma. We found an enhanced early sensory P1, consistent with a reduction in inhibition (disinhibition), a proposed mechanism of short-term visual plasticity. Second, we investigated mechanisms through which representations of surrounding space invade a visually deprived area by probing the outer boundaries of an artificial scotoma. In this case, a later visual component, the N1, was enhanced, suggesting that feedback may provide a source of unmasked, or invading, activity to visually deprived representations.

  3. Space Resources Development: The Link Between Human Exploration and the Long-Term Commercialization of Space

    NASA Technical Reports Server (NTRS)

    Sanders, Gerald B.

    2000-01-01

    In a letter to the NASA Administrator, Dan Goldin, in January of 1999, the Office of Management and Budget (OMB) stated the following . OMB recommends that NASA consider commercialization in a broader context than the more focused efforts to date on space station and space shuttle commercialization. We suggest that NASA examine architectures that take advantage of a potentially robust future commercial infrastructure that could dramatically lower the cost of future human exploration." In response to this letter, the NASA Human Exploration and Development of Space (HEDS) Enterprise launched the BEDS Technology & Commercialization Initiative (HTCI) to link technology and system development for human exploration with the commercial development of space to emphasize the "D" (Development) in BEDS. The development of technologies and capabilities to utilize space resources is the first of six primary focus areas in this program. It is clear that Space Resources Development (SRD) is key for both long-term human exploration of our solar system and to the long-term commercialization of space since: a) it provides the technologies, products, and raw materials to support efficient space transportation and in-space construction and manufacturing, and b) it provides the capabilities and infrastructure to allow outpost growth, self-sufficiency, and commercial space service and utility industry activities.

  4. Lipoprotein lipase, LDL receptors and apo-lipoproteins in human fetal membranes at term.

    PubMed

    Huter, O; Wolf, H J; Schnetzer, A; Pfaller, K

    1997-11-01

    Ultrastructurally, all cells of human fetal membranes strongly exhibit a large amount of lipid deposits throughout pregnancy. Their origin and function is still unknown. The aim of this study was to investigate the localization of key components of lipid metabolism in this tissue. Using immunohistochemical techniques, the distribution of lipoprotein lipase (LPL), low density lipoprotein receptors (LDL receptors), and apo-lipoprotein B and E was investigated in 20 human fetal membranes at term. In addition, electron microscopy was used to study the intracellular localization of lipoprotein-sized particles. Amnionic epithelium and trophoblast cells reacted strongly for LPL. LDL receptors and apo-lipoproteins were present in amnionic epithelium and fibroblasts of the amnion. In none of the investigated cells were lipoprotein-sized particles identified. Similar results were obtained in all 20 cases. The findings indicate that lipoprotein from the amniotic fluid or from the maternal circulation may serve as substrate for lipids in human fetal membranes.

  5. Rationale and systems architecture for a near-term human lunar return

    NASA Astrophysics Data System (ADS)

    Willenberg, H. J.; Siegfried, W. H.

    2001-03-01

    Early human missions to the Moon have landed on six different sites on the lunar surface. These have all been in the low-latitude regions of the near side of the Moon. Early missions were designed primarily to assure crew safety rather than for scientific value. While the later missions added increasingly more challenging science, they remained restricted to near-side, low-latitude sites. Since the 1970s, we have learned considerably more about lunar planetology and resources. A return within the next five to ten years can greatly stimulate future human space exploration activities. We can learn much more about the distribution of lunar resources, especially about hydrogen, hydrated minerals, and water ice because they appear to be abundant near the lunar poles. The presence of hydrogen opens the possibility of industrial use of lunar resources to provide fuel for space transportation throughout the solar system. This paper discusses the rationale for near-term return of human crews to the Moon, and the advantages to be gained by selecting the Moon as the next target for human missions beyond low-Earth orbit. It describes a systems architecture for early missions, including transportation and habitation aspects. Specifically, we describe a primary transportation architecture that emphasizes existing Earth-to-orbit transportation systems, using expendable launch vehicles for cargo delivery and the Space Shuttle and its derivatives for human transportation. Transfer nodes should be located at the International Space Station (ISS) and at the Earth-Moon L1 (libration point). Each of the major systems is described, and the requisite technology readiness is assessed. These systems include Earth-to-orbit transportation, lunar transfer, lunar descent and landing, surface habitation and mobility, and return to Earth. With optimum reliance on currently existing space systems and a technology readiness assessment, we estimate the minimum development time required and perform

  6. Issues, indications, and controversies regarding intratympanic steroid perfusion

    PubMed Central

    Trune, Dennis

    2009-01-01

    Purpose of Review Office based Intratympanic inner ear steroid perfusion treatment (ITPs) for Meniere’s disease, autoimmune inner ear disease and sudden sensorineural hearing loss has been expanding over the past 10-15 years, yet remains controversial. The purpose of this review is to examine the current literature of basic science and human studies of ITPs treatment. Current Findings Animal studies exist regarding the delivery, distribution, biochemical and microbiological changes in the inner ear post ITPs. However, few clinical studies exist of ITPs treatment in sudden sensorineural hearing loss and even less in treating Meniere’s disease. There are no consistent studies regarding drug delivery methods, type and concentration of steroids. Moreover, there are no studies comparing ITPs results to the natural history of Meniere’s disease. Summary ITPs has impacted otology and neurotology practice due to increased utilization. A sound understanding of the basic science and clinical studies is needed to establish long term efficacy of ITPs in controlling hearing loss in Meniere’s disease by comparison to its natural history, as well as, potential application to other pathologies. PMID:18797285

  7. Parametric estimation of ventilation-perfusion ratio distributions.

    PubMed

    Stewart, W E; Mastenbrook, S M

    1983-07-01

    We present a model and rigorous statistical approach for recovery of ventilation-perfusion ratio (V/Q) distribution parameters from multiple inert gas elimination data. We model the lung as a parallel combination of shunt, dead space, and one to three log-normal distributions of gas exchange units. This model provides a natural set of parameters for characterizing V/Q distributions. The log-normal terms are adjustable to represent smooth or sharp peaks in the distribution. Since the peak locations and widths are explicit in the model, very few parameters are needed. We select and estimate the significant parameters of the model by use of standard statistical tests and constrained least squares. This method provides two major advances in V/Q distribution estimation: 1) it allows flexible pooling and statistical comparisons of multiple experiments, and 2) it simultaneously gives both point estimates and 95% probability intervals for the V/Q distribution parameters. We present results of our procedure for data from humans in health, stress, and pulmonary disease. A program package, VQPAR, in FORTRAN is available for implementing the procedure.

  8. Measuring perfusion with light (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jansen, Sanne M. A.; de Bruin, Daniel M.; Faber, Dirk J.; van Leeuwen, Ton G.

    2016-03-01

    There is no gold standard test for perfusion evaluation in surgery. Optical Imaging techniques are able to image tissue at high resolution and in real-time. Laser Speckle Contrast Imaging, Optical Coherence Tomography, Sidestream Darkfield and Incident Darkfield all use the interaction of light with tissue to create an image. To test their feasibility and explore validity in a controlled setting, we created a phantom with the optical properties of tissue and microvascular channels of 30-400 micrometer. With a Hamilton Syringe Pump we mimicked blood flow velocities of 0-20 mm/sec. Images of all different modalities at different blood flow velocities were compared in terms of imaging depth, resoluation and hemodynamic parameters.

  9. Human recombinant erythropoietin alters the flow-dependent vasodilatation of in vitro perfused rat mesenteric arteries with unbalanced endothelial endothelin-1 / nitric oxide ratio.

    PubMed

    Barhoumi, Tlili; Jallat, Isabelle; Berthelot, Alain; Laurant, Pascal

    2011-06-01

    Chronic use of human recombinant erythropoietin (r-HuEPO) is accompanied by serious vascular side effects related to the rise in blood viscosity and shear stress. We investigated the direct effects of r-HuEPO on endothelium and nitric oxide (NO)-dependent vasodilatation induced by shear stress of cannulated and pressurized rat mesenteric resistance arteries. Intravascular flow was increased in the presence or absence of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME; 10(-4) mol/L). In the presence of r-HuEPO, the flow-dependent vasodilatation was attenuated, while L-NAME completely inhibited it. The association of r-HuEPO and L-NAME caused a vasoconstriction in response to the rise in intravascular flow. Bosentan (10(-5) mol/L), an inhibitor of endothelin-1 (ET-1) receptors, corrected the attenuated vasodilatation observed with r-HuEPO and inhibited the vasoconstriction induced by flow in the presence of r-HuEPO and L-NAME. r-HuEPO and L-NAME exacerbated ET-1 vasoconstriction. At shear stress values of 2 and 14 dyn/cm(2) (1 dyn = 10(-5) N), cultured EA.hy926 endothelial cells incubated with r-HuEPO, L-NAME, or both released greater ET-1 than untreated cells. In conclusion, r-HuEPO diminishes flow-induced vasodilatation. This inhibitory effect seems to implicate ET-1 release. NO withdrawal exacerbates the vascular effects of ET-1 in the presence of r-HuEPO. These findings support the importance of a balanced endothelial ET-1:NO ratio to avoid the vasopressor effects of r-HuEPO.

  10. As the world turns: short-term human spatial memory in egocentric and allocentric coordinates.

    PubMed

    Banta Lavenex, Pamela; Lecci, Sandro; Prêtre, Vincent; Brandner, Catherine; Mazza, Christian; Pasquier, Jérôme; Lavenex, Pierre

    2011-05-16

    We aimed to determine whether human subjects' reliance on different sources of spatial information encoded in different frames of reference (i.e., egocentric versus allocentric) affects their performance, decision time and memory capacity in a short-term spatial memory task performed in the real world. Subjects were asked to play the Memory game (a.k.a. the Concentration game) without an opponent, in four different conditions that controlled for the subjects' reliance on egocentric and/or allocentric frames of reference for the elaboration of a spatial representation of the image locations enabling maximal efficiency. We report experimental data from young adult men and women, and describe a mathematical model to estimate human short-term spatial memory capacity. We found that short-term spatial memory capacity was greatest when an egocentric spatial frame of reference enabled subjects to encode and remember the image locations. However, when egocentric information was not reliable, short-term spatial memory capacity was greater and decision time shorter when an allocentric representation of the image locations with respect to distant objects in the surrounding environment was available, as compared to when only a spatial representation encoding the relationships between the individual images, independent of the surrounding environment, was available. Our findings thus further demonstrate that changes in viewpoint produced by the movement of images placed in front of a stationary subject is not equivalent to the movement of the subject around stationary images. We discuss possible limitations of classical neuropsychological and virtual reality experiments of spatial memory, which typically restrict the sensory information normally available to human subjects in the real world.

  11. Early Support of Intracranial Perfusion

    DTIC Science & Technology

    2013-10-01

    automated real-time vital signs monitoring data” was funded by USAF (MSA); UM PI: Deborah Stein  The project, titled “Noninvasive intracranial pressure ...scoring of cerebral perfusion pressure and intracranial pressure provides a Brain Trauma Index that predicts outcome in patients with severe TBI... intracranial pressure dose index: Dynamic 3-D scoring in the assessment of Traumatic Brain Injury Proceedings of American Association for the Surgery of

  12. Intestinal perfusion monitoring using photoplethysmography

    NASA Astrophysics Data System (ADS)

    Akl, Tony J.; Wilson, Mark A.; Ericson, M. Nance; Coté, Gerard L.

    2013-08-01

    In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed.

  13. Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.

    PubMed

    Panfoli, Isabella; Ravera, Silvia; Podestà, Marina; Cossu, Claudia; Santucci, Laura; Bartolucci, Martina; Bruschi, Maurizio; Calzia, Daniela; Sabatini, Federica; Bruschettini, Matteo; Ramenghi, Luca Antonio; Romantsik, Olga; Marimpietri, Danilo; Pistoia, Vito; Ghiggeri, Gianmarco; Frassoni, Francesco; Candiano, Giovanni

    2016-04-01

    Exosomes are secreted nanovesicles that are able to transfer RNA and proteins to target cells. The emerging role of mesenchymal stem cell (MSC) exosomes as promoters of aerobic ATP synthesis restoration in damaged cells, prompted us to assess whether they contain an extramitochondrial aerobic respiration capacity. Exosomes were isolated from culture medium of human MSCs from umbilical cord of ≥37-wk-old newborns or between 28- to 30-wk-old newborns (i.e.,term or preterm infants). Characterization of samples was conducted by cytofluorometry. Oxidative phosphorylation capacity was assessed by Western blot analysis, oximetry, and luminometric and fluorometric analyses. MSC exosomes express functional respiratory complexes I, IV, and V, consuming oxygen. ATP synthesis was only detectable in exosomes from term newborns, suggestive of a specific mechanism that is not completed at an early gestational age. Activities are outward facing and comparable to those detected in mitochondria isolated from term MSCs. MSC exosomes display an unsuspected aerobic respiratory ability independent of whole mitochondria. This may be relevant for their ability to rescue cell bioenergetics. The differential oxidative metabolism of pretermvs.term exosomes sheds new light on the preterm newborn's clinical vulnerability. A reduced ability to repair damaged tissue and an increased capability to cope with anoxic environment for preterm infants can be envisaged.-Panfoli, I., Ravera, S., Podestà, M., Cossu, C., Santucci, L., Bartolucci, M., Bruschi, M., Calzia, D., Sabatini, F., Bruschettini, M., Ramenghi, L. A., Romantsik, O., Marimpietri, D., Pistoia, V., Ghiggeri, G., Frassoni, F., Candiano, G. Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.

  14. A disposable flexible skin patch for clinical optical perfusion monitoring at multiple depths

    NASA Astrophysics Data System (ADS)

    Farkas, Dana L.; Kolodziejski, Noah J.; Stapels, Christopher J.; McAdams, Daniel R.; Fernandez, Daniel E.; Podolsky, Matthew J.; Christian, James F.; Ward, Brent B.; Vartarian, Mark; Feinberg, Stephen E.; Lee, Seung Yup; Parikh, Urmi; Mycek, Mary-Ann; Joyner, Michael J.; Johnson, Christopher P.; Paradis, Norman A.

    2016-03-01

    Stable, relative localization of source and detection fibers is necessary for clinical implementation of quantitative optical perfusion monitoring methods such as diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS). A flexible and compact device design is presented as a platform for simultaneous monitoring of perfusion at a range of depths, enabled by precise location of optical fibers in a robust and secure adhesive patch. We will discuss preliminary data collected on human subjects in a lower body negative pressure model for hypovolemic shock. These data indicate that this method facilitates simple and stable simultaneous monitoring of perfusion at multiple depths and within multiple physiological compartments.

  15. Long-term potentiation (LTP) of human sensory-evoked potentials.

    PubMed

    Kirk, Ian J; McNair, Nicolas A; Hamm, Jeffrey P; Clapp, Wesley C; Mathalon, Daniel H; Cavus, Idil; Teyler, Timothy J

    2010-09-01

    Long-term potentiation (LTP) is the principal candidate synaptic mechanism underlying learning and memory, and has been studied extensively at the cellular and molecular level in laboratory animals. Inquiry into the functional significance of LTP has been hindered by the absence of a human model as, until recently, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non-human preparations. In this brief review, we describe the results of paradigms recently developed in our laboratory for inducing LTP-like changes in visual-, and auditory-evoked potentials. We describe how rapid, repetitive presentation of sensory stimuli leads to a persistent enhancement of components of sensory-evoked potential in normal humans. Experiments to date, investigating the locus, stimulus specificity, and NMDA receptor dependence of these LTP-like changes suggest that they have the essential characteristics of LTP seen in experimental animals. The ability to elicit LTP from non-surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

  16. Visualizing tropoelastin in a long-term human elastic fibre cell culture model

    PubMed Central

    Halm, M.; Schenke-Layland, K.; Jaspers, S.; Wenck, H.; Fischer, F.

    2016-01-01

    Elastin is an essential protein found in a variety of tissues where resilience and flexibility are needed, such as the skin and the heart. When aiming to engineer suitable implants, elastic fibres are needed to allow adequate tissue renewal. However, the visualization of human elastogenesis remains in the dark. To date, the visualization of human tropoelastin (TE) production in a human cell context and its fibre assembly under live cell conditions has not been achieved. Here, we present a long-term cell culture model of human dermal fibroblasts expressing fluorescence-labelled human TE. We employed a lentiviral system to stably overexpress Citrine-labelled TE to build a fluorescent fibre network. Using immunofluorescence, we confirmed the functionality of the Citrine-tagged TE. Furthermore, we visualized the fibre assembly over the course of several days using confocal microscopy. Applying super resolution microscopy, we were able to investigate the inner structure of the elastin–fibrillin-1 fibre network. Future investigations will allow the tracking of TE produced under various conditions. In tissue engineering applications the fluorescent fibre network can be visualized under various conditions or it serves as a tool for investigating fibre degradation processes in disease-in-a-dish-models. PMID:26842906

  17. A Generic Bioheat Transfer Thermal Model for a Perfused Tissue

    PubMed Central

    Vaughan, J. Thomas

    2009-01-01

    A thermal model was needed to predict temperatures in a perfused tissue, which satisfied the following three criteria. One, the model satisfied conservation of energy. Two, the heat transfer rate from blood vessels to tissue was modeled without following a vessel path. Three, the model applied to any unheated and heated tissue. To meet these criteria, a generic bioheat transfer model (BHTM) was derived here by conserving thermal energy in a heated, vascularized, finite tissue and by making a few simplifying assumptions. Two linear, coupled differential equations were obtained with the following two variables: tissue volume averaged temperature and blood volume averaged temperature. The generic model was compared to the widely employed, empirical Pennes’ BHTM. The comparison showed that the Pennes’ perfusion term wCp(1−ε) should be interpreted as a local vasculature dependent heat transfer coefficient term. Suggestions are presented for further adaptations of the general BHTM for specific tissues using imaging techniques and numerical simulations. PMID:19640142

  18. Liver ex-vivo machine perfusion preservation: A review of the methodology and results of large animal studies and clinical trials.

    PubMed

    Marecki, Hazel; Bozorgzadeh, Adel; Porte, Robert; Leuvenink, Henri; Uygun, Korkut; Martins, Paulo

    2017-02-27

    Ex-vivo machine perfusion is a promising way to better preserve livers prior to transplantation. Currently, no methodology has verified benefit over simple cold storage. Before becoming clinically feasible, machine perfusion requires validation in models that reliably predict human performance. Such a model has been found in porcine liver, who's physiological, anatomical, and immunological characteristics closely resemble the human liver. Since the 1930s, researchers have explored machine perfusion as preservation, but only recently have clinical trials been performed. Making this technology clinically available holds the promise of expanding the donor pool through more effective preservation of extended criteria donor livers. Machine perfusion promises to decrease delayed graft function, primary non-function and biliary strictures, all common failure modes of transplanted extended criteria donor livers. While hypothermic machine perfusion has become the standard for kidney ex-vivo preservation, the precise settings and clinical role for liver machine perfusion has not yet been established. In research, there are two schools of thought: normothermic machine perfusion, closely mimicking physiologic conditions, and hypothermic machine perfusion, to maximize preservation. Here, we review the literature for porcine ex-vivo machine perfusion, with aim to summarize perfusion settings and outcomes pertinent to the clinical establishment of machine perfusion. This article is protected by copyright. All rights reserved.

  19. Ultrasound perfusion signal processing for tumor detection

    NASA Astrophysics Data System (ADS)

    Kim, MinWoo; Abbey, Craig K.; Insana, Michael F.

    2016-04-01

    Enhanced blood perfusion in a tissue mass is an indication of neo-vascularity and a sign of a potential malignancy. Ultrasonic pulsed-Doppler imaging is a preferred modality for noninvasive monitoring of blood flow. However, the weak blood echoes and disorganized slow flow make it difficult to detect perfusion using standard methods without the expense and risk of contrast enhancement. Our research measures the efficiency of conventional power-Doppler (PD) methods at discriminating flow states by comparing measurement performance to that of an ideal discriminator. ROC analysis applied to the experimental results shows that power Doppler methods are just 30-50 % efficient at perfusion flows less than 1ml/min, suggesting an opportunity to improve perfusion assessment through signal processing. A new perfusion estimator is proposed by extending the statistical discriminator approach. We show that 2-D perfusion color imaging may be enhanced using this approach.

  20. False memory for face in short-term memory and neural activity in human amygdala.

    PubMed

    Iidaka, Tetsuya; Harada, Tokiko; Sadato, Norihiro

    2014-12-03

    Human memory is often inaccurate. Similar to words and figures, new faces are often recognized as seen or studied items in long- and short-term memory tests; however, the neural mechanisms underlying this false memory remain elusive. In a previous fMRI study using morphed faces and a standard false memory paradigm, we found that there was a U-shaped response curve of the amygdala to old, new, and lure items. This indicates that the amygdala is more active in response to items that are salient (hit and correct rejection) compared to items that are less salient (false alarm), in terms of memory retrieval. In the present fMRI study, we determined whether the false memory for faces occurs within the short-term memory range (a few seconds), and assessed which neural correlates are involved in veridical and illusory memories. Nineteen healthy participants were scanned by 3T MRI during a short-term memory task using morphed faces. The behavioral results indicated that the occurrence of false memories was within the short-term range. We found that the amygdala displayed a U-shaped response curve to memory items, similar to those observed in our previous study. These results suggest that the amygdala plays a common role in both long- and short-term false memory for faces. We made the following conclusions: First, the amygdala is involved in detecting the saliency of items, in addition to fear, and supports goal-oriented behavior by modulating memory. Second, amygdala activity and response time might be related with a subject's response criterion for similar faces.

  1. Assessment of the long-term risks of inadvertent human intrusion

    SciTech Connect

    Wuschke, D.M. )

    1993-01-01

    Canada has conducted an extensive research program on the safe disposal of nuclear fuel wastes. The program has focused on the concept of disposal of spent fuel in durable containers in an engineered facility, or vault, 500 to 1000 m deep in intrusive igneous rock in the Canadian Shield. An essential goal of this program has been to develop and demonstrate a methodology to evaluate the performance of the facility against safety criteria established by Canada's regulatory agency, the Atomic Energy Control Board (AECB). These criteria are expressed in terms of risk, where risk is defined as the sum over all significant scenarios of the product of the probability of the scenario, the magnitude of the resultant dose, and the probability of a health effect per unit dose. This paper describes the methodology developed to assess the long-term risk from inadvertent human intrusion into such a facility and the results of its application to a conceptual design of such a facility.

  2. Heat stress increases long-term human migration in rural Pakistan

    NASA Astrophysics Data System (ADS)

    Mueller, V.; Gray, C.; Kosec, K.

    2014-03-01

    Human migration attributable to climate events has recently received significant attention from the academic and policy communities . Quantitative evidence on the relationship between individual, permanent migration and natural disasters is limited . A 21-year longitudinal survey conducted in rural Pakistan (1991-2012) provides a unique opportunity to understand the relationship between weather and long-term migration. We link individual-level information from this survey to satellite-derived measures of climate variability and control for potential confounders using a multivariate approach. We find that flooding--a climate shock associated with large relief efforts--has modest to insignificant impacts on migration. Heat stress, however--which has attracted relatively little relief--consistently increases the long-term migration of men, driven by a negative effect on farm and non-farm income. Addressing weather-related displacement will require policies that both enhance resilience to climate shocks and lower barriers to welfare-enhancing population movements.

  3. Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans.

    PubMed

    Jungkun, G; Kuss, H J; Gsell, W

    2001-01-01

    The nature of the discrepancy between short-term pharmacokinetic data (hours) on the one hand and long-term pharmacodynamic effects and the clinical latency of therapeutic amelioration on the other hand by tricyclic antidepressants is still unclear. A relapsed sensibilization of neuronal, immunologic, and endocrinologic systems by changes in receptor sensitivity has been proposed. However, the discrepancy may have a strong influence on many aspects of antidepressive therapy in humans. The aim of our study was to demonstrate long-term pharmacodynamic effects by single-dose antidepressive treatment in humans by measuring heart rate parameters in response to neurochemical parameters. 25 young healthy probands, divided into three treatment groups (amitriptyline, n = 10; clomipramine, n = 10; placebo, n = 5), were challenged by a noradrenaline infusion test at baseline and one and 21 days after a single dose of antidepressant. Heart rate and blood pressure as well as plasma levels of antidepressants and of noradrenaline and adrenaline were measured in response to noradrenaline infusion test. Noradrenaline infusion rate to reach an increase in blood pressure of RR > 30 mmHg was significantly decreased for both antidepressants on day 1. The same effect was true for the amitriptyline group on day 21. Furthermore, pretreated probands respond to antidepressants in a different way when compared to untreated probands. Like depressed patients under therapy they respond with a dramatic increase in sensitivity of the alphal-adrenergic receptor. We could demonstrate that the long-term pharmacodynamic effects have a strong influence on antidepressive therapy. A prolonged pharmacodynamic effect influences further clinical studies as well as our thinking about adverse drug effects. In clinical studies, washout periods may be to short to overcome the benefits of a previous medication. Adverse drug effects are often seen during periods when drugs were changed. The negative effect may

  4. Vanadium-mediated lipid peroxidation in microsomes from human term placenta

    SciTech Connect

    Byczkowski, J.Z.; Wan, B.; Kulkarni, A.P.

    1988-11-01

    Vanadium is considered an essential element present in living organisms in trace amounts but it is toxic when introduced in excessive doses to animals and humans. Vanadium compounds are extensively used in modern industry and occupational exposure to high doses of vanadium is quite common. In pregnant mice, vanadium accumulates preferentially in the placenta and to lower extent in fetal skeleton and mammary gland during exposure to radioactive vanadium. Accumulation of vanadium in fetoplacental unit may present threat to the fetus by interacting with enzymes and ion-transporting systems in membranes. It is also possible that accumulation of vanadium with its concomitant reduction to vanadyl may lead to lipid peroxidation, followed by damage to biological membranes, lysosomal enzymes release and destruction of placental tissue. To explore some of these possibilities the authors decided to examine whether vanadate can undergo redox cycling in microsomes from human term placenta (HTP) that can lead to lipid peroxidation.

  5. Full term delivery following cryopreservation of human embryos for 7. 5 years.

    PubMed

    Ben-Ozer, S; Vermesh, M

    1999-06-01

    Successful pregnancy in a 44 year old woman is described following the transfer of embryos which were cryopreserved for 7.5 years. The embryos were obtained during a gamete intra-Fallopian transfer (GIFT) procedure in 1989. To our knowledge this is one of the longest published periods of cryopreservation of embryos which has resulted in a healthy baby. This report illustrates the previously presumed viability and normality of human embryos undergoing long-term cryopreservation. Additionally, it emphasizes the importance for advanced reproductive technique programmes and patients to review and update their embryo status.

  6. Stn1 is critical for telomere maintenance and long-term viability of somatic human cells

    PubMed Central

    Boccardi, Virginia; Razdan, Neetu; Kaplunov, Jessica; Mundra, Jyoti J; Kimura, Masayuki; Aviv, Abraham; Herbig, Utz

    2015-01-01

    Disruption of telomere maintenance pathways leads to accelerated entry into cellular senescence, a stable proliferative arrest that promotes aging-associated disorders in some mammals. The budding yeast CST complex, comprising Cdc13, Stn1, and Ctc1, is critical for telomere replication, length regulation, and end protection. Although mammalian homologues of CST have been identified recently, their role and function for telomere maintenance in normal somatic human cells are still incompletely understood. Here, we characterize the function of human Stn1 in cultured human fibroblasts and demonstrate its critical role in telomere replication, length regulation, and function. In the absence of high telomerase activity, shRNA-mediated knockdown of hStn1 resulted in aberrant and fragile telomeric structures, stochastic telomere attrition, increased telomere erosion rates, telomere dysfunction, and consequently accelerated entry into cellular senescence. Oxidative stress augmented the defects caused by Stn1 knockdown leading to almost immediate cessation of cell proliferation. In contrast, overexpression of hTERT suppressed some of the defects caused by hStn1 knockdown suggesting that telomerase can partially compensate for hStn1 loss. Our findings reveal a critical role for human Stn1 in telomere length maintenance and function, supporting the model that efficient replication of telomeric repeats is critical for long-term viability of normal somatic mammalian cells. PMID:25684230

  7. Stn1 is critical for telomere maintenance and long-term viability of somatic human cells.

    PubMed

    Boccardi, Virginia; Razdan, Neetu; Kaplunov, Jessica; Mundra, Jyoti J; Kimura, Masayuki; Aviv, Abraham; Herbig, Utz

    2015-06-01

    Disruption of telomere maintenance pathways leads to accelerated entry into cellular senescence, a stable proliferative arrest that promotes aging-associated disorders in some mammals. The budding yeast CST complex, comprising Cdc13, Stn1, and Ctc1, is critical for telomere replication, length regulation, and end protection. Although mammalian homologues of CST have been identified recently, their role and function for telomere maintenance in normal somatic human cells are still incompletely understood. Here, we characterize the function of human Stn1 in cultured human fibroblasts and demonstrate its critical role in telomere replication, length regulation, and function. In the absence of high telomerase activity, shRNA-mediated knockdown of hStn1 resulted in aberrant and fragile telomeric structures, stochastic telomere attrition, increased telomere erosion rates, telomere dysfunction, and consequently accelerated entry into cellular senescence. Oxidative stress augmented the defects caused by Stn1 knockdown leading to almost immediate cessation of cell proliferation. In contrast, overexpression of hTERT suppressed some of the defects caused by hStn1 knockdown suggesting that telomerase can partially compensate for hStn1 loss. Our findings reveal a critical role for human Stn1 in telomere length maintenance and function, supporting the model that efficient replication of telomeric repeats is critical for long-term viability of normal somatic mammalian cells.

  8. Retrieval under stress decreases the long-term expression of a human declarative memory via reconsolidation.

    PubMed

    Larrosa, Pablo Nicolás Fernández; Ojea, Alejandro; Ojea, Ignacio; Molina, Victor Alejandro; Zorrilla-Zubilete, María Aurelia; Delorenzi, Alejandro

    2017-03-08

    Acute stress impairs memory retrieval of several types of memories. An increase in glucocorticoids, several minutes after stressful events, is described as essential to the impairing retrieval-effects of stressors. Moreover, memory retrieval under stress can have long-term consequences. Through what process does the reactivated memory under stress, despite the disrupting retrieval effects, modify long-term memories? The reconsolidation hypothesis proposes that a previously consolidated memory reactivated by a reminder enters a vulnerability phase (labilization) during which it is transiently sensitive to modulation, followed by a re-stabilization phase. However, previous studies show that the expression of memories during reminder sessions is not a condition to trigger the reconsolidation process since unexpressed memories can be reactivated and labilized. Here we evaluate whether it is possible to reactivate-labilize a memory under the impairing-effects of a mild stressor. We used a paradigm of human declarative memory whose reminder structure allows us to differentiate between a reactivated-labile memory state and a reactivated but non-labile state. Subjects memorized a list of five cue-syllables associated with their respective response-syllables. Seventy-two hours later, results showed that the retrieval of the paired-associate memory was impaired when tested 20min after a mild stressor (cold pressor stress (CPS)) administration, coincident with cortisol levels increase. Then, we investigated the long-term effects of CPS administration prior to the reminder session. Under conditions where the reminder initiates the reconsolidation process, CPS impaired the long-term memory expression tested 24h later. In contrast, CPS did not show effects when administered before a reminder session that does not trigger reconsolidation. Results showed that memory reactivation-labilization occurs even when retrieval was impaired. Memory reactivation under stress could hinder

  9. Prefrontal dopamine and the dynamic control of human long-term memory

    PubMed Central

    Wimber, M; Schott, B H; Wendler, F; Seidenbecher, C I; Behnisch, G; Macharadze, T; Bäuml, K-H T; Richardson-Klavehn, A

    2011-01-01

    Dopaminergic projections to the prefrontal cortex support higher-order cognitive functions, and are critically involved in many psychiatric disorders that involve memory deficits, including schizophrenia. The role of prefrontal dopamine in long-term memory, however, is still unclear. We used an imaging genetics approach to examine the hypothesis that dopamine availability in the prefrontal cortex selectively affects the ability to suppress interfering memories. Human participants were scanned via functional magnetic resonance imaging while practicing retrieval of previously studied target information in the face of interference from previously studied non-target information. This retrieval practice (RP) rendered the non-target information less retrievable on a later final test—a phenomenon known as retrieval-induced forgetting (RIF). In total, 54 participants were genotyped for the catechol-O-methyltransferase (COMT) Val108/158Met polymorphism. The COMT Val108/158Met genotype showed a selective and linear gene-dose effect on RIF, with the Met allele, which leads to higher prefrontal dopamine availability, being associated with greater RIF. Mirroring the behavioral pattern, the functional magnetic resonance imaging data revealed that Met allele carriers, compared with Val allele carriers, showed a greater response reduction in inhibitory control areas of the right inferior frontal cortex during RP, suggesting that they more efficiently reduced interference. These data support the hypothesis that the cortical dopaminergic system is centrally involved in the dynamic control of human long-term memory, supporting efficient remembering via the adaptive suppression of interfering memories. PMID:22832518

  10. Short and long-term energy intake patterns and their implications for human body weight regulation.

    PubMed

    Chow, Carson C; Hall, Kevin D

    2014-07-01

    Adults consume millions of kilocalories over the course of a few years, but the typical weight gain amounts to only a few thousand kilocalories of stored energy. Furthermore, food intake is highly variable from day to day and yet body weight is remarkably stable. These facts have been used as evidence to support the hypothesis that human body weight is regulated by active control of food intake operating on both short and long time scales. Here, we demonstrate that active control of human food intake on short time scales is not required for body weight stability and that the current evidence for long term control of food intake is equivocal. To provide more data on this issue, we emphasize the urgent need for developing new methods for accurately measuring energy intake changes over long time scales. We propose that repeated body weight measurements can be used along with mathematical modeling to calculate long-term changes in energy intake and thereby quantify adherence to a diet intervention and provide dynamic feedback to individuals that seek to control their body weight.

  11. Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans.

    PubMed

    Soare, Andreea; Cangemi, Roberto; Omodei, Daniela; Holloszy, John O; Fontana, Luigi

    2011-04-01

    Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women (mean age 53.7 ± 9.4 yrs) consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. The CR and EX groups were significantly leaner than the WD group. Energy intake was lower in the CR group (1769 ± 348 kcal/d) than in the WD (2302 ± 668 kcal/d) and EX (2798 ± 760 kcal/d) groups (P < 0.0001). Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups (P ≤ 0.01). Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging.

  12. Functional Maturation of Human Stem Cell-Derived Neurons in Long-Term Cultures

    PubMed Central

    Töpfer, Felix M.; Wood, Phillip G.; Busskamp, Volker; Bamberg, Ernst

    2017-01-01

    Differentiated neurons can be rapidly acquired, within days, by inducing stem cells to express neurogenic transcription factors. We developed a protocol to maintain long-term cultures of human neurons, called iNGNs, which are obtained by inducing Neurogenin-1 and Neurogenin-2 expression in induced pluripotent stem cells. We followed the functional development of iNGNs over months and they showed many hallmark properties for neuronal maturation, including robust electrical and synaptic activity. Using iNGNs expressing a variant of channelrhodopsin-2, called CatCh, we could control iNGN activity with blue light stimulation. In combination with optogenetic tools, iNGNs offer opportunities for studies that require precise spatial and temporal resolution. iNGNs developed spontaneous network activity, and these networks had excitatory glutamatergic synapses, which we characterized with single-cell synaptic recordings. AMPA glutamatergic receptor activity was especially dominant in postsynaptic recordings, whereas NMDA glutamatergic receptor activity was absent from postsynaptic recordings but present in extrasynaptic recordings. Our results on long-term cultures of iNGNs could help in future studies elucidating mechanisms of human synaptogenesis and neurotransmission, along with the ability to scale-up the size of the cultures. PMID:28052116

  13. Above and beyond short-term mating, long-term mating is uniquely tied to human personality.

    PubMed

    Holtzman, Nicholas S; Strube, Michael J

    2013-12-16

    To what extent are personality traits and sexual strategies linked? The literature does not provide a clear answer, as it is based on the Sociosexuality model, a one-dimensional model that fails to measure long-term mating (LTM). An improved two-dimensional model separately assesses long-term and short-term mating (STM; Jackson and Kirkpatrick, 2007). In this paper, we link this two-dimensional model to an array of personality traits (Big 5, Dark Triad, and Schizoid Personality). We collected data from different sources (targets and peers; Study 1), and from different nations (United States, Study 1; India, Study 2). We demonstrate for the first time that, above and beyond STM, LTM captures variation in personality.

  14. The Development of a Thin-Filmed, Non-Invasive Tissue Perfusion Sensor to Quantify Capillary Pressure Occlusion of Explanted Organs.

    PubMed

    OBrien, Timothy J; Roghani, Ali R; Jones, Philip A; Aardema, Charles H; Robertson, John L; Diller, Thomas E

    2016-10-05

    A new thin-filmed perfusion sensor was developed using a heat flux gauge, thin-film thermocouple, and a heating element. This sensor, termed "CHFT+", is an enhancement of the previously established CHFT (combined heat flux - temperature) sensor technology predominately used to quantify the severity of burns [1]. The CHFT+ sensor was uniquely designed to measure tissue perfusion on explanted organs destined for transplantation, but could be functionalized and used in a wide variety of other biomedical applications. Exploiting the thin and semi-flexible nature of the new CHFT+ sensor assembly, perfusion measurements can be made from the underside of the organ - providing a quantitative, indirect measure of capillary pressure occlusion. Results from a live tissue test demonstrated, for the first time, the effects of pressure occlusion on an explanted porcine kidney. CHFT+ sensors were placed on top of and underneath 18 kidneys to measure and compare perfusion at perfusate temperatures of 5˚C and 20˚C. The data collected shows greater perfusion on the topside than the underside of the specimen for the length of the experiment. This indicates that pressure occlusion is truly affecting the perfusion and thus, the overall preservation of explanted organs. Moreover, the results demonstrate the effect of preservation temperature on the tissue vasculature. Focusing on the topside perfusion only, the 20˚C perfusion was greater than the 5˚C perfusion, likely due to the vasoconstrictive response at the lower perfusion temperatures.

  15. Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

    PubMed Central

    Mittal, Pooja; Romero, Roberto; Tarca, Adi L.; Gonzalez, Juan; Draghici, Sorin; Xu, Yi; Dong, Zhong; Nhan-Chang, Chia-Ling; Chaiworapongsa, Tinnakorn; Lye, Stephen; Kusanovic, Juan Pedro; Lipovich, Leonard; Mazaki-Tovi, Shali; Hassan, Sonia S.; Mesiano, Sam; Kim, Chong Jai

    2011-01-01

    Aims To characterize the transcriptome of human myometrium during spontaneous labor at term. Methods Myometrium was obtained from women with (n=19) and without labor (n=20). Illumina® HumanHT-12 microarrays were utilized. Moderated t-tests and False Discovery Rate adjustment of p-values were applied. qRT-PCR was performed for a select set of differentially expressed genes in a separate set of samples. ELISA and Western Blot were utilized to confirm differential protein production in a third sample set. Results 1) 471 genes were differentially expressed; 2) Gene Ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using Signaling Pathway Impact Analysis indicated 6 significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-Stat signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) Systemic Lupus Erythematosus; and f) Chemokine signaling pathway; 3) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2 (PTGS2/COX2), heparin binding EGF-like growth factor (HBEGF), chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5 (LILRA5/LIR9), IL-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta (NFKBIZ), suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 (FKBP5) and aldehyde dehydrogenase (ALDH2) in labor; 4) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group. Conclusions Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene

  16. Differential expression of human placental neurotrophic factors in preterm and term deliveries.

    PubMed

    Dhobale, Madhavi V; Pisal, Hemlata R; Mehendale, Savita S; Joshi, Sadhana R

    2013-12-01

    Neurotrophic factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in development of the placenta and fetal brain. A series of human and animal studies in our department have shown that micronutrients (folic acid, vitamin B12) and omega 3 fatty acids like DHA are all interlinked in the one carbon cycle. Any alterations in one carbon components will lead to changes in methylation patterns that further affect the gene expression at critical periods of development resulting in complications during pregnancy. This may further contribute to risk for neurodevelopmental disorders in children born preterm. Therefore this study for the first time examines the mRNA levels from preterm and term placentae. A total number of 38 women delivering preterm (<37 weeks gestation) and 37 women delivering at term (=>37 weeks gestation) were recruited. The mRNA levels of BDNF and NGF were analyzed by real time quantitative polymerase chain reaction. Our results indicate that BDNF and NGF mRNA levels were lower in preterm group as compared to term group. There was a positive association of placental BDNF and NGF mRNA levels with cord plasma BDNF and NGF levels. The differential expression of BDNF and NGF gene in preterm placentae may also alter the vascular development in preterm deliveries. Our data suggests that the reduced mRNA levels of BDNF and NGF may possibly be a result of altered epigenetic mechanisms and may have an implication for altered fetal programming in children born preterm.

  17. The role of the human cerebellum in short- and long-term habituation of postural responses.

    PubMed

    Schwabe, Achim; Drepper, Johannes; Maschke, Matthias; Diener, Hans Christoph; Timmann, Dagmar

    2004-02-01

    The aim of the present study was to investigate the role of the human cerebellum in short-term (STH) and long-term habituation (LTH) of postural responses to repeated platform perturbations. Ten cerebellar patients and ten age- and sex-matched healthy controls participated. Twenty backward platform translations were applied on each of 5 consecutive days. Changes of postural response size within each day were assessed to determine STH and changes across days to determine LTH. Both controls and cerebellar patients showed a significant reduction of postural response size within each day (i.e. STH). No significant reduction of postural response size was observed across days (i.e. no LTH). Both controls and cerebellar patients, however, showed a tendency of response size to increase across days suggesting long-term sensitization. The amount of changes within and across days did not significantly differ between groups. The present findings suggest that changes of postural response size to repeated perturbations do not depend upon the integrity of the cerebellum.

  18. Long-term impacts of unconventional drilling operations on human and animal health.

    PubMed

    Bamberger, Michelle; Oswald, Robert E

    2015-01-01

    Public health concerns related to the expansion of unconventional oil and gas drilling have sparked intense debate. In 2012, we published case reports of animals and humans affected by nearby drilling operations. Because of the potential for long-term effects of even low doses of environmental toxicants and the cumulative impact of exposures of multiple chemicals by multiple routes of exposure, a longitudinal study of these cases is necessary. Twenty-one cases from five states were followed longitudinally; the follow-up period averaged 25 months. In addition to humans, cases involved food animals, companion animals and wildlife. More than half of all exposures were related to drilling and hydraulic fracturing operations; these decreased slightly over time. More than a third of all exposures were associated with wastewater, processing and production operations; these exposures increased slightly over time. Health impacts decreased for families and animals moving from intensively drilled areas or remaining in areas where drilling activity decreased. In cases of families remaining in the same area and for which drilling activity either remained the same or increased, no change in health impacts was observed. Over the course of the study, the distribution of symptoms was unchanged for humans and companion animals, but in food animals, reproductive problems decreased and both respiratory and growth problems increased. This longitudinal case study illustrates the importance of obtaining detailed epidemiological data on the long-term health effects of multiple chemical exposures and multiple routes of exposure that are characteristic of the environmental impacts of unconventional drilling operations.

  19. Short- and long-term effects of oral vancomycin on the human intestinal microbiota

    PubMed Central

    Isaac, Sandrine; Scher, Jose U.; Djukovic, Ana; Jiménez, Nuria; Littman, Dan R.; Abramson, Steven B.; Pamer, Eric G.; Ubeda, Carles

    2017-01-01

    Background Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown. Methods We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation. The clinical relevance of the observed microbiota perturbations was studied in mice. Results During vancomycin therapy, most intestinal microbiota genera and operational taxonomic units (OTUs) were depleted in all analysed subjects, including all baseline OTUs from the phylum Bacteroidetes. This was accompanied by a vast expansion of genera associated with infections, including Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked differences in microbiota resilience were observed among subjects. While some individuals recovered a microbiota close to baseline composition, in others, up to 89% of abundant OTUs could no longer be detected. The clinical relevance of the observed microbiota changes was further demonstrated in mice, which developed analogous microbiota alterations. During vancomycin treatment, mice were highly susceptible to intestinal colonization by an antibiotic-resistant pathogen and, upon antibiotic cessation, a less-resilient microbiota allowed higher levels of pathogen colonization. Conclusions Oral vancomycin induces drastic and consistent changes in the human intestinal microbiota. Upon vancomycin cessation, the microbiota recovery rate varied considerably among subjects, which could influence, as validated in mice, the level of susceptibility to pathogen intestinal colonization. Our results demonstrate the negative long-term effects of vancomycin, which should be considered as a fundamental aspect of the cost–benefit equation for antibiotic prescription. PMID

  20. Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex

    NASA Technical Reports Server (NTRS)

    Chen, W. R.; Lee, S.; Kato, K.; Spencer, D. D.; Shepherd, G. M.; Williamson, A.

    1996-01-01

    The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

  1. Transcriptomic signatures of villous cytotrophoblast and syncytiotrophoblast in term human placenta.

    PubMed

    Rouault, Christine; Clément, Karine; Guesnon, Mickael; Henegar, Corneliu; Charles, Marie-Aline; Heude, Barbara; Evain-Brion, Danièle; Degrelle, Séverine A; Fournier, Thierry

    2016-08-01

    During pregnancy, the placenta ensures multiple functions, which are directly involved in the initiation, fetal growth and outcome of gestation. The placental tissue involved in maternal-fetal exchanges and in synthesis of pregnancy hormones is the mononucleated villous cytotrophoblast (VCT) which aggregates and fuses to form and renew the syncytiotrophoblast (ST). Knowledge of the gene expression pattern specific to this endocrine and exchanges tissue of human placenta is of major importance to understand functions of this heterogeneous and complex tissue. Therefore, we undertook a global analysis of the gene expression profiles of primary cultured-VCT (n = 6) and in vitro-differentiated-ST (n = 5) in comparison with whole term placental tissue from which mononucleated VCT were isolated. A total of 880 differentially expressed genes (DEG) were observed between VCT/ST compared to whole placenta, and a total of 37 and 137 genes were significantly up and down-regulated, respectively, in VCT compared to ST. The 37 VCT-genes were involved in cellular processes (assembly, organization, and maintenance), whereas the 137 ST-genes were associated with lipid metabolism and cell morphology. In silico, all networks were linked to 3 transcriptional regulators (PPARγ, RARα and NR2F1) which are known to be essential for trophoblast differentiation. A subset of six DEG was validated by RT-qPCR and four by immunohistochemistry. To conclude, recognition of these pathways is fundamental to increase our understanding of the molecular basis of human trophoblast differentiation. The present study provides for the first time a gene expression signature of the VCT and ST compared to their originated term human placental tissue.

  2. Endothelial expression of Fc gamma receptor IIb in the full-term human placenta.

    PubMed

    Mishima, T; Kurasawa, G; Ishikawa, G; Mori, M; Kawahigashi, Y; Ishikawa, T; Luo, S-S; Takizawa, T; Goto, T; Matsubara, S; Takeshita, T; Robinson, J M; Takizawa, T

    2007-01-01

    In the third trimester, human placental endothelial cells express Fc gamma receptor IIb (FcgammaRIIb). This expression is unique because FcgammaRIIb is generally expressed on immune cells and is typically undetectable in adult endothelial cells. Recently, we found a novel FcgammaRIIb-defined, IgG-containing organelle in placental endothelial cells; this organelle may be a key structure for the transcytosis of IgG across the endothelial layer. In this study, we verify the expression of FcgammaRIIb in endothelial placenta cells and use reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing analyses to define the expressed FCGR2B mRNA transcript variant. We also investigated the distribution of FCGR2B mRNA and protein within the vascular tree of the full-term human placenta by RT-PCR and quantitative microscopy. The mRNA sequence of FCGR2B expressed specifically in placental endothelial cells is that of transcript variant 2. FcgammaRIIb expression and synthesis occur throughout the placental vascular tree but do not extend into the umbilical cord. This study provides additional information on FcgammaRIIb expression in the human placenta.

  3. Long Term Maintenance of a Microfluidic 3-D Human Liver Sinusoid

    PubMed Central

    Prodanov, Ljupcho; Jindal, Rohit; Bale, Shyam Sundhar; Hegde, Manjunath; McCarty, William J.; Golberg, Inna; Bhushan, Abhinav; Yarmush, Martin L.; Usta, O. Berk

    2016-01-01

    The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA’s initiative to replicate and replace chronic and acute drug testing in animals. For this purpose we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a-chip using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the liver sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic), urea excretion (detoxification) was observed under flow compared to static cultures. This human liver-on-a-chip should be further evaluated in drug-related studies. PMID:26152452

  4. Long-term maintenance of a microfluidic 3D human liver sinusoid.

    PubMed

    Prodanov, Ljupcho; Jindal, Rohit; Bale, Shyam Sundhar; Hegde, Manjunath; McCarty, William J; Golberg, Inna; Bhushan, Abhinav; Yarmush, Martin L; Usta, Osman Berk

    2016-01-01

    The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA's initiative to replicate and replace chronic and acute drug testing in animals. For this purpose, we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a-chip, using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the liver sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic) and urea excretion (detoxification) were observed under flow compared to static cultures. This human liver-on-a-chip should be further evaluated in drug-related studies.

  5. Long-term human response to uncertain environmental conditions in the Andes

    PubMed Central

    Dillehay, Tom D.; Kolata, Alan L.

    2004-01-01

    Human interaction with the physical environment has increasingly transformed Earth-system processes. Reciprocally, climate anomalies and other processes of environmental change of natural and anthropogenic origin have been affecting, and often disrupting, societies throughout history. Transient impact events, despite their brevity, can have significant long-term impact on society, particularly if they occur in the context of ongoing, protracted environmental change. Major climate events can affect human activities in critical conjunctures that shape particular trajectories of social development. Here we report variable human responses to major environmental events in the Andes with a particular emphasis on the period from anno Domini 500–1500 on the desert north coast of Perú. We show that preindustrial agrarian societies implemented distinct forms of anticipatory response to environmental change and uncertainty. We conclude that innovations in production strategies and agricultural infrastructures in these indigenous societies reflect differential social response to both transient (El Niño–Southern Oscillation events) and protracted (desertification) environmental change. PMID:15024122

  6. Factors implicated in the initiation of human parturition in term and preterm labor: a review.

    PubMed

    Ravanos, Konstantinos; Dagklis, Themistoklis; Petousis, Stamatios; Margioula-Siarkou, Chrysoula; Prapas, Yannis; Prapas, Nikolaos

    2015-01-01

    After accommodating the pregnancy for an average of 40 weeks, the uterus expels the fetus, the placenta and the membranes through the birth canal in a process named parturition. The absolute sequence of events that trigger and sustain human parturition are not yet fully clarified. Evidence suggests that spontaneous preterm and term labor seem to share a common inflammatory pathway. However, there are several other factors being involved in the initiation of human parturition. Placental corticotropin releasing hormone production seems to serve as a placental clock that might be set to ring earlier or later determining the duration of pregnancy and timing of labor. Estrogens do not cause contractions but their properties seem to capacitate uterus to coordinate and enhance contractions. Cytokines, prostaglandins, nitric oxide and steroids seem also to induce ripening by mediating remodeling of the extracellular matrix and collagen. Infection and microbe invasion resulting in chorioamnionitis also represents a common cause of early preterm labour. This review provides an overview of all these factors considered to be implicated in the initiation of human parturition.

  7. The ileal brake--inhibition of jejunal motility after ileal fat perfusion in man.

    PubMed Central

    Spiller, R C; Trotman, I F; Higgins, B E; Ghatei, M A; Grimble, G K; Lee, Y C; Bloom, S R; Misiewicz, J J; Silk, D B

    1984-01-01

    The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents. PMID:6706215

  8. Assessment of myocardial perfusion in patients after the arterial switch operation

    SciTech Connect

    Vogel, M.; Smallhorn, J.F.; Gilday, D.; Benson, L.N.; Ash, J.; Williams, W.G.; Freedom, R.M. )

    1991-02-01

    In 21 patients who had undergone the arterial switch operation, the adequacy of myocardial perfusion was evaluated by thallium-201 computed scintigraphy 2.6 +/- 2 (0.3-7) yr after surgery. Fourteen patients had undergone the arterial switch procedure after pulmonary artery banding and seven as a primary repair. Isoproterenol stress increased the heart rate by at least 55%. Tomographic imaging was performed at peak stress and 3 hr later in the reperfusion phase. Nine patients had perfusion defects. The perfusion defects were located at the left ventricular apex in four (with extension to the inferolateral wall in one), left ventricular anterolateral wall in two, ventricular septum in one, left ventricular inferior wall in one, and right ventricular free wall in one. Some of these defects could be due to myocardial damage at the time of surgery, but these results also raise concern about long-term adequacy of myocardial perfusion following the arterial switch procedure.

  9. UV exposure modulates hemidesmosome plasticity, contributing to long-term pigmentation in human skin.

    PubMed

    Coelho, Sergio G; Valencia, Julio C; Yin, Lanlan; Smuda, Christoph; Mahns, Andre; Kolbe, Ludger; Miller, Sharon A; Beer, Janusz Z; Zhang, Guofeng; Tuma, Pamela L; Hearing, Vincent J

    2015-05-01

    Human skin colour, ie pigmentation, differs widely among individuals, as do their responses to various types of ultraviolet radiation (UV) and their risks of skin cancer. In some individuals, UV-induced pigmentation persists for months to years in a phenomenon termed long-lasting pigmentation (LLP). It is unclear whether LLP is an indicator of potential risk for skin cancer. LLP seems to have similar features to other forms of hyperpigmentation, eg solar lentigines or age spots, which are clinical markers of photodamage and risk factors for precancerous lesions. To investigate what UV-induced molecular changes may persist in individuals with LLP, clinical specimens from non-sunburn-inducing repeated UV exposures (UVA, UVB or UVA + UVB) at 4 months post-exposure (short-term LLP) were evaluated by microarray analysis and dataset mining. Validated targets were further evaluated in clinical specimens from six healthy individuals (three LLP+ and three LLP-) followed for more than 9 months (long-term LLP) who initially received a single sunburn-inducing UVA + UVB exposure. The results support a UV-induced hyperpigmentation model in which basal keratinocytes have an impaired ability to remove melanin that leads to a compensatory mechanism by neighbouring keratinocytes with increased proliferative capacity to maintain skin homeostasis. The attenuated expression of SOX7 and other hemidesmosomal components (integrin α6β4 and plectin) leads to increased melanosome uptake by keratinocytes and points to a spatial regulation within the epidermis. The reduced density of hemidesmosomes provides supporting evidence for plasticity at the epidermal-dermal junction. Altered hemidesmosome plasticity, and the sustained nature of LLP, may be mediated by the role of SOX7 in basal keratinocytes. The long-term sustained subtle changes detected are modest, but sufficient to create dramatic visual differences in skin colour. These results suggest that the hyperpigmentation phenomenon

  10. UV exposure modulates hemidesmosome plasticity, contributing to long-term pigmentation in human skin

    PubMed Central

    Coelho, Sergio G.; Valencia, Julio C.; Yin, Lanlan; Smuda, Christoph; Mahns, Andre; Kolbe, Ludger; Miller, Sharon A.; Beer, Janusz Z.; Zhang, Guofeng; Tuma, Pamela L.; Hearing, Vincent J.

    2014-01-01

    Human skin color, i.e. pigmentation, differs widely among individuals as do their responses to various types of ultraviolet radiation (UV) and their risks of skin cancer. In some individuals UV-induced pigmentation persists for months to years in a phenomenon termed long-lasting pigmentation (LLP). It is unclear whether LLP is an indicator of potential risk for skin cancer. LLP seems to have similar features to other forms of hyperpigmentation, e.g. solar lentigines or age spots, which are clinical markers of photodamage and risk factors for precancerous lesions. To investigate what UV-induced molecular changes may persist in individuals with LLP, clinical specimens from non-sunburn-inducing repeated UV exposures (UVA, UVB or UVA+UVB) at 4 months post-exposure (short-term LLP) were evaluated by microarray analysis and dataset mining. Validated targets were further evaluated in clinical specimens from 6 healthy individuals (3 LLP+ and 3 LLP-) followed for more than 9 months (long-term LLP) who initially received a single sunburn-inducing UVA+UVB exposure. The results support a UV-induced hyperpigmentation model in which basal keratinocytes have an impaired ability to remove melanin that leads to a compensatory mechanism by neighboring keratinocytes with increased proliferative capacity to maintain skin homeostasis. The attenuated expression of SOX7 and other hemidesmosomal components (integrin α6β4 and plectin) leads to increased melanosome uptake by keratinocytes and points to a spatial regulation within the epidermis. The reduced density of hemidesmosomes provides supporting evidence for plasticity at the epidermal-dermal junction. Altered hemidesmosome plasticity, and the sustained nature of LLP, may be mediated by the role of SOX7 in basal keratinocytes. The long-term sustained subtle changes detected are modest, but sufficient to create dramatic visual differences in skin color. These results suggest that the hyperpigmentation phenomenon leading to increased

  11. Long-term use of high-heeled shoes alters the neuromechanics of human walking.

    PubMed

    Cronin, Neil J; Barrett, Rod S; Carty, Christopher P

    2012-03-01

    Human movement requires an ongoing, finely tuned interaction between muscular and tendinous tissues, so changes in the properties of either tissue could have important functional consequences. One condition that alters the functional demands placed on lower limb muscle-tendon units is the use of high-heeled shoes (HH), which force the foot into a plantarflexed position. Long-term HH use has been found to shorten medial gastrocnemius muscle fascicles and increase Achilles tendon stiffness, but the consequences of these changes for locomotor muscle-tendon function are unknown. This study examined the effects of habitual HH use on the neuromechanical behavior of triceps surae muscles during walking. The study population consisted of 9 habitual high heel wearers who had worn shoes with a minimum heel height of 5 cm at least 40 h/wk for a minimum of 2 yr, and 10 control participants who habitually wore heels for less than 10 h/wk. Participants walked at a self-selected speed over level ground while ground reaction forces, ankle and knee joint kinematics, lower limb muscle activity, and gastrocnemius fascicle length data were acquired. In long-term HH wearers, walking in HH resulted in substantial increases in muscle fascicle strains and muscle activation during the stance phase compared with barefoot walking. The results suggest that long-term high heel use may compromise muscle efficiency in walking and are consistent with reports that HH wearers often experience discomfort and muscle fatigue. Long-term HH use may also increase the risk of strain injuries.

  12. Technetium myocardial perfusion agents: an introduction

    SciTech Connect

    English, R.J.; Kozlowski, J.; Tumeh, S.S.; Holman, B.L.

    1987-09-01

    This is the third in a series of four Continuing Education articles on developing radiopharmaceuticals. After reading this article, the reader should be able to: 1) understand the basic concepts of myocardial perfusion imaging; and 2) discuss the advantages of the technetium myocardial perfusion complexes over thallium-201.

  13. Luxury perfusion following anterior ischemic optic neuropathy.

    PubMed

    Friedland, S; Winterkorn, J M; Burde, R M

    1996-09-01

    We present five patients who developed luxury perfusion following anterior ischemic optic neuropathy in whom fluorescein angiography was misinterpreted as "capillary hemangioma" or neovascularization of the disc. In each case, the segment of disc hyperemia corresponded to a spared region of visual field. Luxury perfusion represents a reparative autoregulatory reaction to ischemia.

  14. Myocardial perfusion with rubidium-82. III. Theory relating severity of coronary stenosis to perfusion deficit

    SciTech Connect

    Mullani, N.A.

    1984-11-01

    The relation between the quantitative perfusion deficit, as measured by emission computerized tomography, and the severity of coronary artery stenosis is important for the noninvasive clinical evaluation of coronary artery disease in man. Positron emission tomography allows direct noninvasive measurement of myocardial perfusion and quantification of the size of the perfusion defect. Given this important imformation, a mathematical model has been derived to gauge the severity of a coronary stenosis from quantitative perfusion measurements in the normal and poststenotic regions of the heart. The theoretical basis is presented for relating regional myocardial perfusion and regional perfusion resistance to total, coronary blood flow and resistance at normal resting flow and during maximal coronary vasodilation. The concept of perfusion reserve is presented as a clinical measure of the severity of a stenosis.

  15. [Compromized myocardial perfusion in arrhythmias (author's transl)].

    PubMed

    Simon, H; Neumann, G; Felix, R; Hedde, H; Schaede, A; Thurn, P; Winkler, C

    1977-09-15

    In 7 patients with arrhythmias of various origin the myocardial scintigram displayed either a diffuse or circumscript defect of the perfusion. The coronary arteriogram was normal in all patients. The localized defect of the perfusion in 2 patients was in the region of the upper part of the interventricular septum. Both had a left bundle brunch block. A correlation between the perfusion defect and the electrophysiological abnormality seems probable. The perfusion defect in one of the patients is most probably caused by a previous myocarditis followed by fibrous changes. In the other 6 patients the cause for the perfusion defect is not obvious. A history of myocarditis is missing. The presence of "small vessel disease" in those patients has however to be considered. Our results point to the relation between an abnormality of the microcirculation and arrhythmias in younger patients.

  16. Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging.

    PubMed

    Lin, Wei-Che; Chen, Pei-Chin; Huang, Yung-Cheng; Tsai, Nai-Wen; Chen, Hsiu-Ling; Wang, Hung-Chen; Lin, Tsu-Kung; Chou, Kun-Hsien; Chen, Meng-Hsiang; Chen, Yi-Wen; Lu, Cheng-Hsien

    2016-02-01

    Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning.

  17. Neuroblast long-term cell cultures from human fetal olfactory epithelium respond to odors.

    PubMed

    Vannelli, G B; Ensoli, F; Zonefrati, R; Kubota, Y; Arcangeli, A; Becchetti, A; Camici, G; Barni, T; Thiele, C J; Balboni, G C

    1995-06-01

    Primary cell cultures from human fetal olfactory neuroepithelium have been isolated, cloned, and propagated in continuous in vitro culture for approximately 1 year. The two clones we report here synthesize both neuronal proteins and olfactory-specific markers as well as the putative olfactory neurotransmitter, carnosine. In addition, patchclamp experiments reveal that these cells are electrically excitable. Following exposure to a panel of aromatic chemicals one of the cell cultures shows a specific increase in intracellular cAMP, indicating that some degree of functional maturity is expressed in vitro. The results suggest that these cells originate from the "stem cell" compartment that gives rise to mature olfactory receptor neurons. These long-term cell cultures represent models that will be useful in studying the mechanism(s) of olfaction and the regulation of olfactory neurogenesis and differentiation.

  18. Towards a computational reconstruction of the electrodynamics of premature and full term human labour.

    PubMed

    Aslanidi, O; Atia, J; Benson, A P; van den Berg, H A; Blanks, A M; Choi, C; Gilbert, S H; Goryanin, I; Hayes-Gill, B R; Holden, A V; Li, P; Norman, J E; Shmygol, A; Simpson, N A B; Taggart, M J; Tong, W C; Zhang, H

    2011-10-01

    We apply virtual tissue engineering to the full term human uterus with a view to reconstruction of the spatiotemporal patterns of electrical activity of the myometrium that control mechanical activity via intracellular calcium. The three-dimensional geometry of the gravid uterus has been reconstructed from segmented in vivo magnetic resonance imaging as well as ex vivo diffusion tensor magnetic resonance imaging to resolve fine scale tissue architecture. A late-pregnancy uterine smooth muscle cell model is constructed and bursting analysed using continuation algorithms. These cell models are incorporated into partial differential equation models for tissue synchronisation and propagation. The ultimate objective is to develop a quantitative and predictive understanding of the mechanisms that initiate and regulate labour.

  19. Effects of Long Term Supplementation of Anabolic Androgen Steroids on Human Skeletal Muscle

    PubMed Central

    Yu, Ji-Guo; Bonnerud, Patrik; Eriksson, Anders; Stål, Per S.; Tegner, Yelverton; Malm, Christer

    2014-01-01

    The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained

  20. Short-term hyperoxia does not exert immunologic effects during experimental murine and human endotoxemia

    PubMed Central

    Kiers, Dorien; Gerretsen, Jelle; Janssen, Emmy; John, Aaron; Groeneveld, R.; van der Hoeven, Johannes G.; Scheffer, Gert-Jan; Pickkers, Peter; Kox, Matthijs

    2015-01-01

    Oxygen therapy to maintain tissue oxygenation is one of the cornerstones of critical care. Therefore, hyperoxia is often encountered in critically ill patients. Epidemiologic studies have demonstrated that hyperoxia may affect outcome, although mechanisms are unclear. Immunologic effects might be involved, as hyperoxia was shown to attenuate inflammation and organ damage in preclinical models. However, it remains unclear whether these observations can be ascribed to direct immunosuppressive effects of hyperoxia or to preserved tissue oxygenation. In contrast to these putative anti-inflammatory effects, hyperoxia may elicit an inflammatory response and organ damage in itself, known as oxygen toxicity. Here, we demonstrate that, in the absence of systemic inflammation, short-term hyperoxia (100% O2 for 2.5 hours in mice and 3.5 hours in humans) does not result in increased levels of inflammatory cytokines in both mice and healthy volunteers. Furthermore, we show that, compared with room air, hyperoxia does not affect the systemic inflammatory response elicited by administration of bacterial endotoxin in mice and man. Finally, neutrophil phagocytosis and ROS generation are unaffected by short-term hyperoxia. Our results indicate that hyperoxia does not exert direct anti-inflammatory effects and temper expectations of using it as an immunomodulatory treatment strategy. PMID:26616217

  1. Human Performance in a Realistic Instrument-Control Task during Short-Term Microgravity

    PubMed Central

    Steinberg, Fabian; Kalicinski, Michael; Dalecki, Marc; Bock, Otmar

    2015-01-01

    Previous studies have documented the detrimental effects of microgravity on human sensorimotor skills. While that work dealt with simple, laboratory-type skills, we now evaluate the effects of microgravity on a complex, realistic instrument-control skill. Twelve participants controlled a simulated power plant during the short-term microgravity intervals of parabolic flight as well as during level flight. To this end they watched multiple displays, made strategic decisions and used multiple actuators to maximize their virtual earnings from the power plant. We quantified control efficiency as the participants’ net earnings (revenue minus expenses), motor performance as hand kinematics and dynamics, and stress as cortisol level, self-assessed mood and self-assessed workload. We found that compared to normal gravity, control efficiency substantially decreased in microgravity, hand velocity slowed down, and cortisol level and perceived physical strain increased, but other stress and motor scores didn’t change. Furthermore, control efficiency was not correlated with motor and stress scores. From this we conclude that realistic instrument control was degraded in short-term microgravity. This degradation can’t be explained by the motor and/or stress indicators under study, and microgravity affected motor performance differently in our complex, realistic skill than in the simple, laboratory-type skills of earlier studies. PMID:26083473

  2. Unsupervised Decoding of Long-Term, Naturalistic Human Neural Recordings with Automated Video and Audio Annotations

    PubMed Central

    Wang, Nancy X. R.; Olson, Jared D.; Ojemann, Jeffrey G.; Rao, Rajesh P. N.; Brunton, Bingni W.

    2016-01-01

    Fully automated decoding of human activities and intentions from direct neural recordings is a tantalizing challenge in brain-computer interfacing. Implementing Brain Computer Interfaces (BCIs) outside carefully controlled experiments in laboratory settings requires adaptive and scalable strategies with minimal supervision. Here we describe an unsupervised approach to decoding neural states from naturalistic human brain recordings. We analyzed continuous, long-term electrocorticography (ECoG) data recorded over many days from the brain of subjects in a hospital room, with simultaneous audio and video recordings. We discovered coherent clusters in high-dimensional ECoG recordings using hierarchical clustering and automatically annotated them using speech and movement labels extracted from audio and video. To our knowledge, this represents the first time techniques from computer vision and speech processing have been used for natural ECoG decoding. Interpretable behaviors were decoded from ECoG data, including moving, speaking and resting; the results were assessed by comparison with manual annotation. Discovered clusters were projected back onto the brain revealing features consistent with known functional areas, opening the door to automated functional brain mapping in natural settings. PMID:27148018

  3. Absence of short-term effects of UMTS exposure on the human auditory system.

    PubMed

    Parazzini, Marta; Lutman, Mark E; Moulin, Annie; Barnel, Cécile; Sliwinska-Kowalska, Mariola; Zmyslony, Marek; Hernadi, Istvan; Stefanics, Gabor; Thuroczy, Gyorgy; Ravazzani, Paolo

    2010-01-01

    The aim of this study, which was performed in the framework of the European project EMFnEAR, was to investigate the potential effects of Universal Mobile Telecommunications System (UMTS, also known as 3G) exposure at a high specific absorption rate (SAR) on the human auditory system. Participants were healthy young adults with no hearing or ear disorders. Auditory function was assessed immediately before and after exposure to radiofrequency (RF) radiation, and only the exposed ear was tested. Tests for the assessment of auditory function were hearing threshold level (HTL), distortion product otoacoustic emissions (DPOAE), contralateral suppression of transiently evoked otoacoustic emission (CAS effect on TEOAE), and auditory evoked potentials (AEP). The exposure consisted of speech at a typical conversational level delivered via an earphone to one ear, plus genuine or sham RF-radiation exposure obtained by an exposure system based on a patch antenna and controlled by software. Results from 73 participants did not show any consistent pattern of effects on the auditory system after a 20-min UMTS exposure at 1947 MHz at a maximum SAR over 1 g of 1.75 W/kg at a position equivalent to the cochlea. Analysis entailed a double-blind comparison of genuine and sham exposure. It is concluded that short-term UMTS exposure at this relatively high SAR does not cause measurable immediate effects on the human auditory system.

  4. Serum from humans on long-term calorie restriction enhances stress resistance in cell culture

    PubMed Central

    Salvatore, Francesco; Crosby, Seth D.; Fontana, Luigi

    2013-01-01

    Calorie restriction (CR) without malnutrition is the most robust intervention to slow aging and extend healthy lifespan in experimental model organisms. Several metabolic and molecular adaptations have been hypothesized to play a role in mediating the anti-aging effects of CR, including enhanced stress resistance, reduced oxidative stress and several neuroendocrine modifications. However, little is known about the independent effect of circulating factors in modulating key molecular pathways. In this study, we used sera collected from individuals practicing long-term CR and from age- and sex-matched individuals on a typical US diet to culture human primary fibroblasts and assess the effects on gene expression and stress resistance. We show that treatment of cultured cells with CR sera caused increased expression of stress-response genes and enhanced tolerance to oxidants. Cells cultured in serum from CR individuals showed a 30% increase in resistance to H2O2 damage. Consistently, SOD2 and GPX1 mRNA, two key endogenous antioxidant enzymes, were increased by 2 and 2.5 folds respectively in cells cultured with CR sera. These cellular and molecular adaptations mirror some of the key effects of CR in animals, and further suggest that circulating factors contribute to the CR-mediated protection against oxidative stress and stress-response in humans as well. PMID:23912304

  5. Hemodynamic effects of long-term morphological changes in the human carotid sinus.

    PubMed

    Seong, Jaehoon; Jeong, Woowon; Smith, Nataliya; Towner, Rheal A

    2015-04-13

    Previous investigations of morphology for human carotid artery bifurcation from infancy to young adulthood found substantial growth of the internal carotid artery with advancing age, and the development of the carotid sinus at the root of the internal carotid artery during teenage years. Although the reasons for the appearance of the carotid sinus are not clearly understood yet, it has been hypothesized that the dilation of the carotid sinus serves to support pressure sensing, and slows the blood flow to reduce pulsatility to protect the brain. In order to understand this interesting evolvement at the carotid bifurcation in the aspects of fluid mechanics, we performed in vitro phase-contrast MR flow experiments using compliant silicone replicas of age-dependent carotid artery bifurcations. The silicone models in childhood, adolescence, and adulthood were fabricated using a rapid prototyping technique, and incorporated with a bench-top flow mock circulation loop using a computer-controlled piston pump. The results of the in vitro flow study showed highly complex flow characteristics at the bifurcation in all age-dependent models. However, the highest magnitude of kinetic energy was found at the internal carotid artery in the child model. The high kinetic energy in the internal carotid artery during childhood might be one of the local hemodynamic forces that initiate morphological long-term development of the carotid sinus in the human carotid bifurcation.

  6. Successful five-day perfusion preservation of the canine kidney.

    PubMed

    McAnulty, J F; Ploeg, R J; Southard, J H; Belzer, F O

    1989-01-01

    Over 20 years ago, successful 3-day-perfusion preservation of canine kidneys was obtained. Since then, consistent 5-day preservation has not been reported. In this study, we investigated how the perfusate calcium concentration affected both mitochondrial function and posttransplant viability in dog kidneys preserved for 5 days. Dog kidneys were preserved by machine perfusion (5 degrees C) using a hydroxyethyl starch-gluconate solution that contained either 0.0, 0.5, 1.5, or 5.0 mM calcium. Mitochondria isolated from preserved kidneys has a loss of respiratory control when either 0.0, 1.5, or 5.0 mM calcium were present. However, the use of a perfusate with 0.5 mM calcium preserved the mitochondrial function at levels equivalent to controls for 5 days. Transplantation of kidneys preserved for 5 days with 0.0 or 1.5 mM calcium yielded poor survival (0% and 17%, respectively). The use of a 0.5-mM calcium perfusate increased posttransplant survival to 63% (5 of 8 transplanted). Donor pretreatment of kidneys with chlorpromazine (2.5 mg/kg i.v.) did not improve the function of mitochondria isolated from preserved kidneys but did increase survival in the 1.5-mM calcium group to 67% (4 of 6 transplanted) and in the 0.5 mM calcium group to 100% (7 of 7 transplanted). This is the first report to document consistently successful 5-day preservation of canine kidneys and clearly shows the importance of the perfusate calcium concentration in long-term kidney preservation. The specific mechanism by which calcium or chlorpromazine exert their effect is not known, but it is apparent that excessively high or low concentrations of calcium are damaging to the preserved organ, and an optimal calcium concentration combined with metabolic inhibition of calcium-dependent pathways can significantly improve the function of organs preserved for extended time periods.

  7. The Mouse Isolated Perfused Kidney Technique.

    PubMed

    Czogalla, Jan; Schweda, Frank; Loffing, Johannes

    2016-11-17

    The mouse isolated perfused kidney (MIPK) is a technique for keeping a mouse kidney under ex vivo conditions perfused and functional for 1 hr. This is a prerequisite for studying the physiology of the isolated organ and for many innovative applications that may be possible in the future, including perfusion decellularization for kidney bioengineering or the administration of anti-rejection or genome-editing drugs in high doses to prime the kidney for transplantation. During the time of the perfusion, the kidney can be manipulated, renal function can be assessed, and various pharmaceuticals administered. After the procedure, the kidney can be transplanted or processed for molecular biology, biochemical analysis, or microscopy. This paper describes the perfusate and the surgical technique needed for the ex vivo perfusion of mouse kidneys. Details of the perfusion apparatus are given and data are presented showing the viability of the kidney's preparation: renal blood flow, vascular resistance, and urine data as functional, transmission electron micrographs of different nephron segments as morphological readouts, and western blots of transport proteins of different nephron segments as molecular readout.

  8. Machine Perfusion Enhances Hepatocyte Isolation Yields From Ischemic Livers

    PubMed Central

    Izamis, Maria-Louisa; Perk, Sinem; Calhoun, Candice; Uygun, Korkut; Yarmush, Martin L.; Berthiaume, François

    2015-01-01

    Background High-quality human hepatocytes form the basis of drug safety and efficacy tests, cell-based therapies, and bridge-to-transplantation devices. Presently the only supply of cells derives from an inadequate pool of suboptimal disqualified donor livers. Here we evaluated whether machine perfusion could ameliorate ischemic injury that many of these livers experience prior to hepatocyte isolation. Methods Non-heparinized female Lewis rat livers were exposed to an hour of warm ischemia (34°C) and then perfused for 3 hours. Five different perfusion conditions that utilized the cell isolation apparatus were investigated, namely: (1) modified Williams Medium E and (2) Lifor, both with active oxygenation (95%O2/5%CO2), as well as (3) Lifor passively oxygenated with ambient air (21%O2/0.04%CO2), all at ambient temperatures (20±2°C). At hypothermic temperatures (5±1°C) and under passive oxygenation were (4) University of Wisconsin solution (UW) and (5) Vasosol. Negative and positive control groups comprised livers that had ischemia (WI) and livers that did not (Fresh) prior to cell isolation, respectively. Results Fresh livers yielded 32±9 million cells/g liver while an hour of ischemia reduced the cell yield to 1.6±0.6 million cells/g liver. Oxygenated Williams medium E and Lifor recovered yields of 39±11 and 31±2.3 million cells/g liver, respectively. The passively oxygenated groups produced 15±7 (Lifor), 13±7 (Vasosol), and 10±6 (UW) million cells/g liver. Oxygenated Williams Medium E was most effective at sustaining pH values, avoiding the accumulation of lactate, minimizing edematous weight gain and producing bile during perfusion. Conclusions Machine perfusion results in a dramatic increase in cell yields from livers that have had up to an hour of warm ischemia, but perfusate choice significantly impacts the extent of recovery. Oxygenated Williams Medium E at room temperature is superior to Lifor, UW and Vasosol, largely facilitated by its high

  9. Hydrostatic Isolated Limb Perfusion with Adeno-associated Virus Vectors Enhances Correction of Skeletal Muscle in Pompe Disease

    PubMed Central

    Sun, Baodong; Li, Songtao; Bird, Andrew; Koeberl, Dwight D.

    2010-01-01

    Glycogen storage disease type II (GSD-II; Pompe disease; MIM 232300) stems from the inherited deficiency of acid-α-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. We hypothesized that hydrostatic isolated limb perfusion (ILP) administration of an adeno-associated virus (AAV) vector containing a muscle specific promoter could achieve relatively higher transgene expression in the hindlimb muscles of GAA-knockout (GAA-KO) mice, in comparison with intravenous (IV) administration. ILP adminstration of AAV2/8 vectors encoding alkaline phosphatase or human GAA transduced skeletal muscles of the hindlimb widely, despite the relatively low number of vector particles administered (1×1011), and IV administration of an equivalent vector dose failed to transduce skeletal muscle detectably. Similarly, ILP administration of fewer vector particles of the AAV2/9 vector encoding human GAA (3×1010) transduced skeletal muscles of the hindlimb widely and significantly reduced glycogen content to, in comparison with IV administration. The only advantage for IV administration was moderately high level transduction of cardiac muscle, which demonstrated compellingly that ILP administration sequestered vector particles within the perfused limb. Reduction of glycogen storage in the extensor digitorum longus demonstrated the potential advantage of ILP-mediated delivery of AAV vectors in Pompe disease, because type II myofibers are resistant to enzyme replacement therapy. Thus, ILP will enhance AAV transduction of multiple skeletal muscles while reducing the required dosages in terms of vector particle numbers. PMID:20686508

  10. Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

    PubMed Central

    Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

    2016-01-01

    Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand. PMID:27725720

  11. Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

    NASA Astrophysics Data System (ADS)

    Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

    2016-10-01

    Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

  12. Free-Breathing Cardiac MR Stress Perfusion with Real-Time Slice Tracking

    PubMed Central

    Basha, Tamer A.; Roujol, Sébastien; Kissinger, Kraig V.; Goddu, Beth; Berg, Sophie; Manning, Warren J.; Nezafat, Reza

    2013-01-01

    Purpose To develop a free-breathing cardiac MR perfusion sequence with slice tracking for use after physical exercise. Methods We propose to use a leading navigator, placed immediately before each 2D slice acquisition, for tracking the respiratory motion and updating the slice location in real-time. The proposed sequence was used to acquire CMR perfusion datasets in 12 healthy adult subjects and 8 patients. Images were compared with the conventional perfusion (i.e. without slice tracking) results from the same subjects. The location and geometry of the myocardium were quantitatively analyzed, and the perfusion signal curves were calculated from both sequences to show the efficacy of the proposed sequence. Results The proposed sequence was significantly better compared to the conventional perfusion sequence in terms of qualitative image scores. Changes in the myocardial location and geometry decreased by ~50% in the slice tracking sequence. Furthermore, the proposed sequence had signal curves that are smoother and less noisy. Conclusion The proposed sequence significantly reduces the effect of the respiratory motion on the image acquisition in both rest and stress perfusion scans. PMID:24123153

  13. Ventilation-perfusion imaging in pulmonary papillomatosis

    SciTech Connect

    Espinola, D.; Rupani, H.; Camargo, E.E.; Wagner, H.N. Jr.

    1981-11-01

    Three children with laryngeal papillomas involving the lungs had serial ventilation-perfusion scintigrams to assess results of therapy designed to reduce the bronchial involvement. Different imaging patterns were observed depending on size, number, and location of lesions. In early parenchymal involvement a ventilation-perfusion mismatch was seen. The initial and follow-up studies correlated well with clinical and radiographic findings. This noninvasive procedure is helpful in evaluating ventilatory and perfusion impairment in these patients as well as their response to treatment.

  14. Cochlear perfusion with a viscous fluid.

    PubMed

    Wang, Yi; Olson, Elizabeth S

    2016-07-01

    The flow of viscous fluid in the cochlea induces shear forces, which could provide benefit in clinical practice, for example to guide cochlear implant insertion or produce static pressure to the cochlear partition or wall. From a research standpoint, studying the effects of a viscous fluid in the cochlea provides data for better understanding cochlear fluid mechanics. However, cochlear perfusion with a viscous fluid may damage the cochlea. In this work we studied the physiological and anatomical effects of perfusing the cochlea with a viscous fluid. Gerbil cochleae were perfused at a rate of 2.4 μL/min with artificial perilymph (AP) and sodium hyaluronate (Healon, HA) in four different concentrations (0.0625%, 0.125%, 0.25%, 0.5%). The different HA concentrations were applied either sequentially in the same cochlea or individually in different cochleae. The perfusion fluid entered from the round window and was withdrawn from basal scala vestibuli, in order to perfuse the entire perilymphatic space. Compound action potentials (CAP) were measured after each perfusion. After perfusion with increasing concentrations of HA in the order of increasing viscosity, the CAP thresholds generally increased. The threshold elevation after AP and 0.0625% HA perfusion was small or almost zero, and the 0.125% HA was a borderline case, while the higher concentrations significantly elevated CAP thresholds. Histology of the cochleae perfused with the 0.0625% HA showed an intact Reissner's membrane (RM), while in cochleae perfused with 0.125% and 0.25% HA RM was torn. Thus, the CAP threshold elevation was likely due to the broken RM, likely caused by the shear stress produced by the flow of the viscous fluid. Our results and analysis indicate that the cochlea can sustain, without a significant CAP threshold shift, up to a 1.5 Pa shear stress. Beside these finding, in the 0.125% and 0.25% HA perfusion cases, a temporary CAP threshold shift was observed, perhaps due to the presence and

  15. Inner ear drug delivery via a reciprocating perfusion system in the guinea pig

    PubMed Central

    Chen, Zhiqiang; Kujawa, Sharon G.; McKenna, Michael J.; Fiering, Jason O.; Mescher, Mark J.; Borenstein, Jeffrey T.; Leary Swan, Erin E.; Sewell, William F.

    2007-01-01

    Rapid progress in understanding the molecular mechanisms associated with cochlear and auditory nerve degenerative processes offers hope for the development of gene-transfer and molecular approaches to treat these diseases in patients. For therapies based on these discoveries to become clinically useful, it will be necessary to develop safe and reliable mechanisms for the delivery of drugs into the inner ear, bypassing the blood–labyrinthine barrier. Toward the goal of developing an inner ear perfusion device for human use, a reciprocating microfluidic system that allows perfusion of drugs into the cochlear perilymph through a single inlet hole in scala tympani of the basal turn was developed. The performance of a prototype, extracorporeal reciprocating perfusion system in guinea pigs is described. Analysis of the cochlear distribution of compounds after perfusion took advantage of the place-dependent generation of responses to tones along the length of the cochlea. Perfusion with a control artificial perilymph solution had no effect. Two drugs with well-characterized effects on cochlear physiology, salicylate (5 mM) and DNQX (6,7-Dinitroquinoxaline-2,3-dione; 100 and 300 μM), reversibly altered responses. The magnitude of drug effect decreased with distance from the perfusion pipette for up to 10 mm, and increased with dose and length of application. PMID:16274830

  16. INTRAVENOUS REGIONAL ANTIBIOTIC PERFUSION THERAPY AS AN ADJUNCTIVE TREATMENT FOR DIGITAL LESIONS IN SEABIRDS.

    PubMed

    Fiorello, Christine V

    2017-03-01

    Foot infections are a common problem among seabirds in wildlife rehabilitation. Pododermatitis and digital infections are often challenging to treat because of the presence of suboptimal substrates, abnormal weight-bearing due to injuries, and suboptimal nutritional or health status. Seabirds represent the majority of animals requiring rehabilitation after oil spills, and foot problems are a common reason for euthanasia among these birds. Antibiotic intravenous regional perfusion therapy is frequently used in humans and other species to treat infections of the distal extremities, but it has not been evaluated in seabirds. During the 2015 Refugio oil spill response, four birds with foot lesions (pododermatitis, osteomyelitis, or both) were treated with ampicillin/sulbactam administered intravenously to the affected limb(s) in addition to systemic antibiotics and anti-inflammatories. Three of the birds, all brown pelicans ( Pelecanus occidentalis ) recovered rapidly and were released. Two of these birds had acute pododermatitis and were treated once with intravenous regional perfusion. They were released approximately 3 wk after the perfusion therapy. The third pelican had osteomyelitis of a digit. It was treated twice with intravenous regional perfusion and was released about 1 mo after the initial perfusion therapy. The fourth bird, a Pacific loon ( Gavia pacifica ), was treated once with perfusion therapy but did not respond to treatment and was euthanatized. No serious adverse effects were observed. This technique should be explored further in avian species.

  17. Inhomogeneity of pulmonary perfusion during sustained microgravity on SLS-1

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim; Guy, Harold J. B.; Elliott, Ann R.; West, John B.

    1994-01-01

    We studied the effects of gravity on the inhomogeneity of pulmonary perfusion in humans by performing hyperventilation-breath-hold single-breath measurements before, during, and after 9 days of continuous exposure to microgravity during the Spacelab Life Sciences-1 (SLS-1) mission. In microgravity the indicators of inhomogeneity of perfusion, especially the size of cardiogenic oscillations in expired CO2 and the height of phase IV, were markedly reduced. Cardiogenic oscillations were reduced to approximately 60% of their preflight standing size, and the height of phase IV was between 0 and -8% (a terminal fall became a small terminal rise) of the preflight standing value. The terminal change in expired CO2 was nearly abolished in microgravity, indicating more uniformity of blood flow between lung units that close and those that remain open at the end of expiration. A possible explanation of this observation is the disappearance of gravity-dependent topographic inequality of blood flow. The residual cardiogenic oscillations in expired CO2 imply a persisting inhomogeneity of perfusion in the absence of gravity, probably in lung regions that are not within the same acinus.

  18. Cutaneous toxicity of 2-chloroethyl methyl sulfide in isolated perfused porcine skin.

    PubMed

    King, J R; Monteiro-Riviere, N A

    1990-06-01

    Previous research has shown the isolated perfused porcine skin flap (IPPSF) to be a novel in vitro experimental model for investigating xenobiotic percutaneous absorption. In this study, the IPPSF was used to biochemically and morphologically assess the dermatotoxicity of 2-chloroethyl methyl sulfide (CEMS), a monofunctional analog of the vesicant, sulfur mustard. IPPSFs were perfused in a recirculating perfusion system and were treated with 97% CEMS (n = 4) or served as controls (n = 4). Additional IPPSFs were perfused in a nonrecirculating perfusion system and were treated with CEMS (n = 4) or were controls (n = 4). After dosing, each IPPSF was perfused for 8 hr. Cumulative glucose utilization (GU) and lactate production/glucose utilization ratio (L/GU ratio) were used as viability parameters. The average rate of GU for CEMS was significantly lower than control (p less than 0.05) in the recirculating and nonrecirculating IPPSFs. The L/GU ratio for CEMS was not significantly different (p greater than 0.05) from control for either perfusion system. CEMS resulted in a marked increase in vascular resistance versus control in both perfusion systems. Gross vesicles and bullae formation occurred in six of the CEMS-treated IPPSFs. Light microscopy revealed subepidermal vesicle formation above the basement membrane and extensive basal cell pyknosis in all IPPSFs treated with CEMS. No macroscopic or microscopic lesions were noted in the control flaps. Transmission electron microscopy revealed separation between the lamina lucida and the lamina densa of the basal lamina, with intracellular vacuolization and mitochondrial swelling occurring in the stratum basale and stratum spinosum cells of IPPSFs treated with CEMS. These lesions are similar to those described after human exposure to sulfur mustard. Full characterization of the morphological and biochemical changes seen after topical exposure of the IPPSF to vesicants may shed light on the pathogenesis of cutaneous toxicity

  19. A short term -12° head down tilt does not mimic microgravity in terms of human gonadal function

    NASA Astrophysics Data System (ADS)

    Strollo, Felice; Pecorelli, Lia; Strollo, Giovanna; Morè, Massimo; Riondino, Giuseppe; Masini, Maria Angela; Uva, Bianca Maria

    2006-09-01

    A significant reversible decrease in testosterone (T) has been associated with microgravity in male rodents and humans. Urinary T excretion increases in primates under hypergravity. Hypogonadism is somehow related to abnormally high levels of leptin (L), a hormone produced by the adipose tissue which has been found to increase under microgravity simulation conditions like head down bed rest (HDBR). The aim of this study was to assess hemodynamic and pituitary-adrenal and -gonadal adaptation to an acute HDBR test to be eventually used on a routine basis to get better prepared to next space flights. The Authors performed a 1 hour -12° HDBR in 6 male and 6 female volunteers who underwent heart rate and blood pressure measurement together with a blood draw three times at 30 min intervals from the start to the end of the test for L, T, estradiol (E2), LH, androstenedione (A), cortisol (F), ACTH. 12 age- and sexmatched control subjects followed the same protocol except for keeping the sitting position all the time. According to the ANOVA for repeated measures, no changes occurred in L, T, E2 or LH whereas A, F and ACTH significantly decreased independently of gender. During HDBR systolic blood pressure decreased in both genders, diastolic blood pressure decreased significantly only in men and HR showed a more clear-cut decrease in women than in men. As a conclusion, such an acute steep-slope HDBR protocol may be efficiently used to testing immediate individual haemodynamic or adrenal response to microgravity but is not suitable for studies concerning gonadal adaptation.

  20. Molecular and Immunohistochemical Characterization of Historical Long-Term Preserved Fixed Tissues from Different Human Organs.

    PubMed

    Hühns, Maja; Röpenack, Paula; Erbersdobler, Andreas

    2015-01-01

    University and museum collections are very important sources of biological samples that can be used to asses the past and present genetic diversity of many species. Modern genetic and immunohistochemical techniques can be used on long-term preserved fixed tissues from museum specimens to answer epidemiological questions. A proof of principle was established to apply modern molecular genetics and immunohistochemical methods to these old specimens and to verify the original diagnosis. We analysed 19 specimens from our university collection including human organs that had been in fixative for more than 80 years. The tissues originated from lung, colon, brain, heart, adrenal gland, uterus and skin. We isolated amplifiable DNA from these wet preparations and performed mutational analysis of BRAF, KRAS and EGFR. The tissues were also embedded in paraffin and used for modern histology and immunohistochemistry. Our data show that amplifiable DNA is extractable and ranged from 0.25 to 22.77 μg of total DNA. In three specimens BRAFV600E or KRASG12D mutations were found. Additionally, expression of different proteins like vimentin and GFAP was detected immunohistochemical in six investigated specimens. On the basis of our results the original diagnosis was altered in three specimens. Our work showed that it is possible to extract amplifiable DNA suitable for sequence analysis from long-term fixed tissue. Furthermore, histology and immunohistochemistry is feasible in specimens fixed long time ago. We conclude that these old preparations are suitable for further epidemiological research and that our methods open up new opportunities for future studies.

  1. Molecular and Immunohistochemical Characterization of Historical Long-Term Preserved Fixed Tissues from Different Human Organs

    PubMed Central

    Hühns, Maja; Röpenack, Paula; Erbersdobler, Andreas

    2015-01-01

    University and museum collections are very important sources of biological samples that can be used to asses the past and present genetic diversity of many species. Modern genetic and immunohistochemical techniques can be used on long-term preserved fixed tissues from museum specimens to answer epidemiological questions. A proof of principle was established to apply modern molecular genetics and immunohistochemical methods to these old specimens and to verify the original diagnosis. We analysed 19 specimens from our university collection including human organs that had been in fixative for more than 80 years. The tissues originated from lung, colon, brain, heart, adrenal gland, uterus and skin. We isolated amplifiable DNA from these wet preparations and performed mutational analysis of BRAF, KRAS and EGFR. The tissues were also embedded in paraffin and used for modern histology and immunohistochemistry. Our data show that amplifiable DNA is extractable and ranged from 0.25 to 22.77 μg of total DNA. In three specimens BRAFV600E or KRASG12D mutations were found. Additionally, expression of different proteins like vimentin and GFAP was detected immunohistochemical in six investigated specimens. On the basis of our results the original diagnosis was altered in three specimens. Our work showed that it is possible to extract amplifiable DNA suitable for sequence analysis from long-term fixed tissue. Furthermore, histology and immunohistochemistry is feasible in specimens fixed long time ago. We conclude that these old preparations are suitable for further epidemiological research and that our methods open up new opportunities for future studies. PMID:26252375

  2. Long term PM2.5 estimation and its impact on human health in Beijing, China

    NASA Astrophysics Data System (ADS)

    Zheng, Sheng; Pozzer, Andrea; Cao, Chunxiang

    2014-05-01

    Due to the economic growth and urbanization, the emissions of pollutants have increased significantly in the North China Plain (NCP). Beijing, the capital of China, is located at the northern tip of NCP, and it is considered one of the most densely populated cities with the poorest air quality. This is of major concerns, because of the impact of high pollutants concentration on human health. The present study analyses the characteristics of AOD and the particulate matter with diameter < 2.5 μm (PM2.5) and its impact on human health in the central Beijing areas. We acquire AOD from Aerosol Robotic Network (AERONET) in Beijing from 2001 to 2012. The AOD data are fitted with a lognormal distribution, and the 95% of the cumulative probability is used as the threshold for episodes of high AOD. Most episodes occur in summer, mostly in June, though this is combined with high precipitation. Episodes of high AOD caused by coarse pollutants occur only in March and April, and they are mostly caused by dust from the north. According to wind direction, wind speed, boundary layer height (BLH) and pollutant emission distribution, episodes of high AOD are due to the anthropogenic pollutants from the south (Hebei province). Based on ground PM2.5 observation from the US embassy in Beijing from 2010 to 2011, we establish a relationship between PM2.5and AERONET AOD, including BLH and relative humidity (RH) correction. Thanks to this method, 12 years of PM2.5 are estimated for the Beijing central area, allowing the estimation of long term concentrations of this pollutant. Since there is no obvious difference among the daily PM2.5 of six stations lying in Chaoyang, Dongcheng, and Xicheng district, we use the daily PM2.5 from US embassy station to represent the PM2.5 concentration in these three districts, and calculate yearly premature mortality due to long term exposure to PM2.5among the population with an age of ≥ 30 yr in these three districts.

  3. Cortical reorganization after long-term adaptation to retinal lesions in humans.

    PubMed

    Chung, Susana T L

    2013-11-13

    Single-unit recordings demonstrated that the adult mammalian visual cortex is capable of reorganizing after induced retinal lesions. In humans, whether the adult cortex is capable of reorganizing has only been studied using functional magnetic resonance imaging, with equivocal results. Here, we exploited the phenomenon of visual crowding, a major limitation on object recognition, to show that, in humans with long-standing retinal (macular) lesions that afflict the fovea and thus use their peripheral vision exclusively, the signature properties of crowding are distinctly different from those of the normal periphery. Crowding refers to the inability to recognize objects when the object spacing is smaller than the critical spacing. Critical spacing depends only on the retinal location of the object, scales linearly with its distance from the fovea, and is approximately two times larger in the radial than the tangential direction with respect to the fovea, thus demonstrating the signature radial-tangential anisotropy of the crowding zone. Using retinal imaging combined with behavioral measurements, we mapped out the crowding zone at the precise peripheral retinal locations adopted by individuals with macular lesions as the new visual reference loci. At these loci, the critical spacings are substantially smaller along the radial direction than expected based on the normal periphery, resulting in a lower scaling of critical spacing with the eccentricity of the peripheral locus and a loss in the signature radial-tangential anisotropy of the crowding zone. These results imply a fundamental difference in the substrate of cortical processing in object recognition following long-term adaptation to macular lesions.

  4. Long-Term Treatment of Native LDL Induces Senescence of Cultured Human Endothelial Cells

    PubMed Central

    Oh, Sung-Tack; Park, Hoon; Yoon, Hyun Joong

    2017-01-01

    The study aimed to evaluate whether the treatment of primary cultured human endothelial cells with native low-density lipoprotein (nLDL) could induce their senescence and to uncover some of the putative mechanisms involved. For this purpose, human umbilical vein endothelial cells (HUVECs) were subcultured and/or continuously cultured with nLDL (0, 2, 5, and 10 μg protein/mL), for up to 9 days. The results indicated that nLDL inhibited the proliferation of HUVECs by arresting the cell cycle at G1 phase. The G1-arrested cells showed increase in cytosolic senescence-associated-β-galactosidase (SA-β-Gal) activity, a biomarker of cellular senescence. The causative factor of the cellular senescence was nLDL itself and not oxidized LDL (oxLDL), since blocking LDL receptor (LDLR) with the anti-LDLR antibody opposed the nLDL-induced increase of SA-β-Gal activity and decrease of cellular proliferation. In addition, nLDL-induced cellular senescence by inhibiting the phosphorylation of pRb (G1 arrest) via p53 as well as p16 signal transduction pathways. G1 phase arrest of the senescent cells was not overcome by nLDL removal from the culture medium. Moreover, the nLDL-treated cells produced reactive oxygen species (ROS) dose- and time-dependently. These results suggested, for the first time, that long-term treatment of nLDL could induce the premature senescence of endothelial cells. PMID:28197300

  5. Scaling of cerebral blood perfusion in primates and marsupials.

    PubMed

    Seymour, Roger S; Angove, Sophie E; Snelling, Edward P; Cassey, Phillip

    2015-08-01

    The evolution of primates involved increasing body size, brain size and presumably cognitive ability. Cognition is related to neural activity, metabolic rate and rate of blood flow to the cerebral cortex. These parameters are difficult to quantify in living animals. This study shows that it is possible to determine the rate of cortical brain perfusion from the size of the internal carotid artery foramina in skulls of certain mammals, including haplorrhine primates and diprotodont marsupials. We quantify combined blood flow rate in both internal carotid arteries as a proxy of brain metabolism in 34 species of haplorrhine primates (0.116-145 kg body mass) and compare it to the same analysis for 19 species of diprotodont marsupials (0.014-46 kg). Brain volume is related to body mass by essentially the same exponent of 0.70 in both groups. Flow rate increases with haplorrhine brain volume to the 0.95 power, which is significantly higher than the exponent (0.75) expected for most organs according to 'Kleiber's Law'. By comparison, the exponent is 0.73 in marsupials. Thus, the brain perfusion rate increases with body size and brain size much faster in primates than in marsupials. The trajectory of cerebral perfusion in primates is set by the phylogenetically older groups (New and Old World monkeys, lesser apes) and the phylogenetically younger groups (great apes, including humans) fall near the line, with the highest perfusion. This may be associated with disproportionate increases in cortical surface area and mental capacity in the highly social, larger primates.

  6. Chromium absorption in the vascularly perfused rat intestine

    SciTech Connect

    Dowling, H.J.; Offenbacher, E.G.; Pi-Sunyer, F.X.

    1986-03-01

    The mechanism of chromium (Cr) absorption by the rat small intestine was investigated using a double perfusion technique wherein the luman of the small intestine and the vasculature supplying it were separately perfused. The intestinal perfusate (IP) was a nutrient-rich tissue culture medium (TCM) with added inorganic Cr and /sup 51/Cr. The vascular perfusate (VP) was a Krebs-Ringer bicarbonate solution (KRB) containing 4.7% dextran, 0.1% glucose and 5% human serum. Cr absorption was calculated by the amount of /sup 51/Cr detected in the VP. To determine the transport mechanism for Cr, its absorption into the VP was measured at various Cr concentrations of the IP ranging from 10-400 ppb CrCl/sub 3/. The amount of Cr absorbed into the blood rose linearly with the intestinal Cr concentration suggesting a process of simple diffusion. Manipulations of the VP and IP constituents were made to investigate their effects on Cr absorption. When serum was omitted from the VP, Cr adsorption was suppressed, suggesting that serum component(s) are necessary for optimal Cr absorption. When either of 2 plasma transport proteins (apo-transferrin, albumin) were added to the serum-free VP at physiological levels, Cr absorption returned to, but did not exceed, control levels. When the TCM was replaced with a KRB solution; Cr absorption was suppressed indicating that there are nutrient(s) of the TCM which facilitate Cr absorption. Further suppression occurred when a Cr concentration gradient opposing Cr absorption was created (IP at 100 ppb Cr, VP at 400 ppb Cr).

  7. Evolution of pulmonary perfusion defects demonstrated with contrast-enhanced dynamic MR perfusion imaging.

    PubMed

    Howarth, N R; Beziat, C; Berthezène, Y

    1999-01-01

    Pulmonary perfusion defects can be demonstrated with contrast-enhanced dynamic MR perfusion imaging. We present the case of a patient with a pulmonary artery sarcoma who presented with a post-operative pulmonary embolus and was followed in the post-operative period with dynamic contrast-enhanced MR perfusion imaging. This technique allows rapid imaging of the first passage of contrast material through the lung after bolus injection in a peripheral vein. To our knowledge, this case report is the first to describe the use of this MR technique in showing the evolution of peripheral pulmonary perfusion defects associated with pulmonary emboli.

  8. Analysis of Long-Term Temperature Variations in the Human Body.

    PubMed

    Dakappa, Pradeepa Hoskeri; Mahabala, Chakrapani

    2015-01-01

    Body temperature is a continuous physiological variable. In normal healthy adults, oral temperature is estimated to vary between 36.1°C and 37.2°C. Fever is a complex host response to many external and internal agents and is a potential contributor to many clinical conditions. Despite being one of the foremost vital signs, temperature and its analysis and variations during many pathological conditions has yet to be examined in detail using mathematical techniques. Classical fever patterns based on recordings obtained every 8-12 h have been developed. However, such patterns do not provide meaningful information in diagnosing diseases. Because fever is a host response, it is likely that there could be a unique response to specific etiologies. Continuous long-term temperature monitoring and pattern analysis using specific analytical methods developed in engineering and physics could aid in revealing unique fever responses of hosts and in different clinical conditions. Furthermore, such analysis can potentially be used as a novel diagnostic tool and to study the effect of pharmaceutical agents and other therapeutic protocols. Thus, the goal of our article is to present a comprehensive review of the recent relevant literature and analyze the current state of research regarding temperature variations in the human body.

  9. Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor

    NASA Technical Reports Server (NTRS)

    Margolis, L.; Hatfill, S.; Chuaqui, R.; Vocke, C.; Emmert-Buck, M.; Linehan, W. M.; Duray, P. H.

    1999-01-01

    PURPOSE: To maintain ex vivo integral prostatic tissue including intact stromal and ductal elements using the NASA-designed Rotating Wall Vessel (RWV) which maintains colocalized cells in an environment that promotes both three-dimensional cellular interactions together with the uniform mass transfer of nutrients and metabolic wastes. MATERIALS AND METHODS: Samples of normal prostate were obtained as a byproduct of transurethral prostatectomy or needle biopsy. Prostatic tissue dissected into small 1 x 1 mm. blocks was cultured in the Rotating Wall Vessel (RWV) Bioreactor for various time periods and analyzed using histological, immunochemical, and total cell RNA assays. RESULTS: We report the long term maintenance of benign explanted human prostate tissue grown in simple culture medium, under the simulated microgravity conditions afforded by the RWV bioreactor. Mesenchymal stromal elements including blood vessels and architecturally preserved tubuloglandular acini were maintained for a minimum of 28 days. Cytokeratins, vimentin and TGF-beta2 receptor and ligand were preserved through the entire culture period as revealed by immunocytochemistry. Prostatic acid phosphatase (PAP) was continuously expressed during the culture period, although somewhat decreased. Prostatic specific antigen (PSA) and its transcript were down regulated over time of culture. Prostatic carcinoma cells from the TSU cell line were able to invade RWV-cultured benign prostate tissue explants. CONCLUSIONS: The RWV bioreactor represents an additional new technology for culturing prostate tissue for further investigations concerning the basic physiology and pathobiology of this clinically important tissue.

  10. Long-term economic growth stimulus of human capital preservation in the elderly.

    PubMed

    Manton, Kenneth G; Gu, Xi-Liang; Ullian, Arthur; Tolley, H Dennis; Headen, Alvin E; Lowrimore, Gene

    2009-12-15

    Health care is a crucial factor in US economic growth, because growing health care costs have made US corporations less competitive than their counterparts in countries where central governments assume most of those costs. In this paper we illustrate a second, possibly more powerful, effect of health care expenditures on the long term pace of US economic growth, i.e., that such investments in aging populations helps preserve human capital to later ages. In addition, as current investment in health care improves health and functional status, the future demand for health care as well as future health care costs will be constrained. These are crucial factors in countries experiencing rapid population aging. US labor force projections do not directly represent the effects of health care investment on the health of the future labor force, and federal health cost projections do not reflect the trajectory of health changes. Health dynamic projections suggest the effects of health care investment are large and growth stimulating. Projections done for the time period used by the Congressional Budget Office in budget mark-ups (2010-2020) are presented in the supporting information.

  11. Male mutation bias and possible long-term effects of human activities.

    PubMed

    Cotton, Samuel; Wedekind, Claus

    2010-10-01

    The ability of a population to adapt to changing environments depends critically on the amount and kind of genetic variability it possesses. Mutations are an important source of new genetic variability and may lead to new adaptations, especially if the population size is large. Mutation rates are extremely variable between and within species, and males usually have higher mutation rates as a result of elevated rates of male germ cell division. This male bias affects the overall mutation rate. We examined the factors that influence male mutation bias, and focused on the effects of classical life-history parameters, such as the average age at reproduction and elevated rates of sperm production in response to sexual selection and sperm competition. We argue that human-induced changes in age at reproduction or in sexual selection will affect male mutation biases and hence overall mutation rates. Depending on the effective population size, these changes are likely to influence the long-term persistence of a population.

  12. Effects of Long-Term Dust Exposure on Human Respiratory System Health in Minqin County, China.

    PubMed

    Wang, Jinyu; Li, Sheng; Wang, Shigong; Shang, Kezheng

    2015-01-01

    The aim of this study was to assess the effects of long-term sand dust exposure on human respiratory health. Dust events break out frequently in Minqin County, northwest China, whereas Pingliang City, northwest China, is rarely influenced by dust events. Therefore, Minqin and Pingliang were selected as sand dust exposure region and control area, respectively. The incidence of respiratory system diseases and symptoms was determined through a structured respiratory health questionnaire (ATS-DLD-78-A) and personal interviews. The subjects comprised 728 farmers (Minqin, 424; Pingliang, 304) aged 40 years or older, who had nondocumented occupational history to industrial dust exposure. Prevalences (odds ratio [OR], 95% confidence interval [CI]) of chronic rhinitis, chronic bronchitis, and chronic cough increased 9.6% (3.141, 1.776-5.555), 7.5% (2.468, 1.421-4.286), and 10.2% (1.787, 1.246-2.563) in Minqin comparison with Pingliang, respectively, and the differences were significant (p <.01).

  13. Effect of sexual behavior change on long-term human immunodeficiency virus prevalence among homosexual men.

    PubMed

    Morris, M; Dean, L

    1994-08-01

    Substantial changes in human immunodeficiency virus (HIV)-related sexual behavior have been reported by virtually every survey of homosexual/bisexual men in the last decade. This paper uses a behavior-based simulation to examine how such changes are likely to affect the long-term future of the acquired immunodeficiency syndrome (AIDS) epidemic among homosexual men. Data from the Longitudinal AIDS Impact Project in New York City are used to estimate age-specific patterns of unprotected anogenital contact and behavioral change from 1980 to 1991. Model projections are validated using New York City surveillance data on AIDS incidence from 1981 to 1991. The current levels of unsafe sex reported in the Longitudinal AIDS Impact Project are shown to be almost exactly on the epidemic threshold. If this behavior were maintained, HIV prevalence would slowly decline in the population, but with just one additional unsafe sexual partner per year HIV would instead become endemic, with seroprevalence of about 65% in the oldest group and about 25% in the youngest. Transmission dynamics in the youngest group are analyzed in detail. For this group, the assortative age-matching bias in partner selection patterns raises the unsafe behavior threshold slightly in the long run.

  14. Identification of ATP diphosphohydrolase activity in human term placenta using a novel assay for AMP.

    PubMed

    Papamarcaki, T; Tsolas, O

    1990-09-03

    Human term placenta contains an ATP diphosphohydrolase activity which hydrolyses ATP to ADP and inorganic phosphate and ADP to AMP and a second mole of inorganic phosphate. The activity has a pH optimum between 8.0 and 8.5. Magnesium or calcium ions are required for maximum activity. Other nucleoside phosphates, p-nitrophenyl phosphate or sodium pyrophosphate, are not hydrolysed. The activity is not due to ATPases, or to myokinase, as determined by the use of inhibitors. NaF and NaN3 were found to inhibit strongly the activity thus identifying it as an ATP diphosphohydrolase. A sensitive enzymatic assay for measurement of AMP, one of the products of the reaction, was established, based on the strong inhibition of muscle fructose 1,6-biphosphatase by AMP. The range of the assay was 0.05-0.8 microM AMP. ATP diphosphohydrolase was found to have a rate of AMP production from ADP twice the rate from ATP. Under the same conditions, the assay for Pi release, on the other hand, gave velocities similar to each other for the two substrates. The activity appears to be identical to the ADP-hydrolysing activity in placenta reported by others.

  15. Global approach to simulation: A gateway to long-term human presence in space

    NASA Astrophysics Data System (ADS)

    Collet, J.; Novara, M.

    The establishment of an autonomous European manned space capability is an objective set up by the ESA Council Meeting at the ministerial level, in 1985/1987. ESA's Long-Term Programme Office (LTPO), charged of the preparation of the programme for a European Manned Space Infrastructure (EMSI), started during 1988 to build up an intellectual framework in the domain of long-duration manned space missions. EMSI scope was eventually extended to embrace Moon/Mars missions and bases. Several exploratory studies on problems related to human factors in long-duration space missions were initiated by LTPO. The work of an ad-hoc group of experts (SIMIS Group) has been focused during 1989/1990 on the planning for simulation of such missions with a broad mandate, covering the physiological, psychological and operational aspects of long-duration exposure to microgravity and isolation/confinement. Preliminary results of SIMIS activities are reported. The HYDREMSI experiment, carried out in a terrestrial, analogous environment for 72 days during 1989, is described as an example of the envisaged simulations.

  16. Skeletal muscle proteolysis in response to short-term unloading in humans

    PubMed Central

    Tesch, Per A.; von Walden, Ferdinand; Gustafsson, Thomas; Linnehan, Richard M.; Trappe, Todd A.

    2008-01-01

    Skeletal muscle atrophy is evident after muscle disuse, unloading, or spaceflight and results from decreased protein content as a consequence of decreased protein synthesis, increased protein breakdown or both. At this time, there are essentially no human data describing proteolysis in skeletal muscle undergoing atrophy on Earth or in space, primarily due to lack of valid and accurate methodology. This particular study aimed at assessing the effects of short-term unloading on the muscle contractile proteolysis rate. Eight men were subjected to 72-h unilateral lower limb suspension (ULLS) and intramuscular interstitial levels of the naturally occurring proteolytic tracer 3-methylhistidine (3MH) were measured by means of microdialysis before and on completion of this intervention. The 3MH concentration following 72-h ULLS (2.01 ± 0.22 nmol/ml) was 44% higher (P < 0.05) than before ULLS (1.56 ± 0.20 nmol/ml). The present experimental model and the employed method determining 3MH in microdialysates present a promising tool for monitoring skeletal muscle proteolysis or metabolism of specific muscles during conditions resulting in atrophy caused by, e.g., disuse and real or simulated microgravity. This study provides evidence that the atrophic processes are evoked rapidly and within 72 h of unloading and suggests that countermeasures should be employed in the early stages of space missions to offset or prevent muscle loss during the period when the rate of muscle atrophy is the highest. PMID:18535133

  17. Long-term effects of prenatal x-ray of human females: mortality and morbidity

    SciTech Connect

    Meyer, M.B.; Tonascia, J.

    1981-09-01

    Experimental studies and long-term studies of humans exposed to ionizing radiation in utero and after birth show that these exposures increase the risk of cancer in childhood and in later life. A possible life-shortening effect has also been reported. This study followed to their mid-twenties 1458 women exposed in utero to diagnostic x-rays and 1458 matched, unexposed controls in Baltimore, Maryland, and obtained responses from over 100 women in each group. Information about general health and specific diseases was obtained from questionnaires. Deaths were ascertained through family members and death certificates. Mortality rates were slightly higher among exposure. Exposed women reported poor general health significantly more often than controls. Specific diseases occurred similarly in the two groups, although exposed women reported more epilepsy or fits, more ovarian tumors, and more high blood pressure. These strong correlation between weight and high blood pressure and the heavier weights of exposed women seemed to account for this difference. In summary, these matched exposed and control women, followed to their mid-twenties, experienced similar rates of morbidity and mortality. Radiation-induced cancers and life-shortening effects, if any, might not become evident until older ages.

  18. Long-term effects of prenatal x-ray of human females: growth and development

    SciTech Connect

    Meyer, M.B.; Tonascia, J.

    1981-09-01

    Experimental studies and studies of survivors of in-utero exposure to atomic bomb blasts have shown significant stunting of growth and mental retardation following these exposures. Central nervous system damage following very low dosage of x-ray at around the time of birth has also been observed in experimental animals. This long term followup study of 1458 human females exposed in-utero to diagnostic x-rays and of 1458 matched unexposed controls studied in Baltimore, Maryland, included measurements of height, weight, and school achievement. Women who had been exposed to x-rays in-utero were significantly shorter in their mid-twenties than were their matched, unexposed controls, even after adjustment for other social and economic factors. However, additional followup revealed that mothers of exposed women were also shorter than the control mothers. Short stature appeared to be a selective factor for x-ray during pregnancy (mostly pelvimetry, 1947 to 1952). Mothers' and daughters' heights were similarly correlated among exposed and controlled mother-daughter pairs, suggesting that the height differences between exposed daughters and their controls were due to these selective factors rather than to any direct effect of radiation on growth. Exposed women reported poorer school achievement than control women. However, except for a higher proportion of exposed women leaving school because of pregnancy, these measurements were no longer significantly different when rates were simultaneously adjusted for socioeconomic differences between exposed and control women.

  19. Long-term storage and safe retrieval of human papillomavirus DNA using FTA elute cards.

    PubMed

    Barth, Heidi; Morel, Adrien; Mougin, Christiane; Averous, Gerlinde; Legrain, Michèle; Fender, Muriel; Risch, Simone; Fafi-Kremer, Samira; Velten, Michel; Oudet, Pierre; Baldauf, Jean-Jacques; Stoll-Keller, Françoise

    2016-03-01

    Biobanking or collection and storage of specimens for future research purposes have become an essential tool in many fields of biomedical research and aims to provide a better understanding of disease mechanisms as well as the identification of disease-specific biomarkers that can navigate in complex diseases. In this study, we assessed the use of Flinders Technology Associates (FTA) cards as a long-term storage device for cervical specimens with suspected human papillomavirus (HPV) infections. HPV detection and genotyping results in liquid-based transport media were compared to HPV results from FTA cards. The overall agreement for the presence of any HPV infection between liquid-based medium and FTA cards stored for 1 year at ambient temperature was 100%. Reproducibility analysis of HPV detection and genotyping from FTA cards demonstrated that FTA cards are a reliable medium to store and preserve viral nucleic acids. Biobanking of cervical cells on FTA cards may provide a key resource for epidemiological and retrospective HPV studies.

  20. Long-term variability and impact on human health of biologically active UV radiation in Moscow

    NASA Astrophysics Data System (ADS)

    Zhdanova, Ekaterina; Chubarova, Natalia

    2014-05-01

    the developed classification for Moscow. Booth, C.R. and S. Madronich, 1994: Radiation amplification factors: improved formulation accounts for large increases in ultraviolet radiation associated with Antarctic ozone depletion. In: Ultraviolet Radiation in Antarctica: Measurements and Biological Research [Weiler, C.S. and P.A. Penhale (eds.)]. AGU Antarctic Research Series, 62, Washington, DC, USA, 39-42. Chubarova N.Y., 2008: UV variability in Moscow according to long-term UV measurements and reconstruction model. Atmos.Chem.Phys., 8, 3025-3031 Oriowo, M. et al., 2001:, Action spectrum for in vitro UV-induced cataract using whole lenses. Invest.Ophthalmol.&Vis.Sci, 42, 2596-2602. CIE, 1993: Reference Action Spectra for Ultraviolet Induced Erythema and Pigmentation of Different Human skin Types. CIE Research Note, CIE Technical Collection., N.3 CIE, 2006: Action spectrum for the production of previtamin D3 in human skin, Technical report 174, International commission on illumination

  1. Improved exercise myocardial perfusion during lidoflazine therapy

    SciTech Connect

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-11-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise.

  2. Perfusion visualization and analysis for pulmonary embolism

    NASA Astrophysics Data System (ADS)

    Vaz, Michael S.; Kiraly, Atilla P.; Naidich, David P.; Novak, Carol L.

    2005-04-01

    Given the nature of pulmonary embolism (PE), timely and accurate diagnosis is critical. Contrast enhanced high-resolution CT images allow physicians to accurately identify segmental and sub-segmental emboli. However, it is also important to assess the effect of such emboli on the blood flow in the lungs. Expanding upon previous research, we propose a method for 3D visualization of lung perfusion. The proposed method allows users to examine perfusion throughout the entire lung volume at a single glance, with areas of diminished perfusion highlighted so that they are visible independent of the viewing location. This may be particularly valuable for better accuracy in assessing the extent of hemodynamic alterations resulting from pulmonary emboli. The method also facilitates user interaction and may help identify small peripheral sub-segmental emboli otherwise overlooked. 19 patients referred for possible PE were evaluated by CT following the administration of IV contrast media. An experienced thoracic radiologist assessed the 19 datasets with 17 diagnosed as being positive for PE with multiple emboli. Since anomalies in lung perfusion due to PE can alter the distribution of parenchymal densities, we analyzed features collected from histograms of the computed perfusion maps and demonstrate their potential usefulness as a preliminary test to suggest the presence of PE. These histogram features also offer the possibility of distinguishing distinct patterns associated with chronic PE and may even be useful for further characterization of changes in perfusion or overall density resulting from associated conditions such as pneumonia or diffuse lung disease.

  3. Relation of global and regional left ventricular function to tomographic thallium-201 myocardial perfusion in patients with prior myocardial infarction

    SciTech Connect

    Stratton, J.R.; Speck, S.M.; Caldwell, J.H.; Martin, G.V.; Cerqueira, M.; Maynard, C.; Davis, K.B.; Kennedy, J.W.; Ritchie, J.L.

    1988-07-01

    To determine the relation between regional myocardial perfusion and regional wall motion in humans, tomographic thallium-201 imaging and two-dimensional echocardiography at rest were performed on the same day in 83 patients 4 to 12 weeks after myocardial infarction. Myocardial perfusion and wall motion were assessed independently in five left ventricular regions (total 415 regions). Regional myocardial perfusion was quantitated as a percent of the region infarcted (range 0 to 100%) using a previously validated method. Wall motion was graded on a four point scale as 1 = normal (n = 266 regions), 2 = hypokinesia (n = 64), 3 = akinesia (n = 70), 4 = dyskinesia (n = 13) or not evaluable (n = 2). Regional wall motion correlated directly with the severity of the perfusion deficit (r = 0.68, p less than 0.0001). Among normally contracting regions, the mean perfusion defect score was only 2 +/- 4. Increasingly severe wall motion abnormalities were associated with larger perfusion defect scores (hypokinesia = 6 +/- 5, akinesia = 11 +/- 7 and dyskinesia = 18 +/- 5, all p less than 0.01 versus normal. Among regions with normal wall motion, only 3% had a perfusion defect score greater than or equal to 10. Conversely, among 68 regions with a large (greater than or equal to 10) perfusion defect, only 13% had normal motion whereas 87% had abnormal wall motion. The relation between perfusion and wall motion noted for the entire cohort was also present in subgroups of patients with anterior or inferior infarction. In patients with prior myocardial infarction, the severity of the tomographic thallium perfusion defect correlates directly with echocardiographically defined wall motion abnormalities, both globally and regionally.

  4. Short-term and long-term effects of protein kinase C on the trafficking and stability of human organic anion transporter 3

    PubMed Central

    Zhang, Qiang; Suh, Wonmo; Pan, Zui; You, Guofeng

    2012-01-01

    Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical significance. In the current study, we investigated the short-term and long-term regulation of hOAT3 by protein kinase C (PKC). We showed that short-term activation of PKC by phobol 12-Myristate 13-Acetate (PMA) inhibited hOAT3 activity through accelerating its internalization from cell surface to intracellular recycling endosomes. The colocalization of hOAT3 with EEA1-positive recycling endosomes was demonstrated by immunolocalization with confocal microscopy. Furthermore, we showed that long-term activation of PKC resulted in the enhanced degradation of cell surface hOAT3. The pathways for hOAT3 degradation were further examined using proteasomal and lysosomal inhibitors. Our results showed that both proteasomal inhibitors and the lysosomal inhibitors significantly blocked hOAT3 degradation. These results demonstrate that PKC plays critical roles in the trafficking and the stability of hOAT3. PMID:22773962

  5. Multiwell cell culture plate format with integrated microfluidic perfusion system

    NASA Astrophysics Data System (ADS)

    Domansky, Karel; Inman, Walker; Serdy, Jim; Griffith, Linda G.

    2006-01-01

    A new cell culture analog has been developed. It is based on the standard multiwell cell culture plate format but it provides perfused three-dimensional cell culture capability. The new capability is achieved by integrating microfluidic valves and pumps into the plate. The system provides a means to conduct high throughput assays for target validation and predictive toxicology in the drug discovery and development process. It can be also used for evaluation of long-term exposure to drugs or environmental agents or as a model to study viral hepatitis, cancer metastasis, and other diseases and pathological conditions.

  6. Application of an acoustofluidic perfusion bioreactor for cartilage tissue engineering

    PubMed Central

    Li, Siwei; Glynne-Jones, Peter; Andriotis, Orestis G.; Ching, Kuan Y.; Jonnalagadda, Umesh S.; Oreffo, Richard O. C.; Hill, Martyn

    2014-01-01

    Cartilage grafts generated using conventional static tissue engineering strategies are characterised by low cell viability, suboptimal hyaline cartilage formation and, critically, inferior mechanical competency, which limit their application for resurfacing articular cartilage defects. To address the limitations of conventional static cartilage bioengineering strategies and generate robust, scaffold-free neocartilage grafts of human articular chondrocytes, the present study utilised custom-built microfluidic perfusion bioreactors with integrated ultrasound standing wave traps. The system employed sweeping acoustic drive frequencies over the range of 890 to 910 kHz and continuous perfusion of the chondrogenic culture medium at a low-shear flow rate to promote the generation of three-dimensional agglomerates of human articular chondrocytes, and enhance cartilage formation by cells of the agglomerates via improved mechanical stimulation and mass transfer rates. Histological examination and assessment of micromechanical properties using indentation-type atomic force microscopy confirmed that the neocartilage grafts were analogous to native hyaline cartilage. Furthermore, in the ex vivo organ culture partial thickness cartilage defect model, implantation of the neocartilage grafts into defects for 16 weeks resulted in the formation of hyaline cartilage-like repair tissue that adhered to the host cartilage and contributed to significant improvements to the tissue architecture within the defects, compared to the empty defects. The study has demonstrated the first successful application of the acoustofluidic perfusion bioreactors to bioengineer scaffold-free neocartilage grafts of human articular chondrocytes that have the potential for subsequent use in second generation autologous chondrocyte implantation procedures for the repair of partial thickness cartilage defects. PMID:25272195

  7. Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds.

    PubMed

    Gershlak, Joshua R; Hernandez, Sarah; Fontana, Gianluca; Perreault, Luke R; Hansen, Katrina J; Larson, Sara A; Binder, Bernard Y K; Dolivo, David M; Yang, Tianhong; Dominko, Tanja; Rolle, Marsha W; Weathers, Pamela J; Medina-Bolivar, Fabricio; Cramer, Carole L; Murphy, William L; Gaudette, Glenn R

    2017-05-01

    Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass.

  8. Human color vision deficits induced by accidental laser exposure and potential for long-term recovery

    NASA Astrophysics Data System (ADS)

    Zwick, Harry; Lund, Brian J.; Brown, Jeremiah, Jr.; Stuck, Bruce E.; Loveday, J.

    2003-06-01

    Purpose: To evaluate long term deficits in human color discrimination induced by accidental laser macular damage and assess potential for recovery of color vision deficits. Methods: Nine laser accident cases (Q-switched Neodymium) presenting initially with confined or vitreous macular hemorrhage were evaluated with the Farnsworth-Munsell 100 Hue test within 2 days to 3 months post exposure. Both total as well as partial errors in the blue/yellow (B/Y) and red/green (R/G) regions were assessed. Independent assessment of axis orientation and complexity were obtained via a Fourier series expansion of error scores. Comparisons of both total and partial B/Y and R/G errors were made with age matched normal subjects, idiopathic and juvenile onset macular holes. Confocal Scanning Laser Ophthalmoscopy and Optical Coherence Tomography characterized the presence of retinal traction, intraretinal scar, macular thickness and macular hole formation. Results: Comparison of exposed and non-exposed age matched individuals were significant (P<.001) for both total and partial errors. In four cases where macular injury ranged from mild scar to macular hole, color discrimination errors achieved normal levels in 1 to 12 months post exposure. A mild tritan axis, dominant B/Y ("blue/yellow") errors, and retinal traction were observed in a macular hole case. At 12 months post exposure, traction about the hole disappeared, and total and partial errors were normal. Where damage involved a greater degree of scarring, retinal traction and multiple injury sites, long term recovery of total and partial error recovery was retarded with complex axis makeup. Single exposures in the paramacula produced tritan axes, while multiple exposures within and external to the macula increased total and partial R/G ("red/green") error scores. Total errors increased when paramacular hole enlargement induced macular traction. Such hole formation produced significant increases in total errors, complex axis

  9. Computed tomography perfusion and computed tomography angiography for prediction of clinical outcomes in ischemic stroke patients after thrombolysis

    PubMed Central

    Pan, Jia-wei; Yu, Xiang-rong; Zhou, Shu-yi; Wang, Jian-hong; Zhang, Jun; Geng, Dao-ying; Zhang, Tian-yu; Cheng, Xin; Ling, Yi-feng; Dong, Qiang

    2017-01-01

    Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis. At present, the majority of studies focus on assessing the accuracy of lesion location using imaging methods before treatment, with less attention to predictions of outcomes after thrombolysis. Thus, in the present study, we assessed the efficacy of combined computed tomography (CT) perfusion and CT angiography in predicting clinical outcomes after thrombolysis in ischemic stroke patients. The study included 52 patients who received both CT perfusion and CT angiography. Patients were grouped based on the following criteria to compare clinical outcomes: (1) thrombolytic and non-thrombolytic patients, (2) thrombolytic patients with CT angiography showing the presence or absence of a vascular stenosis, (3) thrombolytic patients with CT perfusion showing the presence or absence of hemodynamic mismatch, and (4) different CT angiography and CT perfusion results. Short-term outcome was assessed by the 24-hour National Institution of Health Stroke Scale score change. Long-term outcome was assessed by the 3-month modified Rankin Scale score. Of 52 ischemic stroke patients, 29 were treated with thrombolysis and exhibited improved short-term outcomes compared with those without thrombolysis treatment (23 patients). Patients with both vascular stenosis and blood flow mismatch (13 patients) exhibited the best short-term outcome, while there was no correlation of long-term outcome with CT angiography or CT perfusion findings. These data suggest that combined CT perfusion and CT angiography are useful for predicting short-term outcome, but not long-term outcome, after thrombolysis. PMID:28250755

  10. Description of an Experiment Investigating Term Relationships as Interpreted by Humans.

    ERIC Educational Resources Information Center

    Rubinoff, Morris; And Others

    An experiment is reported in which 78 subjects examined synonymic and generic-specific relationships among 513 terms compiled from subject indexes of programming textbooks and manuals. Terms were assigned in groups of 20 so that given decisions for terms could be compared for three subjects. The experiment suggested such methodological…

  11. Long-term measurement of impedance in chronically implanted depth and subdural electrodes during responsive neurostimulation in humans.

    PubMed

    Sillay, Karl A; Rutecki, Paul; Cicora, Kathy; Worrell, Greg; Drazkowski, Joseph; Shih, Jerry J; Sharan, Ashwini D; Morrell, Martha J; Williams, Justin; Wingeier, Brett

    2013-09-01

    Long-term stability of the electrode-tissue interface may be required to maintain optimal neural recording with subdural and deep brain implants and to permit appropriate delivery of neuromodulation therapy. Although short-term changes in impedance at the electrode-tissue interface are known to occur, long-term changes in impedance have not previously been examined in detail in humans. To provide further information about short- and long-term impedance changes in chronically implanted electrodes, a dataset from 191 persons with medically intractable epilepsy participating in a trial of an investigational responsive neurostimulation device (the RNS(®) System, NeuroPace, Inc.) was reviewed. Monopolar impedance measurements were available for 391 depth and subdural leads containing a total of 1564 electrodes; measurements were available for median 802 days post-implant (range 28-1634). Although there were statistically significant short-term impedance changes, long-term impedance was stable after one year. Impedances for depth electrodes transiently increased during the third week after lead implantation and impedances for subdural electrodes increased over 12 weeks post-implant, then were stable over the subsequent long-term follow-up. Both depth and subdural electrode impedances demonstrated long-term stability, suggesting that the quality of long-term electrographic recordings (the data used to control responsive brain stimulation) can be maintained over time.

  12. GPU-accelerated voxelwise hepatic perfusion quantification.

    PubMed

    Wang, H; Cao, Y

    2012-09-07

    Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using compute unified device architecture-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, nonlinear least-squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626 400 voxels in a patient's liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10(-6). The method will be useful for generating liver perfusion images in clinical settings.

  13. Improvement of the embalming perfusion method: the innovation and the results by light and scanning electron microscopy.

    PubMed

    Goyri-O'Neill, João; Pais, Diogo; Freire de Andrade, Francisco; Ribeiro, Paulo; Belo, Ana; O'Neill, Assunção; Ramos, Samuel; Neves Marques, Cláudia

    2013-01-01

    Embalming is a chemical process that aims the preservation and sanitization of the human body indefinitely. The technique of embalming is an important tool in teaching and research in anatomy enabling the preservation of cadaveric material in good conditions (lessening any significant structural changes and maintaining the natural appearance). This article presents the results of embalmed cadavers in the course of arterial perfusion, through the use of a perfusion machine, particularly designed to this objective, and which allows the control of the embalming fluid injection process. The influence of this technique and the optimization of its parameters on the final quality of embalming were evaluated by sequential histological analysis of the cadaveric tissues using an original method of classification of samples collected from 17 deceased corpses of the Corpses Donation Office of the Department of Anatomy of Faculdade de Ciências Médicas from Universidade Nova de Lisboa, subject to the embalming technique developed in the Department. We concluded that, with this method, there is a decrease of the decomposition process at the time of embalming, which is effective at long term (over a year), requiring merely the maintenance of the body at low temperatures (4° C) and it is possible to observe that the tissue best preserved over time is muscle, showing a conservation considered optimal.

  14. Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero.

    PubMed Central

    Zanjani, E D; Pallavicini, M G; Ascensao, J L; Flake, A W; Langlois, R G; Reitsma, M; MacKintosh, F R; Stutes, D; Harrison, M R; Tavassoli, M

    1992-01-01

    Hemopoietic stem cells from human fetal liver were transplanted in utero into preimmune fetal sheep (48-54 days of gestation). The fate of donor cells was followed using karyotype analysis, by immunofluorescence labeling with anti-CD antibodies, and by fluorescent in situ hybridization using human-specific DNA probes. Engraftment occurred in 13 of 33 recipients. Of five live born sheep that exhibited chimerism, all expressed human cells in the marrow, whereas three expressed them in blood as well. Engraftment was multilineage (erythroid, myeloid, and lymphoid) and human hemopoietic progenitors (multipotent colony-forming units, colony-forming units-granulocyte, macrophage, and erythroid burst-forming units) capable of forming colonies in vitro were detected in all five lambs for greater than 2 yr. These progenitors responded to human-specific growth factors both in vitro and in vivo. Thus the administration of recombinant human IL-3 and granulocyte macrophage-colony-stimulating factor to chimeric sheep resulted in a 2.1-3.4-fold increase in the relative expression of donor (human) cells. These results demonstrate that the permissive environment of the preimmune fetal sheep provides suitable conditions for the engraftment and long-term multilineage expression of human hemopoietic stem cells in a large animal model. In this model, donor human cells appear to retain certain phenotypic and functional characteristics that can be used to manipulate the size of donor cell pool. PMID:1348253

  15. Individual variation in behavioural responsiveness to humans leads to differences in breeding success and long-term population phenotypic changes.

    PubMed

    Arroyo, Beatriz; Mougeot, François; Bretagnolle, Vincent

    2017-03-01

    Whether human disturbance can lead to directional selection and phenotypic change in behaviour in species with limited behavioural plasticity is poorly understood in wild animal populations. Using a 19-year study on Montagu's harrier, we report a long-term increase in boldness towards humans during nest visits. The probability of females fleeing or being passive during nest visits decreased, while defence intensity steadily increased over the study period. These behavioural responses towards humans were significantly repeatable. The phenotypic composition of the breeding population changed throughout the study period (4-5 harrier generations), with a gradual disappearance of shy individuals, leading to a greater proportion of bolder ones and a more behaviourally homogeneous population. We further show that nest visit frequency increased nest failure probability and reduced productivity of shy females, but not of bold ones. Long-term research or conservation programmes needing nest visits can therefore lead to subtle but relevant population compositional changes that require further attention.

  16. Brain perfusion correlates of visuoperceptual deficits in Mild Cognitive Impairment and mild Alzheimer’s disease

    PubMed Central

    Alegret, Montserrat; Vinyes-Junqué, Georgina; Boada, Mercè; Martínez-Lage, Pablo; Cuberas, Gemma; Espinosa, Ana; Roca, Isabel; Hernández, Isabel; Valero, Sergi; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T.; Tárraga, Lluís

    2012-01-01

    Background Visuoperceptual processing is impaired early in the clinical course of Alzheimer’s disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in Mild Cognitive Impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal and prefrontal regions have been found in early AD and MCI patients. Objectives To confirm the role of the 15-OT in the diagnosis of MCI and AD, and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD and normal aging. Methods Forty-two AD, 42 MCI and 42 healthy elderly control (EC) subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. Results 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Conclusion Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. PMID:20555146

  17. Long-term expression of human adenosine deaminase in mice transplanted with retrovirus-infected hematopoietic stem cells

    SciTech Connect

    Lim, B.; Apperley, J.F.; Orkin, S.H.; Williams, D.A. )

    1989-11-01

    Long-term stable expression of foreign genetic sequences transferred into hematopoietic stem cells by using retroviral vectors constitutes a relevant model for somatic gene therapy. Such stability of expression may depend on vector design, including the presence or absence of specific sequences within the vector, in combination with the nature and efficiency of infection of the hematopoietic target cells. The authors have previously reported successful transfer of human DNA encoding adenosine deaminase (ADA) into CFU-S (colony-forming unit-spleen) stem cells using simplified recombinant retroviral vectors. Human ADA was expressed in CFU-S-derived spleen colonies at levels near to endogenous enzyme. However, because of the lack of an efficient dominant selectable marker and low recombinant viral titers, stability of long-term expression of human ADA was not examined. They report here the development of an efficient method of infection of hematopoietic stem cells (HSC) without reliance on in vitro selection. Peripheral blood samples of 100% of mice transplanted with HSC infected by this protocol exhibit expression of human ADA 30 days after transplantation. Some mice (6 of 13) continue to express human ADA in all lineages after complete hematopoietic reconstitution (4 months). The use of recombinant retroviral vectors that efficiently transfer human ADA cDNA into HSC leading to stable expression of functional ADA in reconstituted mice, provides an experimental framework for future development of approaches to somatic gene therapy.

  18. Regulation of metabolic genes in human skeletal muscle by short-term exercise and diet manipulation.

    PubMed

    Arkinstall, Melissa J; Tunstall, Rebecca J; Cameron-Smith, David; Hawley, John A

    2004-07-01

    Changes in dietary macronutrient intake alter muscle and blood substrate availability and are important for regulating gene expression. However, few studies have examined the effects of diet manipulation on gene expression in human skeletal muscle. The aim of this study was to quantify the extent to which altering substrate availability impacts on subsequent mRNA abundance of a subset of carbohydrate (CHO)- and fat-related genes. Seven subjects consumed either a low- (LOW; 0.7 g/kg body mass CHO) or high- (HIGH; 10 g/kg body mass CHO) CHO diet for 48 h after performing an exhaustive exercise bout to deplete muscle glycogen stores. After intervention, resting muscle and blood samples were taken. Muscle was analyzed for the gene abundances of GLUT4, glycogenin, pyruvate dehydrogenase kinase-4 (PDK-4), fatty acid translocase (FAT/CD36), carnitine palmitoyltransferase I (CPT I), hormone-sensitive lipase (HSL), beta-hydroxyacyl-CoA dehydrogenase (beta-HAD), and uncoupling binding protein-3 (UCP3), and blood samples for glucose, insulin, and free fatty acid (FFA) concentrations. Glycogen-depleting exercise and HIGH-CHO resulted in a 300% increase in muscle glycogen content (P < 0.001) relative to the LOW-CHO condition. FFA concentrations were twofold higher after LOW- vs. HIGH-CHO (P < 0.05). The exercise-diet manipulation exerted a significant effect on transcription of all carbohydrate-related genes, with an increase in GLUT4 and glycogenin mRNA abundance and a reduction in PDK-4 transcription after HIGH-CHO (all P < 0.05). FAT/CD36 (P < 0.05) and UCP3 (P < 0.01) gene transcriptions were increased following LOW-CHO. We conclude that 1) there was a rapid capacity for a short-term exercise and diet intervention to exert coordinated changes in the mRNA transcription of metabolic related genes, and 2) genes involved in glucose regulation are increased following a high-carbohydrate diet.

  19. Taste-Mediated Calming in Premature, Preterm, and Full-Term Human Infants.

    ERIC Educational Resources Information Center

    Smith, Barbara A.; Blass, Elliott M.

    1996-01-01

    Preterm and term infants were given a sucrose solution, a glucose solution, or water during a test period in which the amount of their crying was measured. Sucrose reduced crying in preterm and term infants by 91% and 93%, respectively, and glucose by 86% and 81%, respectively. Water was ineffective in reducing crying in both preterm and term…

  20. Transcriptomic hepatotoxicity signature of chlorpromazine after short- and long-term exposure in primary human sandwich cultures.

    PubMed

    Parmentier, Céline; Truisi, Germaine L; Moenks, Konrad; Stanzel, Sven; Lukas, Arno; Kopp-Schneider, Annette; Alexandre, Eliane; Hewitt, Philip G; Mueller, Stefan O; Richert, Lysiane

    2013-10-01

    Drug-induced liver injury is the most frequent reason for market withdrawal of approved drugs, and is difficult to predict in animal models. Here, we analyzed transcriptomic data derived from short- and long-term cultured primary human hepatocytes (PHH) exposed to the well known human hepatotoxin chlorpromazine (CPZ). Samples were collected from five PHH cultures after short-term (1 and 3 days) and long-term (14 days) repeat daily treatment with 0.1 or 0.2 µM CPZ, corresponding to C(max). Two PHH cultures were additionally treated with 1 µM CPZ, and the three others with 0.02 µM CPZ. Differences in the total number of gene changes were seen between donors and throughout treatment. Specific transcriptomic hepatotoxicity signatures were created for CPZ and consisted of inflammation/hepatitis, cholestasis, and liver proliferation in all five donors, as well as fibrosis and steatosis, which were observed in four of five donors. Necrosis was present in three of five donors, and an indicative signature of cirrhosis was observed after long-term 14-day repeat treatment, also in three of five donors. The inter-donor variability in the inflammatory response to CPZ treatment was associated with variability in the strength of the response of the transcriptomic hepatotoxicity signatures, suggesting that features of inflammation could be related to the idiosyncratic hepatotoxic effects of CPZ in humans.

  1. Cerebral perfusion and psychometric testing in military amateur boxers and controls.

    PubMed Central

    Kemp, P M; Houston, A S; Macleod, M A; Pethybridge, R J

    1995-01-01

    The objective was to compare two neurophysiological variables in active amateur boxers with non-boxing sportsmen. 41 boxers and 27 controls were given psychometric tests: 34 boxers and 34 controls underwent technetium-99m hexamethylpropyleneamineoxime single photon emission computerised tomography (Tc-99m HMPAO SPECT) cerebral perfusion scans. The controls performed better at most aspects of the psychometric tests. Boxers who had fought fewer bouts had a tendency to perform better at psychometric tests than those boxers who had fought more bouts. Tc-99m HMPAO SPECT cerebral perfusion scanning showed that controls had less aberrations in cerebral perfusion than the boxers. In conclusion, significant differences were shown in two neurophysiological variables between young amateur sportsmen who box and those who do not. The long term effects of these findings remain unknown. PMID:7561914

  2. Brain/language relationships identified with diffusion and perfusion MRI: Clinical applications in neurology and neurosurgery.

    PubMed

    Hillis, Argye E

    2005-12-01

    Diffusion and perfusion MRI have contributed to stroke management by identifying patients with tissue "at risk" for further damage in acute stroke. However, the potential usefulness of these imaging modalities, along with diffusion tensor imaging, can be expanded by using these imaging techniques with concurrent assessment of language and other cognitive skills to identify the specific cognitive deficits that are associated with diffusion and perfusion abnormalities in particular brain regions. This paper illustrates how this combined behavioral and imaging methodology can yield information that is useful for predicting specific positive effects of intervention to restore blood flow in hypoperfused regions of brain identified with perfusion MRI, and for predicting negative effects of resection of particular brain regions or fiber bundles. Such data allow decisions about neurological and neurosurgical interventions to be based on specific risks and benefits in terms of functional consequences.

  3. Human Effector / Initiator Gene Sets That Regulate Myometrial Contractility During Term and Preterm Labor

    PubMed Central

    WEINER, Carl P.; MASON, Clifford W.; DONG, Yafeng; BUHIMSCHI, Irina A.; SWAAN, Peter W.; BUHIMSCHI, Catalin S.

    2010-01-01

    Objective Distinct processes govern transition from quiescence to activation during term (TL) and preterm labor (PTL). We sought gene sets responsible for TL and PTL, along with the effector genes necessary for labor independent of gestation and underlying trigger. Methods Expression was analyzed in term and preterm +/− labor (n =6 subjects/group). Gene sets were generated using logic operations. Results 34 genes were similarly expressed in PTL/TL but absent from nonlabor samples (Effector Set). 49 genes were specific to PTL (Preterm Initiator Set) and 174 to TL (Term Initiator Set). The gene ontogeny processes comprising Term Initiator and Effector Sets were diverse, though inflammation was represented in 4 of the top 10; inflammation dominated the Preterm Initiator Set. Comments TL and PTL differ dramatically in initiator profiles. Though inflammation is part of the Term Initiator and the Effector Sets, it is an overwhelming part of PTL associated with intraamniotic inflammation. PMID:20452493

  4. Myocardial perfusion scintigraphy: the evidence

    PubMed Central

    Anagnostopoulos, C.; Cerqueira, M.; Ell, P. J.; Flint, E. J.; Harbinson, M.; Kelion, A. D.; Al-Mohammad, A.; Prvulovich, E. M.; Shaw, L. J.; Tweddel, A. C.

    2003-01-01

    This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by

  5. Early Support of Intracranial Perfusion

    DTIC Science & Technology

    2009-10-01

    for the protocol with pigs and will be submitting to ACURO in the near future. Preliminary experiments performed with human cerebrospinal fluid ...impact traumatic brain injury plus hemorrhagic shock has been successfully developed. • Preliminary experiments performed with human cerebrospinal fluid ...Kreutzer, J. S., Kolakowsky-Hayner, S. A., Marwitz, J. H., & Englander, J. (2003). The relationship between therapy intensity and rehabilitative

  6. Repeatability and reproducibility of optic nerve head perfusion measurements using optical coherence tomography angiography

    NASA Astrophysics Data System (ADS)

    Chen, Chieh-Li; Bojikian, Karine D.; Xin, Chen; Wen, Joanne C.; Gupta, Divakar; Zhang, Qinqin; Mudumbai, Raghu C.; Johnstone, Murray A.; Chen, Philip P.; Wang, Ruikang K.

    2016-06-01

    Optical coherence tomography angiography (OCTA) has increasingly become a clinically useful technique in ophthalmic imaging. We evaluate the repeatability and reproducibility of blood perfusion in the optic nerve head (ONH) measured using optical microangiography (OMAG)-based OCTA. Ten eyes from 10 healthy volunteers are recruited and scanned three times with a 68-kHz Cirrus HD-OCT 5000-based OMAG prototype system (Carl Zeiss Meditec Inc., Dublin, California) centered at the ONH involving two separate visits within six weeks. Vascular images are generated with OMAG processing by detecting the differences in OCT signals between consecutive B-scans acquired at the same retina location. ONH perfusion is quantified as flux, vessel area density, and normalized flux within the ONH for the prelaminar, lamina cribrosa, and the full ONH. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) are used to evaluate intravisit and intervisit repeatability, and interobserver reproducibility. ONH perfusion measurements show high repeatability [CV≤3.7% (intravisit) and ≤5.2% (intervisit)] and interobserver reproducibility (ICC≤0.966) in all three layers by three metrics. OCTA provides a noninvasive method to visualize and quantify ONH perfusion in human eyes with excellent repeatability and reproducibility, which may add additional insight into ONH perfusion in clinical practice.

  7. Quasi-simultaneous multimodal imaging of cutaneous tissue oxygenation and perfusion

    NASA Astrophysics Data System (ADS)

    Ren, Wenqi; Gan, Qi; Wu, Qiang; Zhang, Shiwu; Xu, Ronald

    2015-12-01

    Simultaneous and quantitative assessment of multiple tissue parameters may facilitate more effective diagnosis and therapy in many clinical applications, such as wound healing. However, existing wound assessment methods are typically subjective and qualitative, with the need for sequential data acquisition and coregistration between modalities, and lack of reliable standards for performance evaluation or calibration. To overcome these limitations, we developed a multimodal imaging system for quasi-simultaneous assessment of cutaneous tissue oxygenation and perfusion in a quantitative and noninvasive fashion. The system integrated multispectral and laser speckle imaging technologies into one experimental setup. Tissue oxygenation and perfusion were reconstructed by advanced algorithms. The accuracy and reliability of the imaging system were quantitatively validated in calibration experiments and a tissue-simulating phantom test. The experimental results were compared with a commercial oxygenation and perfusion monitor. Dynamic detection of cutaneous tissue oxygenation and perfusion was also demonstrated in vivo by a postocclusion reactive hyperemia procedure in a human subject and a wound healing process in a wounded mouse model. Our in vivo experiments not only validated the performance of the multimodal imaging system for cutaneous tissue oxygenation and perfusion imaging but also demonstrated its technical potential for wound healing assessment in clinical practice.

  8. Quasi-simultaneous multimodal imaging of cutaneous tissue oxygenation and perfusion.

    PubMed

    Ren, Wenqi; Gan, Qi; Wu, Qiang; Zhang, Shiwu; Xu, Ronald

    2015-12-01

    Simultaneous and quantitative assessment of multiple tissue parameters may facilitate more effective diagnosis and therapy in many clinical applications, such as wound healing. However, existing wound assessment methods are typically subjective and qualitative, with the need for sequential data acquisition and coregistration between modalities, and lack of reliable standards for performance evaluation or calibration. To overcome these limitations, we developed a multimodal imaging system for quasi-simultaneous assessment of cutaneous tissue oxygenation and perfusion in a quantitative and noninvasive fashion. The system integrated multispectral and laser speckle imaging technologies into one experimental setup. Tissue oxygenation and perfusion were reconstructed by advanced algorithms. The accuracy and reliability of the imaging system were quantitatively validated in calibration experiments and a tissue-simulating phantom test. The experimental results were compared with a commercial oxygenation and perfusion monitor. Dynamic detection of cutaneous tissue oxygenation and perfusion was also demonstrated in vivo by a postocclusion reactive hyperemia procedure in a human subject and a wound healing process in a wounded mouse model. Our in vivo experiments not only validated the performance of the multimodal imaging system for cutaneous tissue oxygenation and perfusion imaging but also demonstrated its technical potential for wound healing assessment in clinical practice.

  9. Comparison of Regional Brain Perfusion Levels in Chronically Smoking and Non-Smoking Adults

    PubMed Central

    Durazzo, Timothy C.; Meyerhoff, Dieter J.; Murray, Donna E.

    2015-01-01

    Chronic cigarette smoking is associated with numerous abnormalities in brain neurobiology, but few studies specifically investigated the chronic effects of smoking (compared to the acute effects of smoking, nicotine administration, or nicotine withdrawal) on cerebral perfusion (i.e., blood flow). Predominately middle-aged male (47 ± 11 years of age) smokers (n = 34) and non-smokers (n = 27) were compared on regional cortical perfusion measured by continuous arterial spin labeling magnetic resonance studies at 4 Tesla. Smokers showed significantly lower perfusion than non-smokers in the bilateral medial and lateral orbitofrontal cortices, bilateral inferior parietal lobules, bilateral superior temporal gyri, left posterior cingulate, right isthmus of cingulate, and right supramarginal gyrus. Greater lifetime duration of smoking (adjusted for age) was related to lower perfusion in multiple brain regions. The results indicated smokers showed significant perfusion deficits in anterior cortical regions implicated in the development, progression, and maintenance of all addictive disorders. Smokers concurrently demonstrated reduced blood flow in posterior brain regions that show morphological and metabolic aberrations as well as elevated beta amyloid deposition demonstrated by those with early stage Alzheimer disease. The findings provide additional novel evidence of the adverse effects of cigarette smoking on the human brain. PMID:26193290

  10. Cerebral abnormalities in cocaine abusers: Demonstration by SPECT perfusion brain scintigraphy. Work in progress

    SciTech Connect

    Tumeh, S.S.; Nagel, J.S.; English, R.J.; Moore, M.; Holman, B.L. )

    1990-09-01

    Single photon emission computed tomography (SPECT) perfusion brain scans with iodine-123 isopropyl iodoamphetamine (IMP) were obtained in 12 subjects who acknowledged using cocaine on a sporadic to a daily basis. The route of cocaine administration varied from nasal to intravenous. Concurrent abuse of other drugs was also reported. None of the patients were positive for human immunodeficiency virus. Brain scans demonstrated focal defects in 11 subjects, including seven who were asymptomatic, and no abnormality in one. Among the findings were scattered focal cortical deficits, which were seen in several patients and which ranged in severity from small and few to multiple and large, with a special predilection for the frontal and temporal lobes. No perfusion deficits were seen on I-123 SPECT images in five healthy volunteers. Focal alterations in cerebral perfusion are seen commonly in asymptomatic drug users, and these focal deficits are readily depicted by I-123 IMP SPECT.

  11. Dependence of Brain Intravoxel Incoherent Motion Perfusion Parameters on the Cardiac Cycle

    PubMed Central

    Federau, Christian; Hagmann, Patric; Maeder, Philippe; Müller, Markus; Meuli, Reto; Stuber, Matthias; O’Brien, Kieran

    2013-01-01

    Measurement of microvascular perfusion with Intravoxel Incoherent Motion (IVIM) MRI is gaining interest. Yet, the physiological influences on the IVIM perfusion parameters (“pseudo-diffusion” coefficient D*, perfusion fraction f, and flow related parameter fD*) remain insufficiently characterized. In this article, we hypothesize that D* and fD*, which depend on blood speed, should vary during the cardiac cycle. We extended the IVIM model to include time dependence of D* = D*(t), and demonstrate in the healthy human brain that both parameters D* and fD* are significantly larger during systole than diastole, while the diffusion coefficient D and f do not vary significantly. The results non-invasively demonstrate the pulsatility of the brain’s microvasculature. PMID:24023649

  12. Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation.

    PubMed

    Wang, Ling; Mohan, Chandra

    2016-09-01

    This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, non-invasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease.

  13. Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation

    PubMed Central

    2016-01-01

    Abstract This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, non-invasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease. PMID:28191530

  14. Importance of climate, forest fires and human population size on the long-term boreal forest dynamics in Northern Europe

    NASA Astrophysics Data System (ADS)

    Kuosmanen, Niina; Seppä, Heikki; Alenius, Teija; Bradshaw, Richard; Clear, Jennifer; Filimonova, Fludmila; Heikkilä, Maija; Renssen, Hans; Tallavaara, Miikka; Reitalu, Triin

    2016-04-01

    Palaeoecological data provides valuable information for understanding the processes behind the past changes in forest composition, and hence can provide important knowledge regarding the potential effects of future changes in climate on boreal vegetation. Furthermore, it is essential to consider both regional and local factors in order to better understand the processes behind the boreal forest dynamics. The relative importance of climate, forest fires and human population size on long-term boreal forest composition were statistically investigated at regional and local scales in Fennoscandia. Statistical method variation partitioning was employed to assess the relative importance of these three variables. Fossil pollen data reflecting long-term boreal forest composition, at both regional (lake records) and local (small hollow records) scales from Russia, Finland and Sweden, were used as response matrix. Climate, generated from a climate model and oxygen isotope data, past forest fires generated from sedimentary charcoal data and human population size derived from radiocarbon dated archaeological findings were used as potential drivers of long-term boreal vegetation. Though the results clearly demonstrate that climate is the main driver of long-term vegetation changes at the regional scale, the role of climate notably is smaller at local scale and the influence of local site specific factors increases. However, the relative importance of forest fires on long-term changes in boreal forest composition remain generally low both at regional and local scale. The relatively low importance of both climate and forest fires on the variation in long-term boreal forest composition at local scale demonstrates the complexity of factors affecting stand-scale forest dynamics. In general, the relative importance of human population size on long-term changes in boreal vegetation was low. However, this was the first time that this type of human population size data was statistically

  15. The plasma cyclic-AMP response to noise in humans and rats—short-term exposure to various noise levels

    NASA Astrophysics Data System (ADS)

    Iwamoto, M.; Dodo, H.; Ishii, F.; Yoneda, J.; Yamazaki, S.; Goto, H.

    1988-12-01

    Rats were exposed to short-term noise which was found to activate the hypothalamohypophyseal-adrenal system and result in a decrease of adrenal ascorbic acid (AAA) and an increase of serum corticosterone (SCS). The threshold limit value lay between 60 and 70 dB(A). To characterize better the effect of noise on the human hypothalamo-hypophyseal-adrenal system, a large group of subjects was exposed to short-term noise at 85 dB(A) and higher, and tested for levels of adrenocortical steroid (cortisol) and anterior pituitary hormones such as ACTH, growth hormone (GH) and prolactin (PRL). Results in humans showed hyperfunction of the hypothalamo-pituitary system. However, as the responses in rats and humans differed, a further experiment was performed using C-AMP, a second messenger mediating many of the effects of a variety of hormones. Plasma C-AMP in humans and rats increased significantly after exposure to noise greater than 70 dB(A). We suggest that plasma C-AMP could be useful as a sensitive index for noise-related stress in the daily living environment of humans and rats.

  16. Imaging of myocardial perfusion with magnetic resonance.

    PubMed

    Barkhausen, Jörg; Hunold, Peter; Jochims, Markus; Debatin, Jörg F

    2004-06-01

    Coronary artery disease (CAD) is currently the leading cause of death in developed nations. Reflecting the complexity of cardiac function and morphology, noninvasive diagnosis of CAD represents a major challenge for medical imaging. Although coronary artery stenoses can be depicted with magnetic resonance (MR) and computed tomography (CT) techniques, its functional or hemodynamic impact frequently remains elusive. Therefore, there is growing interest in other, target organ-specific parameters such as myocardial function at stress and first-pass myocardial perfusion imaging to assess myocardial blood flow. This review explores the pathophysiologic background, recent technical developments, and current clinical status of first-pass MR imaging (MRI) of myocardial perfusion.

  17. Expansion and long-term culture of human spermatogonial stem cells via the activation of SMAD3 and AKT pathways.

    PubMed

    Guo, Ying; Liu, Linhong; Sun, Min; Hai, Yanan; Li, Zheng; He, Zuping

    2015-08-01

    Spermatogonial stem cells (SSCs) can differentiate into spermatids, reflecting that they could be used in reproductive medicine for treating male infertility. SSCs are able to become embryonic stem-like cells with the potentials of differentiating into numerous cell types of the three germ layers and they can transdifferentiate to mature and functional cells of other lineages, highlighting significant applications of human SSCs for treating human diseases. However, human SSCs are very rare and a long-term culture system of human SSCs has not yet established. This aim of study was to isolate, identify and culture human SSCs for a long period. We isolated GPR125-positive spermatogonia with high purity and viability from adult human testicular tissues utilizing the two-step enzymatic digestion and magnetic-activated cell sorting with antibody against GPR125. These freshly isolated cells expressed a number of markers for SSCs, including GPR125, PLZF, GFRA1, RET, THY1, UCHL1 and MAGEA4, but not the hallmarks for spermatocytes and spermatozoa, e.g. SYCP1, SYCP3, PRM1, and TNP1. The isolated human SSCs could be cultured for two months with a significant increase of cell number with the defined medium containing growth factors and hydrogel. Notably, the expression of numerous SSC markers was maintained during the cultivation of human SSCs. Furthermore, SMAD3 and AKT phosphorylation was enhanced during the culture of human SSCs. Collectively, these results suggest that human SSCs can be cultivated for a long period and expanded whilst retaining an undifferentiated status via the activation of SMAD3 and AKT pathways. This study could provide sufficient cells of SSCs for their basic research and clinic applications in reproductive and regenerative medicine.

  18. Distinctiveness enhances long-term event memory in non-human primates, irrespective of reinforcement.

    PubMed

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-04-13

    Non-human primates are capable of recalling events that occurred as long as 3 years ago, and are able to distinguish between similar events; akin to human memory. In humans, distinctiveness enhances memory for events, however, it is unknown whether the same occurs in non-human primates. As such, we tested three great ape species on their ability to remember an event that varied in distinctiveness. Across three experiments, apes witnessed a baiting event in which one of three identical containers was baited with food. After a delay of 2 weeks, we tested their memory for the location of the baited container. Apes failed to recall the baited container when the event was undistinctive (Experiment 1), but were successful when it was distinctive (Experiment 2), although performance was equally good in a less-distinctive condition. A third experiment (Experiment 3) confirmed that distinctiveness, independent of reinforcement, was a consistent predictor of performance. These findings suggest that distinctiveness may enhance memory for events in non-human primates in the same way as in humans, and provides further evidence of basic similarities between the ways apes and humans remember past events.

  19. Effects of laser acupuncture on blood perfusion rate

    NASA Astrophysics Data System (ADS)

    Wang, Xian-ju; Zeng, Chang-chun; Liu, Han-ping; Liu, Song-hao; Liu, Liang-gang

    2006-09-01

    Based on Pennes equation, the influences of the intensity and the impulse frequency of laser acupuncture on the point tissues' blood flow perfusion rate are discussed. We find that the blood perfusion rate of point tissue increases with the intensity of laser acupuncture increasing. After impulse laser acupuncture the point tissue blood perfusion rate increase little, but after continuum laser acupuncture the point tissues blood perfusion rate increase much.

  20. A hybrid microsystem for parallel perfusion experiments on living cells

    NASA Astrophysics Data System (ADS)

    Greve, Frauke; Seemann, Livia; Hierlemann, Andreas; Lichtenberg, Jan

    2007-08-01

    A fully integrated microchip device for performing a complete and automated sample-perfusion experiment on living cells is presented. Cells were trapped and immobilized in a defined grid pattern inside a small 0.5 µl volume incubation chamber by pneumatic anchoring on 1000 5-µm orifices. This new cell trapping technique assures a precise and repeatable cell quantity for each experiment and enables the formation of a homogeneous cell population in the incubation chamber. The microsystem includes a perforated silicon chip seamlessly integrated by a new embedding technique in a larger elastomer substrate, which features the microfluidic network. The latter forms the incubation chamber and allows for economic logarithmic dilution of the sample reagent over a range of three orders of magnitude with subsequent perfusion of the cell population. First, the logarithmic dilution stage was validated using quantitative fluorescent imaging of fluorescein solution. Then, the cell adhesion and culturing inside the incubation chamber was studied using primary normal human dermal fibroblasts (NHDFs). The cells adhered well on laminin-coated surfaces and proliferated to form a confluent cell layer after 6 days in vitro. Finally, the complete system was tested by a perfusion experiment with cultured NHDFs, which were exposed to a fluorescent cell tracker at dilutions of 100 µm, 10 µm, 1 µm, 0.1 µm and 0 µm at a flow rate of 1.25 µl min-1 for 20 min. Fluorescence imaging of the cell array after incubation and image analysis showed a logarithmic relationship between sample concentration and the fluorescence signal. This paper describes the fabrication of the components and the assembly of the microsystem, the design approach and the validation of the sample diluter, cell-adhesion and cell-culturing experiments over several days.

  1. Strategies for Prospecting and Extracting Water on Mars for Long-Term Human Exploration

    NASA Astrophysics Data System (ADS)

    Rolley, R. J.; Saikia, S. J.

    2017-02-01

    We aim to develop a specific set of criteria to classify water reserves on Mars, and to design water prospecting and extraction systems for various human landing sites using a requirements-driven framework.

  2. Perfusion MRI: The Five Most Frequently Asked Clinical Questions

    PubMed Central

    Essig, Marco; Nguyen, Thanh Binh; Shiroishi, Mark S.; Saake, Marc; Provenzale, James M.; Enterline, David S.; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

    2013-01-01

    OBJECTIVE This article addresses questions that radiologists frequently ask when planning, performing, processing, and interpreting MRI perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23971482

  3. Preterm birth is associated with an increased fundamental frequency of spontaneous crying in human infants at term-equivalent age

    PubMed Central

    Shinya, Yuta; Kawai, Masahiko; Niwa, Fusako; Myowa-Yamakoshi, Masako

    2014-01-01

    Human infant crying has been researched as a non-invasive tool for assessing neurophysiological states at an early developmental stage. Little is known about the acoustic features of spontaneous cries in preterm infants, although their pain-induced cries are at a higher fundamental frequency (F0) before term-equivalent age. In this study, we investigated the effects of gestational age, body size at recording and intrauterine growth retardation (IUGR) on the F0 of spontaneous cries in healthy preterm and full-term infants at term-equivalent age. We found that shorter gestational age was significantly associated with higher F0, although neither smaller body size at recording nor IUGR was related to increased F0 in preterm infants. These findings suggest that the increased F0 of spontaneous cries is not caused by their smaller body size, but instead might be caused by more complicated neurophysiological states owing to their different intrauterine and extrauterine experiences. PMID:25122740

  4. Short- and Long-Term Effects of Unpredictable Repeated Negative Stimuli on Japanese Quail's Fear of Humans

    PubMed Central

    Laurence, Agathe; Lumineau, Sophie; Calandreau, Ludovic; Arnould, Cécile; Leterrier, Christine; Boissy, Alain; Houdelier, Cécilia

    2014-01-01

    Numerous aversive events occur in poultry production, and if repeated and unpredictable, can result in an impaired welfare. Some events such as handling can be perceived negatively and it is of interest to understand how humans' behaviour could affect poultry's behaviours and especially its avoidance of humans. Our aim was to evaluate short- and long-lasting effects of a 3-week procedure involving unpredictable repeated negative stimuli (URNS) applied during the post-juvenile period on quail's reactivity to humans. We compared the reactions of two sets of quail: URNS was applied to one set (treated quail) and the other set was left undisturbed (control quail). When two weeks old, treated quail were exposed to a variety of negative stimuli, either applied automatically or involving human presence. One and seven weeks after the termination of the procedure, the reactivity of control and treated quail to a passive human being was evaluated. Furthermore, the experimenter with her hand on a trough containing a mealworm assessed the propensity of quail of both groups to habituate to feed close to a human being. In the presence of a seated observer, treated quail were more inhibited and more alert than control quail. Likewise, seven weeks after the end of the URNS procedure, more treated than control quail adopted a fear posture. Moreover, whereas control quail spent as much time in the different areas of their cages, treated quail spent more time in the rear part of their cages. Finally, whereas control quail habituated gradually to feed near the experimenter's hand, treated quail did not. All these tests evidence negative short- and long-term effects on treated quail's reactivity to a passive human being and on their habituation to a human being when her presence is positively reinforced. This highlights the importance of young poultry's experience with humans in production. PMID:24668017

  5. Short- and long-term effects of unpredictable repeated negative stimuli on Japanese quail's fear of humans.

    PubMed

    Laurence, Agathe; Lumineau, Sophie; Calandreau, Ludovic; Arnould, Cécile; Leterrier, Christine; Boissy, Alain; Houdelier, Cécilia

    2014-01-01

    Numerous aversive events occur in poultry production, and if repeated and unpredictable, can result in an impaired welfare. Some events such as handling can be perceived negatively and it is of interest to understand how humans' behaviour could affect poultry's behaviours and especially its avoidance of humans. Our aim was to evaluate short- and long-lasting effects of a 3-week procedure involving unpredictable repeated negative stimuli (URNS) applied during the post-juvenile period on quail's reactivity to humans. We compared the reactions of two sets of quail: URNS was applied to one set (treated quail) and the other set was left undisturbed (control quail). When two weeks old, treated quail were exposed to a variety of negative stimuli, either applied automatically or involving human presence. One and seven weeks after the termination of the procedure, the reactivity of control and treated quail to a passive human being was evaluated. Furthermore, the experimenter with her hand on a trough containing a mealworm assessed the propensity of quail of both groups to habituate to feed close to a human being. In the presence of a seated observer, treated quail were more inhibited and more alert than control quail. Likewise, seven weeks after the end of the URNS procedure, more treated than control quail adopted a fear posture. Moreover, whereas control quail spent as much time in the different areas of their cages, treated quail spent more time in the rear part of their cages. Finally, whereas control quail habituated gradually to feed near the experimenter's hand, treated quail did not. All these tests evidence negative short- and long-term effects on treated quail's reactivity to a passive human being and on their habituation to a human being when her presence is positively reinforced. This highlights the importance of young poultry's experience with humans in production.

  6. A proposed lexicon of terms and concepts for human-bear management in North America

    USGS Publications Warehouse

    Hopkins, John B.; Herrero, Stephen; Shideler, Richard T.; Gunther, Kerry A.; Schwartz, Charles C.; Kalinowski, Steven T.

    2010-01-01

    We believe that communication within and among agency personnel in the United States and Canada about the successes and failures of their human–bear (Ursidae) management programs will increase the effectiveness of these programs and of bear research. To communicate more effectively, we suggest agencies clearly define terms and concepts used in human–bear management and use them in a consistent manner. We constructed a human–bear management lexicon of terms and concepts using a modified Delphi method to provide a resource that facilitates more effective communication among human–bear management agencies. Specifically, we defined 40 terms and concepts in human–bear management and suggest definitions based on discussions with 13 other professionals from the United States and Canada. Although new terms and concepts will emerge in the future and definitions will evolve as we learn more about bear behavior and ecology, our purpose is to suggest working definitions for terms and concepts to help guide human–bear management and research activities in North America. Applications or revisions of these definitions may be useful outside of North America.

  7. Longitudinal Study of Cytokine Expression, Lipid Profile and Neuronal Growth Factors in Human Breast Milk from Term and Preterm Deliveries.

    PubMed

    Collado, Maria Carmen; Santaella, Marina; Mira-Pascual, Laia; Martínez-Arias, Elena; Khodayar-Pardo, Parisá; Ros, Gaspar; Martínez-Costa, Cecilia

    2015-10-19

    Breast milk (BM) is considered as a reference for infant nutrition. The role of bioactive components, such as cytokines, hormones, growth factors (GFs) and fatty acids (FAs) is poorly known, but they might be implicated in immune response development. The aim of this study was to identify the lipid profile and the spectrum of cytokines and neuronal GF in BM samples and analyse the influence of gestational age and lactation time on these components. This study used a longitudinal prospective method for the characterization of cytokines, FAs and GFs global profiles in 120 BM samples from 40 healthy mothers (20 preterm and 20 term) collected as colostrum, transitional and mature milk. The cytokines were analysed by protein array (Ray Bio® Human Cytokine Array G6. Ray Biotech, Inc. Norcross, GA, USA) and the FAs were analysed by gas chromatography. The FA profile was similar between the term and the preterm BM samples. Omega-3-α-linoleic and docosahexaenoic acid (DHA) and omega-6-linoleic acid were the most abundant in the term and preterm samples during lactation. Omega-3 ETA and omega-3 EPA we observed exclusively in the preterm samples. The cytokine profile showed a different trend based on gestational age. A significantly higher expression of neurotrophic factors was found in the mature preterm milk samples as compared to the mature term samples. Our study is the first to identify the influence and interactions of perinatal factors on cytokine, GFs and FAs in human milk.

  8. Prospective surface marker-based isolation and expansion of fetal endothelial colony-forming cells from human term placenta.

    PubMed

    Patel, Jatin; Seppanen, Elke; Chong, Mark S K; Yeo, Julie S L; Teo, Erin Y L; Chan, Jerry K Y; Fisk, Nicholas M; Khosrotehrani, Kiarash

    2013-11-01

    The term placenta is a highly vascularized tissue and is usually discarded upon birth. Our objective was to isolate clinically relevant quantities of fetal endothelial colony-forming cells (ECFCs) from human term placenta and to compare them to the well-established donor-matched umbilical cord blood (UCB)-derived ECFCs. A sorting strategy was devised to enrich for CD45-CD34+CD31Lo cells prior to primary plating to obtain pure placental ECFCs (PL-ECFCs) upon culture. UCB-ECFCs were derived using a well-described assay. PL-ECFCs were fetal in origin and expressed the same cell surface markers as UCB-ECFCs. Most importantly, a single term placenta could yield as many ECFCs as 27 UCB donors. PL-ECFCs and UCB-ECFCs had similar in vitro and in vivo vessel forming capacities and restored mouse hind limb ischemia in similar proportions. Gene expression profiles were only minimally divergent between PL-ECFCs and UCB-ECFCs, probably reflecting a vascular source versus a circulating source. Finally, PL-ECFCs and UCB-ECFCs displayed similar hierarchies between high and low proliferative colonies. We report a robust strategy to isolate ECFCs from human term placentas based on their cell surface expression. This yielded much larger quantities of ECFCs than UCB, but the cells were comparable in immunophenotype, gene expression, and in vivo functional ability. We conclude that PL-ECFCs have significant bio-banking and clinical translatability potential.

  9. Longitudinal Study of Cytokine Expression, Lipid Profile and Neuronal Growth Factors in Human Breast Milk from Term and Preterm Deliveries

    PubMed Central

    Collado, Maria Carmen; Santaella, Marina; Mira-Pascual, Laia; Martínez-Arias, Elena; Khodayar-Pardo, Parisá; Ros, Gaspar; Martínez-Costa, Cecilia

    2015-01-01

    Breast milk (BM) is considered as a reference for infant nutrition. The role of bioactive components, such as cytokines, hormones, growth factors (GFs) and fatty acids (FAs) is poorly known, but they might be implicated in immune response development. The aim of this study was to identify the lipid profile and the spectrum of cytokines and neuronal GF in BM samples and analyse the influence of gestational age and lactation time on these components. This study used a longitudinal prospective method for the characterization of cytokines, FAs and GFs global profiles in 120 BM samples from 40 healthy mothers (20 preterm and 20 term) collected as colostrum, transitional and mature milk. The cytokines were analysed by protein array (Ray Bio® Human Cytokine Array G6. Ray Biotech, Inc. Norcross, GA, USA) and the FAs were analysed by gas chromatography. The FA profile was similar between the term and the preterm BM samples. Omega-3-α-linoleic and docosahexaenoic acid (DHA) and omega-6-linoleic acid were the most abundant in the term and preterm samples during lactation. Omega-3 ETA and omega-3 EPA we observed exclusively in the preterm samples. The cytokine profile showed a different trend based on gestational age. A significantly higher expression of neurotrophic factors was found in the mature preterm milk samples as compared to the mature term samples. Our study is the first to identify the influence and interactions of perinatal factors on cytokine, GFs and FAs in human milk. PMID:26492267

  10. Absence of center of mass control for leg abduction in long-term weightlessness in humans.

    PubMed

    Pedrocchi, Alessandra; Baroni, Guido; Mouchnino, Laurence; Ferrigno, Giancarlo; Pedotti, Antonio; Massion, Jean

    2002-02-22

    The present investigation describes for the first time leg lateral abduction performance during long-term microgravity exposure. Two astronauts took part in the experiments, starting 2 weeks into the mission and lasting for 5 months. Results on joint angles kinematics confirm previous investigations on parabolic flights, showing good task fulfillment for both subjects. Special interest was focused on whole body center of mass (CM) positioning. As in short-term microgravity, no initial CM lateral shift toward the 'supporting' leg was observed. In contrast with short-term microgravity and ground-based experiments, no stabilization of the CM medio-lateral position was found but a significant shift of CM toward the moving leg was observed. This suggests that the adaptation to sustained weightlessness might have led to a microgravity-specific motor strategy for leg abduction, which was not focused on CM strategy.

  11. Impact of human milk pasteurization on the kinetics of peptide release during in vitro dynamic term newborn digestion.

    PubMed

    Deglaire, Amélie; De Oliveira, Samira C; Jardin, Julien; Briard-Bion, Valérie; Emily, Mathieu; Ménard, Olivia; Bourlieu, Claire; Dupont, Didier

    2016-07-01

    Holder pasteurization (62.5°C, 30 min) ensures sanitary quality of donor's human milk but also denatures beneficial proteins. Understanding whether this further impacts the kinetics of peptide release during gastrointestinal digestion of human milk was the aim of the present paper. Mature raw (RHM) or pasteurized (PHM) human milk were digested (RHM, n = 2; PHM, n = 3) by an in vitro dynamic system (term stage). Label-free quantitative peptidomics was performed on milk and digesta (ten time points). Ascending hierarchical clustering was conducted on "Pasteurization × Digestion time" interaction coefficients. Preproteolysis occurred in human milk (159 unique peptides; RHM: 91, PHM: 151), mostly on β-casein (88% of the endogenous peptides). The predicted cleavage number increased with pasteurization, potentially through plasmin activation (plasmin cleavages: RHM, 53; PHM, 76). During digestion, eight clusters resumed 1054 peptides from RHM and PHM, originating for 49% of them from β-casein. For seven clusters (57% of peptides), the kinetics of peptide release differed between RHM and PHM. The parent protein was significantly linked to the clustering (p-value = 1.4 E-09), with β-casein and lactoferrin associated to clusters in an opposite manner. Pasteurization impacted selectively gastric and intestinal kinetics of peptide release in term newborns, which may have further nutritional consequences.

  12. Assessing environmental factors to the replacement of Neanderthals by modern humans in terms of eco-cultural niche modelling

    NASA Astrophysics Data System (ADS)

    Kondo, Yasuhisa; Sano, Katsuhiro; Kadowaki, Seiji; Naganuma, Masaki; Omori, Takayuki; Yoneda, Minoru; Nishiaki, Yoshihiro

    2014-05-01

    Eco-cultural niche modelling (ECNM) is an application of ecological niche modelling (ENM) to estimate the human niche in response to environmental settings. The niche probability is calculated for each spatial pixel, based on (1) the location of known archaeological sites as occurrence data and (2) environmental factors such palaeoclimate (temperature and precipitation), palaeovegetation (biome) and palaeotopography (elevation, slope and aspect). Some ENM software packages, including MaxEnt (maximum entropy model), output the percentage of contribution for each environmental factor, and therefore it is possible to identify and evaluate environmental constraints to the geographic expansion of human populations. Based on this thought, the authors applied ECNM to Palaeolithic stone tool industries in Europe and Siberia at 50-46 kya, the time period during which the first anatomically modern humans (AMHs) are presumed to have appeared in those regions, under the assumption that stone tool groups may reflect different human groups in terms of subsistence strategy. The preliminary results suggested that the population using Emiran and related industries (Bohunician and Bachokirian) were likely to construct their niches in the geographic zones where the long-term variability of the coldest month temperature was larger than in those occupied by the populations using the Late Mousterian, Szeletian and Châtelperronean stone tool industries.

  13. Lung Perfusion Scanning in Hepatic Cirrhosis

    PubMed Central

    Stanley, N. N.; Ackrill, P.; Wood, J.

    1972-01-01

    Abnormal lung perfusion scans using radioactive particles were found in five out of six cases of hepatic cirrhosis with arterial hypoxaemia. None had clinical evidence of cardiopulmonary disease or signs of pulmonary embolism on arteriography. The scan defects are probably caused by a disorder of the pulmonary microvasculature, which may show regional variation in severity. ImagesFIG. 1FIG. 2 PMID:4645896

  14. Coupling between resting cerebral perfusion and EEG.

    PubMed

    O'Gorman, R L; Poil, S-S; Brandeis, D; Klaver, P; Bollmann, S; Ghisleni, C; Lüchinger, R; Martin, E; Shankaranarayanan, A; Alsop, D C; Michels, L

    2013-07-01

    While several studies have investigated interactions between the electroencephalography (EEG) and functional magnetic resonance imaging BOLD signal fluctuations, less is known about the associations between EEG oscillations and baseline brain haemodynamics, and few studies have examined the link between EEG power outside the alpha band and baseline perfusion. Here we compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of healthy adults (n = 16, ten females, median age: 27 years, range 21-48) during an eyes closed rest condition. Correlations emerged between perfusion and global average EEG power in low (delta: 2-4 Hz and theta: 4-7 Hz), middle (alpha: 8-13 Hz), and high (beta: 13-30 Hz and gamma: 30-45 Hz) frequency bands in both cortical and sub-cortical regions. The correlations were predominately positive in middle and high-frequency bands, and negative in delta. In addition, central alpha frequency positively correlated with perfusion in a network of brain regions associated with the modulation of attention and preparedness for external input, and central theta frequency correlated negatively with a widespread network of cortical regions. These results indicate that the coupling between average EEG power/frequency and local cerebral blood flow varies in a frequency specific manner. Our results are consistent with longstanding concepts that decreasing EEG frequencies which in general map onto decreasing levels of activation.

  15. Nuclear cardiology: Myocardial perfusion and function

    SciTech Connect

    Seldin, D.W. )

    1991-08-01

    Myocardial perfusion studies continue to be a major focus of research, with new investigations of the relationship of exercise-redistribution thallium imaging to diagnosis, prognosis, and case management. The redistribution phenomenon, which seemed to be fairly well understood a few years ago, is now recognized to be much more complex than originally thought, and various strategies have been proposed to clarify the meaning of persistent defects. Pharmacologic intervention with dipyridamole and adenosine has become available as an alternative to exercise, and comparisons with exercise imaging and catheterization results have been described. Thallium itself is no longer the sole single-photon perfusion radiopharmaceutical; two new technetium agents are now widely available. In addition to perfusion studies, advances in the study of ventricular function have been made, including reports of studies performed in conjunction with technetium perfusion studies, new insights into cardiac physiology, and the prognostic and case-management information that function studies provide. Finally, work has continued with monoclonal antibodies for the identification of areas of myocyte necrosis. 41 references.

  16. A reappraisal of retrograde cerebral perfusion

    PubMed Central

    2013-01-01

    Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients. PMID:23977600

  17. Asynchronicity of facial blood perfusion in migraine.

    PubMed

    Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A; Kamshilin, Alexei A; Närhi, Matti; Karjalainen, Pasi A; Giniatullin, Rashid

    2013-01-01

    Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology.

  18. Asynchronicity of Facial Blood Perfusion in Migraine

    PubMed Central

    Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A.; Kamshilin, Alexei A.; Närhi, Matti; Karjalainen, Pasi A.; Giniatullin, Rashid

    2013-01-01

    Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology. PMID:24324592

  19. Perfusion computed tomography in patients with stroke thrombolysis

    PubMed Central

    Kawano, Hiroyuki; Bivard, Andrew; Lin, Longting; Ma, Henry; Cheng, Xin; Aviv, Richard; O’Brien, Billy; Butcher, Kenneth; Lou, Min; Zhang, Jingfen; Jannes, Jim; Dong, Qiang; Levi, Christopher R.

    2017-01-01

    Abstract See Saver (doi:10.1093/awx020) for a scientific commentary on this article. Stroke shortens an individual’s disability-free life. We aimed to assess the relative prognostic influence of pre- and post-treatment perfusion computed tomography imaging variables (e.g. ischaemic core and penumbral volumes) compared to standard clinical predictors (such as onset-to-treatment time) on long-term stroke disability in patients undergoing thrombolysis. We used data from a prospectively collected international, multicentre, observational registry of acute ischaemic stroke patients who had perfusion computed tomography and computed tomography angiography before treatment with intravenous alteplase. Baseline perfusion computed tomography and follow-up magnetic resonance imaging were analysed to derive the baseline penumbra volume, baseline ischaemic core volume, and penumbra salvaged from infarction. The primary outcome measure was the effect of imaging and clinical variables on Disability-Adjusted Life Year. Clinical variables were age, sex, National Institutes of Health Stroke Scale score, and onset-to-treatment time. Age, sex, country, and 3-month modified Rankin Scale were extracted from the registry to calculate disability-adjusted life-year due to stroke, such that 1 year of disability-adjusted life-year equates to 1 year of healthy life lost due to stroke. There were 772 patients receiving alteplase therapy. The number of disability-adjusted life-year days lost per 1 ml of baseline ischaemic core volume was 17.5 (95% confidence interval, 13.2–21.9 days, P < 0.001). For every millilitre of penumbra salvaged, 7.2 days of disability-adjusted life-year days were saved (β = −7.2, 95% confidence interval, −10.4 to −4.1 days, P < 0.001). Each minute of earlier onset-to-treatment time resulted in a saving of 4.4 disability-free days after stroke (1.3–7.5 days, P = 0.006). However, after adjustment for imaging variables, onset-to-treatment time was not

  20. Possible psycho-physiological consequences of human long-term space missions

    NASA Astrophysics Data System (ADS)

    Belisheva, N. K.; Lammer, H.; Biernat, H. K.; Kachanova, T. L.; Kalashnikova, I. V.

    Experiments carried out on the Earth s surface during different years and under contrast periods of solar activity have shown that the functional state of biosystems including the human organisms are controlled by global and local geocosmical agents Our finding have a close relation to space research because they demonstrate the reactions of biosystems on variations of global and local geocosmical agents and the mechanisms of modulations of biosystems state by geocosmical agents We revealed the role of variations of the geomagnetic field for the stimulation of immune systems functional state of peripheral blood human brain growth of microflora skin covers and pathogenic microorganisms The study of the psycho-physiological state of the human organism has demonstrated that an increase of the neutron intensity near the Earth s surface is associated with anxiety decrease of normal and increase of paradox reactions of examinees The analysis of the human brain functional state in dependent on the geomagnetic variation structure dose under exposure to the variations of geomagnetic field in a certain amplitude-frequency range and also the intensity of the nucleon component of secondary cosmic rays showed that the stable and unstable states of the human brain are determined by geomagnetic field variations and the intensity of the nucleon component The stable state of the brain manifested under the periodic oscillations of the geomagnetic field in a certain amplitude-frequency range The low level of geomagnetic activity associated with an

  1. Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioral profiles.

    PubMed

    Melega, William P; Jorgensen, Matthew J; Laćan, Goran; Way, Baldwin M; Pham, Jamie; Morton, Grenvill; Cho, Arthur K; Fairbanks, Lynn A

    2008-05-01

    Methamphetamine (METH)-associated alterations in the human striatal dopamine (DA) system have been identified with positron emission tomography (PET) imaging and post-mortem studies but have not been well correlated with behavioral changes or cumulative METH intake. Animal studies that model some aspects of human long-term METH abuse can establish dose-dependency profiles of both behavioral changes and potential brain neurotoxicities for identifying consequences of particular cumulative exposures. Based on parameters from human and our monkey pharmacokinetic studies, we modeled a prevalent human METH exposure of daily multiple doses in socially housed vervet monkeys. METH doses were escalated over 33 weeks, with final dosages resulting in estimated peak plasma METH concentrations of 1-3 microM, a range measured in human abusers. With larger METH doses, progressive increases in abnormal behavior and decreases in social behavior were observed on 'injection' days. Anxiety increased on 'no injection' days while aggression decreased throughout the study. Thereafter, during 3 weeks abstinence, differences in baseline vs post-METH behaviors were not observed. Post-mortem analysis of METH brains showed 20% lower striatal DA content while autoradiography studies of precommissural striatum showed 35% lower [3H]WIN35428 binding to the DA transporter. No statistically significant changes were detected for [3H]dihydrotetrabenazine binding to the vesicular monoamine transporter (METH-lower by 10%) or for [3H]SCH 23390 and [3H]raclopride binding to DA D1 and D2 receptors, respectively. Collectively, this long-term, escalating dose METH exposure modeling a human abuse pattern, not associated with high-dose binges, resulted in dose-dependent behavioral effects and caused persistent changes in presynaptic striatal DA system integrity.

  2. In situ measurements of magnetic nanoparticles after placenta perfusion

    NASA Astrophysics Data System (ADS)

    Müller, Robert; Gläser, Marcus; Göhner, Claudia; Seyfarth, Lydia; Schleussner, Ekkehard; Hofmann, Andreas; Fritzsche, Wolfgang

    2015-04-01

    Nanoparticles (NP) present promising tools for medical applications. However, the investigation of their spatial and temporal distribution is hampered by missing in-situ particle detection and quantification technologies. The placenta perfusion experiment represents an interesting model for the study of the particle distribution at a biological barrier. It allows the ex-vivo investigation of the permeability of the placenta for materials of interest. We introduce an approach based on a magnetic system for an in situ measurement of the concentration of magnetic NPs in such an experiment. A previously off-line utilized magnetic readout device (sensitivity of ≈10-8 Am2) was used for long term measurements of magnetic NP of 100-150 nm size range in a closed circuit of a placenta perfusion. It represents a semiquantitative approach. The behavior of particles in the placenta and in the measurement system was studied, as well as the influence of particle surface modifications. The results suggest a transfer of a low amount of particles from the maternal to the fetal blood circuit.

  3. Myocardial Perfusion SPECT Imaging in Patients after Percutaneous Coronary Intervention.

    PubMed

    Georgoulias, Panagiotis; Valotassiou, Varvara; Tsougos, Ioannis; Demakopoulos, Nikolaos

    2010-05-01

    Coronary artery disease (CAD) is the most prevalent form of cardiovascular disease affecting about 13 million Americans, while more than one million percutaneous transluminal intervention (PCI) procedures are performed annually in the USA. The relative high occurrence of restenosis, despite stent implementation, seems to be the primary limitation of PCI. Over the last decades, single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), has proven an invaluable tool for the diagnosis of CAD and patients' risk stratification, providing useful information regarding the decision about revascularization and is well suited to assess patients after intervention. Information gained from post-intervention MPI is crucial to differentiate patients with angina from those with exo-cardiac chest pain syndromes, to assess peri-intervention myocardial damage, to predict-detect restenosis after PCI, to detect CAD progression in non-revascularized vessels, to evaluate the effects of intervention if required for occupational reasons and to evaluate patients' long-term prognosis. On the other hand, chest pain and exercise electrocardiography are largely unhelpful in identifying patients at risk after PCI.Although there are enough published data demonstrating the value of myocardial perfusion SPECT imaging in patients after PCI, there is still debate on whether or not these tests should be performed routinely.

  4. Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein in human fetal membranes throughout pregnancy and at term.

    PubMed

    Brown, N L; Slater, D M; Alvi, S A; Elder, M G; Sullivan, M H; Bennett, P R

    1999-07-01

    Lipoxygenase metabolites may be involved in human parturition. 5-lipoxygenase (5-LOX) catalyses the first steps in the synthesis of leukotrienes from arachidonic acid, and its activity is dependent on 5-LOX activating protein (FLAP). The expression of 5-LOX and FLAP were investigated in fetal membranes to determine whether there are changes with gestational age or at term with the onset of labour. No significant differences were found in the expression of 5-LOX or FLAP mRNA in the amnion at different gestational ages or at term. In the chorion-decidua, 5-LOX mRNA expression was significantly higher in the first trimester of pregnancy than in the second and third trimesters. At term, there was a significant increase in both 5-LOX mRNA and protein expression in the chorion-decidua in the time after labour, compared with the time before labour. The expression of FLAP mRNA was also significantly higher in the chorion-decidua in the first trimester of pregnancy compared with the third trimester, and at term in the time after labour compared with the time before labour. Expression of FLAP protein was not studied, as an antibody is not currently available. These results are consistent with a role for 5-LOX and FLAP in the control of parturition at term, and also suggest an involvement earlier in pregnancy.

  5. Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation-like pain amplification in humans.

    PubMed

    Henrich, Florian; Magerl, Walter; Klein, Thomas; Greffrath, Wolfgang; Treede, Rolf-Detlef

    2015-09-01

    Long-term potentiation in the spinal dorsal horn requires peptidergic C-fibre activation in animals. Perceptual correlates of long-term potentiation following high-frequency electrical stimulation in humans include increased sensitivity to electrical stimuli at the high frequency stimulation site (homotopic pain-long-term potentiation) and increased sensitivity to pinprick surrounding the high frequency stimulation site (heterotopic pain-long-term potentiation, equivalent to secondary hyperalgaesia). To characterize the peripheral fibre populations involved in induction of pain-long-term potentiation, we performed two selective nerve block experiments in 30 healthy male volunteers. Functional blockade of TRPV1-positive nociceptors by high-concentration capsaicin (verified by loss of heat pain) significantly reduced pain ratings to high frequency stimulation by 47% (P < 0.001), homotopic pain-long-term potentiation by 71% (P < 0.01), heterotopic pain-long-term potentiation by 92% (P < 0.001) and the area of secondary hyperalgesia by 76% (P < 0.001). The selective blockade of A-fibre conduction by nerve compression (verified by loss of first pain to pinprick) significantly reduced pain ratings to high frequency stimulation by 37% (P < 0.01), but not homotopic pain-long-term potentiation (-5%). It had a marginal effect on heterotopic pain-long-term potentiation (-35%, P = 0.059), while the area of secondary hyperalgesia remained unchanged (-2%, P = 0.88). In conclusion, all nociceptor subclasses contribute to high frequency stimulation-induced pain (with a relative contribution of C > Aδ fibres, and an equal contribution of TRPV1-positive and TRPV1-negative fibres). TRPV1-positive C-fibres are the main inducers of both homotopic and heterotopic pain-long-term potentiation. TRPV1-positive A-fibres contribute substantially to the induction of heterotopic pain-long-term potentiation. TRPV1-negative C-fibres induce a component of homotopic self-facilitation but not

  6. Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population

    PubMed Central

    Amen, Daniel G.; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A.

    2016-01-01

    Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This

  7. Effect of Long-Term Hyperbaric Stress on Ammonia Metabolism in Humans

    DTIC Science & Technology

    1978-09-01

    collection, In humans, research has shown that amylase secretion, serum was frozen for subsequent determination of blood another indicator of ANS activity...have shown that the urea 30o concentration in saliva from the parotid duct is positive- 26 ly correlated with plasma urea concentration. In fact, I

  8. A comparative biomechanical analysis of term fetal membranes in human and domestic species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to biomechanically characterize and compare human, porcine, equine, and ovine fetal membranes. Noncontact metrology was used for topographic analyses. Uniaxial tensile testing was performed to resolve specific biomechanical values. Puncture force and radial stresses we...

  9. Feasibility of quantitative lung perfusion by 4D CT imaging by a new dynamic-scanning protocol in an animal model

    NASA Astrophysics Data System (ADS)

    Wang, Yang; Goldin, Jonathan G.; Abtin, Fereidoun G.; Brown, Matt; McNitt-Gray, Mike

    2008-03-01

    The purpose of this study is to test a new dynamic Perfusion-CT imaging protocol in an animal model and investigate the feasibility of quantifying perfusion of lung parenchyma to perform functional analysis from 4D CT image data. A novel perfusion-CT protocol was designed with 25 scanning time points: the first at baseline and 24 scans after a bolus injection of contrast material. Post-contrast CT scanning images were acquired with a high sampling rate before the first blood recirculation and then a relatively low sampling rate until 10 minutes after administrating contrast agent. Lower radiation techniques were used to keep the radiation dose to an acceptable level. 2 Yorkshire swine with pulmonary emboli underwent this perfusion- CT protocol at suspended end inspiration. The software tools were designed to measure the quantitative perfusion parameters (perfusion, permeability, relative blood volume, blood flow, wash-in & wash-out enhancement) of voxel or interesting area of lung. The perfusion values were calculated for further lung functional analysis and presented visually as contrast enhancement maps for the volume being examined. The results show increased CT temporal sampling rate provides the feasibility of quantifying lung function and evaluating the pulmonary emboli. Differences between areas with known perfusion defects and those without perfusion defects were observed. In conclusion, the techniques to calculate the lung perfusion on animal model have potential application in human lung functional analysis such as evaluation of functional effects of pulmonary embolism. With further study, these techniques might be applicable in human lung parenchyma characterization and possibly for lung nodule characterization.

  10. The CD44+ALDH+ Population of Human Keratinocytes Is Enriched for Epidermal Stem Cells with Long-Term Repopulating Ability

    PubMed Central

    Szabo, Akos Z.; Fong, Stephen; Yue, Lili; Zhang, Kai; Strachan, Lauren R.; Scalapino, Kenneth; Mancianti, Maria Laura; Ghadially, Ruby

    2014-01-01

    Like for other somatic tissues, isolation of a pure population of stem cells has been a primary goal in epidermal biology. We isolated discrete populations of freshly obtained human neonatal keratinocytes (HNKs) using previously untested candidate stem cell markers aldehyde dehydrogenase (ALDH) and CD44 as well as the previously studied combination of integrin α6 and CD71. An in vivo transplantation assay combined with limiting dilution analysis was used to quantify enrichment for long-term repopulating cells in the isolated populations. The ALDH+CD44+ population was enriched 12.6-fold for long-term repopulating epidermal stem cells (EpiSCs) and the integrin α6hiCD71lo population was enriched 5.6-fold, over unfractionated cells. In addition to long-term repopulation, CD44+ALDH+ keratinocytes exhibited other stem cell properties. CD44+ALDH+ keratinocytes had self-renewal ability, demonstrated by increased numbers of cells expressing nuclear Bmi-1, serial transplantation of CD44+ALDH+ cells, and holoclone formation in vitro. CD44+ALDH+ cells were multipotent, producing greater numbers of hair follicle-like structures than CD44−ALDH− cells. Furthermore, 58% ± 7% of CD44+ALDH+ cells exhibited label-retention. In vitro, CD44+ALDH+ cells showed enhanced colony formation, in both keratinocyte and embryonic stem cell growth media. In summary, the CD44+ALDH+ population exhibits stem cell properties including long-term epidermal regeneration, multipotency, label retention, and holoclone formation. This study shows that it is possible to quantify the relative number of EpiSCs in human keratinocyte populations using long-term repopulation as a functional test of stem cell nature. Future studies will combine isolation strategies as dictated by the results of quantitative transplantation assays, in order to achieve a nearly pure population of EpiSCs. PMID:23335266

  11. Simultaneous myocardial strain and dark-blood perfusion imaging using a displacement-encoded MRI pulse sequence.

    PubMed

    Le, Yuan; Stein, Ashley; Berry, Colin; Kellman, Peter; Bennett, Eric E; Taylor, Joni; Lucas, Katherine; Kopace, Rael; Chefd'Hotel, Christophe; Lorenz, Christine H; Croisille, Pierre; Wen, Han

    2010-09-01

    The purpose of this study is to develop and evaluate a displacement-encoded pulse sequence for simultaneous perfusion and strain imaging. Displacement-encoded images in two to three myocardial slices were repeatedly acquired using a single-shot pulse sequence for 3 to 4 min, which covers a bolus infusion of Gadolinium contrast. The magnitudes of the images were T(1) weighted and provided quantitative measures of perfusion, while the phase maps yielded strain measurements. In an acute coronary occlusion swine protocol (n = 9), segmental perfusion measurements were validated against microsphere reference standard with a linear regression (slope 0.986, R(2) = 0.765, Bland-Altman standard deviation = 0.15 mL/min/g). In a group of ST-elevation myocardial infarction patients (n = 11), the scan success rate was 76%. Short-term contrast washout rate and perfusion are highly correlated (R(2) = 0.72), and the pixelwise relationship between circumferential strain and perfusion was better described with a sigmoidal Hill curve than linear functions. This study demonstrates the feasibility of measuring strain and perfusion from a single set of images.

  12. Simultaneous Myocardial Strain and Dark-Blood Perfusion Imaging Using a Displacement-Encoded MRI Pulse Sequence

    PubMed Central

    Le, Yuan; Stein, Ashley; Berry, Colin; Kellman, Peter; Bennett, Eric E.; Taylor, Joni; Lucas, Katherine; Kopace, Rael; Chefd’Hotel, Christophe; Lorenz, Christine H.; Croisille, Pierre; Wen, Han

    2010-01-01

    The purpose of this study is to develop and evaluate a displacement-encoded pulse sequence for simultaneous perfusion and strain imaging. Displacement-encoded images in 2–3 myocardial slices were repeatedly acquired using a single shot pulse sequence for 3 to 4 minutes, which covers a bolus infusion of Gd. The magnitudes of the images were T1 weighted and provided quantitative measures of perfusion, while the phase maps yielded strain measurements. In an acute coronary occlusion swine protocol (n=9), segmental perfusion measurements were validated against microsphere reference standard with a linear regression (slope 0.986, R2 = 0.765, Bland-Altman standard deviation = 0.15 ml/min/g). In a group of ST-elevation myocardial infarction(STEMI) patients (n=11), the scan success rate was 76%. Short-term contrast washout rate and perfusion are highly correlated (R2=0.72), and the pixel-wise relationship between circumferential strain and perfusion was better described with a sigmoidal Hill curve than linear functions. This study demonstrates the feasibility of measuring strain and perfusion from a single set of images. PMID:20544714

  13. Retinal research using the perfused mammalian eye.

    PubMed

    Niemeyer, G

    2001-05-01

    The effort to isolate and maintain alive in vitro an intact mammalian eye is rewarded by the full control provided over the arterial input and exclusion of systemic regulatory or compensatory mechanisms. Electrical recording of typical light-evoked field potentials from retina and optic nerve can be complemented by single-cell recording. Thus, light-induced electrical activity reflects the function of the retinal pigment epithelium, of the layers of the retina and of the ganglion cells or their axons. Retinal function in vitro is documented by electrophysiological and morphological methods revealing subtle features of retinal information processing as well as optic nerve signals that approach-at threshold stimulus intensity-the human psychophysical threshold. Such sensitivity of third-order retinal neurons is described for the first time. This well controlled in vitro preparation has been used successfully for biophysical, metabolic and pharmacological studies. Examples are provided that demonstrate the marked sensibility of the rod system to changes in glucose supply. Moreover, histochemical identification of glycogen stores revealed labeling of the second- and third-order neurons subserving the rod system, in addition to labeling of Müller (glial) cells in the cat retina. The glycogen content of the cat retina is augmented by prolonged anesthesia, largely depleted by ischemia after enucleation and enhanced by insulin. Pharmacological experiments using agonists and antagonists of putative retinal neurotransmitters are summarized and outlined using the muscarinic cholinergic agonist QNB as an example. Actions and uptake of the neuromodulator adenosine are presented in detail, including inhibitory effects on physiologically characterized ganglion cells. Neuronal effects of adenosine are distinguished from those resulting from vasodilatation and from glycogenolysis induced by the neuromodulator. To open the blood-retina barrier, a hyperosmotic challenge can be

  14. The Snackbot: Documenting the Design of a Robot for Long-term Human-Robot Interaction

    DTIC Science & Technology

    2009-03-01

    quality snacks would be a useful application for a long-term product and service in these buildings. Most snacks that do exist are highly caloric, and...think about the emergent qualities of the product and service, which might not be recognized if the system were analyzed in component parts rather...functional arms that hold a tray, used for carrying snacks (Figure 2). The tray is equipped with 12 load cells; each is capable of measuring a weight range

  15. Effects of long term low- and high-dose sodium arsenite exposure in human transitional cells

    PubMed Central

    He, Jianming; Wang, Feng; Luo, Fen; Chen, Xuedan; Liang, Xi; Jiang, Wenbin; Huang, Zhizhong; Lei, Jiafan; Shan, Fabo; Xu, Xueqing

    2017-01-01

    Epidemiological studies have revealed the association between increased risk of bladder cancer and chronic arsenic exposure. Here, we explored biological effects of arsenic in T24. Microarray analysis was applied to analyze mRNA in T24 following 0, 2 or 5 μM sodium arsenite (As) exposure for 72 hours. Long term (up to 140 days) low-dose (200 nM) and high-dose (1,000 nM) As decreased E-cadherin protein level through different mechanisms because the mRNA levels of E-cadherin increased following low-dose As exposure but decreased following high-dose As exposure. Long term As increased the protein levels of N-cadherin, vimentin, β-catenin, and slug. Low-dose As exposure resulted in a change in the morphology of T24 cells from an epithelial to a mesenchymal-like appearance. Knockdown of E-cadherin increased the protein levels of N-cadherin, vimentin, β-catenin, and slug. Cell proliferation and growth of T24 with or without As exposure for 100 days were assayed using EdU and WST, respectively. Low-dose As exposure increased cell proliferation and growth while high-dose As exposure decreased both. Long term As activated p53 on account of increasing protein levels of p53, p-p53 (Ser15), and mRNA levels of p21. These demonstrate that arsenic exposure exerts multiple effects. Long term low- or high-dose arsenic induces epithelial-mesenchymal transition, likely via downregulation of E-cadherin, activates p53, and differently affects cell proliferation/growth. PMID:28337271

  16. Selective cerebral perfusion for cerebral protection: what we do know

    PubMed Central

    Tang, Gilbert H. L.

    2013-01-01

    Selective antegrade cerebral perfusion (SACP) for aortic arch surgery has evolved considerably since it was first reported. Various pressure rates have been investigated through animal models, as has the effect of warmer perfusate temperatures and hematocrit. Clinical research into pH management, the role of unilateral and bilateral perfusion, and core temperatures have further refined the procedure. We recommend the following protocol for SACP: perfusion pressure between 40-60 mmHg, flow rates between 6-10 mL/kg/min, and perfusate temperature of 20-28 °C; core cooling to 18-30 °C contingent on duration of arrest; alpha-stat pH management; hematocrit between 25-30%; near infrared spectroscopy to monitor cerebral perfusion; and bilateral perfusion when prolonged durations of SACP is anticipated. PMID:23977601

  17. [Changes in blood lipids in humans during long-term ski crossing in the Extreme North].

    PubMed

    Panin, L E; Ostanina, L S

    1991-01-01

    Serum lipids were measured in the men who made two ski crosses in the Far North during polar night. The first trip, which was to train the athletes, took 17 days and the second took 38 days. In both studies, lipid mobilization and utilization increased, which led to changes in the lipid spectrum: decrease of the concentration of LDL and, in the second trip, of VLDL and HDL3, and increase of the concentration of HDL2 and cholesterol HDL. In the second trip, lipids were most intensively utilized: lipolysis enhanced and free fatty acids declined. This was also indicated by an increase of the capillary-venous difference in terms of the total fraction of LDL and VLDL as well as free fatty acids. At the end of the second trip, the positive capillary-venous difference in terms of LDL and VLDL and, accordingly, the negative capillary-venous difference in terms of HDL2 and HDL3 increased. At the end of both trips the synthesis of transport lipids grew; in the most strenuous second trip, their active utilization in the working organs was stronger.

  18. Explosions and human health: the long-term effects of blast injury.

    PubMed

    Finlay, Sarah E; Earby, Michelle; Baker, David J; Murray, Virginia S G

    2012-08-01

    The immediate patterns of injury from explosions are well documented, from both military and civil experience. However, few studies have focused on less immediately apparent health consequences and latent effects of explosions in survivors, emergency responders and the surrounding community. This review aimed to analyze the risks to health following an explosion in a civil setting. A comprehensive review of the open literature was conducted, and data on 10 relevant military, civilian and industrial events were collected. Events were selected according to availability of published studies and involvement of large numbers of people injured. In addition, structured interviews with experts in the field were conducted, and existing national guidelines reviewed. The review revealed significant and potentially long-term health implications affecting various body systems and psychological well-being following exposure to an explosion. An awareness of the short- and long-term health effects of explosions is essential in screening for blast injuries, and identifying latent pathologies that could otherwise be overlooked in stressful situations with other visually distracting injuries and, often, mass casualties. Such knowledge would guide responsible medical staff in implementing early appropriate interventions to reduce the burden of long-term sequelae. Effective planning and response strategies would ensure accessibility of appropriate health care resources and evidence-based information in the aftermath of an explosion.

  19. Representation of Instantaneous and Short-Term Loudness in the Human Cortex

    PubMed Central

    Thwaites, Andrew; Glasberg, Brian R.; Nimmo-Smith, Ian; Marslen-Wilson, William D.; Moore, Brian C. J.

    2016-01-01

    Acoustic signals pass through numerous transforms in the auditory system before perceptual attributes such as loudness and pitch are derived. However, relatively little is known as to exactly when these transformations happen, and where, cortically or sub-cortically, they occur. In an effort to examine this, we investigated the latencies and locations of cortical entrainment to two transforms predicted by a model of loudness perception for time-varying sounds: the transforms were instantaneous loudness and short-term loudness, where the latter is hypothesized to be derived from the former and therefore should occur later in time. Entrainment of cortical activity was estimated from electro- and magneto-encephalographic (EMEG) activity, recorded while healthy subjects listened to continuous speech. There was entrainment to instantaneous loudness bilaterally at 45, 100, and 165 ms, in Heschl's gyrus, dorsal lateral sulcus, and Heschl's gyrus, respectively. Entrainment to short-term loudness was found in both the dorsal lateral sulcus and superior temporal sulcus at 275 ms. These results suggest that short-term loudness is derived from instantaneous loudness, and that this derivation occurs after processing in sub-cortical structures. PMID:27199645

  20. Changes in the long-term hydrological regimes and the impacts of human activities in the main Wei River, China

    NASA Astrophysics Data System (ADS)

    Zhang, Hongbo; Huang, Qiang; Zhang, Qiang; Gu, Lei; Chen, Keyu; Yu, Qijun

    2016-03-01

    Under the combined influence of climate changes and human activities, the hydrological regime of the Wei River shows remarkable variations which have caused many issues in the Wei River in recent decades, such as a lack of freshwater, water pollution, disastrous flooding and channel sedimentation. Hence, hydrological regime changes and potential human-induced impacts have been drawing increasing attention from local government and hydrologists. This study investigates hydrological regime changes in the natural and measured runoff series at four hydrological stations on the main Wei River and quantifies features of their long-term change by analysing their historical annual and seasonal runoff data using several approaches, i.e., continuous wavelet transform, cross-wavelet, wavelet coherence, trend-free pre-whitening Mann-Kendall test and detrended fluctuation analysis. By contrasting two different analysis results between natural and measured river runoff series, the impacts of human activities on the long-term hydrological regime were investigated via the changes of spatio-temporal distribution in dominant periods, the trends and long-range memory of river runoff. The results show : (a) that periodic properties of the streamflow changes are the result of climate, referring to precipitation changes in particular, while human activities play a minor role; (b) a significant decreasing trend can be observed in the natural streamflow series along the entire main stream of the Wei River and the more serious decrease emerging in measured flow should result from human-induced influences in recent decades; and (c) continuous decreasing streamflow in the Wei River will trigger serious shortages of freshwater in the future, which may challenge the sustainability and safety of water resources development in the river basin, and should be paid great attention before 2020.

  1. Hydrostatic isolated limb perfusion with adeno-associated virus vectors enhances correction of skeletal muscle in Pompe disease.

    PubMed

    Sun, B; Li, S; Bird, A; Koeberl, D D

    2010-12-01

    Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the inherited deficiency of acid-α-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. We hypothesized that hydrostatic isolated limb perfusion (ILP) administration of an adeno-associated virus (AAV) vector containing a muscle-specific promoter could achieve relatively higher transgene expression in the hindlimb muscles of GAA-knockout (GAA-KO) mice, in comparison with intravenous (IV) administration. ILP administration of AAV2/8 vectors encoding alkaline phosphatase or human GAA-transduced skeletal muscles of the hindlimb widely, despite the relatively low number of vector particles administered (1 × 10¹¹), and IV administration of an equivalent vector dose failed to transduce skeletal muscle detectably. Similarly, ILP administration of fewer vector particles of the AAV2/9 vector encoding human GAA (3 × 10¹⁰) transduced skeletal muscles of the hindlimb widely and significantly reduced glycogen content to, in comparison with IV administration. The only advantage for IV administration was moderately high-level transduction of cardiac muscle, which demonstrated compellingly that ILP administration sequestered vector particles within the perfused limb. Reduction of glycogen storage in the extensor digitorum longus demonstrated the potential advantage of ILP-mediated delivery of AAV vectors in Pompe disease, because type II myofibers are resistant to enzyme replacement therapy. Thus, ILP will enhance AAV transduction of multiple skeletal muscles while reducing the required dosages in terms of vector particle numbers.

  2. Temporal Segmentation of Human Short-Term Behavior in Everyday Activities and Interview Sessions

    NASA Astrophysics Data System (ADS)

    Lemke, Matthias R.; Schleidt, Margret

    Human behavior is structured by serial order and timing of functionally related groups of movements with a duration of a few seconds. These elementary action units have been described in ethological studies during unstaged everyday behavior, but not during interview sessions. Psychomotor alterations are relevant for differential diagnosis and treatment, and psychiatric patients are generally evaluated during interview sessions. Therefore the time structure of upper limb movements (n=764) of healthy subjects (n=22) were studied using videotaped interviews and frame-by-frame analysis and compared to movements (n=530) of unstaged human everyday behavior (n=154). The number of action units, but not their duration, was correlated inversely with self-reported impairment of mood and pleasure experience in healthy persons. The temporal distribution of movements in interview sessions did not differ from the time patterns of everyday behavior. This method could be a promising tool to investigate time patterns of movements and psychomotor alterations in psychiatric patients during interview sessions.

  3. Pulmonary ventilation and perfusion abnormalities and ventilation perfusion imbalance in children with pulmonary atresia or extreme tetralogy of Fallot

    SciTech Connect

    Dowdle, S.C.; Human, D.G.; Mann, M.D. )

    1990-08-01

    Xenon-133 lung ventilation and perfusion scans were done preoperatively after cardiac catheterization and cineangiocardiography in 19 children; 6 had pulmonary atresia with an intact ventricular septum and hypoplastic right ventricle, 4 pulmonary atresia with associated complex univentricular heart, and 9 extreme Tetralogy of Fallot. The four patients with discrepancies in the sizes of the left and right pulmonary arteries on angiography had marked asymmetry of pulmonary perfusion and ventilation-perfusion imbalance on scintigraphy. Similar degrees of asymmetry and imbalance were present in 6 of the 15 children with equal-size pulmonary vessels. Asymmetry of pulmonary perfusion and ventilation-perfusion imbalance were associated with a poor prognosis.

  4. Changes of protein profile of human urine after long-term orbital flights.

    PubMed

    Pastushkova, L Kh; Valeeva, O A; Kononikhin, A S; Nikolaev, E N; Larina, I M; Dobrokhotov, I V; Popov, I A; Pochuev, V I; Kireev, K S

    2013-12-01

    We analyzed protein profile of urine samples obtained from 7 Russian cosmonauts (age 35-51 years), participants of space flights on the International Space Station lasting for 169-199 days. Gradient chromatography with linear increase of eluent proportion was carried out in a system consisting of an Agilent 1100 chromatograph (Agilent Technologies Inc.) and a hybrid mass-spectrometer LTQ-FT Ultra (Thermo). The obtained results help to understand changes in the human body induced by space flight factors.

  5. Human migration to space: Alternative technological approaches for long-term adaptation to extraterrestrial environments and the implications for human evolution

    NASA Astrophysics Data System (ADS)

    Lockard, Elizabeth Song

    As humans embark upon the next phase of Space exploration---establishing human outposts in low-Earth orbit, on the Moon, and on Mars---the scope of human factors must expand beyond the meager requirements for short-term missions to Space to include issues of comfort and well-being necessary for long-term durations. However, to habitate---to dwell in a place---implies more than creature comforts in order to adapt. Human factors research must also include a phenomenological perspective---an understanding of how we experience the places we live in---in order for a community to be robust and to thrive. The first phase of migration will be an especially tenuous one requiring intensive technological intervention. The modes by which those technologies are implemented will have significant bearing on the process of human adaptation: the nature of the mediation can be either one of domination, subordination, avoidance, or integration. Ultimately, adaptation is best ensured if symbiotic processes of negotiation and cooperation between subject and environment are espoused over acts of conquest or acquiescence. The adaptive mechanisms we choose to develop and employ will have wider implications for long-range human evolution. The transformations we will undergo will be influenced by both the initial decision to migrate to Space (technological), as well as the actual conditions of Space (environmental). Migration to extraterrestrial environments will be unequivocally the most profound catalyst for evolution in the history of humankind---not only for the human species itself but also for the new environments we will eventually inhabit. At the same time, we also find ourselves---via a new generation of bio-, nano-, and digital technologies---in the position to consciously and willfully direct our own evolution. Technology has always been transformative, but in the not-so-distant future, we will soon possess the capacity to radically re-invent ourselves in almost any way

  6. Effect of General Anesthesia in Infancy on Long-Term Recognition Memory in Humans and Rats

    PubMed Central

    Stratmann, Greg; Lee, Joshua; Sall, Jeffrey W; Lee, Bradley H; Alvi, Rehan S; Shih, Jennifer; Rowe, Allison M; Ramage, Tatiana M; Chang, Flora L; Alexander, Terri G; Lempert, David K; Lin, Nan; Siu, Kasey H; Elphick, Sophie A; Wong, Alice; Schnair, Caitlin I; Vu, Alexander F; Chan, John T; Zai, Huizhen; Wong, Michelle K; Anthony, Amanda M; Barbour, Kyle C; Ben-Tzur, Dana; Kazarian, Natalie E; Lee, Joyce YY; Shen, Jay R; Liu, Eric; Behniwal, Gurbir S; Lammers, Cathy R; Quinones, Zoel; Aggarwal, Anuj; Cedars, Elizabeth; Yonelinas, Andrew P; Ghetti, Simona

    2014-01-01

    Anesthesia in infancy impairs performance in recognition memory tasks in mammalian animals, but it is unknown if this occurs in humans. Successful recognition can be based on stimulus familiarity or recollection of event details. Several brain structures involved in recollection are affected by anesthesia-induced neurodegeneration in animals. Therefore, we hypothesized that anesthesia in infancy impairs recollection later in life in humans and rats. Twenty eight children ages 6–11 who had undergone a procedure requiring general anesthesia before age 1 were compared with 28 age- and gender-matched children who had not undergone anesthesia. Recollection and familiarity were assessed in an object recognition memory test using receiver operator characteristic analysis. In addition, IQ and Child Behavior Checklist scores were assessed. In parallel, thirty three 7-day-old rats were randomized to receive anesthesia or sham anesthesia. Over 10 months, recollection and familiarity were assessed using an odor recognition test. We found that anesthetized children had significantly lower recollection scores and were impaired at recollecting associative information compared with controls. Familiarity, IQ, and Child Behavior Checklist scores were not different between groups. In rats, anesthetized subjects had significantly lower recollection scores than controls while familiarity was unaffected. Rats that had undergone tissue injury during anesthesia had similar recollection indices as rats that had been anesthetized without tissue injury. These findings suggest that general anesthesia in infancy impairs recollection later in life in humans and rats. In rats, this effect is independent of underlying disease or tissue injury. PMID:24910347

  7. Ecological consequences of human niche construction: Examining long-term anthropogenic shaping of global species distributions

    PubMed Central

    Boivin, Nicole L.; Zeder, Melinda A.; Fuller, Dorian Q.; Crowther, Alison; Larson, Greger; Erlandson, Jon M.; Denham, Tim; Petraglia, Michael D.

    2016-01-01

    The exhibition of increasingly intensive and complex niche construction behaviors through time is a key feature of human evolution, culminating in the advanced capacity for ecosystem engineering exhibited by Homo sapiens. A crucial outcome of such behaviors has been the dramatic reshaping of the global biosphere, a transformation whose early origins are increasingly apparent from cumulative archaeological and paleoecological datasets. Such data suggest that, by the Late Pleistocene, humans had begun to engage in activities that have led to alterations in the distributions of a vast array of species across most, if not all, taxonomic groups. Changes to biodiversity have included extinctions, extirpations, and shifts in species composition, diversity, and community structure. We outline key examples of these changes, highlighting findings from the study of new datasets, like ancient DNA (aDNA), stable isotopes, and microfossils, as well as the application of new statistical and computational methods to datasets that have accumulated significantly in recent decades. We focus on four major phases that witnessed broad anthropogenic alterations to biodiversity—the Late Pleistocene global human expansion, the Neolithic spread of agriculture, the era of island colonization, and the emergence of early urbanized societies and commercial networks. Archaeological evidence documents millennia of anthropogenic transformations that have created novel ecosystems around the world. This record has implications for ecological and evolutionary research, conservation strategies, and the maintenance of ecosystem services, pointing to a significant need for broader cross-disciplinary engagement between archaeology and the biological and environmental sciences. PMID:27274046

  8. Benzodiazepine self-administration in humans and laboratory animals--implications for problems of long-term use and abuse.

    PubMed

    Griffiths, R R; Weerts, E M

    1997-11-01

    Drug reinforcement may represent the primary behavioral-pharmacological mechanism underlying two types of problematic use of benzodiazepines--recreational abuse by polydrug abusers and inappropriate chronic use by patients. High dose polydrug abuse for the purpose of getting high is readily recognized as a significant social problem. Inappropriate chronic benzodiazepine use is more subtle but relatively common: for anxiolytics, 36% of past-year users (3% of the adult population in the US) report using these drugs for 4 consecutive months or longer. The risks of such long-term use are much better documented than the benefits. This paper provides a current review of various problems that have been identified with the long-term use and the recreational abuse of benzodiazepines, including memory impairment, risk of accidents, falls and hip fractures in the elderly, a withdrawal syndrome, brain damage, overuse in the elderly, overuse by chronic pain patients, overuse by alcoholics and recreational abuse among alcoholics and polydrug abusers. A comprehensive review of the literature on benzodiazepine reinforcing effects in humans and laboratory animals is also provided. Drug self-administration studies in humans and laboratory animals provide models of both types of problematic benzodiazepine use. Recreational abuse of benzodiazepines has been modeled in human research with polydrug abusers and in laboratory animal studies, which show that the reinforcing effect of benzodiazepines is intermediate relative to other sedative compounds and is increased in subjects with histories of previous sedative drug self-administration. The problem of inappropriate long-term use of benzodiazepines by people without histories of drug abuse has been partially modeled in human studies showing that benzodiazepines function as reinforcers in subjects with anxiety, insomnia, and histories of moderate alcohol consumption, and in preclinical studies showing stable, low-rate benzodiazepine self

  9. The Groningen hypothermic liver perfusion pump: functional evaluation of a new machine perfusion system.

    PubMed

    van der Plaats, A; Maathuis, M H J; 'T Hart, N A; Bellekom, A A; Hofker, H S; van der Houwen, E B; Verkerke, G J; Leuvenink, H G D; Verdonck, P; Ploeg, R J; Rakhorst, G

    2006-12-01

    To improve preservation of donor livers, we have developed a portable hypothermic machine perfusion (HMP) system as an alternative for static cold storage. A prototype of the system was built and evaluated on functionality. Evaluation criteria included 24 h of adequate pressure controlled perfusion, sufficient oxygenation, a maintained 0-4 degrees C temperature and sterile conditions. Porcine livers were perfused with pump pressures that were set at 4 mmHg (continuous, portal vein) and 30/20 mmHg, at 60 BPM (pulsatile, hepatic artery). Control livers were preserved using the clinical golden standard: static cold storage. In the HMP group, pressure, flow and temperature were continuously monitored for 24 h. At time-points t = 0, 2, 4, 8, 12, and 24 h samples of University of Wisconsin machine preservation solution were taken for measurement of partial oxygen pressure (pO(2)) and lacto-dehydrogenase. Biopsies in every lobe were taken for histology and electron microscopy; samples of ice, preservation solution, liver surface, and bile were taken and cultured to determine sterility. Results showed that temperature was maintained at 0-4 degrees C; perfusion pressure was maintained at 4 mmHg and 30/20 mmHg for portal vein and hepatic artery, respectively. Flow was approximately 350 and 80 ml/min, respectively, but decreased in the portal vein, probably due to edema formation. Arterial pO(2) was kept at 100 kPa. Histology showed complete perfusion of the liver with no major damage to hepatocytes, bile ducts, and non-parenchymal cells compared to control livers. The machine perfusion system complied to the design criteria and will have to demonstrate the superiority of machine perfusion over cold storage in transplant experiments.

  10. Long-Term Live Cell Imaging of Cell Migration: Effects of Pathogenic Fungi on Human Epithelial Cell Migration.

    PubMed

    Wöllert, Torsten; Langford, George M

    2016-01-01

    Long-term live cell imaging was used in this study to determine the responses of human epithelial cells to pathogenic biofilms formed by Candida albicans. Epithelial cells of the skin represent the front line of defense against invasive pathogens such as C. albicans but under certain circumstances, especially when the host's immune system is compromised, the skin barrier is breached. The mechanisms by which the fungal pathogen penetrates the skin and invade the deeper layers are not fully understood. In this study we used keratinocytes grown in culture as an in vitro model system to determine changes in host cell migration and the actin cytoskeleton in response to virulence factors produced by biofilms of pathogenic C. albicans. It is clear that changes in epithelial cell migration are part of the response to virulence factors secreted by biofilms of C. albicans and the actin cytoskeleton is the downstream effector that mediates cell migration. Our goal is to understand the mechanism by which virulence factors hijack the signaling pathways of the actin cytoskeleton to alter cell migration and thereby invade host tissues. To understand the dynamic changes of the actin cytoskeleton during infection, we used long-term live cell imaging to obtain spatial and temporal information of actin filament dynamics and to identify signal transduction pathways that regulate the actin cytoskeleton and its associated proteins. Long-term live cell imaging was achieved using a high resolution, multi-mode epifluorescence microscope equipped with specialized light sources, high-speed cameras with high sensitivity detectors, and specific biocompatible fluorescent markers. In addition to the multi-mode epifluorescence microscope, a spinning disk confocal long-term live cell imaging system (Olympus CV1000) equipped with a stage incubator to create a stable in vitro environment for long-term real-time and time-lapse microscopy was used. Detailed descriptions of these two long-term live

  11. Bile salt-stimulated lipase of human milk: characterization of the enzyme from preterm and term milk

    SciTech Connect

    Freed, L.M.; Hamosh, P.; Hamosh, M.

    1986-03-01

    The bile salt-stimulated lipase (BSSL) of human milk is an important digestive enzyme in the newborn whose pancreatic function is immature. Milk from mothers delivering premature infants (preterm milk) has similar levels of BSSL activity to that of mothers of term infants (term milk). This study has determined whether the BSSL in preterm milk has the same characteristics as that in term milk. Milk samples were collected during the first 12 wk of lactation from seven mothers of infants born at 26-30 wk (very preterm, VPT), 31-37 wk (preterm, PT) and 37-42 wk (term, T) gestation. BSSL activity was measured using /sup 3/H-triolein emulsion as substrate. Time course, bile salt and enzyme concentration, pH and pH stability were studied, as well as inhibition of BSSL by eserine. The characteristics of BSSL from preterm and term milk were identical as were comparisons between colostrum and mature milk BSSL. BSSL from all milk sources had a neutral-to-alkaline pH optimum (pH 7.3-8.9), was stable at low pH for 60 min, and was 95-100% inhibited by eserine (greater than or equal to 0.6 mM). BSSL activity, regardless of enzyme source, was bile-salt dependent and was stimulated only by primary bile salts (taurocholate, glycocholate). The data indicate that the BSSL in milks of mothers delivering as early as 26 wk gestation is identical to that in term milk.

  12. Long-Term Persistence of Prevalently Detected Human Papillomavirus Infections in the Absence of Detectable Cervical Precancer and Cancer

    PubMed Central

    Rodríguez, Ana Cecilia; Burk, Robert D.; Herrero, Rolando; Wacholder, Sholom; Hildesheim, Allan; Morales, Jorge; Rydzak, Greg; Schiffman, Mark

    2011-01-01

    Background. Detailed descriptions of long-term persistence of human papillomavirus (HPV) in the absence of cervical precancer are lacking. Methods. In a large, population-based natural study conducted in Guanacaste, Costa Rica, we studied a subset of 810 initially HPV-positive women with ≥3 years of active follow-up with ≥3 screening visits who had no future evidence of cervical precancer. Cervical specimens were tested for >40 HPV genotypes using a MY09/11 L1-targeted polymerase chain reaction method. Results. Seventy-two prevalently-detected HPV infections (5%) in 58 women (7%) persisted until the end of the follow-up period (median duration of follow-up, 7 years) without evidence of cervical precancer. At enrollment, women with long-term persistence were more likely to have multiple prevalently-detected HPV infections (P <.001) than were women who cleared their baseline HPV infections during follow-up. In a logistic regression model, women with long-term persistence were more likely than women who cleared infections to have another newly-detected HPV infection detectable at ≥3 visits (odds ratio, 2.6; 95% confidence interval, 1.2–5.6). Conclusions. Women with long-term persistence of HPV infection appear to be generally more susceptible to other HPV infections, especially longer-lasting infections, than are women who cleared their HPV infections. PMID:21343148

  13. Lipoxygenase-another pathway for glutathione conjugation of xenobiotics: A study with human term placental lipoxygenase and ethacrynic acid.

    PubMed

    Kulkarni, A P; Sajan, M

    1999-11-15

    In this study, we examined the ability of human term placental lipoxygenase (HTPLO) to catalyze glutathione (GSH) conjugate formation from ethacrynic acid (EA) in the presence of linoleic acid (LA) and GSH. HTPLO purified by affinity chromatography was used in all the experiments. The results indicate that the process of EA-SG is enzymatic in nature. The reaction shows dependence on pH, the enzyme, and the concentration of GSH, LA, and EA. The optimal assay conditions to observe a maximal rate of EA-SG formation required the presence of 0.3 mM LA, 0.2 mM EA, 2.0 mM GSH, and approximately 300 microg HTPLO in the reaction medium buffered at pH 9.0. Under the experimental conditions employed, the reaction exhibited K(m) values of 1.1 mM, 200 microM, and 130 microM for GSH, LA, and EA, respectively. The estimated specific activity of HTPLO-catalyzed EA-GS formation was approximately 4.4 +/- 0.4 micromol/min/mg protein. This rate is more than twofold greater than the rate noted for the reaction mediated by the purified human term placental glutathione transferase. Under physiologically relevant conditions (20 microM LA, 2.0 mM GSH, at pH 7.4), HTPLO produced EA-SG at 56% of the maximal rate noted under optimal assay conditions. Nordihydroguaiaretic acid, the classical inhibitor of different lipoxygenases, significantly blocked the reaction. It is proposed that free radicals are involved in the process of EA-SG formation by HTPLO. The evidence gathered in this in vitro study suggests for the first time that lipoxygenase present in the human term placenta is capable of EA-SG formation.

  14. Probabilistic assessment of the influence of lake properties in long-term radiation doses to humans.

    PubMed

    Pohjola, Jari; Turunen, Jari; Lipping, Tarmo; Ikonen, Ari T K

    2016-11-01

    The assessment processes concerning the safety of nuclear waste repositories include the modelling of radionuclide transport in biosphere and the evaluation of the doses to the most affected humans. In this paper, a scenario, in which a contaminated lake is the water source for drinking water, irrigation water and watering of livestock, is presented. The objective of the paper is to probabilistically study the influence of lake properties as parameters in the assessment scenario. The properties of the lake are a result of previously conducted probabilistic studies, where the land uplift of the terrain surrounding the repositories and the formation of water bodies were studied in a 10,000-year time span using Monte Carlo simulation. The lake is formed at 3000 years from present day and the changing properties of the lake have been used in the study. The studied radionuclides (36)Cl, (135)Cs, (129)I, (237)Np, (90)Sr, (99)Tc and (238)U enter the lake with a rate of 1 Bq/year. The transport process from the lake water to humans is described and the doses (dose conversion factors) to adult humans are evaluated based on a study on average food consumption. Sensitivity analysis is used for identifying the parameters having the most influence on the outcome of the dose. Based on the results from the sensitivity analysis, the volumetric outflow rate of the lake and the volume of the lake were taken into closer consideration. The results show the influence of probabilistically derived geomorphic lake input parameters on the dose.

  15. Short-term sertraline treatment suppresses sympathetic nervous system activity in healthy human subjects.

    PubMed

    Shores, M M; Pascualy, M; Lewis, N L; Flatness, D; Veith, R C

    2001-05-01

    Increased sympathetic nervous system (SNS) activity has been associated with stress, major depression, aging, and several medical conditions. This study assessed the effect of the selective serotonin reuptake inhibitor (SSRI), sertraline, on sympathetic nervous system (SNS) activity in healthy subjects. Twelve healthy volunteers participated in a double-blind, placebo-controlled, norepinephrine (NE) kinetic study, in which the effects of sertraline on SNS activity were ascertained by determining NE plasma concentrations and NE plasma appearance rates and clearance rates in sertraline or placebo conditions. Subjects received 50 mg of sertraline or placebo for two days and then one week later underwent the same protocol with the other drug. By single compartmental analysis, plasma NE appearance rates were significantly lower in the sertraline compared to the placebo condition (0.26+/-0.10 vs 0.40+/-0.23 microg/m(2)/min; P=0.04). Our study found that the net effect of short-term SSRI treatment is an apparent suppression of SNS activity as indicated by a decreased plasma NE appearance rate in the sertraline condition. If this preliminary finding can be extended to long-term treatment of patients, this could have significant therapeutic relevance for treating depression in elderly patients or those with cardiac disease, in which elevated SNS activity may exacerbate underlying medical conditions.

  16. The long-term benefits of human generosity in indirect reciprocity.

    PubMed

    Wedekind, Claus; Braithwaite, Victoria A

    2002-06-25

    Among the theories that have been proposed to explain the evolution of altruism are direct reciprocity and indirect reciprocity. The idea of the latter is that helping someone or refusing to do so has an impact on one's reputation within a group. This reputation is constantly assessed and reassessed by others and is taken into account by them in future social interactions. Generosity in indirect reciprocity can evolve if and only if it eventually leads to a net benefit in the long term. Here, we show that this key assumption is met. We let 114 students play for money in an indirect and a subsequent direct reciprocity game. We found that although being generous, i.e., giving something of value to others, had the obvious short-term costs, it paid in the long run because it builds up a reputation that is rewarded by third parties (who thereby themselves increase their reputation). A reputation of being generous also provided an advantage in the subsequent direct reciprocity game, probably because it builds up trust that can lead to more stable cooperation.

  17. Identification and localization of netrin-4 and neogenin in human first trimester and term placenta.

    PubMed

    Dakouane-Giudicelli, M; Duboucher, C; Fortemps, J; Salama, S; Brulé, A; Rozenberg, P; de Mazancourt, P

    2012-09-01

    We describe here for the first time the characterization of family member of netrins, netrin-4 and its receptor neogenin, during the development of the placenta. By using western blots and RT-PCR, we demonstrated the presence of netrin-4 and its receptor neogenin protein as well as their transcripts. Using immunohistochemistry, we studied the distribution of netrin-4 and neogenin in both the first trimester and term placenta. We observed staining of netrin-4 in villous and extravillous cytotrophoblasts, syncytiotrophoblast, and endothelial cells whereas staining in stromal cells was faint. In decidua, we observed netrin-4 labelling in glandular epithelial cells, perivascular decidualized cells, and endothelial cells. However, neogenin was absent in villous and extravillous cytotrophoblasts and was expressed only on syncytiotrophoblast and placental stromal cells in the first trimester and at term placenta. The pattern of distribution suggests that a functional netrin-4-neogenin pathway might be restricted to syncytiotrophoblasts, mesenchymal cells, and villous endothelial cells. This pathway function might vary with its localization in the placenta. It is possibly involved in angiogenesis, morphogenesis, and differentiation.

  18. The influence of natural feeding on human health: short- and long-term perspectives

    PubMed Central

    Woźniak, Urszula; Czyżewska, Krystyna

    2014-01-01

    Breastfeeding is the most appropriate way to nourish infants. It promotes proper physical and intellectual development of the child. Human milk is unique and impossible to replicate with any other kind of food. However, using maternal milk not only has beneficial effects on the infant's health but it can also help to prevent illnesses in adulthood. Breastfeeding improves immunity and consequently decreases the occurrence of infections, especially those of the gastrointestinal tract and respiratory tract. Moreover, it helps to reduce the risk of some disorders such as allergies, diabetes mellitus type 1, obesity and arterial hypertension. PMID:24868292

  19. Long-term administration of inulin-type fructans has no significant lipid-lowering effect in normolipidemic humans.

    PubMed

    Forcheron, Fabien; Beylot, Michel

    2007-08-01

    Short-term studies have shown that the addition to diet of inulin-type fructans, a nondigestible carbohydrate, may have a plasma lipid-lowering effect in humans. Whether this beneficial effect persists during long-term administration has not been determined. The study was aimed at determining whether a prolonged (6 months) administration of inulin-type fructans to healthy subjects has a lipid-lowering action. In a double-blind, randomized, placebo-controlled study, 17 healthy subjects were studied before and after 6 months of daily administration of placebo (8 subjects) or 10 g of a mix of inulin and oligofructose (9 subjects). During this 6-month period, they consumed their usual diet and did not modify their everyday way of life. We measured plasma lipid concentrations; cholesterol synthesis and hepatic lipogenesis; and adipose tissue and circulating mononuclear cell messenger RNA concentrations of key regulatory genes of cholesterol metabolism. Compared with the administration of placebo, the administration of inulin-type fructans had no effect on plasma triacylglycerol concentrations and hepatic lipogenesis and induced only a nonsignificant trend for decreased plasma total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol concentration. Cholesterol synthesis was not significantly modified. Of all the messenger RNA concentrations measured, none was significantly modified by the administration of inulin-type fructans. In conclusion, contrary to what was observed in short-term studies, we observed no significant beneficial effect of a long-term (6-month) administration of inulin-type fructans on plasma lipids in healthy human subjects.

  20. The longer-term effects of human capital enrichment programs on poverty and inequality: Oportunidades in Mexico*

    PubMed Central

    McKee, Douglas; Todd, Petra E.

    2012-01-01

    Previous empirical research has shown that Mexico’s Oportunidades program has succeeded in increasing schooling and improving health of disadvantaged children. This paper studies the program’s potential longer-term consequences for the poverty and inequality of these children. It adapts methods developed in DiNardo, Fortin and Lemieux (1996) and incorporates existing experimental estimates of the program’s effects on human capital to analyze how Oportunidades will affect future earnings of program participants. We nonparametrically simulate earnings distributions, with and without the program, and predict that Oportunidades will increase future mean earnings but have only modest effects on poverty rates and earnings inequality. PMID:22577618

  1. Transmission of human hepatitis C virus from patients in secondary cells for long term culture

    PubMed Central

    Revie, Dennis; Braich, Ravi S; Bayles, David; Chelyapov, Nickolas; Khan, Rafat; Geer, Cheryl; Reisman, Richard; Kelley, Ann S; Prichard, John G; Salahuddin, S Zaki

    2005-01-01

    Infection by human hepatitis C virus (HCV) is the principal cause of post-transfusion hepatitis and chronic liver diseases worldwide. A reliable in vitro culture system for the isolation and analysis of this virus is not currently available, and, as a consequence, HCV pathogenesis is poorly understood. We report here the first robust in vitro system for the isolation and propagation of HCV from infected donor blood. This system involves infecting freshly prepared macrophages with HCV and then transmission of macrophage-adapted virus into freshly immortalized B-cells from human fetal cord blood. Using this system, newly isolated HCV have been replicated in vitro in continuous cultures for over 130 weeks. These isolates were also transmitted by cell-free methods into different cell types, including B-cells, T-cells and neuronal precursor cells. These secondarily infected cells also produced in vitro transmissible infectious virus. Replication of HCV-RNA was validated by RT-PCR analysis and by in situ hybridization. Although nucleic acid sequencing of the HCV isolate reported here indicates that the isolate is probably of type 1a, other HCV types have also been isolated using this system. Western blot analysis shows the synthesis of major HCV structural proteins. We present here, for the first time, a method for productively growing HCV in vitro for prolonged periods of time. This method allows studies related to understanding the replication process, viral pathogenesis, and the development of anti-HCV drugs and vaccines. PMID:15840164

  2. Long-term neural and physiological phenotyping of a single human

    PubMed Central

    Poldrack, Russell A.; Laumann, Timothy O.; Koyejo, Oluwasanmi; Gregory, Brenda; Hover, Ashleigh; Chen, Mei-Yen; Gorgolewski, Krzysztof J.; Luci, Jeffrey; Joo, Sung Jun; Boyd, Ryan L.; Hunicke-Smith, Scott; Simpson, Zack Booth; Caven, Thomas; Sochat, Vanessa; Shine, James M.; Gordon, Evan; Snyder, Abraham Z.; Adeyemo, Babatunde; Petersen, Steven E.; Glahn, David C.; Reese Mckay, D.; Curran, Joanne E.; Göring, Harald H. H.; Carless, Melanie A.; Blangero, John; Dougherty, Robert; Leemans, Alexander; Handwerker, Daniel A.; Frick, Laurie; Marcotte, Edward M.; Mumford, Jeanette A.

    2015-01-01

    Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders. PMID:26648521

  3. Methodological and technological implications of quantitative human movement analysis in long term space flights.

    PubMed

    Ferrigno, G; Baroni, G; Pedotti, A

    1999-04-01

    In the frame of the 179-days EUROMIR '95 space mission, two in-flight experiments foresaw the analysis of three-dimensional human movements in microgravity. For this aim, a space qualified opto-electronic motion analyser based on passive markers was installed onboard the MIR Space Station. The paper describes the experimental procedures designed in order to face technical and operational limitations imposed by the critical environment of the orbital module. The reliability of the performed analysis is discussed, focusing two related aspects: accuracy in three-dimensional marker localisation and data comparability among different experimental sessions. The effect of the critical experimental set-up and of TV cameras optical distortions is evaluated on in-flight acquired data, by performing an analysis on Euclidean distance conservation on rigid bodies. An optimisation method for the recovering of a unique reference frame throughout the whole mission is described. Results highlight the potentiality that opto-electronics and close-range photogrammetry have for automatic motion analysis onboard orbital modules. The discussion of the obtained results provides general suggestions for the implementation of experimental human movement analysis in critical environments, based on the suitable trade-off between external constraints and achievable analysis reliability.

  4. Integrity of the Human Faecal Microbiota following Long-Term Sample Storage.

    PubMed

    Kia, Elahe; Wagner Mackenzie, Brett; Middleton, Danielle; Lau, Anna; Waite, David W; Lewis, Gillian; Chan, Yih-Kai; Silvestre, Marta; Cooper, Garth J S; Poppitt, Sally D; Taylor, Michael W

    2016-01-01

    In studies of the human microbiome, faecal samples are frequently used as a non-invasive proxy for the study of the intestinal microbiota. To obtain reliable insights, the need for bacterial DNA of high quality and integrity following appropriate faecal sample collection and preservation steps is paramount. In a study of dietary mineral balance in the context of type 2 diabetes (T2D), faecal samples were collected from healthy and T2D individuals throughout a 13-day residential trial. These samples were freeze-dried, then stored mostly at -20°C from the trial date in 2000/2001 until the current research in 2014. Given the relative antiquity of these samples (~14 years), we sought to evaluate DNA quality and comparability to freshly collected human faecal samples. Following the extraction of bacterial DNA, gel electrophoresis indicated that our DNA extracts were more sheared than extracts made from freshly collected faecal samples, but still of sufficiently high molecular weight to support amplicon-based studies. Likewise, spectrophotometric assessment of extracts revealed that they were of high quality and quantity. A subset of bacterial 16S rRNA gene amplicons were sequenced using Illumina MiSeq and compared against publicly available sequence data representing a similar cohort analysed by the American Gut Project (AGP). Notably, our bacterial community profiles were highly consistent with those from the AGP data. Our results suggest that when faecal specimens are stored appropriately, the microbial profiles are preserved and robust to extended storage periods.

  5. The biostability of cardiac lead insulation materials as assessed from long-term human implants.

    PubMed

    Wilkoff, Bruce L; Rickard, John; Tkatchouk, Ekaterina; Padsalgikar, Ajay D; Gallagher, Genevieve; Runt, James

    2016-02-01

    Accelerated in vitro biostability studies are useful for making relativistic comparisons between materials. However, no in vitro study can completely replicate the complex biochemical and biomechanical environment that a material experiences in the human body. To overcome this limitation, three insulation materials [Optim™ insulation (OPT), Pellethane® 55D (P55D), and silicone elastomer] from cardiac leads that were clinically implanted for up to five years were characterized using visual inspection, SEM, ATR-FTIR, GPC, and tensile testing. Surface cracking was not observed in OPT or silicone samples. Shallow cracking was observed in 17/41 (41%) explanted P55D samples. ATR-FTIR indicated minor surface oxidation in some OPT and P55D samples. OPT molecular weight decreased modestly (∼20%) at 2-3 years before stabilizing at 4-5 years. OPT tensile strength decreased modestly (∼25%) at 2-3 years before stabilizing at 4-5 years. OPT elongation at 4-5 years was unchanged from controls. P55D had no significant changes in molecular weight or tensile properties. Overall, results for OPT and P55D were consistent with and limited to cosmetic surface oxidation. Silicone demonstrated excellent biostability with no identifiable degradation. This study of explanted cardiac leads revealed that OPT, P55D, and silicone elastomer demonstrate similar and excellent biostability through five years of implantation in human patients.

  6. Imaging of drug effects in perfused liver

    NASA Astrophysics Data System (ADS)

    Dammann, Marc; Mahlke, Christine; Kessler, Manfred D.

    2002-06-01

    Various medications affect the systemic circulation and organ oxygenation causing dilatation or constriction of blood vessels. Imminent liver failure can be generated by reduced perfusion of different origins. In this case hepatic vasodilatation would be a therapeutical approach for improving patient's condition. Our examinations have been performed in perfused rat liver using spectrometric methods. Two defined areas of the liver were measured punctually. We compared the influence of Tetramethylpyrazine and Glyceroltrinitrate on hemoglobin oxygenation (HbO2) and concentration (Hb-conc.) in rat liver after application of Norepinephrine, which caused a mid decrease in hemoglobin oxygenation of 47,9 %. Both increased the HbO2, but differed from each other in manner of time and extent. Tetramethylpyrazine indicated a longer effect than Glyceroltrinitrate. Furthermore, HbO2 and Hb-conc. showed a conversed relation. From the shape of the absorption spectra it is possible to derive the oxygenation of hemoglobin.

  7. Effect of cardiac dysrhythmia on cerebral perfusion.

    PubMed

    Sand, B J; Rose, H B; Barker, W F

    1976-07-01

    Extracranial carotid arterial obstructive disease has been the entity most commonly associated with transient cerebrovascular insufficiency. A nonobstructive, frequently overlooked cause of cerebral ischemia is cardiac dysrhythmia. We have explored this by observations of experimental animals and of man. Blood flow and pressure in the carotid arteries of dogs were shown to be decreased by mechnically induced premature ventricular contractions. The significance of the cardiogenic contribution to altered cerebrovascular perfusion was studied by ocular and brachial plethysmography in 210 patients suspected by history of having carotid arterial insufficiency. Of the 210 patients, 62 demonstrated abnormal ocular plethysmographic recordings, and of those, nine had dysrhythmias associated with significant deficits of ocular perfusion. Five patients whose recordings were technically suitable for publication are presented to demonstrate the bizarre ocular plethysmographic recordings seen during the dysrhythmic cycle.

  8. Augmented myocardial perfusion reserve after coronary angioplasty quantified by positron emission tomography with H2(15)O

    SciTech Connect

    Walsh, M.N.; Geltman, E.M.; Steele, R.L.; Kenzora, J.L.; Ludbrook, P.A.; Sobel, B.E.; Bergmann, S.R. )

    1990-01-01

    Effects of coronary angioplasty on myocardial flow reserve have been difficult to characterize noninvasively because conventional imaging techniques cannot quantitate blood flow in absolute terms. The effects of coronary angioplasty on myocardial perfusion and perfusion reserve were delineated with positron emission tomography and oxygen-15-labeled water (H2(15)O) in 13 patients before and after single vessel angioplasty. In 11 patients, angioplasty was successful (minimal cross-sectional area increased from 0.60 +/- 0.59 to 3.45 +/- 1.09 mm2, p less than 0.001). In these patients, regional H2(15)O radioactivity (the ratio of nutritional perfusion in regions distal to the stenosis compared with regions supplied by angiographically normal arteries) at rest before angioplasty was 55 +/- 22% of peak myocardial radioactivity and did not increase significantly afterward (70 +/- 16%, p = NS). However, after administration of intravenous dipyridamole, hyperemic perfusion in regions distal to a stenosis averaged only 39 +/- 18% of peak myocardial counts before angioplasty, but increased to 66 +/- 22% after angioplasty (p less than 0.02). Perfusion reserve in the two patients in whom angioplasty was angiographically unsuccessful showed no change. Quantitative estimates of perfusion in absolute rather than relative terms were obtained with positron emission tomographic data from seven of the patients with successful angioplasty. At rest, perfusion in regions distal to a stenosis was not different from the values in regions supplied by normal coronary arteries (1.54 +/- 0.54 compared with 1.46 +/- 0.38 ml/g per min, p = NS).

  9. Co-culture of mesenchymal-like stromal cells derived from human foreskin permits long term propagation and differentiation of human embryonic stem cells.

    PubMed

    Mamidi, Murali Krishna; Pal, Rajarshi; Mori, Nor Azah Binti; Arumugam, Greetha; Thrichelvam, Saratha Thevi; Noor, Puteri J; Abdullah, Hj Mohamad Farouk; Gupta, Pawan Kumar; Das, Anjan Kumar; Zakaria, Zubaidah; Bhonde, Ramesh

    2011-05-01

    Among the different parameters governing the successful derivation and expansion of human embryonic stem cells (hESC), feeder layers play the most important role. Human feeders in form of human mesenchymal stromal cells (hMSCs) and human foreskin fibroblasts (HFFs) lay the foundation for eradication of animal-derived hESC culture system. In this study we explored the potential of human foreskin derived mesenchymal like stromal cells (HF-MSCs) to support self renewal and pluripotency of hESC. The MSCs isolated from human foreskin were found to be resistant to standard concentrations and duration of mitomycin-C treatment. Growth pattern, gene profiling (Oct-4, Nanog, Sox-2, Rex-1), cytoskeletal protein expression (vimentin, nestin) and tri-lineage differentiation potential into adipocytes, chondrocytes and osteocytes confirmed their mesenchymal stromal cell status. Further, the HF-MSCs were positive for CD105, CD166, CD73, CD44, CD90, SSEA-4, and negative for CD34, CD45, HLA-DR cell-surface markers and were found to exhibit BM-MSC-like characteristics. hESC lines co-cultured with HF-MSC feeders showed expression of expected pluripotent transcription factors Oct-4, Nanog, Sox-2, GDF-3, Rex-1, STELLAR, ABCG2, Dppa5, hTERT; surface markers SSEA-4, TRA-1-81 and maintained their cytogenetic stability during long term passaging. These novel feeders also improved the formation of embryoid bodies (EBs) from hESC which produced cell types representing three germ layers. This culture system has the potential to aid the development of clinical-grade hESCs for regenerative medicine and drug screening. Further, we envisage foreskin can serve as a valuable source of alternative MSCs for specific therapeutic applications.

  10. Extra-auditory responses to long-term intermittent noise stimulation in humans.

    PubMed

    Fruhstorfer, B; Hensel, H

    1980-12-01

    Respiration, heart rate, cutaneous blood flow, and electroencephalogram (EEG) reactions to long-term intermittent noise exposure were recorded from 13 volunteers (20-29 yr) with normal hearing and vegetative reactivity. They received daily within 1 h 12 noise stimuli (16 s 100 dB (A) white noise) for 10 or 21 days, respectively. Most subjects reported partial subjective adaptation to the noise. Heart rate adapted within a session but did not change considerably during successive days. Vascular responses did not change during one session but diminished mainly during the first 10 days. Noise responses in the EEG remained constant, but a decrease in vigilance occurred during the whole experimental series. Respiration responses were unpredictable and showed no trend within the sessions. It was concluded that certain physiological responses adapt to loud noise but that the time course of adaptation is different. Therefore a general statement about physiological noise adaptation is not possible.

  11. Long-term experiments to better understand soil-human interactions

    NASA Astrophysics Data System (ADS)

    Bormann, B. T.; Homann, P. S.

    2011-12-01

    Interactions between soils and people may be transforming global conditions, but the interactions are poorly understood. Changes in soils have proven difficult to quantify, especially in complex ecosystems manifesting large spatiotemporal variability. Long-term ecosystem experiments that evaluate soil change and demonstrate alternative choices are important to understanding changes, discovering new controls and drivers, and influencing decisions. Inspired by agriculture studies, like Rothamsted, the US Forest Service established in 1990 a network of operational-scale experiments across the Pacific Northwest to evaluate long-term effects of different forest management and disturbance regimes. With a strong experimental design, these experiments are now helping to better understand the long-term effects of managing tree harvesting (clearcutting and thinning), woody debris, and tree and understory species composition, and-serendipitously-the effects of fire. Initial results from the Southern Oregon experimental site indicate surprisingly rapid soil changes in some regimes but not others. We've also learned that rapid change presents challenges to repeat sampling. We present our sample-archive and comparable-layer approaches that seek to accommodate changes in surface elevation, aggregation and disaggregation, and mineral-soil exports. Thinning mature forest stands (80-100 yrs old) did not significantly change soil C in 11-yrs. A small upper-layer C increase was observed after thinning, but it was similar to the control. Significant increases in upper-layer soil N were observed with most treatments, but all increases were similar to the control. Leaving woody debris had little effect. The most remarkable change occurred when mature stands were clearcut and Douglas-firs were planted and tended. Associated with rapid growth of Douglas-fir, an average of 8 Mg C ha-1 was lost from weathered soil 4-18 cm deep. This contrasts with clearcuts where early-seral hardwoods and

  12. Short-term high-fat diet increases postprandial trimethylamine-N-oxide in humans.

    PubMed

    Boutagy, Nabil E; Neilson, Andrew P; Osterberg, Kristin L; Smithson, Andrew T; Englund, Tessa R; Davy, Brenda M; Hulver, Matthew W; Davy, Kevin P

    2015-10-01

    The gut microbiota plays an obligatory role in the metabolism of nutrients containing trimethylamine moieties, such as L-carnitine and choline, leading to the production of the proatherogenic trimethylamine-N-oxide (TMAO). We hypothesized that a short-term, high-fat diet would increase fasting and postprandial plasma concentrations of TMAO in response to a high-fat meal challenge. Following a 2-week eucaloric control diet, 10 nonobese men (18-30 years) consumed a eucaloric, high-fat diet (55% fat) for 5 days. Plasma TMAO was measured after a 12-hour fast and each hour after for 4 hours following a high-fat meal (63% fat) at baseline and after the high-fat diet using ultraperformance liquid chromatography/ tandem mass spectrometry. Fasting plasma TMAO did not increase significantly following the high-fat diet (1.83 ± 0.21 vs 1.6 ± 0.24 μmol/L). However, plasma TMAO was higher at hour 1 (2.15 ± 0.28 vs 1.7 ± 0.30 μmol/L), hour 2 (2.3 ± 0.29 vs 1.8 ± 0.32 μmol/L), hour 3 (2.4 ± 0.34 vs 1.58 ± 0.19 μmol/L), and hour 4 (2.51 ± 0.33 vs 1.5 ± 0.12 μmol/L) (all P < .05) following the high-fat diet as compared with the baseline postprandial response. In conclusion, a short-term, high-fat diet does not increase fasting plasma TMAO concentrations but appears to increase postprandial TMAO concentrations in healthy, nonobese, young men. Future studies are needed to determine the mechanisms responsible for these observations.

  13. Arousal Rather than Basic Emotions Influence Long-Term Recognition Memory in Humans

    PubMed Central

    Marchewka, Artur; Wypych, Marek; Moslehi, Abnoos; Riegel, Monika; Michałowski, Jarosław M.; Jednoróg, Katarzyna

    2016-01-01

    Emotion can influence various cognitive processes, however its impact on memory has been traditionally studied over relatively short retention periods and in line with dimensional models of affect. The present study aimed to investigate emotional effects on long-term recognition memory according to a combined framework of affective dimensions and basic emotions. Images selected from the Nencki Affective Picture System were rated on the scale of affective dimensions and basic emotions. After 6 months, subjects took part in a surprise recognition test during an fMRI session. The more negative the pictures the better they were remembered, but also the more false recognitions they provoked. Similar effects were found for the arousal dimension. Recognition success was greater for pictures with lower intensity of happiness and with higher intensity of surprise, sadness, fear, and disgust. Consecutive fMRI analyses showed a significant activation for remembered (recognized) vs. forgotten (not recognized) images in anterior cingulate and bilateral anterior insula as well as in bilateral caudate nuclei and right thalamus. Further, arousal was found to be the only subjective rating significantly modulating brain activation. Higher subjective arousal evoked higher activation associated with memory recognition in the right caudate and the left cingulate gyrus. Notably, no significant modulation was observed for other subjective ratings, including basic emotion intensities. These results emphasize the crucial role of arousal for long-term recognition memory and support the hypothesis that the memorized material, over time, becomes stored in a distributed cortical network including the core salience network and basal ganglia. PMID:27818626

  14. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans

    PubMed Central

    Fontana, Luigi; Meyer, Timothy E.; Klein, Samuel; Holloszy, John O.

    2004-01-01

    Little is known regarding the long-term effects of caloric restriction (CR) on the risk for atherosclerosis. We evaluated the effect of CR on risk factors for atherosclerosis in individuals who are restricting food intake to slow aging. We studied 18 individuals who had been on CR for an average of 6 years and 18 age-matched healthy individuals on typical American diets. We measured serum lipids and lipoproteins, fasting plasma glucose and insulin, blood pressure (BP), high-sensitivity C-reactive protein (CRP), platelet-derived growth factor AB (PDGF-AB), body composition, and carotid artery intima-media thickness (IMT). The CR group were leaner than the comparison group (body mass index, 19.6 ± 1.9 vs. 25.9 ± 3.2 kg/m2; percent body fat, 8.7 ± 7% vs. 24 ± 8%). Serum total cholesterol (Tchol), low-density lipoprotein cholesterol, ratio of Tchol to high-density lipoprotein cholesterol (HDL-C), triglycerides, fasting glucose, fasting insulin, CRP, PDFG-AB, and systolic and diastolic BP were all markedly lower, whereas HDL-C was higher, in the CR than in the American diet group. Medical records indicated that the CR group had serum lipid-lipoprotein and BP levels in the usual range for individuals on typical American diets, and similar to those of the comparison group, before they began CR. Carotid artery IMT was ≈40% less in the CR group than in the comparison group. Based on a range of risk factors, it appears that long-term CR has a powerful protective effect against atherosclerosis. This interpretation is supported by the finding of a low carotid artery IMT. PMID:15096581

  15. Imaging considerations for a technetium-99m myocardial perfusion agent

    SciTech Connect

    English, R.J.; Jones, A.G.; Davison, A.; Lister-James, J.; Campbell, S.; Holman, B.L.

    1986-03-01

    Myocardial perfusion imaging with /sup 201/Tl chloride suffers from a number of physical, geometric, and dosimetric constraints that could be diminished if an agent labeled with /sup 99m/Tc were available. The cationic complex /sup 99m/Tc hexakis-(t-butylisonitrile)technetium(I) ((/sup 99m/Tc)TBI) has been shown to concentrate in the myocardial tissue of both animals and humans, with preliminary clinical studies demonstrating a number of technical attributes not possible with /sup 201/Tl. Technetium-99m-TBI is a promising myocardial imaging agent that may permit high quality planar, gated, and tomographic imaging of both myocardial ischemia and infarction with reduced imaging times and improved resolution.

  16. Noncontact blood perfusion mapping in clinical applications

    NASA Astrophysics Data System (ADS)

    Iakovlev, Dmitry; Dwyer, Vincent; Hu, Sijung; Silberschmidt, Vadim

    2016-04-01

    Non-contact imaging photoplethysmography (iPPG) to detect pulsatile blood microcirculation in tissue has been selected as a successor to low spatial resolution and slow scanning blood perfusion techniques currently employed by clinicians. The proposed iPPG system employs a novel illumination source constructed of multiple high power LEDs with narrow spectral emission, which are temporally modulated and synchronised with a high performance sCMOS sensor. To ensure spectrum stability and prevent thermal wavelength drift due to junction temperature variations, each LED features a custom-designed thermal management system to effectively dissipate generated heat and auto-adjust current flow. The use of a multi-wavelength approach has resulted in simultaneous microvascular perfusion monitoring at various tissue depths, which is an added benefit for specific clinical applications. A synchronous detection algorithm to extract weak photoplethysmographic pulse-waveforms demonstrated robustness and high efficiency when applied to even small regions of 5 mm2. The experimental results showed evidences that the proposed system could achieve noticeable accuracy in blood perfusion monitoring by creating complex amplitude and phase maps for the tissue under examination.

  17. Regulation of skeletal muscle perfusion during exercise

    NASA Technical Reports Server (NTRS)

    Delp, M. D.; Laughlin, M. H.

    1998-01-01

    For exercise to be sustained, it is essential that adequate blood flow be provided to skeletal muscle. The local vascular control mechanisms involved in regulating muscle perfusion during exercise include metabolic control, endothelium-mediated control, propagated responses, myogenic control, and the muscle pump. The primary determinant of muscle perfusion during sustained exercise is the metabolic rate of the muscle. Metabolites from contracting muscle diffuse to resistance arterioles and act directly to induce vasodilation, or indirectly to inhibit noradrenaline release from sympathetic nerve endings and oppose alpha-adrenoreceptor-mediated vasoconstriction. The vascular endothelium also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that are prominent in establishing basal vascular tone, but these substances do not appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth muscle cells may also be involved in propagating vasodilator signals along arterioles to parent and daughter vessels. Myogenic autoregulation does not appear to be involved in the exercise hyperemia in muscle, but the rhythmic propulsion of blood from skeletal muscle veins facilitates venous return to the heart and muscle perfusion. It appears that the primary determinants of sustained exercise hyperemia in skeletal muscle are metabolic vasodilation and increased vascular conductance via the muscle pump. Additionally, sympathetic neural control is important in regulating muscle blood flow during exercise.

  18. Inhomogeneity of pulmonary perfusion during sustained microgravity

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim; Guy, Harold J. B.; Elliott, Ann R.; West, John B.

    1994-01-01

    The effects of gravity on the inhomogeneity of pulmonary perfusion in man were studied by performing hyperventilation-breathhold single-breath measurements before, during and after 9 days of continuous exposure to microgravity. In microgravity the indicators of inhomogeneity of perfusion, especially the size of cardiogenic oscillations in expired CO2 and the height of phase 4, were both markedly reduced. Cardiogenic oscillations were reduced to approximately 60 of their preflight standing size, while the height of phase 4 was between 0 and -8% (a terminal fall became a small terminal rise) of preflights standing. The terminal change in CO2 was nearly abolished in microgravity indicating more uniformity of blood flow between lung units that close at the end of expiration and units that remain open. This may result from the disappearance of gravity-dependent topographical inequality of blood flow. The residual cardiographic oscillations in expired CO2 imply a persisting inhomogeneity of perfusion in the absence of gravity at a level larger than acinar.

  19. Vascular perfusion in horses with chronic laminitis.

    PubMed

    Hood, D M; Grosenbaugh, D A; Slater, M R

    1994-05-01

    Vascular perfusion casts were used to define and characterise the macroscopic perfusion defects present in the distal digit of 11 horses affected by chronic laminitis. Five clinically normal horses were used as controls. Based on clinical history and clinical status, horses with chronic laminitis were classified as being potentially treatable or clinically refractory. Eleven macroscopic vascular defects were noted in the casts from horses with laminitis. Four types of lesions were identified in the submural laminar circulation, 3 in the coronary bed and 4 were associated with the solar circulation. Multiple defects were present and a definite trend was noted for the perfusion defects to be worse in the casts of clinically refractory subjects than in those considered treatable. This information suggests that evaluation of circulatory status should add significantly to the ability to separate treatable from clinically refractory patients. Results also indicated that ventral displacement of the third phalanx (sinkers) and compression of the solar vasculature are more prevalent than is presently thought.

  20. Dynamic CT perfusion measurement in a cardiac phantom.

    PubMed

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

    2015-10-01

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

  1. Epidemiological study on long-term effects of pesticides on human health*

    PubMed Central

    Paccagnella, B.; Ghezzo, F.; Prati, L.; Fedrazzoni, U.; Belloni, G.

    1971-01-01

    Two rural areas in Italy with different rates of pesticide usage were subjected to a cross-sectional investigation, based on the identification of organochlorine compounds in the environment and in human fatty tissues and on the determination of their concentration and a prospective investigation, based on the collection of data of past and present pathology and symptomatology from two stratified random groups of inhabitants of both areas. The cross-sectional investigation showed only small differences in environmental pollution and no differences in the storage of organochlorine compounds in fatty tissues in the two areas. The prospective investigation showed a higher prevalence of pathology and symptomatology in the population of the area where pesticides were used in larger quantities. Several haematochemical tests were used in an attempt to differentiate between populations at different levels of risk of toxic damage, but without success. PMID:5316616

  2. Fixation and long-term storage of human lymphocytes for surface marker analysis by flow cytometry.

    PubMed

    Lal, R B; Edison, L J; Chused, T M

    1988-05-01

    A method to preserve stained human lymphocytes for subsequent cell surface analysis by flow cytometry (FCM) is described. Cells stained with fluorescein isothiocyanate (FITC) and phycoerythrin (PE)-conjugated monoclonal antibodies and then fixed in 1% paraformaldehyde, followed by extensive washing and resuspension in 1% BSA medium, could be stored at 4 degrees C for at least 2 weeks prior to FCM analysis without significant alteration in the light scatter or fluorescence properties of the cells. Furthermore, the method was also suitable for analyzing lymphocytes that express T-cell activation markers in certain disease conditions. In addition, we have identified monoclonal antibody combinations that discriminate different lymphocyte subsets that are satisfactory for multiparameter analysis after 2 weeks of storage. This method should prove useful for enumerating lymphocyte subsets in field study sites remote from flow cytometry laboratories.

  3. Long-term maintenance of human induced pluripotent stem cells by automated cell culture system

    PubMed Central

    Konagaya, Shuhei; Ando, Takeshi; Yamauchi, Toshiaki; Suemori, Hirofumi; Iwata, Hiroo

    2015-01-01

    Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem (iPS) cells, are regarded as new sources for cell replacement therapy. These cells can unlimitedly expand under undifferentiated conditions and be differentiated into multiple cell types. Automated culture systems enable the large-scale production of cells. In addition to reducing the time and effort of researchers, an automated culture system improves the reproducibility of cell cultures. In the present study, we newly designed a fully automated cell culture system for human iPS maintenance. Using an automated culture system, hiPS cells maintained their undifferentiated state for 60 days. Automatically prepared hiPS cells had a potency of differentiation into three germ layer cells including dopaminergic neurons and pancreatic cells. PMID:26573336

  4. Short-term effect of cryotherapy on human scleral tissue by atomic force microscopy.

    PubMed

    Lee, Seung Jun; Choi, Samjin; Kim, Moo Sang; Cheong, Youjin; Kwak, Hyung-Woo; Park, Hun-Kuk; Jin, Kyung-Hyun

    2013-01-01

    This study investigated the inflammatory effect of cryotherapy application on collagen matrix network in human infant sclera. Donor scleral tissues taken from three infant patients divided into five groups: control group, sham-treated group, and three cryotreated groups. In the cryotherapy groups, the sclera was treated for 5 s, 10 s, and 20 s with -80°C freezing by a cryosurgical system. The cryotreated reactions were examined using double histological analysis with hematoxylin-eosin and Masson's trichrome, and atomic force microscopy analysis to quantify the diameter and D-banding of collagen fibrils. The infant scleral tissues treated with cryotherapy showed a significantly increased collagen density associated with inflammatory response (p < 0.05), increased fibril diameter (p < 0.005) compared to the scleral tissues in the control group. The results directly suggest that the cryotherapy affects the morphology of scleral collagen.

  5. Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex.

    PubMed

    Sale, Martin V; Nydam, Abbey S; Mattingley, Jason B

    2017-03-01

    Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis (APB) muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 min following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity.

  6. Integrity of the Human Faecal Microbiota following Long-Term Sample Storage

    PubMed Central

    Kia, Elahe; Wagner Mackenzie, Brett; Middleton, Danielle; Lau, Anna; Waite, David W.; Lewis, Gillian; Chan, Yih-Kai; Silvestre, Marta; Cooper, Garth J. S.; Poppitt, Sally D.; Taylor, Michael W.

    2016-01-01

    In studies of the human microbiome, faecal samples are frequently used as a non-invasive proxy for the study of the intestinal microbiota. To obtain reliable insights, the need for bacterial DNA of high quality and integrity following appropriate faecal sample collection and preservation steps is paramount. In a study of dietary mineral balance in the context of type 2 diabetes (T2D), faecal samples were collected from healthy and T2D individuals throughout a 13-day residential trial. These samples were freeze-dried, then stored mostly at -20°C from the trial date in 2000/2001 until the current research in 2014. Given the relative antiquity of these samples (~14 years), we sought to evaluate DNA quality and comparability to freshly collected human faecal samples. Following the extraction of bacterial DNA, gel electrophoresis indicated that our DNA extracts were more sheared than extracts made from freshly collected faecal samples, but still of sufficiently high molecular weight to support amplicon-based studies. Likewise, spectrophotometric assessment of extracts revealed that they were of high quality and quantity. A subset of bacterial 16S rRNA gene amplicons were sequenced using Illumina MiSeq and compared against publicly available sequence data representing a similar cohort analysed by the American Gut Project (AGP). Notably, our bacterial community profiles were highly consistent with those from the AGP data. Our results suggest that when faecal specimens are stored appropriately, the microbial profiles are preserved and robust to extended storage periods. PMID:27701448

  7. A Porcine Anterior Segment Perfusion and Transduction Model With Direct Visualization of the Trabecular Meshwork

    PubMed Central

    Loewen, Ralitsa T.; Roy, Pritha; Park, Daniel B.; Jensen, Adrianna; Scott, Gordon; Cohen-Karni, Devora; Fautsch, Michael P.; Schuman, Joel S.; Loewen, Nils A.

    2016-01-01

    Purpose To establish a consistent and affordable, high quality porcine anterior segment perfusion and transduction model that allows direct visualization of the trabecular meshwork. Methods Porcine anterior segments were cultured within 2 hours of death by removing lens and uvea and securing in a specially designed petri dish with a thin bottom to allow direct visualization of the trabecular meshwork with minimal distortion. Twenty-two control eyes (CO) with a constant flow rate were compared to eight gravity perfused eyes (COgr, 15 mm Hg). We established gene delivery to the TM using eGFP expressing feline immunodeficiency virus (FIV) vector GINSIN at 108 transducing units (TU) per eye (GINSIN_8, n = 8) and 107 TU (GINSIN_7, n = 8). Expression was assessed for 14 days before histology was obtained. Results Pig eyes were a reliable source for consistent and high quality anterior segment cultures with a low failure rate of 12%. Control eyes had an intraocular pressure (IOP) of 15.8 ± 1.9 mm Hg at fixed pump perfusion with 3 μL/min compared to gravity perfused COgr with imputed 3.7 ± 1.6 μL/min. Vector GINSIN_8 eyes experienced a transient posttransduction IOP increase of 44% that resolved at 48 hours; this was not observed in GINSIN_7 eyes. Expression was higher in GINSIN_8 than in GINSIN_7 eyes. Trabecular meshwork architecture was well preserved. Conclusions Compared with previously used human donor eyes, this inexpensive porcine anterior segment perfusion model is of sufficient, repeatable high quality to develop strategies of TM bioengineering. Trabecular meshwork could be observed directly. Despite significant anatomic differences, effects of transduction replicate the main aspects of previously explored human, feline and rodent models. PMID:27002293

  8. The effect of captopril on thallium 201 myocardial perfusion in systemic sclerosis

    SciTech Connect

    Kahan, A.; Devaux, J.Y.; Amor, B.; Menkes, C.J.; Weber, S.; Venot, A.; Strauch, G. )

    1990-04-01

    In systemic sclerosis, abnormalities of myocardial perfusion are common and may be caused by a disturbance of the coronary microcirculation. We evaluated the long-term effect of captopril (75 to 150 mg per day) on thallium 201 myocardial perfusion in 12 normotensive patients with systemic sclerosis. Captopril significantly decreased the mean (+/- SD) number of segments with thallium 201 myocardial perfusion defects (6.5 +/- 1.9 at baseline and 4.4 +/- 2.7 after 1 year of treatment with captopril; p less than 0.02) and increased the mean global thallium score (9.6 +/- 1.7 at baseline and 11.4 +/- 2.1 after captopril; p less than 0.05). In a control group of eight normotensive patients with systemic sclerosis who did not receive captopril, no significant modification in thallium results occurred. Side effects with captopril included hypotension (six patients), taste disturbances (one patient), and skin rash (one patient). These side effects subsided when the dosage was reduced. These findings demonstrate that captopril improves thallium 201 myocardial perfusion in patients with systemic sclerosis and may therefore have a beneficial effect on scleroderma myocardial disease.

  9. Changes of perfusion of microvascular free flaps in the head and neck: a prospective clinical study.

    PubMed

    Mücke, Thomas; Rau, Andrea; Merezas, Andreas; Kanatas, Anastasios; Mitchell, David A; Wagenpfeil, Stefan; Wolff, Klaus-Dietrich; Steiner, Timm

    2014-11-01

    Reconstruction with a free flap is routine in head and neck surgery. However, reliable assessment of perfusion can be difficult, so we prospectively evaluated it in 4 types of microvascular free flaps in the oral cavity (n=196) and assessed differences in blood flow by non-invasive monitoring with a laser Doppler flowmetry unit. We measured oxygen saturation, haemoglobin concentration, and velocity on the surface of the flap preoperatively at the donor site, and on the flap on the first, second, and seventh postoperative days, and after 4 weeks in 186/196 patients, mean (SD) age of 60 (13) years. We studied the radial forearm (n=76, 41%), fibular (n=45, 24%), anterolateral thigh (n=53, 28%), and soleus perforator (n=12, 7%) flaps. The values for the radial forearm flap differed significantly from the others. There were significant differences in haemoglobin concentrations between the fibular and soleus perforator flaps, and between the anterolateral thigh and soleus perforator flaps (p=0.002 each). Free flaps are unique in the way that perfusion develops after microvascular anastomoses. Knowledge of how each flap is perfused may indicate different patterns of healing that could potentially influence long term rehabilitation and detection of future deficits in perfusion.

  10. Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

    PubMed

    Fanning, Rebecca A; McMorrow, Jason P; Campion, Deirdre P; Carey, Michael F; O'Connor, John J

    2013-01-05

    The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

  11. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

    PubMed

    Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

    2011-11-01

    Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

  12. Micropatterning Facilitates the Long-Term Growth and Analysis of iPSC-Derived Individual Human Neurons and Neuronal Networks.

    PubMed

    Burbulla, Lena F; Beaumont, Kristin G; Mrksich, Milan; Krainc, Dimitri

    2016-08-01

    The discovery of induced pluripotent stem cells (iPSCs) and their application to patient-specific disease models offers new opportunities for studying the pathophysiology of neurological disorders. However, current methods for culturing iPSC-derived neuronal cells result in clustering of neurons, which precludes the analysis of individual neurons and defined neuronal networks. To address this challenge, cultures of human neurons on micropatterned surfaces are developed that promote neuronal survival over extended periods of time. This approach facilitates studies of neuronal development, cellular trafficking, and related mechanisms that require assessment of individual neurons and specific network connections. Importantly, micropatterns support the long-term stability of cultured neurons, which enables time-dependent analysis of cellular processes in living neurons. The approach described in this paper allows mechanistic studies of human neurons, both in terms of normal neuronal development and function, as well as time-dependent pathological processes, and provides a platform for testing of new therapeutics in neuropsychiatric disorders.

  13. Chondrogenesis in perfusion bioreactors using porous silk scaffolds and hESC-derived MSCs.

    PubMed

    Tiğli, R Seda; Cannizaro, Chris; Gümüşderelioğlu, Menemşe; Kaplan, David L

    2011-01-01

    Tissue engineered cartilage can be grown in vitro with the use of cell-scaffold constructs and bioreactors. The present study was designed to investigate the effects of perfusion bioreactors on the chondrogenic potential of engineered constructs prepared from porous silk fibroin scaffolds seeded with human embryonic stem cell (hESC)-derived mesencyhmal stem cells (MSCs). After four weeks of incubation, constructs cultured in perfusion bioreactors showed significantly higher amounts of glycosaminoglycans (GAGs) (p < 0.001), DNA (p < 0.001), total collagen (p < 0.01), and collagen II (p < 0.01) in comparison to static culture. Mechanical stiffness of constructs increased 3.7-fold under dynamic culture conditions and RT-PCR results concluded that cells cultured in perfusion bioreactors highly expressed (p < 0.001) cartilage-related genes when compared with static culture. Distinct differences were noted in tissue morphology, including polygonal extracellular matrix structure of engineered constructs in thin superficial zones and an inner zone under static and dynamic conditions, respectively. The results suggest that the utility of perfusion bioreactors to modulate the growth of tissue-engineered cartilage and enhance tissue growth in vitro.

  14. Dual-mode quantitative imaging of wound tissue oxygenation and perfusion

    NASA Astrophysics Data System (ADS)

    Qin, Ruogu; Huang, Jiwei; Xu, Jeff S.; Ding, Liya; Gnyawali, Surya; Sen, Chandan K.; Huang, Kun; Xu, Ronald X.

    2010-02-01

    Accurate assessment of wound oxygenation and perfusion is important for evaluating wound healing/regression and guiding following therapeutic processes. However, many existing techniques and clinical practices are subjective and qualitative due to background bias, tissue heterogeneity, and inter-patient variation. To overcome these limitations, we developed a dual-modal imaging system for in vivo, non-invasive, real-time quantitative assessment of wound tissue oxygenation and perfusion. The imaging system integrated a broadband light source, a high-resolution CCD camera, a highly sensitive thermal camera, and a liquid crystal tunable filter. A user-friendly interface was developed to control all the components systematically. Advanced algorithms were explored for reliable reconstruction of tissue oxygenation and appropriate co-registration between thermal images and multispectral images. Dual-mode oxygenation and perfusion imaging was demonstrated on both benchtop models and human subjects, and compared with measurements using other methods, such as Laser Doppler and tissue oximeter. The test results suggested that the dual-modal imaging system has the potential for non-contact real-time imaging of wound tissue oxygenation and perfusion.

  15. Optimization of flow-sensitive alternating inversion recovery (FAIR) for perfusion functional MRI of rodent brain.

    PubMed

    Nasrallah, Fatima A; Lee, Eugene L Q; Chuang, Kai-Hsiang

    2012-11-01

    Arterial spin labeling (ASL) MRI provides a noninvasive method to image perfusion, and has been applied to map neural activation in the brain. Although pulsed labeling methods have been widely used in humans, continuous ASL with a dedicated neck labeling coil is still the preferred method in rodent brain functional MRI (fMRI) to maximize the sensitivity and allow multislice acquisition. However, the additional hardware is not readily available and hence its application is limited. In this study, flow-sensitive alternating inversion recovery (FAIR) pulsed ASL was optimized for fMRI of rat brain. A practical challenge of FAIR is the suboptimal global inversion by the transmit coil of limited dimensions, which results in low effective labeling. By using a large volume transmit coil and proper positioning to optimize the body coverage, the perfusion signal was increased by 38.3% compared with positioning the brain at the isocenter. An additional 53.3% gain in signal was achieved using optimized repetition and inversion times compared with a long TR. Under electrical stimulation to the forepaws, a perfusion activation signal change of 63.7 ± 6.3% can be reliably detected in the primary somatosensory cortices using single slice or multislice echo planar imaging at 9.4 T. This demonstrates the potential of using pulsed ASL for multislice perfusion fMRI in functional and pharmacological applications in rat brain.

  16. No short-term effects of digital mobile radio telephone on the awake human electroencephalogram

    SciTech Connect

    Roeschke, J.; Mann, K.

    1997-05-01

    A recent study reported the results of an exploratory study of alterations of the quantitative sleep profile due to the effects of a digital mobile radio telephone. Rapid eye movement (REM) was suppressed, and the spectral power density in the 8--13 Hz frequency range during REM sleep was altered. The aim of the present study was to illuminate the influence of digital mobile radio telephone on the awake electroencephalogram (EEG) of healthy subjects. For this purpose, the authors investigated 34 male subjects in a single-blind cross-over design experiment by measuring spontaneous EEGs under closed-eyes condition from scalp positions C{sub 3} and C{sub 4} and comparing the effects of an active and an inactive digital mobile radio telephone (GSM) system. During exposure of nearly 3.5 min to the 900 MHz electromagnetic field pulsed at a frequency of 217 Hz and with a pulse width of 580 {micro}s, the authors could not detect any difference in the awake EEGs in terms of spectral power density measures.

  17. Microgravity alters respiratory sinus arrhythmia and short-term heart rate variability in humans

    NASA Technical Reports Server (NTRS)

    Migeotte, P-F; Prisk, G. Kim; Paiva, M.; West, J. B. (Principal Investigator)

    2003-01-01

    We studied heart rate (HR), heart rate variability (HRV), and respiratory sinus arrhythmia (RSA) in four male subjects before, during, and after 16 days of spaceflight. The electrocardiogram and respiration were recorded during two periods of 4 min controlled breathing at 7.5 and 15 breaths/min in standing and supine postures on the ground and in microgravity. Low (LF)- and high (HF)-frequency components of the short-term HRV (< or =3 min) were computed through Fourier spectral analysis of the R-R intervals. Early in microgravity, HR was decreased compared with both standing and supine positions and had returned to the supine value by the end of the flight. In microgravity, overall variability, the LF-to-HF ratio, and RSA amplitude and phase were similar to preflight supine values. Immediately postflight, HR increased by approximately 15% and remained elevated 15 days after landing. LF/HF was increased, suggesting an increased sympathetic control of HR standing. The overall variability and RSA amplitude in supine decreased postflight, suggesting that vagal tone decreased, which coupled with the decrease in RSA phase shift suggests that this was the result of an adaptation of autonomic control of HR to microgravity. In addition, these alterations persisted for at least 15 days after return to normal gravity (1G).

  18. Long‐term recovery of the human corneal endothelium after toxic injury by benzalkonium chloride

    PubMed Central

    Hughes, E H; Pretorius, M; Eleftheriadis, H; Liu, C S C

    2007-01-01

    Introduction The inadvertent intra‐ocular administration of benzalkonium chloride‐preserved hydroxypropyl methylcellulose during cataract surgery at another hospital in 1999 resulted in toxic corneal endothelial injury and profound postoperative corneal oedema as a result of endothelial decompensation. The long‐term effect of this adverse event was assessed. Methods All 19 patients were invited to return for examination including corneal endothelial specular microscopy and pachymetry seven years after the incident. Results were compared with data from one year after the incident. Results Five patients attended for examination, one had received a penetrating keratoplasty and was, therefore, excluded. Ten patients had died and four had moved out of the region and were unable to attend. All four study patients were pain free and achieved 6/12 or better. Mean central corneal thickness reduced by 13% from 652.6 μm at one year to 563.4 μm. Mean central corneal endothelial cell density (n  =  3) increased 28% from 663.7 cells/mm2 at one year to 835.7 cells/mm2 (p<0.05). Conclusions After toxic injury, corneal endothelial function may have a remarkable capacity for recovery even after the first postoperative year. The rise in central endothelial cell density may represent cell migration from less affected areas or cellular proliferation. Should this unfortunate event recur, clinicians may expect continued recovery beyond one year. PMID:17504856

  19. High-dose short-term administration of naringin did not alter talinolol pharmacokinetics in humans.

    PubMed

    Nguyen, M A; Staubach, P; Tamai, I; Langguth, P

    2015-02-20

    Naringin is considered the major causative ingredient of the inhibition of intestinal drug uptake by grapefruit juice. Moreover, it is contained in highly dosed nutraceuticals available on the market. A controlled, open, randomized, crossover study was performed in 10 healthy volunteers to investigate the effect of high-dose naringin on the bioavailability of talinolol, a substrate of intestinal organic anion-transporting polypeptide (OATP)-mediated uptake. Following 6-day supplementation with 3 capsules of 350 mg naringin daily, 100mg talinolol were administered orally with 3 capsules of the same dietary supplement (1050 mg naringin) on the seventh day. This test treatment was compared to 100mg talinolol only (control). The results showed that short-term high-dose naringin supplementation did not significantly affect talinolol pharmacokinetics. Geometric mean ratios of test versus control ranged between 0.90 and 0.98 for talinolol c(max), AUC(0-48 h), AUC(0-∞), t(1/2) and A(e(0-48 h)). The high dose may provoke inhibition of the efflux transporter P-glycoprotein (P-gp) which counteracts the uptake inhibition. As disintegration and dissolution processes are required for the solid dosage form, dissolved naringin may arrive at the site of interaction after talinolol is already absorbed. In conclusion, the effect of nutraceuticals on drug pharmacokinetics can deviate from that observed when administered as food component due to the different dose and dosage form.

  20. Appetitive long-term taste conditioning enhances human visually evoked EEG responses.

    PubMed

    Viemose, Ida; Møller, Per; Laugesen, Jakob L; Schachtman, Todd R; Manoharan, Thukirtha; Christoffersen, Gert R J

    2013-09-15

    Long-term effects of learned associations between an image and a taste have not been studied with electromagnetic brain scanning techniques. The possibility that taste conditioning may change sensory image processing was investigated in young adult subjects. EEG-responses evoked by images were recorded before and after a training session using an image as conditioned stimulus and a pleasant taste as unconditioned stimulus. The results showed that in posterior electrodes placed over visual cortex areas, the following changes occurred after conditioning: (1) the amplitude and duration of the N2-P3 waves in the visual evoked potentials were enhanced; (2) the N2 and P3 peak delays were shortened; (3) power induced by image presentation was enhanced in the delta and theta frequency bands; (4) cross-hemispheric delta and theta coherences among the posterior electrodes were enhanced; (5) calculations of the underlying whole brain distribution of currents using swLORETA showed elevated current densities in posterior voxels. None of the above changes occurred in a sham-trained control group. In electrodes placed over the prefrontal cortex, delta and theta power also rose significantly. It is suggested that the appetitive taste conditioning potentiated synaptic activity in visual cortex networks and that this led to an increased speed of image processing.

  1. Anococcygeal Raphe Revisited: A Histological Study Using Mid-Term Human Fetuses and Elderly Cadavers

    PubMed Central

    Arakawa, Takashi; Abe, Hiroshi; Abe, Shinichi; Cho, Baik Hwan; Murakami, Gen; Sugihara, Kenichi

    2012-01-01

    Purpose We recently demonstrated the morphology of the anococcygeal ligament. As the anococcygeal ligament and raphe are often confused, the concept of the anococcygeal raphe needs to be re-examined from the perspective of fetal development, as well as in terms of adult morphology. Materials and Methods We examined the horizontal sections of 15 fetuses as well as adult histology. From cadavers, we obtained an almost cubic tissue mass containing the dorsal wall of the anorectum, the coccyx and the covering skin. Most sections were stained with hematoxylin and eosin or Masson-trichrome solution. Results The adult ligament contained both smooth and striated muscle fibers. A similar band-like structure was seen in fetuses, containing: 1) smooth muscle fibers originating from the longitudinal muscle coat of the anal canal and 2) striated muscle fibers from the external anal sphincter (EAS). However, in fetuses, the levator ani muscle did not attach to either the band or the coccyx. Along and around the anococcygeal ligament, we did not find any aponeurotic tissue with transversely oriented fibers connecting bilateral levator ani slings. Instead, in adults, a fibrous tissue mass was located at a gap between bilateral levator ani slings; this site corresponded to the dorsal side of the ligament and the EAS in the immediately deep side of the natal skin cleft. Conclusion We hypothesize that a classically described raphe corresponds to the specific subcutaneous tissue on the superficial or dorsal side of the anococcygeal ligament. PMID:22665356

  2. Long-term effects of 'ecstasy' abuse on the human brain studied by FDG PET.

    PubMed

    Buchert, R; Obrocki, J; Thomasius, R; Väterlein, O; Petersen, K; Jenicke, L; Bohuslavizki, K H; Clausen, M

    2001-08-01

    The popular recreational drug, 'ecstasy', mainly contains 3,4-methylenedioxymethamphetamine (MDMA) as the psychotropic agent. MDMA is suspected of causing neurotoxic lesions to the serotonergic system as demonstrated by animal studies, examinations of human cerebrospinal fluid, and the first positron emission tomography (PET) studies using the serotonin transporter ligand [11C]-McN5652. Damage of serotonergic afferents might mediate long-lasting alterations of cerebral glucose metabolism as a secondary effect. To study a relationship between ecstasy use and long-lasting alterations, PET using 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) was performed in 93 ecstasy users and 27 subjects without any known history of illicit-drug abuse. As an index of glucose metabolism, mean normalized FDG uptake was determined in both groups using a computerized brain atlas, and was compared for a selected number of brain regions. FDG uptake was normalized in each individual by dividing local FDG uptake by the maximum FDG uptake in the individual's brain. Within the group of ecstasy users we examined the relationship between FDG uptake and cumulative ecstasy dose, time since last ecstasy ingestion at the time of PET scanning, and age at first ecstasy use, respectively. Normalized FDG uptake was reduced within the striatum and amygdala of ecstasy users when compared to controls. No statistically significant correlation of the FDG uptake and the cumulative dose of ecstasy was detected. A positive correlation was found in the cingulate between FDG uptake and the time since last ecstasy ingestion. As compared to the control group, normalized FDG uptake in the cingulate was reduced in ecstasy users who took ecstasy during the last 6 months, while it was elevated in former ecstasy users who did not consume ecstasy for more than 1 year. FDG uptake was significantly more affected in ecstasy users who started to consume ecstasy before the age of 18 years. In conclusion, ecstasy abuse causes long

  3. Biomedical Analyses of Mice Body Hair Exposed to Long-term Space Flight as a Compliment of Human Research

    NASA Astrophysics Data System (ADS)

    Mukai, Chiaki

    Introduction: To understand the effect of space environment characterized by microgravity and radiation on protein and mineral metabolisms is important for developing the countermeasures to the adverse effects happening on the astronauts who stay long-term in space. Thus JAXA has started a human research to study the effects of long-term exposure in space flight on gene expression and mineral metabolism by analyzing astronaut's hair grown in space since December 2009 (Experiment nicknamed "HAIR"). Ten human subjects who are the crew of the International Space Station (ISS) will be expected to complete this experiment. Thanks to the tissue sharing program of space-flown mice which is presented and organized by AGI(Italian Space Agency), we can also have an opportunity to analyze rodents samples which will greatly compliment human hair experiment by enable us to conduct more detailed analysis with the expansion of skin analysis which is not include in human experiment. The purpose of this flown-mice experiment is to study the effects of long-term exposure to space environment such as microgravity and space radiation on mineral and protein metabolism, the biological responses to the stress levels, and the initial process of skin carcinogenesis by analyzing hair shaft, its root cells, and skin. Approach and Method In this experiment, we analyzed hair shaft, hair root and skin. Hair samples with skin were taken from 3-month space-flown mice and ground-control mice in the AGI's tissue sharing program in 2009. The sample numbers of space-flown mice and control-mice were three and six, respectively. And they were at the Mice Drawer System (MDS) in ISS and in the laboratory of Geneva University. For the hair shaft, the mineral balance is investi-gated by energy dispersive X-ray spectroscopy (SEM-EDX). For hair root, the extracted RNA undergoes DNA microarray analysis, and will be further examined particular interests of gene-expression by real time Reverse Transcription

  4. Perfusion phantom: An efficient and reproducible method to simulate myocardial first-pass perfusion measurements with cardiovascular magnetic resonance.

    PubMed

    Chiribiri, Amedeo; Schuster, Andreas; Ishida, Masaki; Hautvast, Gilion; Zarinabad, Niloufar; Morton, Geraint; Otton, James; Plein, Sven; Breeuwer, Marcel; Batchelor, Philip; Schaeffter, Tobias; Nagel, Eike

    2013-03-01

    The aim of this article is to describe a novel hardware perfusion phantom that simulates myocardial first-pass perfusion allowing comparisons between different MR techniques and validation of the results against a true gold standard. MR perfusion images were acquired at different myocardial perfusion rates and variable doses of gadolinium and cardiac output. The system proved to be sensitive to controlled variations of myocardial perfusion rate, contrast agent dose, and cardiac output. It produced distinct signal intensity curves for perfusion rates ranging from 1 to 10 mL/mL/min. Quantification of myocardial blood flow by signal deconvolution techniques provided accurate measurements of perfusion. The phantom also proved to be very reproducible between different sessions and different operators. This novel hardware perfusion phantom system allows reliable, reproducible, and efficient simulation of myocardial first-pass MR perfusion. Direct comparison between the results of image-based quantification and reference values of flow and myocardial perfusion will allow development and validation of accurate quantification methods.

  5. In vivo barrier challenge and long-term recovery in human facial skin.

    PubMed

    Gorcea, Mihaela; Hadgraft, Jonathan; Lane, Majella E; Moore, David J

    2013-06-01

    Recently, we developed a biophysical approach to characterize in vivo facial cheek skin as a function of stratum corneum (SC) depth, barrier function and during a 24-h recovery period. The current study extends this work and characterizes the human facial cheek after barrier challenge and, for the first time, facial SC barrier recovery over a 4-week period. Changes in the corneocyte size over the 4-week recovery period, and correlations with changes in Trans-Epidermal Water Loss (TEWL) were monitored. This approach allows complete characterization of SC barrier function after a full biological regeneration of the SC barrier following tape stripping. The structural and compositional changes in facial cheek were investigated using Attenuated Total Reflectance-Fourier Transform Infra Red (ATR-FTIR) spectroscopy, tape stripping, TEWL measurements and image analysis combined with optical microscopy to characterize the SC depth profile during the tape stripping stress and over 4-week recovery period. TEWL increased significantly from baseline after sequential tape stripping. Corneocyte size decreased with successive tape stripping. An inverse direct correlation was determined between TEWL and corneocyte surface area. After 4 weeks, the corneocyte size and TEWL for the facial cheek recovered 100% from the tape stripping procedure. The in vivo ATR-FTIR data demonstrated that lipid and sebum components on the surface of the facial cheek SC recovered within 24 h post tape stripping, whereas protein (Amide II) and water components recovered after 1 week.

  6. Treatment of anal human papillomavirus-associated disease: a long term outcome study.

    PubMed

    Nathan, M; Hickey, N; Mayuranathan, L; Vowler, S L; Singh, N

    2008-07-01

    Treatment for human papillomavirus (HPV)-associated anal canal disease has been unsatisfactory. The objective of our study was to determine the treatment outcome in our cohort with anal HPV disease. Overall, 181 patients were evaluated over a median period of 19.1 months (range = 2.8-125.5). Eighty-eight patients (48.6%) with high-grade anal intraepithelial neoplasia (AIN) and 82 patients (45.3%) with low-grade AIN underwent treatment. One hundred and forty-one patients (77.9%) received laser ablative treatment as an outpatient procedure. The treatment yielded cure, defined as a disease-free state at 12 months after treatment, in 63.0% (114/181). Median time to cure for the cohort was 31.5 months (95% confidence interval: 23.0-40.0). Treatment outcome showed no evidence of being affected by age, sexual preference, history of smoking or presence of high-grade disease. Median time to cure was significantly affected by a positive HIV status (P = 0.02) and the extent (volume) of the disease (P = 0.01). Contrary to the current view that treatment of HPV-related anal disease is difficult, unrewarding due to recurrences and may lead to substantial morbidity, we demonstrate that effective treatment is possible for both low- and high-grade AIN. These findings should help with the general desire to introduce screening for AIN for at-risk groups.

  7. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in newborn macaques

    PubMed Central

    Hessell, Ann J.; Jaworski, J. Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F.; Hammond, Katherine B.; Cheever, Tracy A.; Barnette, Philip T.; Legasse, Alfred W.; Planer, Shannon; Stanton, Jeffrey J.; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S.; Axthelm, Michael K.; Lewis, Anne; Hirsch, Vanessa M.; Graham, Barney S.; Mascola, John R.; Sacha, Jonah B.; Haigwood, Nancy L.

    2016-01-01

    Prevention of mother to child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested anti-HIV-1 human neutralizing monoclonal antibodies (NmAb) as post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with SHIVSF162P3. On days 1, 4, 7, and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h following administration. Replicating virus was found in multiple tissues by day 1 in animals without treatment. All NmAb-treated macaques were free of virus in blood and tissues at 6 months post-exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged following CD8+ T cell depletion. These results suggest early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. PMID:26998834

  8. Human papillomavirus and the long-term risk of cervical neoplasia.

    PubMed

    van der Graaf, Yolanda; Molijn, Anco; Doornewaard, Heleen; Quint, Wim; van Doorn, Leen-Jan; van den Tweel, Jan

    2002-07-15

    The risk of cervical neoplasia for women with normal Papanicolaou smears was calculated for those whose smears were human papillomavirus (HPV) positive and those whose smears were HPV negative. Data on 347 cases and controls were analyzed in a population-based, nested case-control study. Cases (n = 77) were women who participated in the Utrecht screening program (1976-1984) in the Netherlands and who developed cervical intraepithelial neoplasia 3 or microinvasive or invasive squamous cervical cancer after having a negative smear (1980-1986). Controls (n = 270) were matched on age (+/-5 years) and follow-up period. DNA was isolated from the Papanicolaou smears and was tested for the presence of HPV DNA by using the ultrasensitive broad-spectrum, general short-fragment polymerase chain reaction. HPV was found in 55 (71%) of the baseline smears of the 77 cases and in 31 (11%) of those of the 270 controls. The age-adjusted odds ratios for developing cervical intraepithelial neoplasia or microinvasive or invasive cervical cancer were 19.2 (95 percent confidence interval (CI): 10.3, 35.7) for HPV positivity in general, 5.4 (95% CI: 1.5, 19.5) for infection with low-risk HPV genotypes, 24.0 (95% CI: 12.4, 46.4) for high-risk HPV genotypes, and 104.8 (95% CI: 29.5, 372.7) for HPV type 16.

  9. Modulation of cholesterol transport by maternal hypercholesterolemia in human full-term placenta

    PubMed Central

    Ma, Wei-wei; Cai, Xue-ping; Le, Zhi-yin; Xiao, Rong; Zhou, Qi; Yu, Huan-ling

    2017-01-01

    The significance of maternal cholesterol transporting to the fetus under normal as well as pathological circumstances is less understood. The objective of this study was to observe the effects of maternal hypercholesterolemia on placental cholesterol transportation. Human full-time placenta, maternal and venous cord blood were sampled at delivery from the pregnant women with serum total cholesterol (TC) concentrations at third trimester higher than 7.25 mM (n = 19) and the pregnant women with normal TC concentrations (n = 19). Serum lipids and expression of genes related to cholesterol transportation were measured by western blot or real-time PCR. The results indicated that serum TC, high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) levels were significantly increased, in pregnancies, but decreased in cord blood in hypercholesterolemic group compared to the matched control group. All the subjects were no-drinking, non-smoker, and gestational disease free. The mRNA expression of lipoprotein receptors, including LDLR and VLDLR were significantly increased, while the protein expression of PCSK9 was significantly increased in hypercholesterolemic placenta. In conclusion, maternal hypercholesterolemia might decrease the transportation of cholesterol from mother to fetus because of the high levels of PCSK9 protein expression. PMID:28199412

  10. Long-term effects of prenatal x-ray of human females: reproductive experience

    SciTech Connect

    Meyer, M.B.; Tonascia, J.

    1981-09-01

    A cohort of singleton black human females exposed to diagnostic x-ray in utero and controls matched by parity, hospital of birth and birthdate have been followed to ages 25 to 30 years in Baltimore, Maryland. The search for possible effects of prenatal irradiation has focused on health, growth, development, and reproductive experience of exposed and control women. This paper reports findings related to reproductive experience. From an original data set of 1458 matched exposed-control pairs of women, questionnaire responses were received from 1109 exposed and 1124 control women including 852 each from pairs in which both the exposed and control woman responded. After careful search for alternative explanations of the findings, the authors concluded that females exposed in utero to low doses of x-ray (probably 1 to 5 rads) had significant increases in their rates of early onset of menses, births at age 15 years or less, numbers of living children, stillbirths, and sterilizing operations by their mid-twenties. These findings are compatible with animal studies in which prenatal irradiation kills many oocytes, but accelerates the development of remaining cells to stages more closely correlated with fertility. Although these animals subsequently became sterile, this cannot be tested in the current study because significantly more of the irradiated women have had surgical sterilizations.

  11. Human Term Placental Cells: Phenotype, Properties and New Avenues in Regenerative Medicine

    PubMed Central

    Caruso, Maddalena; Evangelista, Marco; Parolini, Ornella

    2012-01-01

    The human placenta has long been the subject of scientific interest due to the important roles which it performs during pregnancy in sustaining the fetus and maintaining fetomaternal tolerance. More recently, however, researchers have begun to investigate the possibility that the placenta’s utility may extend beyond fetal development to act as a source of cells with clinically relevant properties. Indeed, several groups have reported the isolation of cells from different placental regions which display both multilineage differentiation potential and immunomodulatory properties in vitro. Furthermore, these cells have also been shown to secrete soluble factors involved in pathophysiological processes that may aid tissue repair. Cells with such features will clearly find application in the field of regenerative medicine for the repair/regeneration of damaged or diseased tissues or organs. In line with these promising findings, several preclinical and clinical studies conducted to date argue in strong favor of the therapeutic utility of placenta-derived cells for the treatment of several diseases. Although much work remains to be conducted in order to fully understand the properties of placental cells and the mechanisms which underlie their beneficial effects in vivo, data reported to date nonetheless provide compelling evidence in support of the placenta as a cell source for use in regenerative medicine. PMID:24551761

  12. Human health risk from arsenical pesticide contaminated soils: a long-term greenhouse study.

    PubMed

    Quazi, Shahida; Sarkar, Dibyendu; Datta, Rupali

    2013-11-15

    Arsenic (As) bioaccessibility is an important factor in estimating human health risk. Bioaccessibility of As in soils is primarily dependent on As adsorption, which varies with residence time. This study evaluated the effect of soil aging on potential lifetime cancer risk associated with chronic exposure to As contaminated soils. Four soils, chosen based on their differences in As reactivity, were amended with two arsenical pesticides--sodium arsenate, and dimethylarsinic acid (DMA) at two rates (675 and 1500 mg kg(-1)). Rice was used as the test crop. Soil was sampled immediately after spiking, after 6 months, 1 year, and 3 years. Bioaccessible and total soil As concentrations were used to calculate lifetime excess cancer risk (ECR), which decreased significantly with soil-pesticide equilibration time. Immokalee soil, with the least As adsorption capacity, showed the highest decrease in ECR after 6 months resulting in values lower than the USEPA's cancer risk range of 1 × 10(-4) to 1 × 10(-6). For all other soils, the ECR was much higher than the target range even after 3 years. In the absence of significant changes in As bioaccessibility with time, the total soil As concentration more directly influenced the changes in ECR values with soil aging.

  13. Long term effects of climate on human adaptation in the middle Gila River Valley, Arizona, America.

    PubMed

    Zhu, Tianduowa; Ertsen, M W; van der Giesen, N C

    The Hohokam, an irrigation-based society in the American South West, used the river valleys of the Salt and Gila Rivers between 500 and 1500 AD to grow their crops. Such irrigated crops are linking human agency, water sources and the general natural environment. In order to grow crops, water available through rain and river flows needs to be diverted to land where the plants are grown. With a focus on the Gila River, this paper uses the potential harvest of maize (a main Hohokam crop) as a proxy for evaluating the influence of natural water availability and climatic changes on irrigation options for maize. Available climate variables derived from tree-ring proxies are downscaled. These downscaled data are used as input for a crop growth model for the entire sequence of Hohokam occupation along the Gila River. The results of the crop model are used to discuss the potential influence of climatic variability on Hohokam irrigation and society. The results will show that climatic change alone cannot be used as an explanation for developments in Hohokam irrigation. Societal development resulting in growing population and extensive irrigation systems increasing pressure on water sources over time would have been a key factor to include to understand Hohokam society between 500 and 1500 AD.

  14. Long-term stability of parameters of antioxidant status in human serum.

    PubMed

    Jansen, E H J M; Beekhof, P K; Cremers, J W J M; Viezeliene, D; Muzakova, V; Skalicky, J

    2013-07-01

    The antioxidant status of serum or plasma can be determined using several commercially available assays. Here, four different assays, total antioxidant status (TAS), its second-generation assay (TAS2), biological antioxidant potential (BAP), and enzymatic assay using horseradish peroxidase (EAOC), were applied on human serum samples to test the temperature stability of antioxidants, upon storage of serum for 12 months. The two or three most commonly used temperatures for storage, that is, - 20, - 70 (or - 80), and - 196°C, were selected. The general conclusion is that all assays were stable at the temperatures tested. In addition, there were almost no statistically significant differences between the samples stored at different temperatures. Only the rank order of the EAOC assay was not very good in samples stored at - 20°C. Also three components contributing to the total antioxidant capacity, uric acid, creatinine and bilirubin, showed no statistically significant differences between the temperatures. Therefore, storage at - 20°C is sufficient to maintain a proper assay outcome of most of the total antioxidant assays, although storage at - 70/80°C is to be preferred for longer storage times.

  15. Short-term effects of GSM mobiles phones on spectral components of the human electroencephalogram.

    PubMed

    Maby, Emmanuel; Le Bouquin Jeannes, Régine; Faucon, Gérard

    2006-01-01

    The aim of the study was to investigate whether the GSM (global system for mobile) signals affect the electrical activity of the human brain. Nine healthy subjects and six temporal epileptic patients were exposed to radiofrequencies emitted by a GSM mobile phone signals. Electroencephalographic (EEG) signals were recorded using surface electrodes with and without radiofrequency. In order to obtain a reference, a control session was also carried out. The spectral attributes of the EEG signals recorded by surface electrodes were analyzed. The significant decrease of spectral correlation coefficients under radiofrequency influence showed that the GSM signal altered the spectral arrangement of the EEG activity for healthy subjects as well as epileptic patients. For the healthy subjects, the EEG spectral energy decreased on the studied frequency band [0-40 Hz] and more precisely on occipital electrodes for the alpha-band. For the epileptic patients, these modifications were demonstrated by an increase of the power spectral density of the EEG signal. Nevertheless, these biological effects on the EEG are not sufficient to put forward some electrophysiological hypothesis.

  16. Perfusion culture-induced template-assisted assembling of cell-laden microcarriers is a promising route for fabricating macrotissues.

    PubMed

    Wang, Xiu; Jiao, Qingling; Zhang, Songjie; Ye, Zhaoyang; Zhou, Yan; Tan, Wen-Song

    2014-11-01

    Mass transfer limitation in conventional top-down tissue engineering makes it impossible to fabricate large size viable tissue replacements. In the present study, we aimed at performing a systemic investigation of the assembling process in perfusion culture for fabricating centimeter-scale macrotissues from cell-laden microcarriers following a bottom-up modular approach. Cells (human fibroblasts, human mesenchymal stem cells, or HepG2 cells) were seeded onto microcarriers (Cytopore-2 or CultiSpher S) in spinner flasks and cultured for 14 days and subsequently transferred to a perfusion chamber for assembling. It was found that growth of different cells on different microcarriers varied and aggregation of cell-laden microcarriers was favored with CultiSpher S. After perfusion culture for 14 days, while all microtissues could assemble into integral macrotissues, macrotissues of HepG2 cells were structurally most inferior and the assembling of cell-laden CultiSpher S led to a significant shrinkage. By designing perfusion chamber and using agar-based templates, tubular, disc, and alphabetic letter-shaped macrotissues could be easily fabricated, suggesting template-assisted assembling. Importantly, it was revealed that there existed both optimal perfusion culture time (21 days) and packing condition (1/4 compression) for the assembling of microtissues. This study lays a solid foundation for future applications of this microtissue assembling technique in tissue engineering.

  17. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor.

    PubMed

    Maddipati, Krishna Rao; Romero, Roberto; Chaiworapongsa, Tinnakorn; Zhou, Sen-Lin; Xu, Zhonghui; Tarca, Adi L; Kusanovic, Juan Pedro; Munoz, Hernan; Honn, Kenneth V

    2014-11-01

    Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography-mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti-inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition.

  18. Full-term pregnancy induces a specific genomic signature in the human breast.

    PubMed

    Russo, Jose; Balogh, Gabriela A; Russo, Irma H

    2008-01-01

    Breast cancer risk has traditionally been linked to nulliparity or late first full-term pregnancy, whereas young age at first childbirth, multiparity, and breast-feeding are associated with a reduced risk. Early pregnancy confers protection by inducing breast differentiation, which imprints a specific and permanent genomic signature in experimental rodent models. For testing whether the same phenomenon was detectable in the atrophic breast of postmenopausal parous women, we designed a case-control study for the analysis of the gene expression profile of RNA extracted from epithelial cells microdissected from normal breast tissues obtained from 18 parous and 7 nulliparous women free of breast pathology (controls), and 41 parous and 8 nulliparous women with history of breast cancer (cases). RNA was hybridized to cDNA glass microarrays containing 40,000 genes; arrays were scanned and the images were analyzed using ImaGene software version 4.2. Normalization and statistical analysis were carried out using Linear Models for Microarrays and GeneSight software for hierarchical clustering. The parous control group contained 2,541 gene sequences representing 18 biological processes that were differentially expressed in comparison with the other three groups. Hierarchical clustering of these genes revealed that the combined parity/absence of breast cancer data generated a distinct genomic profile that differed from those of the breast cancer groups, irrespective of parity history, and from the nulliparous cancer-free group, which has been traditionally identified as a high-risk group. The signature that identifies those women in whom parity has been protective will serve as a molecular biomarker of differentiation for evaluating the potential use of preventive agents.

  19. Effect of Short-Term Thyroxine Administration on Energy Metabolism and Mitochondrial Efficiency in Humans

    PubMed Central

    Johannsen, Darcy L.; Galgani, Jose E.; Johannsen, Neil M.; Zhang, Zhengyu; Covington, Jeffrey D.; Ravussin, Eric

    2012-01-01

    The physiologic effects of triiodothyronine (T3) on metabolic rate are well-documented; however, the effects of thyroxine (T4) are less clear despite its wide-spread use to treat thyroid-related disorders and other non-thyroidal conditions. Here, we investigated the effects of acute (3-day) T4 supplementation on energy expenditure at rest and during incremental exercise. Furthermore, we used a combination of in situ and in vitro approaches to measure skeletal muscle metabolism before and after T4 treatment. Ten healthy, euthyroid males were given 200 µg T4 (levothyroxine) per day for 3 days. Energy expenditure was measured at rest and during exercise by indirect calorimetry, and skeletal muscle mitochondrial function was assessed by in situ ATP flux (31P MRS) and in vitro respiratory control ratio (RCR, state 3/state 4 rate of oxygen uptake using a Clark-type electrode) before and after acute T4 treatment. Thyroxine had a subtle effect on resting metabolic rate, increasing it by 4% (p = 0.059) without a change in resting ATP demand (i.e., ATP flux) of the vastus lateralis. Exercise efficiency did not change with T4 treatment. The maximal capacity to produce ATP (state 3 respiration) and the coupled state of the mitochondria (RCR) were reduced by approximately 30% with T4 (p = 0.057 and p = 0.04, respectively). Together, the results suggest that T4, although less metabolically active than T3, reduces skeletal muscle efficiency and modestly increases resting metabolism even after short-term supplementation. Our findings may be clinically relevant given the expanding application of T4 to treat non-thyroidal conditions such as obesity and weight loss. PMID:22844412

  20. Cerebral perfusion pressure and abnormal intracranial pressure wave forms: their relation to outcome in birth asphyxia.

    PubMed

    Raju, T N; Vidyasagar, D; Papazafiratou, C

    1981-06-01

    Intracranial pressure (ICP) studies were carried out in 14 infants with severe birth asphyxia and brain damage. A markedly low cerebral perfusion pressure (CPP) was noted in infants who died and in 1 infant who survived with cerebral palsy. The long-term ICP tracing revealed negative waves and plateau waves in 2 infants. Cushing response was noted in 2 infants who had elevated ICP. The value and significance of evaluated CPP and of abnormal waveforms are discussed.

  1. Long-Term Green Tea Supplementation Does Not Change the Human Gut Microbiota

    PubMed Central

    Janssens, Pilou L. H. R.; Penders, John; Hursel, Rick; Budding, Andries E.; Savelkoul, Paul H. M.; Westerterp-Plantenga, Margriet S.

    2016-01-01

    Background Green tea catechins may play a role in body weight regulation through interactions with the gut microbiota. Aim We examined whether green tea supplementation for 12 weeks induces changes in composition of the human gut microbiota. Methods 58 Caucasian men and women were included in a randomized, placebo-controlled design. For 12 weeks, subjects consumed either green tea (>0.56 g/d epigallocatechin-gallate + 0.28 ∼ 0.45 g/d caffeine) or placebo capsules. Fecal samples were collected twice (baseline, vs. week 12) for analyses of total bacterial profiles by means of IS-profiling, a 16S-23S interspacer region-based profiling method. Results No significant changes between baseline and week 12 in subjects receiving green tea or placebo capsules, and no significant interactions between treatment (green tea or placebo) and time (baseline and week 12) were observed for body composition. Analysis of the fecal samples in subjects receiving green tea and placebo showed similar bacterial diversity and community structures, indicating there were no significant changes in bacterial diversity between baseline and week 12 in subjects receiving green tea capsules or in subjects receiving placebo capsules. No significant interactions were observed between treatment (green tea or placebo) and time (baseline and week 12) for the gut microbial diversity. Although, there were no significant differences between normal weight and overweight subjects in response to green tea, we did observe a reduced bacterial alpha diversity in overweight as compared to normal weight subjects (p = 0.002). Conclusion Green tea supplementation for 12 weeks did not have a significant effect on composition of the gut microbiota. Trial Registration ClinicalTrials.gov NCT01556321 PMID:27054321

  2. Cytotrophoblast, Not Syncytiotrophoblast, Dominates Glycolysis and Oxidative Phosphorylation in Human Term Placenta

    PubMed Central

    Kolahi, Kevin S.; Valent, Amy M.; Thornburg, Kent L.

    2017-01-01

    The syncytiotrophoblast (SCT) at the maternal-fetal interface has been presumed to be the primary driver of placental metabolism, and the underlying progenitor cytotrophoblast cells (CTB) an insignificant contributor to placental metabolic activity. However, we now show that the metabolic rate of CTB is much greater than the SCT. The oxygen consumption and extracellular acidification rate, a measure of glycolysis, are both greater in CTB than in SCT in vitro (CTB: 96 ± 16 vs SCT: 46 ± 14 pmol O2 × min−1 × 100 ng DNA−1, p < 0.001) and (CTB: 43 ± 6.7 vs SCT 1.4 ± 1.0 ∆mpH × min−1 × 100 ng DNA−1, p < 0.0001). Mitochondrial activity, as determined by using the mitochondrial activity-dependent dye Mitotracker CM-H2TMRosa, is higher in CTB than in SCT in culture and living explants. These data cast doubt on the previous supposition that the metabolic rate of the placenta is dominated by the SCT contribution. Moreover, differentiation into SCT leads to metabolic suppression. The normal suppression of metabolic activity during CTB differentiation to SCT is prevented with a p38 MAPK signaling inhibitor and epidermal growth factor co-treatment. We conclude that the undifferentiated CTB, in contrast to the SCT, is highly metabolically active, has a high level of fuel flexibility, and contributes substantially to global metabolism in the late gestation human placenta. PMID:28230167

  3. Long term observation of low-power diode laser welding after penetrating keratoplasty in human patients

    NASA Astrophysics Data System (ADS)

    Rossi, Francesca; Matteini, Paolo; Pini, Roberto; Menabuoni, Luca; Lenzetti, Ivo

    2010-02-01

    Low power diode laser welding is a recently developed technique used as a support tool for conventional suturing in ophthalmic surgery. The main application is in penetrating keratoplasty: in the last four years (2005-2009), clinical trials were performed at the Ophthalmic Department of Prato, Italy). In penetrating keratoplasty, diode laser welding is used to assure the transplanted corneal button in its final position. The donor tissue is positioned in the recipient eye and 8-16 single stitches are apposed. The surgical wound is then stained with a saturated (10% w/w) sterile water solution of Indocyanine Green (ICG), it is washed with sterile water and then a diode laser (810 nm, 13 W/cm2) is used to induce the sealing of the wound. The laser light induces a thermal effect, localized in the stained tissue. In vivo and ex vivo studies in animal models evidenced that welding induces a modification of the corneal collagen architecture through the wound walls, thus enabling a short healing time and a good restoration of the tissue. In this study on human subjects, we confirmed the results evidenced in animal models, by morphological observations. In two cases out of 60, transplant rejection was observed. It was thus possible to study the efficacy of laser welding in the closure of the wound one year after implant. Direct morphological observation evidenced good strengthens of the welded tissue. Histological analysis pointed out a good restoration of the regular collagen architecture at the external perimeter of the corneal button, where laser welding was performed, showing the occurrence of a correct and effective wound healing process.

  4. Perfusion MRI: The Five Most Frequently Asked Technical Questions

    PubMed Central

    Essig, Marco; Shiroishi, Mark S.; Nguyen, Thanh Binh; Saake, Marc; Provenzale, James M.; Enterline, David; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

    2013-01-01

    OBJECTIVE This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23255738

  5. Perfusion Scintigraphy and Patient Selection for Lung Volume Reduction Surgery

    PubMed Central

    Chandra, Divay; Lipson, David A.; Hoffman, Eric A.; Hansen-Flaschen, John; Sciurba, Frank C.; DeCamp, Malcolm M.; Reilly, John J.; Washko, George R.

    2010-01-01

    Rationale: It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS). Objectives: To study the role of perfusion scintigraphy in patient selection for LVRS. Methods: We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non–high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non–upper lobe–predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy. Measurements and Main Results: Among 284 of 1,045 patients with upper lobe–predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe–predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non–upper lobe–predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information. Conclusions: Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe–predominant emphysema when there is low rather than high perfusion to the upper lung. PMID:20538961

  6. Microvascular Perfusion Changes following Transarterial Hepatic Tumor Embolization

    PubMed Central

    Johnson, Carmen Gacchina; Sharma, Karun V.; Levy, Elliot B.; Woods, David L.; Morris, Aaron H.; Bacher, John D.; Lewis, Andrew L.; Wood, Bradford J.; Dreher, Matthew R.

    2015-01-01

    Purpose To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints. Materials and Methods Rabbit Vx2 liver tumors were embolized with 100–300-µm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3–5 per group; 18 total). Results Mean microvascular density was 70 vessels/mm2 ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31+ structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis. Conclusions Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy. PMID:26321051

  7. Measurement of continuous distributions of ventilation-perfusion ratios - Theory

    NASA Technical Reports Server (NTRS)

    Wagner, P. D.; Saltzman, H. A.; West, J. B.

    1974-01-01

    The resolution of the technique considered is sufficient to describe smooth distributions containing blood flow to unventilated regions (shunt), ventilation to unperfused regions (dead space), and up to three additional modes over the range of finite ventilation-perfusion ratios. In particular, areas whose ventilation-perfusion ratios are low can be separated from unventilated regions and those whose ventilation-perfusion ratios are high can similarly be distinguished from unperfused areas.

  8. Scintigraphic perfusion patterns in patients with diffuse lung disease

    SciTech Connect

    Newman, G.E.; Sullivan, D.C.; Gottschalk, A.; Putman, C.E.

    1982-04-01

    Perfusion scintigrams of 55 patients with radiographic evidence of diffuse lung disease were reviewed. Thirty-nine had acute and/or chronic changes caused by congestive heart failure, and 16 had diffuse reticulonodular disease. A normal or near-normal perfusion pattern was seen in 40/55 (73%), and this finding was equally common in the two groups. The authors conclude that perfusion scintigraphy is useful in excluding pulmonary embolism in patients with radiographic evidence of diffuse, symmetrical lung disease.

  9. Maternal obesity modulates intracellular lipid turnover in the human term placenta

    PubMed Central

    Hirschmugl, B; Desoye, G; Catalano, P; Klymiuk, I; Scharnagl, H; Payr, S; Kitzinger, E; Schliefsteiner, C; Lang, U; Wadsack, C; Hauguel-de Mouzon, S

    2017-01-01

    Background: Obesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development. Objectives: We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women. Subjects/Methods: Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays. Results: Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04–1.24 mg g−1, P<0.05) vs lean (0.84, CI 0.72–1.02 mg g−1) women. Among target genes examined, six showed positive correlation (P<0.05) with maternal pre-pregnancy BMI, namely ATGL (PNPLA2), FATP1 (SLC27A1), FATP3 (SLC27A3), PLIN2, PPARG and CGI-58 (ABHD5). CGI-58 protein abundance was twofold higher (P<0.001) in placentas of obese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, P<0.001 and R=0.64, P<0.001, respectively). CGI-58 and PLIN2 were primarily located in the syncytiotrophoblast and, were upregulated (1.38- and 500-fold, respectively) upon oleic acid and insulin treatment of cultured trophoblast cells. Conclusion: Pre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG

  10. Effects of transforming growth factor-beta on long-term human cord blood monocyte cultures

    SciTech Connect

    Orcel, P.; Bielakoff, J.; De Vernejoul, M.C. )

    1990-02-01

    Transforming growth factor-beta (TGF-beta) modulates growth and differentiation in many cell types and is abundant in bone matrix. We recently showed that human cord blood monocytes cultured in the presence of 1,25(OH)2D3 acquire some features of osteoclast precursors. Since TGF-beta has been shown to influence bone resorption in organ culture, we have studied the effect of TGF-beta (1-1,000 pg/ml) on cord blood monocyte cultures. These cells were cultured on plastic substrate during 3 weeks in the presence of 20% horse serum and 10(-9) M 1,25(OH)2D3. TGF-beta, from a concentration of 10 pg/ml in the culture medium, decreased in a dose dependent manner the formation of multinucleated cells. At a concentration of TGF-beta of 1 ng/ml, the multinucleated cells were reduced to 2.1% +/- 0.3%, compared to 19.3% +/- 1.5% in control cultures. TGF-beta inhibited in a dose-dependent manner the proliferation of cord blood monocytes as assessed by 3H-thymidine incorporation at 7 and 14 days of culture. The fusion index was also decreased by 3 weeks of treatment with TGF-beta. Indomethacin did not reverse the inhibitory effects of TGF-beta. The expression of the osteoclastic phenotype was assessed using two different antibodies: 23C6, a monoclonal antibody directed against the vitronectin receptor, which is highly expressed by osteoclasts but not by adult monocytes, and an antibody to HLA-DR, which is not present on osteoclast. TGF-beta decreased the expression of HLA-DR and increased in a dose-dependent manner the proportion of 23C6-labeled cells; these results suggest that TGF-beta could modulate a differentiation effect to the osteoclastic phenotype. However, when cord blood monocytes were cultured on devitalized rat calvariae prelabeled with 45Ca, TGF-beta did not induce any 45Ca release from bone cultured with monocytes.

  11. Perfusion lung scanning: differentiation of primary from thromboembolic pulmonary hypertension

    SciTech Connect

    Lisbona, R.; Kreisman, H.; Novales-Diaz, J.; Derbekyan, V.

    1985-01-01

    Of eight patients with pulmonary arterial hypertension, final diagnosis established by autopsy or angiography, four had primary hypertension and four hypertension from thromboembolism. The perfusion lung scan was distinctly different in the two groups. The lung scan in primary pulmonary hypertension was associated with nonsegmental, patchy defects of perfusion, while in thromboembolic hypertensives it was characterized by segmental and/or lobar defects of perfusion with or without subsegmental defects. The perfusion lung scan is a valuable, noninvasive study in the evaluation of the patient with pulmonary hypertension of undetermined cause and in the exclusion of occult large-vessel pulmonary thromboembolism.

  12. New imaging technology: measurement of myocardial perfusion by contrast echocardiography

    NASA Technical Reports Server (NTRS)

    Rubin, D. N.; Thomas, J. D.

    2000-01-01

    Myocardial perfusion imaging has long been a goal for the non-invasive echocardiographic assessment of the heart. However, many factors at play in perfusion imaging have made this goal elusive. Harmonic imaging and triggered imaging with newer contrast agents have made myocardial perfusion imaging potentially practical in the very near future. The application of indicator dilution theory to the coronary circulation and bubble contrast agents is fraught with complexities and sources of error. Therefore, quantification of myocardial perfusion by non-invasive echocardiographic imaging requires further investigation in order to make this technique clinically viable.

  13. Extracorporeal Free Flap Perfusion in Case of Prolonged Ischemia Time.

    PubMed

    Taeger, C D; Präbst, K; Beier, J P; Meyer, A; Horch, R E

    2016-04-01

    In free flap surgery, a clinically established concept still has to be found for the reduction of ischemia-related cell damage in the case of prolonged ischemia. Although promising results using ex