WorldWideScience

Sample records for stimulation alters tissue

  1. Modelling the impact of altered axonal morphometry on the response of regenerative nervous tissue to electrical stimulation through macro-sieve electrodes

    Science.gov (United States)

    Zellmer, Erik R.; MacEwan, Matthew R.; Moran, Daniel W.

    2018-04-01

    Objective. Regenerated peripheral nervous tissue possesses different morphometric properties compared to undisrupted nerve. It is poorly understood how these morphometric differences alter the response of the regenerated nerve to electrical stimulation. In this work, we use computational modeling to explore the electrophysiological response of regenerated and undisrupted nerve axons to electrical stimulation delivered by macro-sieve electrodes (MSEs). Approach. A 3D finite element model of a peripheral nerve segment populated with mammalian myelinated axons and implanted with a macro-sieve electrode has been developed. Fiber diameters and morphometric characteristics representative of undisrupted or regenerated peripheral nervous tissue were assigned to core conductor models to simulate the two tissue types. Simulations were carried out to quantify differences in thresholds and chronaxie between undisrupted and regenerated fiber populations. The model was also used to determine the influence of axonal caliber on recruitment thresholds for the two tissue types. Model accuracy was assessed through comparisons with in vivo recruitment data from chronically implanted MSEs. Main results. Recruitment thresholds of individual regenerated fibers with diameters  >2 µm were found to be lower compared to same caliber undisrupted fibers at electrode to fiber distances of less than about 90-140 µm but roughly equal or higher for larger distances. Caliber redistributions observed in regenerated nerve resulted in an overall increase in average recruitment thresholds and chronaxie during whole nerve stimulation. Modeling results also suggest that large diameter undisrupted fibers located close to a longitudinally restricted current source such as the MSE have higher average recruitment thresholds compared to small diameter fibers. In contrast, large diameter regenerated nerve fibers located in close proximity of MSE sites have, on average, lower recruitment thresholds

  2. I. Lipid metabolism stimulated by altered intracellular calcium in cultured fibroblasts. II. Regulation of the activity of rat adipose tissue lipoprotein lipase

    International Nuclear Information System (INIS)

    Chang Wang, Huei-Hsiang Lisa.

    1988-01-01

    The cell killing process of 3T3 Swiss mouse fibroblasts stimulated by Ca 2+ plus A23187, a Ca 2+ ionophore has been studied. The aim of this research is to understand the biochemical mechanism of this process, i.e, to elucidate the step involved and to characterize the enzymes involved with each steps in the lipid metabolism stimulated in cultured fibroblasts undergoing a toxic death response. Parallel 3T3 cultures biosynthetically labeled with lipid precursors were examined under Ca 2+ -mediated killing conditions. Labeled lipids were extracted and analyzed by thin-layer chromatography and autoradiography. Evidence for activation of a phosphatidylinositol-specific phospholipase C has been obtained in injured 3T3 cells labeled with [ 3 H]glycerol and [ 3 H]inositol. To simplify the system for studying the lipoprotein lipase reaction, our laboratory prepared the chromophore containing a substrate: 1,2-dipalmitoyl-3-β-2-furylacryloyltriacylglycerol (DPFATG). By using this artificial lipid we could readily investigate the lipoprotein lipase reactions, since the absorbance change directly represents the hydrolysis of the chromophoric side chain of the substrate

  3. Connective tissue alteration in abdominal wall hernia

    DEFF Research Database (Denmark)

    Henriksen, N A; Yadete, D H; Sørensen, Lars Tue

    2011-01-01

    The aetiology and pathogenesis of abdominal wall hernia formation is complex. Optimal treatment of hernias depends on a full understanding of the pathophysiological mechanisms involved in their formation. The aim of this study was to review the literature on specific collagen alterations in abdom...

  4. Multi-axial mechanical stimulation of tissue engineered cartilage: Review

    Directory of Open Access Journals (Sweden)

    S D Waldman

    2007-04-01

    Full Text Available The development of tissue engineered cartilage is a promising new approach for the repair of damaged or diseased tissue. Since it has proven difficult to generate cartilaginous tissue with properties similar to that of native articular cartilage, several studies have used mechanical stimuli as a means to improve the quantity and quality of the developed tissue. In this study, we have investigated the effect of multi-axial loading applied during in vitro tissue formation to better reflect the physiological forces that chondrocytes are subjected to in vivo. Dynamic combined compression-shear stimulation (5% compression and 5% shear strain amplitudes increased both collagen and proteoglycan synthesis (76 ± 8% and 73 ± 5%, respectively over the static (unstimulated controls. When this multi-axial loading condition was applied to the chondrocyte cultures over a four week period, there were significant improvements in both extracellular matrix (ECM accumulation and the mechanical properties of the in vitro-formed tissue (3-fold increase in compressive modulus and 1.75-fold increase in shear modulus. Stimulated tissues were also significantly thinner than the static controls (19% reduction suggesting that there was a degree of ECM consolidation as a result of long-term multi-axial loading. This study demonstrated that stimulation by multi-axial forces can improve the quality of the in vitro-formed tissue, but additional studies are required to further optimize the conditions to favour improved biochemical and mechanical properties of the developed tissue.

  5. Sympathetic stimulation alters left ventricular relaxation and chamber size.

    Science.gov (United States)

    Burwash, I G; Morgan, D E; Koilpillai, C J; Blackmore, G L; Johnstone, D E; Armour, J A

    1993-01-01

    Alterations in left ventricular (LV) contractility, relaxation, and chamber dimensions induced by efferent sympathetic nerve stimulation were investigated in nine anesthetized open-chest dogs in sinus rhythm. Supramaximal stimulation of acutely decentralized left stellate ganglia augmented heart rate, LV systolic pressure, and rate of LV pressure rise (maximum +dP/dt, 1,809 +/- 191 to 6,304 +/- 725 mmHg/s) and fall (maximum -dP/dt, -2,392 +/- 230 to -4,458 +/- 482 mmHg/s). It also reduced the time constant of isovolumic relaxation, tau (36.5 +/- 4.8 to 14.9 +/- 1.1 ms). Simultaneous two-dimensional echocardiography recorded reductions in end-diastolic and end-systolic LV cross-sectional chamber areas (23 and 31%, respectively), an increase in area ejection fraction (32%), and increases in end-diastolic and end-systolic wall thicknesses (14 and 13%, respectively). End-systolic and end-diastolic wall stresses were unchanged by stellate ganglion stimulation (98 +/- 12 to 95 +/- 9 dyn x 10(3)/cm2; 6.4 +/- 2.4 to 2.4 +/- 0.3 dyn x 10(3)/cm2, respectively). Atrial pacing to similar heart rates did not alter monitored indexes of contractility. Dobutamine and isoproterenol induced changes similar to those resulting from sympathetic neuronal stimulation. These data indicate that when the efferent sympathetic nervous system increases left ventricular contractility and relaxation, concomitant reductions in systolic and diastolic dimensions of that chamber occur that are associated with increasing wall thickness such that LV wall stress changes are minimized.

  6. A Novel bioreactor with mechanical stimulation for skeletal tissue engineering

    Directory of Open Access Journals (Sweden)

    M. Petrović

    2009-01-01

    Full Text Available The provision of mechanical stimulation is believed to be necessary for the functional assembly of skeletal tissues, which are normally exposed to a variety of biomechanical signals in vivo. In this paper, we present a development and validation of a novel bioreactor aimed for skeletal tissue engineering that provides dynamic compression and perfusion of cultivated tissues. Dynamic compression can be applied at frequencies up to 67.5 Hz and displacements down to 5 m thus suitable for the simulation of physiological conditions in a native cartilage tissue (0.1-1 Hz, 5-10 % strain. The bioreactor also includes a load sensor that was calibrated so to measure average loads imposed on tissue samples. Regimes of the mechanical stimulation and acquisition of load sensor outputs are directed by an automatic control system using applications developed within the LabView platform. In addition, perfusion of tissue samples at physiological velocities (10–100 m/s provides efficient mass transfer, as well as the possibilities to expose the cells to hydrodynamic shear and simulate the conditions in a native bone tissue. Thus, the novel bioreactor is suited for studies of the effects of different biomechanical signals on in vitro regeneration of skeletal tissues, as well as for the studies of newly formulated biomaterials and cell biomaterial interactions under in vivo-like settings.

  7. Immunohistochemical and Morphofunctional Studies of Skeletal Muscle Tissues with Electric Nerve Stimulation by In Vivo Cryotechnique

    International Nuclear Information System (INIS)

    Fukasawa, Yuki; Ohno, Nobuhiko; Saitoh, Yurika; Saigusa, Takeshi; Arita, Jun; Ohno, Shinichi

    2015-01-01

    In this study, morphological and immunohistochemical alterations of skeletal muscle tissues during persistent contraction were examined by in vivo cryotechnique (IVCT). Contraction of gastrocnemius muscles was induced by sciatic nerve stimulation. The IVCT was performed immediately, 3 min or 10 min after the stimulation start. Prominent ripples of muscle fibers or wavy deformation of sarcolemma were detected immediately after the stimulation, but they gradually diminished to normal levels during the stimulation. The relative ratio of sarcomere and A band lengths was the highest in the control group, but it immediately decreased to the lowest level and then gradually recovered at 3 min or 10 min. Although histochemical intensity of PAS reaction was almost homogeneous in muscle tissues of the control group or immediately after the stimulation, it decreased at 3 min or 10 min. Serum albumin was immunolocalized as dot-like patterns within some muscle fibers at 3 min stimulation. These patterns became more prominent at 10 min, and the dots got larger and saccular in some sarcoplasmic regions. However, IgG1 and IgM were immunolocalized in blood vessels under nerve stimulation conditions. Therefore, IVCT was useful to capture the morphofunctional and metabolic changes of heterogeneous muscle fibers during the persistent contraction

  8. Can ultrasound be used to stimulate nerve tissue?

    Directory of Open Access Journals (Sweden)

    Norton Stephen J

    2003-03-01

    Full Text Available Abstract Background The stimulation of nerve or cortical tissue by magnetic induction is a relatively new tool for the non-invasive study of the brain and nervous system. Transcranial magnetic stimulation (TMS, for example, has been used for the functional mapping of the motor cortex and may have potential for treating a variety of brain disorders. Methods and Results A new method of stimulating active tissue is proposed by propagating ultrasound in the presence of a magnetic field. Since tissue is conductive, particle motion created by an ultrasonic wave will induce an electric current density generated by Lorentz forces. An analytical derivation is given for the electric field distribution induced by a collimated ultrasonic beam. An example shows that peak electric fields of up to 8 V/m appear to be achievable at the upper range of diagnostic intensities. This field strength is about an order of magnitude lower than fields typically associated with TMS; however, the electric field gradients induced by ultrasound can be quite high (about 60 kV/m2 at 4 MHz, which theoretically play a more important role in activation than the field magnitude. The latter value is comparable to TMS-induced gradients. Conclusion The proposed method could be used to locally stimulate active tissue by inducing an electric field in regions where the ultrasound is focused. Potential advantages of this method compared to TMS is that stimulation of cortical tissue could be highly localized as well as achieved at greater depths in the brain than is currently possible with TMS.

  9. Indirect Low-Intensity Ultrasonic Stimulation for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Hyoungshin Park

    2010-01-01

    Full Text Available Low-intensity ultrasound (LIUS treatment has been shown to increase mass transport, which could benefit tissue grafts during the immediate postimplant period, when blood supply to the implanted tissue is suboptimal. In this in vitro study, we investigated effects of LIUS stimulation on dye diffusion, proliferation, metabolism, and tropomyosin expression of muscle cells (C2C12 and on tissue viability and gene expression of human adipose tissue organoids. We found that LIUS increased dye diffusion within adjacent tissue culture wells and caused anisotropic diffusion patterns. This effect was confirmed by a hydrophone measurement resulting in acoustic pressure 150–341 Pa in wells. Cellular studies showed that LIUS significantly increased proliferation, metabolic activity, and expression of tropomyosin. Adipose tissue treated with LIUS showed significantly increased metabolic activity and the cells had similar morphology to normal unilocular adipocytes. Gene analysis showed that tumor necrosis factor-alpha expression (a marker for tissue damage was significantly lower for stimulated organoids than for control groups. Our data suggests that LIUS could be a useful modality for improving graft survival in vivo.

  10. Altered morphology of liver and pancreas tissues of offsprings of ...

    African Journals Online (AJOL)

    The relationship between consumption of charred meat, which is believed to be rich in nitrosamine by pregnant mothers and the adverse effects on the growth of their offsprings, alterations in morphology of tissues like liver and pancreas were studied. Meat was subjected to charcoal fire roasting without curing and was ...

  11. Modeling of light absorption in tissue during infrared neural stimulation

    Science.gov (United States)

    Thompson, Alexander C.; Wade, Scott A.; Brown, William G. A.; Stoddart, Paul R.

    2012-07-01

    A Monte Carlo model has been developed to simulate light transport and absorption in neural tissue during infrared neural stimulation (INS). A range of fiber core sizes and numerical apertures are compared illustrating the advantages of using simulations when designing a light delivery system. A range of wavelengths, commonly used for INS, are also compared for stimulation of nerves in the cochlea, in terms of both the energy absorbed and the change in temperature due to a laser pulse. Modeling suggests that a fiber with core diameter of 200 μm and NA=0.22 is optimal for optical stimulation in the geometry used and that temperature rises in the spiral ganglion neurons are as low as 0.1°C. The results show a need for more careful experimentation to allow different proposed mechanisms of INS to be distinguished.

  12. Compact biomedical pulsed signal generator for bone tissue stimulation

    Science.gov (United States)

    Kronberg, James W.

    1993-01-01

    An apparatus for stimulating bone tissue for stimulating bone growth or treating osteoporosis by applying directly to the skin of the patient an alternating current electrical signal comprising wave forms known to simulate the piezoelectric constituents in bone. The apparatus may, by moving a switch, stimulate bone growth or treat osteoporosis, as desired. Based on low-power CMOS technology and enclosed in a moisture-resistant case shaped to fit comfortably, two astable multivibrators produce the desired waveforms. The amplitude, pulse width and pulse frequency, and the subpulse width and subpulse frequency of the waveforms are adjustable. The apparatus, preferably powered by a standard 9-volt battery, includes signal amplitude sensors and warning signals indicate an output is being produced and the battery needs to be replaced.

  13. Peripheral nerve magnetic stimulation: influence of tissue non-homogeneity

    Directory of Open Access Journals (Sweden)

    Papazov Sava P

    2003-12-01

    Full Text Available Abstract Background Peripheral nerves are situated in a highly non-homogeneous environment, including muscles, bones, blood vessels, etc. Time-varying magnetic field stimulation of the median and ulnar nerves in the carpal region is studied, with special consideration of the influence of non-homogeneities. Methods A detailed three-dimensional finite element model (FEM of the anatomy of the wrist region was built to assess the induced currents distribution by external magnetic stimulation. The electromagnetic field distribution in the non-homogeneous domain was defined as an internal Dirichlet problem using the finite element method. The boundary conditions were obtained by analysis of the vector potential field excited by external current-driven coils. Results The results include evaluation and graphical representation of the induced current field distribution at various stimulation coil positions. Comparative study for the real non-homogeneous structure with anisotropic conductivities of the tissues and a mock homogeneous media is also presented. The possibility of achieving selective stimulation of either of the two nerves is assessed. Conclusion The model developed could be useful in theoretical prediction of the current distribution in the nerves during diagnostic stimulation and therapeutic procedures involving electromagnetic excitation. The errors in applying homogeneous domain modeling rather than real non-homogeneous biological structures are demonstrated. The practical implications of the applied approach are valid for any arbitrary weakly conductive medium.

  14. Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

    International Nuclear Information System (INIS)

    Badylak, S.F.; Babbs, C.F.

    1984-01-01

    The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 0 C and 45 0 for 20 minutes) were studied by light and electron microscopy. Normal muscle and Walker 256 tumors showed vascular damage at 5 minutes post-heating (PH), followed by suppuration and thrombosis at 6 and 48 hours PH, and by regeneration and repair at 7 days PH. Endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive ischemic injury occurred for at least 48 hours PH. Two hyperthermia treatments, separated by a 30 or 60 minute cooling interval, were applied to rats implanted with Walker 256 tumors. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results characterized the sequential morphologic alterations following hyperthermia treatment and showed that: 1) vascular damage contributed to the immediate and latent cytotoxic effects of hyperthermia, 2) selective heating occurred in the neoplastic tissue disrupted by prior heat treatment, and 3) not all neoplasms are responsive to hyperthermia treatment

  15. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  16. A dual flow bioreactor with controlled mechanical stimulation for cartilage tissue engineering

    NARCIS (Netherlands)

    Spitters, Tim; Leijten, Jeroen Christianus Hermanus; Deus, F.D.; Costa, I.B.F.; van Apeldoorn, Aart A.; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2013-01-01

    In cartilage tissue engineering bioreactors can create a controlled environment to study chondrocyte behavior under mechanical stimulation or produce chondrogenic grafts of clinically relevant size. Here we present a novel bioreactor, which combines mechanical stimulation with a two compartment

  17. Thermal Stimulation Alters Cervical Spinal Cord Functional Connectivity in Humans.

    Science.gov (United States)

    Weber, Kenneth A; Sentis, Amy I; Bernadel-Huey, Olivia N; Chen, Yufen; Wang, Xue; Parrish, Todd B; Mackey, Sean

    2018-01-15

    The spinal cord has an active role in the modulation and transmission of the neural signals traveling between the body and the brain. Recent advancements in functional magnetic resonance imaging (fMRI) have made the in vivo examination of spinal cord function in humans now possible. This technology has been recently extended to the investigation of resting state functional networks in the spinal cord, leading to the identification of distinct patterns of spinal cord functional connectivity. In this study, we expand on the previous work and further investigate resting state cervical spinal cord functional connectivity in healthy participants (n = 15) using high resolution imaging coupled with both seed-based functional connectivity analyses and graph theory-based metrics. Within spinal cord segment functional connectivity was present between the left and right ventral horns (bilateral motor network), left and right dorsal horns (bilateral sensory network), and the ipsilateral ventral and dorsal horns (unilateral sensory-motor network). Functional connectivity between the spinal cord segments was less apparent with the connectivity centered at the region of interest and spanning spinal cord functional network was demonstrated to be state-dependent as thermal stimulation of the right ventrolateral forearm resulted in significant disruption of the bilateral sensory network, increased network global efficiency, and decreased network modularity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Alteration of political belief by non- invasive brain stimulation

    Directory of Open Access Journals (Sweden)

    Caroline eChawke

    2016-01-01

    Full Text Available People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing and reduced affiliation with opposing political candidates. As such, this study used a method of non- invasive brain simulation (tRNS to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant’s initial political orientation and the political campaign advertisement they were exposed to.

  19. Alteration of Political Belief by Non-invasive Brain Stimulation

    Science.gov (United States)

    Chawke, Caroline; Kanai, Ryota

    2016-01-01

    People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to. PMID:26834603

  20. Obesity alters adipose tissue macrophage iron content and tissue iron distribution.

    Science.gov (United States)

    Orr, Jeb S; Kennedy, Arion; Anderson-Baucum, Emily K; Webb, Corey D; Fordahl, Steve C; Erikson, Keith M; Zhang, Yaofang; Etzerodt, Anders; Moestrup, Søren K; Hasty, Alyssa H

    2014-02-01

    Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFe(hi), and the remaining ATMs are referred to as MFe(lo). In lean mice, ~25% of the ATMs are MFe(hi); this percentage decreases in obesity owing to the recruitment of MFe(lo) macrophages. Similar to MFe(lo) cells, MFe(hi) ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFe(hi) ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFe(hi) iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFe(hi) ATM phenotype and their reduced capacity to handle iron.

  1. Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.

    Directory of Open Access Journals (Sweden)

    Danny Gauvreau

    Full Text Available BACKGROUND: Obesity is considered as a systemic chronic low grade inflammation characterized by increased serum pro-inflammatory proteins and accumulation of macrophages within white adipose tissue (WAT of obese patients. C5L2, a 7-transmembrane receptor, serves a dual function, binding the lipogenic hormone acylation stimulating protein (ASP, and C5a, involved in innate immunity. AIM: We evaluated the impact of C5L2 on macrophage infiltration in WAT of wildtype (Ctl and C5L2 knock-out (C5L2(-/- mice over 6, 12 and 24 weeks on a chow diet and moderate diet-induced obesity (DIO conditions. RESULTS: In Ctl mice, WAT C5L2 and C5a receptor mRNA increased (up to 10-fold both over time and with DIO. By contrast, in C5L2(-/-, there was no change in C5aR in WAT. C5L2(-/- mice displayed higher macrophage content in WAT, varying by time, fat depot and diet, associated with altered systemic and WAT cytokine patterns compared to Ctl mice. However, in all cases, the M1 (pro- vs M2 (anti-inflammatory macrophage proportion was unchanged but C5L2(-/- adipose tissue secretome appeared to be more chemoattractant. Moreover, C5L2(-/- mice have increased food intake, increased WAT, and altered WAT lipid gene expression, which is reflected systemically. Furthermore, C5L2(-/- mice have altered glucose/insulin metabolism, adiponectin and insulin signalling gene expression in WAT, which could contribute to development of insulin resistance. CONCLUSION: Disruption of C5L2 increases macrophage presence in WAT, contributing to obesity-associated pathologies, and further supports a dual role of complement in WAT. Understanding this effect of the complement system pathway could contribute to targeting treatment of obesity and its comorbidities.

  2. Application of electrical stimulation for functional tissue engineering in vitro and in vivo

    Science.gov (United States)

    Park, Hyoungshin (Inventor); Freed, Lisa (Inventor); Vunjak-Novakovic, Gordana (Inventor); Langer, Robert (Inventor); Radisic, Milica (Inventor)

    2013-01-01

    The present invention provides new methods for the in vitro preparation of bioartificial tissue equivalents and their enhanced integration after implantation in vivo. These methods include submitting a tissue construct to a biomimetic electrical stimulation during cultivation in vitro to improve its structural and functional properties, and/or in vivo, after implantation of the construct, to enhance its integration with host tissue and increase cell survival and functionality. The inventive methods are particularly useful for the production of bioartificial equivalents and/or the repair and replacement of native tissues that contain electrically excitable cells and are subject to electrical stimulation in vivo, such as, for example, cardiac muscle tissue, striated skeletal muscle tissue, smooth muscle tissue, bone, vasculature, and nerve tissue.

  3. Excessive Sensory Stimulation during Development Alters Neural Plasticity and Vulnerability to Cocaine in Mice.

    Science.gov (United States)

    Ravinder, Shilpa; Donckels, Elizabeth A; Ramirez, Julian S B; Christakis, Dimitri A; Ramirez, Jan-Marino; Ferguson, Susan M

    2016-01-01

    Early life experiences affect the formation of neuronal networks, which can have a profound impact on brain function and behavior later in life. Previous work has shown that mice exposed to excessive sensory stimulation during development are hyperactive and novelty seeking, and display impaired cognition compared with controls. In this study, we addressed the issue of whether excessive sensory stimulation during development could alter behaviors related to addiction and underlying circuitry in CD-1 mice. We found that the reinforcing properties of cocaine were significantly enhanced in mice exposed to excessive sensory stimulation. Moreover, although these mice displayed hyperactivity that became more pronounced over time, they showed impaired persistence of cocaine-induced locomotor sensitization. These behavioral effects were associated with alterations in glutamatergic transmission in the nucleus accumbens and amygdala. Together, these findings suggest that excessive sensory stimulation in early life significantly alters drug reward and the neural circuits that regulate addiction and attention deficit hyperactivity. These observations highlight the consequences of early life experiences and may have important implications for children growing up in today's complex technological environment.

  4. Norepinephrine turnover in brown adipose tissue is stimulated by a single meal

    International Nuclear Information System (INIS)

    Glick, Z.; Raum, W.J.

    1986-01-01

    A single meal stimulates brown adipose tissue (BAT) thermogenesis in rats. In the present study the role of norepinephrine in this thermogenic response was assessed from the rate of its turnover in BAT after a single test meal. For comparison, norepinephrine turnover was determined in the heart and spleen. A total of 48 male Wistar rats (200 g) were trained to eat during two feeding sessions per day. On the experimental day, one group (n = 24) was meal deprived and the other (n = 24) was given a low-protein high-carbohydrate test meal for 2 h. The synthesis inhibition method with α-methyl-p-tyrosine was employed to determine norepinephrine turnover from its concentration at four hourly time points after the meal. Tissue concentrations of norepinephrine were determined by radioimmunoassay. Norepinephrine concentration and turnover rate were increased more than threefold in BAT of the meal-fed compared with the meal-deprived rats. Neither were significantly altered by the meal in the heart or spleen. The data suggest that norepinephrine mediates a portion of the thermic effect of meals that originate in BAT

  5. Review on patents for mechanical stimulation of articular cartilage tissue engineering

    NARCIS (Netherlands)

    Donkelaar, van C.C.; Schulz, R.M.

    2008-01-01

    To repair articular cartilage defects in osteoarthritic patients with three-dimensional tissue engineered chondrocyte grafts, requires the formation of new cartilage with sufficient mechanical properties. The premise is that mechanical stimulation during the culturing process is necessary to reach

  6. Referred pain and cutaneous responses from deep tissue electrical pain stimulation in the groin

    DEFF Research Database (Denmark)

    Aasvang, E K; Werner, M U; Kehlet, H

    2015-01-01

    , supporting individual differences in anatomy and sensory processing. Future studies investigating the responses to deep tissue electrical stimulation in persistent postherniotomy pain patients may advance our understanding of underlying pathophysiological mechanisms and strategies for treatment...

  7. Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.

    Science.gov (United States)

    Wang, Chao-Yung; Shie, Shian-Sen; Wen, Ming-Shien; Hung, Kuo-Chun; Hsieh, I-Chang; Yeh, Ta-Sen; Wu, Delon

    2015-12-15

    A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to β-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4. Copyright © 2015, American Association for the Advancement of Science.

  8. Postural stability is altered by the stimulation of pain but not warm receptors in humans

    Directory of Open Access Journals (Sweden)

    Corbeil Philippe

    2003-10-01

    -noxious stimulation (40 degrees C of the small diameter afferents is not a sufficiently intense sensory stimulation to alter the control of posture. A painful stimulation (45 degrees C of the skin thermoreceptors, however, yielded a deterioration of the postural control system. The observed deteriorating effects of the combined stimulation of nociceptors and Ia afferents (when ankle tendons were vibrated could result from the convergence of these afferents at the spinal level. This could certainly lead to the hypothesis that individuals suffering from lower limb pain present alterations of the postural control mechanisms; especially populations already at risk of falling (for example, frail elderly or populations suffering from concomitant lower limb pain and sensory deficits (for example, diabetic polyneuropathy.

  9. Postural stability is altered by the stimulation of pain but not warm receptors in humans.

    Science.gov (United States)

    Blouin, Jean-Sébastien; Corbeil, Philippe; Teasdale, Normand

    2003-10-17

    sufficiently intense sensory stimulation to alter the control of posture. A painful stimulation (45 degrees C) of the skin thermoreceptors, however, yielded a deterioration of the postural control system. The observed deteriorating effects of the combined stimulation of nociceptors and Ia afferents (when ankle tendons were vibrated) could result from the convergence of these afferents at the spinal level. This could certainly lead to the hypothesis that individuals suffering from lower limb pain present alterations of the postural control mechanisms; especially populations already at risk of falling (for example, frail elderly) or populations suffering from concomitant lower limb pain and sensory deficits (for example, diabetic polyneuropathy).

  10. Alteration in adenylate cyclase response to aminergic stimulation following neonatal x-irradiation

    International Nuclear Information System (INIS)

    Chronister, R.B.; Palmer, G.C.; Gerbrandt, L.

    1980-01-01

    X-irradiation of the rat neonatal hippocampus produces severe alterations in the architectonic features of the mature hippocampus. The most prominent alteration is a marked depletion of the granule cells of the dentate gyrus, with a subsequent realignment of CA 4 cells. The present data also show that norepinephrine (NE), dopamine and histamine stimulation of adenylate cyclase activity is severely attenuated in the hippocampi of irradiated animals. This failure suggests that the NE fibers of irradiated subjects, although normal in content of NE, are not functional in some of their NE-effector actions

  11. Designing electrical stimulated bioreactors for nerve tissue engineering

    Science.gov (United States)

    Sagita, Ignasius Dwi; Whulanza, Yudan; Dhelika, Radon; Nurhadi, Ibrahim

    2018-02-01

    Bioreactor provides a biomimetic ecosystem that is able to culture cells in a physically controlled system. In general, the controlled-parameters are temperature, pH, fluid flow, nutrition flow, etc. In this study, we develop a bioreactor that specifically targeted to culture neural stem cells. This bioreactor could overcome some limitations of conventional culture technology, such as petri dish, by providing specific range of observation area and a uniform treatment. Moreover, the microfluidic bioreactor, which is a small-controlled environment, is able to observe as small number of cells as possible. A perfusion flow is applied to mimic the physiological environment in human body. Additionally, this bioreactor also provides an electrical stimulation which is needed by neural stem cells. In conclusion, we found the correlation between the induced shear stress with geometric parameters of the bioreactor. Ultimately, this system shall be used to observe the interaction between stimulation and cell growth.

  12. Ultrasonic stimulation of peripheral nervous tissue: an investigation into mechanisms

    International Nuclear Information System (INIS)

    Wright, C J; Saffari, N; Rothwell, J

    2015-01-01

    Neuro-stimulation has wide ranging clinical and research potential but this is currently limited either by low resolution, penetration or by highly invasive procedures. It has been reported in previous studies that ultrasound is able to elicit a neuro-stimulatory effect at a higher resolution than other non-invasive approaches but both the underlying mechanism that makes this possible and the practical details of how it can be implemented are still poorly understood. The current study has identified the main issues that need to be resolved in the field, proposing several different approaches to tackling these areas. An isolated in vitro peripheral nerve bundle was chosen as a simple model to demonstrate and investigate the neuro-stimulatory effect after preliminary results showed successful stimulation in a skin-nerve preparation. Early results from the nerve bundle show successful neurostimulation, indicating that structures in the peripheral nerve axon are sensitive to ultrasound. Further research using this model should reveal more precisely what structures are being affected and how to optimise the effect, helping to inform the design of future procedures and devices used in in vivo applications

  13. Altered tissue mineralization, increased hepatic lipid and inhibited ...

    African Journals Online (AJOL)

    Mineral homeostasis is often disrupted in intrauterine growth retardation (IUGR) infants. Most studies focus on calcium or phosphorus metabolism of IUGR infants via determining serum mineral concentrations instead of tissues. This study was conducted to investigate the effects of IUGR on the mineralization and ...

  14. Carbendazim alters kidney morphology, kidney function tests, tissue ...

    African Journals Online (AJOL)

    of oxidative stress and serum micro-elements in rats fed protein-energy ... diet, protein-energy malnutrition did not exacerbate lesions which were contrary to tissue MDA which was elevated in LPC. ... metabolism in animals and this is proportional to the level of .... generally higher in the carbendazim-treated rats which ...

  15. Transcranial Magnetic Stimulation with Intermittent Theta Burst Stimulation Alters Corticospinal Output in Patients with Chronic Incomplete Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Hunter J. Fassett

    2017-08-01

    Full Text Available Intermittent theta burst stimulation (iTBS is intended primarily to alter corticospinal excitability, creating an attractive opportunity to alter neural output following incomplete spinal cord injury (SCI. This study is the first to assess the effects of iTBS in SCI. Eight individuals with chronic incomplete SCI were studied. Sham or real iTBS was delivered (to each participant over primary motor and somatosensory cortices in separate sessions. Motor-evoked potential (MEP recruitment curves were obtained from the flexor carpi radialis muscle before and after iTBS. Results indicate similar responses for iTBS to both motor and somatosensory cortex and reduced MEPs in 56.25% and increased MEPs in 25% of instances. Sham stimulation exceeded real iTBS effects in the remaining 18.25%. It is our opinion that observing short-term neuroplasticity in corticospinal output in chronic SCI is an important advance and should be tested in future studies as an opportunity to improve function in this population. We emphasize the need to re-consider the importance of the direction of MEP change following a single session of iTBS since the relationship between MEP direction and motor function is unknown and multiple sessions of iTBS may yield very different directional results. Furthermore, we highlight the importance of including sham control in the experimental design. The fundamental point from this pilot research is that a single session of iTBS is often capable of creating short-term change in SCI. Future sham-controlled randomized trials may consider repeat iTBS sessions to promote long-term changes in corticospinal excitability.

  16. Olfactory tubercle stimulation alters odor preference behavior and recruits forebrain reward and motivational centers

    Directory of Open Access Journals (Sweden)

    Brynn J FitzGerald

    2014-03-01

    Full Text Available Rodents show robust behavioral responses to odors, including strong preferences or aversions for certain odors. The neural mechanisms underlying the effects of odors on these behaviors in animals are not well understood. Here, we provide an initial proof-of-concept study into the role of the olfactory tubercle (OT, a structure with known anatomical connectivity with both brain reward and olfactory structures, in regulating odor-motivated behaviors. We implanted c57bl/6 male mice with an ipsilateral bipolar electrode into the OT to administer electric current and thereby yield gross activation of the OT. We confirmed that electrical stimulation of the OT was rewarding, with mice frequently self-administering stimulation on a fixed ratio schedule. In a separate experiment, mice were presented with either fox urine or peanut odors in a three-chamber preference test. In absence of OT stimulation, significant preference for the peanut odor chamber was observed which was abolished in the presence of OT stimulation. Perhaps providing a foundation for this modulation in behavior, we found that OT stimulation significantly increased the number of c-Fos positive neurons in not only the OT, but also in forebrain structures essential to motivated behaviors, including the nucleus accumbens and lateral septum. The present results support the notion that the OT is integral to the display of motivated behavior and possesses the capacity to modulate odor hedonics either by directly altering odor processing or perhaps by indirect actions on brain reward and motivation structures.

  17. Tissue heterogeneity as a mechanism for localized neural stimulation by applied electric fields

    International Nuclear Information System (INIS)

    Miranda, P C; Correia, L; Salvador, R; Basser, P J

    2007-01-01

    We investigate the heterogeneity of electrical conductivity as a new mechanism to stimulate excitable tissues via applied electric fields. In particular, we show that stimulation of axons crossing internal boundaries can occur at boundaries where the electric conductivity of the volume conductor changes abruptly. The effectiveness of this and other stimulation mechanisms was compared by means of models and computer simulations in the context of transcranial magnetic stimulation. While, for a given stimulation intensity, the largest membrane depolarization occurred where an axon terminates or bends sharply in a high electric field region, a slightly smaller membrane depolarization, still sufficient to generate action potentials, also occurred at an internal boundary where the conductivity jumped from 0.143 S m -1 to 0.333 S m -1 , simulating a white-matter-grey-matter interface. Tissue heterogeneity can also give rise to local electric field gradients that are considerably stronger and more focal than those impressed by the stimulation coil and that can affect the membrane potential, albeit to a lesser extent than the two mechanisms mentioned above. Tissue heterogeneity may play an important role in electric and magnetic 'far-field' stimulation

  18. Tissue heterogeneity as a mechanism for localized neural stimulation by applied electric fields

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, P C [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Correia, L [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Salvador, R [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Basser, P J [Section on Tissue Biophysics and Biomimetics, NICHD, National Institutes of Health, Bethesda, MD 20892-1428 (United States)

    2007-09-21

    We investigate the heterogeneity of electrical conductivity as a new mechanism to stimulate excitable tissues via applied electric fields. In particular, we show that stimulation of axons crossing internal boundaries can occur at boundaries where the electric conductivity of the volume conductor changes abruptly. The effectiveness of this and other stimulation mechanisms was compared by means of models and computer simulations in the context of transcranial magnetic stimulation. While, for a given stimulation intensity, the largest membrane depolarization occurred where an axon terminates or bends sharply in a high electric field region, a slightly smaller membrane depolarization, still sufficient to generate action potentials, also occurred at an internal boundary where the conductivity jumped from 0.143 S m{sup -1} to 0.333 S m{sup -1}, simulating a white-matter-grey-matter interface. Tissue heterogeneity can also give rise to local electric field gradients that are considerably stronger and more focal than those impressed by the stimulation coil and that can affect the membrane potential, albeit to a lesser extent than the two mechanisms mentioned above. Tissue heterogeneity may play an important role in electric and magnetic 'far-field' stimulation.

  19. Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

    Science.gov (United States)

    Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

    2015-02-01

    Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    Directory of Open Access Journals (Sweden)

    Richard A Lasher

    2012-12-01

    Full Text Available Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06 but less than half of the native postnatal day 12 (0.90 ± 0.06 and adult (0.91 ± 0.04 myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal

  1. Charge and energy minimization in electrical/magnetic stimulation of nervous tissue.

    Science.gov (United States)

    Jezernik, Saso; Sinkjaer, Thomas; Morari, Manfred

    2010-08-01

    In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

  2. A hybrid stimulation strategy for suppression of spiral waves in cardiac tissue

    Energy Technology Data Exchange (ETDEWEB)

    Xu Binbin, E-mail: xubinbin@hotmail.fr [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France); Jacquir, Sabir, E-mail: sjacquir@u-bourgogne.fr [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France); Laurent, Gabriel; Bilbault, Jean-Marie [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France); Binczak, Stephane, E-mail: stbinc@u-bourgogne.fr [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France)

    2011-08-15

    Highlights: > Simulation of a cardiac tissue by a modified 2D FitzHugh-Nagumo model. > Stimulation of monophasic impulsions from a grid of electrodes to the cardiac tissue. > Propose a method by modifying the tissue's sodium channels and electrical stimulation. > The method leading to suppress spiral waves without generating new ones. > Optimal parameters of a successful suppression of spiral waves are investigated. - Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia whose mechanisms are thought to be mainly due to the self perpetuation of spiral waves (SW). To date, available treatment strategies (antiarrhythmic drugs, radiofrequency ablation of the substrate, electrical cardioversion) to restore and to maintain a normal sinus rhythm have limitations and are associated with AF recurrences. The aim of this study was to assess a way of suppressing SW by applying multifocal electrical stimulations in a simulated cardiac tissue using a 2D FitzHugh-Nagumo model specially convenient for AF investigations. We identified stimulation parameters for successful termination of SW. However, SW reinduction, following the electrical stimuli, leads us to develop a hybrid strategy based on sodium channel modification for the simulated tissue.

  3. Altered frontocingulate activation during aversive interoceptive processing in young adults transitioning to problem stimulant use

    Directory of Open Access Journals (Sweden)

    Jennifer Lorraine Stewart

    2013-11-01

    Full Text Available Problems associated with stimulant use have been linked to frontocingulate, insular, and thalamic dysfunction during decision-making and alterations in interoceptive processing. However, little is known about how interoception and decision-making interact and contribute to dysfunctions that promote the transition from recreational drug use to abuse or dependence. Here, we investigate brain activation in response to reward, punishment, and uncertainty during an aversive interoceptive challenge in current and former stimulant (cocaine and amphetamine users using functional magnetic resonance imaging (fMRI. Young adults previously identified as recreational users (n=184 were followed up three years later. Of these, 18 individuals progressed to problem stimulant use (PSU, whereas 15 desisted stimulant use (DSU. PSU, DSU, and 14 healthy comparison subjects (CTL performed a two-choice prediction task at three fixed error rates (20%=reward, 50%=uncertainty, 80%=punishment during which they anticipated and experienced episodes of inspiratory breathing load. Although groups did not differ in insula activation or subjective breathing load ratings, PSU exhibited lower right inferior frontal gyrus (IFG and bilateral anterior cingulate (ACC activation than DSU and CTL during aversive interoceptive processing as well as lower right IFG in response to decision making involving uncertainty. However, PSU exhibited greater bilateral IFG activation than DSU and CTL while making choices within the context of punishing feedback, and both PSU and DSU showed lower thalamic activation during breathing load than CTL. Findings suggest that frontocingulate attenuation, reflecting reduced resources devoted to goal maintenance and action selection in the presence of uncertainty and interoceptive perturbations, may be a biomarker for susceptibility to problem stimulant use.

  4. Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

    Science.gov (United States)

    Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

    2009-01-01

    This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

  5. Oral supplementation of Bifidobacterium longum strain BR-108 alters cecal microbiota by stimulating gut immune system in mice irrespectively of viability.

    Science.gov (United States)

    Makioka, Yuko; Tsukahara, Takamitsu; Ijichi, Tetsuo; Inoue, Ryo

    2018-03-20

    Effect on cecal microbiota and gene expression of various cytokines in ileal Peyer's patches and cecal tissues were compared between viable and heat-killed Bifidobacterium longum strain BR-108 (BR-108) using a mouse model. Irrespectively of viability, oral supplementation of BR-108 altered the cecal microbiota and stimulated gene expression of cytokines such as IL-6 and IL-10 in ileal Peyer's patches and cecal tissue of mice. In addition, BR-108 supplementation significantly affected the relative abundance of bacterial genera and family, Oscillospira, Bacteroides and S24-7. The abundance of these bacterial genera and family strongly correlated with gene expression induced by BR-108. This study demonstrated that the effect of heat-killed BR-108 on the mouse cecal microbiota is similar to that of viable BR-108, most likely due to stimulation of the gut immune system by both heat-killed and viable BR-108 is also similar.

  6. Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat.

    Directory of Open Access Journals (Sweden)

    Bertrand Degos

    Full Text Available Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.

  7. Co-culture with infrapatellar fat pad differentially stimulates proteoglycan synthesis and accumulation in cartilage and meniscus tissues.

    Science.gov (United States)

    Nishimuta, James F; Bendernagel, Monica F; Levenston, Marc E

    2017-09-01

    Although osteoarthritis is widely viewed as a disease of the whole joint, relatively few studies have focused on interactions among joint tissues in joint homeostasis and degeneration. In particular, few studies have examined the effects of the infrapatellar fat pad (IFP) on cartilaginous tissues. The aim of this study was to test the hypothesis that co-culture with healthy IFP would induce degradation of cartilage and meniscus tissues. Bovine articular cartilage, meniscus, and IFP were cultured isolated or as cartilage-fat or meniscus-fat co-cultures for up to 14 days. Conditioned media were assayed for sulfated glycosaminoglycan (sGAG) content, nitrite content, and matrix metalloproteinase (MMP) activity, and explants were assayed for sGAG and DNA contents. Co-cultures exhibited increased cumulative sGAG release and sGAG release rates for both cartilage and meniscus, and the cartilage (but not meniscus) exhibited a substantial synergistic effect of co-culture (sGAG release in co-culture was significantly greater than the summed release from isolated cartilage and fat). Fat co-culture did not significantly alter the sGAG content of either cartilage or meniscus explants, indicating that IFP co-culture stimulated net sGAG production by cartilage. Nitrite release was increased relative to isolated tissue controls in co-cultured meniscus, but not the cartilage, with no synergistic effect of co-culture. Interestingly, MMP-2 production was decreased by co-culture for both cartilage and meniscus. This study demonstrates that healthy IFP may modulate joint homeostasis by stimulating sGAG production in cartilage. Counter to our hypothesis, healthy IFP did not promote degradation of either cartilage or meniscus tissues.

  8. The duration of gonadotropin stimulation does not alter the clinical pregnancy rate in IVF or ICSI cycles.

    Science.gov (United States)

    Purandare, N; Emerson, G; Kirkham, C; Harrity, C; Walsh, D; Mocanu, E

    2017-08-01

    Ovarian stimulation is an essential part of assisted reproduction treatments. Research on whether the duration of stimulation alters the success in assisted reproduction has not been conclusive. The purpose of the study was to establish whether the duration of ovarian stimulation alters the success in assisted reproduction treatments. All fresh (non-donor) stimulation cycles performed in an academic tertiary referral ART centre over a period of 18 years, between 1st January 1997 and 31st December 2014, were identified. Data were prospectively and electronically collected. IVF and ICSI cycles were analysed independently. Each category was then subdivided into assisted reproduction cycles where the antagonist, long (down regulation) and flare protocol were used. Clinical pregnancy was the main outcome measured. A total of 10,478 stimulation cycles (6011 fresh IVF and 4467 fresh ICSI) reaching egg collection were included. We showed no significant difference in CP rates in IVF cycles for the long (p = 0.082), antagonist (p = 0.217) or flare (p = 0.741) protocol cycles or in ICSI cycles with the long (p = 0.223), antagonist (p = 0.766) or the flare (p = 0.690) protocol with regards the duration of stimulation. The duration of stimulation does not alter the CP rate in ICSI or IVF cycles using the long, antagonist or flare stimulation protocol.

  9. Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

    Science.gov (United States)

    Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

    2017-01-01

    Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Effect of training on epinephrine-stimulated lipolysis determined by microdialysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, B; Simonsen, L; Bülow, J

    1995-01-01

    glycerol concentrations (Tr: 129 +/- 36 microM; Sed: 119 +/- 56) did not differ between groups. It is concluded that in intact subcutaneous adipose tissue epinephrine-stimulated blood flow is enhanced, whereas lipolytic sensitivity to epinephrine is the same in trained compared with untrained subjects.......Trained humans (Tr) have a higher fat oxidation during submaximal physical work than sedentary humans (Sed). To investigate whether this reflects a higher adipose tissue lipolytic sensitivity to catecholamines, we infused epinephrine (0.3 nmol.kg-1.min-1) for 65 min in six athletes and six...... sedentary young men. Glycerol was measured in arterial blood, and intercellular glycerol concentrations in abdominal subcutaneous adipose tissue were measured by microdialysis. Adipose tissue blood flow was measured by 133Xe-washout technique. From these measurements adipose tissue lipolysis was calculated...

  11. Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism.

    Science.gov (United States)

    Jansen, S W; Akintola, A A; Roelfsema, F; van der Spoel, E; Cobbaert, C M; Ballieux, B E; Egri, P; Kvarta-Papp, Z; Gereben, B; Fekete, C; Slagboom, P E; van der Grond, J; Demeneix, B A; Pijl, H; Westendorp, R G J; van Heemst, D

    2015-06-19

    Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.

  12. Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

    Science.gov (United States)

    Wang, Bo; Wang, Guangjun; To, Filip; Butler, J Ryan; Claude, Andrew; McLaughlin, Ronald M; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

    2013-09-03

    Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.

  13. Long-duration transcutaneous electric acupoint stimulation alters small-world brain functional networks.

    Science.gov (United States)

    Zhang, Yue; Jiang, Yin; Glielmi, Christopher B; Li, Longchuan; Hu, Xiaoping; Wang, Xiaoying; Han, Jisheng; Zhang, Jue; Cui, Cailian; Fang, Jing

    2013-09-01

    Acupuncture, which is recognized as an alternative and complementary treatment in Western medicine, has long shown efficiencies in chronic pain relief, drug addiction treatment, stroke rehabilitation and other clinical practices. The neural mechanism underlying acupuncture, however, is still unclear. Many studies have focused on the sustained effects of acupuncture on healthy subjects, yet there are very few on the topological organization of functional networks in the whole brain in response to long-duration acupuncture (longer than 20 min). This paper presents a novel study on the effects of long-duration transcutaneous electric acupoint stimulation (TEAS) on the small-world properties of brain functional networks. Functional magnetic resonance imaging was used to construct brain functional networks of 18 healthy subjects (9 males and 9 females) during the resting state. All subjects received both TEAS and minimal TEAS (MTEAS) and were scanned before and after each stimulation. An altered functional network was found with lower local efficiency and no significant change in global efficiency for healthy subjects after TEAS, while no significant difference was observed after MTEAS. The experiments also showed that the nodal efficiencies in several paralimbic/limbic regions were altered by TEAS, and those in middle frontal gyrus and other regions by MTEAS. To remove the psychological effects and the baseline, we compared the difference between diffTEAS (difference between after and before TEAS) and diffMTEAS (difference between after and before MTEAS). The results showed that the local efficiency was decreased and that the nodal efficiencies in frontal gyrus, orbitofrontal cortex, anterior cingulate gyrus and hippocampus gyrus were changed. Based on those observations, we conclude that long-duration TEAS may modulate the short-range connections of brain functional networks and also the limbic system. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties.

    Science.gov (United States)

    Salinas, Evelia Y; Hu, Jerry C; Athanasiou, Kyriacos

    2018-04-26

    The use of tissue-engineered articular cartilage (TEAC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in vivo use are yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC. This review focuses on the use of mechanical stimulation to attain and enhance the properties of AC constructs needed to translate these implants to the clinic. In vivo, mechanical loading at maximal and supramaximal physiological levels has been shown to be detrimental to AC through the development of degenerative changes. In contrast, multiple studies have revealed that during culture, mechanical stimulation within narrow ranges of magnitude and duration can produce anisotropic, mechanically robust AC constructs with high cellular viability. Significant progress has been made in evaluating a variety of mechanical stimulation techniques on TEAC, either alone or in combination with other stimuli. These advancements include determining and optimizing efficacious loading parameters (e.g., duration and frequency) to yield improvements in construct design criteria, such as collagen II content, compressive stiffness, cell viability, and fiber organization. With the advancement of mechanical stimulation as a potent strategy in AC tissue engineering, a compendium detailing the results achievable by various stimulus regimens would be of great use for researchers in academia and industry. The objective is to list the qualitative and quantitative effects that can be attained when direct compression, hydrostatic pressure, shear, and tensile

  15. Novel systems for the application of isolated tensile, compressive, and shearing stimulation of distraction callus tissue.

    Directory of Open Access Journals (Sweden)

    Nicholaus Meyers

    Full Text Available Distraction osteogenesis is a procedure widely used for the correction of large bone defects. However, a high complication rate persists, likely due to insufficient stability during maturation. Numerical fracture healing models predict bone regeneration under different mechanical conditions allowing fixation stiffness optimization. However, most models apply a linear elastic material law inappropriate for the transient stresses/strains present during limb lengthening or segment transport. They are also often validated using in vivo osteotomy models lacking precise mechanical regulation due to the unavoidable stimulation of secondary interfragmentary motion during ambulation under finitely stiff fixation. Therefore, in order to create a robust numerical model of distraction osteogenesis, it is necessary to both characterize the new tissue's viscoelasticity during distraction and determine the influence of strictly isolated stimulation in each loading mode (tension, compression, and shear to account for potential differences in mechanical and histological response.Two electromechanical fixators with integrated load cells were designed to precisely perform and monitor in vivo lateral distraction and isolated stimulation in sheep tibiae using a mobile, hydroxyapatite-coated titanium plate. The novel surgical procedure circumvents osteotomy, eliminating the undesirable and unquantifiable mechanical stimulation during ambulation.After a 10-day post-surgery latency period, two 0.275 mm distraction steps were performed daily for 10 days. The load cell collected data before, during, and after each distraction step and was terminated after no less than one minute from the time of distraction. A 7-day consolidation period separated the distraction phase and 18-day stimulation phase. Stimulation was carried out in isolated tension, compression, or shear while recording force/time data. Each stimulation session consisted of 120 cycles with a magnitude of

  16. Neuropathic Pain Medication Use Does Not Alter Outcomes of Spinal Cord Stimulation for Lower Extremity Pain.

    Science.gov (United States)

    Maher, Dermot P; Martins, Yuri Chaves; Doshi, Tina; Bicket, Mark; Zhang, Kui; Hanna, George; Ahmed, Shihab

    2018-01-01

    Spinal cord stimulation (SCS) for the treatment of lower extremity pain is believed to the result of increased activity in the descending inhibitory and decreased activity in the ascending excitatory tracts. Evidence suggests that the analgesia afforded by SCS may be altered using certain neuropathic pain medications that also modulate neurotransmitters in these sensory tracts. We hypothesize that neuropathic pain medications may alter the response to SCS therapy. One hundred and fifteen subjects undergoing SCS therapy for lower extremity pain were retrospectively examined. The pharmacologic profile, including stable use of neuropathic and opioid medications, were recorded. Three separate logistic regression models examined the odds ratio of primary outcomes; a successful SCS trial, a 50% decrease in pain or a 50% reduction in opioid use one year after implant. Neither the use of opioids or neuropathic pain medications were associated with changes in the odds of a successful SCS trial or a 50% pain reduction. A higher dose of chronic opioids use prior to a trial was associated with greater odds of having a 50% reduction in opioid use following implant. OR 1.02, 95% CI 1.01-1.02, p-value neuropathic pain medications did not change the odds of either a successful SCS trial, or of experiencing a 50% reduction in pain at one year. The association between higher opioid doses and greater odds of a 50% reduction in opioid use may be the reflective of SCS's ability to reduce opioid reliance in chronic pain patients. © 2017 International Neuromodulation Society.

  17. Cryopreservation of testicular tissue before long-term testicular cell culture does not alter in vitro cell dynamics

    NARCIS (Netherlands)

    Baert, Yoni; Braye, Aude; Struijk, Robin B.; van Pelt, Ans M. M.; Goossens, Ellen

    2015-01-01

    To assess whether testicular cell dynamics are altered during long-term culture after testicular tissue cryopreservation. Experimental basic science study. Reproductive biology laboratory. Testicular tissue with normal spermatogenesis was obtained from six donors. None. Detection and comparison of

  18. Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats.

    Science.gov (United States)

    Huang, Rong; Xue, Xinli; Li, Shengxian; Wang, Yuying; Sun, Yun; Liu, Wei; Yin, Huiyong; Tao, Tao

    2018-03-30

    The metabolism of polyunsaturated fatty acids (PUFAs) remains poorly characterized in ovarian tissues of patients with polycystic ovary syndrome (PCOS). This study aimed to explore alterations in the levels of PUFAs and their metabolites in serum and ovarian tissues in a PCOS rat model treated with a high-fat diet and andronate. Levels of PUFAs and their metabolites were measured using gas/liquid chromatography-mass spectrometry after the establishment of a PCOS rat model. Only 3 kinds of PUFAs [linoleic acid, arachidonic acid (AA) and docosahexaenoic acid] were detected in both the circulation and ovarian tissues of the rats, and their concentrations were lower in ovarian tissues than in serum. Moreover, significant differences in the ovarian levels of AA were observed between control, high-fat diet-fed and PCOS rats. The levels of prostaglandins, AA metabolites via the cyclooxygenase (COX) pathway, in ovarian tissues of the PCOS group were significantly increased compared to those in the controls. Further studies on the mechanism underlying this phenomenon showed a correlation between decreased expression of phosphorylated cytosolic phospholipase A2 (p-cPLA2) and increased mRNA and protein expression of COX2, potentially leading to a deeper understanding of altered AA and prostaglandin levels in ovarian tissues of PCOS rats. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  19. Maternal tissue is involved in stimulant reception by seeds of the parasitic plant Orobanche.

    Science.gov (United States)

    Plakhine, Dina; Tadmor, Yaakov; Ziadne, Hammam; Joel, Daniel M

    2012-04-01

    A fundamental element in the evolution of obligate root-parasitic angiosperms is their ability to germinate only in response to chemical stimulation by roots, to ensure contact with a nearby nourishing host. The aim of this study was to explore inheritance of the unique germination control in this group of plants. Analysis was made of the segregation of spontaneous (non-induced) germination that appeared in hybrid progenies derived from crosses between Orobanche cernua and O. cumana, which, like all other Orobanche species, are totally dependent on chemical stimulation for the onset of germination, and show negligible spontaneous germination in their natural seed populations. F(1) and F(2) seeds did not germinate in the absence of chemical stimulation, but significant spontaneous germination was found in some F(3) seed families. This indicates that the prevention of non-induced germination in Orobanche seeds, i.e. dependence on an external chemical stimulation for seed germination, is genetically controlled, that this genetic control is expressed in a seed tissue with maternal origin (presumably the perisperm that originates from the nucellus) and that genetic variation for this trait exists in Orobanche species. Similar segregation results were obtained in reciprocal crosses, suggesting that stimulated germination is controlled by nuclear genes.

  20. Fiber-based tissue identification for electrode placement in deep brain stimulation neurosurgery (Conference Presentation)

    Science.gov (United States)

    DePaoli, Damon T.; Lapointe, Nicolas; Goetz, Laurent; Parent, Martin; Prudhomme, Michel; Cantin, Léo.; Galstian, Tigran; Messaddeq, Younès.; Côté, Daniel C.

    2016-03-01

    Deep brain stimulation's effectiveness relies on the ability of the stimulating electrode to be properly placed within a specific target area of the brain. Optical guidance techniques that can increase the accuracy of the procedure, without causing any additional harm, are therefore of great interest. We have designed a cheap optical fiber-based device that is small enough to be placed within commercially available DBS stimulating electrodes' hollow cores and that is capable of sensing biological information from the surrounding tissue, using low power white light. With this probe we have shown the ability to distinguish white and grey matter as well as blood vessels, in vitro, in human brain samples and in vivo, in rats. We have also repeated the in vitro procedure with the probe inserted in a DBS stimulating electrode and found the results were in good agreement. We are currently validating a second fiber optic device, with micro-optical components, that will result in label free, molecular level sensing capabilities, using CARS spectroscopy. The final objective will be to use this data in real time, during deep brain stimulation neurosurgery, to increase the safety and accuracy of the procedure.

  1. Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner

    Science.gov (United States)

    Forney, Laura A.; Lenard, Natalie R.; Stewart, Laura K.

    2018-01-01

    Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE) containing quercetin on subcutaneous (inguinal, IWAT) vs. visceral (epididymal, EWAT) white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 μg/day quercetin or high fat plus ROE containing 50 μg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms. PMID:29562620

  2. Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner

    Directory of Open Access Journals (Sweden)

    Laura A. Forney

    2018-03-01

    Full Text Available Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE containing quercetin on subcutaneous (inguinal, IWAT vs. visceral (epididymal, EWAT white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 μg/day quercetin or high fat plus ROE containing 50 μg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms.

  3. Effect of training on epinephrine-stimulated lipolysis determined by microdialysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, Bente; Simonsen, L; Bülow, J

    1995-01-01

    Trained humans (Tr) have a higher fat oxidation during submaximal physical work than sedentary humans (Sed). To investigate whether this reflects a higher adipose tissue lipolytic sensitivity to catecholamines, we infused epinephrine (0.3 nmol.kg-1.min-1) for 65 min in six athletes and six....... During epinephrine infusion intercellular glycerol concentrations were lower, but adipose tissue blood flow was higher in trained compared with sedentary subjects (P ... glycerol concentrations (Tr: 129 +/- 36 microM; Sed: 119 +/- 56) did not differ between groups. It is concluded that in intact subcutaneous adipose tissue epinephrine-stimulated blood flow is enhanced, whereas lipolytic sensitivity to epinephrine is the same in trained compared with untrained subjects....

  4. Structure and component alteration of rabbit Achilles tendon in tissue culture.

    Science.gov (United States)

    Hosaka, Yoshinao; Ueda, Hiromi; Yamasaki, Tadatsugu; Suzuki, Daisuke; Matsuda, Naoya; Takehana, Kazushige

    2005-12-01

    The aim of this study was to investigate alterations of cultured tendon tissues to determine whether tissue culture is a useful method for biological analyses of the tendon. Tendon tissues for tissue culture were isolated from Achilles tendons of rabbits. The tendon segments were placed one segment per well and incubated in growth medium consisting of Dullbecco's modified Eagle's medium supplemented with 5% fetal bovine serum at 37 degrees C in a humidified atmosphere with 5% CO(2) for various periods. The alignment of collagen fibrils was preserved for 48 h, but tendon structure has disintegrated at 96 h. Alcian blue staining and gelatine zymography revealed that proteoglycan markedly diminished and that matrix metalloproteinase (MMPs) activity was upregulated sharply at 72 and 96 h. The ratio of collagen fibrils with large diameter had increased and the mean diameter and mass average diameter value had reached maximum at 48 h. The values then decreased and mean diameters at 72 and 96 h were significantly different from that at 48 h. At 96 h, the ratio of collagen fibrils with small diameters had increased and collagen fibrils with large diameters had disappeared. These findings indicate that structural alteration is possible to be induced by disintegration of collagen fibrils and disappearance of glycosaminoglycans from extracellular matrix (ECM), subsequent of upregulation of MMPs activity. Although the study period is limited, the tissue culture method is available for investigating cell-ECM interaction in tendons.

  5. Omega-6 Fat Supplementation Alters Lipogenic Gene Expression in Bovine Subcutaneous Adipose Tissue

    OpenAIRE

    Joseph, Sandeep J.; Pratt, Scott L.; Pavan, Enrique; Rekaya, Romdhane; Duckett., Susan K.

    2010-01-01

    In contrast to rodents, adipose tissue serves as the major site of lipogenesis and storage reservoir for excess dietary energy in cattle. Research in rodents shows that adding corn oil (57% C18:2 n-6) to the diet alters lipogenesis enhancing deposition of omega-6 fatty acids. This study examines changes in lipogenic gene expression of subcutaneous adipose tissue from eighteen steers fed increasing levels of dietary corn oil [0 (NONE), 0.31 kg/d (MED) and 0.62 kg/d (HI)] using two platforms, q...

  6. Improved Selectivity From a Wavelength Addressable Device for Wireless Stimulation of Neural Tissue

    Directory of Open Access Journals (Sweden)

    Elif Ç. Seymour

    2014-02-01

    Full Text Available Electrical neural stimulation with micro electrodes is a promising technique for restoring lost functions in the central nervous system as a result of injury or disease. One of the problems related to current neural stimulators is the tissue response due to the connecting wires and the presence of a rigid electrode inside soft neural tissue. We have developed a novel, optically activated, microscale photovoltaic neurostimulator based on a custom layered compound semiconductor heterostructure that is both wireless and has a comparatively small volume. Optical activation provides a wireless means of energy transfer to the neurostimulator, eliminating wires and the associated complications. This neurostimulator was shown to evoke action potentials and a functional motor response in the rat spinal cord. In this work, we extend our design to include wavelength selectivity and thus allowing independent activation of devices. As a proof of concept, we fabricated two different microscale devices with different spectral responsivities in the near-infrared region. We assessed the improved addressability of individual devices via wavelength selectivity as compared to spatial selectivity alone through on-bench optical measurements of the devices in combination with an in vivo light intensity profile in the rat cortex obtained in a previous study. We show that wavelength selectivity improves the individual addressability of the floating stimulators, thus increasing the number of devices that can be implanted in close proximity to each other.

  7. Insulin signaling in various equine tissues under basal conditions and acute stimulation by intravenously injected insulin.

    Science.gov (United States)

    Warnken, Tobias; Brehm, Ralph; Feige, Karsten; Huber, Korinna

    2017-10-01

    The aim of the study was to analyze key proteins of the equine insulin signaling cascade and their extent of phosphorylation in biopsies from muscle tissue (MT), liver tissue (LT), and nuchal AT, subcutaneous AT, and retroperitoneal adipose tissues. This was investigated under unstimulated (B1) and intravenously insulin stimulated (B2) conditions, which were achieved by injection of insulin (0.1 IU/kg bodyweight) and glucose (150 mg/kg bodyweight). Twelve warmblood horses aged 15 ± 6.8 yr (yr), weighing 559 ± 79 kg, and with a mean body condition score of 4.7 ± 1.5 were included in the study. Key proteins of the insulin signaling cascade were semiquantitatively determined using Western blotting. Furthermore, modulation of the cascade was assessed. The basal expression of the proteins was only slightly influenced during the experimental period. Insulin induced a high extent of phosphorylation of insulin receptor in LT (P < 0.01) but not in MT. Protein kinase B and mechanistic target of rapamycin expressed a higher extent of phosphorylation in all tissues in B2 biopsies. Adenosine monophosphate protein kinase, as a component related to insulin signaling, expressed enhanced phosphorylation in MT (P < 0.05) and adipose tissues (nuchal AT P < 0.05; SCAT P < 0.01; retroperitoneal adipose tissue P < 0.05), but not in LT at B2. Tissue-specific variations in the acute response of insulin signaling to intravenously injected insulin were observed. In conclusion, insulin sensitivity in healthy horses is based on a complex concerted action of different tissues by their variations in the molecular response to insulin. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Autologous Cartilage Chip Transplantation Improves Repair Tissue Composition Compared With Marrow Stimulation.

    Science.gov (United States)

    Christensen, Bjørn Borsøe; Olesen, Morten Lykke; Lind, Martin; Foldager, Casper Bindzus

    2017-06-01

    Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Controlled laboratory study. Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P cartilage repair tissue compared with MST at 6 months postoperatively. Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

  9. Esthetic outcome and alterations of soft tissue around single implant crowns: a 2-year prospective study.

    Science.gov (United States)

    Gu, Ying-Xin; Shi, Jun-Yu; Zhuang, Long-Fei; Qiao, Shi-Chong; Xu, You-You; Lai, Hong-Chang

    2015-08-01

    The aim of this prospective study was to assess the esthetic outcome and alterations of peri-implant soft tissue using tissue-level implants. Furthermore, the influencing factors, including grafting and gingival biotype, of esthetic outcome of peri-implant soft tissue were also evaluated. Of 38 patients with single missing anterior tooth in maxilla were treated with a Straumann (®) Standard Plus SLA implant. Bone augmentation was performed in 24 patients. Follow-up was conducted at 12 and 24 months after definitive crowns placement. Esthetic outcome using the pink esthetic score/white esthetic score (PES/WES) and clinical parameters were evaluated. The mean PES/WES value at baseline, 1-year, and 2-year examination was 13.79, 14.87, and 14.96. Significant improvement was found between baseline and 1-year examination (P esthetic area. Favorable short-term esthetic outcome and stability of soft tissue around single implant crowns can be expected in patients with or without graft. However, graft procedures might have an unfavorable effect on the esthetic outcome. Gingival biotype can be considered as prognostic factor for esthetic outcome. RCTs with long-term follow-up are needed to provide evidence for the long-term stability of peri-implant soft tissue using tissue-level implant systems. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Low-intensity infrared lasers alter actin gene expression in skin and muscle tissue

    International Nuclear Information System (INIS)

    Fonseca, A S; Mencalha, A L; Campos, V M A; Ferreira-Machado, S C; Peregrino, A A F; Magalhães, L A G; Geller, M; Paoli, F

    2013-01-01

    The biostimulative effect of low-intensity lasers is the basis for treatment of diseases in soft tissues. However, data about the influence of biostimulative lasers on gene expression are still scarce. The aim of this work was to evaluate the effects of low-intensity infrared lasers on the expression of actin mRNA in skin and muscle tissue. Skin and muscle tissue of Wistar rats was exposed to low-intensity infrared laser radiation at different fluences and frequencies. One and 24 hours after laser exposure, tissue samples were withdrawn for total RNA extraction, cDNA synthesis and evaluation of actin gene expression by quantitative polymerase chain reaction. The data obtained show that laser radiation alters the expression of actin mRNA differently in skin and muscle tissue of Wistar rats depending of the fluence, frequency and time after exposure. The results could be useful for laser dosimetry, as well as to justify the therapeutic protocols for treatment of diseases of skin and muscle tissues based on low-intensity infrared laser radiation. (paper)

  11. Amount of prenatal visual stimulation alters incubation times and postnatal preferences in leopard geckos (Eublepharis macularius).

    Science.gov (United States)

    Sleigh, M J; Birchard, G F

    2001-09-01

    The authors exposed gecko (Eublepharis macularius) embryos to patterned visual stimulation beginning at either 1 week or 2 weeks prior to hatching. Embryos exposed to the substantially augmented amount of prenatal visual stimulation hatched significantly earlier than the embryos either exposed to the moderately augmented prenatal visual stimulation or not exposed to any prenatal visual stimulation (p geckos in all conditions failed to exhibit a preference for either stimulus.

  12. Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients

    Directory of Open Access Journals (Sweden)

    Verde Roberta

    2010-04-01

    Full Text Available Abstract Background The endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT of subjects with both obesity and type 2 diabetes (OBT2D, characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB. Design and Methods The levels of anandamide and 2-AG, and of the anandamide-related PPARα ligands, oleoylethanolamide (OEA and palmitoylethanolamide (PEA, in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp. Results As compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p Conclusions The observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners and 2-AG in obesity and type 2 diabetes.

  13. Contactless remote induction of shear waves in soft tissues using a transcranial magnetic stimulation device

    International Nuclear Information System (INIS)

    Grasland-Mongrain, Pol; Miller-Jolicoeur, Erika; Cloutier, Guy; Tang, An; Catheline, Stefan

    2016-01-01

    This study presents the first observation of shear waves induced remotely within soft tissues. It was performed through the combination of a transcranial magnetic stimulation device and a permanent magnet. A physical model based on Maxwell and Navier equations was developed. Experiments were performed on a cryogel phantom and a chicken breast sample. Using an ultrafast ultrasound scanner, shear waves of respective amplitudes of 5 and 0.5 μm were observed. Experimental and numerical results were in good agreement. This study constitutes the framework of an alternative shear wave elastography method. (paper)

  14. Contactless remote induction of shear waves in soft tissues using a transcranial magnetic stimulation device

    Science.gov (United States)

    Grasland-Mongrain, Pol; Miller-Jolicoeur, Erika; Tang, An; Catheline, Stefan; Cloutier, Guy

    2016-03-01

    This study presents the first observation of shear waves induced remotely within soft tissues. It was performed through the combination of a transcranial magnetic stimulation device and a permanent magnet. A physical model based on Maxwell and Navier equations was developed. Experiments were performed on a cryogel phantom and a chicken breast sample. Using an ultrafast ultrasound scanner, shear waves of respective amplitudes of 5 and 0.5 μm were observed. Experimental and numerical results were in good agreement. This study constitutes the framework of an alternative shear wave elastography method.

  15. Diet-induced obesity alters protein synthesis: Tissue-specific effects in fasted vs. fed mice

    OpenAIRE

    Anderson, Stephanie R.; Gilge, Danielle A.; Steiber, Alison L.; Previs, Stephen F.

    2008-01-01

    The influence of obesity on protein dynamics is not clearly understood. We have designed experiments to test the hypothesis that obesity impairs the stimulation of tissue-specific protein synthesis following nutrient ingestion. C57BL/6J mice were randomized into two groups: group 1 (control, n = 16) were fed a low-fat, high-carbohydrate diet and group 2 (experimental, n = 16) were fed a high-fat, low-carbohydrate diet ad libitum for 9 weeks. On the experiment day, all mice were fasted for 6 h...

  16. Expanded polytetrafluoroethylene membrane alters tissue response to implanted Ahmed glaucoma valve.

    Science.gov (United States)

    DeCroos, Francis Char; Ahmad, Sameer; Kondo, Yuji; Chow, Jessica; Mordes, Daniel; Lee, Maria Regina; Asrani, Sanjay; Allingham, R Rand; Olbrich, Kevin C; Klitzman, Bruce

    2009-07-01

    Long-term intraocular pressure control by glaucoma drainage implants is compromised by the formation of an avascular fibrous capsule that surrounds the glaucoma implant and increases aqueous outflow resistance. It is possible to alter this fibrotic tissue reaction and produce a more vascularized and potentially more permeable capsule around implanted devices by enclosing them in a porous membrane. Ahmed glaucoma implants modified with an outer 5-microm pore size membrane (termed porous retrofitted implant with modified enclosure or PRIME-Ahmed) and unmodified glaucoma implants were implanted into paired rabbit eyes. After 6 weeks, the devices were explanted and subject to histological analysis. A tissue response containing minimal vascularization, negligible immune response, and a thick fibrous capsule surrounded the unmodified Ahmed glaucoma implant. In comparison, the tissue response around the PRIME-Ahmed demonstrated a thinner fibrous capsule (46.4 +/- 10.8 microm for PRIME-Ahmed versus 94.9 +/- 21.2 microm for control, p vascularized near the tissue-material interface. A prominent chronic inflammatory response was noted as well. Encapsulating the aqueous outflow pathway with a porous membrane produces a more vascular tissue response and thinner fibrous capsule compared with a standard glaucoma implant plate. Enhanced vascularity and a thinner fibrous capsule may reduce aqueous outflow resistance and improve long-term glaucoma implant performance.

  17. Total Thyroidectomy for Thyroid Cancer Followed by Thyroid Storm due to Thyrotropin Receptor Antibody Stimulation of Metastatic Thyroid Tissue

    DEFF Research Database (Denmark)

    Folkestad, Lars; Brandt, Frans; Brix, Thomas

    2017-01-01

    BACKGROUND: Graves disease (GD) is an autoimmune condition characterized by the presence of antibodies against the thyrotropin receptor (TRAB), which stimulate the thyroid gland to produce excess thyroid hormone. Theoretically, TRAB could stimulate highly differentiated thyroid cancer tissue and...... treatment continued until after the fourth RAI dose. Hypothyroidism did not occur until following the fifth RAI treatment. SUMMARY AND CONCLUSIONS: We present a patient initially diagnosed with thyrotoxicosis and subsequently with metastatic follicular variant of papillary thyroid cancer. It is suggested...... that TRAB stimulated the highly differentiated extrathyroidal metastatic thyroid tissue to produce excessive amounts of thyroid hormone, delayed diagnosis, and potential aggravation of the course of thyroid cancer....

  18. Altered distributions of bone tissue mineral and collagen properties in women with fragility fractures.

    Science.gov (United States)

    Wang, Zhen Xiang; Lloyd, Ashley A; Burket, Jayme C; Gourion-Arsiquaud, Samuel; Donnelly, Eve

    2016-03-01

    Heterogeneity of bone tissue properties is emerging as a potential indicator of altered bone quality in pathologic tissue. The objective of this study was to compare the distributions of tissue properties in women with and without histories of fragility fractures using Fourier transform infrared (FTIR) imaging. We extended a prior study that examined the relationship of the mean FTIR properties to fracture risk by analyzing in detail the widths and the tails of the distributions of FTIR properties in biopsies from fracture and non-fracture cohorts. The mineral and matrix properties of cortical and trabecular iliac crest tissue were compared in biopsies from women with a history of fragility fracture (+Fx; n=21, age: mean 54±SD 15y) and with no history of fragility fracture (-Fx; n=12, age: 57±5y). A subset of the patients included in the -Fx group were taking estrogen-plus-progestin hormone replacement therapy (HRT) (-Fx+HRT n=8, age: 58±5y) and were analyzed separately from patients with no history of HRT (-Fx-HRT n=4, age: 56±7y). When the FTIR parameter mean values were examined by treatment group, the trabecular tissue of -Fx-HRT patients had a lower mineral:matrix ratio (M:M) and collagen maturity (XLR) than that of -Fx+HRT patients (-22% M:M, -18% XLR) and +Fx patients (-17% M:M, -18% XLR). Across multiple FTIR parameters, tissue from the -Fx-HRT group had smaller low-tail (5th percentile) values than that from the -Fx+HRT or +Fx groups. In trabecular collagen maturity and crystallinity (XST), the -Fx-HRT group had smaller low-tail values than those in the -Fx+HRT group (-16% XLR, -5% XST) and the +Fx group (-17% XLR, -7% XST). The relatively low values of trabecular mineral:matrix ratio and collagen maturity and smaller low-tail values of collagen maturity and crystallinity observed in the -Fx-HRT group are characteristic of younger tissue. Taken together, our data suggest that the presence of newly formed tissue that includes small/imperfect crystals

  19. ''Normal'' tissues from humans exposed to radium contain an alteration in the c-mos locus

    International Nuclear Information System (INIS)

    Huberman, E.; Schlenker, R.A.; Hardwick, J.P.

    1989-01-01

    The structures of a number of human proto-oncogenes from persons with internal systemic exposure to radium were analyzed by restriction enzyme digestion and southern blotting of their DNA. Two extra c-mos Eco R1 restriction-fragment-length bands of 5.0 kb and 5.5 kb were found in tissue DNA from six of seven individuals. The extra c-mos bands were detected in DNA from many, but not all, of the tissues of the individuals exposed to radium. Our results suggest that the c-mos restriction-fragment-length alterations (RFLA) found in individuals exposed to radium were induced rather than inherited, are epigenetic in origin, and most likely result from changes in the methylation of bases surrounding the single exon of the c-mos proto-oncogene. 7 refs., 3 figs., 2 tabs

  20. Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue

    Directory of Open Access Journals (Sweden)

    N.M. Jadavji

    2015-06-01

    Full Text Available Methylenetetrahydrofolate reductase (MTHFR is an enzyme key regulator in folate metabolism. Deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAM. In the brain, SAM donates methyl groups to catechol-O-methyltransferase (COMT, which is involved in neurotransmitter analysis. Using the MTHFR-deficient mouse model the purpose of this study was to investigate levels of monoamine neurotransmitters and amino acid levels in brain tissue. MTHFR deficiency affected levels of both glutamate and γ-aminobutyric acid in within the cerebellum and hippocampus. Mthfr−/− mice had reduced levels of glutamate in the amygdala and γ-aminobutyric acid in the thalamus. The excitatory mechanisms of homocysteine through activation of the N-methyl-d-aspartate receptor in brain tissue might alter levels of glutamate and γ-aminobutyric acid.

  1. Introducing graph theory to track for neuroplastic alterations in the resting human brain: a transcranial direct current stimulation study.

    Science.gov (United States)

    Polanía, Rafael; Paulus, Walter; Antal, Andrea; Nitsche, Michael A

    2011-02-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function by functional connectivity and graph theoretical analysis of the BOLD fMRI spontaneous activity. fMRI resting-state datasets were acquired immediately before and after 10-min bipolar tDCS during rest, with the anode placed over the left primary motor cortex (M1) and the cathode over the contralateral frontopolar cortex. For each dataset, grey matter voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal connectivity degree and minimum path length maps were calculated and compared before and after tDCS. Nodal minimum path lengths significantly increased in the left somatomotor (SM1) cortex after anodal tDCS, which means that the number of direct functional connections from the left SM1 to topologically distant grey matter voxels significantly decreased. In contrast, functional coupling between premotor and superior parietal areas with the left SM1 significantly increased. Additionally, the nodal connectivity degree in the left posterior cingulate cortex (PCC) area as well as in the right dorsolateral prefrontal cortex (right DLPFC) significantly increased. In summary, we provide initial support that tDCS-induced neuroplastic alterations might be related to functional connectivity changes in the human brain. Additionally, we propose our approach as a powerful method to track for neuroplastic changes in the human brain. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Nishimoto, Sachiko; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Murata, Chie; Kim-Kaneyama, Joo-Ri; Sato, Fukiko; Bando, Masahiro; Yagi, Shusuke; Soeki, Takeshi; Hayashi, Tetsuya; Imoto, Issei; Sakaue, Hiroshi; Shimabukuro, Michio; Sata, Masataka

    2016-03-01

    Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9 (-/-) ) macrophages. Fat-fed Tlr9 (-/-) mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9 (-/-) mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography-determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.

  3. Expression of HIF-1{alpha} in irradiated tissue is altered by topical negative-pressure therapy

    Energy Technology Data Exchange (ETDEWEB)

    Grimm, A.; Stange, S.; Labanaris, A.; Horch, R.E. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Plastic and Hand Surgery; Dimmler, A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Pathology; Sauer, R.; Grabenbauer, G. [Erlangen-Nuernberg Univ. (Germany). Dept. of Radiation Oncology

    2007-03-15

    Background and Purpose: Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients. Material and Methods: With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1{alpha} (hypoxia-inducible factor-1{alpha}), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples. Results: In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1{alpha}-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples. Conclusion: This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1{alpha} expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1{alpha} concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation-induced tissue

  4. Expression of HIF-1α in irradiated tissue is altered by topical negative-pressure therapy

    International Nuclear Information System (INIS)

    Grimm, A.; Stange, S.; Labanaris, A.; Horch, R.E.; Dimmler, A.; Sauer, R.; Grabenbauer, G.

    2007-01-01

    Background and Purpose: Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients. Material and Methods: With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1α (hypoxia-inducible factor-1α), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples. Results: In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1α-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples. Conclusion: This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1α expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1α concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation-induced tissue injury, further investigations of HIF

  5. Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats

    Directory of Open Access Journals (Sweden)

    Yingli Lu

    2016-11-01

    Full Text Available Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n=10 each: control, sedentary hypoxic living for 1 to 4 weeks (SH1, SH2, SH3, and SH4, living and exercise training in normoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4, and living and exercise training in hypoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4. Epididymal adipose tissue expression levels of leptin and leptin receptor were determined. Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3-4 weeks resulted in lower Lee index (P<0.05 to P<0.01, and higher expression of leptin and leptin receptor (P<0.05 to P<0.01 in adipose tissue. Conclusion: In a rodent model of altitude training, living and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

  6. Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

    International Nuclear Information System (INIS)

    Ananthanarayanan, Vijayalakshmi; Deaton, Ryan J; Yang, Ximing J; Pins, Michael R; Gann, Peter H

    2006-01-01

    Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered 'near' and 'far', respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. 'Near' normal glands had higher Mcm-2 indices compared to 'far' glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend

  7. Tissue culture-induced genetic and epigenetic alterations in rice pure-lines, F1 hybrids and polyploids.

    Science.gov (United States)

    Wang, Xiaoran; Wu, Rui; Lin, Xiuyun; Bai, Yan; Song, Congdi; Yu, Xiaoming; Xu, Chunming; Zhao, Na; Dong, Yuzhu; Liu, Bao

    2013-05-05

    Genetic and epigenetic alterations can be invoked by plant tissue culture, which may result in heritable changes in phenotypes, a phenomenon collectively termed somaclonal variation. Although extensive studies have been conducted on the molecular nature and spectrum of tissue culture-induced genomic alterations, the issue of whether and to what extent distinct plant genotypes, e.g., pure-lines, hybrids and polyploids, may respond differentially to the tissue culture condition remains poorly understood. We investigated tissue culture-induced genetic and epigenetic alterations in a set of rice genotypes including two pure-lines (different subspecies), a pair of reciprocal F1 hybrids parented by the two pure-lines, and a pair of reciprocal tetraploids resulted from the hybrids. Using two molecular markers, amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP), both genetic and DNA methylation alterations were detected in calli and regenerants from all six genotypes, but genetic alteration is more prominent than epigenetic alteration. While significant genotypic difference was observed in frequencies of both types of alterations, only genetic alteration showed distinctive features among the three types of genomes, with one hybrid (N/9) being exceptionally labile. Surprisingly, difference in genetic alteration frequencies between the pair of reciprocal F1 hybrids is much greater than that between the two pure-line subspecies. Difference also exists in the pair of reciprocal tetraploids, but is to a less extent than that between the hybrids. The steady-state transcript abundance of genes involved in DNA repair and DNA methylation was significantly altered in both calli and regenerants, and some of which were correlated with the genetic and/or epigenetic alterations. Our results, based on molecular marker analysis of ca. 1,000 genomic loci, document that genetic alteration is the major cause of somaclonal variation in rice

  8. Biological Activity Alterations of Human Amniotic Membrane Pre and Post Irradiation Tissue Banking.

    Science.gov (United States)

    Nemr, Waleed; Bashandy, A S; Araby, Eman; Khamiss, O

    Innate immunity of Human Amniotic Membrane (HAM) and its highly active secretome that rich with various types of growth factors and anti-inflammatory substances proposed it as a promising material for many medical studies and applications. This study evaluate the biological activity of cultivated HAM pre and post tissue banking process in which freeze-dried HAM was sterilized by 25 KGray (kGy) dose of γ radiation. The HAM's antimicrobial activity, viability, growth of isolated human amniotic epithelial cells (HAECs), hematopoietic stimulation of co-cultivated murine bone marrow cells (mammalian model), scaffold efficiency for fish brain building up (non-mammalian model) and self re-epithelialization after trypsin denuding treatment were examined as supposed biological activity features. Native HAM revealed viability indications and was active to kill all tested microorganisms; 6 bacterial species (3 Gram-positive and 3 Gram-negative) and Candida albicans as a pathogenic fungus. Also, HAM activity promoted colony formation of murine hematopoietic cells, Tilapia nilotica brain fragment building-up and self re-epithelialization after trypsin treatment. In contrary, radiation-based tissue banking of HAM caused HAM cellular death and consequently lacked almost all of examined biological activity features. Viable HAM was featured with biological activity than fixed HAM prepared by irradiation tissue banking.

  9. Role of percent tissue altered on ectasia after LASIK in eyes with suspicious topography.

    Science.gov (United States)

    Santhiago, Marcony R; Smadja, David; Wilson, Steven E; Krueger, Ronald R; Monteiro, Mario L R; Randleman, J Bradley

    2015-04-01

    To investigate the association of the percent tissue altered (PTA) with the occurrence of ectasia after LASIK in eyes with suspicious preoperative corneal topography. This retrospective comparative case-control study compared associations of reported ectasia risk factors in 129 eyes, including 57 eyes with suspicious preoperative Placido-based corneal topography that developed ectasia after LASIK (suspect ectasia group), 32 eyes with suspicious topography that remained stable for at least 3 years after LASIK (suspect control group), and 30 eyes that developed ectasia with bilateral normal topography (normal topography ectasia group). Groups were subdivided based on topographic asymmetry into high- or low-suspect groups. The PTA, preoperative central corneal thickness (CCT), residual stromal bed (RSB), and age (years) were evaluated in univariate and multivariate analyses. Average PTA values for normal topography ectasia (45), low-suspect ectasia (39), high-suspect ectasia (36), low-suspect control (32), and high-suspect control (29) were significantly different from one another in all comparisons (P topography ectasia groups, and CCT was not significantly different between any groups. Stepwise logistic regression revealed the PTA as the most significant independent variable (P topography. Less tissue alteration, or a lower PTA value, was necessary to induce ectasia in eyes with more remarkable signs of topographic abnormality, and PTA provided better discriminative capabilities than RSB for all study populations. Copyright 2015, SLACK Incorporated.

  10. Endovascular optical coherence tomography ex vivo: venous wall anatomy and tissue alterations after endovenous therapy

    International Nuclear Information System (INIS)

    Meissner, Oliver A.; Schmedt, Claus-Georg; Steckmeier, Bernd M.; Hunger, Kathrin; Reiser, Maximilian; Mueller-Lisse, Ullrich; Hetterich, Holger; Rieber, Johannes; Sroka, Ronald; Babaryka, Gregor; Siebert, Uwe

    2007-01-01

    Endovascular optical coherence tomography (OCT) is a new imaging modality providing histology-like information of the venous wall. Radiofrequency ablation (RFA) and laser therapy (ELT) are accepted alternatives to surgery. This study evaluated OCT for qualitative assessment of venous wall anatomy and tissue alterations after RFA and ELT in bovine venous specimens. One hundred and thirty-four venous segments were obtained from ten ex-vivo bovine hind limbs. OCT signal characteristics for different wall layers were assessed in 180/216 (83%) quadrants from 54 normal venous cross-sections. Kappa statistics (κ) were used to calculate intra- and inter-observer agreement. Qualitative changes after RFA (VNUS-Closure) and ELT (diode laser 980 nm, energy densities 15 Joules (J)/cm, 25 J/cm, 35 J/cm) were described in 80 venous cross-sections. Normal veins were characterized by a three-layered appearance. After RFA, loss of three-layered appearance and wall thickening at OCT corresponded with circular destruction of tissue structures at histology. Wall defects after ELT ranged from non-transmural punctiform damage to complete perforation, depending on the energy density applied. Intra- and inter-observer agreement for reading OCT images was very high (0.90 and 0.88, respectively). OCT allows for reproducible evaluation of normal venous wall and alterations after endovenous therapy. OCT could prove to be valuable for optimizing endovenous therapy in vivo. (orig.)

  11. Herring parasite and tissue alterations following the Exxon Valdez oil spill

    International Nuclear Information System (INIS)

    Moles, A.D.; Rice, S.D.; Okihiro, M.S.

    1993-01-01

    The authors examined the intensity and prevalence of larval nematodes (Anisakis simplex) and alterations in selected tissues of spawning Pacific herring (Clupea harengus pallasi) exposed to crude oil, in the laboratory under controlled conditions and in Prince William Sound 14 days after the Exxon Valdez oil spill. In the laboratory, intensity and prevalence of nematodes in the body cavities of herring exposed to the water-soluble fraction of oil declined when exposed to doses above 1.2 mg/L total aromatics. In Prince William Sound, nematodes were rare in spawning herring from oiled sites and abundant among herring from areas outside the spill. Oil exposure apparently induced the nematodes to migrate from the body cavity to the body wall with the lower intensity reflecting a change in parasite location. A coccidian, Eimeria clupearum, was found in greater numbers in oil-exposed herring. To verify exposure effects and to link parasite and tissue alteration with oil exposure, histological examination was used. Liver coagulative necrosis indicated hepatotoxic exposure. Necrosis was followed by macrophage aggregation in the resolution phase. The laboratory exposures allowed confirmation of oil exposure in Prince William Sound and permitted analysis of effects on two internal parasites

  12. Lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues.

    Science.gov (United States)

    Carrion, Ricardo; Brasky, Kathleen; Mansfield, Keith; Johnson, Curtis; Gonzales, Monica; Ticer, Anysha; Lukashevich, Igor; Tardif, Suzette; Patterson, Jean

    2007-06-01

    Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

  13. Blood transfusion in preterm infants improves intestinal tissue oxygenation without alteration in blood flow.

    Science.gov (United States)

    Banerjee, J; Leung, T S; Aladangady, N

    2016-11-01

    The objective of the study was to investigate the splanchnic blood flow velocity and oximetry response to blood transfusion in preterm infants according to postnatal age. Preterm infants receiving blood transfusion were recruited to three groups: 1-7 (group 1; n = 20), 8-28 (group 2; n = 21) and ≥29 days of life (group 3; n = 18). Superior mesenteric artery (SMA) peak systolic (PSV) and diastolic velocities were measured 30-60 min pre- and post-transfusion using Doppler ultrasound scan. Splanchnic tissue haemoglobin index (sTHI), tissue oxygenation index (sTOI) and fractional tissue oxygen extraction (sFTOE) were measured from 15-20 min before to post-transfusion using near-infrared spectroscopy. The mean pretransfusion Hb in group 1, 2 and 3 was 11, 10 and 9 g/dl, respectively. The mean (SD) pretransfusion SMA PSV in group 1, 2 and 3 was 0·63 (0·32), 0·81 (0·33) and 0·97 (0·40) m/s, respectively, and this did not change significantly following transfusion. The mean (SD) pretransfusion sTOI in group 1, 2 and 3 was 36·7 (19·3), 44·6 (10·4) and 41·3 (10·4)%, respectively. The sTHI and sTOI increased (P transfusion in all groups. On multivariate analysis, changes in SMA PSV and sTOI following blood transfusion were not associated with PDA, feeding, pretransfusion Hb and mean blood pressure. Pretransfusion baseline splanchnic tissue oximetry and blood flow velocity varied with postnatal age. Blood transfusion improved intestinal tissue oxygenation without altering mesenteric blood flow velocity irrespective of postnatal ages. © 2016 International Society of Blood Transfusion.

  14. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J.; Morrison, Shaun F.

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis. PMID:24570653

  15. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis.

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J; Morrison, Shaun F

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis.

  16. Glucose-stimulated calcium dynamics in islets of Langerhans in acute mouse pancreas tissue slices.

    Directory of Open Access Journals (Sweden)

    Andraž Stožer

    Full Text Available In endocrine cells within islets of Langerhans calcium ions couple cell stimulation to hormone secretion. Since the advent of modern fluorimetry, numerous in vitro studies employing primarily isolated mouse islets have investigated the effects of various secretagogues on cytoplasmic calcium, predominantly in insulin-secreting beta cells. Due to technical limitations, insights of these studies are inherently limited to a rather small subpopulation of outermost cells. The results also seem to depend on various factors, like culture conditions and duration, and are not always easily reconcilable with findings in vivo. The main controversies regard the types of calcium oscillations, presence of calcium waves, and the level of synchronized activity. Here, we set out to combine the in situ acute mouse pancreas tissue slice preparation with noninvasive fluorescent calcium labeling and subsequent confocal laser scanning microscopy to shed new light on the existing controversies utilizing an innovative approach enabling the characterization of responses in many cells from all layers of islets. Our experiments reproducibly showed stable fast calcium oscillations on a sustained plateau rather than slow oscillations as the predominant type of response in acute tissue slices, and that calcium waves are the mechanistic substrate for synchronization of oscillations. We also found indirect evidence that even a large amplitude calcium signal was not sufficient and that metabolic activation was necessary to ensure cell synchronization upon stimulation with glucose. Our novel method helped resolve existing controversies and showed the potential to help answer important physiological questions, making it one of the methods of choice for the foreseeable future.

  17. Stimulate The Growth of Rice Using Endophytic Bacteria from Lowland Rice Plant Tissue

    Directory of Open Access Journals (Sweden)

    Nuni Gofar

    2015-07-01

    Full Text Available Exploration and selection of endophytic bacteria from healthy food crops grown in lowland ecosystem is important to be conducted in order to get growth-stimulating endophytic bacteria at soil with low fertility level so that capable to optimize initial growth of food crops and subsequently can increase productivity level of lowland soil.The research objective was to isolate and to test the IAA-producing endophytic bacteria isolate in stimulating the rice crop growth at lowland area. Endophytic bacteria are isolated from tissues of rice, corn and peanut crops which grown at shallow swamp land in Ogan Ilir and Ogan Komering Ilir Districts, South Sumatra, Indonesia. There was nine isolates of nitrogen-fixer endophytic bacteria that capable to contribute IAA phytohormone into their growth media. The P31 isolate from rice crop tisssue of 2 months old produce the best rice sprouts than other isolates. This isolate can contribute of about 10 mg kg-1 IAA to its growth medium and increase the crowns dry weight and the roots dry weight respectively with magnitudes of 133% and 225% compared to control treatment. Concentration and absorbtion of N for rice crops innoculated with P31 isolates had increased by 169% and 400%, recpectively. The P31 isolates had been identified as Burkholderia pseudomallei (also known as Pseudomonas pseudomallei.

  18. Subthalamic Nucleus Deep Brain Stimulation Alters Prefrontal Correlates of Emotion Induction.

    Science.gov (United States)

    Bick, Sarah K B; Folley, Bradley S; Mayer, Jutta S; Park, Sohee; Charles, P David; Camalier, Corrie R; Pallavaram, Srivatsan; Konrad, Peter E; Neimat, Joseph S

    2017-04-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task. We used near infrared spectroscopy to monitor prefrontal cortex hemodynamic changes during an emotion induction task. Seven DBS patients were tested sequentially in the stimulation-on and stimulation-off states while on dopaminergic medication. Patients watched a series of positive, negative, and neutral videos. The general linear model was used to compare prefrontal oxygenated hemoglobin concentration between DBS states. Deep brain stimulation was correlated with prefrontal oxygenated hemoglobin changes relative to the stimulation off state in response to both positive and negative videos. These changes were specific to emotional stimuli and were not seen during neutral stimuli. These results suggest that STN stimulation influences the prefrontal cortical representation of positive and negative emotion induction. © 2016 International Neuromodulation Society.

  19. Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis.

    Science.gov (United States)

    Lind, Anne-Li; Emami Khoonsari, Payam; Sjödin, Marcus; Katila, Lenka; Wetterhall, Magnus; Gordh, Torsten; Kultima, Kim

    2016-08-01

    Electrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. Two different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks. Eighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3). Previously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain. © 2016 International Neuromodulation Society.

  20. Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Miller, V., E-mail: vmiller@coe.drexel.edu; Lin, A.; Brettschneider, J.; Fridman, G.; Fridman, A. [AJ Drexel Plasma Institute, Drexel University, Camden, New Jersey 08103 (United States); Kako, F.; Gabunia, K.; Kelemen, S.; Autieri, M. [Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 (United States)

    2015-12-15

    Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.

  1. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location.

    Science.gov (United States)

    Crago, Patrick E; Makowski, Nathaniel S

    2014-10-01

    Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

  2. Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running.

    Directory of Open Access Journals (Sweden)

    Gregory N Ruegsegger

    Full Text Available In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA. IPA was chosen to assist in the understanding of complex 'omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10-11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05 between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life.

  3. Does the application site of spinal manipulative therapy alter spinal tissues loading?

    Science.gov (United States)

    Funabashi, Martha; Nougarou, François; Descarreaux, Martin; Prasad, Narasimha; Kawchuk, Gregory N

    2018-01-31

    Previous studies found that the intervertebral disc (IVD) experiences the greatest loads during spinal manipulation therapy (SMT). Based on that, this study aimed to determine if loads experienced by spinal tissues are significantly altered when the application site of SMT is changed. A biomechanical robotic serial dissection study. Thirteen porcine cadaveric motion segments. Forces experienced by lumbar spinal tissues. A servo-controlled linear actuator provided standardized 300 N SMT simulations to six different cutaneous locations of the porcine lumbar spine: L2-L3 and L3-L4 facet joints (FJ), L3 and L4 transverse processes (TVP), and the space between the FJs and the TVPs (BTW). Vertebral kinematics were tracked optically using indwelling bone pins; the motion segment was removed and mounted in a parallel robot equipped with a six-axis load cell. Movements of each SMT application at each site were replayed by the robot with the intact specimen and following the sequential removal of spinal ligaments, FJs and IVD. Forces induced by SMT were recorded, and specific axes were analyzed using linear mixed models. Analyses yielded a significant difference (p<.05) in spinal structures loads as a function of the application site. Spinal manipulative therapy application at the L3 vertebra caused vertebral movements and forces between L3 and L4 spinal segment in the opposite direction to when SMT was applied at L4 vertebra. Additionally, SMT applications over the soft tissue between adjacent vertebrae significantly decreased spinal structure loads. Applying SMT with a constant force at different spinal levels creates different relative kinetics of the spinal segments and load spinal tissues in significantly different magnitudes. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.

    Science.gov (United States)

    Rogalska, Anna; Kuter, Katarzyna; Żelazko, Aleksandra; Głogowska-Gruszka, Anna; Świętochowska, Elżbieta; Nowak, Przemysław

    2017-04-01

    The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

  5. Deep brain stimulation of the subthalamic nucleus alters frontal activity during spatial working memory maintenance of patients with Parkinson's disease.

    Science.gov (United States)

    Mayer, Jutta S; Neimat, Joseph; Folley, Bradley S; Bourne, Sarah K; Konrad, Peter E; Charles, David; Park, Sohee

    2016-08-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). The STN may represent an important relay station not only in the motor but also the associative cortico-striato-thalamocortical pathway. Therefore, STN stimulation may alter cognitive functions, such as working memory (WM). We examined cortical effects of STN-DBS on WM in early PD patients using functional near-infrared spectroscopy. The effects of dopaminergic medication on WM were also examined. Lateral frontal activity during WM maintenance was greater when patients were taking dopaminergic medication. STN-DBS led to a trend-level worsening of WM performance, accompanied by increased lateral frontal activity during WM maintenance. These findings suggest that STN-DBS in PD might lead to functional modifications of the basal ganglia-thalamocortical pathway during WM maintenance.

  6. Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.

    Science.gov (United States)

    Barclay, M; Constable, R; James, N R; Thorne, P R; Montgomery, J M

    2016-06-14

    Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Vagus Nerve Stimulation Reduces Cocaine Seeking and Alters Plasticity in the Extinction Network

    Science.gov (United States)

    Childs, Jessica E.; DeLeon, Jaime; Nickel, Emily; Kroener, Sven

    2017-01-01

    Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic…

  8. Photochemical alteration of organic carbon draining permafrost soils shifts microbial metabolic pathways and stimulates respiration.

    Science.gov (United States)

    Ward, Collin P; Nalven, Sarah G; Crump, Byron C; Kling, George W; Cory, Rose M

    2017-10-03

    In sunlit waters, photochemical alteration of dissolved organic carbon (DOC) impacts the microbial respiration of DOC to CO 2 . This coupled photochemical and biological degradation of DOC is especially critical for carbon budgets in the Arctic, where thawing permafrost soils increase opportunities for DOC oxidation to CO 2 in surface waters, thereby reinforcing global warming. Here we show how and why sunlight exposure impacts microbial respiration of DOC draining permafrost soils. Sunlight significantly increases or decreases microbial respiration of DOC depending on whether photo-alteration produces or removes molecules that native microbial communities used prior to light exposure. Using high-resolution chemical and microbial approaches, we show that rates of DOC processing by microbes are likely governed by a combination of the abundance and lability of DOC exported from land to water and produced by photochemical processes, and the capacity and timescale that microbial communities have to adapt to metabolize photo-altered DOC.The role of dissolved organic carbon (DOC) photo-alteration in the microbial respiration of DOC to CO 2 is unclear. Here, the authors show that the impact of this mechanism depends on whether photo-alteration of DOC produces or removes molecules used by native microbial communities prior to light exposure.

  9. Altered functional magnetic resonance imaging responses to nonpainful sensory stimulation in fibromyalgia patients.

    Science.gov (United States)

    López-Solà, Marina; Pujol, Jesus; Wager, Tor D; Garcia-Fontanals, Alba; Blanco-Hinojo, Laura; Garcia-Blanco, Susana; Poca-Dias, Violant; Harrison, Ben J; Contreras-Rodríguez, Oren; Monfort, Jordi; Garcia-Fructuoso, Ferran; Deus, Joan

    2014-11-01

    Fibromyalgia (FM) is a disorder characterized by chronic pain and enhanced responses to acute noxious events. However, the sensory systems affected in FM may extend beyond pain itself, as FM patients show reduced tolerance to non-nociceptive sensory stimulation. Characterizing the neural substrates of multisensory hypersensitivity in FM may thus provide important clues about the underlying pathophysiology of the disorder. The aim of this study was to characterize brain responses to non-nociceptive sensory stimulation in FM patients and their relationship to subjective sensory sensitivity and clinical pain severity. Functional magnetic resonance imaging (MRI) was used to assess brain response to auditory, visual, and tactile motor stimulation in 35 women with FM and 25 matched controls. Correlation and mediation analyses were performed to establish the relationship between brain responses and 3 types of outcomes: subjective hypersensitivity to daily sensory stimulation, spontaneous pain, and functional disability. Patients reported increased subjective sensitivity (increased unpleasantness) in response to multisensory stimulation in daily life. Functional MRI revealed that patients showed reduced task-evoked activation in primary/secondary visual and auditory areas and augmented responses in the insula and anterior lingual gyrus. Reduced responses in visual and auditory areas were correlated with subjective sensory hypersensitivity and clinical severity measures. FM patients showed strong attenuation of brain responses to nonpainful events in early sensory cortices, accompanied by an amplified response at later stages of sensory integration in the insula. These abnormalities are associated with core FM symptoms, suggesting that they may be part of the pathophysiology of the disease. Copyright © 2014 by the American College of Rheumatology.

  10. Assessment of deep tissue hyperalgesia in the groin – a method comparison of electrical vs. pressure stimulation

    DEFF Research Database (Denmark)

    Aasvang, E K; Werner, M U; Kehlet, H

    2014-01-01

    BACKGROUND: Deep pain complaints are more frequent than cutaneous in post-surgical patients, and a prevalent finding in quantitative sensory testing studies. However, the preferred assessment method - pressure algometry - is indirect and tissue unspecific, hindering advances in treatment and prev......BACKGROUND: Deep pain complaints are more frequent than cutaneous in post-surgical patients, and a prevalent finding in quantitative sensory testing studies. However, the preferred assessment method - pressure algometry - is indirect and tissue unspecific, hindering advances in treatment...... thresholds to pressure algometry, by performing identical test-retest sequences 10 days apart, in deep tissues in the groin region. Electrical stimulation was performed by five up-and-down staircase series of single impulses of 0.04 ms duration, starting from 0 mA in increments of 0.2 mA until a threshold......: The presented tissue-specific direct deep tissue electrical stimulation technique has equal or superior reliability compared with the indirect tissue-unspecific stimulation by pressure algometry. This method may facilitate advances in mechanism based preventive and treatment strategies in acute and chronic post...

  11. Chronic consumption of fructose rich soft drinks alters tissue lipids of rats

    Directory of Open Access Journals (Sweden)

    Botezelli Jose D

    2010-06-01

    Full Text Available Abstract Background Fructose-based diets are apparently related to the occurrence of several metabolic dysfunctions, but the effects of the consumption of high amounts of fructose on body tissues have not been well described. The aim of this study was to analyze the general characteristics and the lipid content of different tissues of rats after chronic ingestion of a fructose rich soft drink. Methods Forty-five Wistar rats were used. The rats were divided into three groups (n = 15 and allowed to consume water (C, light Coca Cola ® (L or regular Coca Cola® (R as the sole source of liquids for eight weeks. Results The R group presented significantly higher daily liquid intake and significantly lower food intake than the C and L groups. Moreover, relative to the C and L groups, the R group showed higher triglyceride concentrations in the serum and liver. However, the L group animals presented lower values of serum triglycerides and cholesterol than controls. Conclusions Based on the results, it can be concluded that daily ingestion of a large amount of fructose- rich soft drink resulted in unfavorable alterations to the lipid profile of the rats.

  12. Periodontal tissue activation by vibration: intermittent stimulation by resonance vibration accelerates experimental tooth movement in rats.

    Science.gov (United States)

    Nishimura, Makoto; Chiba, Mirei; Ohashi, Toshiro; Sato, Masaaki; Shimizu, Yoshiyuki; Igarashi, Kaoru; Mitani, Hideo

    2008-04-01

    Accelerating the speed of orthodontic tooth movement should contribute to the shortening of the treatment period. This would be beneficial because long treatment times are a negative aspect of orthodontic treatment. In this study, we evaluated the effects of mechanical stimulation by resonance vibration on tooth movement, and we showed the cellular and molecular mechanisms of periodontal ligament responses. The maxillary first molars of 6-week-old male Wistar rats were moved to the buccal side by using an expansive spring for 21 days (n = 6, control group), and the amount of tooth movement was measured. Additional vibrational stimulation (60 Hz, 1.0 m/s(2)) was applied to the first molars by using a loading vibration system for 8 minutes on days 0, 7, and 14 during orthodontic tooth movement (n = 6, experimental group). The animals were killed under anesthesia, and each maxilla was dissected. The specimens were fixed, decalcified, and embedded in paraffin. Sections were used for immunohistochemical analysis of receptor activator of NF kappa B ligand (RANKL) expression. The number of osteoclasts in the alveolar bone was counted by using TRAP staining, and the amount of root resorption was measured in sections stained with hematoxylin and eosin. The average resonance frequency of the maxillary first molar was 61.02 +/- 8.38 Hz. Tooth movement in the experimental group was significantly greater than in the control group (P vibration might accelerate orthodontic tooth movement via enhanced RANKL expression in the periodontal ligament without additional damage to periodontal tissues such as root resorption.

  13. Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice

    Directory of Open Access Journals (Sweden)

    Michael J. Haley

    2017-10-01

    Full Text Available Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids. Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.

  14. Impact of uncertain head tissue conductivity in the optimization of transcranial direct current stimulation for an auditory target

    Science.gov (United States)

    Schmidt, Christian; Wagner, Sven; Burger, Martin; van Rienen, Ursula; Wolters, Carsten H.

    2015-08-01

    Objective. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to modify neural excitability. Using multi-array tDCS, we investigate the influence of inter-individually varying head tissue conductivity profiles on optimal electrode configurations for an auditory cortex stimulation. Approach. In order to quantify the uncertainty of the optimal electrode configurations, multi-variate generalized polynomial chaos expansions of the model solutions are used based on uncertain conductivity profiles of the compartments skin, skull, gray matter, and white matter. Stochastic measures, probability density functions, and sensitivity of the quantities of interest are investigated for each electrode and the current density at the target with the resulting stimulation protocols visualized on the head surface. Main results. We demonstrate that the optimized stimulation protocols are only comprised of a few active electrodes, with tolerable deviations in the stimulation amplitude of the anode. However, large deviations in the order of the uncertainty in the conductivity profiles could be noted in the stimulation protocol of the compensating cathodes. Regarding these main stimulation electrodes, the stimulation protocol was most sensitive to uncertainty in skull conductivity. Finally, the probability that the current density amplitude in the auditory cortex target region is supra-threshold was below 50%. Significance. The results suggest that an uncertain conductivity profile in computational models of tDCS can have a substantial influence on the prediction of optimal stimulation protocols for stimulation of the auditory cortex. The investigations carried out in this study present a possibility to predict the probability of providing a therapeutic effect with an optimized electrode system for future auditory clinical and experimental procedures of tDCS applications.

  15. Transcranial direct current stimulation over the parietal cortex alters bias in item and source memory tasks.

    Science.gov (United States)

    Pergolizzi, Denise; Chua, Elizabeth F

    2016-10-01

    Neuroimaging data have shown that activity in the lateral posterior parietal cortex (PPC) correlates with item recognition and source recollection, but there is considerable debate about its specific contributions. Performance on both item and source memory tasks were compared between participants who were given bilateral transcranial direct current stimulation (tDCS) over the parietal cortex to those given prefrontal or sham tDCS. The parietal tDCS group, but not the prefrontal group, showed decreased false recognition, and less bias in item and source discrimination tasks compared to sham stimulation. These results are consistent with a causal role of the PPC in item and source memory retrieval, likely based on attentional and decision-making biases. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Electroconvulsive Stimulation, but not Chronic Restraint Stress, Causes Structural Alterations in Adult Rat Hippocampus

    DEFF Research Database (Denmark)

    Olesen, Mikkel V.; Wörtwein, Gitta; Pakkenberg, Bente

    2015-01-01

    The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible...... changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number...... of newly formed neurons in the hippocampal subgranular zone. Also estimated were the total number of neurons and the volume of the granule cell layer in adult rats subjected to chronic restraint stress and electroconvulsive stimulation either alone or in combination. We found that chronic restraint stress...

  17. Mechanical stimulation of mesenchymal stem cells: Implications for cartilage tissue engineering.

    Science.gov (United States)

    Fahy, Niamh; Alini, Mauro; Stoddart, Martin J

    2018-01-01

    Articular cartilage is a load-bearing tissue playing a crucial mechanical role in diarthrodial joints, facilitating joint articulation, and minimizing wear. The significance of biomechanical stimuli in the development of cartilage and maintenance of chondrocyte phenotype in adult tissues has been well documented. Furthermore, dysregulated loading is associated with cartilage pathology highlighting the importance of mechanical cues in cartilage homeostasis. The repair of damaged articular cartilage resulting from trauma or degenerative joint disease poses a major challenge due to a low intrinsic capacity of cartilage for self-renewal, attributable to its avascular nature. Bone marrow-derived mesenchymal stem cells (MSCs) are considered a promising cell type for cartilage replacement strategies due to their chondrogenic differentiation potential. Chondrogenesis of MSCs is influenced not only by biological factors but also by the environment itself, and various efforts to date have focused on harnessing biomechanics to enhance chondrogenic differentiation of MSCs. Furthermore, recapitulating mechanical cues associated with cartilage development and homeostasis in vivo, may facilitate the development of a cellular phenotype resembling native articular cartilage. The goal of this review is to summarize current literature examining the effect of mechanical cues on cartilage homeostasis, disease, and MSC chondrogenesis. The role of biological factors produced by MSCs in response to mechanical loading will also be examined. An in-depth understanding of the impact of mechanical stimulation on the chondrogenic differentiation of MSCs in terms of endogenous bioactive factor production and signaling pathways involved, may identify therapeutic targets and facilitate the development of more robust strategies for cartilage replacement using MSCs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:52-63, 2018. © 2017 Orthopaedic Research

  18. Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

    OpenAIRE

    Jansen, S. W.; Akintola, A. A.; Roelfsema, F.; van der Spoel, E.; Cobbaert, C. M.; Ballieux, B. E.; Egri, P.; Kvarta-Papp, Z.; Gereben, B.; Fekete, C.; Slagboom, P. E.; van der Grond, J.; Demeneix, B. A.; Pijl, H.; Westendorp, R. G. J.

    2015-01-01

    Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT a...

  19. Postural stability is altered by the stimulation of pain but not warm receptors in humans

    OpenAIRE

    Corbeil Philippe; Blouin Jean-Sébastien; Teasdale Normand

    2003-01-01

    Abstract Background It is now recognized that large diameter myelinated afferents provide the primary source of lower limb proprioceptive information for maintaining an upright standing position. Small diameter afferents transmitting noxious stimuli, however, can also influence motor behaviors. Despite the possible influence of pain on motor behaviors, the effects of pain on the postural control system have not been well documented. Methods Two cutaneous heat stimulations (experiment 1: non-n...

  20. Framing susceptibility in a risky choice game is altered by galvanic vestibular stimulation.

    Science.gov (United States)

    Preuss, Nora; Kalla, Roger; Müri, Rene; Mast, Fred W

    2017-06-07

    Recent research provides evidence that galvanic vestibular stimulation (GVS) has a modulating effect on somatosensory perception and spatial cognition. However, other vestibular stimulation techniques have induced changes in affective control and decision making. The aim of this study was to investigate the effect of GVS on framing susceptibility in a risky-choice game. The participants were to decide between a safe and a risky option. The safe option was framed either positively or negatively. During the task, the participants were exposed to either left anodal/right cathodal GVS, right anodal/left cathodal GVS, or sham stimulation (control condition). While left anodal/right cathodal GVS activated more right-hemispheric vestibular brain areas, right anodal/left cathodal GVS resulted in more bilateral activation. We observed increased framing susceptibility during left anodal/right cathodal GVS, but no change in framing susceptibility during right anodal/left cathodal GVS. We propose that GVS results in increased reliance on the affect heuristic by means of activation of cortical and subcortical vestibular-emotional brain structures and that this effect is modulated by the lateralization of the vestibular cortex.

  1. Short Communication: Immunohistochemical localization of the immune cell marker CD68 in bovine adipose tissue: impact of tissue alterations and excessive fat accumulation in dairy cows.

    Science.gov (United States)

    Häussler, S; Germeroth, D; Laubenthal, L; Ruda, L F; Rehage, J; Dänicke, S; Sauerwein, H

    2017-01-01

    With the onset of lactation energy from feed intake is mostly insufficient to meet the requirements of dairy cows. Lipid mobilization from adipose tissue (AT) could lead to a compromised inflammatory response enhancing the incidence for diseases. In addition, tissue alterations can occur, displaying areas of necrosis and inflammation. Furthermore, over-conditioned cows mobilizing more lipids from AT than thin cows are prone to develop metabolic disorders. This might lead to an increased infiltration of phagocytic immune cells into AT. In the present study, CD68 positive cells were localized in AT from 10 early lactating Holstein cows displaying different grades of AT alterations. Biopsies were sampled from visceral and subcutaneous AT and the number of CD68 positive cells was immunohistochemically determined. In addition, AT biopsies from over-conditioned, non-pregnant, non-lactating cows (n=8) were immunohistochemically analyzed for CD68 positive cells. The percentage of CD68 positive cells was less than 2% in AT biopsies with tissue alterations and in AT from over-conditioned cows. Therefore, immune cell infiltration demonstrated via the localization of CD68 positive cells seems to play only a minor role in AT from over-conditioned cows as well as in different bovine AT depots with tissue alterations. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats.

    Directory of Open Access Journals (Sweden)

    Sandra Geschka

    Full Text Available A direct pharmacological stimulation of soluble guanylate cyclase (sGC is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521, have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension.Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1 in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1.Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.

  3. Ionizing Radiation Stimulates Expression of Pro-Osteoclastogenic Genes in Marrow and Skeletal Tissue

    Science.gov (United States)

    Alwood, J. S.; Shahnazari, M.; Chicana, B.; Schreurs, A. S.; Kumar, A.; Bartolini, A.; Shirazi-Fard, Y.; Globus, R. K.

    2015-01-01

    Exposure to ionizing radiation can cause rapid mineral loss and increase bone-resorbing osteoclasts within metabolically-active, cancellous-bone tissue leading to structural deficits. To better understand mechanisms involved in rapid, radiation-induced bone loss, we determined the influence of total-body irradiation on expression of select cytokines known both to stimulate osteoclastogenesis and contribute to inflammatory bone disease. Adult (16wk), male C57BL/6J mice were exposed to either 2Gy gamma rays (137Cs, 0.8Gy/min) or heavy ions (56Fe, 600MeV, 0.50-1.1Gy/min); this dose corresponds to either a single fraction of radiotherapy (typical total dose is =10Gy) or accumulates over long-duration, interplanetary missions. Serum, marrow, and mineralized tissue were harvested 4hrs-7d later. Gamma irradiation caused a prompt (2.6-fold within 4hrs) and persistent (peaking at 4.1-fold within 1d) rise in the expression of the obligate osteoclastogenic cytokine, receptor activator of nuclear factor kappaB-ligand (Rankl) within marrow cells over controls. Similarly, Rankl expression peaked in marrow cells within 3d of iron exposure (9.2-fold). Changes in Rankl expression induced by gamma irradiation preceded and overlapped with a rise in expression of other pro-osteoclastic cytokines in marrow (e.g., monocyte chemotactic protein-1 increased 11.9-fold, tumor necrosis factor-alpha increased 1.7- fold over controls). Marrow expression of the RANKL decoy receptor, osteoprotegerin (Opg), also rose after irradiation (11.3-fold). The ratio Rankl/Opg in marrow was increased 1.8-fold, a net pro-resorption balance. As expected, radiation increased a serum marker of resorption (tartrate resistant acid phosphatase) and led to cancellous bone loss (16% decrease in bone volume/total volume) through reduced trabecular struts. We conclude that total-body irradiation (gamma or heavy-ion) caused temporal, concerted regulation of gene expression within marrow and mineralized tissue for

  4. Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

    Directory of Open Access Journals (Sweden)

    Daina S. E. Dickins

    2015-01-01

    Full Text Available Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years underwent intermittent theta burst stimulation (iTBS whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS.

  5. Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

    Science.gov (United States)

    Dickins, Daina S. E.; Sale, Martin V.

    2015-01-01

    Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS. PMID:26064691

  6. Metabonomic Analysis Reveals Efficient Ameliorating Effects of Acupoint Stimulations on the Menopause-caused Alterations in Mammalian Metabolism

    Science.gov (United States)

    Zhang, Limin; Wang, Yulan; Xu, Yunxiang; Lei, Hehua; Zhao, Ying; Li, Huihui; Lin, Xiaosheng; Chen, Guizhen; Tang, Huiru

    2014-01-01

    Acupoint stimulations are effective in ameliorating symptoms of menopause which is an unavoidable ageing consequence for women. To understand the mechanistic aspects of such treatments, we systematically analyzed the effects of acupoint laser-irradiation and catgut-embedding on the ovariectomy-induced rat metabolic changes using NMR and GC-FID/MS methods. Results showed that ovariectomization (OVX) caused comprehensive metabolic changes in lipid peroxidation, glycolysis, TCA cycle, choline and amino acid metabolisms. Both acupoint laser-irradiation and catgut-embedding ameliorated the OVX-caused metabonomic changes more effectively than hormone replacement therapy (HRT) with nilestriol. Such effects of acupoint stimulations were highlighted in alleviating lipid peroxidation, restoring glucose homeostasis and partial reversion of the OVX-altered amino acid metabolism. These findings provided new insights into the menopause effects on mammalian biochemistry and beneficial effects of acupoint stimulations in comparison with HRT, demonstrating metabonomics as a powerful approach for potential applications in disease prognosis and developments of effective therapies.

  7. Mechanical stimulation to stimulate formation of a physiological collagen architecture in tissue-engineered cartilage; a numerical study

    NARCIS (Netherlands)

    Khoshgoftar, M.; Donkelaar, van C.C.; Ito, K.

    2011-01-01

    The load-bearing capacity of today's tissue-engineered (TE) cartilage is insufficient. The arcade-like collagen network in native cartilage plays an important role in its load-bearing properties. Inducing the formation of such collagen architecture in engineered cartilage can, therefore, enhance

  8. Inflammation alters AMPA-stimulated calcium responses in dorsal striatal D2 but not D1 spiny projection neurons.

    Science.gov (United States)

    Winland, Carissa D; Welsh, Nora; Sepulveda-Rodriguez, Alberto; Vicini, Stefano; Maguire-Zeiss, Kathleen A

    2017-11-01

    Neuroinflammation precedes neuronal loss in striatal neurodegenerative diseases and can be exacerbated by the release of proinflammatory molecules by microglia. These molecules can affect trafficking of AMPARs. The preferential trafficking of calcium-permeable versus impermeable AMPARs can result in disruptions of [Ca 2+ ] i and alter cellular functions. In striatal neurodegenerative diseases, changes in [Ca 2+ ] i and L-type voltage-gated calcium channels (VGCCs) have been reported. Therefore, this study sought to determine whether a proinflammatory environment alters AMPA-stimulated [Ca 2+ ] i through calcium-permeable AMPARs and/or L-type VGCCs in dopamine-2- and dopamine-1-expressing striatal spiny projection neurons (D2 and D1 SPNs) in the dorsal striatum. Mice expressing the calcium indicator protein, GCaMP in D2 or D1 SPNs, were utilized for calcium imaging. Microglial activation was assessed by morphology analyses. To induce inflammation, acute mouse striatal slices were incubated with lipopolysaccharide (LPS). Here we report that LPS treatment potentiated AMPA responses only in D2 SPNs. When a nonspecific VGCC blocker was included, we observed a decrease of AMPA-stimulated calcium fluorescence in D2 but not D1 SPNs. The remaining agonist-induced [Ca 2+ ] i was mediated by calcium-permeable AMPARs because the responses were completely blocked by a selective calcium-permeable AMPAR antagonist. We used isradipine, the highly selective L-type VGCC antagonist to determine the role of L-type VGCCs in SPNs treated with LPS. Isradipine decreased AMPA-stimulated responses selectively in D2 SPNs after LPS treatment. Our findings suggest that dorsal striatal D2 SPNs are specifically targeted in proinflammatory conditions and that L-type VGCCs and calcium-permeable AMPARs are important mediators of this effect. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy

    Directory of Open Access Journals (Sweden)

    Marjo J. den Broeder

    2017-04-01

    Full Text Available Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (Danio rerio. We used label-free Stimulated Raman Scattering (SRS microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf and compared standard feed conditions (StF to a high fat diet (HFD or high glucose diet (HGD. We also exposed zebrafish embryos to a non-toxic concentration of tributyltin (TBT, 1 nM or Tris(1,3-dichloroisopropylphosphate (TDCiPP, 0.5 µM from 0–6 dpf and reared larvae to 15 dpf under StF. Potential molecular mechanisms of altered adipogenesis were examined by qPCR. Diet-dependent modulation of adipogenesis was observed, with HFD resulting in a threefold increase in larvae with adipocytes, compared to StF and HGD. Developmental exposure to TBT but not TDCiPP significantly increased adipocyte differentiation. The expression of adipogenic genes such as pparda, lxr and lepa was altered in response to HFD or chemicals. This study shows that SRS microscopy can be successfully applied to zebrafish to visualize and quantify adipogenesis, and is a powerful approach for identifying obesogenic chemicals in vivo.

  10. Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy

    Science.gov (United States)

    den Broeder, Marjo J.; Moester, Miriam J. B.; Kamstra, Jorke H.; Cenijn, Peter H.; Davidoiu, Valentina; Kamminga, Leonie M.; Ariese, Freek; de Boer, Johannes F.; Legler, Juliette

    2017-01-01

    Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (Danio rerio). We used label-free Stimulated Raman Scattering (SRS) microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf) and compared standard feed conditions (StF) to a high fat diet (HFD) or high glucose diet (HGD). We also exposed zebrafish embryos to a non-toxic concentration of tributyltin (TBT, 1 nM) or Tris(1,3-dichloroisopropyl)phosphate (TDCiPP, 0.5 µM) from 0–6 dpf and reared larvae to 15 dpf under StF. Potential molecular mechanisms of altered adipogenesis were examined by qPCR. Diet-dependent modulation of adipogenesis was observed, with HFD resulting in a threefold increase in larvae with adipocytes, compared to StF and HGD. Developmental exposure to TBT but not TDCiPP significantly increased adipocyte differentiation. The expression of adipogenic genes such as pparda, lxr and lepa was altered in response to HFD or chemicals. This study shows that SRS microscopy can be successfully applied to zebrafish to visualize and quantify adipogenesis, and is a powerful approach for identifying obesogenic chemicals in vivo. PMID:28441764

  11. Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

    DEFF Research Database (Denmark)

    Jansen, S W; Akintola, A A; Roelfsema, F

    2015-01-01

    hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring...... of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis...... may favour longevity without altering energy metabolism....

  12. Evaluation of alteration in mucogingival line location following use of subepithelial connective tissue graft

    Directory of Open Access Journals (Sweden)

    Saber Fariba

    2010-01-01

    Full Text Available Aim and Objective : The aim of this study is to evaluate the positional changes that occur in mucogingival line following the use of subepithelial connective tissue graft (SCTG. Materials and Methods : In 19 Miller class I or II gingival recession defects, distance between mucogingival line (MGL and cemento-enamel junction, also width of keratinized and attached gingiva, and clinical attachment level were measured. SCTG were used for covering the exposed roots. A fore mentioned parameters were repeated at 3, 6 and 12 months after surgery and alterations were measured. Paired t test was used to analyze the results. Results : MGL had been moved in coronal direction (4.39 ± 0.77 mm on average during surgical approach. After 1 year, MGL shifted 2.11 ± 0.7 mm apically. In accordance with this apical shift, a significant increase in the width of keratinized and attached gingival width (2.89 ± 0.63 mm and 2.82 ± 0.5 mm, respectively was seen (P < 0.05. Conclusion : MGL tended to revert back to its original position following the use of SCTG, and this reversion is accompanied with an increase in the keratinized and attached gingival width.

  13. ALTERATION OF MUSCLE FUNCTION AFTER ELECTRICAL STIMULATION BOUT OF KNEE EXTENSORS AND FLEXORS

    Directory of Open Access Journals (Sweden)

    Marc Vanderthommen

    2012-12-01

    Full Text Available The purpose was to study the effects on muscle function of an electrical stimulation bout applied unilaterally on thigh muscles in healthy male volunteers. One group (ES group, n = 10 received consecutively 100 isometric contractions of quadriceps and 100 isometric contractions of hamstrings (on-off ratio 6-6 s induced by neuromuscular electrical stimulations (NMES. Changes in muscle torque, muscle soreness (0-10 VAS, muscle stiffness and serum creatine kinase (CK activity were assessed before the NMES exercise (pre-ex as well as 24h (d+1, 48h (d+2 and 120h (d+5 after the bout. A second group (control group, n = 10 were submitted to the same test battery than the ES group and with the same time-frame. The between-group comparison indicated a significant increase in VAS scores and in serum levels of CK only in the ES group. In the ES group, changes were more pronounced in hamstrings than in quadriceps and peaked at d+2 (quadriceps VAS scores = 2.20 ± 1.55 a.u. (0 at pre-ex; hamstrings VAS scores = 3.15 ± 2.14 a.u. (0 at pre-ex; hip flexion angle = 62 ± 5° (75 ± 6° at pre-ex; CK activity = 3021 ± 2693 IU·l-1 (136 ± 50 IU·l-1 at pre-ex. The results of the present study suggested the occurrence of muscle damage that could have been induced by the peculiar muscle recruitment in NMES and the resulting overrated mechanical stress. The sensitivity to the damaging effects of NMES appeared higher in the hamstrings than in quadriceps muscles

  14. K+-induced alterations in airway muscle responsiveness to electrical field stimulation

    International Nuclear Information System (INIS)

    Murlas, C.; Ehring, G.; Suszkiw, J.; Sperelakis, N.

    1986-01-01

    We investigated possible pre- and postsynaptic effects of K+-induced depolarization on ferret tracheal smooth muscle (TSM) responsiveness to cholinergic stimulation. To assess electromechanical activity, cell membrane potential (Em) and tension (Tm) were simultaneously recorded in buffer containing 6, 12, 18, or 24 mM K+ before and after electrical field stimulation (EFS) or exogenous acetylcholine (ACh). In 6 mM K+, Em was -58.1 +/- 1.0 mV (mean +/- SE). In 12 mM K+, Em was depolarized to -52.3 +/- 0.9 mV, basal Tm did not change, and both excitatory junctional potentials and contractile responses to EFS at short stimulus duration were larger than in 6 mM K+. No such potentiation occurred at a higher K+, although resting Em and Tm increased progressively above 12 mM K+. The sensitivity of ferret TSM to exogenous ACh appeared unaffected by K+. To determine whether the hyperresponsiveness in 12 mM K+ was due, in part, to augmented ACh release from intramural airway nerves, experiments were done using TSM preparations incubated with [3H]choline to measure [3H]ACh release at rest and during EFS. Although resting [3H]ACh release increased progressively in higher K+, release evoked by EFS was maximal in 12 mM K+ and declined in higher concentrations. We conclude that small elevations in the extracellular K+ concentration augment responsiveness of the airways, by increasing the release of ACh both at rest and during EFS from intramural cholinergic nerve terminals. Larger increases in K+ appear to be inhibitory, possibly due to voltage-dependent effects that occur both pre- and postsynaptically

  15. Tissue expander-stimulated lengthening of arteries for the treatment of midaortic syndrome in children.

    Science.gov (United States)

    Kim, Heung Bae; Vakili, Khashayar; Ramos-Gonzalez, Gabriel J; Stein, Deborah R; Ferguson, Michael A; Porras, Diego; Lock, James E; Chaudry, Gulraiz; Alomari, Ahmad; Fishman, Steven J

    2018-01-17

    Midaortic syndrome (MAS) is a rare condition characterized by stenosis of the abdominal aorta. Patients with disease refractory to medical management will usually require either endovascular therapy or surgery with use of prosthetic graft material for bypass or patch angioplasty. We report our early experience with a novel approach using a tissue expander (TE) to lengthen the normal native arteries in children with MAS, allowing primary aortic repair without the need for prosthetic graft material. We conducted a retrospective review of patients with MAS undergoing the TE-stimulated lengthening of arteries (TESLA) procedure at our institution from 2010 to 2014. Data are presented as mean (range). Five patients aged 4.8 years (3-8 years) underwent the TESLA procedure. Stages of this procedure include the following: stage I, insertion of retroaortic TE; stage II, serial TE injections; and stage III, final repair with excision of aortic stenosis and primary end-to-end aortic anastomosis. Stage II was completed in 4 months (1-9 months) with 12 (7-20) TE injections. Goal lengthening was achieved in all patients. Stage III could not be completed in one patient because of extreme aortic inflammation, which precluded safe excision of the aortic stenosis and required use of a prosthetic bypass graft. The other four patients completed stage III with two (one to three) additional vessels also requiring reconstruction (renal or mesenteric arteries). At 3.2 years (1-6 years) of follow-up, all patients are doing well. The TESLA procedure allows surgical correction of MAS without the need for prosthetic grafts in young children who are still growing. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  16. NLRC5 knockdown in chicken macrophages alters response to LPS and poly (I:C stimulation

    Directory of Open Access Journals (Sweden)

    Lian Ling

    2012-03-01

    Full Text Available Abstract Background NLRC5 is a member of the CARD domain containing, nucleotide-binding oligomerization (NOD-like receptor (NLR family, which recognizes pathogen-associated molecular patterns (PAMPs and initiates an innate immune response leading to inflammation and/or cell death. However, the specific role of NLRC5 as a modulator of the inflammatory immune response remains controversial. It has been reported to be a mediator of type I IFNs, NF-kB, and MHC class I gene. But no study on NLRC5 function has been reported to date in chickens. In the current study, we investigated the role of NLRC5 in the regulation of IFNA, IFNB, IL-6, and MHC class I in the chicken HD11 macrophage cell line, by using RNAi technology. HD11 cells were transfected with one of five siRNAs (s1, s2, s3, negative-siRNA, or a mixture of s1, s2, s3-siRNAs. After 24 hours, cells were exposed to LPS or poly (I:C or a vehicle control. Gene expression of NLRC5, IFNA, IFNB, IL-6, and MHC class I at 2, 4, 6, and 8 hours post stimulation (hps was quantified by qPCR. Results The expression of NLRC5, IFNA, IFNB, and IL-6 genes in negative irrelevant transfection controls was up-regulated at 2 hps after LPS treatment compared to the vehicle controls. S3-siRNA effectively knocked down NLRC5 expression at 4 hps, and the expression of IFNA and IFNB (but not IL-6 and MHC class I was also down-regulated at 4 hps in s3-siRNA transfected cells, compared to negative irrelevant transfection controls. Stimulation by LPS appeared to relatively restore the decrease in NLRC5, IFNA, and IFNB expression, but the difference is not significant. Conclusions Functional characterization of chicken NLRC5 in an in vitro system demonstrated its importance in regulating intracellular molecules involved in inflammatory response. The knockdown of NLRC5 expression negatively mediates gene expression of IFNA and IFNB in the chicken HD11 cell line; therefore, NLRC5 likely has a role in positive regulation of

  17. Tissue expander stimulated lengthening of arteries (TESLA) induces early endothelial cell proliferation in a novel rodent model.

    Science.gov (United States)

    Potanos, Kristina; Fullington, Nora; Cauley, Ryan; Purcell, Patricia; Zurakowski, David; Fishman, Steven; Vakili, Khashayar; Kim, Heung Bae

    2016-04-01

    We examine the mechanism of aortic lengthening in a novel rodent model of tissue expander stimulated lengthening of arteries (TESLA). A rat model of TESLA was examined with a single stretch stimulus applied at the time of tissue expander insertion with evaluation of the aorta at 2, 4 and 7day time points. Measurements as well as histology and proliferation assays were performed and compared to sham controls. The aortic length was increased at all time points without histologic signs of tissue injury. Nuclear density remained unchanged despite the increase in length suggesting cellular hyperplasia. Cellular proliferation was confirmed in endothelial cell layer by Ki-67 stain. Aortic lengthening may be achieved using TESLA. The increase in aortic length can be achieved without tissue injury and results at least partially from cellular hyperplasia. Further studies are required to define the mechanisms involved in the growth of arteries under increased longitudinal stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.

    2016-01-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4+ with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na+-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression. PMID:27009341

  19. Understanding the biophysical effects of transcranial magnetic stimulation on brain tissue: the bridge between brain stimulation and cognition.

    Science.gov (United States)

    Neggers, Sebastiaan F W; Petrov, Petar I; Mandija, Stefano; Sommer, Iris E C; van den Berg, Nico A T

    2015-01-01

    Transcranial magnetic stimulation (TMS) is rapidly being adopted in neuroscience, medicine, psychology, and biology, for basic research purposes, diagnosis, and therapy. However, a coherent picture of how TMS affects neuronal processing, and especially how this in turn influences behavior, is still largely unavailable despite several studies that investigated aspects of the underlying neurophysiological effects of TMS. Perhaps as a result from this "black box approach," TMS studies show a large interindividual variability in applied paradigms and TMS treatment outcome can be quite variable, hampering its general efficacy and introduction into the clinic. A better insight into the biophysical, neuronal, and cognitive mechanisms underlying TMS is crucial in order to apply it effectively in the clinic and to increase our understanding of brain-behavior relationship. Therefore, computational and experimental efforts have been started recently to understand and control the effect TMS has on neuronal functioning. Especially, how the brain shapes magnetic fields induced by a TMS coil, how currents are generated locally in the cortical surface, and how they interact with complex functional neuronal circuits within and between brain areas are crucial to understand the observed behavioral changes and potential therapeutic effects resulting from TMS. Here, we review the current knowledge about the biophysical underpinnings of single-pulse TMS and argue how to move forward to fully understand and exploit the powerful technique that TMS can be. © 2015 Elsevier B.V. All rights reserved.

  20. Comparing the magnetic resonant coupling radiofrequency stimulation to the traditional approaches: Ex-vivo tissue voltage measurement and electromagnetic simulation analysis

    Science.gov (United States)

    Yeung, Sai Ho; Pradhan, Raunaq; Feng, Xiaohua; Zheng, Yuanjin

    2015-09-01

    Recently, the design concept of magnetic resonant coupling has been adapted to electromagnetic therapy applications such as non-invasive radiofrequency (RF) stimulation. This technique can significantly increase the electric field radiated from the magnetic coil at the stimulation target, and hence enhancing the current flowing through the nerve, thus enabling stimulation. In this paper, the developed magnetic resonant coupling (MRC) stimulation, magnetic stimulation (MS) and transcutaneous electrical nerve stimulation (TENS) are compared. The differences between the MRC RF stimulation and other techniques are presented in terms of the operating mechanism, ex-vivo tissue voltage measurement and electromagnetic simulation analysis. The ev-vivo tissue voltage measurement experiment is performed on the compared devices based on measuring the voltage induced by electromagnetic induction at the tissue. The focusing effect, E field and voltage induced across the tissue, and the attenuation due to the increase of separation between the coil and the target are analyzed. The electromagnetic stimulation will also be performed to obtain the electric field and magnetic field distribution around the biological medium. The electric field intensity is proportional to the induced current and the magnetic field is corresponding to the electromagnetic induction across the biological medium. The comparison between the MRC RF stimulator and the MS and TENS devices revealed that the MRC RF stimulator has several advantages over the others for the applications of inducing current in the biological medium for stimulation purposes.

  1. Comparing the magnetic resonant coupling radiofrequency stimulation to the traditional approaches: Ex-vivo tissue voltage measurement and electromagnetic simulation analysis

    Directory of Open Access Journals (Sweden)

    Sai Ho Yeung

    2015-09-01

    Full Text Available Recently, the design concept of magnetic resonant coupling has been adapted to electromagnetic therapy applications such as non-invasive radiofrequency (RF stimulation. This technique can significantly increase the electric field radiated from the magnetic coil at the stimulation target, and hence enhancing the current flowing through the nerve, thus enabling stimulation. In this paper, the developed magnetic resonant coupling (MRC stimulation, magnetic stimulation (MS and transcutaneous electrical nerve stimulation (TENS are compared. The differences between the MRC RF stimulation and other techniques are presented in terms of the operating mechanism, ex-vivo tissue voltage measurement and electromagnetic simulation analysis. The ev-vivo tissue voltage measurement experiment is performed on the compared devices based on measuring the voltage induced by electromagnetic induction at the tissue. The focusing effect, E field and voltage induced across the tissue, and the attenuation due to the increase of separation between the coil and the target are analyzed. The electromagnetic stimulation will also be performed to obtain the electric field and magnetic field distribution around the biological medium. The electric field intensity is proportional to the induced current and the magnetic field is corresponding to the electromagnetic induction across the biological medium. The comparison between the MRC RF stimulator and the MS and TENS devices revealed that the MRC RF stimulator has several advantages over the others for the applications of inducing current in the biological medium for stimulation purposes.

  2. Comparing the magnetic resonant coupling radiofrequency stimulation to the traditional approaches: Ex-vivo tissue voltage measurement and electromagnetic simulation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Yeung, Sai Ho; Pradhan, Raunaq; Feng, Xiaohua; Zheng, Yuanjin [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2015-09-15

    Recently, the design concept of magnetic resonant coupling has been adapted to electromagnetic therapy applications such as non-invasive radiofrequency (RF) stimulation. This technique can significantly increase the electric field radiated from the magnetic coil at the stimulation target, and hence enhancing the current flowing through the nerve, thus enabling stimulation. In this paper, the developed magnetic resonant coupling (MRC) stimulation, magnetic stimulation (MS) and transcutaneous electrical nerve stimulation (TENS) are compared. The differences between the MRC RF stimulation and other techniques are presented in terms of the operating mechanism, ex-vivo tissue voltage measurement and electromagnetic simulation analysis. The ev-vivo tissue voltage measurement experiment is performed on the compared devices based on measuring the voltage induced by electromagnetic induction at the tissue. The focusing effect, E field and voltage induced across the tissue, and the attenuation due to the increase of separation between the coil and the target are analyzed. The electromagnetic stimulation will also be performed to obtain the electric field and magnetic field distribution around the biological medium. The electric field intensity is proportional to the induced current and the magnetic field is corresponding to the electromagnetic induction across the biological medium. The comparison between the MRC RF stimulator and the MS and TENS devices revealed that the MRC RF stimulator has several advantages over the others for the applications of inducing current in the biological medium for stimulation purposes.

  3. Alteration of phospholipase D activity in the rat tissues by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, M. S. [Korea Univ., Seoul (Korea, Republic of). Coll. of Medicine; Cho, Y. J. [Hanyang Univ., Seoul (Korea, Republic of). Coll. of Medicine; Choi, M. U. [Seoul National Univ. (Korea, Republic of). Coll. of Natural Sciences

    1997-09-01

    Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid (PA) and choline. Recently, PLD has been drawing much attentions and considered to be associated with cancer process since it is involved in cellular signal transduction. In this experiment, oleate-PLD activities were measured in various tissues of the living rats after whole body irradiation. The reaction mixture for the PLD assay contained 0.1{mu}Ci 1,2-di[1-{sup 14}C]palmitoyl phosphatidylcholine, 0.5mM phosphatidylcholine, 5mM sodium oleate, 0.2% taurodeoxycholate, 50mM HEPES buffer(pH 6.5), 10mM CaCl{sub 2}, and 25mM KF. phosphatidic acid, the reaction product, was separated by TLC and its radioactivity was measured with a scintillation counter. The whole body irradiation was given to the female Wistar rats via Cobalt 60 Teletherapy with field size of 10cm x 10cm and an exposure of 2.7Gy per minute to the total doses of 10Gy and 25Gy. Among the tissues examined, PLD activity in lung was the highest one and was followed by kidney, skeletal muscle, brain, spleen, bone marrow, thymus, and liver. Upon irradiation, alteration of PLD activity was observed in thymus, spleen, lung, and bone marrow. Especially PLD activities of the spleen and thymus revealed the highest sensitivity toward {gamma}-ray with more than two times amplification in their activities. In contrast, the PLD activity of bone marrow appears to be reduced to nearly 30%. Irradiation effect was hardly detected in liver which showed the lowest PLD activity. The PLD activities affected most sensitively by the whole-body irradiation seem to be associated with organs involved in immunity and hematopoiesis. This observation strongly indicates that the PLD is closely related to the physiological function of these organs. Furthermore, radiation stress could offer an important means to explore the phenomena covering from cell proliferation to cell death on these organs. (author).

  4. Electrical stimulation attenuates morphological alterations and prevents atrophy of the denervated cranial tibial muscle.

    Science.gov (United States)

    Bueno, Cleuber Rodrigo de Souza; Pereira, Mizael; Favaretto, Idvaldo Aparecido; Bortoluci, Carlos Henrique Fachin; Santos, Thais Caroline Pereira Dos; Dias, Daniel Ventura; Daré, Letícia Rossi; Rosa, Geraldo Marco

    2017-01-01

    To investigate if electrical stimulation through Russian current is able to maintain morphology of the cranial tibial muscle of experimentally denervated rats. Thirty-six Wistar rats were divided into four groups: the Initial Control Group, Final Control Group, Experimental Denervated and Treated Group, Experimental Denervated Group. The electrostimulation was performed with a protocol of Russian current applied three times per week, for 45 days. At the end, the animals were euthanized and histological and morphometric analyses were performed. Data were submitted to statistical analysis with a significance level of pprotocolo de corrente russa aplicada três vezes por semanas, durante 45 dias. Ao final, os animais foram eutanasiados e, em seguida, foram realizadas as análises histológica e morfométrica. Os dados foram submetidos à análise estatística, com nível de significância de p<0,05. Os Grupos Experimental Desnervado e o Grupo Experimental Desnervado Tratado apresentaram área de secção transversal da fibra menor quando comparados ao Grupo Controle Final. Entretanto, constatou-se diferença significativa entre o Grupo Experimental Desnervado e o Grupo Experimental Desnervado Tratado, mostrando que a estimulação elétrica minimizou atrofia muscular. Ainda, observou-se que o Grupo Experimental Desnervado Tratado apresentou resultados semelhantes ao Grupo Controle Inicial. A estimulação elétrica por meio da corrente russa foi favorável na manutenção da morfologia do músculo tibial cranial desnervado experimentalmente, minimizando a atrofia muscular.

  5. Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Elizabeth S.; Kawahara, Rebeca [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Kadowaki, Marina K. [Universidade Estadual do Oeste do Parana, Cascavel, PR (Brazil); Amstalden, Hudson G.; Noleto, Guilhermina R.; Cadena, Silvia Maria S.C.; Winnischofer, Sheila M.B. [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Martinez, Glaucia R., E-mail: grmartinez@ufpr.br [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil)

    2012-09-10

    Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. -- Highlights: Black-Right-Pointing-Pointer Melanogenesis stimulation by L-tyrosine+NH{sub 4}Cl in B16-F10 melanoma cells increases ROS levels. Black-Right-Pointing-Pointer Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G1 phase. Black-Right-Pointing-Pointer Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism. Black-Right-Pointing-Pointer RT-qPCR analysis confirmed alterations of metabolic targets after melanogenesis stimulation.

  6. Key Aging-Associated Alterations in Primary Microglia Response to Beta-Amyloid Stimulation

    Directory of Open Access Journals (Sweden)

    Cláudia Caldeira

    2017-08-01

    Full Text Available Alzheimer’s disease (AD is characterized by a progressive cognitive decline and believed to be driven by the self-aggregation of amyloid-β (Aβ peptide into oligomers and fibrils that accumulate as senile plaques. It is widely accepted that microglia-mediated inflammation is a significant contributor to disease pathogenesis; however, different microglia phenotypes were identified along AD progression and excessive Aβ production was shown to dysregulate cell function. As so, the contribution of microglia to AD pathogenesis remains to be elucidated. In this study, we wondered if isolated microglia cultured for 16 days in vitro (DIV would react differentially from the 2 DIV cells upon treatment with 1000 nM Aβ1–42 for 24 h. No changes in cell viability were observed and morphometric alterations associated to microglia activation, such as volume increase and process shortening, were obvious in 2 DIV microglia, but less evident in 16 DIV cells. These cells showed lower phagocytic, migration and autophagic properties after Aβ treatment than the 2 DIV cultured microglia. Reduced phagocytosis may derive from increased CD33 expression, reduced triggering receptor expressed on myeloid cells 2 (TREM2 and milk fat globule-EGF factor 8 protein (MFG-E8 levels, which were mainly observed in 16 DIV cells. Activation of inflammatory mediators, such as high mobility group box 1 (HMGB1 and pro-inflammatory cytokines, as well as increased expression of Toll-like receptor 2 (TLR2, TLR4 and fractalkine/CX3C chemokine receptor 1 (CX3CR1 cell surface receptors were prominent in 2 DIV microglia, while elevation of matrix metalloproteinase 9 (MMP9 was marked in 16 DIV cells. Increased senescence-associated β-galactosidase (SA-β-gal and upregulated miR-146a expression that were observed in 16 DIV cells showed to increase by Aβ in 2 DIV microglia. Additionally, Aβ downregulated miR-155 and miR-124, and reduced the CD11b+ subpopulation in 2 DIV microglia, while

  7. Anatomical Alterations in Plant Tissues Induced by Plant-Parasitic Nematodes

    Directory of Open Access Journals (Sweden)

    Juan E. Palomares-Rius

    2017-11-01

    Full Text Available Plant-parasitic nematodes (PPNs interact with plants in different ways, for example, through subtle feeding behavior, migrating destructively through infected tissues, or acting as virus-vectors for nepoviruses. They are all obligate biotrophic parasites as they derive their nutrients from living cells which they modify using pharyngeal gland secretions prior to food ingestion. Some of them can also shield themselves against plant defenses to sustain a relatively long lasting interaction while feeding. This paper is centered on cell types or organs that are newly induced in plants during PPN parasitism, including recent approaches to their study based on molecular biology combined with cell biology-histopathology. This issue has already been reviewed extensively for major PPNs (i.e., root-knot or cyst nematodes, but not for other genera (viz. Nacobbus aberrans, Rotylenchulus spp.. PPNs have evolved with plants and this co-evolution process has allowed the induction of new types of plant cells necessary for their parasitism. There are four basic types of feeding cells: (i non-hypertrophied nurse cells; (ii single giant cells; (iii syncytia; and (iv coenocytes. Variations in the structure of these cells within each group are also present between some genera depending on the nematode species viz. Meloidogyne or Rotylenchulus. This variability of feeding sites may be related in some way to PPN life style (migratory ectoparasites, sedentary ectoparasites, migratory ecto-endoparasites, migratory endoparasites, or sedentary endoparasites. Apart from their co-evolution with plants, the response of plant cells and roots are closely related to feeding behavior, the anatomy of the nematode (mainly stylet size, which could reach different types of cells in the plant, and the secretory fluids produced in the pharyngeal glands. These secretory fluids are injected through the stylet into perforated cells where they modify plant cytoplasm prior to food removal

  8. Administration of granulocyte-colony stimulating factor accompanied with a balanced diet improves cardiac function alterations induced by high fat diet in mice.

    Science.gov (United States)

    Daltro, Pâmela Santana; Alves, Paula Santana; Castro, Murilo Fagundes; Azevedo, Carine M; Vasconcelos, Juliana Fraga; Allahdadi, Kyan James; de Freitas, Luiz Antônio Rodrigues; de Freitas Souza, Bruno Solano; Dos Santos, Ricardo Ribeiro; Soares, Milena Botelho Pereira; Macambira, Simone Garcia

    2015-12-03

    High fat diet (HFD) is a major contributor to the development of obesity and cardiovascular diseases due to the induction of cardiac structural and hemodynamic abnormalities. We used a model of diabetic cardiomyopathy in C57Bl/6 mice fed with a HFD to investigate the effects of granulocyte-colony stimulating factor (G-CSF), a cytokine known for its beneficial effects in the heart, on cardiac anatomical and functional abnormalities associated with obesity and type 2 diabetes. Groups of C57Bl/6 mice were fed with standard diet (n = 8) or HFD (n = 16). After 36 weeks, HFD animals were divided into a group treated with G-CSF + standard diet (n = 8) and a vehicle control group + standard diet (n = 8). Cardiac structure and function were assessed by electrocardiography, echocardiography and treadmill tests, in addition to the evaluation of body weight, fasting glicemia, insulin and glucose tolerance at different time points. Histological analyses were performed in the heart tissue. HFD consumption induced metabolic alterations characteristic of type 2 diabetes and obesity, as well as cardiac fibrosis and reduced exercise capacity. Upon returning to a standard diet, obese mice body weight returned to non-obese levels. G-CSF administration accelerated the reduction in of body weight in obese mice. Additionally, G-CSF treatment reduced insulin levels, diminished heart fibrosis, increased exercise capacity and reversed cardiac alterations, including bradycardia, elevated QRS amplitude, augmented P amplitude, increased septal wall thickness, left ventricular posterior thickening and cardiac output reduction. Our results indicate that G-CSF administration caused beneficial effects on obesity-associated cardiac impairment.

  9. Desensitization of human adipose tissue to adrenaline stimulation studied by microdialysis

    DEFF Research Database (Denmark)

    Stallknecht, B; Bülow, J; Frandsen, E

    1997-01-01

    . However, lipolytic responses to adrenaline decreased markedly during repeated stimulation at a given concentration. Further, arterial glycerol and free fatty acid concentrations varied directly with arterial adrenaline concentrations and showed reduced responses upon repeated exposure. 4. The increase...

  10. β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Darimont Christian

    2004-08-01

    Full Text Available Abstract Background Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114 could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. Methods Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study. Results In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG and diacylglycerol (DAG accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet. Conclusions These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.

  11. The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue

    Directory of Open Access Journals (Sweden)

    Li Qi-Jing

    2002-06-01

    Full Text Available Abstract Background During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Factor (cCAF, is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM is abundant. We hypothesized that cCAF stimulates fibroblasts to produce these matrix molecules. Results Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but not collagen III. Studies in culture and in vivo show that tenascin stimulation can also be achieved by the N-terminal 15 aas of the protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do not involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF is chemotactic for fibroblasts and accelerates their migration. Conclusions These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of the repair process may have important application to healing of impaired wounds.

  12. Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

    Science.gov (United States)

    Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

    2016-01-01

    Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

  13. Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men.

    Science.gov (United States)

    Cedernaes, Jonathan; Osler, Megan E; Voisin, Sarah; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Zierath, Juleen R; Schiöth, Helgi B; Benedict, Christian

    2015-09-01

    Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

  14. Modifying the Genetic Regulation of Bone and Cartilage Cells and Associated Tissue by EMF Stimulation Fields and Uses Thereof

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor); Shackelford, Linda C. (Inventor)

    2014-01-01

    An apparatus and method to modify the genetic regulation of mammalian tissue, bone, or any combination. The method may be comprised of the steps of tuning at least one predetermined profile associated with at least one time-varying stimulation field thereby resulting in at least one tuned time-varying stimulation field comprised of at least one tuned predetermined profile, wherein said at least one tuned predetermined profile is comprised of a plurality of tuned predetermined figures of merit and is controllable through at least one of said plurality of tuned predetermined figures of merit, wherein said plurality of predetermined tuned figures of merit is comprised of a tuned B-Field magnitude, tuned rising slew rate, tuned rise time, tuned falling slew rate, tuned fall time, tuned frequency, tuned wavelength, and tuned duty cycle; and exposing mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination to said at least one tuned time-varying stimulation field comprised of said at least one tuned predetermined profile for a predetermined tuned exposure time or plurality of tuned exposure time sequences.

  15. Engineering skeletal muscle tissues from murine myoblast progenitor cells and application of electrical stimulation

    NARCIS (Netherlands)

    Schaft, van der D.W.J.; Spreeuwel, van A.C.C.; Boonen, K.J.M.; Langelaan, M.L.P.; Bouten, C.V.C.; Baaijens, F.P.T.

    2013-01-01

    Engineered muscle tissues can be used for several different purposes, which include the production of tissues for use as a disease model in vitro, e.g. to study pressure ulcers, for regenerative medicine and as a meat alternative 1. The first reported 3D muscle constructs have been made many years

  16. Effects of a combined mechanical stimulation protocol: Value for skeletal muscle tissue engineering

    NARCIS (Netherlands)

    Boonen, K.J.M.; Langelaan, M.L.P.; Polak, R.B.; Schaft, van der D.W.J.; Baaijens, F.P.T.; Post, M.J.

    2010-01-01

    Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications for regenerative medicine, in vitro physiological model systems, and in vitro meat production. Besides conventional biochemical cues to promote muscle tissue maturation in vitro, biophysical stimuli

  17. Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns

    Science.gov (United States)

    Ajarem, Jamaan S.; Al-Basher, Gadh; Allam, Ahmed A.

    2017-01-01

    Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns. PMID:28588748

  18. Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and β2-agonist use

    Science.gov (United States)

    Hastie, Annette T; Wu, Min; Foster, Gayle C; Hawkins, Gregory A; Batra, Vikas; Rybinski, Katherine A; Cirelli, Rosemary; Zangrilli, James G; Peters, Stephen P

    2006-01-01

    Background Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Methods Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β2-adrenergic receptor haplotype determination. Results Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Conclusion Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to β-agonist. The decreased

  19. Alterations in vasodilator-stimulated phosphoprotein (VASP phosphorylation: associations with asthmatic phenotype, airway inflammation and β2-agonist use

    Directory of Open Access Journals (Sweden)

    Cirelli Rosemary

    2006-02-01

    Full Text Available Abstract Background Vasodilator-stimulated phosphoprotein (VASP mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1 injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2 regular in vivo β2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Methods Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β2-adrenergic receptor haplotype determination. Results Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Conclusion Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to

  20. Acetaldehyde stimulation of net gluconeogenic carbon movement from applied malic acid in tomato fruit pericarp tissue

    International Nuclear Information System (INIS)

    Halinska, A.; Frenkel, C.

    1991-01-01

    Applied acetaldehyde is known to lead to sugar accumulation in fruit including tomatoes (Lycopersicon esculentum) presumably due to stimulation of gluconeogenesis. This conjecture was examined using tomato fruit pericarp discs as a test system and applied l-[U- 14 C]malic acid as the source for gluconeogenic carbon mobilization. Results indicate that malic and perhaps other organic acids are carbon sources for gluconeogenesis occurring normally in ripening tomatoes. The process is stimulated by acetaldehyde apparently by attenuating the fructose-2,6-biphosphate levels. The mode of the acetaldehyde regulation of fructose-2,6-biphosphate metabolism awaits clarification

  1. Alteration of putative amino acid levels and morphological findings in neural tissues of methylmercury-intoxicated mice

    Energy Technology Data Exchange (ETDEWEB)

    Hirayama, K.; Inouye, M.; Fujisaki, T.

    1985-04-01

    Methylmercury chloride was administered PO to male Kud:ddY mice at a dose of 5 mg/kg/day for 20 days. The contents of taurine, aspartate, glutamate, glycine, and ..gamma..-aminobutyric acid were determined in tissue and crude synaptosomal (P/sub 2/) fraction of cerebellum, cerebral cortex, and spinal cord of methylmercury-treated mice with or without ataxia. In the cerebellum of ataxic mice, increased levels of taurine and glycine were found in the tissue and P/sub 2/ fraction, and increased levels of glutamate were found in the P/sub 2/ fraction. In the cerebral cortex, the levels of ..gamma..-aminobutylic acid decreased in the tissue and in the P/sub 2/ fraction of ataxic mice, but increased levels were found in the tissue of non-ataxic mice. A decreased asparate level in the cerebral cortex of ataxic mice and an increased taurine level in the cerebral cortex of non-ataxic mice were also found. In the spinal cord of ataxic mice, taurine increased in the tissue and in the P/sub 2/ fraction. Glutamate level decreased in the spinal cord of ataxic mice, but increased in the P/sub 2/ fraction of non-ataxic mice. Increased glycine levels in the P/sub 2/ fraction of the spinal cord were also found in non-axtaxic mice. Histologically, some degenerative changes were demonstrated in the cerebral and cerebellar cortices of ataxic mice. Such changes were also present to a mild degree in non-ataxic mice. In conclusion, methylmercury treatment altered the levels of putative neurotransmitter amino acids in neutral tissue of mice. These alterations might be caused by specific neural cell dysfunction and could be related to the appearance of ataxia.

  2. Alteration of Diastereoisomeric and Enantiomeric Profiles of Hexabromocyclododecanes (HBCDs) in Adult Chicken Tissues, Eggs, and Hatchling Chickens.

    Science.gov (United States)

    Zheng, Xiaobo; Qiao, Lin; Sun, Runxia; Luo, Xiaojun; Zheng, Jing; Xie, Qilai; Sun, Yuxin; Mai, Bixian

    2017-05-16

    The concentrations and enantiomer fractions (EFs) of α-, β-, and γ-hexabromocyclododecanes (HBCDs) were measured in chicken diet sources (soil and chicken feed), home-raised adult chicken (Gallus domesticus) tissues, eggs during incubation, and hatchling chicken tissues. HBCD concentrations were not detected-0.69 ng/g dry weight (dw) and 25.6-48.4 ng/g dw in chicken feed and soil, respectively. HBCDs were detected in all adult chicken tissues, except the brain, at median levels of 13.1-44.0 ng/g lipid weight (lw). The proportions of α-HBCD in total HBCDs increased from 51% in soil to more than 87% in adult chicken tissues. The accumulation ratios (ARs) of α-HBCD from diet to adult chicken tissues were 4.27 for liver, 11.2 for fat, and 7.64-12.9 for other tissues, respectively. The AR and carry-over rate (COR) of α-HBCD from diet to eggs were 22.4 and 0.226, respectively. The concentrations of α-HBCD in hatchling chicken liver (median: 35.4 ng/g lw) were significantly lower than those in hatchling chicken pectoral muscle (median: 130 ng/g lw). The EFs of α-HBCD decreased from soil to adult chicken tissues and from eggs to hatchling chicken liver. Meanwhile, the EFs of γ-HBCD increased from soil to adult chicken tissues. These results indicate the preferential enrichment of (-)-α-HBCD and (+)-γ-HBCD in chickens. The alteration of diastereoisomeric and enantiomeric patterns of HBCDs might be influenced by the different absorption and elimination rates of the six HBCD enantiomers as well as variations in HBCD metabolism in chickens.

  3. Tissue specific responses alter the biomass accumulation in wheat under gradual and sudden salt stress

    Directory of Open Access Journals (Sweden)

    Yumurtaci A.

    2012-11-01

    Full Text Available Salinity is one the major limiting environmental factors which has negative side effects on crop production. The purpose of this study was to investigate the differences between the gradual and sudden salt stress effects on biomass accumulation associated with whole plant development in three different tissues of two wheat species ( Triticum aestivum and Triticum durum under hydroponic conditions in the long term. Considering the effects of sudden and gradual stress for biomass accumulation, while importance of salinity x genotype interaction for fresh weights was 5%, association for salinity x tissue type was found as 1% important. Interestingly, root branching and development of lateral roots were much more negatively affected by gradual stress rather than sudden salt application. Our results demonstrated that root and leaf were both critical tissues to test the salt tolerance by physiologically but sheath tissue might be used as an alternative source of variation for solving the interactions between root and leaves in wheat.

  4. Altered Protein Composition of Subcutaneous Adipose Tissue in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Joanna Gertow

    2017-11-01

    Discussion: These findings demonstrate that adipose tissue of CKD patients shows signs of inflammation and disturbed functionality, thus potentially contributing to the unfavorable metabolic profile and increased risk of CVD in these patients.

  5. Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner.

    Science.gov (United States)

    Munir, Hafsa; Ward, Lewis S C; Sheriff, Lozan; Kemble, Samuel; Nayar, Saba; Barone, Francesca; Nash, Gerard B; McGettrick, Helen M

    2017-06-01

    Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage-induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC isolated from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα-treated endothelial cells (EC), but MSC-derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL-6 and TGFβ1 signalling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them, and mature adipocytes from adipose tissue were all immunoprotective. Thus disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive "abnormal" adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immunoprotective phenotype. Stem Cells 2017;35:1636-1646. © 2017 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  6. Beneficial Effects of Coenzyme Q10 in Reduction of Testicular Tissue Alteration Following Induction of Diabetes in Adult Rats

    Directory of Open Access Journals (Sweden)

    Kianifard Davoud

    2015-03-01

    Full Text Available Background and Aims: Various types of infertility are associated with uncontrolled hyperglycemia and diabetes. Development of oxidative stress is one the most important factors in the alteration of spermatogenesis in diabetic conditions. Consequently, the reduction of oxidative stress with antioxidant compounds can be effective in the reduction of tissue alterations. The aim of this study was to evaluate the efficacy of coenzyme Q10 in improvement of spermatogenesis in adult diabetic rats. Material and Methods: 32 adult rats were divided into four groups of control and treatment. Coenzyme Q10 (10 mg/kg body weight - b.w. was administrated to one control and one diabetic (intraperitoneal injection of 45 mg/kg b.w. of Streptozotocin groups. Blood concentrations of FSH, LH and Testosterone were measured. Histology of testicular tissue and sperm analysis were considered for evaluation of spermatogenesis. Results: Administration of Coenzyme Q10 led to increase of pituitary gonadotropins levels in diabetic rats. Testosterone levels were not changed significantly. Testicular morphology, spermatogenic indices and sperm analysis were improved in treated diabetic rats. Conclusions: The results of this study suggest that the use of Coenzyme Q10 has positive effects in reduction of spermatogenic alterations following induction of experimental diabetes in rats.

  7. Alteration of gene expression profile in Niemann-Pick type C mice correlates with tissue damage and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mary C Vázquez

    Full Text Available BACKGROUND: Niemann-Pick type C disease (NPC is a neurovisceral lipid storage disorder mainly characterized by unesterified cholesterol accumulation in lysosomal/late endosomal compartments, although there is also an important storage for several other kind of lipids. The main tissues affected by the disease are the liver and the cerebellum. Oxidative stress has been described in various NPC cells and tissues, such as liver and cerebellum. Although considerable alterations occur in the liver, the pathological mechanisms involved in hepatocyte damage and death have not been clearly defined. Here, we assessed hepatic tissue integrity, biochemical and oxidative stress parameters of wild-type control (Npc1(+/+; WT and homozygous-mutant (Npc1(-/-; NPC mice. In addition, the mRNA abundance of genes encoding proteins associated with oxidative stress, copper metabolism, fibrosis, inflammation and cholesterol metabolism were analyzed in livers and cerebella of WT and NPC mice. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed various oxidative stress parameters in the liver and hepatic and cerebellum gene expression in 7-week-old NPC1-deficient mice compared with control animals. We found signs of inflammation and fibrosis in NPC livers upon histological examination. These signs were correlated with increased levels of carbonylated proteins, diminished total glutathione content and significantly increased total copper levels in liver tissue. Finally, we analyzed liver and cerebellum gene expression patterns by qPCR and microarray assays. We found a correlation between fibrotic tissue and differential expression of hepatic as well as cerebellar genes associated with oxidative stress, fibrosis and inflammation in NPC mice. CONCLUSIONS/SIGNIFICANCE: In NPC mice, liver disease is characterized by an increase in fibrosis and in markers associated with oxidative stress. NPC is also correlated with altered gene expression, mainly of genes involved in oxidative stress

  8. Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues

    Directory of Open Access Journals (Sweden)

    Harkema Jack R

    2011-07-01

    Full Text Available Abstract Background Prior studies have demonstrated a link between air pollution and metabolic diseases such as type II diabetes. Changes in adipose tissue and its mitochondrial content/function are closely associated with the development of insulin resistance and attendant metabolic complications. We investigated changes in adipose tissue structure and function in brown and white adipose depots in response to chronic ambient air pollutant exposure in a rodent model. Methods Male ApoE knockout (ApoE-/- mice inhaled concentrated fine ambient PM (PM 2.5 or filtered air (FA for 6 hours/day, 5 days/week, for 2 months. We examined superoxide production by dihydroethidium staining; inflammatory responses by immunohistochemistry; and changes in white and brown adipocyte-specific gene profiles by real-time PCR and mitochondria by transmission electron microscopy in response to PM2.5 exposure in different adipose depots of ApoE-/- mice to understand responses to chronic inhalational stimuli. Results Exposure to PM2.5 induced an increase in the production of reactive oxygen species (ROS in brown adipose depots. Additionally, exposure to PM2.5 decreased expression of uncoupling protein 1 in brown adipose tissue as measured by immunohistochemistry and Western blot. Mitochondrial number was significantly reduced in white (WAT and brown adipose tissues (BAT, while mitochondrial size was also reduced in BAT. In BAT, PM2.5 exposure down-regulated brown adipocyte-specific genes, while white adipocyte-specific genes were differentially up-regulated. Conclusions PM2.5 exposure triggers oxidative stress in BAT, and results in key alterations in mitochondrial gene expression and mitochondrial alterations that are pronounced in BAT. We postulate that exposure to PM2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction.

  9. Subsurface femtosecond tissue alteration: selectively photobleaching macular degeneration pigments in near retinal contact.

    Science.gov (United States)

    Manevitch, Zakhariya; Lewis, Aaron; Levy, Carol; Zeira, Evelyne; Banin, Eyal; Manevitch, Alexandra; Khatchatouriants, Artium; Pe'er, Jacob; Galun, Eithan; Hemo, Itzhak

    2012-06-14

    This paper uses advances in the ultrafast manipulation of light to address a general need in medicine for a clinical approach that can provide a solution to a variety of disorders requiring subsurface tissue manipulation with ultralow collateral damage. Examples are age-related macular degeneration (AMD), fungal infections, tumors surrounded by overlying tissue, cataracts, etc. Although lasers have revolutionized the use of light in clinical settings, most lasers employed in medicine cannot address such problems of depth-selective tissue manipulation. This arises from the fact that they are mostly based on one photon based laser tissue interactions that provide a cone of excitation where the energy density is sufficiently high to excite heat or fluorescence in the entire cone. Thus, it is difficult to excite a specific depth of a tissue without affecting the overlying surface. However, the advent of femtosecond (fs) lasers has caused a revolution in multiphoton microscopy (Zipfel et al. Nat. Biotechnol. 2003, 21, 1369-1377; Denk et al. Science 1990, 248, 73-76) and fabrication (Kawata et al. Nature 2001, 412, 697-698). With such lasers, the photon energy density is only high enough for multiphoton processes in the focal volume, and this opens a new direction to address subsurface tissue manipulation. Here we show in an AMD animal model, Ccr2 KO knockout mutant mice, noninvasive, selective fs two-photon photobleaching of pigments associated with AMD that accumulate under and in ultraclose proximity to the overlying retina. Pathological evidence is presented that indicates the lack of collateral damage to the overlying retina or other surrounding tissue.

  10. ADENOSINE RECEPTOR STIMULATION BY POLYDEOXYRIBONUCLEOTIDE IMPROVES TISSUE REPAIR AND SYMPTOMOLOGY IN EXPERIMENTAL COLITIS.

    Directory of Open Access Journals (Sweden)

    Giovanni Pallio

    2016-08-01

    Full Text Available Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodelling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodelling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN, to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitro-benzene-sulfonic acid (DNBS, 25mg diluted in 0.8ml 50% ethanol. After 6 hrs, animals were randomized to receive either PDRN (8mg/kg/i.p., or PDRN + the A2A antagonist (DMPX; 10mg/kg/i.p., or vehicle (0.8 ml saline solution daily. In the second model, dextran sodium sulphate (DSS was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 hrs animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxydase activity, and malondialdheyde. All these effects were abolished by the concomitant administration of the A2a antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

  11. The Effect of Variation in Permittivity of Different Tissues on Induced Electric Field in the Brain during Transcranial Magnetic Stimulation

    Science.gov (United States)

    Hadimani, Ravi; Porzig, Konstantin; Crowther, Lawrence; Brauer, Hartmut; Toepfer, Hannes; Jiles, David; Department of Electrical and Computer Engineering, Iowa State University Team; Department of Advanced Electromagnetics, Ilmenau University of Technology Team

    2013-03-01

    Estimation of electric field in the brain during Transcranial Magnetic Stimulation (TMS) requires knowledge of the electric property of brain tissue. Grey and white matters have unusually high relative permittivities of ~ 106 at low frequencies. However, relative permittivity of cerebrospinal fluid is ~ 102. With such a variation it is necessary to consider the effect of boundaries. A model consisting of 2 hemispheres was used in the model with the properties of one hemisphere kept constant at σ1 = 0.1Sm-1 and ɛr 1 = 10 while the properties of the second hemisphere were changed kept at σ2 = 0.1Sm-1 to 2Sm-1 and ɛr 2 = 102 to 105. A 70 mm diameter double coil was used as the source of the magnetic field. The amplitude of the current in the coil was 5488 A at a frequency of 2.9 kHz. The results show that the electric field, E induced during magnetic stimulation is independent of the relative permittivity, ɛr and varies with the conductivity. Thus the variation in E, calculated with homogeneous and heterogeneous head models was due to variation in conductivity of the tissues and not due to variation in permittivities.

  12. Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue

    Science.gov (United States)

    Armstrong, James P. K.; Shakur, Rameen; Horne, Joseph P.; Dickinson, Sally C.; Armstrong, Craig T.; Lau, Katherine; Kadiwala, Juned; Lowe, Robert; Seddon, Annela; Mann, Stephen; Anderson, J. L. Ross; Perriman, Adam W.; Hollander, Anthony P.

    2015-06-01

    Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show that pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer-surfactant complexes can provide a reservoir of oxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achieved through the development of a new cell functionalization methodology based on polymer-surfactant conjugation, which allows the delivery of functional proteins to the hMSC membrane. This new approach circumvents the need for cell surface engineering using protein chimerization or genetic transfection, and we demonstrate that the surface-modified hMSCs retain their ability to proliferate and to undergo multilineage differentiation. The functionalization technology is facile, versatile and non-disruptive, and in addition to tissue oxygenation, it should have far-reaching application in a host of tissue engineering and cell-based therapies.

  13. A histopathologic investigation on the effects of electrical stimulation on periodontal tissue regeneration in experimental bony defects in dogs.

    Science.gov (United States)

    Kaynak, Deniz; Meffert, Roland; Günhan, Meral; Günhan, Omer

    2005-12-01

    One endpoint of periodontal therapy is to regenerate the structure lost due to periodontal disease. In the periodontium, gingival epithelium is regenerated by oral epithelium. Underlying connective tissue, periodontal ligament, bone, and cementum are derived from connective tissue. Primitive connective tissue cells may develop into osteoblasts and cementoblasts, which form bone and cementum. Several procedural advances may support these regenerations; however, the regeneration of alveolar bone does not always occur. Therefore, bone stimulating factors are a main topic for periodontal reconstructive research. The present study was designed to examine histopathologically whether the application of an electrical field could demonstrate enhanced alveolar and cementum regeneration and modify tissue factors. Seven beagle dogs were used for this experiment. Mandibular left and right sides served as control and experimental sides, respectively, and 4-walled intrabony defects were created bilaterally between the third and fourth premolars. The experimental side was treated with a capacitively coupled electrical field (CCEF) (sinusoidal wave, 60 kHz, and 5 V peak-to-peak), applied for 14 hours per day. The following measurements were performed on the microphotographs: 1) the distance from the cemento-enamel junction to the apical notch (CEJ-AN) and from the crest of newly formed bone (alveolar ridge) to the apical notch (AR-AN); 2) the thickness of new cementum in the apical notch region; and 3) the length of junctional epithelium. The following histopathologic parameters were assessed by a semiquantitative subjective method: 1) inflammatory cell infiltration (ICI); 2) cellular activity of the periodontal ligament; 3) number and morphology of osteoclasts; 4) resorption lacunae; and 5) osteoblastic activity. The results showed that the quantity of new bone fill and the mean value of the thickness of the cementum were significantly higher for the experimental side (P 0

  14. Microstructure alterations in beef intramuscular connective tissue caused by hydrodynamic pressure processing

    Science.gov (United States)

    Scanning electron microscopy (SEM) was utilized to evaluate microstructural changes in intramuscular connective tissue of beef semimembranosus muscle subjected to hydrodynamic pressure processing (HDP). Samples were HDP treated in a plastic container (HDP-PC) or a steel commercial unit (HDP-CU). C...

  15. Tissue culture-induced alteration in cytosine methylation in new rice ...

    African Journals Online (AJOL)

    Zizania DNA introgression could induce a large number of genetic and epigenetic changes of the new rice recombinant inbred lines genome. In this present study, we employed inter-simple sequence repeat (ISSR) to further study the genetic and epigenetic changes that are induced by tissue culture. Changes induced by ...

  16. C60 exposure induced tissue damage and gene expression alterations in the earthworm Lumbricus rubellus

    NARCIS (Netherlands)

    Ploeg, van der M.J.C.; Handy, R.D.; Heckmann, L.H.; Hout, van der A.; Brink, van den N.W.

    2013-01-01

    Effects of C60 exposure (0, 15 or 154 mg/kg soil) on the earthworm Lumbricus rubellus were assessed at the tissue and molecular level, in two experiments. In the first experiment, earthworms were exposed for four weeks, and in the second lifelong. In both experiments, gene expression of heat shock

  17. Altered Loyalties of Neuronal Markers in Cultured Slices of Resected Human Brain Tissue

    NARCIS (Netherlands)

    Verwer, Ronald W. H.; Sluiter, Arja A.; Balesar, Rawien A.; Baayen, Johannes C.; Speijer, Dave; Idema, Sander; Swaab, Dick F.

    2016-01-01

    Organotypic cultures from normal neocortical tissue obtained at epilepsy surgery show a severe injury response. This response involves both neuronal degeneration and the proliferation of reactive cells. A salient feature of the reactive cells is the co-expression of microglial and astrocytic

  18. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?

    OpenAIRE

    Lean, M E J; Malkova, D

    2015-01-01

    The aim of this article is to review the research into the main peripheral appetite signals altered in human obesity, together with their modifications after body weight loss with diet and exercise and after bariatric surgery, which may be relevant to strategies for obesity treatment. Body weight homeostasis involves the gut?brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. The list of peripheral anorexigenic and or...

  19. A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference.

    Science.gov (United States)

    Cramer, Dina; Serrano, Luis; Schaefer, Martin H

    2016-11-10

    Copy number alterations (CNAs) in cancer patients show a large variability in their number, length and position, but the sources of this variability are not known. CNA number and length are linked to patient survival, suggesting clinical relevance. We have identified genes that tend to be mutated in samples that have few or many CNAs, which we term CONIM genes (COpy Number Instability Modulators). CONIM proteins cluster into a densely connected subnetwork of physical interactions and many of them are epigenetic modifiers. Therefore, we investigated how the epigenome of the tissue-of-origin influences the position of CNA breakpoints and the properties of the resulting CNAs. We found that the presence of heterochromatin in the tissue-of-origin contributes to the recurrence and length of CNAs in the respective cancer type.

  20. Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development.

    Science.gov (United States)

    Degnim, Amy C; Hoskin, Tanya L; Arshad, Muhammad; Frost, Marlene H; Winham, Stacey J; Brahmbhatt, Rushin A; Pena, Alvaro; Carter, Jodi M; Stallings-Mann, Melody L; Murphy, Linda M; Miller, Erin E; Denison, Lori A; Vachon, Celine M; Knutson, Keith L; Radisky, Derek C; Visscher, Daniel W

    2017-07-15

    Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD). Experimental Design: A breast tissue matched case-control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm 2 for CD4 + T cells, CD8 + T cells, CD20 + B cells, and CD68 + macrophages and quantification of positive pixel measure for CD11c (dendritic cells). Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8 + T cells, CD11c + dendritic cells, CD20 + B cells, and CD68 + macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20 + cell density ( P = 0.04). Nearly 42% of BBD cases had no CD20 + B cells in evaluated lobules compared with 28% of BBD controls ( P = 0.02). The absence of CD20 + cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4-23.1) for subsequent breast cancer risk. Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. Clin Cancer Res; 23(14); 3945-52. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Bouffard Nicole A

    2009-12-01

    Full Text Available Abstract Background Although the connective tissues forming the fascial planes of the back have been hypothesized to play a role in the pathogenesis of chronic low back pain (LBP, there have been no previous studies quantitatively evaluating connective tissue structure in this condition. The goal of this study was to perform an ultrasound-based comparison of perimuscular connective tissue structure in the lumbar region in a group of human subjects with chronic or recurrent LBP for more than 12 months, compared with a group of subjects without LBP. Methods In each of 107 human subjects (60 with LBP and 47 without LBP, parasagittal ultrasound images were acquired bilaterally centered on a point 2 cm lateral to the midpoint of the L2-3 interspinous ligament. The outcome measures based on these images were subcutaneous and perimuscular connective tissue thickness and echogenicity measured by ultrasound. Results There were no significant differences in age, sex, body mass index (BMI or activity levels between LBP and No-LBP groups. Perimuscular thickness and echogenicity were not correlated with age but were positively correlated with BMI. The LBP group had ~25% greater perimuscular thickness and echogenicity compared with the No-LBP group (ANCOVA adjusted for BMI, p Conclusion This is the first report of abnormal connective tissue structure in the lumbar region in a group of subjects with chronic or recurrent LBP. This finding was not attributable to differences in age, sex, BMI or activity level between groups. Possible causes include genetic factors, abnormal movement patterns and chronic inflammation.

  2. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats

    Directory of Open Access Journals (Sweden)

    Charlene eDiepenbroek

    2013-12-01

    Full Text Available Deep brain stimulation (DBS of the nucleus accumbens (NAc is an effective therapy for obsessive compulsive disorder (OCD and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of one hour. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients.

  3. A Novel Pulsatile Bioreactor for Mechanical Stimulation of Tissue Engineered Cardiac Constructs

    Directory of Open Access Journals (Sweden)

    Günther Eissner

    2011-07-01

    Full Text Available After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro.

  4. Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering microscopy (Conference Presentation)

    Science.gov (United States)

    Hu, Fanghao; Chen, Zhixing; Zhang, Luyuan; Shen, Yihui; Wei, Lu; Min, Wei

    2016-03-01

    Glucose is consumed as an energy source by virtually all living organisms, from bacteria to humans. Its uptake activity closely reflects the cellular metabolic status in various pathophysiological transformations, such as diabetes and cancer. Extensive efforts such as positron emission tomography, magnetic resonance imaging and fluorescence microscopy have been made to specifically image glucose uptake activity but all with technical limitations. Here, we report a new platform to visualize glucose uptake activity in live cells and tissues with subcellular resolution and minimal perturbation. A novel glucose analogue with a small alkyne tag (carbon-carbon triple bond) is developed to mimic natural glucose for cellular uptake, which can be imaged with high sensitivity and specificity by targeting the strong and characteristic alkyne vibration on stimulated Raman scattering (SRS) microscope to generate a quantitative three dimensional concentration map. Cancer cells with differing metabolic characteristics can be distinguished. Heterogeneous uptake patterns are observed in tumor xenograft tissues, neuronal culture and mouse brain tissues with clear cell-cell variations. Therefore, by offering the distinct advantage of optical resolution but without the undesirable influence of bulky fluorophores, our method of coupling SRS with alkyne labeled glucose will be an attractive tool to study energy demands of living systems at the single cell level.

  5. Tissue localization and fate in mice of injected multipotential colony-stimulating factor

    International Nuclear Information System (INIS)

    Metcalf, D.; Nicola, N.A.

    1988-01-01

    The hemopoietic regulator multipotential colony-stimulating factor [Multi-CSF (interleukin 3)] has proliferative effects on a wide range of hemopoietic cells in vitro and in vivo. Native or recombination Multi-CSF injected intravenoulsy into adult mice had an initial half-life of 3-5 min and a second phase of 50 min. Clear labeling of hemopoietic cells was observed in the bone marrow and spleen of mice injected intravenously with recombinant 125 I-labeled Multi-CSF showing that injected Multi-CSF can obtain access to such cells in situ. A high proportion of injected 125 I-labeled Multi-CSF of both types became localized in the liver and in the kidney (in cells of the Bowman's capsule and proximal renal tubules). The kidney appeared to be an active site of degradation of Multi-CSF with the early appearance of low molecular weight labeled material in the urine

  6. Altering the architecture of tissue engineered hypertrophic cartilaginous grafts facilitates vascularisation and accelerates mineralisation.

    Directory of Open Access Journals (Sweden)

    Eamon J Sheehy

    Full Text Available Cartilaginous tissues engineered using mesenchymal stem cells (MSCs can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossification. Inspired by this developmental feature, the objective of this study was to promote endochondral ossification of an engineered cartilaginous construct through modification of scaffold architecture. Our hypothesis was that the introduction of channels into MSC-seeded hydrogels would firstly facilitate the in vitro development of scaled-up hypertrophic cartilaginous tissues, and secondly would accelerate vascularisation and mineralisation of the graft in vivo. MSCs were encapsulated into hydrogels containing either an array of micro-channels, or into non-channelled 'solid' controls, and maintained in culture conditions known to promote a hypertrophic cartilaginous phenotype. Solid constructs accumulated significantly more sGAG and collagen in vitro, while channelled constructs accumulated significantly more calcium. In vivo, the channels acted as conduits for vascularisation and accelerated mineralisation of the engineered graft. Cartilaginous tissue within the channels underwent endochondral ossification, producing lamellar bone surrounding a hematopoietic marrow component. This study highlights the potential of utilising engineering methodologies, inspired by developmental skeletal processes, in order to enhance endochondral bone regeneration strategies.

  7. Altering the architecture of tissue engineered hypertrophic cartilaginous grafts facilitates vascularisation and accelerates mineralisation.

    Science.gov (United States)

    Sheehy, Eamon J; Vinardell, Tatiana; Toner, Mary E; Buckley, Conor T; Kelly, Daniel J

    2014-01-01

    Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossification. Inspired by this developmental feature, the objective of this study was to promote endochondral ossification of an engineered cartilaginous construct through modification of scaffold architecture. Our hypothesis was that the introduction of channels into MSC-seeded hydrogels would firstly facilitate the in vitro development of scaled-up hypertrophic cartilaginous tissues, and secondly would accelerate vascularisation and mineralisation of the graft in vivo. MSCs were encapsulated into hydrogels containing either an array of micro-channels, or into non-channelled 'solid' controls, and maintained in culture conditions known to promote a hypertrophic cartilaginous phenotype. Solid constructs accumulated significantly more sGAG and collagen in vitro, while channelled constructs accumulated significantly more calcium. In vivo, the channels acted as conduits for vascularisation and accelerated mineralisation of the engineered graft. Cartilaginous tissue within the channels underwent endochondral ossification, producing lamellar bone surrounding a hematopoietic marrow component. This study highlights the potential of utilising engineering methodologies, inspired by developmental skeletal processes, in order to enhance endochondral bone regeneration strategies.

  8. Electrical vs manual acupuncture stimulation in a rat model of polycystic ovary syndrome: different effects on muscle and fat tissue insulin signaling.

    Directory of Open Access Journals (Sweden)

    Julia Johansson

    Full Text Available In rats with dihydrotestosterone (DHT-induced polycystic ovary syndrome (PCOS, repeated low-frequency electrical stimulation of acupuncture needles restores whole-body insulin sensitivity measured by euglycemic hyperinsulinemic clamp. We hypothesized that electrical stimulation causing muscle contractions and manual stimulation causing needle sensation have different effects on insulin sensitivity and related signaling pathways in skeletal muscle and adipose tissue, with electrical stimulation being more effective in DHT-induced PCOS rats. From age 70 days, rats received manual or low-frequency electrical stimulation of needles in abdominal and hind limb muscle five times/wk for 4-5 wks; controls were handled but untreated rats. Low-frequency electrical stimulation modified gene expression (decreased Tbc1d1 in soleus, increased Nr4a3 in mesenteric fat and protein expression (increased pAS160/AS160, Nr4a3 and decreased GLUT4 by western blot and increased GLUT4 expression by immunohistochemistry in soleus muscle; glucose clearance during oral glucose tolerance tests was unaffected. Manual stimulation led to faster glucose clearance and modified mainly gene expression in mesenteric adipose tissue (increased Nr4a3, Mapk3/Erk, Adcy3, Gsk3b, but not protein expression to the same extent; however, Nr4a3 was reduced in soleus muscle. The novel finding is that electrical and manual muscle stimulation affect glucose homeostasis in DHT-induced PCOS rats through different mechanisms. Repeated electrical stimulation regulated key functional molecular pathways important for insulin sensitivity in soleus muscle and mesenteric adipose tissue to a larger extent than manual stimulation. Manual stimulation improved whole-body glucose tolerance, an effect not observed after electrical stimulation, but did not affect molecular signaling pathways to the same extent as electrical stimulation. Although more functional signaling pathways related to insulin sensitivity

  9. MR imaging of soft tissue alterations after total hip arthroplasty: comparison of classic surgical approaches

    Energy Technology Data Exchange (ETDEWEB)

    Agten, Christoph A.; Sutter, Reto; Pfirrmann, Christian W.A. [Balgrist University Hospital, Radiology, Zurich (Switzerland); University of Zurich, Faculty of Medicine, Zurich (Switzerland); Dora, Claudio [Balgrist University Hospital, Orthopedic Surgery, Zurich (Switzerland); University of Zurich, Faculty of Medicine, Zurich (Switzerland)

    2017-03-15

    To compare soft-tissue changes after total hip arthroplasty with posterior, direct-lateral, anterolateral, or anterior surgical approaches. MRI of 120 patients after primary total hip arthroplasty (30 per approach) were included. Each MRI was assessed by two readers regarding identification of surgical access, fatty muscle atrophy (Goutallier classification), tendon quality (0 = normal, 1 = tendinopathy, 2 = partial tear, 3 = avulsion), and fluid collections. Readers were blinded to the surgical approach. Surgical access was correctly identified in all cases. The direct lateral approach showed highest Goutallier grades and tendon damage for gluteus minimus muscle (2.07-2.67 and 2.00-2.77; p = 0.017 and p = 0.001 for readers 1 and 2, respectively) and tendon (2.30/1.67; p < 0.0005 for reader 1/2), and the lateral portion of the gluteus medius tendon (2.77/2.20; p < 0.0005 for reader 1/2). The posterior approach showed highest Goutallier grades and tendon damage for external rotator muscles (1.97-2.67 and 1.57-2.40; p < 0.0005-0.006 for reader 1/2) and tendons (1.41-2.45 and 1.93-2.76; p < 0.0005 for reader 1/2). The anterolateral and anterior approach showed less soft tissue damage. Fluid collections showed no differences between the approaches. MRI is well suited to identify surgical approaches after THA. The anterior and anterolateral approach showed less soft tissue damage compared to the posterior and direct lateral approach. (orig.)

  10. Fructose increases corticosterone production in association with NADPH metabolism alterations in rat epididymal white adipose tissue.

    Science.gov (United States)

    Prince, Paula D; Santander, Yanina A; Gerez, Estefania M; Höcht, Christian; Polizio, Ariel H; Mayer, Marcos A; Taira, Carlos A; Fraga, Cesar G; Galleano, Monica; Carranza, Andrea

    2017-08-01

    Metabolic syndrome is an array of closely metabolic disorders that includes glucose intolerance/insulin resistance, central obesity, dyslipidemia, and hypertension. Fructose, a highly lipogenic sugar, has profound metabolic effects in adipose tissue, and has been associated with the etiopathology of many components of the metabolic syndrome. In adipocytes, the enzyme 11 β-HSD1 amplifies local glucocorticoid production, being a key player in the pathogenesis of central obesity and metabolic syndrome. 11 β-HSD1 reductase activity is dependent on NADPH, a cofactor generated by H6PD inside the endoplasmic reticulum. Our focus was to explore the effect of fructose overload on epididymal white adipose tissue (EWAT) machinery involved in glucocorticoid production and NADPH and oxidants metabolism. Male Sprague-Dawley rats fed with a fructose solution (10% (w/v) in tap water) during 9 weeks developed some characteristic features of metabolic syndrome, such as hypertriglyceridemia, and hypertension. In addition, high levels of plasma and EWAT corticosterone were detected. Activities and expressions of H6PD and 11 β-HSD1, NAPDH content, superoxide anion production, expression of NADPH oxidase 2 subunits, and indicators of oxidative metabolism were measured. Fructose overloaded rats showed an increased potential in oxidant production respect to control rats. In parallel, in EWAT from fructose overloaded rats we found higher expression/activity of H6PD and 11 β-HSD1, and NADPH/NADP + ratio. Our in vivo results support that fructose overload installs in EWAT conditions favoring glucocorticoid production through higher H6PD expression/activity supplying NADPH for enhanced 11 β-HSD1 expression/activity, becoming this tissue a potential extra-adrenal source of corticosterone under these experimental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Altered lipid metabolism in residual white adipose tissues of Bscl2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Weiqin Chen

    Full Text Available Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2 disease. We previously reported that Bscl2 (-/- mice develop lipodystrophy of white adipose tissue (WAT due to unbridled lipolysis. The residual epididymal WAT (EWAT displays a browning phenotype with much smaller lipid droplets (LD and higher expression of brown adipose tissue marker proteins. Here we used targeted lipidomics and gene expression profiling to analyze lipid profiles as well as genes involved in lipid metabolism in WAT of wild-type and Bscl2(-/- mice. Analysis of total saponified fatty acids revealed that the residual EWAT of Bscl2(-/- mice contained a much higher proportion of oleic 18:1n9 acid concomitant with a lower proportion of palmitic 16:0 acid, as well as increased n3- polyunsaturated fatty acids (PUFA remodeling. The acyl chains in major species of triacylglyceride (TG and diacylglyceride (DG in the residual EWAT of Bscl2(-/- mice were also enriched with dietary fatty acids. These changes could be reflected by upregulation of several fatty acid elongases and desaturases. Meanwhile, Bscl2(-/- adipocytes from EWAT had increased gene expression in lipid uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and peroxisomal β-oxidation genes were also markedly increased in Bscl2(-/- adipocytes, highlighting that these machineries were accelerated to shunt the lipolysis liberated fatty acids through uncoupling to dissipate energy. The residual subcutaneous white adipose tissue (ScWAT was not browning but displays similar changes in lipid metabolism. Overall, our data emphasize that, other than being essential for adipocyte differentiation, Bscl2 is also important in fatty acid remodeling and energy homeostasis.

  12. MR imaging of soft tissue alterations after total hip arthroplasty: comparison of classic surgical approaches

    International Nuclear Information System (INIS)

    Agten, Christoph A.; Sutter, Reto; Pfirrmann, Christian W.A.; Dora, Claudio

    2017-01-01

    To compare soft-tissue changes after total hip arthroplasty with posterior, direct-lateral, anterolateral, or anterior surgical approaches. MRI of 120 patients after primary total hip arthroplasty (30 per approach) were included. Each MRI was assessed by two readers regarding identification of surgical access, fatty muscle atrophy (Goutallier classification), tendon quality (0 = normal, 1 = tendinopathy, 2 = partial tear, 3 = avulsion), and fluid collections. Readers were blinded to the surgical approach. Surgical access was correctly identified in all cases. The direct lateral approach showed highest Goutallier grades and tendon damage for gluteus minimus muscle (2.07-2.67 and 2.00-2.77; p = 0.017 and p = 0.001 for readers 1 and 2, respectively) and tendon (2.30/1.67; p < 0.0005 for reader 1/2), and the lateral portion of the gluteus medius tendon (2.77/2.20; p < 0.0005 for reader 1/2). The posterior approach showed highest Goutallier grades and tendon damage for external rotator muscles (1.97-2.67 and 1.57-2.40; p < 0.0005-0.006 for reader 1/2) and tendons (1.41-2.45 and 1.93-2.76; p < 0.0005 for reader 1/2). The anterolateral and anterior approach showed less soft tissue damage. Fluid collections showed no differences between the approaches. MRI is well suited to identify surgical approaches after THA. The anterior and anterolateral approach showed less soft tissue damage compared to the posterior and direct lateral approach. (orig.)

  13. Tissue alterations in the pirarucu, Arapaima gigas, infected by Goezia spinulosa (Nematoda).

    Science.gov (United States)

    Menezes, Rodrigo Caldas; Dos Santos, Sonia Maria Cursino; Ceccarelli, Paulo Sérgio; Tavares, Luiz Eduardo Roland; Tortelly, Rogério; Luque, José Luis

    2011-01-01

    Five specimens of Arapaima gigas caught in the Araguaia River (State of Mato Grosso, Brazil) were investigated for helminths in 2004. Numerous adult specimens of the rhapidascarid nematode Goezia spinulosa were found in stomach ulcers in all the specimens of A. gigas and were surrounded by thickening of the mucosa. The gastric glands of all the fish were necrotic and there was a severe and diffuse inflammatory reaction composed of eosinophils (which were predominant), lymphocytes and rare macrophages in the mucosa, submucosa and muscle layer. This is the first report of tissue lesion occurrences in this host, in the presence of G. spinulosa, and it confirms the high pathogenicity of this parasite species.

  14. Feeding a high-concentrate corn straw diet induced epigenetic alterations in the mammary tissue of dairy cows.

    Directory of Open Access Journals (Sweden)

    Guozhong Dong

    Full Text Available The objective of this study was to investigate the effects of feeding a high-concentrate corn straw (HCS diet (65% concentrate+35% corn straw on the epigenetic changes in the mammary tissue of dairy cows in comparison with a low-concentrate corn straw (LCS diet (46% concentrate+54% corn straw and with a low-concentrate mixed forage (LMF diet (46% concentrate+54% mixed forage.Multiparous mid-lactation Chinese Holstein cows were fed one of these three diets for 6 weeks, at which time blood samples and mammary tissue samples were collected. Mammary arterial and venous blood samples were analyzed for lipopolysaccharide (LPS concentrations while mammary tissue samples were assayed for histone H3 acetylation and the methylation of specific genes associated with fat and protein synthesis.Extraction of histones and quantification of histone H3 acetylation revealed that acetylation was significantly reduced in cows fed the HCS diet, as compared with cows fed the LCS diet. Cows fed the HCS diet had significantly higher LPS concentrations in the mammary arterial blood, as compared with cows fed the LCS diet. We found that the extent of histone H3 acetylation was negatively correlated with LPS concentrations. The methylation of the stearoyl-coenzyme A desaturase gene associated with milk fat synthesis was increased in cows fed the HCS diet. By contrast, methylation of the gene encoding the signal transducer and activator of transcription 5A was reduced in cows fed the HCS diet, suggesting that feeding a high-concentrate corn straw diet may alter the methylation of specific genes involved in fat and protein synthesis in the mammary tissue of dairy cows.Feeding the high-concentrate diet induced epigenetic changes in the mammary tissues of dairy cows, possibly through effecting the release of differing amounts of LPS into the mammary blood.

  15. Acute exposure of mercury chloride stimulates the tissue regeneration program and reactive oxygen species production in the Drosophila midgut.

    Science.gov (United States)

    Chen, Zhi; Wu, Xiaochun; Luo, Hongjie; Zhao, Lingling; Ji, Xin; Qiao, Xianfeng; Jin, Yaping; Liu, Wei

    2016-01-01

    We used Drosophila as an animal model to study the digestive tract in response to the exposure of inorganic mercury (HgCl2). We found that after oral administration, mercury was mainly sequestered within the midgut. This resulted in increased cell death, which in turn stimulated the tissue regeneration program, including accelerated proliferation and differentiation of the intestinal stem cells (ISCs). We further demonstrated that these injuries correlate closely with the excessive production of the reactive oxygen species (ROS), as vitamin E, an antioxidant reagent, efficiently suppressed the HgCl2-induced phenotypes of midgut and improved the viability. We propose that the Drosophila midgut could serve as a suitable model to study the treatment of acute hydrargyrism on the digestive systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Fatty acid alterations caused by PCBs (Aroclor 1242) and copper in adipose tissue around lymph nodes of mink

    International Nuclear Information System (INIS)

    Kaekelae, R.; Hyvaerinen, H.

    1999-01-01

    Fatty acid composition was determined in adipose tissue surrounding the mesenteric lymph nodes of mink (Mustela vison) exposed to polychlorinated biphenyls (PCBs: 1 mg Aroclor 1242 in food day -1 for 28 days) and/or copper (62 mg kg -1 food). These specific adipose tissues are known to have functional relationships with lymphocytes, and proliferation of cultured lymphocytes is influenced by the quality of fatty acids available in media. In six experimental groups the diet was based on freshwater fish, and in two groups it was based on marine fish. These basal diets differed in terms of fatty acid composition and content of fat-soluble vitamins A 1 and E. The fatty acid composition of membrane phospholipids (PL) responded to PCBs more than that of triacylglycerols (TG). The effects of copper were small. In female minks fed a diet of freshwater fish, the proportion of highly unsaturated fatty acids in PL decreased by 5 wt.% due to PCBs, and the acids seemed to be replaced by monounsaturated fatty acids (9 wt.% increase of total). This decrease of highly unsaturated fatty acids in PL was milder in minks on the marine fish diet rich in fat-soluble vitamins. In TG of minks on the marine diet, however, PCBs decreased the proportion of docosahexaenoic acid (22:6n-3). The possibility that these alterations in the fatty acid metabolism of adipose tissue supporting the lymph nodes affect immune function during PCB exposure should be studied further. Interestingly, the quality of the fish diet affected the magnitude of the alterations. The fatty acid responses may also differ between males and females. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  17. Leptospira interrogans stably infects zebrafish embryos, altering phagocyte behavior and homing to specific tissues.

    Directory of Open Access Journals (Sweden)

    J Muse Davis

    2009-06-01

    Full Text Available Leptospirosis is an extremely widespread zoonotic infection with outcomes ranging from subclinical infection to fatal Weil's syndrome. Despite the global impact of the disease, key aspects of its pathogenesis remain unclear. To examine in detail the earliest steps in the host response to leptospires, we used fluorescently labelled Leptospira interrogans serovar Copenhageni to infect 30 hour post fertilization zebrafish embryos by either the caudal vein or hindbrain ventricle. These embryos have functional innate immunity but have not yet developed an adaptive immune system. Furthermore, they are optically transparent, allowing direct visualization of host-pathogen interactions from the moment of infection. We observed rapid uptake of leptospires by phagocytes, followed by persistent, intracellular infection over the first 48 hours. Phagocytosis of leptospires occasionally resulted in formation of large cellular vesicles consistent with apoptotic bodies. By 24 hours, clusters of infected phagocytes were accumulating lateral to the dorsal artery, presumably in early hematopoietic tissue. Our observations suggest that phagocytosis may be a key defense mechanism in the early stages of leptospirosis, and that phagocytic cells play roles in immunopathogenesis and likely in the dissemination of leptospires to specific target tissues.

  18. Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications.

    Science.gov (United States)

    Fortunato, Tiago M; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A; Pula, Giordano

    2016-05-04

    Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs.

  19. Liposomal α-galactosylceramide is taken up by gut-associated lymphoid tissue and stimulates local and systemic immune responses.

    Science.gov (United States)

    Kaneko, Kan; McDowell, Arlene; Ishii, Yasuyuki; Hook, Sarah

    2017-12-01

    α-Galactosylceramide (α-GalCer), a synthetic glycosphingolipid that exhibits potent immunostimulatory effects through activation of natural killer T (NKT) cells, can be used to treat conditions such as atopy, cancer, infection and autoimmunity. Administration of therapeutics through the oral route has advantages such as patient convenience, safety and reduced cost; however, there has been little research to investigate whether oral delivery of α-GalCer is possible. The aim of this study was therefore to determine whether α-GalCer formulated in either DMSO/Tween 80 or in liposomes, could access lymphoid tissue and stimulate immune activation following oral administration. Fluorescently labelled cationic liposomes incorporating α-GalCer were prepared, characterized and administered by oral gavage to fasted mice. Liposomes were detected inside the Peyer's patches (PPs), in the subepithelial dome just under the follicle-associated epithelium. CD11b + cells and CD11c + were shown to have taken up the formulation in a higher proportion compared to the total cell proportion in the PPs, suggesting that cells with these markers may be the prominent antigen-presenting cells involved in selective uptake. Finally, the liposomal formulation demonstrated a higher degree of immune stimulation compared to the DMSO/Tween 80 solubilized α-GalCer in the PPs, mesenteric lymph nodes and spleen as shown by the increased expression of IL-4 mRNA expression and increased proportion of NKT cells at 6 h and 3 days after administration. These results show that oral delivery of a liposomal α-GalCer can stimulate local and systemic immune responses to a different degree compared to the non-liposomal form. © 2017 Royal Pharmaceutical Society.

  20. Effects of heat stimulation and l-ascorbic acid 2-phosphate supplementation on myogenic differentiation of artificial skeletal muscle tissue constructs.

    Science.gov (United States)

    Ikeda, Kazushi; Ito, Akira; Sato, Masanori; Kanno, Shota; Kawabe, Yoshinori; Kamihira, Masamichi

    2017-05-01

    Although skeletal muscle tissue engineering has been extensively studied, the physical forces produced by tissue-engineered skeletal muscles remain to be improved for potential clinical utility. In this study, we examined the effects of mild heat stimulation and supplementation of a l-ascorbic acid derivative, l-ascorbic acid 2-phosphate (AscP), on myoblast differentiation and physical force generation of tissue-engineered skeletal muscles. Compared with control cultures at 37°C, mouse C2C12 myoblast cells cultured at 39°C enhanced myotube diameter (skeletal muscle hypertrophy), whereas mild heat stimulation did not promote myotube formation (differentiation rate). Conversely, AscP supplementation resulted in an increased differentiation rate but did not induce skeletal muscle hypertrophy. Following combined treatment with mild heat stimulation and AscP supplementation, both skeletal muscle hypertrophy and differentiation rate were enhanced. Moreover, the active tension produced by the tissue-engineered skeletal muscles was improved following combined treatment. These findings indicate that tissue culture using mild heat stimulation and AscP supplementation is a promising approach to enhance the function of tissue-engineered skeletal muscles. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Biological alterations resulting from chronic lung irradiation. II. Connective tissue alterations following inhalation of 144Ce fused clay aerosol in beagle dogs

    International Nuclear Information System (INIS)

    Pickrell, J.A.; Harris, D.V.; Pfleger, R.C.; Benjamin, S.A.; Belasich, J.J.; Jones, R.K.; McClellan, R.O.

    1975-01-01

    Beagle dogs were exposed by inhalation to an aerosol of 144 Ce clay to quantitate the relationship between pulmonary radiation dose and induced fibrosis. Collagen, elastin, glucosamine, and the ratios of elastin/collagen, hydroxyproline/hydroxylysine, and hydroxyproline/proline were determined to indicate changes in connective tissue constituents. Total lung collagen was partitioned into native collagen, soluble collagen, and ultrafilterable hydroxyproline peptides. Increased total lung collagen correlated best with increasing cumulative radiation dose and increasing time after inhalation exposure. The increase in total lung collagen was not seen until more than 4 mo after exposure and a cumulative dose of about 40,000 rad. Soluble collagen and low molecular weight hydroxyproline peptide quantities both increased at 2 mo after exposure and cumulative doses of 20,000 to 27,000 rad. A variable elastin response apparently was not related to either increasing time or increasing radiation dose after exposure. These results indicate that collagen accumulation is an important factor in pulmonary fibrosis. Although collagen synthesis and breakdown were both activated at a relatively early time after inhalation, a significant increase in native collagen (scarring) occurred only when the metabolic balance was altered by protracted time or irradiation after exposure. The interrelationships observed in this study provide insight into the mechanism of fibrosis induced by chronic pulmonary injury. (U.S.)

  2. Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain.

    Science.gov (United States)

    Nordberg, Rachel C; Bodle, Josie C; Loboa, Elizabeth G

    2018-01-01

    It is critical that human adipose stem cell (hASC) tissue-engineering therapies possess appropriate mechanical properties in order to restore function of the load bearing tissues of the musculoskeletal system. In an effort to elucidate the hASC response to mechanical stimulation and develop mechanically robust tissue engineered constructs, recent research has utilized a variety of mechanical loading paradigms including cyclic tensile strain, cyclic hydrostatic pressure, and mechanical unloading in simulated microgravity. This chapter describes methods for applying these mechanical stimuli to hASC to direct differentiation for functional tissue engineering of the musculoskeletal system.

  3. Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats.

    Directory of Open Access Journals (Sweden)

    Mônica G Corrêa

    Full Text Available This study investigated some immunological features by experimental periodontitis (EP and rheumatoid arthritis (RA disease interact in destructive processes in arthritic rats. Rats were assigned to the following groups: EP +RA; RA; EP; and Negative Control. RA was induced by immunizations with type-II collagen and a local immunization with Complete Freund's adjuvant in the paw. Periodontitis was induced by ligating the right first molars. The serum level of rheumatoid factor (RF and anti-citrullinated protein antibody (ACCPA were measured before the induction of EP (T1 and at 28 days after (T2 by ELISA assay. ACCPA levels were also measured in the gingival tissue at T2. The specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for the quantification of interleukin IL-1β, IL-4, IL-6, IL-17 and TNF-α using a Luminex/MAGpix assay. Paw edema was analyzed using a plethysmometer. Periodontitis increased the RF and ACCPA levels in the serum and in the gingival tissue, respectively. Besides, the level of paw swelling was increased by EP and remained in progress until the end of the experiment, when EP was associated with RA. Greater values of IL-17 were observed only when RA was present, in spite of PE. It can be concluded that periodontitis increases rheumatic factor serum levels and citrullinated proteins level in gingival tissues and alter cytokine balance in arthritic rats; at the same time, arthritis increases periodontal destruction, confirming the bidirectional interaction between diseases.

  4. Influence of vascular endothelial growth factor stimulation and serum deprivation on gene activation patterns of human adipose tissue-derived stromal cells

    DEFF Research Database (Denmark)

    Tratwal, Josefine; Mathiasen, Anders Bruun; Juhl, Morten

    2015-01-01

    INTRODUCTION: Stimulation of mesenchymal stromal cells and adipose tissue-derived stromal cells (ASCs) with vascular endothelial growth factor (VEGF) has been used in multiple animal studies and clinical trials for regenerative purposes. VEGF stimulation is believed to promote angiogenesis and VEGF...... stimulation is usually performed under serum deprivation. Potential regenerative molecular mechanisms are numerous and the role of contributing factors is uncertain. The aim of the current study was to investigate the effect of in vitro serum deprivation and VEGF stimulation on gene expression patterns...... of ASCs. METHODS: Gene expressions of ASCs cultured in complete medium, ASCs cultured in serum-deprived medium and ASCs stimulated with VEGF in serum-deprived medium were compared. ASC characteristics according to criteria set by the International Society of Cellular Therapy were confirmed by flow...

  5. Soft tissue sarcoma: how can posttreatment alterations be distinguished from recurrences?; Weichteilsarkome: Wie lassen sich posttherapeutische Veraenderungen von Rezidiven unterscheiden

    Energy Technology Data Exchange (ETDEWEB)

    Noebauer-Huhmann, I.M. [Universitaetsklinik fuer Radiologie und Nuklearmedizin, Abteilung fuer Neuroradiologie und Muskuloskeletale Radiologie, Wien (Austria); Grieser, T. [Klinikum Augsburg, Klinik fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Augsburg (Germany)

    2017-11-15

    The recognition of recurrent soft tissue sarcomas and the differentiation from post-treatment alterations is complex. This article aims to assist the clinical radiologist in the systematic evaluation of local follow-up imaging in soft tissue sarcoma patients. Soft tissue sarcomas encompass multiple entities with different recurrence rates and follow-up intervals. Approved and up to date recommendations are provided, including imaging techniques. The past medical history of the patient, the clinical situation and previous therapies should be known in detail, including surgery, radiation therapy and chemotherapy. Previous imaging results should be consulted, if available. This article describes the time-dependent imaging spectrum of local post-therapeutic as well as local treatment-related complications. These include early complications, such as seromas, hematomas and infections, as well as late complications, including edema, fibrosis and joint stiffness, and also inflammatory pseudotumors, which may occur after variable time intervals. The imaging appearance of local recurrent and radiation-associated sarcoma are elucidated. In particular, magnetic resonance imaging (MRI) criteria are provided, which may help in differentiating post-therapeutic alterations from recurrent soft tissue sarcomas. (orig.) [German] Die Erkennung von Weichteilsarkomrezidiven und ihre Differenzierung von posttherapeutischen Veraenderungen sind komplex. Der Beitrag soll dem klinisch taetigen Radiologen helfen, lokale Nachkontrollen systematisch zu beurteilen. Voraussetzungen sind einerseits die genaue Kenntnis der klinischen und therapeutischen Anamnese und der aktuellen klinischen Situation sowie andererseits eine adaequate Untersuchungstechnik, fuer die Empfehlungen gegeben werden, und ein Vergleich mit der initialen Bildgebung. Der Beitrag gibt einen Ueberblick ueber Rezidivhaeufigkeiten und Therapiemodalitaeten wie der Operation, Bestrahlung und Chemotherapie. Er beschreibt das MR

  6. Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins

    Directory of Open Access Journals (Sweden)

    Khanichi N. Charles

    2017-10-01

    Full Text Available Summary: Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice. : Deterioration of metabolic health is a hallmark of aging and generally thought to be detrimental to longevity. Charles et al. utilize FABP-deficient mice as a model to demonstrate that the preservation of metabolic health in this model persists throughout life, even under metabolic stress, but does not increase longevity. Keywords: fatty acid binding protein, aging, calorie restriction, metabolic health, inflammation, metaflammation, diabetes, obesity, de novo lipogenesis

  7. Motor unit recruitment strategies are altered during deep-tissue pain.

    Science.gov (United States)

    Tucker, Kylie; Butler, Jane; Graven-Nielsen, Thomas; Riek, Stephan; Hodges, Paul

    2009-09-02

    Muscle pain is associated with decreased motor unit discharge rate during constant force contractions. As discharge rate is a determinant of force, other adaptations in strategy must explain force maintenance during pain. Our aim was to determine whether motor unit recruitment strategies are altered during pain to maintain force despite reduced discharge rate. Motor unit discharge behavior was recorded in two muscles, one with (quadriceps) and one without [flexor pollicis longus (FPL)] synergists. Motor units were recruited during matched low-force contractions with and without experimentally induced pain, and at higher force without pain. A total of 52 and 34 units were recorded in quadriceps and FPL, respectively, during low-force contractions with and without pain. Of these, 20 quadriceps and 9 FPL units were identified during both trials. The discharge rate of these units reduced during pain in both muscles [quadriceps: 8.7 (1.5) to 7.5 (1.3) Hz, p units discharged only with or without pain, but not in both conditions. Only one-third of the additional units recruited during pain (quadriceps n = 7/19, FPL n = 3/15) were those expected given orderly recruitment of the motor unit pool as determined during higher-force contractions. We conclude that reduced motor unit discharge rate with pain is accompanied by changes in the population of units used to maintain force. The recruitment of new units is partly inconsistent with generalized inhibition of the motoneuron pool predicted by the "pain adaptation" theory, and provides the basis for a new mechanism of motor adaptation with pain.

  8. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?

    Science.gov (United States)

    Lean, M E J; Malkova, D

    2016-04-01

    The aim of this article is to review the research into the main peripheral appetite signals altered in human obesity, together with their modifications after body weight loss with diet and exercise and after bariatric surgery, which may be relevant to strategies for obesity treatment. Body weight homeostasis involves the gut-brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. The list of peripheral anorexigenic and orexigenic physiological factors in both animals and humans is intimidating and expanding, but anorexigenic glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and orexigenic ghrelin from the gastrointestinal tract, pancreatic polypeptide (PP) from the pancreas and anorexigenic leptin from adiposites remain the most widely studied hormones. Homeostatic control of food intake occurs in humans, although its relative importance for eating behaviour is uncertain, compared with social and environmental influences. There are perturbations in the gut-brain axis in obese compared with lean individuals, as well as in weight-reduced obese individuals. Fasting and postprandial levels of gut hormones change when obese individuals lose weight, either with surgical or with dietary and/or exercise interventions. Diet-induced weight loss results in long-term changes in appetite gut hormones, postulated to favour increased appetite and weight regain while exercise programmes modify responses in a direction expected to enhance satiety and permit weight loss and/or maintenance. Sustained weight loss achieved by bariatric surgery may in part be mediated via favourable changes to gut hormones. Future work will be necessary to fully elucidate the role of each element of the axis, and whether modifying these signals can reduce the risk of obesity.

  9. Noise exposure alters long-term neural firing rates and synchrony in primary auditory and rostral belt cortices following bimodal stimulation.

    Science.gov (United States)

    Takacs, Joseph D; Forrest, Taylor J; Basura, Gregory J

    2017-12-01

    We previously demonstrated that bimodal stimulation (spinal trigeminal nucleus [Sp5] paired with best frequency tone) altered neural tone-evoked and spontaneous firing rates (SFRs) in primary auditory cortex (A1) 15 min after pairing in guinea pigs with and without noise-induced tinnitus. Neural responses were enhanced (+10 ms) or suppressed (0 ms) based on the bimodal pairing interval. Here we investigated whether bimodal stimulation leads to long-term (up to 2 h) changes in tone-evoked and SFRs and neural synchrony (correlate of tinnitus) and if the long-term bimodal effects are altered following noise exposure. To obviate the effects of permanent hearing loss on the results, firing rates and neural synchrony were measured three weeks following unilateral (left ear) noise exposure and a temporary threshold shift. Simultaneous extra-cellular single-unit recordings were made from contralateral (to noise) A1 and dorsal rostral belt (RB); an associative auditory cortical region thought to influence A1, before and after bimodal stimulation (pairing intervals of 0 ms; simultaneous Sp5-tone and +10 ms; Sp5 precedes tone). Sixty and 120 min after 0 ms pairing tone-evoked and SFRs were suppressed in sham A1; an effect only preserved 120 min following pairing in noise. Stimulation at +10 ms only affected SFRs 120 min after pairing in sham and noise-exposed A1. Within sham RB, pairing at 0 and +10 ms persistently suppressed tone-evoked and SFRs, while 0 ms pairing in noise markedly enhanced tone-evoked and SFRs up to 2 h. Together, these findings suggest that bimodal stimulation has long-lasting effects in A1 that also extend to the associative RB that is altered by noise and may have persistent implications for how noise damaged brains process multi-sensory information. Moreover, prior to bimodal stimulation, noise damage increased neural synchrony in A1, RB and between A1 and RB neurons. Bimodal stimulation led to persistent changes in neural synchrony in

  10. Composition of Dietary Fat Source Shapes Gut Microbiota Architecture and Alters Host Inflammatory Mediators in Mouse Adipose Tissue

    Science.gov (United States)

    Huang, Edmond; Leone, Vanessa; Devkota, Suzanne; Wang, Yunwei; Brady, Matthew; Chang, Eugene

    2013-01-01

    Background Growing evidence shows that dietary factors can dramatically alter the gut microbiome in ways that contribute to metabolic disturbance and progression of obesity. In this regard, mesenteric adipose tissue has been implicated in mediating these processes through the elaboration of pro-inflammatory adipokines. In this study, we examined the relationship of these events by determining the effects of dietary fat content and source on gut microbiota, as well as the effects on adipokine profiles of mesenteric and peripheral adipocytes. Methods Adult male C57Bl/6 mice were fed milk fat-, lard-(SFA sources), or safflower oil (PUFA)- based high fat diets for four weeks. Body mass and food consumption were measured. Stool 16S rRNA was isolated and analyzed via T-RFLP as well as variable V3-4 sequence tags via next gen sequencing. Mesenteric and gonadal adipose samples were analyzed for both lipogenic and inflammatory mediators via qRT-PCR. Results High-fat feedings caused more weight gain with concomitant increases in caloric consumption relative to low-fat diets. Additionally, each of the high fat diets induced dramatic and specific 16S rRNA phylogenic profiles that were associated with different inflammatory and lipogenic mediator profile of mesenteric and gonadal fat depots. Conclusions Our findings support the notion that dietary fat composition can both reshape the gut microbiota as well as alter host adipose tissue inflammatory/lipogenic profiles. They also demonstrate the interdependency of dietary fat source, commensal gut microbiota, and inflammatory profile of mesenteric fat that can collectively impact the host metabolic state. PMID:23639897

  11. Even mild respiratory distress alters tissue oxygenation significantly in preterm infants during neonatal transition

    International Nuclear Information System (INIS)

    Schwaberger, Bernhard; Pichler, Gerhard; Binder, Corinna; Pocivalnik, Mirjam; Urlesberger, Berndt; Avian, Alexander

    2014-01-01

    Near-infrared spectroscopy (NIRS) enables continuous non-invasive measurements of regional oxygen saturation (rSO 2 ). The aim was to evaluate the dynamics of rSO 2 of the brain, preductal and postductal tissues during postnatal transition in preterm infants with and without respiratory support (RS). This single-centre study was designed as an exploratory prospective observational study. Fifty one preterm infants (≥ 30 + 0 and < 37 + 0 weeks) delivered by caesarean section were included. RS using a T-Piece-Resuscitator and supplemental oxygen were given according to guidelines. NIRS measurements were carried out by using Invos Monitor (Covidien; USA) for the first 15 min of life. Three NIRS transducers were attached on the forehead (rSO 2 brain), the right forearm (rSO 2 arm) and the left lower leg (rSO 2 leg). Two groups were compared based on need for RS: normal transition (NT) and RS group. Results: In NT group rSO 2 brain increased over time and was significantly higher than rSO 2 arm, whereas in RS group rSO 2 brain and rSO 2 arm increased without significant differences. Courses of rSO 2 arm and rSO 2 leg increased over time and showed a converging pattern with initially lower values of rSO 2 leg in NT group and a diverging pattern with lower levels of rSO 2 leg in RS group. Overall, rSO 2 levels were higher in NT compared to RS group. Conclusion: Our findings indicate that the decreased rSO 2 levels in RS group compared to NT group are not only caused by lower arterial oxygen saturation levels, but also by a compromised perfusion even in infants with only mild respiratory distress. (paper)

  12. Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism.

    Directory of Open Access Journals (Sweden)

    David John Kennaway

    Full Text Available The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight. Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism.

  13. Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient.

    Directory of Open Access Journals (Sweden)

    Ling Ye

    Full Text Available BACKGROUND: Sorafenib, the drug used as first line treatment for hepatocellular carcinoma (HCC, is metabolized by cytochrome P450 (CYP 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT 1A9-mediated glucuronidation. Liver diseases are associated with reduced CYP and UGT activities, which can considerably affect drug metabolism, leading to drug toxicity. Thus, understanding the metabolism of therapeutic compounds in patients with liver diseases is necessary. However, the metabolism characteristic of sorafenib has not been systematically determined in HCC patients. METHODS: Sorafenib metabolism was tested in the pooled and individual tumor hepatic microsomes (THLMs and adjacent normal hepatic microsomes (NHLMs of HCC patients (n = 18. Commercial hepatic microsomes (CHLMs were used as a control. In addition, CYP3A4 and UGT1A9 protein expression in different tissues were measured by Western blotting. RESULTS: The mean rates of oxidation and glucuronidation of sorafenib were significantly decreased in the pooled THLMs compared with those in NHLMs and CHLMs. The maximal velocity (Vmax of sorafenib oxidation and glucuronidation were approximately 25-fold and 2-fold decreased in the pooled THLMs, respectively, with unchanged Km values. The oxidation of sorafenib in individual THLMs sample was significantly decreased (ranging from 7 to 67-fold than that in corresponding NHLMs sample. The reduction of glucuronidation in THLMs was observed in 15 out of 18 patients' samples. Additionally, the level of CYP3A4 and UGT1A9 expression were both notably decreased in the pooled THLMs. CONCLUSIONS: Sorafenib metabolism was remarkably decreased in THLMs. This result was associated with the down regulation of the protein expression of CYP3A4 and UGT1A9.

  14. Alendronate treatment alters bone tissues at multiple structural levels in healthy canine cortical bone.

    Science.gov (United States)

    Acevedo, Claire; Bale, Hrishikesh; Gludovatz, Bernd; Wat, Amy; Tang, Simon Y; Wang, Mingyue; Busse, Björn; Zimmermann, Elizabeth A; Schaible, Eric; Allen, Matthew R; Burr, David B; Ritchie, Robert O

    2015-12-01

    Bisphosphonates are widely used to treat osteoporosis, but have been associated with atypical femoral fractures (AFFs) in the long term, which raises a critical health problem for the aging population. Several clinical studies have suggested that the occurrence of AFFs may be related to the bisphosphonate-induced changes of bone turnover, but large discrepancies in the results of these studies indicate that the salient mechanisms responsible for any loss in fracture resistance are still unclear. Here the role of bisphosphonates is examined in terms of the potential deterioration in fracture resistance resulting from both intrinsic (plasticity) and extrinsic (shielding) toughening mechanisms, which operate over a wide range of length-scales. Specifically, we compare the mechanical properties of two groups of humeri from healthy beagles, one control group comprising eight females (oral doses of saline vehicle, 1 mL/kg/day, 3 years) and one treated group comprising nine females (oral doses of alendronate used to treat osteoporosis, 0.2mg/kg/day, 3 years). Our data demonstrate treatment-specific reorganization of bone tissue identified at multiple length-scales mainly through advanced synchrotron x-ray experiments. We confirm that bisphosphonate treatments can increase non-enzymatic collagen cross-linking at molecular scales, which critically restricts plasticity associated with fibrillar sliding, and hence intrinsic toughening, at nanoscales. We also observe changes in the intracortical architecture of treated bone at microscales, with partial filling of the Haversian canals and reduction of osteon number. We hypothesize that the reduced plasticity associated with BP treatments may induce an increase in microcrack accumulation and growth under cyclic daily loadings, and potentially increase the susceptibility of cortical bone to atypical (fatigue-like) fractures. Published by Elsevier Inc.

  15. ESKIMO1 disruption in Arabidopsis alters vascular tissue and impairs water transport.

    Directory of Open Access Journals (Sweden)

    Valérie Lefebvre

    Full Text Available Water economy in agricultural practices is an issue that is being addressed through studies aimed at understanding both plant water-use efficiency (WUE, i.e. biomass produced per water consumed, and responses to water shortage. In the model species Arabidopsis thaliana, the ESKIMO1 (ESK1 gene has been described as involved in freezing, cold and salt tolerance as well as in water economy: esk1 mutants have very low evapo-transpiration rates and high water-use efficiency. In order to establish ESK1 function, detailed characterization of esk1 mutants has been carried out. The stress hormone ABA (abscisic acid was present at high levels in esk1 compared to wild type, nevertheless, the weak water loss of esk1 was independent of stomata closure through ABA biosynthesis, as combining mutant in this pathway with esk1 led to additive phenotypes. Measurement of root hydraulic conductivity suggests that the esk1 vegetative apparatus suffers water deficit due to a defect in water transport. ESK1 promoter-driven reporter gene expression was observed in xylem and fibers, the vascular tissue responsible for the transport of water and mineral nutrients from the soil to the shoots, via the roots. Moreover, in cross sections of hypocotyls, roots and stems, esk1 xylem vessels were collapsed. Finally, using Fourier-Transform Infrared (FTIR spectroscopy, severe chemical modifications of xylem cell wall composition were highlighted in the esk1 mutants. Taken together our findings show that ESK1 is necessary for the production of functional xylem vessels, through its implication in the laying down of secondary cell wall components.

  16. Altered expression of estrogen receptor-α variant messenger RNAs between adjacent normal breast and breast tumor tissues

    International Nuclear Information System (INIS)

    Leygue, Etienne; Dotzlaw, Helmut; Watson, Peter H; Murphy, Leigh C

    2000-01-01

    -positive subset (n =8; P =0.023, Wilcoxon signed-rank test; Fig 2b). Two PCR products were obtained that corresponded to WT ER and ERD5 complementary DNAs (Fig 3a). As shown in Figure 3b, a statistically significant higher relative expression of ERD5 messenger RNA was observed in tumor components when this expression was measurable in both normal and adjacent tumor tissues (n =15; P =0.035, Wilcoxon signed-rank test). A statistically significant higher ERC4 messenger RNA expression was found in ER-positive/PR-positive tumors as compared with matched normal breast tissues. ERC4 variant messenger RNA has previously been demonstrated to be more highly expressed in ER-positive tumors that showed poor as opposed to tumors that showed good prognostic characteristics. Interestingly, we also have reported similar levels of expression of ERC4 messenger RNA in primary breast tumors and their concurrent axillary lymph node metastases. Taken together, these data suggest that the putative role of the ERC4 variant might be important at different phases of breast tumorigenesis and tumor progression; alteration of ERC4 messenger RNA expression and resulting modifications in ER signaling pathway probably occur before breast cancer cells acquire the ability to metastasize. Transient expression assays revealed that the protein encoded by ERC4 messenger RNA was unable to activate the transcription of an estrogen-responsive element-reporter gene or to modulate the wild-type ER protein activity. The biologic significance of the changes observed in ERC4 messenger RNA expression during breast tumorigenesis remains to be determined. A higher relative expression of ERD3 messenger RNA in the normal breast tissue components compared with adjacent neoplastic tissue was found in the ER-positive subgroup. These data are in agreement with the recently published report of Erenburg et al, who showed a decreased relative expression of ERD3 messenger RNA in neoplastic breast tissues compared with independent

  17. Different stimulation frequencies alter synchronous fluctuations in motor evoked potential amplitude of intrinsic hand muscles – a TMS study.

    Directory of Open Access Journals (Sweden)

    Martin Victor Sale

    2016-03-01

    Full Text Available The amplitude of motor-evoked potentials (MEPs elicited with transcranial magnetic stimulation (TMS varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic rates, and compared this with pseudo-random (aperiodic timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz and one aperiodic frequency (mean 0.2 Hz. MEPs (n = 50 were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs.

  18. Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles—a TMS Study

    Science.gov (United States)

    Sale, Martin V.; Rogasch, Nigel C.; Nordstrom, Michael A.

    2016-01-01

    The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs. PMID:27014031

  19. Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias.

    Science.gov (United States)

    Ott, Derek V M; Ullsperger, Markus; Jocham, Gerhard; Neumann, Jane; Klein, Tilmann A

    2011-07-15

    The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of the dorsolateral prefrontal cortex (DLPFC) in reinforcement learning, we applied continuous theta-burst stimulation (cTBS) either to the left or right DLPFC, or to the vertex as a control region, respectively, prior to the performance of a probabilistic learning task in an fMRI environment. While there was no influence of cTBS on learning performance per se, we observed a stimulation-dependent modulation of reward vs. punishment sensitivity: Left-hemispherical DLPFC stimulation led to a more reward-guided performance, while right-hemispherical cTBS induced a more avoidance-guided behavior. FMRI results showed enhanced prediction error coding in the ventral striatum in subjects stimulated over the left as compared to the right DLPFC. Both behavioral and imaging results are in line with recent findings that left, but not right-hemispherical stimulation can trigger a release of dopamine in the ventral striatum, which has been suggested to increase the relative impact of rewards rather than punishment on behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. The effect of mechanical stimulation on the maturation of TDSCs-poly(L-lactide-co-e-caprolactone)/collagen scaffold constructs for tendon tissue engineering.

    Science.gov (United States)

    Xu, Yuan; Dong, Shiwu; Zhou, Qiang; Mo, Xiumei; Song, Lei; Hou, Tianyong; Wu, Jinglei; Li, Songtao; Li, Yudong; Li, Pei; Gan, Yibo; Xu, Jianzhong

    2014-03-01

    Mechanical stimulation plays an important role in the development and remodeling of tendons. Tendon-derived stem cells (TDSCs) are an attractive cell source for tendon injury and tendon tissue engineering. However, these cells have not yet been fully explored for tendon tissue engineering application, and there is also lack of understanding to the effect of mechanical stimulation on the maturation of TDSCs-scaffold construct for tendon tissue engineering. In this study, we assessed the efficacy of TDSCs in a poly(L-lactide-co-ε-caprolactone)/collagen (P(LLA-CL)/Col) scaffold under mechanical stimulation for tendon tissue engineering both in vitro and in vivo, and evaluated the utility of the transplanted TDSCs-scaffold construct to promote rabbit patellar tendon defect regeneration. TDSCs displayed good proliferation and positive expressed tendon-related extracellular matrix (ECM) genes and proteins under mechanical stimulation in vitro. After implanting into the nude mice, the fluorescence imaging indicated that TDSCs had long-term survival, and the macroscopic evaluation, histology and immunohistochemistry examinations showed high-quality neo-tendon formation under mechanical stimulation in vivo. Furthermore, the histology, immunohistochemistry, collagen content assay and biomechanical testing data indicated that dynamically cultured TDSCs-scaffold construct could significantly contributed to tendon regeneration in a rabbit patellar tendon window defect model. TDSCs have significant potential to be used as seeded cells in the development of tissue-engineered tendons, which can be successfully fabricated through seeding of TDSCs in a P(LLA-CL)/Col scaffold followed by mechanical stimulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Distribution of internal pressure around bony prominences: implications to deep tissue injury and effectiveness of intermittent electrical stimulation.

    Science.gov (United States)

    Solis, Leandro R; Liggins, Adrian; Uwiera, Richard R E; Poppe, Niek; Pehowich, Enid; Seres, Peter; Thompson, Richard B; Mushahwar, Vivian K

    2012-08-01

    The overall goal of this project is to develop interventions for the prevention of deep tissue injury (DTI), a form of pressure ulcers that originates in deep tissue around bony prominences. The present study focused on: (1) obtaining detailed measures of the distribution of pressure experienced by tissue around the ischial tuberosities, and (2) investigating the effectiveness of intermittent electrical stimulation (IES), a novel strategy for the prevention of DTI, in alleviating pressure in regions at risk of breakdown due to sustained loading. The experiments were conducted in adult pigs. Five animals had intact spinal cords and healthy muscles and one had a spinal cord injury that led to substantial muscle atrophy at the time of the experiment. A force-controlled servomotor was used to load the region of the buttocks to levels corresponding to 25%, 50% or 75% of each animal's body weight. A pressure transducer embedded in a catheter was advanced into the tissue to measure pressure along a three dimensional grid around the ischial tuberosity of one hind leg. For all levels of external loading in intact animals, average peak internal pressure was 2.01 ± 0.08 times larger than the maximal interfacial pressure measured at the level of the skin. In the animal with spinal cord injury, similar absolute values of internal pressure as that in intact animals were recorded, but the substantial muscle atrophy produced larger maximal interfacial pressures. Average peak internal pressure in this animal was 1.43 ± 0.055 times larger than the maximal interfacial pressure. Peak internal pressure was localized within a ±2 cm region medio-laterally and dorso-ventrally from the bone in intact animals and ±1 cm in the animal with spinal cord injury. IES significantly redistributed internal pressure, shifting the peak values away from the bone in spinally intact and injured animals. These findings provide critical information regarding the relationship between internal and

  2. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Sulin Cheng

    Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

  3. Alteration of the bone tissue material properties in type 1 diabetes mellitus: A Fourier transform infrared microspectroscopy study.

    Science.gov (United States)

    Mieczkowska, Aleksandra; Mansur, Sity Aishah; Irwin, Nigel; Flatt, Peter R; Chappard, Daniel; Mabilleau, Guillaume

    2015-07-01

    Type 1 diabetes mellitus (T1DM) is a severe disorder characterized by hyperglycemia and hypoinsulinemia. A higher occurrence of bone fractures has been reported in T1DM, and although bone mineral density is reduced in this disorder, it is also thought that bone quality may be altered in this chronic pathology. Vibrational microscopies such as Fourier transform infrared microspectroscopy (FTIRM) represent an interesting approach to study bone quality as they allow investigation of the collagen and mineral compartment of the extracellular matrix in a specific bone location. However, as spectral feature arising from the mineral may overlap with those of the organic component, the demineralization of bone sections should be performed for a full investigation of the organic matrix. The aims of the present study were to (i) develop a new approach, based on the demineralization of thin bone tissue section to allow a better characterization of the bone organic component by FTIRM, (ii) to validate collagen glycation and collagen integrity in bone tissue and (iii) to better understand what alterations of tissue material properties in newly forming bone occur in T1DM. The streptozotocin-injected mouse (150 mg/kg body weight, injected at 8 weeks old) was used as T1DM model. Animals were randomly allocated to control (n = 8) or diabetic (n = 10) groups and were sacrificed 4 weeks post-STZ injection. Bones were collected at necropsy, embedded in polymethylmethacrylate and sectioned prior to examination by FTIRM. FTIRM collagen parameters were collagen maturity (area ratio between 1660 and 1690 cm(-1) subbands), collagen glycation (area ratio between the 1032 cm(-1) subband and amide I) and collagen integrity (area ratio between the 1338 cm(-1) subband and amide II). No significant differences in the mineral compartment of the bone matrix could be observed between controls and STZ-injected animals. On the other hand, as compared with controls, STZ-injected animals presented with

  4. Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging

    DEFF Research Database (Denmark)

    Reichkendler, M. H.; Auerbach, P.; Rosenkilde, M.

    2013-01-01

    abdominal SAT compared with CON but not in either intra- or retroperitoneal VAT. Total adipose tissue mass decreased in both exercise groups, and the decrease was distributed equally among subcutaneous and intra-abdominal depots. In conclusion, aerobic exercise training increases insulin-stimulated glucose...

  5. Does hearing in response to soft-tissue stimulation involve skull vibrations? A within-subject comparison between skull vibration magnitudes and hearing thresholds.

    Science.gov (United States)

    Chordekar, Shai; Perez, Ronen; Adelman, Cahtia; Sohmer, Haim; Kishon-Rabin, Liat

    2018-04-03

    Hearing can be elicited in response to bone as well as soft-tissue stimulation. However, the underlying mechanism of soft-tissue stimulation is under debate. It has been hypothesized that if skull vibrations were the underlying mechanism of hearing in response to soft-tissue stimulation, then skull vibrations would be associated with hearing thresholds. However, if skull vibrations were not associated with hearing thresholds, an alternative mechanism is involved. In the present study, both skull vibrations and hearing thresholds were assessed in the same participants in response to bone (mastoid) and soft-tissue (neck) stimulation. The experimental group included five hearing-impaired adults in whom a bone-anchored hearing aid was implanted due to conductive or mixed hearing loss. Because the implant is exposed above the skin and has become an integral part of the temporal bone, vibration of the implant represented skull vibrations. To ensure that middle-ear pathologies of the experimental group did not affect overall results, hearing thresholds were also obtained in 10 participants with normal hearing in response to stimulation at the same sites. We found that the magnitude of the bone vibrations initiated by the stimulation at the two sites (neck and mastoid) detected by the laser Doppler vibrometer on the bone-anchored implant were linearly related to stimulus intensity. It was therefore possible to extrapolate the vibration magnitudes at low-intensity stimulation, where poor signal-to-noise ratio limited actual recordings. It was found that the vibration magnitude differences (between soft-tissue and bone stimulation) were not different than the hearing threshold differences at the tested frequencies. Results of the present study suggest that bone vibration magnitude differences can adequately explain hearing threshold differences and are likely to be responsible for the hearing sensation. Thus, the present results support the idea that bone and soft-tissue

  6. A Low-Protein, High-Carbohydrate Diet Stimulates Thermogenesis in the Brown Adipose Tissue of Rats via ATF-2.

    Science.gov (United States)

    de França, Suélem A; dos Santos, Maísa P; Przygodda, Franciele; Garófalo, Maria Antonieta R; Kettelhut, Isis C; Magalhães, Diego A; Bezerra, Kalinne S; Colodel, Edson M; Flouris, Andreas D; Andrade, Cláudia M B; Kawashita, Nair H

    2016-03-01

    The aim of this study was to evaluate thermogenesis in the interscapular brown adipose tissue (IBAT) of rats submitted to low-protein, high-carbohydrate (LPHC) diet and the involvement of adrenergic stimulation in this process. Male rats (~100 g) were submitted to LPHC (6%-protein; 74%-carbohydrate) or control (C; 17%-protein; 63%-carbohydrate) isocaloric diets for 15 days. The IBAT temperature was evaluated in the rats before and after the administration of noradrenaline (NA) (20 µg 100 g b w(-1) min(-1)). The expression levels of uncoupling protein 1 (UCP1) and other proteins involved in the regulation of UCP1 expression were determined by Western blot (Student's t test, P ≤ 0.05). The LPHC diet promoted a 1.1 °C increase in the basal temperature of IBAT when compared with the basal temperature in the IBAT of the C group. NA administration promoted a 0.3 °C increase in basal temperature in the IBAT of the C rats and a 0.5 °C increase in the IBAT of the LPHC group. The level of UCP1 increased 60% in the IBAT of LPHC-fed rats, and among the proteins involved in its expression, such as β3-AR and α1-AR, there was a 40% increase in the levels of p38-MAPK and a 30% decrease in CREB when compared to the C rats. The higher sympathetic flux to IBAT, which is a consequence of the administration of the LPHC diet to rats, activates thermogenesis and increases the expression of UCP1 in the tissue. Our results suggest that the increase in UCP1 content may occur via p38 MAPK and ATF2.

  7. Stimulation of Slack K+ channels alters mass at the plasma membrane by triggering dissociation of a phosphatase-regulatory complex

    Science.gov (United States)

    Fleming, Matthew R.; Brown, Maile R.; Kronengold, Jack; Zhang, Yalan; Jenkins, David P.; Barcia, Gulia; Nabbout, Rima; Bausch, Anne E.; Ruth, Peter; Lukowski, Robert; Navaratnam, Dhasakumar S.; Kaczmarek, Leonard K.

    2016-01-01

    Summary Human mutations in the cytoplasmic C-terminal domain of Slack sodium-activated potassium (KNa) channels result in childhood epilepsy with severe intellectual disability. Slack currents can be increased by pharmacological activators or by phosphorylation of a Slack C-terminal residue by protein kinase C. Using an optical biosensor assay, we find that Slack channel stimulation in neurons or transfected cells produces loss of mass near the plasma membrane. Slack mutants associated with intellectual disability fail to trigger any change in mass. The loss of mass results from the dissociation of the protein phosphatase 1 (PP1) targeting protein, Phactr-1, from the channel. Phactr1 dissociation is specific to wild-type Slack channels and is not observed when related potassium channels are stimulated. Our findings suggest that Slack channels are coupled to cytoplasmic signaling pathways, and that dysregulation of this coupling may trigger the aberrant intellectual development associated with specific childhood epilepsies. PMID:27545877

  8. Stimulation of Slack K+ Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex

    Directory of Open Access Journals (Sweden)

    Matthew R. Fleming

    2016-08-01

    Full Text Available Human mutations in the cytoplasmic C-terminal domain of Slack sodium-activated potassium (KNa channels result in childhood epilepsy with severe intellectual disability. Slack currents can be increased by pharmacological activators or by phosphorylation of a Slack C-terminal residue by protein kinase C. Using an optical biosensor assay, we find that Slack channel stimulation in neurons or transfected cells produces loss of mass near the plasma membrane. Slack mutants associated with intellectual disability fail to trigger any change in mass. The loss of mass results from the dissociation of the protein phosphatase 1 (PP1 targeting protein, Phactr-1, from the channel. Phactr1 dissociation is specific to wild-type Slack channels and is not observed when related potassium channels are stimulated. Our findings suggest that Slack channels are coupled to cytoplasmic signaling pathways and that dysregulation of this coupling may trigger the aberrant intellectual development associated with specific childhood epilepsies.

  9. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Kucerova, Lucia; Skolekova, Svetlana; Matuskova, Miroslava; Bohac, Martin; Kozovska, Zuzana

    2013-01-01

    Mesenchymal stromal cells (MSCs) represent heterogeneous cell population suitable for cell therapies in regenerative medicine. MSCs can also substantially affect tumor biology due to their ability to be recruited to the tumor stroma and interact with malignant cells via direct contacts and paracrine signaling. The aim of our study was to characterize molecular changes dictated by adipose tissue-derived mesenchymal stromal cells (AT-MSCs) and the effects on drug responses in human breast cancer cells SKBR3. The tumor cells were either directly cocultured with AT-MSCs or exposed to MSCs-conditioned medium (MSC-CM). Changes in cell biology were evaluated by kinetic live cell imaging, fluorescent microscopy, scratch wound assay, expression analysis, cytokine secretion profiling, ATP-based viability and apoptosis assays. The efficiency of cytotoxic treatment in the presence of AT-MSCs or MSCs-CM was analyzed. The AT-MSCs altered tumor cell morphology, induced epithelial-to-mesenchymal transition, increased mammosphere formation, cell confluence and migration of SKBR3. These features were attributed to molecular changes induced by MSCs-secreted cytokines and chemokines in breast cancer cells. AT-MSCs significantly inhibited the proliferation of SKBR3 cells in direct cocultures which was shown to be dependent on the SDF-1α/CXCR4 signaling axis. MSC-CM-exposed SKBR3 or SKBR3 in direct coculture with AT-MSCs exhibited increased chemosensitivity and induction of apoptosis in response to doxorubicin and 5-fluorouracil. Our work further highlights the multi-level nature of tumor-stromal cell interplay and demonstrates the capability of AT-MSCs and MSC-secreted factors to alter the anti-tumor drug responses

  10. Altering Conventional to High Density Spinal Cord Stimulation: An Energy Dose-Response Relationship in Neuropathic Pain Therapy.

    Science.gov (United States)

    Wille, Frank; Breel, Jennifer S; Bakker, Eric W P; Hollmann, Markus W

    2017-01-01

    To examine whether converting from conventional Spinal Cord Stimulation (SCS) to High Density (HD) SCS reduces neuropathic pain over a period of 12 months in patients with failed SCS therapy. Retrospective, open label, single center, consecutive case series of 30 neuropathic pain patients (Failed Back Surgery Syndrome [FBSS], Complex Regional Pain Syndrome [CRPS], and polyneuropathy [NP]). Patients with an initial adequate response to conventional SCS, but in whom pain increased over time, were included (Numeric Rating Scales [NRS] >6). These patients were stimulated with HD-SCS parameters and followed-up for 12 months. We report pain intensity, measured with NRS, before SCS implantation, 1 and 3 months after starting SCS with conventional stimulation, and after 1, 6, and 12 months of HD SCS. Pain reduction with conventional stimulation was initially adequate (NRS mean 8.6 to 5.3 at three months postimplant) but increased over time to a mean NRS of 7.7 at the time of reprogramming. NRS scores decreased significantly to 4.3 (p = 0.015) after reprogramming from conventional SCS (30 Hz, 300 µsec, 3.0 V) to HD SCS (409 Hz, range 130-1000 Hz, 409 µsec, 2.4V) in the patients still using HD-SCS at 12 months. In the nonresponders (patients who stopped HD-SCS for any reason), 76% had a diagnosis of FBSS. Almost half of the patients aborting HD-SCS preferred to feel paresthesias despite better pain relief. There was a significant difference between nonresponders and responders regarding the amount of electrical energy delivered to the spinal cord. Neuropathic pain suppression is significantly enhanced after converting from failed conventional SCS to HD SCS in patients with FBSS, CRPS, and NP over a measured period of 12 months. There appears to be a dose-related response between the amount of energy delivered to the spinal cord and clinical effect. © 2016 International Neuromodulation Society.

  11. Anodal transcranial direct current stimulation over right dorsolateral prefrontal cortex alters decision making during approach-avoidance conflict.

    Science.gov (United States)

    Chrysikou, Evangelia G; Gorey, Claire; Aupperle, Robin L

    2017-03-01

    Approach-avoidance conflict (AAC) refers to situations associated with both rewarding and threatening outcomes. The AAC task was developed to measure AAC decision-making. Approach behavior during this task has been linked to self-reported anxiety sensitivity and has elicited anterior cingulate, insula, caudate and right dorsolateral prefrontal cortex (dlPFC) activity, with right lateral PFC tracking the extent of approach behavior. Guided by these results, we used excitatory transcranial direct current stimulation (tDCS) to demonstrate the causal involvement of right dlPFC in AAC decision-making. Participants received anodal tDCS at 1.5mA over either left or right dlPFC or sham stimulation, while performing the AAC task and a control short-term memory task. Analyses of variance (ANOVA) revealed that for individuals with high anxiety sensitivity excitatory right (but not left or sham) dlPFC stimulation elicited measurable decreases in approach behavior during conflict. Excitatory left (but not right or sham) dlPFC simulation improved performance on the control task. These results support a possible asymmetry between the contributions of right and left dlPFC to AAC resolution during emotional decision-making. Increased activity in right dlPFC may contribute to anxiety-related symptoms and, as such, serve as a neurobehavioral target of anxiolytic treatments aiming to decrease avoidance behavior. © The Author (2016). Published by Oxford University Press.

  12. Perinatal exposure to PCB 153, but not PCB 126, alters bone tissue composition in female goat offspring

    International Nuclear Information System (INIS)

    Lundberg, Rebecca; Lyche, Jan L.; Ropstad, Erik; Aleksandersen, Mona; Roenn, Monika; Skaare, Janneche U.; Larsson, Sune; Orberg, Jan; Lind, P. Monica

    2006-01-01

    The aim of this study was to investigate if environmentally relevant doses of the putative estrogenic non dioxin-like PCB 153 and the dioxin-like PCB 126 caused changes in bone tissue in female goat offspring following perinatal exposure. Goat dams were orally dosed with PCB 153 in corn oil (98 μg/kg body wt/day) or PCB 126 (49 ng/kg body wt/day) from day 60 of gestation until delivery. The offspring were exposed to PCB in utero and through mother's milk. The suckling period lasted for 6 weeks. Offspring metacarpal bones were analysed using peripheral quantitative computed tomography (pQCT) after euthanisation at 9 months of age. The diaphyseal bone was analysed at a distance of 18% and 50% of the total bone length, and the metaphyseal bone at a distance of 9%. Also, biomechanical three-point bending of the bones was conducted, with the load being applied to the mid-diaphyseal pQCT measure point (50%). PCB 153 exposure significantly decreased the total cross-sectional area (125 mm 2 ± 4) versus non-exposed (142 mm 2 ± 5), decreased the marrow cavity (38 mm 2 ± 4) versus non-exposed (50 mm 2 ± 3) and decreased the moment of resistance (318 mm 3 ± 10) versus non-exposed (371 mm 3 ± 20) at the diaphyseal 18% measure point. At the metaphyseal measure point, the trabecular bone mineral density (121 mg/cm 3 ± 5) was increased versus non-exposed (111 mg/cm 3 ± 3). PCB 126 exposure did not produce any observable changes in bone tissue. The biomechanical testing of the bones did not show any significant changes in bone strength after PCB 153 or PCB 126 exposure. In conclusion, perinatal exposure to PCB 153, but not PCB 126, resulted in altered bone composition in female goat offspring

  13. Circulating and Tissue-Resident CD4+ T Cells With Reactivity to Intestinal Microbiota Are Abundant in Healthy Individuals and Function Is Altered During Inflammation.

    Science.gov (United States)

    Hegazy, Ahmed N; West, Nathaniel R; Stubbington, Michael J T; Wendt, Emily; Suijker, Kim I M; Datsi, Angeliki; This, Sebastien; Danne, Camille; Campion, Suzanne; Duncan, Sylvia H; Owens, Benjamin M J; Uhlig, Holm H; McMichael, Andrew; Bergthaler, Andreas; Teichmann, Sarah A; Keshav, Satish; Powrie, Fiona

    2017-11-01

    Interactions between commensal microbes and the immune system are tightly regulated and maintain intestinal homeostasis, but little is known about these interactions in humans. We investigated responses of human CD4 + T cells to the intestinal microbiota. We measured the abundance of T cells in circulation and intestinal tissues that respond to intestinal microbes and determined their clonal diversity. We also assessed their functional phenotypes and effects on intestinal resident cell populations, and studied alterations in microbe-reactive T cells in patients with chronic intestinal inflammation. We collected samples of peripheral blood mononuclear cells and intestinal tissues from healthy individuals (controls, n = 13-30) and patients with inflammatory bowel diseases (n = 119; 59 with ulcerative colitis and 60 with Crohn's disease). We used 2 independent assays (CD154 detection and carboxy-fluorescein succinimidyl ester dilution assays) and 9 intestinal bacterial species (Escherichia coli, Lactobacillus acidophilus, Bifidobacterium animalis subsp lactis, Faecalibacterium prausnitzii, Bacteroides vulgatus, Roseburia intestinalis, Ruminococcus obeum, Salmonella typhimurium, and Clostridium difficile) to quantify, expand, and characterize microbe-reactive CD4 + T cells. We sequenced T-cell receptor Vβ genes in expanded microbe-reactive T-cell lines to determine their clonal diversity. We examined the effects of microbe-reactive CD4 + T cells on intestinal stromal and epithelial cell lines. Cytokines, chemokines, and gene expression patterns were measured by flow cytometry and quantitative polymerase chain reaction. Circulating and gut-resident CD4 + T cells from controls responded to bacteria at frequencies of 40-4000 per million for each bacterial species tested. Microbiota-reactive CD4 + T cells were mainly of a memory phenotype, present in peripheral blood mononuclear cells and intestinal tissue, and had a diverse T-cell receptor Vβ repertoire. These

  14. Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering.

    Science.gov (United States)

    Parvizi, Mojtaba; Bolhuis-Versteeg, Lydia A M; Poot, André A; Harmsen, Martin C

    2016-07-01

    Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-β1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-β1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well-aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre-differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-β1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: a tDCS-fMRI study.

    Science.gov (United States)

    Weber, Matthew J; Messing, Samuel B; Rao, Hengyi; Detre, John A; Thompson-Schill, Sharon L

    2014-08-01

    Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. Copyright © 2014 Wiley Periodicals, Inc.

  16. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    International Nuclear Information System (INIS)

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-01-01

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life

  17. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    Energy Technology Data Exchange (ETDEWEB)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  18. Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.

    Science.gov (United States)

    Amour, Julien; Loyer, Xavier; Le Guen, Morgan; Mabrouk, Nejma; David, Jean-Stéphane; Camors, Emmanuel; Carusio, Nunzia; Vivien, Benoît; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno

    2007-09-01

    In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic

  19. Experimental exposure of African catfish Clarias Gariepinus (Burchell, 1822 to phenol: Clinical evaluation, tissue alterations and residue assessment

    Directory of Open Access Journals (Sweden)

    Mai D. Ibrahem

    2012-04-01

    Full Text Available There is lack of information regarding; the toxicological and pathological consequences of phenol stressed Clarias gariepinus; as well as; the susceptibility of the stressed fish to disease occurrence. Static renewal bioassay was experimentally conducted to evaluate the toxic effects of phenol on the African catfish C. gariepinus. Ninety-six-hour acute toxicity tests revealed that the median lethal concentration of phenol (LC50 is 35 mg/L by immersion. Four experimental fish groups were assigned for 3 weeks exposure test; three were exposed 20%, 50% and 70% LC50, the fourth control fish group received a vehicle of dechlorinated water. Abnormal signs including cessation of feeding, nervous manifestations; skin expressed perfuses mucous, black patches with skin erosion and ulcerations in the later stages. All observations were correlated to the time and dose of exposure. Post mortem examination revealed adhesion of the internal organs. For tissue alterations; Skin, gills, brain, liver and kidney showed variable degrees of degenerative changes and necrosis. Muscle residues shown in mean ± SE were 4.3 ± 0.05 and 6.65 ± 0.05 ppm in groups that received 20 and 50% LD50, respectively. Infection with Aeromonas hydrophila resulted in high percent of mortalities with a non significant difference between the challenged fish groups. The study cleared that phenol is toxic to C. gariepinus under experimental conditions.

  20. An aqueous extract of Curcuma longa (turmeric) rhizomes stimulates insulin release and mimics insulin action on tissues involved in glucose homeostasis in vitro.

    Science.gov (United States)

    Mohankumar, Sureshkumar; McFarlane, James R

    2011-03-01

    Curcuma longa (turmeric) has been used widely as a spice, particularly in Asian countries. It is also used in the Ayurvedic system of medicine as an antiinflammatory and antimicrobial agent and for numerous other curative properties. The aim of this study was to investigate the effects of an aqueous extract of Curcuma longa (AEC) on tissues involved in glucose homeostasis. The extract was prepared by soaking 100 g of ground turmeric in 1 L of water, which was filtered and stored at -20°C prior to use. Pancreas and muscle tissues of adult mice were cultured in DMEM with 5 or 12 mmol/L glucose and varying doses of extract. The AEC stimulated insulin secretion from mouse pancreatic tissues under both basal and hyperglycaemic conditions, although the maximum effect was only 68% of that of tolbutamide. The AEC induced stepwise stimulation of glucose uptake from abdominal muscle tissues in the presence and absence of insulin, and the combination of AEC and insulin significantly potentiated the glucose uptake into abdominal muscle tissue. However, this effect was attenuated by wortmannin, suggesting that AEC possibly acts via the insulin-mediated glucose uptake pathway. In summary, water soluble compounds of turmeric exhibit insulin releasing and mimicking actions within in vitro tissue culture conditions. Copyright © 2010 John Wiley & Sons, Ltd.

  1. Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

    Science.gov (United States)

    Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

    2012-11-01

    Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  2. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  3. Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues.

    Science.gov (United States)

    Padron, Alvaro Souto; Neto, Ruy Andrade Louzada; Pantaleão, Thiago Urgal; de Souza dos Santos, Maria Carolina; Araujo, Renata Lopes; de Andrade, Bruno Moulin; da Silva Leandro, Monique; de Castro, João Pedro Saar Werneck; Ferreira, Andrea Claudia Freitas; de Carvalho, Denise Pires

    2014-06-01

    In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet. Our aim was to evaluate the effects of chronic 3,5-T2 administration on the hypothalamus-pituitary-thyroid axis, body mass gain, adipose tissue mass, and body oxygen consumption in Wistar rats from 3 to 6 months of age. The rats were treated daily with 3,5-T2 (25, 50, or 75 μg/100 g body weight, s.c.) for 90 days between the ages of 3 and 6 months. The administration of 3,5-T2 suppressed thyroid function, reducing not only thyroid iodide uptake but also thyroperoxidase, NADPH oxidase 4 (NOX4), and thyroid type 1 iodothyronine deiodinase (D1 (DIO1)) activities and expression levels, whereas the expression of the TSH receptor and dual oxidase (DUOX) were increased. Serum TSH, 3,3',5-triiodothyronine, and thyroxine were reduced in a 3,5-T2 dose-dependent manner, whereas oxygen consumption increased in these animals, indicating the direct action of 3,5-T2 on this physiological variable. Type 2 deiodinase activity increased in both the hypothalamus and the pituitary, and D1 activities in the liver and kidney were also increased in groups treated with 3,5-T2. Moreover, after 3 months of 3,5-T2 administration, body mass and retroperitoneal fat pad mass were significantly reduced, whereas the heart rate and mass were unchanged. Thus, 3,5-T2 acts as a direct stimulator of energy expenditure and reduces body mass gain; however, TSH suppression may develop secondary to 3,5-T2 administration. © 2014 The authors.

  4. Extension of Tissue Plasminogen Activator Treatment Window by Granulocyte-Colony Stimulating Factor in a Thromboembolic Rat Model of Stroke

    Directory of Open Access Journals (Sweden)

    Ike C. dela Peña

    2018-05-01

    Full Text Available When given beyond 4.5 h of stroke onset, tissue plasminogen activator (tPA induces deleterious side effects in the ischemic brain, notably, hemorrhagic transformation (HT. We examined the efficacy of granulocyte-colony stimulating factor (G-CSF in reducing delayed tPA-induced HT, cerebral infarction, and neurological deficits in a thromboembolic (TE stroke model, and whether the effects of G-CSF were sustained for longer periods of recovery. After stroke induction, rats were given intravenous saline (control, tPA (10 mg/kg, or G-CSF (300 μg/kg + tPA 6 h after stroke. We found that G-CSF reduced delayed tPA-associated HT by 47%, decreased infarct volumes by 33%, and improved motor and neurological deficits by 15% and 25%, respectively. It also prevented delayed tPA treatment-induced mortality by 46%. Immunohistochemistry showed 1.5- and 1.8-fold enrichment of the endothelial progenitor cell (EPC markers CD34+ and VEGFR2 in the ischemic cortex and striatum, respectively, and 1.7- and 2.8-fold increases in the expression of the vasculogenesis marker von Willebrand factor (vWF in the ischemic cortex and striatum, respectively, in G-CSF-treated rats compared with tPA-treated animals. Flow cytometry revealed increased mobilization of CD34+ cells in the peripheral blood of rats given G-CSF. These results corroborate the efficacy of G-CSF in enhancing the therapeutic time window of tPA for stroke treatment via EPC mobilization and enhancement of vasculogenesis.

  5. Stimulation of Slack K(+) Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex.

    Science.gov (United States)

    Fleming, Matthew R; Brown, Maile R; Kronengold, Jack; Zhang, Yalan; Jenkins, David P; Barcia, Gulia; Nabbout, Rima; Bausch, Anne E; Ruth, Peter; Lukowski, Robert; Navaratnam, Dhasakumar S; Kaczmarek, Leonard K

    2016-08-30

    Human mutations in the cytoplasmic C-terminal domain of Slack sodium-activated potassium (KNa) channels result in childhood epilepsy with severe intellectual disability. Slack currents can be increased by pharmacological activators or by phosphorylation of a Slack C-terminal residue by protein kinase C. Using an optical biosensor assay, we find that Slack channel stimulation in neurons or transfected cells produces loss of mass near the plasma membrane. Slack mutants associated with intellectual disability fail to trigger any change in mass. The loss of mass results from the dissociation of the protein phosphatase 1 (PP1) targeting protein, Phactr-1, from the channel. Phactr1 dissociation is specific to wild-type Slack channels and is not observed when related potassium channels are stimulated. Our findings suggest that Slack channels are coupled to cytoplasmic signaling pathways and that dysregulation of this coupling may trigger the aberrant intellectual development associated with specific childhood epilepsies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. [Altered expressions of alkane monooxygenase and hypoxia inducible factor-1α expression in lung tissue of rat hypoxic pulmonary hypertension].

    Science.gov (United States)

    Deng, Hua-jun; Yuan, Ya-dong

    2013-10-29

    To explore the altered expressions of alkane monooxygenase (AlkB) and hypoxia-inducible factor-1α (HIF-1α) in a rat model of hypoxic pulmonary arterial hypertension. Twenty Wistar rats were divided randomly into normal control and hypoxia groups after 1-week adaptive feeding. Hypoxia group was raised in a homemade organic glass tank with a 24-h continuous supply of air and nitrogen atmospheric mixed gas. And the oxygen concentration of (10.0 ± 0.5)% was controlled by oxygen monitoring control system. The control group was maintained in room air. Both groups stayed in the same room with the same diet. After 8 weeks, the level of mean pulmonary pressure (mPAP) was measured by right-heart catheterization, right ventricular hypertrophy index (RVHI) calculated by the ratio of right ventricle to left ventricle plus septum and hypoxic pulmonary vascular remodeling (HPSR) observed under microscope. And the levels of AlkB and HIF-1α mRNA and protein in lungs were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. At 8 weeks post-hypoxia, compared with the control group [11.0 ± 0.7 mm Hg (1 mm Hg = 0.133 kPa), 0.210 ± 0.035], the levels of mPAP and RVHI in hypoxia group (33.3 ± 1.3 mm Hg, 0.448 ± 0.013) increased significantly (both P < 0.05), the expressions of AlkB mRNA and protein in pulmonary tissue decreased significantly (0.338 ± 0.085 vs 0.688 ± 0.020, P < 0.01) (0.483 ± 0.052 vs 0.204 ± 0.010, P < 0.01), and the expressions of HIF-1α mRNA and protein increased significantly (0.790 ± 0.161 vs 0.422 ± 0.096, P < 0.01) (0.893 ± 0.080 vs 0.346 ± 0.008, P < 0.01). The down-regulation of AlkB in lung tissue may increase the activity of HIF-1 to participate in the occurrence and development of pulmonary hypertension.

  7. Studies on neurotransmitter-stimulated phospholipid metabolism with cerebral tissue suspensions: a possible biochemical correlate of synaptogenesis in normal and undernourished rats

    International Nuclear Information System (INIS)

    Reddy, P.V.; Sastry, P.S.

    1979-01-01

    The phenomenon of neurotransmitter-stimulated incorporation of 32 Pi into phosphatidic acid and inositol phosphatides (neurotransmitter effect) in developing brain was studied in vitro as a possible measure of synaptogenesis. While the neurotransmitter effect was not observed with brain homogenates, highly consistent and significant effects were noted with brain tissue suspensions obtained by passing the tissue through nylon bolting cloth. The magnitude of the effect decreased with the increase in mesh number. Maximum stimulations obtained with the 33 mesh adult brain cortex preparations (mean +- S.E.M. of 6 experiments) were 203 +- 8%, 316 +- 17% and 150 +8% with 10 -3 M acetylcholine (ACh) + 10 -3 M eserine; 10 -2 M norepinephrine (NE) and 10 -2 M serotonin (5-HT), respectively. (Auth.)

  8. Moderate caloric restriction during gestation in rats alters adipose tissue sympathetic innervation and later adiposity in offspring.

    Directory of Open Access Journals (Sweden)

    Ana Paula García

    Full Text Available Maternal prenatal undernutrition predisposes offspring to higher adiposity in adulthood. Mechanisms involved in these programming effects, apart from those described in central nervous system development, have not been established. Here we aimed to evaluate whether moderate caloric restriction during early pregnancy in rats affects white adipose tissue (WAT sympathetic innervation in the offspring, and its relationship with adiposity development. For this purpose, inguinal and retroperitoneal WAT (iWAT and rpWAT, respectively were analyzed in male and female offspring of control and 20% caloric-restricted (from 1-12 d of pregnancy (CR dams. Body weight (BW, the weight, DNA-content, morphological features and the immunoreactive tyrosine hydroxylase and Neuropeptide Y area (TH+ and NPY+ respectively, performed by immunohistochemistry of both fat depots, were studied at 25 d and 6 m of age, the latter after 2 m exposure to high fat diet. At 6 m of life, CR males but not females, exhibited greater BW, and greater weight and total DNA-content in iWAT, without changes in adipocytes size, suggesting the development of hyperplasia in this depot. However, in rpWAT, CR males but not females, showed larger adipocyte diameter, with no changes in DNA-content, suggesting the development of hypertrophy. These parameters were not different between control and CR animals at the age of 25 d. In iWAT, both at 25 d and 6 m, CR males but not females, showed lower TH(+ and NPY(+, suggesting lower sympathetic innervation in CR males compared to control males. In rpWAT, at 6 m but not at 25 d, CR males but not females, showed lower TH(+ and NPY(+. Thus, the effects of caloric restriction during gestation on later adiposity and on the differences in the adult phenotype between internal and subcutaneous fat depots in the male offspring may be associated in part with specific alterations in sympathetic innervation, which may impact on WAT architecture.

  9. Acute exposure to space flight results in evidence of reduced lymph Transport, tissue fluid Shifts, and immune alterations in the rat gastrointestinal system

    Science.gov (United States)

    Cromer, W. E.; Zawieja, D. C.

    2018-05-01

    Space flight causes a number of alterations in physiological systems, changes in the immunological status of subjects, and altered interactions of the host to environmental stimuli. We studied the effect of space flight on the lymphatic system of the gastrointestinal tract which is responsible for lipid transport and immune surveillance which includes the host interaction with the gut microbiome. We found that there were signs of tissue damage present in the space flown animals that was lacking in ground controls (epithelial damage, crypt morphological changes, etc.). Additionally, morphology of the lymphatic vessels in the tissue suggested a collapsed state at time of harvest and there was a profound change in the retention of lipid in the villi of the ileum. Contrary to our assumptions there was a reduction in tissue fluid volume likely associated with other fluid shifts described. The reduction of tissue fluid volume in the colon and ileum is a likely contributing factor to the state of the lymphatic vessels and lipid transport issues observed. There were also associated changes in the number of MHC-II+ immune cells in the colon tissue, which along with reduced lymphatic competence would favor immune dysfunction in the tissue. These findings help expand our understanding of the effects of space flight on various organ systems. It also points out potential issues that have not been closely examined and have to potential for the need of countermeasure development.

  10. Improved solar light stimulated charge separation of g-C3N4 through self-altering acidic treatment

    Science.gov (United States)

    Leong, Kah Hon; Lim, Ping Feng; Sim, Lan Ching; Punia, Varun; Pichiah, Saravanan

    2018-02-01

    Herein, we report the use of acid treatment to treat g-C3N4 nanostructured by a direct and facile synthesis route. The adopted treatment enhanced photoactivity of g-C3N4 and reflected in the removal of recalcitrant organic pollutant, Bisphenol A under direct sunlight. A complete removal of Bisphenol A was attained in a short duration (225 min) as compared to pure g-C3N4. The analysis clearly substantiated the robustness of acid exfoliation that promoted a blue shift, extended the conjugated length of its respective conduction and valance band. It also drastically prolonged the recombination rate of charge carriers, by producing excess of unpaired electrons in the conduction band for active radicals' generation. Thus, this new findings could offer a new sight of self-alteration in improving the photoactivity of complex organic pollutants for sustainable environmental remediation.

  11. Insulin alters the target size of the peripheral cyclic AMP phosphodiesterase but not the integral cyclic GMP-stimulated cyclic AMP phosphodiesterase in liver plasma membranes

    International Nuclear Information System (INIS)

    Wallace, A.V.; Martin, B.R.; Houslay, M.D.

    1990-01-01

    Radiation inactivation of the two high affinity cyclic AMP phosphodiesterases (PDE) found in liver plasma membranes afforded an estimation of their molecular target sizes in situ. The activity of the peripheral plasma membrane PDE decayed as a single exponential with a target size corresponding to a monomer of circa 54 kDa. The integral, cyclic GMP-stimulated PDE decayed as a dimer of circa 125 kDa. Preincubation of plasma membranes with insulin (10nM), prior to irradiation, caused the target size of only the peripheral plasma membrane PDE to increase. We suggest that insulin addition causes the peripheral plasma membrane PDE to alter its coupling to an integral plasma membrane protein with a target size of circa 90 kDa

  12. Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization

    Science.gov (United States)

    Stafford, Jason H.; Hirai, Takahisa; Deng, Lei; Chernikova, Sophia B.; Urata, Kimiko; West, Brian L.; Brown, J. Martin

    2016-01-01

    Background Glioblastoma (GBM) may initially respond to treatment with ionizing radiation (IR), but the prognosis remains extremely poor because the tumors invariably recur. Using animal models, we previously showed that inhibiting stromal cell–derived factor 1 signaling can prevent or delay GBM recurrence by blocking IR-induced recruitment of myeloid cells, specifically monocytes that give rise to tumor-associated macrophages. The present study was aimed at determining if inhibiting colony stimulating factor 1 (CSF-1) signaling could be used as an alternative strategy to target pro-tumorigenic myeloid cells recruited to irradiated GBM. Methods To inhibit CSF-1 signaling in myeloid cells, we used PLX3397, a small molecule that potently inhibits the tyrosine kinase activity of the CSF-1 receptor (CSF-1R). Combined IR and PLX3397 therapy was compared with IR alone using 2 different human GBM intracranial xenograft models. Results GBM xenografts treated with IR upregulated CSF-1R ligand expression and increased the number of CD11b+ myeloid-derived cells in the tumors. Treatment with PLX3397 both depleted CD11b+ cells and potentiated the response of the intracranial tumors to IR. Median survival was significantly longer for mice receiving combined therapy versus IR alone. Analysis of myeloid cell differentiation markers indicated that CSF-1R inhibition prevented IR-recruited monocyte cells from differentiating into immunosuppressive, pro-angiogenic tumor-associated macrophages. Conclusion CSF-1R inhibition may be a promising strategy to improve GBM response to radiotherapy. PMID:26538619

  13. Chronic Deep Brain Stimulation of the Hypothalamic Nucleus in Wistar Rats Alters Circulatory Levels of Corticosterone and Proinflammatory Cytokines

    Science.gov (United States)

    Calleja-Castillo, Juan Manuel; De La Cruz-Aguilera, Dora Luz; Manjarrez, Joaquín; Velasco-Velázquez, Marco Antonio; Morales-Espinoza, Gabriel; Moreno-Aguilar, Julia; Hernández, Maria Eugenia; Aguirre-Cruz, Lucinda

    2013-01-01

    Deep brain stimulation (DBS) is a therapeutic option for several diseases, but its effects on HPA axis activity and systemic inflammation are unknown. This study aimed to detect circulatory variations of corticosterone and cytokines levels in Wistar rats, after 21 days of DBS-at the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl), unilateral cervical vagotomy (UCVgX), or UCVgX plus DBS. We included the respective control (C) and sham (S) groups (n = 6 rats per group). DBS treated rats had higher levels of TNF-α (120%; P < 0.01) and IFN-γ (305%; P < 0.001) but lower corticosterone concentration (48%; P < 0.001) than C and S. UCVgX animals showed increased corticosterone levels (154%; P < 0.001) versus C and S. UCVgX plus DBS increased IL-1β (402%; P < 0.001), IL-6 (160%; P < 0.001), and corsticosterone (178%; P < 0.001 versus 48%; P < 0.001) compared with the C and S groups. Chronic DBS at VMHvl induced a systemic inflammatory response accompanied by a decrease of HPA axis function. UCVgX rats experienced HPA axis hyperactivity as result of vagus nerve injury; however, DBS was unable to block the HPA axis hyperactivity induced by unilateral cervical vagotomy. Further studies are necessary to explore these findings and their clinical implication. PMID:24235973

  14. Progressive obesity alters the steroidogenic response to ovulatory stimulation and increases the abundance of mRNAs stored in the ovulated oocyte.

    Science.gov (United States)

    Pohlmeier, William E; Xie, Fang; Kurz, Scott G; Lu, Ningxia; Wood, Jennifer R

    2014-08-01

    Obese women who are able to attain pregnancy are at increased risk for early-pregnancy loss due, in part, to reduced oocyte quality. We and others have demonstrated that female Lethal Yellow (LY) mice and female C57BL/6 mice fed a high fat diet (B6-HFD) exhibit phenotypes consistent with human obesity. These studies also showed that zygotes collected from LY and B6-HFD females have reduced developmental competence. The current hypothesis is that LY and B6-HFD females exhibit an abnormal response to gonadotropin stimulation compared to C57BL/6 controls fed normal rodent chow (B6-ND), resulting in the ovulation of oocytes with an altered molecular phenotype which may contribute to its reduced developmental competence. To test this hypothesis, age-matched B6-ND, B6-HFD, and LY females were stimulated with exogenous gonadotropins, then circulating hormone levels and the phenotypes of ovulated oocytes were analyzed. There was no difference in ovulation rate or in the percentage of morphologically abnormal oocytes collected from the oviduct of any females. Progesterone and progesterone/estradiol ratios, however, were increased in B6-HFD and LY compared to B6-ND females 16 hr post-human chorionic gonadotropin treatment. The transcript abundance of several candidate oocyte genes was also increased in B6-HFD- and LY-derived oocytes compared to B6-ND-derived oocytes. These data suggest that increased insulin and leptin levels of obese females elevated circulating progesterone concentrations, altered transcriptional activity during oocyte growth, and/or impaired mechanisms of RNA translation and degradation during oocyte maturation. These changes in mRNA abundance likely contribute to reduced oocyte quality and the subsequent poor embryogenesis associated with obesity. © 2014 Wiley Periodicals, Inc.

  15. Age and haplotype variations within FADS1 interact and associate with alterations in fatty acid composition in human male cortical brain tissue.

    Directory of Open Access Journals (Sweden)

    Erika Freemantle

    Full Text Available Fatty acids (FA play an integral role in brain function and alterations have been implicated in a variety of complex neurological disorders. Several recent genomic studies have highlighted genetic variability in the fatty acid desaturase (FADS1/2/3 gene cluster as an important contributor to FA alterations in serum lipids as well as measures of FA desaturase index estimated by ratios of relevant FAs. The contribution to alterations of FAs within the brain by local synthesis is still a matter of debate. Thus, the impact of genetic variants in FADS genes on gene expression and brain FA levels is an important avenue to investigate.Analyses were performed on brain tissue from prefrontal cortex Brodmann area 47 (BA47 of 61 male subjects of French Canadian ancestry ranging in age from young adulthood to middle age (18-58 years old, with the exception of one teenager (15 years old. Haplotype tagging SNPs were selected using the publicly available HapMap genotyping dataset in conjunction with Haploview. DNA sequencing was performed by the Sanger method and gene expression was measured by quantitative real-time PCR. FAs in brain tissue were analysed by gas chromatography. Variants in the FADS1 gene region were sequenced and analyzed for their influence on both FADS gene expression and FAs in brain tissue.Our results suggest an association of the minor haplotype with alteration in estimated fatty acid desaturase activity. Analysis of the impact of DNA variants on expression and alternative transcripts of FADS1 and FADS2, however, showed no differences. Furthermore, there was a significant interaction between haplotype and age on certain brain FA levels.This study suggests that genetic variability in the FADS genes cluster, previously shown to be implicated in alterations in peripheral FA levels, may also affect FA composition in brain tissue, but not likely by local synthesis.

  16. Dual-dye optical mapping after myocardial infarction: does the site of ventricular stimulation alter the properties of electrical propagation?

    Science.gov (United States)

    Saba, Samir; Mathier, Michael A; Mehdi, Haider; Liu, Tong; Choi, Bum-Rak; London, Barry; Salama, Guy

    2008-02-01

    Myocardial infarction (MI) disrupts electrical conduction in affected ventricular areas. We investigated the effect of MI on the regional voltage and calcium (Ca) signals and their propagation properties, with special attention to the effect of the site of ventricular pacing on these properties. New Zealand White rabbits were divided into four study groups: sham-operated (C, n = 6), MI with no pacing (MI, n = 7), MI with right ventricular pacing (MI + RV, n = 6), and MI with BIV pacing (MI + BIV, n = 7). At 4 weeks, hearts were excised, perfused, and optically mapped. As previously shown, systolic and diastolic dilation of the LV were prevented by BIV pacing, as was the reduction in LV fractional shortening. Four weeks after MI, optical mapping revealed markedly reduced action potential amplitudes and conduction velocities (CV) in MI zones, and these increased gradually in the border zone and normal myocardial areas. Also, Ca transients were absent in the infarcted areas and increased gradually 3-5 mm from the border of the normal zone. Neither BIV nor RV pacing affected these findings in any of the MI, border, or normal zones. MI has profound effects on the regional electrical and Ca signals and on their propagation properties in this rabbit model. The absence of differences in these parameters by study group suggests that altering the properties of myocardial electrical conduction and Ca signaling are unlikely mechanisms by which BIV pacing confers its benefits. Further studies into the regional, cellular, and molecular benefits of BIV pacing are therefore warranted.

  17. How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

    Science.gov (United States)

    Lang, Nicolas; Siebner, Hartwig R; Ward, Nick S; Lee, Lucy; Nitsche, Michael A; Paulus, Walter; Rothwell, John C; Lemon, Roger N; Frackowiak, Richard S

    2005-07-01

    Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

  18. The main features of electrical stimulation of biological tissues by implant electrodes: study from engineering perspective and equipment development to produce

    International Nuclear Information System (INIS)

    Suarez Bagnasco, D.; Alvarez Alonso, J.; Suarez Antola, R.

    2004-08-01

    The main features of electrical stimulation of biological tissues by implant electrodes are studied.These electrodes are applied in neural prostheses and cardiac pacing.Threshold phenomena are stressed and some aspects related with implant electrode design are discussed. A fairly through theoretical research about the optimal pulse shape for electrical stimulation of biological tissues is done.The excitation functional is introduced as a criterium to identify threshold pulses of electric current. We obtain the optimal pulse shapes that minimize the energy dissipated in tissues, or the energy taken by the load seen by the pulse generator, amongst other criteria.We show how these pulse shapes can be determined from experimentally measured strength-duration (S-D) curves using rectangular pulses of current. The development of a prototype of a new equipment is described.The equipment may be used to measure S-D curves and with this information it is able to syntetize the abovementioned optimal pulse shapes. The top-down design process is presented, involving both hardware and software.The construction and assembling of the prototype, as well as the implementation of software are described.Some testing and measures with the prototype, including test with biological tissues are described and assessed

  19. Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Götz Pilarczyk

    2016-01-01

    Full Text Available The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.

  20. The role of shear stress and altered tissue properties on endothelial to mesenchymal transformation and tumor-endothelial cell interaction.

    Science.gov (United States)

    Mina, Sara G; Huang, Peter; Murray, Bruce T; Mahler, Gretchen J

    2017-07-01

    Tumor development is influenced by stromal cells in aspects including invasion, growth, angiogenesis, and metastasis. Activated fibroblasts are one group of stromal cells involved in cancer metastasis, and one source of activated fibroblasts is endothelial to mesenchymal transformation (EndMT). EndMT begins when the endothelial cells delaminate from the cell monolayer, lose cell-cell contacts, lose endothelial markers such as vascular endothelial-cadherin (VE-cadherin), gain mesenchymal markers like alpha-smooth muscle actin (α-SMA), and acquire mesenchymal cell-like properties. A three-dimensional (3D) culture microfluidic device was developed for investigating the role of steady low shear stress (1 dyne/cm 2 ) and altered extracellular matrix (ECM) composition and stiffness on EndMT. Shear stresses resulting from fluid flow within tumor tissue are relevant to both cancer metastasis and treatment effectiveness. Low and oscillatory shear stress rates have been shown to enhance the invasion of metastatic cancer cells through specific changes in actin and tubulin remodeling. The 3D ECM within the device was composed of type I collagen and glycosaminoglycans (GAGs), hyaluronic acid and chondroitin sulfate. An increase in collagen and GAGs has been observed in the solid tumor microenvironment and has been correlated with poor prognosis in many different cancer types. In this study, it was found that ECM composition and low shear stress upregulated EndMT, including upregulation of mesenchymal-like markers (α-SMA and Snail) and downregulated endothelial marker protein and gene expression (VE-cadherin). Furthermore, this novel model was utilized to investigate the role of EndMT in breast cancer cell proliferation and migration. Cancer cell spheroids were embedded within the 3D ECM of the microfluidic device. The results using this device show for the first time that the breast cancer spheroid size is dependent on shear stress and that the cancer cell migration rate

  1. [Impact of Different Percent Tissue Altered Values on Visual Outcome after Refractive Small Incision Lenticule Extraction (ReLEx SMILE)].

    Science.gov (United States)

    Breyer, D R H; Hagen, P; Kaymak, H; Klabe, K; Auffarth, G U; Kretz, F T A

    2017-01-01

    Purpose   To compare the visual outcomes after ReLEx SMILE treatment of eyes with low and high PTA values (PTA: percent tissue altered) within a follow-up period of up to 3 years and to assess whether a high PTA value might contribute to the development of keratectasia, as is the case for LASIK. Methods   This retrospective analysis comprises results from 313 eyes (189 patients) with a PTA value of less than 40 % and of 373 eyes (213 patients) with a PTA value of at least 40 %. Preoperatively and up to 3 years after SMILE surgery, refraction values, monocular corrected (CDVA) and uncorrected distant visual acuity (UDVA) and wavefront data were evaluated. Results   One to 3 years after surgery, the group with PTA lines in 1.1 % (0.0 %) of the cases. Loss of one line occurred in 1.1 % (3.6 %) of the eyes, whereas 97.7 % (96.4 %) remained unchanged or gained lines. With respect to predictability of the spherical equivalent, 92.0 % (78.6 %) of the eyes were within ± 0.5D and 97.7 % (92.9 %) were within ± 1.0D. The group with high PTA values displayed a slightly but significantly greater undercorrection of about 0,25D. 74.4 % (71.8 %) achieved UDVA of at least 20/20 and 96.5 % (87.1 %) achieved at least 20/25. The mean UDVA was - 0.03 ± 0.10logMAR (0.01 ± 0.12logMAR) and its mean difference to the preoperative CDVA was 0.00 ± 0.09logMAR (0.03 ± 0.12logMAR). Conclusion   ReLEx SMILE is a safe and effective corneal refractive treatment, even for PTA values of 40 % and more. Eyes with high PTA values did not display any evidence of keratectasia development within the 3-year follow-up of this study. Georg Thieme Verlag KG Stuttgart · New York.

  2. Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain?liver axis

    OpenAIRE

    Yang, B; Ren, Q; Zhang, J-c; Chen, Q-X; Hashimoto, K

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF...

  3. Adipose tissue-derived mesenchymal stem cells acquire bone cell-like responsiveness to fluid shear stress on osteogenic stimulation

    NARCIS (Netherlands)

    Knippenberg, M.; Helder, M.N.; Doulabi, B.Z.; Semeins, C.M.; Wuisman, P.I.J.M.; Klein-Nulend, J.

    2005-01-01

    To engineer bone tissue, mechanosensitive cells are needed that are able to perform bone cell-specific functions, such as (re)modeling of bone tissue. In vivo, local bone mass and architecture are affected by mechanical loading, which is thought to provoke a cellular response via loading-induced

  4. Polyethylene and methyl methacrylate particle-stimulated inflammatory tissue and macrophages up-regulate bone resorption in a murine neonatal calvaria in vitro organ system.

    Science.gov (United States)

    Ren, Weiping; Wu, Bin; Mayton, Lois; Wooley, Paul H

    2002-09-01

    There is considerable evidence that orthopaedic wear debris plays a crucial role in the pathology of aseptic loosening of joint prostheses. This study examined the effect of inflammatory membranes stimulated with methyl methacrylate and polyethylene on bone resorption, using the murine air pouch model. The capacity of RAW 264.7 mouse macrophages exposed to polymer particles to produce factors affecting bone metabolism was also studied. Neonatal calvaria bones were co-cultured with either pouch membranes or conditioned media from activated macrophages. Bone resorption was measured by the release of calcium from cultured bones, and the activity of tartrate-resistant acid phosphatase in both bone sections and culture medium was also assayed. Results showed that inflammatory pouch membrane activated by methyl methacrylate and polyethylene enhanced osteoclastic bone resorption. Conditioned media from particles stimulated mouse macrophages also stimulated bone resorption, although this effect was weaker than resorption induced by inflammatory pouch membranes. The addition of the particles directly into the medium of cultured calvaria bones had little effect on bone resorption. Our observations indicate that both inflammatory tissue and macrophages provoked by particles can stimulate bone resorption in cultured mouse neonatal calvaria bones. This simple in vitro bone resorption system allows us to investigate the fundamental cellular and molecular mechanism of wear debris induced bone resorption and to screen potential therapeutic approaches for aseptic loosening.

  5. Correlating lesion size and location to deficits after ischemic stroke: the influence of accounting for altered peri-necrotic tissue and incidental silent infarcts

    Directory of Open Access Journals (Sweden)

    Black Sandra E

    2010-01-01

    Full Text Available Abstract Background Investigators frequently quantify and evaluate the location and size of stroke lesions to help uncover cerebral anatomical correlates of deficits observed after first-ever stroke. However, it is common to discover silent infarcts such as lacunes in patients identified clinically as 'first-ever' stroke, and it is unclear if including these incidental findings may impact lesion-based investigations of brain-behaviour relationships. There is also debate concerning how to best define the boundaries of necrotic stroke lesions that blend in an ill-defined way into surrounding tissue, as it is unclear whether including this altered peri-necrotic tissue region may influence studies of brain-behaviour relationships. Therefore, for patients with clinically overt stroke, we examined whether including altered peri-necrotic tissue and incidental silent strokes influenced either lesion volume correlations with a measure of sensorimotor impairment or the anatomical localization of this impairment established using subtraction lesion analysis. Methods Chronic stroke lesions of 41 patients were manually traced from digital T1-MRI to sequentially include the: necrotic lesion core, altered peri-necrotic tissue, silent lesions in the same hemisphere as the index lesion, and silent lesions in the opposite hemisphere. Lesion volumes for each region were examined for correlation with motor impairment scores, and subtraction analysis was used to highlight anatomical lesion loci associated with this deficit. Results For subtraction lesion analysis, including peri-necrotic tissue resulted in a larger region of more frequent damage being seen in the basal ganglia. For correlational analysis, only the volume of the lesion core was significantly associated with motor impairment scores (r = -0.35, p = 0.025. In a sub-analysis of patients with small subcortical index lesions, adding silent lesions in the opposite hemisphere to the volume of the index

  6. Altering the swelling pressures within in vitro engineered cartilage is predicted to modulate the configuration of the collagen network and hence improve tissue mechanical properties.

    Science.gov (United States)

    Nagel, Thomas; Kelly, Daniel J

    2013-06-01

    Prestress in the collagen network has a significant impact on the material properties of cartilaginous tissues. It is closely related to the recruitment configuration of the collagen network which defines the transition from lax collagen fibres to uncrimped, load-bearing collagen fibres. This recruitment configuration can change in response to alterations in the external environmental conditions. In this study, the influence of changes in external salt concentration or sequential proteoglycan digestion on the configuration of the collagen network of tissue engineered cartilage is investigated using a previously developed computational model. Collagen synthesis and network assembly are assumed to occur in the tissue configuration present during in vitro culture. The model assumes that if this configuration is more compact due to changes in tissue swelling, the collagen network will adapt by lowering its recruitment stretch. When returned to normal physiological conditions, these tissues will then have a higher prestress in the collagen network. Based on these assumptions, the model demonstrates that proteoglycan digestion at discrete time points during culture as well as culture in a hypertonic medium can improve the functionality of tissue engineered cartilage, while culture in hypotonic solution is detrimental to the apparent mechanical properties of the graft. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. A Cost-Effective Culture System for the In Vitro Assembly, Maturation, and Stimulation of Advanced Multilayered Multiculture Tubular Tissue Models.

    Science.gov (United States)

    Loy, Caroline; Pezzoli, Daniele; Candiani, Gabriele; Mantovani, Diego

    2018-01-01

    The development of tubular engineered tissues is a challenging research area aiming to provide tissue substitutes but also in vitro models to test drugs, medical devices, and even to study physiological and pathological processes. In this work, the design, fabrication, and validation of an original cost-effective tubular multilayered-tissue culture system (TMCS) are reported. By exploiting cellularized collagen gel as scaffold, a simple moulding technique and an endothelialization step on a rotating system, TMCS allowed to easily prepare in 48 h, trilayered arterial wall models with finely organized cellular composition and to mature them for 2 weeks without any need of manipulation. Multilayered constructs incorporating different combinations of vascular cells are compared in terms of cell organization and viscoelastic mechanical properties demonstrating that cells always progressively aligned parallel to the longitudinal direction. Also, fibroblast compacted less the collagen matrix and appeared crucial in term of maturation/deposition of elastic extracellular matrix. Preliminary studies under shear stress stimulation upon connection with a flow bioreactor are successfully conducted without damaging the endothelial monolayer. Altogether, the TMCS herein developed, thanks to its versatility and multiple functionalities, holds great promise for vascular tissue engineering applications, but also for other tubular tissues such as trachea or oesophagus. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

    Science.gov (United States)

    Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

    2016-10-14

    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2 fl/fl ) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2 fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β 2 -adrenergic receptor (β 2 AR) agonist, was significantly enhanced in MLC-Cre:GRK2 fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β 2 AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy*

    Science.gov (United States)

    Woodall, Benjamin P.; Woodall, Meryl C.; Luongo, Timothy S.; Grisanti, Laurel A.; Tilley, Douglas G.; Elrod, John W.; Koch, Walter J.

    2016-01-01

    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2fl/fl) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. PMID:27566547

  10. Tissue factor pathway inhibitor (TFPI) release after heparin stimulation is increased in Type 1 diabetic patients with albuminuria

    NARCIS (Netherlands)

    Leurs, PB; van Oerle, R; Hamulyak, K; Wolffenbuttel, BHR

    Aims To study heparin-stimulated TFPI release in relation to complications in Type 1 diabetic patients. Subjects and methods Nineteen uncomplicated Type 1 diabetic patients (group I) were compared with 18 patients with retinopathy (group II), and nine patients with retinopathy and albuminuria (group

  11. Microfluidic culture chamber for the long-term perfusion and precise chemical stimulation of organotypic brain tissue slices

    DEFF Research Database (Denmark)

    Caicedo, H. H.; Vignes, M.; Brugg, B.

    2010-01-01

    We have developed a microfluidic perfusion-based culture system to study long-term in-vitro responses of organo-typic brain slices exposed to localized neurochemical stimulation. Using this microperfusion chamber we show that hip-pocampal organotypic brain slices cultures grown on nitrocellulose ...

  12. Tissue and serum samples of patients with papillary thyroid cancer with and without benign background demonstrate different altered expression of proteins

    Directory of Open Access Journals (Sweden)

    Mardiaty Iryani Abdullah

    2016-09-01

    Full Text Available Background Papillary thyroid cancer (PTC is mainly diagnosed using fine-needle aspiration biopsy. This most common form of well-differentiated thyroid cancer occurs with or without a background of benign thyroid goiter (BTG. Methods In the present study, a gel-based proteomics analysis was performed to analyse the expression of proteins in tissue and serum samples of PTC patients with (PTCb; n = 6 and without a history of BTG (PTCa; n = 8 relative to patients with BTG (n = 20. This was followed by confirmation of the levels of proteins which showed significant altered abundances of more than two-fold difference (p < 0.01 in the tissue and serum samples of the same subjects using ELISA. Results The data of our study showed that PTCa and PTCb distinguish themselves from BTG in the types of tissue and serum proteins of altered abundance. While higher levels of alpha-1 antitrypsin (A1AT and heat shock 70 kDa protein were associated with PTCa, lower levels of A1AT, protein disulfide isomerase and ubiquitin-conjugating enzyme E2 N seemed apparent in the PTCb. In case of the serum proteins, higher abundances of A1AT and alpha 1-beta glycoprotein were detected in PTCa, while PTCb was associated with enhanced apolipoprotein A-IV and alpha 2-HS glycoprotein (AHSG. The different altered expression of tissue and serum A1AT as well as serum AHSG between PTCa and PTCb patients were also validated by ELISA. Discussion The distinctive altered abundances of the tissue and serum proteins form preliminary indications that PTCa and PTCb are two distinct cancers of the thyroid that are etiologically and mechanistically different although it is currently not possible to rule out that they may also be due other reasons such as the different stages of the malignant disease. These proteins stand to have a potential use as tissue or serum biomarkers to discriminate the three different thyroid neoplasms although this requires further validation in clinically

  13. Study of the agroindustrial alterations induced by the irradiated tissue culture in sugar cane, variety NA 56-79

    International Nuclear Information System (INIS)

    Figueiredo Junior, O.

    1991-01-01

    The use of plant tissue culture and the application of gamma radiation as mutation inducing agents, in the sugar cane plant, variety NA 5679, are studied. The variation in the contents of brix, pol, fiber, purity, extraction, phosphorus, nitrogen, reducing sugars as well as the morphological characteristics are analysed. The 'callus' obtained by the tissue culture were irradiated with 20, 40, and 60 Gy doses. The statistical analysis indicated that the method of tissue culture may, eventually, increase the contents of the technological parameters and the dosages of gamma radiation were not efficient for such purpose. (M.A.C.)

  14. Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models

    Directory of Open Access Journals (Sweden)

    Dota A

    2013-01-01

    Full Text Available Atsuyoshi Dota, Yuko Takaoka-Shichijo, Masatsugu NakamuraOphthalmic Research and Development Center, Santen Pharmaceutical Co, Ltd, Ikoma-shi, Nara, JapanPurpose: The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models.Methods: Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model.Results: Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score.Conclusion: These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.Keywords: gefarnate, fluorescein staining, rose bengal permeability, rabbit, cat, dry eye

  15. Deep brain stimulation of the amygdala alleviates fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory.

    Science.gov (United States)

    Sui, Li; Huang, SiJia; Peng, BinBin; Ren, Jie; Tian, FuYing; Wang, Yan

    2014-07-01

    Deep brain stimulation (DBS) of the amygdala has been demonstrated to modulate hyperactivity of the amygdala, which is responsible for the symptoms of post-traumatic stress disorder (PTSD), and thus might be used for the treatment of PTSD. However, the underlying mechanism of DBS of the amygdala in the modulation of the amygdala is unclear. The present study investigated the effects of DBS of the amygdala on synaptic transmission and synaptic plasticity at cortical inputs to the amygdala, which is critical for the formation and storage of auditory fear memories, and fear memories. The results demonstrated that auditory fear conditioning increased single-pulse-evoked field excitatory postsynaptic potentials in the cortical-amygdala pathway. Furthermore, auditory fear conditioning decreased the induction of paired-pulse facilitation and long-term potentiation, two neurophysiological models for studying short-term and long-term synaptic plasticity, respectively, in the cortical-amygdala pathway. In addition, all these auditory fear conditioning-induced changes could be reversed by DBS of the amygdala. DBS of the amygdala also rescued auditory fear conditioning-induced enhancement of long-term retention of fear memory. These findings suggested that DBS of the amygdala alleviating fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory may underlie the neuromodulatory role of DBS of the amygdala in activities of the amygdala.

  16. Altering gait by way of stimulation of the plantar surface of the foot: the immediate effect of wearing textured insoles in older fallers

    Directory of Open Access Journals (Sweden)

    Hatton Anna L

    2012-04-01

    Full Text Available Abstract Background Evidence suggests that textured insoles can alter gait and standing balance by way of enhanced plantar tactile stimulation. However, to date, this has not been explored in older people at risk of falling. This study investigated the immediate effect of wearing textured insoles on gait and double-limb standing balance in older fallers. Methods Thirty older adults >65 years (21 women, mean [SD] age 79.0 [7.1], with self-reported history of ≥2 falls in the previous year, conducted tests of level-ground walking over 10 m (GAITRite system, and double-limb standing with eyes open and eyes closed over 30 seconds (Kistler force platform under two conditions: wearing textured insoles (intervention and smooth (control insoles in their usual footwear. Results Wearing textured insoles caused significantly lower gait velocity (P = 0.02, step length (P = 0.04 and stride length (P = 0.03 compared with wearing smooth insoles. No significant differences were found in any of the balance parameters (P > 0.05. Conclusions A textured insole worn by older adults with a history of falls significantly lowers gait velocity, step length and stride length, suggesting that this population may not have an immediate benefit from this type of intervention. The effects of prolonged wear remain to be investigated.

  17. Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Jarrar Bashir M

    2011-09-01

    Full Text Available Abstract Background Gold nanoparticles (GNPs have important application for cell labeling and imaging, drug delivery, diagnostic and therapeutic purposes mainly in cancer. Nanoparticles (NPs are being increasingly exploited for medical applications. The aim of the present study was to investigate the particle-size and period effects of administration of GNPs on the renal tissue in an attempt to address their potential toxicity. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days to investigate particle-size effect of GNPs on the renal tissue. Animals were randomly divided into groups, 6 GNPs-treated rats groups and one control group. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days, size 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Stained sections of control and treated rats kidneys were examined for renal tissue alterations induced by GNPs. Results In comparison with respective control rats, exposure to GNPs doses has produced the following renal tubular alterations: cloudy swelling, vacuolar degeneration, hyaline droplets and casts, anisokaryosis, karopyknosis, karyorrhexis and karyolysis. The glomeruli showed moderate congestion with no hypercelluraity, mesangial proliferation or basement membrane thickening. The histological alterations were mainly seen in the cortex and the proximal renal convoluted tubules were more affected than the distal ones. Conclusions The induced histological alterations might be an indication of injured renal tubules due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. The findings may suggest that GNPs interact with proteins and enzymes of the renal tissue

  18. High-grain diet feeding altered the composition and functions of the rumen bacterial community and caused the damage to the laminar tissues of goats.

    Science.gov (United States)

    Zhang, R Y; Jin, W; Feng, P F; Liu, J H; Mao, S Y

    2018-03-19

    In the current intensive production system, ruminants are often fed high-grain (HG) diets. However, this feeding pattern often causes rumen metabolic disorders and may further trigger laminitis, the exact mechanism is not clear. This study investigated the effect of HG diet feeding on fermentative and microbial changes in the rumen and on the expression of pro-inflammatory cytokines and matrix metalloproteinases (MMPs) in the lamellar tissue. In all, 12 male goats were fed a hay diet (0% grain; n=6) or an HG diet (56.5% grain; n=6). On day 50 of treatment, samples of blood, rumen content, and lamellar tissue of hooves of goats were collected. The data showed that compared with the hay group, HG-fed goats had lower (Pdiet feeding altered the composition of rumen bacterial community, and correspondingly, the results suggested that their functions in the HG group were also altered. HG diet feeding increased (Pbacterial community, and lead to higher levels of LPS in the peripheral blood, and further activated the inflammatory response in lamellar tissues, which may progress to the level of laminar damage.

  19. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    Cheng, Sulin; Wiklund, Petri; Autio, Reija; Borra, Ronald; Ojanen, Xiaowei; Xu, Leiting; Törmäkangas, Timo; Alen, Markku

    2015-01-01

    BACKGROUND: Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD. METHODS: Hepatic fat content was

  20. Effect of exercise training on in vivo insulin-stimulated glucose uptake in intra-abdominal adipose tissue in rats

    DEFF Research Database (Denmark)

    Enevoldsen, L H; Stallknecht, B; Fluckey, J D

    2000-01-01

    Intra-abdominal obesity may be crucial in the pathogenesis of the insulin-resistance syndrome, and training may alleviate this condition. We compared insulin-mediated glucose uptake in vivo in three intra-abdominal adipose tissues (ATs; retroperitoneal, parametrial, and mesenteric) and in subcuta......Intra-abdominal obesity may be crucial in the pathogenesis of the insulin-resistance syndrome, and training may alleviate this condition. We compared insulin-mediated glucose uptake in vivo in three intra-abdominal adipose tissues (ATs; retroperitoneal, parametrial, and mesenteric...

  1. Effects of hippocampal high-frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats.

    Science.gov (United States)

    Luna-Munguía, Hiram; Meneses, Alfredo; Peña-Ortega, Fernando; Gaona, Andres; Rocha, Luisa

    2012-01-01

    Hippocampal high frequency electrical stimulation (HFS) at 130 Hz has been proposed as a therapeutical strategy to control neurological disorders such as intractable temporal lobe epilepsy (TLE). This study was carried out to determine the effects of hippocampal HFS on the memory process and the probable involvement of amino acids. Using the autoshaping task, we found that animals receiving hippocampal HFS showed augmented short-term, but not long-term memory formation, an effect blocked by bicuculline pretreatment and associated with enhanced tissue levels of amino acids in hippocampus. In addition, microdialysis experiments revealed high extracellular levels of glutamate, aspartate, glycine, taurine, and alanine during the application of hippocampal HFS. In contrast, GABA release augmented during HFS and remained elevated for more than 1 h after the stimulation was ended. HFS had minimal effects on glutamine release. The present results suggest that HFS has an activating effect on specific amino acids in normal hippocampus that may be involved in the enhanced short-term memory formation. These data further provide experimental support for the concept that hippocampus may be a promising target for focal stimulation to treat intractable seizures in humans. Copyright © 2010 Wiley Periodicals, Inc., Inc.

  2. Higher number of pentosidine cross-links induced by ribose does not alter tissue stiffness of cancellous bone

    Energy Technology Data Exchange (ETDEWEB)

    Willems, Nop M.B.K., E-mail: n.willems@acta.nl [Dept. of Orthodontics, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Gustav Mahlerlaan 3004, 1081 LA Amsterdam (Netherlands); Dept. of Oral Cell Biology and Functional Anatomy, MOVE Research Institute, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Gustav Mahlerlaan 3004, 1081 LA Amsterdam (Netherlands); Langenbach, Geerling E.J. [Dept. of Oral Cell Biology and Functional Anatomy, MOVE Research Institute, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Gustav Mahlerlaan 3004, 1081 LA Amsterdam (Netherlands); Stoop, Reinout [Dept. of Metabolic Health Research, TNO, P.O. Box 2215, 2301 CE Leiden (Netherlands); Toonder, Jaap M.J. den [Dept. of Mechanical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven (Netherlands); Mulder, Lars [Dept. of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven (Netherlands); Zentner, Andrej [Dept. of Orthodontics, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Gustav Mahlerlaan 3004, 1081 LA Amsterdam (Netherlands); Everts, Vincent [Dept. of Oral Cell Biology and Functional Anatomy, MOVE Research Institute, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Gustav Mahlerlaan 3004, 1081 LA Amsterdam (Netherlands)

    2014-09-01

    The role of mature collagen cross-links, pentosidine (Pen) cross-links in particular, in the micromechanical properties of cancellous bone is unknown. The aim of this study was to examine nonenzymatic glycation effects on tissue stiffness of demineralized and non-demineralized cancellous bone. A total of 60 bone samples were derived from mandibular condyles of six pigs, and assigned to either control or experimental groups. Experimental handling included incubation in phosphate buffered saline alone or with 0.2 M ribose at 37 °C for 15 days and, in some of the samples, subsequent complete demineralization of the sample surface using 8% EDTA. Before and after experimental handling, bone microarchitecture and tissue mineral density were examined by means of microcomputed tomography. After experimental handling, the collagen content and the number of Pen, hydroxylysylpyridinoline (HP), and lysylpyridinoline (LP) cross-links were estimated using HPLC, and tissue stiffness was assessed by means of nanoindentation. Ribose treatment caused an up to 300-fold increase in the number of Pen cross-links compared to nonribose-incubated controls, but did not affect the number of HP and LP cross-links. This increase in the number of Pen cross-links had no influence on tissue stiffness of both demineralized and nondemineralized bone samples. These findings suggest that Pen cross-links do not play a significant role in bone tissue stiffness. - Highlights: • The assessment of effects of glycation in bone using HPLC, microCT, and nanoindentation • Ribose incubation: 300‐fold increase in the number of pentosidine cross-links • 300‐fold increase in the number of pentosidine cross-links: no changes in bone tissue stiffness.

  3. Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

    Science.gov (United States)

    Garcia-Knight, Miguel A; Nduati, Eunice; Hassan, Amin S; Gambo, Faith; Odera, Dennis; Etyang, Timothy J; Hajj, Nassim J; Berkley, James Alexander; Urban, Britta C; Rowland-Jones, Sarah L

    2015-01-01

    Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy

  4. Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

    Directory of Open Access Journals (Sweden)

    Miguel A Garcia-Knight

    Full Text Available Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42 and HU (n = 28 Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of

  5. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    Science.gov (United States)

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  6. The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras.

    Science.gov (United States)

    Fu, Qiang; Deng, Chen-Liang; Zhao, Ren-Yan; Wang, Ying; Cao, Yilin

    2014-01-01

    Urethral defects are common and frequent disorders and are difficult to treat. Simple natural or synthetic materials do not provide a satisfactory curative solution for long urethral defects, and urethroplasty with large areas of autologous tissues is limited and might interfere with wound healing. In this study, adipose-derived stem cells were used. These cells can be derived from a wide range of sources, have extensive expansion capability, and were combined with oral mucosal epithelial cells to solve the problem of finding seeding cell sources for producing the tissue-engineered urethras. We also used the synthetic biodegradable polymer poly-glycolic acid (PGA) as a scaffold material to overcome issues such as potential pathogen infections derived from natural materials (such as de-vascular stents or animal-derived collagen) and differing diameters. Furthermore, we used a bioreactor to construct a tissue-engineered epithelial-muscular lumen with a double-layer structure (the epithelial lining and the muscle layer). Through these steps, we used an epithelial-muscular lumen built in vitro to repair defects in a canine urethral defect model (1 cm). Canine urethral reconstruction was successfully achieved based on image analysis and histological techniques at different time points. This study provides a basis for the clinical application of tissue engineering of an epithelial-muscular lumen. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Preliminary analysis of proteome alterations in non-aneurysmal, internal mammary artery tissue from patients with abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Kidholm, Christina Lund; Beck, Hans Christian; Madsen, Julie Bukh

    2018-01-01

    with AAA and 33 sex- and age-matched controls without AAA. Samples were selected from a biobank of leftover internal mammary arterial tissue gathered at coronary by-pass operations. Results We identified and quantitated 877 proteins, of which 44 were differentially expressed between the two groups (nominal...

  8. Expression of inflammation-related genes is altered in gastric tissue of patients with advanced stages of NAFLD.

    Science.gov (United States)

    Mehta, Rohini; Birerdinc, Aybike; Neupane, Arpan; Shamsaddini, Amirhossein; Afendy, Arian; Elariny, Hazem; Chandhoke, Vikas; Baranova, Ancha; Younossi, Zobair M

    2013-01-01

    Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD) and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB) gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH). Expression levels of soluble interleukin 1 receptor antagonist (IL1RN) were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8), chemokine (C-C motif) ligand 4 (CCL4), and its receptor chemokine (C-C motif) receptor type 5 (CCR5) showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

  9. Expression of Inflammation-Related Genes Is Altered in Gastric Tissue of Patients with Advanced Stages of NAFLD

    Directory of Open Access Journals (Sweden)

    Rohini Mehta

    2013-01-01

    Full Text Available Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH. Expression levels of soluble interleukin 1 receptor antagonist (IL1RN were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8, chemokine (C-C motif ligand 4 (CCL4, and its receptor chemokine (C-C motif receptor type 5 (CCR5 showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

  10. Altered vocal fold kinematics in synthetic self-oscillating models that employ adipose tissue as a lateral boundary condition.

    Science.gov (United States)

    Saidi, Hiba; Erath, Byron D.

    2015-11-01

    The vocal folds play a major role in human communication by initiating voiced sound production. During voiced speech, the vocal folds are set into sustained vibrations. Synthetic self-oscillating vocal fold models are regularly employed to gain insight into flow-structure interactions governing the phonation process. Commonly, a fixed boundary condition is applied to the lateral, anterior, and posterior sides of the synthetic vocal fold models. However, physiological observations reveal the presence of adipose tissue on the lateral surface between the thyroid cartilage and the vocal folds. The goal of this study is to investigate the influence of including this substrate layer of adipose tissue on the dynamics of phonation. For a more realistic representation of the human vocal folds, synthetic multi-layer vocal fold models have been fabricated and tested while including a soft lateral layer representative of adipose tissue. Phonation parameters have been collected and are compared to those of the standard vocal fold models. Results show that vocal fold kinematics are affected by adding the adipose tissue layer as a new boundary condition.

  11. Alteration of gene expression in mammary gland tissue of dairy cows in response to dietary unsaturated fatty acids

    NARCIS (Netherlands)

    Mach Casellas, N.; Jacobs, A.A.A.; Kruijt, L.; Baal, van J.; Smits, M.C.J.

    2014-01-01

    The aim of this study was to determine the effects of unprotected dietary unsaturated fatty acids (UFA) from different plant oils on gene expression in the mammary gland of grazing dairy cows. Milk composition and gene expression in the mammary gland tissue were evaluated in grazing dairy cows

  12. Alterations of the amplitude of low-frequency fluctuation in healthy subjects with theta-burst stimulation of the cortex of the suprahyoid muscles.

    Science.gov (United States)

    Ruan, Xiuhang; Xu, Guangqing; Gao, Cuihua; Liu, Lingling; Liu, Yanli; Jiang, Lisheng; Chen, Xin; Yu, Shaode; Jiang, Xinqing; Lan, Yue; Wei, Xinhua

    2017-12-04

    Theta burst stimulation (TBS) has emerged as a promising tool for the treatment of swallowing disorders; however, the short-term after-effects of brain activation induced by TBS remain unknown. Here, we measured the changes in spontaneous brain activation using the amplitude of low-frequency fluctuation (ALFF) approach in subjects who underwent different TBS protocols. Sixty right-handed healthy participants (male, n=30; female, n=30; mean age=23.5y) were recruited in this study and randomly assigned to three groups that underwent three different TBS protocols. In group 1, continuous TBS (cTBS) was positioned on the left hemisphere of the suprahyoid muscle cortex. For group 2, intermittent TBS (iTBS) was placed on the left hemisphere of the suprahyoid muscle cortex. Group 3 underwent combined cTBS/iTBS protocols in which iTBS on the right hemisphere was performed immediately after completing cTBS on the left suprahyoid muscle cortex. Compared to pre-TBS, post-cTBS showed decreased ALFF in the anterior cingulate gyrus (BA 32); post-iTBS induced an increase in ALFF in the bilateral precuneus (BA 7); and post-cTBS/iTBS induced a decrease in ALFF in the brainstem, and resulted in increased ALFF in the middle cingulate gyrus (BA 24) as well as the left precentral gyrus (BA 6). Compared the effect of post-TBS protocols, increased ALFF was found in left posterior cerebellum lobe and left inferior parietal lobule (BA 40) (post-cTBS vs post-iTBS), and decreased ALFF exhibited in paracentral lobule (BA 4) (post-iTBS vs post-cTBS/iTBS). These findings indicate that multiple brain areas involved in swallowing regulation after stimulation of TBS over the suprahyoid muscles. cTBS induces decreased after-effects while iTBS results in increased after-effects on spontaneous brain activation. Moreover, iTBS can eliminate the after-effects of cTBS applied on the contralateral swallowing cortex and alter the activity of contralateral motor cortex and brainstem. Our findings provide a

  13. Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

    Science.gov (United States)

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

    2015-01-01

    Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions.

  14. Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.

    Science.gov (United States)

    Tanaka, Mitsuru; Yasuoka, Akihito; Shimizu, Manae; Saito, Yoshikazu; Kumakura, Kei; Asakura, Tomiko; Nagai, Toshitada

    2017-01-01

    To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H) containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45 in energy percent, respectively). The rats consumed the diets for 9 weeks and were subjected to biochemical and DNA microarray analyses. The rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher liver TG and cholesterol content than rats in the L-group. The analysis of differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene ontology analysis of these L vs H DEGs indicated that those related to fatty acid synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These reversed liver DEGs included M-up/H-down genes ( Sds for gluconeogenesis from amino acids) and M-down/H-up genes ( Gpd2 for gluconeogenesis from glycerol, Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation and synthesis of fatty acids were inhibited in these tissues. These results indicate that the alteration of dietary C-F balance differentially affects the transcriptomes of metabolizing and energy-storing tissues.

  15. Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue.

    Science.gov (United States)

    Taraballi, Francesca; Bauza, Guillermo; McCulloch, Patrick; Harris, Josh; Tasciotti, Ennio

    2017-12-01

    Musculoskeletal reconstruction is an ongoing challenge for surgeons as it is required for one out of five patients undergoing surgery. In the past three decades, through the close collaboration between clinicians and basic scientists, several regenerative strategies have been proposed. These have emerged from interdisciplinary approaches that bridge tissue engineering with material science, physiology, and cell biology. The paradigm behind tissue engineering is to achieve regeneration and functional recovery using stem cells, bioactive molecules, or supporting materials. Although plenty of preclinical solutions for bone and cartilage have been presented, only a few platforms have been able to move from the bench to the bedside. In this review, we highlight the limitations of musculoskeletal regeneration and summarize the most relevant acellular tissue engineering approaches. We focus on the strategies that could be most effectively translate in clinical practice and reflect on contemporary and cutting-edge regenerative strategies in surgery. Stem Cells Translational Medicine 2017;6:2186-2196. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  16. Alterations of total non stimulated salivary flow in patients with squamous cell carcinoma of the mouth and oropharynx submitted to hyperfractionated radiation therapy

    International Nuclear Information System (INIS)

    Guebur, Maria Isabela; Rapoport, Abrao; Sassi, Laurindo Moacir; Oliveira, Benedito Valdecir de; Ramos, Gyl Henrique Albrecht; Pereira, Jose Carlos Gasparin

    2004-01-01

    Prevention and early diagnosis are actually the most effective measures that we dispose to improve the prognostic of the malignant tumors. The mouth and oropharynx tumors are treated with success, when early diagnosed. The radiotherapy is almost always one of the selected treatments for these tumors. When cancer is diagnosed in advanced stages, many a time the treatment needs to be carried out swiftly to be efficient, and consequently the radio therapist use the hyperfractionated therapy, with the patient receiving two lower doses of radiation in two sessions daily, amounting to a higher daily dosage, of about 160 cGy/2x/day. When the major salivary glands are present in the radiated field, the xerostomia appears by the second week of treatment (1500 to 2000 cGy), changing the patient's health, and causing difficulties for him to eat, speak and sleep. The objective of this study was to evaluate the quantitative alterations of the total non stimulated salivate flow of patients who underwent hyperfractionated therapy for the treatment of squamous cell carcinoma of mouth and oropharynx. Samples of twelve male patients saliva from Erasto Gaertner Hospital in Curitiba, PR, Brazil, were examined. Two samples of saliva were collected from each patient, the first one before the beginning of the radiotherapy, and the second at the end of the treatment. As a result, we obtained salivary loss in 91.7% of the patients, with a percentage of total salivary flow loss of 62.9%, registered in the second collection. We concluded that the hyperfractionated therapy causes a marked xerostomia when the major salivary glands are in the radiated field. (author)

  17. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

    OpenAIRE

    Rebouche, C J; Engel, A G

    1984-01-01

    The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine wa...

  18. Altered expression of hypoxia-inducible factor-1α (HIF-1α and its regulatory genes in gastric cancer tissues.

    Directory of Open Access Journals (Sweden)

    Jihan Wang

    Full Text Available Tissue hypoxia induces reprogramming of cell metabolism and may result in normal cell transformation and cancer progression. Hypoxia-inducible factor 1-alpha (HIF-1α, the key transcription factor, plays an important role in gastric cancer development and progression. This study aimed to investigate the underlying regulatory signaling pathway in gastric cancer using gastric cancer tissue specimens. The integration of gene expression profile and transcriptional regulatory element database (TRED was pursued to identify HIF-1α ↔ NFκB1 → BRCA1 → STAT3 ← STAT1 gene pathways and their regulated genes. The data showed that there were 82 differentially expressed genes that could be regulated by these five transcription factors in gastric cancer tissues and these genes formed 95 regulation modes, among which seven genes (MMP1, TIMP1, TLR2, FCGR3A, IRF1, FAS, and TFF3 were hub molecules that are regulated at least by two of these five transcription factors simultaneously and were associated with hypoxia, inflammation, and immune disorder. Real-Time PCR and western blot showed increasing of HIF-1α in mRNA and protein levels as well as TIMP1, TFF3 in mRNA levels in gastric cancer tissues. The data are the first study to demonstrate HIF-1α-regulated transcription factors and their corresponding network genes in gastric cancer. Further study with a larger sample size and more functional experiments is needed to confirm these data and then translate into clinical biomarker discovery and treatment strategy for gastric cancer.

  19. Growth hormone receptor antagonist (GHA) transgenic mice have increased subcutaneous adipose tissue mass, altered glucose homeostasis, and no change in white adipose tissue cellular senescence

    Science.gov (United States)

    Comisford, Ross; Lubbers, Ellen R.; Householder, Lara; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L.; List, Edward O.; Kopchick, John J.; Berryman, Darlene E.

    2015-01-01

    Background Growth hormone (GH) resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests long-lived GH resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. OBJECTIVE The objective of this study was to examine white adipose tissue (WAT) senescence, WAT distribution, and glucose homeostasis in dwarf growth hormone receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. METHODS 18mo old female GHA mice and wild type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose, and glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase (SA-β-gal) staining to quantify the senescent cell burden and real time qPCR to quantify gene expression of senescence markers p16 and IL-6. RESULTS GHA mice had a 22% reduction in total body weight, 33% reduction in lean mass, and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p<.05) and a 1.7 fold increase in extra-/intraperitoneal WAT ratio compared to controls (p<.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. CONCLUSIONS Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin

  20. Chronic alcohol abuse in men alters bone mechanical properties by affecting both tissue mechanical properties and microarchitectural parameters.

    Science.gov (United States)

    Cruel, M; Granke, M; Bosser, C; Audran, M; Hoc, T

    2017-06-01

    Alcohol-induced secondary osteoporosis in men has been characterized by higher fracture prevalence and a modification of bone microarchitecture. Chronic alcohol consumption impairs bone cell activity and results in an increased fragility. A few studies highlighted effects of heavy alcohol consumption on some microarchitectural parameters of trabecular bone. But to date and to our knowledge, micro- and macro-mechanical properties of bone of alcoholic subjects have not been investigated. In the present study, mechanical properties and microarchitecture of trabecular bone samples from the iliac crest of alcoholic male patients (n=15) were analyzed and compared to a control group (n=8). Nanoindentation tests were performed to determine the tissue's micromechanical properties, micro-computed tomography was used to measure microarchitectural parameters, and numerical simulations provided the apparent mechanical properties of the samples. Compared to controls, bone tissue from alcoholic patients exhibited an increase of micromechanical properties at tissue scale, a significant decrease of apparent mechanical properties at sample scale, and significant changes in several microarchitectural parameters. In particular, a crucial role of structure model index (SMI) on mechanical properties was identified. 3D microarchitectural parameters are at least as important as bone volume fraction to predict bone fracture risk in the case of alcoholic patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Flavanol-Enriched Cocoa Powder Alters the Intestinal Microbiota, Tissue and Fluid Metabolite Profiles, and Intestinal Gene Expression in Pigs.

    Science.gov (United States)

    Jang, Saebyeol; Sun, Jianghao; Chen, Pei; Lakshman, Sukla; Molokin, Aleksey; Harnly, James M; Vinyard, Bryan T; Urban, Joseph F; Davis, Cindy D; Solano-Aguilar, Gloria

    2016-04-01

    Consumption of cocoa-derived polyphenols has been associated with several health benefits; however, their effects on the intestinal microbiome and related features of host intestinal health are not adequately understood. The objective of this study was to determine the effects of eating flavanol-enriched cocoa powder on the composition of the gut microbiota, tissue metabolite profiles, and intestinal immune status. Male pigs (5 mo old, 28 kg mean body weight) were supplemented with 0, 2.5, 10, or 20 g flavanol-enriched cocoa powder/d for 27 d. Metabolites in serum, urine, the proximal colon contents, liver, and adipose tissue; bacterial abundance in the intestinal contents and feces; and intestinal tissue gene expression of inflammatory markers and Toll-like receptors (TLRs) were then determined. O-methyl-epicatechin-glucuronide conjugates dose-dependently increased (Pcocoa powder. The concentration of 3-hydroxyphenylpropionic acid isomers in urine decreased as the dose of cocoa powder fed to pigs increased (75-85%,Pcocoa powder/d, respectively. Moreover, consumption of cocoa powder reducedTLR9gene expression in ileal Peyer's patches (67-80%,Pcocoa powder/d compared with pigs not supplemented with cocoa powder. This study demonstrates that consumption of cocoa powder by pigs can contribute to gut health by enhancing the abundance ofLactobacillusandBifidobacteriumspecies and modulating markers of localized intestinal immunity. © 2016 American Society for Nutrition.

  2. Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging.

    Science.gov (United States)

    Lemkaddem, Alia; Daducci, Alessandro; Kunz, Nicolas; Lazeyras, François; Seeck, Margitta; Thiran, Jean-Philippe; Vulliémoz, Serge

    2014-01-01

    Focal epilepsy is increasingly recognized as the result of an altered brain network, both on the structural and functional levels and the characterization of these widespread brain alterations is crucial for our understanding of the clinical manifestation of seizure and cognitive deficits as well as for the management of candidates to epilepsy surgery. Tractography based on Diffusion Tensor Imaging allows non-invasive mapping of white matter tracts in vivo. Recently, diffusion spectrum imaging (DSI), based on an increased number of diffusion directions and intensities, has improved the sensitivity of tractography, notably with respect to the problem of fiber crossing and recent developments allow acquisition times compatible with clinical application. We used DSI and parcellation of the gray matter in regions of interest to build whole-brain connectivity matrices describing the mutual connections between cortical and subcortical regions in patients with focal epilepsy and healthy controls. In addition, the high angular and radial resolution of DSI allowed us to evaluate also some of the biophysical compartment models, to better understand the cause of the changes in diffusion anisotropy. Global connectivity, hub architecture and regional connectivity patterns were altered in TLE patients and showed different characteristics in RTLE vs LTLE with stronger abnormalities in RTLE. The microstructural analysis suggested that disturbed axonal density contributed more than fiber orientation to the connectivity changes affecting the temporal lobes whereas fiber orientation changes were more involved in extratemporal lobe changes. Our study provides further structural evidence that RTLE and LTLE are not symmetrical entities and DSI-based imaging could help investigate the microstructural correlate of these imaging abnormalities.

  3. Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging

    Directory of Open Access Journals (Sweden)

    Alia Lemkaddem

    2014-01-01

    Global connectivity, hub architecture and regional connectivity patterns were altered in TLE patients and showed different characteristics in RTLE vs LTLE with stronger abnormalities in RTLE. The microstructural analysis suggested that disturbed axonal density contributed more than fiber orientation to the connectivity changes affecting the temporal lobes whereas fiber orientation changes were more involved in extratemporal lobe changes. Our study provides further structural evidence that RTLE and LTLE are not symmetrical entities and DSI-based imaging could help investigate the microstructural correlate of these imaging abnormalities.

  4. Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

    International Nuclear Information System (INIS)

    Gimpel, Charlotte; Pohl, Martin; Jung, Bernd A.; Jung, Sabine; Brado, Johannes; Odening, Katja E.; Schwendinger, Daniel; Burkhardt, Barbara; Geiger, Julia; Arnold, Raoul

    2017-01-01

    Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V E ), late diastolic (V A ) and peak systolic (V S ) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz base -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz mid -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz apex -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr base -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr mid -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr apex -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

  5. Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Gimpel, Charlotte; Pohl, Martin [Medical Center - University of Freiburg, Department of General Pediatrics, Adolescent Medicine and Neonatology, Center for Pediatrics, Freiburg (Germany); Jung, Bernd A. [Inselspital Bern, Institute of Diagnostic, Interventional and Pediatric Radiology, Bern (Switzerland); Jung, Sabine [Medical Center - University of Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Brado, Johannes; Odening, Katja E. [University Heart Center Freiburg, Department of Cardiology and Angiology I, Freiburg (Germany); Schwendinger, Daniel [University Children' s Hospital Zurich, Zurich (Switzerland); Burkhardt, Barbara [University Children' s Hospital Zurich, Pediatric Heart Center, Zurich (Switzerland); Geiger, Julia [University Children' s Hospital Zurich, Department of Radiology, Zurich (Switzerland); Northwestern University, Department of Radiology, Chicago, IL (United States); Arnold, Raoul [University Hospital Heidelberg, Department of Pediatric and Congenital Cardiology, Heidelberg (Germany)

    2017-02-15

    Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V{sub E}), late diastolic (V{sub A}) and peak systolic (V{sub S}) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz{sub base} -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz{sub mid} -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz{sub apex} -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr{sub base} -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr{sub mid} -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr{sub apex} -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

  6. Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children.

    Science.gov (United States)

    Landgraf, Kathrin; Rockstroh, Denise; Wagner, Isabel V; Weise, Sebastian; Tauscher, Roy; Schwartze, Julian T; Löffler, Dennis; Bühligen, Ulf; Wojan, Magdalena; Till, Holger; Kratzsch, Jürgen; Kiess, Wieland; Blüher, Matthias; Körner, Antje

    2015-04-01

    Accumulation of fat mass in obesity may result from hypertrophy and/or hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in adults. Here we assessed early alterations in AT biology and function by comprehensive experimental and clinical characterization of 171 AT samples from lean and obese children aged 0 to 18 years. We show an increase in adipocyte size and number in obese compared with lean children beginning in early childhood. These alterations in AT composition in obese children were accompanied by decreased basal lipolytic activity and significantly enhanced stromal vascular cell proliferation in vitro, potentially underlying the hypertrophy and hyperplasia seen in obese children, respectively. Furthermore, macrophage infiltration, including the formation of crown-like structures, was increased in AT of obese children from 6 years on and was associated with higher hs-CRP serum levels. Clinically, adipocyte hypertrophy was not only associated with leptin serum levels but was highly and independently correlated with HOMA-IR as a marker of insulin resistance in children. In summary, we show that adipocyte hypertrophy is linked to increased inflammation in AT in obese children, thereby providing evidence that obesity-associated AT dysfunction develops in early childhood and is related to insulin resistance. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes

    DEFF Research Database (Denmark)

    Heinemeier, K M; Skovgaard, D; Bayer, M L

    2012-01-01

    was increased, while collagen I was unchanged, and decreases were seen in noncollagen matrix components (fibromodulin and biglycan), matrix degrading enzymes, transforming growth factor-ß1, and connective tissue growth factor. In conclusion, the tested model could not be validated as a model for Achilles...... tendinopathy, as the rats were able to adapt to 12 wk of uphill running without any signs of tendinopathy. Improved mechanical properties were observed, as well as changes in gene-expression that were distinctly different from what is seen in tendinopathy and in response to short-term tendon loading....

  8. The effect of magnetic stimulation on the osteogenic and chondrogenic differentiation of human stem cells derived from the adipose tissue (hASCs)

    Energy Technology Data Exchange (ETDEWEB)

    Lima, João; Gonçalves, Ana I.; Rodrigues, Márcia T.; Reis, Rui L. [3Bs Research Group–Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães (Portugal); ICVS/3Bs–PT Government Associate Laboratory, Braga/Guimarães (Portugal); Gomes, Manuela E., E-mail: megomes@dep.uminho.pt [3Bs Research Group–Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães (Portugal); ICVS/3Bs–PT Government Associate Laboratory, Braga/Guimarães (Portugal)

    2015-11-01

    The use of magnetic nanoparticles (MNPs) towards the musculoskeletal tissues has been the focus of many studies, regarding MNPs ability to promote and direct cellular stimulation and orient tissue responses. This is thought to be mainly achieved by mechano-responsive pathways, which can induce changes in cell behavior, including the processes of proliferation and differentiation, in response to external mechanical stimuli. Thus, the application of MNP-based strategies in tissue engineering may hold potential to propose novel solutions for cell therapy on bone and cartilage strategies to accomplish tissue regeneration. The present work aims at studying the influence of MNPs on the osteogenic and chondrogenic differentiation of human adipose derived stem cells (hASCs). MNPs were incorporated in hASCs and cultured in medium supplemented for osteogenic and chondrogenic differentiation. Cultures were maintained up to 28 days with/without an external magnetic stimulus provided by a magnetic bioreactor, to determine if the MNPs alone could affect the osteogenic or chondrogenic phenotype of the hASCs. Results indicate that the incorporation of MNPs does not negatively affect the viability nor the proliferation of hASCs. Furthermore, Alizarin Red staining evidences an enhancement in extracellular (ECM) mineralization under the influence of an external magnetic field. Although not as evident as for osteogenic differentiation, Toluidine blue and Safranin-O stainings also suggest the presence of a cartilage-like ECM with glycosaminoglycans and proteoglycans under the magnetic stimulus provided. Thus, MNPs incorporated in hASCs under the influence of an external magnetic field have the potential to induce differentiation towards the osteogenic and chondrogenic lineages. - Highlights: • Cellular viability was not negatively influenced by the nanoparticles. • Chondrogenic medium influences more the synthesis of cartilage-like ECM than MNPs. • Synergetic effect among

  9. The effect of magnetic stimulation on the osteogenic and chondrogenic differentiation of human stem cells derived from the adipose tissue (hASCs)

    International Nuclear Information System (INIS)

    Lima, João; Gonçalves, Ana I.; Rodrigues, Márcia T.; Reis, Rui L.; Gomes, Manuela E.

    2015-01-01

    The use of magnetic nanoparticles (MNPs) towards the musculoskeletal tissues has been the focus of many studies, regarding MNPs ability to promote and direct cellular stimulation and orient tissue responses. This is thought to be mainly achieved by mechano-responsive pathways, which can induce changes in cell behavior, including the processes of proliferation and differentiation, in response to external mechanical stimuli. Thus, the application of MNP-based strategies in tissue engineering may hold potential to propose novel solutions for cell therapy on bone and cartilage strategies to accomplish tissue regeneration. The present work aims at studying the influence of MNPs on the osteogenic and chondrogenic differentiation of human adipose derived stem cells (hASCs). MNPs were incorporated in hASCs and cultured in medium supplemented for osteogenic and chondrogenic differentiation. Cultures were maintained up to 28 days with/without an external magnetic stimulus provided by a magnetic bioreactor, to determine if the MNPs alone could affect the osteogenic or chondrogenic phenotype of the hASCs. Results indicate that the incorporation of MNPs does not negatively affect the viability nor the proliferation of hASCs. Furthermore, Alizarin Red staining evidences an enhancement in extracellular (ECM) mineralization under the influence of an external magnetic field. Although not as evident as for osteogenic differentiation, Toluidine blue and Safranin-O stainings also suggest the presence of a cartilage-like ECM with glycosaminoglycans and proteoglycans under the magnetic stimulus provided. Thus, MNPs incorporated in hASCs under the influence of an external magnetic field have the potential to induce differentiation towards the osteogenic and chondrogenic lineages. - Highlights: • Cellular viability was not negatively influenced by the nanoparticles. • Chondrogenic medium influences more the synthesis of cartilage-like ECM than MNPs. • Synergetic effect among

  10. The effect of magnetic stimulation on the osteogenic and chondrogenic differentiation of human stem cells derived from the adipose tissue (hASCs)

    Science.gov (United States)

    Lima, João; Gonçalves, Ana I.; Rodrigues, Márcia T.; Reis, Rui L.; Gomes, Manuela E.

    2015-11-01

    The use of magnetic nanoparticles (MNPs) towards the musculoskeletal tissues has been the focus of many studies, regarding MNPs ability to promote and direct cellular stimulation and orient tissue responses. This is thought to be mainly achieved by mechano-responsive pathways, which can induce changes in cell behavior, including the processes of proliferation and differentiation, in response to external mechanical stimuli. Thus, the application of MNP-based strategies in tissue engineering may hold potential to propose novel solutions for cell therapy on bone and cartilage strategies to accomplish tissue regeneration. The present work aims at studying the influence of MNPs on the osteogenic and chondrogenic differentiation of human adipose derived stem cells (hASCs). MNPs were incorporated in hASCs and cultured in medium supplemented for osteogenic and chondrogenic differentiation. Cultures were maintained up to 28 days with/without an external magnetic stimulus provided by a magnetic bioreactor, to determine if the MNPs alone could affect the osteogenic or chondrogenic phenotype of the hASCs. Results indicate that the incorporation of MNPs does not negatively affect the viability nor the proliferation of hASCs. Furthermore, Alizarin Red staining evidences an enhancement in extracellular (ECM) mineralization under the influence of an external magnetic field. Although not as evident as for osteogenic differentiation, Toluidine blue and Safranin-O stainings also suggest the presence of a cartilage-like ECM with glycosaminoglycans and proteoglycans under the magnetic stimulus provided. Thus, MNPs incorporated in hASCs under the influence of an external magnetic field have the potential to induce differentiation towards the osteogenic and chondrogenic lineages.

  11. GH signaling in human adipose and muscle tissue during 'feast and famine': amplification of exercise stimulation following fasting compared to glucose administration.

    Science.gov (United States)

    Vendelbo, Mikkel H; Christensen, Britt; Grønbæk, Solbritt B; Høgild, Morten; Madsen, Michael; Pedersen, Steen B; Jørgensen, Jens O L; Jessen, Niels; Møller, Niels

    2015-09-01

    Fasting and exercise stimulates, whereas glucose suppresses GH secretion, but it is uncertain how these conditions impact GH signaling in peripheral tissues. To test the original 'feast and famine hypothesis' by Rabinowitz and Zierler, according to which the metabolic effects of GH are predominant during fasting, we specifically hypothesized that fasting and exercise act in synergy to increase STAT-5b target gene expression. Eight healthy men were studied on two occasions in relation to a 1 h exercise bout: i) with a concomitant i.v. glucose infusion ('feast') and ii) after a 36 h fast ('famine'). Muscle and fat biopsy specimens were obtained before, immediately after, and 30 min after exercise. GH increased during exercise on both examination days and this effect was amplified by fasting, and free fatty acid (FFA) levels increased after fasting. STAT-5b phosphorylation increased similarly following exercise on both occasions. In adipose tissue, suppressors of cytokine signaling 1 (SOCS1) and SOCS2 were increased after exercise on the fasting day and both fasting and exercise increased cytokine inducible SH2-containing protein (CISH). In muscle, SOCS2 and CISH mRNA were persistently increased after fasting. Muscle SOCS1, SOCS3, and CISH mRNA expression increased, whereas SOCS2 decreased after exercise on both examination days. This study demonstrates that fasting and exercise act in tandem to amplify STAT-5b target gene expression (SOCS and CISH) in adipose and muscle tissue in accordance with the 'feast and famine hypothesis'; the adipose tissue signaling responses, which hitherto have not been scrutinized, may play a particular role in promoting FFA mobilization. © 2015 European Society of Endocrinology.

  12. Growth Hormone Receptor Antagonist Transgenic Mice Have Increased Subcutaneous Adipose Tissue Mass, Altered Glucose Homeostasis and No Change in White Adipose Tissue Cellular Senescence.

    Science.gov (United States)

    Comisford, Ross; Lubbers, Ellen R; Householder, Lara A; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L; List, Edward O; Kopchick, John J; Berryman, Darlene E

    2016-01-01

    Growth hormone (GH)-resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests that long-lived GH-resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. The objective of this study was to examine WAT senescence, WAT distribution and glucose homeostasis in dwarf GH receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. 18-month-old female GHA mice and wild-type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose as well as glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase staining to quantify the senescent cell burden, and real-time qPCR to quantify gene expression of senescence markers p16 and IL-6. GHA mice had a 22% reduction in total body weight, a 33% reduction in lean mass and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p < 0.05) and a 1.7-fold increase in extra-/intraperitoneal WAT ratio compared to controls (p < 0.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin sensitivity, but no change in cellular senescence. The similar abundance of

  13. Alterations in Somatostatin Cells and Biochemical Parameters Following Zinc Supplementation in Gastrointestinal Tissue of St reptozotocin-Induced Diabetic Rats

    International Nuclear Information System (INIS)

    Bolkent, Sema; Bolkent, Sehnaz; Yanardag, Refiye; Mutlu, Ozgur; Yildirim, Sukriye

    2006-01-01

    Chronic hyperglycemia in diabetes is a major causative factor of free radical generation which further leads to many secondary diabetic complications via the damage to cellular proteins, membrane lipids, and nucleic acids. Zinc is an essential trace element in all living systems and plays a structural role in many proteins and enzymes. Somatostatin is known to have inhibitory effects on various gastrointestinal functions. Therefore, we determined somatostatin protein production and secretion levels, and biochemical and light microscopical changes following zinc supplementation in the gastrointestinal tract of streptozotocin (STZ)-diabetic rats. The animals were divided into four groups: Group I: control (untreated) animals; Group II: control animals given zinc sulfate; Group III: diabetic animals; and Group IV: diabetic animals given zinc sulfate. Zinc sulfate was given to the animals by gavage at a daily dose of 100 mg/kg body weight for 60 days. Diabetes was induced by intraperitoneal (i.p.) injection of STZ in a single dose of 65 mg/kg. For histological studies, stomach and duodenum tissues were fixed in Bouin solution and sections stained with Masson’s trichrome and Periodic-Acid-Schiff. Tissue homogenates were used for protein, lipid peroxidation (LPO), glutathione (GSH), and nonenzymatic glycosylation (NEG) analyses. Zinc supplementation to the STZ-diabetic rats revealed the protective effect of zinc on these parameters. Zinc supplementation may contribute to prevent at least some complications of diabetes mellitus

  14. Silica inhalation altered telomere length and gene expression of telomere regulatory proteins in lung tissue of rats.

    Science.gov (United States)

    Shoeb, Mohammad; Joseph, Pius; Kodali, Vamsi; Mustafa, Gul; Farris, Breanne Y; Umbright, Christina; Roberts, Jenny R; Erdely, Aaron; Antonini, James M

    2017-12-11

    Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT. Lung tissues and blood samples were collected from rats at 4, 32, and 44 wk after exposure to 15 mg/m 3 of silica × 6 h/d × 5 d. Controls were exposed to air. At all-time points, RTEL1 expression was significantly decreased in lung tissue of the silica-exposed animals compared to controls. Also, significant increases in telomere length and TERT were observed in the silica group at 4 and 32 wk. Telomere length, RTEL1 and TERT expression may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung disease and tumorigeneses.

  15. Specific inflammatory response of Anemonia sulcata (Cnidaria) after bacterial injection causes tissue reaction and enzymatic activity alteration.

    Science.gov (United States)

    Trapani, M R; Parisi, M G; Parrinello, D; Sanfratello, M A; Benenati, G; Palla, F; Cammarata, M

    2016-03-01

    The evolution of multicellular organisms was marked by adaptations to protect against pathogens. The mechanisms for discriminating the ''self'' from ''non-self" have evolved into a long history of cellular and molecular strategies, from damage repair to the co-evolution of host-pathogen interactions. We investigated the inflammatory response in Anemonia sulcata (Cnidaria: Anthozoa) following injection of substances that varied in type and dimension, and observed clear, strong and specific reactions, especially after injection of Escherichia coli and Vibrio alginolyticus. Moreover, we analyzed enzymatic activity of protease, phosphatase and esterase, showing how the injection of different bacterial strains alters the expression of these enzymes and suggesting a correlation between the appearance of the inflammatory reaction and the modification of enzymatic activities. Our study shows for the first time, a specific reaction and enzymatic responses following injection of bacteria in a cnidarian. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Ovarian stimulation and embryo banking for fertility preservation in a woman with severe mixed connective tissue disease: Is it safe?

    Science.gov (United States)

    Sioulas, Vasileios D; Gracia, Clarisa R

    2012-03-01

    To report the first case of using assisted reproductive technologies (ART) for fertility preservation in a patient with mixed connective tissue disease (MCTD), secondary pulmonary hypertension (PH) and antiphospholipid syndrome (APS). Case-report and review of the literature. Academic infertility practice and tertiary care center. A 25-year-old woman with MCTD, complicated with PH and APS, who was scheduled for gonadotoxic therapy Controlled ovarian hyperstimulation, egg retrieval, embryo banking. Successful ART cycle leading to embryo banking without worsening her underlying disease. Following successful embryo cryopreservation, the patient experienced respiratory failure and other severe complications, resulting in a prolonged hospital stay. Controlled ovarian hyperstimulation for embryo banking in women with MCTD, PH and APS may pose a risk for potentially catastrophic complications. A multidisciplinary approach to these patients is necessary to optimize the outcomes of such procedures. More data are needed regarding the safety of fertility preservation technologies in patients with complex medical diseases.

  17. Direct transplantation of native pericytes from adipose tissue: A new perspective to stimulate healing in critical size bone defects.

    Science.gov (United States)

    König, Matthias A; Canepa, Daisy D; Cadosch, Dieter; Casanova, Elisa; Heinzelmann, Michael; Rittirsch, Daniel; Plecko, Michael; Hemmi, Sonja; Simmen, Hans-Peter; Cinelli, Paolo; Wanner, Guido A

    2016-01-01

    Fractures with a critical size bone defect (e.g., open fracture with segmental bone loss) are associated with high rates of delayed union and non-union. The prevention and treatment of these complications remain a serious issue in trauma and orthopaedic surgery. Autologous cancellous bone grafting is a well-established and widely used technique. However, it has drawbacks related to availability, increased morbidity and insufficient efficacy. Mesenchymal stromal cells can potentially be used to improve fracture healing. In particular, human fat tissue has been identified as a good source of multilineage adipose-derived stem cells, which can be differentiated into osteoblasts. The main issue is that mesenchymal stromal cells are a heterogeneous population of progenitors and lineage-committed cells harboring a broad range of regenerative properties. This heterogeneity is also mirrored in the differentiation potential of these cells. In the present study, we sought to test the possibility to enrich defined subpopulations of stem/progenitor cells for direct therapeutic application without requiring an in vitro expansion. We enriched a CD146+NG2+CD45- population of pericytes from freshly isolated stromal vascular fraction from mouse fat tissue and tested their osteogenic differentiation capacity in vitro and in vivo in a mouse model for critical size bone injury. Our results confirm the ability of enriched CD146+NG2+CD45- cells to efficiently generate osteoblasts in vitro, to colonize cancellous bone scaffolds and to successfully contribute to regeneration of large bone defects in vivo. This study represents proof of principle for the direct use of enriched populations of cells with stem/progenitor identity for therapeutic applications. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  18. Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters retinoid homeostasis in maternal and perinatal tissues of the Holtzman rat

    International Nuclear Information System (INIS)

    Kransler, Kevin M.; Tonucci, David A.; McGarrigle, Barbara P.; Napoli, Joseph L.; Olson, James R.

    2007-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most widely studied environmental contaminants, causes a variety of adverse health effects including teratogenesis and altered development which may be related to disruptions in retinoid homeostasis. The purpose of this study was to determine the effect that gestational administration of TCDD has on retinoid homeostasis in both pregnant Holtzman rats and developing fetuses and neonates. A single oral dose of TCDD (0, 1.5, 3, or 6 μg/kg) was administered to pregnant rats on gestation day 10, with fetuses analyzed on gestation days 17 and 20, and neonates analyzed on post natal day 7. Exposure to TCDD generally produced decreases in the concentrations of retinyl esters, such as retinyl palmitate, and retinol in maternal and perinatal liver and lung, while increasing levels in the maternal kidney. Additionally, perinatal hepatic retinol binding protein 1-dependent retinyl ester hydrolysis was also decrease by TCDD. Sensitivity of the developing perinates to TCDD appeared to have an age-related component demonstrated by an increased rate of mortality and significant alterations to body weight and length on post natal day 7 relative to that observed at gestation day 20. A unique observation made in this study was a significant decrease in lung weight observed in the perinates exposed to TCDD. Taken together, these data demonstrate that TCDD significantly alters retinoid homeostasis in tissues of the developing fetus and neonate, suggesting that their unique sensitivity to TCDD may at least be in part the result of altered retinoid homeostasis

  19. Exercise decreases lipogenic gene expression in adipose tissue and alters adipocyte cellularity during weight regain after weight loss.

    Directory of Open Access Journals (Sweden)

    Erin Danielle Giles

    2016-02-01

    Full Text Available Exercise is a potent strategy to facilitate long-term weight maintenance. In addition to increasing energy expenditure and reducing appetite, exercise also favors the oxidation of dietary fat, which likely helps prevent weight re-gain. It is unclear whether this exercise-induced metabolic shift is due to changes in energy balance, or whether exercise imparts additional adaptations in the periphery that limit the storage and favor the oxidation of dietary fat. To answer this question, adipose tissue lipid metabolism and related gene expression were studied in obese rats following weight loss and during the first day of relapse to obesity. Mature, obese rats were weight-reduced for 2 weeks with or without daily treadmill exercise (EX. Rats were weight maintained for 6 weeks, followed by relapse on: a ad libitum low fat diet (LFD, b ad libitum LFD plus EX, or c a provision of LFD to match the positive energy imbalance of exercised, relapsing animals. 24h retention of dietary- and de novo-derived fat were assessed directly using 14C palmitate/oleate and 3H20, respectively. Exercise decreased the size, but increased the number of adipocytes in both retroperitoneal (RP and subcutaneous (SC adipose depots, and prevented the relapse-induced increase in adipocyte size. Further, exercise decreased the expression of genes involved in lipid uptake (CD36 & LPL, de novo lipogenesis (FAS, ACC1, and triacylglycerol synthesis (MGAT & DGAT in RP adipose during relapse following weight loss. This was consistent with the metabolic data, whereby exercise reduced retention of de novo-derived fat even when controlling for the positive energy imbalance. The decreased trafficking of dietary fat to adipose tissue with exercise was explained by reduced energy intake which attenuated energy imbalance during refeeding. Despite having decreased expression of lipogenic genes, the net retention of de novo-derived lipid was higher in both the RP and SC adipose of exercising

  20. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport

    International Nuclear Information System (INIS)

    Rebouche, C.J.; Engel, A.G.

    1984-01-01

    The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and ''other tissues'') was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract

  1. Transcranial magnetic stimulation in schizophrenia.

    Science.gov (United States)

    Zaman, Rashid; Thind, Dilraj; Kocmur, Marga

    2008-11-01

    Transcranial magnetic stimulation (TMS) is a non-invasive and painless way of stimulating the neural tissue (cerebral cortex, spinal roots, and cranial and peripheral nerves). The first attempts at stimulating the neural tissue date back to 1896 by d'Arsonval; however, it was successfully carried out by Barker and colleagues in Sheffield, UK, in 1985. It soon became a useful tool in neuroscience for neurophysiologists and neurologists and psychiatrists. The original single-pulse TMS, largely used as an investigative tool, was further refined and developed in the early 1990s into what is known as repetitive TMS (rTMS), having a frequency range of 1-60 Hz. The stimulation by both TMS and rTMS of various cortical regions displayed alteration of movement, mood, and behavior, leading researchers to investigate a number of psychiatric and neuropsychiatric disorders, as well as to explore its therapeutic potential. There is now a large amount of literature on the use of TMS/rTMS in depression; however, its use in schizophrenia, both as an investigative and certainly as a therapeutic tool is relatively recent with a limited but increasing number of publications. In this article, we will outline the principles of TMS/rTMS and critically review their use in schizophrenia both as investigative and potential therapeutic tools.

  2. Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect.

    Science.gov (United States)

    Filho, Paulo Ricardo Marques; Vercelino, Rafael; Cioato, Stefania Giotti; Medeiros, Liciane Fernandes; de Oliveira, Carla; Scarabelot, Vanessa Leal; Souza, Andressa; Rozisky, Joanna Ripoll; Quevedo, Alexandre da Silva; Adachi, Lauren Naomi Spezia; Sanches, Paulo Roberto S; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

    2016-01-04

    Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, PtDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, PtDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, PtDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels

  3. The role of mechanical loading in ligament tissue engineering.

    Science.gov (United States)

    Benhardt, Hugh A; Cosgriff-Hernandez, Elizabeth M

    2009-12-01

    Tissue-engineered ligaments have received growing interest as a promising alternative for ligament reconstruction when traditional transplants are unavailable or fail. Mechanical stimulation was recently identified as a critical component in engineering load-bearing tissues. It is well established that living tissue responds to altered loads through endogenous changes in cellular behavior, tissue organization, and bulk mechanical properties. Without the appropriate biomechanical cues, new tissue formation lacks the necessary collagenous organization and alignment for sufficient load-bearing capacity. Therefore, tissue engineers utilize mechanical conditioning to guide tissue remodeling and improve the performance of ligament grafts. This review provides a comparative analysis of the response of ligament and tendon fibroblasts to mechanical loading in current bioreactor studies. The differential effect of mechanical stimulation on cellular processes such as protease production, matrix protein synthesis, and cell proliferation is examined in the context of tissue engineering design.

  4. Adaptive Redox Response of Mesenchymal Stromal Cells to Stimulation with Lipopolysaccharide Inflammagen: Mechanisms of Remodeling of Tissue Barriers in Sepsis

    Directory of Open Access Journals (Sweden)

    Nikolai V. Gorbunov

    2013-01-01

    Full Text Available Acute bacterial inflammation is accompanied by excessive release of bacterial toxins and production of reactive oxygen and nitrogen species (ROS and RNS, which ultimately results in redox stress. These factors can induce damage to components of tissue barriers, including damage to ubiquitous mesenchymal stromal cells (MSCs, and thus can exacerbate the septic multiple organ dysfunctions. The mechanisms employed by MSCs in order to survive these stress conditions are still poorly understood and require clarification. In this report, we demonstrated that in vitro treatment of MSCs with lipopolysaccharide (LPS induced inflammatory responses, which included, but not limited to, upregulation of iNOS and release of RNS and ROS. These events triggered in MSCs a cascade of responses driving adaptive remodeling and resistance to a “self-inflicted” oxidative stress. Thus, while MSCs displayed high levels of constitutively present adaptogens, for example, HSP70 and mitochondrial Sirt3, treatment with LPS induced a number of adaptive responses that included induction and nuclear translocation of redox response elements such as NFkB, TRX1, Ref1, Nrf2, FoxO3a, HO1, and activation of autophagy and mitochondrial remodeling. We propose that the above prosurvival pathways activated in MSCs in vitro could be a part of adaptive responses employed by stromal cells under septic conditions.

  5. Modified n-HA/PA66 scaffolds with chitosan coating for bone tissue engineering: cell stimulation and drug release.

    Science.gov (United States)

    Zou, Qin; Li, Junfeng; Niu, Lulu; Zuo, Yi; Li, Jidong; Li, Yubao

    2017-09-01

    The dipping-drying procedure and cross-linking method were used to make drug-loaded chitosan (CS) coating on nano-hydroxyapatite/polyamide66 (nHA/PA66) composite porous scaffold, endowing the scaffold controlled drug release functionality. The prefabricated scaffold was immersed into an aqueous drug/CS solution in a vacuum condition and then crosslinked by vanillin. The structure, porosity, composition, compressive strength, swelling ratio, drug release and cytocompatibility of the pristine and coating scaffolds were investigated. After coating, the scaffold porosity and pore interconnection were slightly decreased. Cytocompatibility performance was observed through an in vitro experiment based on cell attachment and the MTT assay by MG63 cells which revealed positive cell viability and increasing proliferation over the 11-day period in vitro. The drug could effectively release from the coated scaffold in a controlled fashion and the release rate was sustained for a long period and highly dependent on coating swelling, suggesting the possibility of a controlled drug release. Our results demonstrate that the scaffold with drug-loaded crosslinked CS coating can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to be a promising high performance biomaterial in bone tissue engineering.

  6. Brittle stalk 2 encodes a putative glycosylphosphatidylinositol-anchored protein that affects mechanical strength of maize tissues by altering the composition and structure of secondary cell walls.

    Science.gov (United States)

    Ching, Ada; Dhugga, Kanwarpal S; Appenzeller, Laura; Meeley, Robert; Bourett, Timothy M; Howard, Richard J; Rafalski, Antoni

    2006-10-01

    A spontaneous maize mutant, brittle stalk-2 (bk2-ref), exhibits dramatically reduced tissue mechanical strength. Reduction in mechanical strength in the stalk tissue was highly correlated with a reduction in the amount of cellulose and an uneven deposition of secondary cell wall material in the subepidermal and perivascular sclerenchyma fibers. Cell wall accounted for two-thirds of the observed reduction in dry matter content per unit length of the mutant stalk in comparison to the wildtype stalk. Although the cell wall composition was significantly altered in the mutant in comparison to the wildtype stalks, no compensation by lignin and cell wall matrix for reduced cellulose amount was observed. We demonstrate that Bk2 encodes a Cobra-like protein that is homologous to the rice Bc1 protein. In the bk2-ref gene, a 1 kb transposon-like element is inserted in the beginning of the second exon, disrupting the open reading frame. The Bk2 gene was expressed in the stalk, husk, root, and leaf tissues, but not in the embryo, endosperm, pollen, silk, or other tissues with comparatively few or no secondary cell wall containing cells. The highest expression was in the isolated vascular bundles. In agreement with its role in secondary wall formation, the expression pattern of the Bk2 gene was very similar to that of the ZmCesA10, ZmCesA11, and ZmCesA12 genes, which are known to be involved in secondary wall formation. We have isolated an independent Mutator-tagged allele of bk2, referred to as bk2-Mu7, the phenotype of which is similar to that of the spontaneous mutant. Our results demonstrate that mutations in the Bk2 gene affect stalk strength in maize by interfering with the deposition of cellulose in the secondary cell wall in fiber cells.

  7. Tissue-associated bacterial alterations in rectal carcinoma patients revealed by 16S rRNA community profiling

    Directory of Open Access Journals (Sweden)

    Andrew Maltez Thomas

    2016-12-01

    Full Text Available Sporadic and inflammatory forms of colorectal cancer (CRC account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases. Also, the common use of fecal samples to study microbial communities may reflect disease state but possibly not the tumor microenvironment. We performed this study to evaluate differences in bacterial communities found in tissue samples of 18 rectal-cancer subjects when compared to 18 non-cancer controls. Samples were collected during exploratory colonoscopy (non-cancer group or during surgery for tumor excision (rectal-cancer group. High throughput 16S rRNA amplicon sequencing of the V4-V5 region was conducted on the Ion PGM platform, reads were filtered using Qiime and clustered using UPARSE. We observed significant increases in species richness and diversity in rectal cancer samples, evidenced by the total number of OTUs and the Shannon and Simpson indexes. Enterotyping analysis divided our cohort into two groups, with the majority of rectal cancer samples clustering into one enterotype, characterized by a greater abundance of Bacteroides and Dorea. At the phylum level, rectal-cancer samples had increased abundance of candidate phylum OD1 (also known as Parcubacteria whilst non-cancer samples had increased abundance of Planctomycetes. At the genera level, rectal-cancer samples had higher abundances of Bacteroides, Phascolarctobacterium, Parabacteroides, Desulfovibrio and Odoribacter whereas non-cancer samples had higher abundances of Pseudomonas, Escherichia, Acinetobacter, Lactobacillus and Bacillus. Two Bacteroides fragilis OTUs were more abundant among rectal-cancer patients seen through 16S rRNA amplicon sequencing, whose presence was confirmed by immunohistochemistry and enrichment verified

  8. Altered gene expression in pulmonary tissue of tryptophan hydroxylase-1 knockout mice: implications for pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Richard B Rothman

    Full Text Available The use of fenfluramines can increase the risk of developing pulmonary arterial hypertension (PAH in humans, but the mechanisms responsible are unresolved. A recent study reported that female mice lacking the gene for tryptophan hydroxylase-1 (Tph1(-/- mice were protected from PAH caused by chronic dexfenfluramine, suggesting a pivotal role for peripheral serotonin (5-HT in the disease process. Here we tested two alternative hypotheses which might explain the lack of dexfenfluramine-induced PAH in Tph1(-/- mice. We postulated that: 1 Tph1(-/- mice express lower levels of pulmonary 5-HT transporter (SERT when compared to wild-type controls, and 2 Tph1(-/- mice display adaptive changes in the expression of non-serotonergic pulmonary genes which are implicated in PAH. SERT was measured using radioligand binding methods, whereas gene expression was measured using microarrays followed by quantitative real time PCR (qRT-PCR. Contrary to our first hypothesis, the number of pulmonary SERT sites was modestly up-regulated in female Tph1(-/- mice. The expression of 51 distinct genes was significantly altered in the lungs of female Tph1(-/- mice. Consistent with our second hypothesis, qRT-PCR confirmed that at least three genes implicated in the pathogenesis of PAH were markedly up-regulated: Has2, Hapln3 and Retlna. The finding that female Tph1(-/- mice are protected from dexfenfluramine-induced PAH could be related to compensatory changes in pulmonary gene expression, in addition to reductions in peripheral 5-HT. These observations emphasize the intrinsic limitation of interpreting data from studies conducted in transgenic mice that are not fully characterized.

  9. Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging?

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available Accumulation of DNA damage leading to stem cell exhaustion has been proposed to be a principal mechanism of aging. Using 53BP1-foci as a marker for DNA double-strand breaks (DSBs, hair follicle stem cells (HFSCs in mouse epidermis were analyzed for age-related DNA damage response (DDR. We observed increasing amounts of 53BP1-foci during the natural aging process independent of telomere shortening and after protracted low-dose radiation, suggesting substantial accumulation of DSBs in HFSCs. Electron microscopy combined with immunogold-labeling showed multiple small 53BP1 clusters diffusely distributed throughout the highly compacted heterochromatin of aged HFSCs, but single large 53BP1 clusters in irradiated HFSCs. These remaining 53BP1 clusters did not colocalize with core components of non-homologous end-joining, but with heterochromatic histone modifications. Based on these results we hypothesize that these lesions were not persistently unrepaired DSBs, but may reflect chromatin rearrangements caused by the repair or misrepair of DSBs. Flow cytometry showed increased activation of repair proteins and damage-induced chromatin modifications, triggering apoptosis and cellular senescence in irradiated, but not in aged HFSCs. These results suggest that accumulation of DNA damage-induced chromatin alterations, whose structural dimensions reflect the complexity of the initial genotoxic insult, may lead to different DDR events, ultimately determining the biological outcome of HFSCs. Collectively, our findings support the hypothesis that aging might be largely the remit of structural changes to chromatin potentially leading to epigenetically induced transcriptional deregulation.

  10. Excitatory amino acid receptor blockade within the caudal pressor area and rostral ventrolateral medulla alters cardiovascular responses to nucleus raphe obscurus stimulation in rats

    Directory of Open Access Journals (Sweden)

    Silva N.F.

    2002-01-01

    Full Text Available Pressor responses elicited by stimulation of the nucleus raphe obscurus (NRO depend on the integrity of the rostral ventrolateral medulla (RVLM. Therefore, to test the participation of excitatory amino acid (EAA receptors in the cardiovascular responses evoked by NRO stimulation (1 ms, 100 Hz, 40-70 µA, for 10 s, the EAA antagonist kynurenic acid (Kyn was microinjected at different sites in the ventrolateral medullar surface (2.7 nmol/200 nl of male Wistar rats (270-320 g, N = 39 and NRO stimulation was repeated. The effects of NRO stimulation were: hypertension (deltaMAP = +43 ± 1 mmHg, P<0.01, bradycardia (deltaHR = -30 ± 7 bpm, P<0.01 and apnea. Bilateral microinjection of Kyn into the RVLM, which did not change baseline parameters, almost abolished the bradycardia induced by NRO stimulation (deltaHR = -61 ± 3 before vs -2 ± 3 bpm after Kyn, P<0.01, N = 7. Unilateral microinjection of Kyn into the CVLM did not change baseline parameters or reduce the pressor response to NRO stimulation (deltaMAP = +46 ± 5 before vs +48 ± 5 mmHg after Kyn, N = 6. Kyn bilaterally microinjected into the caudal pressor area reduced blood pressure and heart rate and almost abolished the pressor response to NRO stimulation (deltaMAP = +46 ± 4 mmHg before vs +4 ± 2 mmHg after Kyn, P<0.01, N = 7. These results indicate that EAA receptors on the medullary ventrolateral surface play a role in the modulation of the cardiovascular responses induced by NRO stimulation, and also suggest that the RVLM participates in the modulation of heart rate responses and that the caudal pressor area modulates the pressor response following NRO stimulation.

  11. Toll-like receptor 6 and connective tissue growth factor are significantly upregulated in mitomycin-C-treated urothelial carcinoma cells under hydrostatic pressure stimulation.

    Science.gov (United States)

    Chen, Shao-Kuan; Chung, Chih-Ang; Cheng, Yu-Che; Huang, Chi-Jung; Chen, Wen-Yih; Ruaan, Ruoh-Chyu; Li, Chuan; Tsao, Chia-Wen; Hu, Wei-Wen; Chien, Chih-Cheng

    2014-06-01

    Urothelial carcinoma (UC) is the most common histologic subtype of bladder cancer. The administration of mitomycin C (MMC) into the bladder after transurethral resection of the bladder tumor (TURBT) is a common treatment strategy for preventing recurrence after surgery. We previously applied hydrostatic pressure combined with MMC in UC cells and found that hydrostatic pressure synergistically enhanced MMC-induced UC cell apoptosis through the Fas/FasL pathways. To understand the alteration of gene expressions in UC cells caused by hydrostatic pressure and MMC, oligonucleotide microarray was used to explore all the differentially expressed genes. After bioinformatics analysis and gene annotation, Toll-like receptor 6 (TLR6) and connective tissue growth factor (CTGF) showed significant upregulation among altered genes, and their gene and protein expressions with each treatment of UC cells were validated by quantitative real-time PCR and immunoblotting. Under treatment with MMC and hydrostatic pressure, UC cells showed increasing apoptosis using extrinsic pathways through upregulation of TLR6 and CTGF.

  12. A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation.

    Science.gov (United States)

    Bjørndal, Bodil; Berge, Christ; Ramsvik, Marie Sannes; Svardal, Asbjørn; Bohov, Pavol; Skorve, Jon; Berge, Rolf K

    2013-10-07

    There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNFα). hTNFα mice (C57BL/6 hTNFα) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ∆6 and ∆9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-γ level was observed. Plasma carnitine and the carnitine precursor γ-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal β-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.

  13. Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus).

    Science.gov (United States)

    Lattin, Christine R; Romero, L Michael

    2014-07-15

    The physiological stress response results in release of glucocorticoid hormones such as corticosterone (CORT). Whereas short-term activation of this response helps animals cope with environmental stressors, chronic activation can result in negative effects including metabolic dysregulation and reproductive failure. However, there is no consensus hormonal profile of a chronically stressed animal, suggesting that researchers may need to look beyond hormone titers to interpret the impacts of chronic stress. In this study, we brought wild house sparrows (Passer domesticus) into captivity. We then compared glucocorticoid and mineralocorticoid receptor concentrations in sparrows exposed either to a standardized chronic stress protocol (n=26) or to standard husbandry conditions (controls; n=20). We used radioligand binding assays to quantify receptors in whole brain, liver, kidneys, spleen, gonads, gastrocnemius and pectoralis muscle, omental and subcutaneous fat, and bib and back skin. In most tissues, CORT receptors did not differ between controls and stressed animals, although we found marginal increases in receptor density in kidney and testes in stressed birds at some time points. Only in pectoralis muscle was there a robust effect of chronic stress, with both receptor types higher in stressed animals. Increased pectoralis sensitivity to CORT with chronic stress may be part of the underlying mechanism for muscle wasting in animals administered exogenous CORT. Furthermore, the change in pectoralis was not paralleled by gastrocnemius receptors. This difference may help explain previous reports of a greater effect of CORT on pectoralis than on other muscle types, and indicate that birds use this muscle as a protein reserve. © 2014. Published by The Company of Biologists Ltd.

  14. Studies of gene expression and activity of hexokinase, phosphofructokinase and glycogen synthase in human skeletal muscle in states of altered insulin-stimulated glucose metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H

    1999-01-01

    been reported to increase the basal concentration of muscle GS mRNA in NIDDM patients to a level similar to that seen in control subjects although insulin-stimulated glucose disposal rates remain reduced in NIDDM patients. In the insulin resistant states examined so far, basal and insulin-stimulated......When whole body insulin-stimulated glucose disposal rate is measured in man applying the euglycaemic, hyperinsulinaemic clamp technique it has been shown that approximately 75% of glucose is taken up by skeletal muscle. After the initial transport step, glucose is rapidly phosphorylated to glucose...... critical roles in glucose oxidation/glycolysis and glucose storage, respectively. Glucose transporters and glycogen synthase activities are directly and acutely stimulated by insulin whereas the activities of hexokinases and phosphofructokinase may primarily be allosterically regulated. The aim...

  15. Alterations to proteome and tissue recovery responses in fish liver caused by a short-term combination treatment with cadmium and benzo[a]pyrene

    International Nuclear Information System (INIS)

    Costa, P.M.; Chicano-Galvez, E.; Lopez Barea, J.; DelValls, T.A.; Costa, M.H.

    2010-01-01

    The livers of soles (Solea senegalensis) injected with subacute doses of cadmium (Cd), benzo[a]pyrene (B[a]P), or their combination, were screened for alterations to cytosolic protein expression patterns, complemented by cytological and histological analyses. Cadmium and B[a]P, but not combined, induced hepatocyte apoptosis and Kupfer cell hyperplasia. Proteomics, however, suggested that apoptosis was triggered through distinct pathways. Cadmium and B[a]P caused upregulation of different anti-oxidative enzymes (peroxiredoxin and glutathione peroxidase, respectively) although co-exposure impaired induction. Similarly, apoptosis was inhibited by co-exposure, to which may have contributed a synergistic upregulation of tissue metalloproteinase inhibitor, β-actin and a lipid transport protein. The regulation factors of nine out of eleven identified proteins of different types revealed antagonistic or synergistic effects between Cd and B[a]P at the prospected doses after 24 h of exposure. The results indicate that co-exposure to Cd and B[a]P may enhance toxicity by impairing specific responses and not through cumulative damage. - The interaction between cadmium and benzo[a]pyrene impairs specific responses to toxicity and tissue repair mechanisms.

  16. Data Mining of Small RNA-Seq Suggests an Association Between Prostate Cancer and Altered Abundance of 5′ Transfer RNA Halves in Seminal Fluid and Prostatic Tissues

    Directory of Open Access Journals (Sweden)

    Joseph M Dhahbi

    2018-02-01

    Full Text Available Extracellular RNAs are gaining clinical interest as biofluid-based noninvasive markers for diseases, especially cancer. In particular, derivatives of transfer RNA (tRNA are emerging as a new class of small-noncoding RNAs with high biomarker potential. We and others previously reported alterations in serum levels of specific tRNA halves in disease states including cancer. Here, we explored seminal fluid for tRNA halves as potential markers of prostate cancer. We found that 5′ tRNA halves are abundant in seminal fluid and are elevated in prostate cancer relative to noncancer patients. Importantly, most of these tRNA halves are also detectable in prostatic tissues, and a subset were increased in malignant relative to adjacent normal tissue. These findings emphasize the potential of 5′ tRNA halves as noninvasive markers for prostate cancer screening and diagnosis and provide leads for future work to elucidate a putative role of the 5′ tRNA halves in carcinogenesis.

  17. Inhibition of COX1/2 alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury.

    Science.gov (United States)

    Dearth, Christopher L; Slivka, Peter F; Stewart, Scott A; Keane, Timothy J; Tay, Justin K; Londono, Ricardo; Goh, Qingnian; Pizza, Francis X; Badylak, Stephen F

    2016-02-01

    muscle injury model. The COX1/2 inhibitor, Aspirin, was found to mitigate the ECM scaffold-mediated constructive remodeling response both in an in vitro co-culture system and an in vivo rat model of skeletal muscle injury. The results presented herein provide data showing that NSAIDs may significantly alter tissue remodeling outcomes when a biomaterial is used in a regenerative medicine/tissue engineering application. Thus, the decision to prescribe NSAIDs to manage the symptoms of inflammation post-ECM scaffold implantation should be carefully considered. Published by Elsevier Ltd.

  18. Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

    Science.gov (United States)

    Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

    2018-04-12

    Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright

  19. Increased expression of C-reactive protein gene in inflamed gingival tissues could be derived from endothelial cells stimulated with interleukin-6.

    Science.gov (United States)

    Maekawa, Tomoki; Tabeta, Koichi; Kajita-Okui, Keiko; Nakajima, Takako; Yamazaki, Kazuhisa

    2011-11-01

    Epidemiological studies have suggested periodontitis as a risk factor for ischemic heart disease. High sensitive C-reactive protein (hs-CRP), a predictor of cardiovascular risk, is elevated in periodontitis patients. Therefore, local infection-induced elevation of systemic CRP could account for the relationship between the 2 diseases. However, the underlying mechanism of CRP production in the periodontal tissues has not been fully elucidated. Therefore, the aim of the present study was to clarify the mechanism of CRP production in periodontal tissues. Gene expression of CRP in gingival biopsies was analysed by quantitative PCR. Human gingival epithelial cells (HGECs), human gingival fibroblasts (HGFBs), and human coronary artery endothelial cells (HCAECs) were characterized for CRP-producing ability by incubating with interleukin (IL)-1β, IL-6, soluble IL-6 receptor (sIL-6R), and Porphyromonas gingivalis strain W83. Gene expression of CRP is significantly elevated in periodontitis lesions compared with gingivitis lesions. HCAECs, but not HGECs and HGFBs, produced CRP in response to IL-6 and IL-1β in the presence of sIL-6R. In contrast to IL-6, the effect of IL-1β on CRP production was indirect via induction of IL-6. IL-1β was produced by HGECs and HGFBs with stimulation of P. gingivalis antigens. These results suggest that CRP induced locally by periodontal infection may play another role in the pathogenesis of periodontal disease, and to a much lesser extent, has the potential to modulate systemic CRP level by extra-hepatic CRP production. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Prevotella intermedia stimulates tissue-type plasminogen activator and plasminogen activator inhibitor-2 expression via multiple signaling pathways in human periodontal ligament cells.

    Science.gov (United States)

    Guan, Su-Min; He, Jian-Jun; Zhang, Ming; Shu, Lei

    2011-06-01

    Prevotella intermedia is an important periodontal pathogen that induces various inflammatory and immune responses. In this study, we investigated the effects of P. intermedia on the plasminogen system in human periodontal ligament (hPDL) cells and explored the signaling pathways involved. Using semi-quantitative reverse transcription (RT)-PCR and quantitative real-time RT-qPCR, we demonstrated that P. intermedia challenge increased tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-2 expression in a concentration- and time-dependent manner, but exerted no influence on urokinase-type plasminogen activator and PAI-1mRNA expression in hPDL cells. Prevotella intermedia stimulation also enhanced tPA protein secretion as confirmed by enzyme-linked immunosorbent assay. Western blot results revealed that P. intermedia treatment increased phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38). ERK, JNK and protein kinase C inhibitors significantly attenuated the P. intermedia-induced tPA and PAI-2 expression. Furthermore, p38 and phosphatidylinositol 3-kinase inhibitors markedly decreased PAI-2 expression, whereas they showed no or little inhibition on tPA expression. In contrast, inhibition of protein kinase A greatly enhanced the upregulatory effect of P. intermedia on tPA and PAI-2 expression. Our results suggest that P. intermedia may contribute to periodontal tissue destruction by upregulating tPA and PAI-2 expression in hPDL cells via multiple signaling pathways. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  1. Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice: distinct early response compared with single trauma or "double-hit" injury.

    Science.gov (United States)

    Weckbach, Sebastian; Hohmann, Christoph; Braumueller, Sonja; Denk, Stephanie; Klohs, Bettina; Stahel, Philip F; Gebhard, Florian; Huber-Lang, Markus S; Perl, Mario

    2013-02-01

    The exact alterations of the immune system after polytrauma leading to sepsis and multiple-organ failure are poorly understood. Thus, the early local and systemic inflammatory and apoptotic response was characterized in a new polytrauma model and compared with the alterations seen after single or combined injuries. Anesthetized C57BL/6 mice were subjected to either blunt bilateral chest trauma (Tx), closed head injury, right femur fracture including contralateral soft tissue injury, or a combination of injuries (PTx). After 2 hours or 6 hours, animals were sacrificed, and the systemic as well as the local pulmonary immune response (bronchoalveolar lavage [BAL]/plasma cytokines, lung myeloperoxidase [MPO] activity, and alveolocapillary barrier dysfunction) were evaluated along with lung/brain apoptosis (lung caspase 3 Western blotting, immunohistochemistry, and polymorphonuclear leukocytes [PMN] Annexin V). Hemoglobin, PO2 saturation, and pH did not differ between the experimental groups. Local BAL cytokines/chemokines were significantly increased in almost all groups, which included Tx. There was no further enhancement of this local inflammatory response in the lungs in case of PTx. At 2 hours, all groups except sham and closed head injury alone revealed an increased activity of lung MPO. However, 6 hours after injury, lung MPO remained increased only in the PTx group. Increased BAL protein levels were found, reflecting enhanced lung leakage in all groups with Tx 6 hours after trauma. Only after PTx was neutrophil apoptosis significantly decreased, whereas lung caspase 3 and plasma interleukin 6/keratinocyte chemoattractant (KC) were substantially increased. The combination of different injuries leads to an earlier systemic inflammatory response when compared with the single insults. Interestingly, only after PTx but not after single or double hits was lung apoptosis increased, and PMN apoptosis was decreased along with a prolonged presence of neutrophils in the

  2. 2,5-hexanedione (HD) treatment alters calmodulin, Ca2+/calmodulin-dependent protein kinase II, and protein kinase C in rats' nerve tissues

    International Nuclear Information System (INIS)

    Wang Qingshan; Hou Liyan; Zhang Cuili; Zhao Xiulan; Yu Sufang; Xie, Ke-Qin

    2008-01-01

    Calcium-dependent mechanisms, particularly those mediated by Ca 2+ /calmodulin (CaM)-dependent protein kinase II (CaMKII), have been implicated in neurotoxicant-induced neuropathy. However, it is unknown whether similar mechanisms exist in 2,5-hexanedione (HD)-induced neuropathy. For that, we investigated the changes of CaM, CaMKII, protein kinase C (PKC) and polymerization ratios (PRs) of NF-L, NF-M and NF-H in cerebral cortex (CC, including total cortex and some gray), spinal cord (SC) and sciatic nerve (SN) of rats treated with HD at a dosage of 1.75 or 3.50 mmol/kg for 8 weeks (five times per week). The results showed that CaM contents in CC, SC and SN were significantly increased, which indicated elevation of Ca 2+ concentrations in nerve tissues. CaMKII contents and activities were also increased in CC and were positively correlated with gait abnormality, but it could not be found in SC and SN. The increases of PKC contents and activities were also observed in SN and were positively correlated with gait abnormality. Except for that of NF-M in CC, the PRs of NF-L, NF-M and NF-H were also elevated in nerve tissues, which was consistent with the activation of protein kinases. The results suggested that CaMKII might be partly (in CC but not in SC and SN) involved in HD-induced neuropathy. CaMKII and PKC might mediate the HD neurotoxicity by altering the NF phosphorylation status and PRs

  3. Proteomic analysis on the alteration of protein expression in the early-stage placental villous tissue of electromagnetic fields associated with cell phone exposure.

    Science.gov (United States)

    Luo, Qiong; Jiang, Ying; Jin, Min; Xu, Jian; Huang, He-Feng

    2013-09-01

    To explore the possible adverse effects and search for cell phone electromagnetic field (EMF)-responsive proteins in human early reproduction, a proteomics approach was employed to investigate the changes in protein expression profile induced by cell phone EMF in human chorionic tissues of early pregnancy in vivo. Volunteer women about 50 days pregnant were exposed to EMF at the average absorption rate of 1.6 to 8.8 W/kg for 1 hour with the irradiation device placed 10 cm away from the umbilicus at the midline of the abdomen. The changes in protein profile were examined using 2-dimensional electrophoresis (2-DE). Up to 15 spots have yielded significant change at least 2- to 2.5-folds up or down compared to sham-exposed group. Twelve proteins were identified- procollagen-proline, eukaryotic translation elongation factor 1 delta, chain D crystal structure of human vitamin D-binding protein, thioredoxin-like 3, capping protein, isocitrate dehydrogenase 3 alpha, calumenin, Catechol-O-methyltransferase protein, proteinase inhibitor 6 (PI-6; SerpinB6) protein, 3,2-trans-enoyl-CoA isomerase protein, chain B human erythrocyte 2,3-bisphosphoglycerate mutase, and nucleoprotein. Cell phone EMF might alter the protein profile of chorionic tissue of early pregnancy, during the most sensitive stage of the embryos. The exposure to EMF may cause adverse effects on cell proliferation and development of nervous system in early embryos. Furthermore, 2-DE coupled with mass spectrometry is a promising approach to elucidate the effects and search for new biomarkers for environmental toxic effects.

  4. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

    Directory of Open Access Journals (Sweden)

    María Eugenia Hernandez

    2013-01-01

    Full Text Available Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily, chemical stress (hydrocortisone treatment, 50 mg/Kg weight, mixed stress (restraint plus hydrocortisone, or control treatment (without stress for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  5. Quantitative Proteomics Analysis of Altered Protein Expression in the Placental Villous Tissue of Early Pregnancy Loss Using Isobaric Tandem Mass Tags

    Directory of Open Access Journals (Sweden)

    Xiaobei Ni

    2014-01-01

    Full Text Available Many pregnant women suffer miscarriages during early gestation, but the description of these early pregnancy losses (EPL can be somewhat confusing because of the complexities of early development. Thus, the identification of proteins with different expression profiles related to early pregnancy loss is essential for understanding the comprehensive pathophysiological mechanism. In this study, we report a gel-free tandem mass tags- (TMT- labeling based proteomic analysis of five placental villous tissues from patients with early pregnancy loss and five from normal pregnant women. The application of this method resulted in the identification of 3423 proteins and 19647 peptides among the patient group and the matched normal control group. Qualitative and quantitative proteomic analysis revealed 51 proteins to be differentially abundant between the two groups (≥1.2-fold, Student's t-test, P<0.05. To obtain an overview of the biological functions of the proteins whose expression levels altered significantly in EPL group, gene ontology analysis was performed. We also investigated the twelve proteins with a difference over 1.5-fold using pathways analysis. Our results demonstrate that the gel-free TMT-based proteomic approach allows the quantification of differences in protein expression levels, which is useful for obtaining molecular insights into early pregnancy loss.

  6. Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism.

    Science.gov (United States)

    Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S

    2013-08-01

    The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  7. Immediate placement and restoration of implants in the aesthetic zone with a trimodal approach: soft tissue alterations and its relation to gingival biotype.

    Science.gov (United States)

    Cabello, Gustavo; Rioboo, María; Fábrega, Javier G

    2013-10-01

    papilla level was present in all cases at 1 year, with mean changes of 0.38 mm ( ± 0.60) for the mesial and 0.80 mm ( ± 0.90) of the distal papilla, respectively. No correlation could be established between the soft tissue changes and the periodontal biotype of the patient. Within the limitations of this study, the good aesthetic outcome and minimal complications seem to validate the trimodal approach protocol as a reliable and simple protocol to place and restore immediate implants in the aesthetic zone. No correlation between the patient's gingival biotype and the soft tissue alterations could be established. Additional studies are needed to verify long-term aesthetic results with this approach and to better define and quantify biotypes. © 2012 John Wiley & Sons A/S.

  8. Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages

    International Nuclear Information System (INIS)

    Zhou, Zhao-Hua; Kumari, Namita; Nekhai, Sergei; Clouse, Kathleen A.; Wahl, Larry M.; Yamada, Kenneth M.; Dhawan, Subhash

    2013-01-01

    Highlights: •Lipopolysaccharide stimulation of heme oxygenase-1 (HO-1) ameliorated HIV-1 infection of primary human macrophages. •The partial protection by HO-1 against HIV infection was associated with induction of chemokines such as MIP1α and MIP1β. •This mechanism explains lipopolysaccharide-stimulated HO-1-mediated inhibition of HIV-1 infection of macrophages. -- Abstract: We have elucidated a putative mechanism for the host resistance against HIV-1 infection of primary human monocyte-derived macrophages (MDM) stimulated with lipopolysaccharide (LPS). We show that LPS-activated MDM both inhibited HIV-1 entry into the cells and were refractory to post-entry productive viral replication. LPS-treated cells were virtually negative for mature virions as revealed by transmission electron microscopy. LPS activation of MDM markedly enhanced the expression of heme oxygenase-1 (HO-1), a potent inducible cytoprotective enzyme. Increased HO-1 expression was accompanied by elevated production of macrophage inflammatory chemokines (MIP1α and MIP1β) by LPS-activated MDM, significantly decreased surface chemokine receptor-5 (CCR-5) expression, and substantially reduced virus replication. Treatment of cells with HO-1 inhibitor SnPP IX (tin protoporphyrin IX) attenuated the LPS-mediated responses, HIV-1 replication and secretion of MIP1α, MIP1β, and LD78β chemokines with little change in surface CCR-5 expression. These results identify a novel role for HO-1 in the modulation of host immune response against HIV infection of MDM

  9. Metallothionein-I overexpression alters brain inflammation and stimulates brain repair in transgenic mice with astrocyte-targeted interleukin-6 expression

    DEFF Research Database (Denmark)

    Penkowa, Milena; Camats, Jordi; Giralt, Mercedes

    2003-01-01

    injury, such as a cryolesion, demonstrate a neuroprotective role of IL-6. Thus, the GFAP-IL-6 mice showed faster tissue repair and decreased oxidative stress and apoptosis compared with control litter-mate mice. The neuroprotective factors metallothionein-I+II (MT-I+II) were upregulated by the cryolesion...... the inflammatory response, decreased oxidative stress and apoptosis significantly, and increased brain tissue repair in comparison with either GFAP-IL-6 or control litter-mate mice. Overall, the results demonstrate that brain MT-I+II proteins are fundamental neuroprotective factors....

  10. Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine ("Ecstasy").

    Science.gov (United States)

    Taylor, J R; Jentsch, J D

    2001-07-15

    Psychomotor stimulant drugs can produce long-lasting changes in neurochemistry and behavior after multiple doses. In particular, neuroadaptations within corticolimbic brain structures that mediate incentive learning and motivated behavior have been demonstrated after chronic exposure to cocaine, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As stimulus-reward learning is likely relevant to addictive behavior (i.e., augmented conditioned reward and stimulus control of behavior), we have investigated whether prior repeated administration of psychomotor stimulant drugs (of abuse, including cocaine, d-amphetamine, or MDMA, would affect the acquisition of Pavlovian approach behavior. Water-deprived rats were tested for the acquisition of Pavlovian approach behavior after 5 days treatment with cocaine (15-20 mg/kg once or twice daily), d-amphetamine (2.5 mg/kg once or twice daily), or MDMA (2.5 mg/kg twice daily) followed by a 7-day, drug-free period. Prior repeated treatment with cocaine or d-amphetamine produced a significant enhancement of acquisition of Pavlovian approach behavior, indicating accelerated stimulus-reward learning, whereas MDMA administration produced increased inappropriate responding, indicating impulsivity. Abnormal drug-induced approach behavior was found to persist throughout the testing period. These studies demonstrate that psychomotor stimulant-induced sensitization can produce long-term alterations in stimulus-reward learning and impulse control that may contribute to the compulsive drug taking that typifies addiction.

  11. (p-ClPhSe)2 stimulates carbohydrate metabolism and reverses the metabolic alterations induced by high fructose load in rats.

    Science.gov (United States)

    Quines, Caroline B; Rosa, Suzan G; Chagas, Pietro M; Velasquez, Daniela; Prado, Vinicius C; Nogueira, Cristina W

    2017-09-01

    The modern life leads to excess consumption of food rich in fructose; however, the long-term changes in carbohydrate and lipid metabolism could lead to metabolic dysfunction in humans. The present study evaluated the in vitro insulin-mimetic action of p-chloro-diphenyl diselenide (p-ClPhSe) 2 . The second aim of this study was to investigate if (p-ClPhSe) 2 reverses metabolic dysfunction induced by fructose load in Wistar rats. The insulin-mimetic action of (p-ClPhSe) 2  at concentrations of 50 and 100 μM was determined in slices of rat skeletal muscle. (p-ClPhSe) 2  at a concentration of 50 μM stimulated the glucose uptake by 40% in skeletal muscle. A dose-response curve revealed that (p-ClPhSe) 2  at a dose of 25 mg/kg reduced (∼20%) glycemia in rats treated with fructose (5 g/kg, i.g.). The administration of fructose impaired the liver homeostasis and (p-ClPhSe) 2 (25 mg/kg) protected against the increase (∼25%) in the G-6-Pase and isocitrate dehydrogenase activities and reduced the triglyceride content (∼25%) in the liver. (p-ClPhSe) 2 regulated the liver homeostasis by stimulating hexokinase activity (∼27%), regulating the TCA cycle activity (increased the ATP and citrate synthase activity (∼15%)) and increasing the glycogen levels (∼67%). In conclusion, (p-ClPhSe) 2 stimulated carbohydrate metabolism and reversed metabolic dysfunction in rats fed with fructose. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion

    Directory of Open Access Journals (Sweden)

    Kathrin eHoppenrath

    2016-03-01

    Full Text Available Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV fast-spiking interneurons (FSIs, evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs of FSIs start to grow around postnatal day 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo – in vitro whole-cell patch clamp recordings from pre-labelled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28 and older animals (PD40-62. Slices of verum iTBS-treated rats further showed higher rates of spontaneous EPSCs. Based on these and previous findings we conclude that FSIs are particularly sensitive to theta-burst stimulation during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

  13. A multi-channel stimulator and electrode array providing a rotating current whirlpool for electrical stimulation of wounds.

    Science.gov (United States)

    Petrofsky, J; Suh, H J; Fish, A; Hernandez, V; Abdo, A; Collins, K; Mendoza, E; Yang, T-N

    2008-01-01

    When electrical stimulation is used on wounds, the electrical current has difficulty penetrating areas where there is necrotic tissue. Further, for an irregularly shaped wound, current distribution is poor in some areas of the wound since conventional two-electrode delivery systems provide the greatest current in a line directly between the electrodes. A new stimulator and electrode system is described which uses three electrodes spaced around a wound to disperse current more evenly. The stimulator senses tissue impedance and then redirects current by altering its Thevenin's output impedance for each electrode; each of the three electrodes becomes the active one in sequence while the remaining are the sink electrodes. Eight subjects were examined to test the stimulator. Electrical stimulation was applied to the skin above the quadriceps muscle at currents of 15 mA in six subjects without wounds and in two subjects with wounds. The relationship between electrode position and current dispersion on the skin was examined with a two-electrode vs. a three-electrode system to set stimulation parameters for the computer. The results showed that the three-electrode system could (1) detect areas of the skin with high impedance; (2) compensate by altering the Thevenin's output impedance at each of the three electrodes to shift current to high impedance areas; (3) provide uniform current across the skin as assessed by skin current and blood flow measurements with a laser Doppler flow imager.

  14. Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials.

    Science.gov (United States)

    La Cesa, S; Di Stefano, G; Leone, C; Pepe, A; Galosi, E; Alu, F; Fasolino, A; Cruccu, G; Valeriani, M; Truini, A

    2018-01-01

    In the neurophysiological assessment of patients with neuropathic pain, laser evoked potentials (LEPs), contact heat evoked potentials (CHEPs) and the evoked potentials by the intraepidermal electrical stimulation via concentric needle electrode are widely agreed as nociceptive specific responses; conversely, the nociceptive specificity of evoked potentials by surface concentric electrode (SE-PREPs) is still debated. In this neurophysiological study we aimed at verifying the nociceptive specificity of SE-PREPs. We recorded LEPs, CHEPs and SE-PREPs in eleven healthy participants, before and after epidermal denervation produced by prolonged capsaicin application. We also used skin biopsy to verify the capsaicin-induced nociceptive nerve fibre loss in the epidermis. We found that whereas LEPs and CHEPs were suppressed after capsaicin-induced epidermal denervation, the surface concentric electrode stimulation of the same denervated skin area yielded unchanged SE-PREPs. The suppression of LEPs and CHEPs after nociceptive nerve fibre loss in the epidermis indicates that these techniques are selectively mediated by nociceptive system. Conversely, the lack of SE-PREP changes suggests that SE-PREPs do not provide selective information on nociceptive system function. Capsaicin-induced epidermal denervation abolishes laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs), but leaves unaffected pain-related evoked potentials by surface concentric electrode (SE-PREPs). These findings suggest that unlike LEPs and CHEPs, SE-PREPs are not selectively mediated by nociceptive system. © 2017 European Pain Federation - EFIC®.

  15. Ethanol modulation of mammalian BK channels in excitable tissues: molecular targets and their possible contribution to alcohol-induced altered behavior

    Directory of Open Access Journals (Sweden)

    Alex M. Dopico

    2014-12-01

    Full Text Available In most tissues, the function of calcium- and voltage-gated potassium (BK channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naïve preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of molecular factors, including levels of activating ligand (cytosolic calcium, BK subunit composition and posttranslational modifications, and the channel’s lipid microenvironment. These factors seem to allosterically regulate a direct interaction between ethanol and a recognition pocket of discrete dimensions recently mapped to the channel-forming (slo1 subunit. Type of ethanol exposure also plays a role in the final BK response to the drug: in several central nervous system regions (e.g., striatum, primary sensory neurons, and supraoptic nucleus, acute exposure to ethanol reduces neuronal excitability by enhancing BK activity. In contrast, protracted or repetitive ethanol administration may alter BK subunit composition and membrane expression, rendering the BK complex insensitive to further ethanol exposure. In neurohypophysial axon terminals, ethanol potentiation of BK channel activity leads to a reduction in neuropeptide release. In vascular smooth muscle, however, ethanol inhibition of BK current leads to cell contraction and vascular constriction.

  16. Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle.

    Science.gov (United States)

    Li, Yin; Hamilton, Katherine J; Lai, Anne Y; Burns, Katherine A; Li, Leping; Wade, Paul A; Korach, Kenneth S

    2014-03-01

    Diethylstilbestrol (DES) is a synthetic estrogen associated with adverse effects on reproductive organs. DES-induced toxicity of the mouse seminal vesicle (SV) is mediated by estrogen receptor α (ERα), which alters expression of seminal vesicle secretory protein IV (Svs4) and lactoferrin (Ltf) genes. We examined a role for nuclear receptor activity in association with DNA methylation and altered gene expression. We used the neonatal DES exposure mouse model to examine DNA methylation patterns via bisulfite conversion sequencing in SVs of wild-type (WT) and ERα-knockout (αERKO) mice. The DNA methylation status at four specific CpGs (-160, -237, -306, and -367) in the Svs4 gene promoter changed during mouse development from methylated to unmethylated, and DES prevented this change at 10 weeks of age in WT SV. At two specific CpGs (-449 and -459) of the Ltf gene promoter, DES altered the methylation status from methylated to unmethylated. Alterations in DNA methylation of Svs4 and Ltf were not observed in αERKO SVs, suggesting that changes of methylation status at these CpGs are ERα dependent. The methylation status was associated with the level of gene expression. In addition, gene expression of three epigenetic modifiers-DNMT3A, MBD2, and HDAC2-increased in the SV of DES-exposed WT mice. DES-induced hormonal toxicity resulted from altered gene expression of Svs4 and Ltf associated with changes in DNA methylation that were mediated by ERα. Alterations in gene expression of DNMT3A, MBD2, and HDAC2 in DES-exposed male mice may be involved in mediating the changes in methylation status in the SV. Li Y, Hamilton KJ, Lai AY, Burns KA, Li L, Wade PA, Korach KS. 2014. Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle. Environ Health Perspect 122:262-268; http://dx.doi.org/10.1289/ehp.1307351.

  17. Overexpression of cyclic adenosine monophosphate effluent protein MRP4 induces an altered response to β-adrenergic stimulation in the senescent rat heart.

    Science.gov (United States)

    Carillion, Aude; Feldman, Sarah; Jiang, Cheng; Atassi, Fabrice; Na, Na; Mougenot, Nathalie; Besse, Sophie; Hulot, Jean-Sébastien; Riou, Bruno; Amour, Julien

    2015-02-01

    In the senescent heart, the positive inotropic response to β-adrenoceptor stimulation is reduced, partly by dysregulation of β1- and β3-adrenoceptors. The multidrug resistance protein 4 (MRP4) takes part in the control of intracellular cyclic adenosine monophosphate concentration by controlling its efflux but the role of MRP4 in the β-adrenergic dysfunction of the senescent heart remains unknown. The β-adrenergic responses to isoproterenol were investigated in vivo (stress echocardiography) and in vitro (isolated cardiomyocyte by Ionoptix with sarcomere shortening and calcium transient) in young (3 months old) and senescent (24 months old) rats pretreated or not with MK571, a specific MRP4 inhibitor. MRP4 was quantified in left ventricular homogenates by Western blotting. Data are mean ± SD expressed as percent of baseline value. The positive inotropic effect of isoproterenol was reduced in senescent rats in vivo (left ventricular shortening fraction 120 ± 16% vs. 158 ± 20%, P < 0.001, n = 16 rats) and in vitro (sarcomere shortening 129 ± 37% vs. 148 ± 35%, P = 0.004, n = 41 or 43 cells) as compared to young rats. MRP4 expression increased 3.6-fold in senescent compared to young rat myocardium (P = 0.012, n = 8 rats per group). In senescent rats, inhibition of MRP4 by MK571 restored the positive inotropic effect of isoproterenol in vivo (143 ± 11%, n = 8 rats). In vitro in senescent cardiomyocytes pretreated with MK571, both sarcomere shortening (161 ± 45% vs. 129 ± 37%, P = 0.007, n = 41 cells per group) and calcium transient amplitude (132 ± 25% vs. 113 ± 27%, P = 0.007) increased significantly. MRP4 overexpression contributes to the reduction of the positive inotropic response to β-adrenoceptor stimulation in the senescent heart.

  18. Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion.

    Science.gov (United States)

    Hoppenrath, Kathrin; Härtig, Wolfgang; Funke, Klaus

    2016-01-01

    Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo-in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29-38, evident as higher rates of induced action potential firing at low current injections (100-200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26-28) and older animals (PD40-62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

  19. Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

    Science.gov (United States)

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

    2016-03-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole-cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, β-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3-D constructs for cartilage tissue engineering.

    Science.gov (United States)

    Hilz, Florian M; Ahrens, Philipp; Grad, Sibylle; Stoddart, Martin J; Dahmani, Chiheb; Wilken, Frauke L; Sauerschnig, Martin; Niemeyer, Philipp; Zwingmann, Jörn; Burgkart, Rainer; von Eisenhart-Rothe, Rüdiger; Südkamp, Norbert P; Weyh, Thomas; Imhoff, Andreas B; Alini, Mauro; Salzmann, Gian M

    2014-02-01

    Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production. © 2013 Wiley Periodicals, Inc.

  1. Structural effects of sprifermin in knee osteoarthritis: a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial.

    Science.gov (United States)

    Roemer, Frank W; Aydemir, Aida; Lohmander, Stefan; Crema, Michel D; Marra, Monica Dias; Muurahainen, Norma; Felson, David T; Eckstein, Felix; Guermazi, Ali

    2016-07-09

    A recent publication on efficacy of Sprifermin for knee osteoarthritis (OA) using quantitatively MRI-defined central medial tibio-femoral compartment cartilage thickness as the structural primary endpoint reported no statistically significant dose response. However, Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral tibio-femoral cartilage thickness. Based on these preliminary promising data a post-hoc analysis of secondary assessment and endpoints was performed to evaluate potential effects of Sprifermin on semi-quantitatively evaluated structural MRI parameters. Aim of the present analysis was to determine effects of sprifermin on several knee joint tissues over a 12 month period. 1.5 T or 3 T MRIs were acquired at baseline and 12 months follow-up using a standard protocol. MRIs were read according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring system (in 14 articular subregions) by four muskuloskeletal radiologists independently. Analyses focused on semiquantitative changes in the 100 μg subgroup and matching placebo of multiple MRI-defined structural alterations. Analyses included a delta-subregional and delta-sum approach for the whole knee and the medial and lateral tibio-femoral (MTFJ, LTFJ), and patello-femoral (PFJ) compartments, taking into account number of subregions showing no change, improvement or worsening and changes in the sum of subregional scores. Mann-Whitney - Wilcoxon tests assessed differences between groups. Fifty-seven and 18 patients were included in the treatment and matched placebo subgroups. Less worsening of cartilage damage was observed from baseline to 12 months in the PFJ (0.02, 95 % confidence interval (CI) (-0.04, 0.08) vs. placebo 0.22, 95 % CI (-0.05, 0.49), p = 0.046). For bone marrow lesions (BMLs), more improvement was observed from 6 to 12 months for whole knee analyses (-0.14, 95 % CI (-0.48, 0.19) vs. placebo 0.44, 95

  2. Common variants in the hERG (KCNH2) voltage-gated potassium channel are associated with altered fasting and glucose-stimulated plasma incretin and glucagon responses

    DEFF Research Database (Denmark)

    Engelbrechtsen, Line; Mahendran, Yuvaraj; Jonsson, Anna

    2018-01-01

    BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused by a dysfun......BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused...... by a dysfunctional Kv11.1 voltage-gated potassium channel. Based on these findings in patients with rare variants in hERG, we hypothesized that common variants in hERG may also lead to alterations in glucose homeostasis. Subsequently, we aimed to evaluate the effect of two common gain-of-function variants in hERG...... in hERG on QT-interval and circulation levels of incretins, insulin and glucagon. The Danish population-based Inter99 cohort (n = 5895) was used to assess the effect of common variants on QT-interval. The Danish ADDITION-PRO cohort was used (n = 1329) to study genetic associations with levels of GLP-1...

  3. Transforming growth factor-β1 and its receptor soluble endoglin are altered in polycystic ovary syndrome during controlled ovarian stimulation.

    Science.gov (United States)

    Tal, Reshef; Seifer, David B; Shohat-Tal, Aya; Grazi, Richard V; Malter, Henry E

    2013-08-01

    To evaluate the relationship between transforming growth factor (TGF)-β1 and its receptor, soluble endoglin (sENG), in the serum and follicular fluid of women with polycystic ovarian syndrome (PCOS) compared with that of non-PCOS normal ovulating women during controlled ovarian stimulation (COS). Prospective case-control study. Academic-affiliated assisted reproductive technology unit. Fourteen PCOS and 14 matched non-PCOS control women undergoing COS. Serum was collected on day 3 (baseline), day of hCG, and day of retrieval. Follicular fluid (FF) was collected on day of oocyte retrieval. ELISA was performed to determine TGF-β1 and sENG protein levels. Serum and FF levels of TGF-β1 and sENG. Serum TGF-β1 did not change significantly during COS but was increased in PCOS compared with non-PCOS women on day 3 and days of hCG administration and oocyte retrieval. Serum sENG increased after hCG administration only in the non-PCOS control group. In addition, serum sENG was decreased in PCOS compared with non-PCOS control women on the days of hCG and retrieval. Accordingly, the bioavailability of TGF-β1 (TGF-β1/sENG ratio) was increased in women with PCOS compared with non-PCOS controls at all three time points. No differences in either factor were noted in FF between groups. The increased TGF-β1 bioavailability in PCOS is not only due to increased TGF-β1 levels but also to decreased levels of its receptor, sENG. These data suggest that increased TGF-β1 bioavailability may contribute to the pathogenesis of PCOS and its increased risk for ovarian hyperstimulation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Deficiencies of the lipid-signaling enzymes phospholipase D1 and D2 alter cytoskeletal organization, macrophage phagocytosis, and cytokine-stimulated neutrophil recruitment.

    Directory of Open Access Journals (Sweden)

    Wahida H Ali

    Full Text Available Cell migration and phagocytosis ensue from extracellular-initiated signaling cascades that orchestrate dynamic reorganization of the actin cytoskeleton. The reorganization is mediated by effector proteins recruited to the site of activity by locally-generated lipid second messengers. Phosphatidic acid (PA, a membrane phospholipid generated by multiple enzyme families including Phospholipase D (PLD, has been proposed to function in this role. Here, we show that macrophages prepared from mice lacking either of the classical PLD isoforms PLD1 or PLD2, or wild-type macrophages whose PLD activity has been pharmacologically inhibited, display isoform-specific actin cytoskeleton abnormalities that likely underlie decreases observed in phagocytic capacity. Unexpectedly, PA continued to be detected on the phagosome in the absence of either isoform and even when all PLD activity was eliminated. However, a disorganized phagocytic cup was observed as visualized by imaging PA, F-actin, Rac1, an organizer of the F-actin network, and DOCK2, a Rac1 activator, suggesting that PLD-mediated PA production during phagocytosis is specifically critical for the integrity of the process. The abnormal F-actin reorganization additionally impacted neutrophil migration and extravasation from the vasculature into interstitial tissues. Although both PLD1 and PLD2 were important in these processes, we also observed isoform-specific functions. PLD1-driven processes in particular were observed to be critical in transmigration of macrophages exiting the vasculature during immune responses such as those seen in acute pancreatitis or irritant-induced skin vascularization.

  5. Subcutaneous adipose tissue macropage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kB stress pathway

    Science.gov (United States)

    The goal was to examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), Beta-cell function, and SAT gene expression. SAT biopsies were obtained from...

  6. Tissue specificity for incorporation of [3H]thymidine by the 10- to 12-somite mouse embryo: alteration by acute exposure to hydroxyurea

    International Nuclear Information System (INIS)

    Miller, S.A.; Runner, M.N.

    1978-01-01

    Radioautograms from 10- to 12-somite mouse embryos labelled for 30 min in vitro with [ 3 H]thymidine were examined for frequency and intensity of incorporation. Results from ten tissues showed that values ranged from 82% of nuclei with a mean of 16.6 grains for visceral yolk sac to 17% of nuclei labelled with a mean of 4.4 grains for epithelium of the anterior gut tube. Labelling in the ten tissues indicated (1) a tissue-specific spectrum of incorporation of [ 3 H]thymidine, (2) close correlation between frequency and intensity of labelling within a tissue and (3) asymmetrical quantities of incorporation between right and left somatopleure. Treatment with hydroxyurea in vitro reduced the frequency of labelled nuclei by 85% to 17% of control values. Mean numbers of grains over treated nuclei, 3.3 to 4.6 grains, were well above background but were clustered below the low end of the control range. Tissues exposed to hydroxyurea showed (1) labelling of significant numbers of nuclei, (2) inhibition of labelling in selected tissues and (3) equalization of bilateral asymmetry in quantity (frequency and intensity) of incorporation in somatopleure. The selective reduction of thymidine incorporation and equalization of asymmetrical rates of proliferation may constitute mechanisms by which hydroxyurea causes abnormal morphogenesis. (author)

  7. Concise Review: Mesenchymal Stem Cells Ameliorate Tissue Injury via Secretion of Tumor Necrosis Factor-α Stimulated Protein/Gene 6

    Directory of Open Access Journals (Sweden)

    Zhigang He

    2014-01-01

    Full Text Available Numerous reports have described therapeutic benefits in various disease models after administration of the adult stem/progenitor cells from bone marrow or other tissues referred to as mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs. They all showed that one of the important effects of MSCs is to act against excessive inflammatory responses and repair the damaged tissues. The therapeutic benefits of MSCs were initially interpreted by their migration, engraftment, and differentiation into target tissues. However, remarkable anatomical structural repairs and functional improvements were increasingly observed with a small number of or even no MSCs in the injured tissues. This suggests that most beneficial effects are largely due to paracrine secretions or cell-to-cell contacts that have multiple effects involving modulation of inflammatory and immune responses. Currently, the therapeutic benefits of MSCs are in part explained by the cells being activated by signals from injured tissues to express an anti-inflammatory protein, tumor-necrosis-factor-α-induced protein 6. This important mechanism of action has attracted increasing attention, and therefore we conducted this review to summarize the latest research.

  8. The dynamic DNA methylation landscape of the mutL homolog 1 shore is altered by MLH1-93G>A polymorphism in normal tissues and colorectal cancer.

    Science.gov (United States)

    Savio, Andrea J; Mrkonjic, Miralem; Lemire, Mathieu; Gallinger, Steven; Knight, Julia A; Bapat, Bharat

    2017-01-01

    Colorectal cancers (CRCs) undergo distinct genetic and epigenetic alterations. Expression of mutL homolog 1 ( MLH1 ), a mismatch repair gene that corrects DNA replication errors, is lost in up to 15% of sporadic tumours due to mutation or, more commonly, due to DNA methylation of its promoter CpG island. A single nucleotide polymorphism (SNP) in the CpG island of MLH1 ( MLH1 -93G>A or rs1800734) is associated with CpG island hypermethylation and decreased MLH1 expression in CRC tumours. Further, in peripheral blood mononuclear cell (PBMC) DNA of both CRC cases and non-cancer controls, the variant allele of rs1800734 is associated with hypomethylation at the MLH1 shore, a region upstream of its CpG island that is less dense in CpG sites . To determine whether this genotype-epigenotype association is present in other tissue types, including colorectal tumours, we assessed DNA methylation in matched normal colorectal tissue, tumour, and PBMC DNA from 349 population-based CRC cases recruited from the Ontario Familial Colorectal Cancer Registry. Using the semi-quantitative real-time PCR-based MethyLight assay, MLH1 shore methylation was significantly higher in tumour tissue than normal colon or PBMCs ( P  MLH1 was not associated with MSI status or promoter CpG island hypermethylation, regardless of genotype. To confirm these results, bisulfite sequencing was performed in matched tumour and normal colorectal specimens from six CRC cases, including two cases per genotype (wildtype, heterozygous, and homozygous variant). Bisulfite sequencing results corroborated the methylation patterns found by MethyLight, with significant hypomethylation in normal colorectal tissue of variant SNP allele carriers. These results indicate that the normal tissue types tested (colorectum and PBMC) experience dynamic genotype-associated epigenetic alterations at the MLH1 shore, whereas tumour DNA incurs aberrant hypermethylation compared to normal DNA.

  9. Systematic Review of Soft Tissue Alterations and Esthetic Outcomes Following Immediate Implant Placement and Restoration of Single Implants in the Anterior Maxilla.

    Science.gov (United States)

    Khzam, Nabil; Arora, Himanshu; Kim, Paul; Fisher, Anthony; Mattheos, Nikos; Ivanovski, Saso

    2015-12-01

    The aim of this review is to assess the outcome of single-tooth immediate implant placement and restoration (IPR) in the maxillary anterior region, with a particular emphasis on soft tissue and esthetic outcomes. An electronic search in Medline, EBSCOhost, and Ovid (PubMed) was performed to identify studies that reported on soft tissue outcomes following immediate placement and restoration of implants in the maxillary esthetic region with a mean follow-up of ≥1 year. Nineteen studies on single implants inserted immediately into fresh extraction sockets and provisionally restored in the maxillary esthetic region were included. Soft tissue changes were found to be acceptable, with most studies reporting mean gingival recession of 0.27 ± 0.38 mm and mean papillary height loss of 0.23 ± 0.27 mm after follow-up of ≥1 year. Advanced buccal recession (>1 mm) occurred in 11% of cases. Long-term follow-up studies (>2 years) reported that the interdental papillae, in particular, showed a tendency to rebound over time. The few studies that reported on patient-centered outcomes showed a high level of patient satisfaction with the outcomes of IPR treatment. The IPR protocol resulted in generally acceptable soft tissue and esthetic outcomes, with suboptimal results reported in ≈11% of low-risk cases. Factors such as preoperative tissue biotype or use of a flap or connective tissue graft did not significantly influence soft tissue and esthetic outcomes. Long-term prospective controlled clinical trials are necessary to identify factors that may influence the esthetic outcomes associated with IPR.

  10. Soapwort extract supplementation alters antioxidant status of serum, liver and heart tissues in growing Japanese quails reared under chronic intermittent cold stress

    Directory of Open Access Journals (Sweden)

    Bestami Dalkilic

    2017-01-01

    Full Text Available Antioxidant effect of dietary soapwort extract supplementation was studied in growing Japanese quails suffering from chronic intermittent cold stress. For this purpose, a total of ninety 15-d-old quails were divided into three groups with three replicates. Chronic intermittent cold stress was applied every night between 22.00 to 06.00 h; starting at 14 °C for the first week, and gradually weekly lowered to 8 °C. Three groups were fed with corn-soy based standard diets supplemented with 0, 50, and 100 ppm soapwort extract for four weeks. At the end of the study, three males and three females were slaughtered to determine total antioxidant and oxidant status of serum, malondialdehyde, glutathione, glutathione peroxidase activity, superoxide dismutase of liver and heart tissues. Although the dietary soapwort extract had no effect on serum total antioxidant capacity, it significantly lowered the total oxidant status of serum in cold stressed quails. Glutathione and superoxide dismutase enzyme activity of liver and heart tissues were similar among groups. While the dietary soapwort extract had no effect on glutathione peroxidase activity of the heart tissue, it significantly increased glutathione peroxidase activity in the liver tissue. In relation to the control group, malondialdehyde concentrations in the liver and heart tissues were significantly lower in soapwort extract groups. These data suggest that dietary soapwort extract could alleviate the detrimental effects of oxidative stress in growing Japanese quails exposed to cold stress.

  11. Effective visualization of suppressed thyroid tissue by means of baseline 99mTc-methoxy isobutyl isonitrile in comparison with 99mTc-pertechnetate scintigraphy after TSH stimulation.

    Science.gov (United States)

    Vattimo, A; Bertelli, P; Burroni, L

    1992-01-01

    Baseline 99mTc-MIBI thyroid scintigraphy was compared with 99mTc-pertechnetate scintigraphy after TSH stimulation in seven patients with suppressed thyroid tissue due to an autonomously functioning thyroid nodule (AFTN). In all patients the suppressed thyroid tissue was visualized by means of both baseline 99mTc-MIBI and post-TSH 99mTc-pertechnetate scintigraphy, and in some cases the former technique provided better visualization. In one patient presenting a "warm" nodule T3-suppression did not affect the nodular/extranodular uptake ratio of 99mTc-MIBI, whereas the 99mTc-pertechnetate uptake ratio increased significantly. This leads us to hypothesize that the thyroid uptake of 99mTc-MIBI is not related to TSH control, but rather to other mechanisms such as the blood flow. Since exogenous TSH is no longer available, 99mTc-MIBI scintigraphy can be successfully used in the place of repeated 99mTc-pertechnetate scintigraphy after TSH stimulation in the assessment of AFTN.

  12. Altered DNA Methylation and Differential Expression of Genes Influencing Metabolism and Inflammation in Adipose Tissue From Subjects With Type 2 Diabetes

    DEFF Research Database (Denmark)

    Nilsson, Emma; Jansson, Per Anders; Perfilyev, Alexander

    2014-01-01

    Genetics, epigenetics, and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent...... case-control cohorts. In adipose tissue from diabetic twins, we found decreased expression of genes involved in oxidative phosphorylation; carbohydrate, amino acid, and lipid metabolism; and increased expression of genes involved in inflammation and glycan degradation. The most differentially expressed...... genes included ELOVL6, GYS2, FADS1, SPP1 (OPN), CCL18, and IL1RN. We replicated these results in adipose tissue from an independent case-control cohort. Several candidate genes for obesity and T2D (e.g., IRS1 and VEGFA) were differentially expressed in discordant twins. We found a heritable contribution...

  13. Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils (Meriones unguiculatus

    Directory of Open Access Journals (Sweden)

    Luciana L.A. Ventura

    2017-03-01

    Full Text Available Background Nowadays, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This leads the body to a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to characterize the metabolic and adipose tissue changes resulting from a diet rich in fats and simple sugars in gerbils. Methods We divided 14 gerbils into two experimental groups that received a diet rich in simple carbohydrates and fats with 5,86 kcal/g (OB, n = 7 or a standard diet with 4.15 kcal/g (CT; n = 7 for 11 weeks. The animals had free access to water and food. The animal weight and food consumption were measured weekly. Blood, adipose tissue and liver of each animal were collected at the end of experiment. The following parameters were determined: cholesterol (COL, triglycerides (TGL and glycemia (GLI in the plasma; cytokines (IL-6, IL-10 and TNF-α and hormones (adiponectin and leptin in adipose tissue; activity of superoxide dismutase (SOD and catalase (CAT, extraction and differentiation of fat and histology in liver. Results The consumption of a diet rich in simple carbohydrates and fats led to increased total body weight and increased relative weights of liver and adipose tissue. In addition, we observed increased fasting glucose levels and circulating triglycerides, along with high TNF-α production in adipose tissue and increased total fat, cholesterol and triglyceride contents in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, the animals of this group showed depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels in

  14. Embryonic exposure to an aqueous coal dust extract results in gene expression alterations associated with the development and function of connective tissue and the hematological system, immunological and inflammatory disease, and cancer in zebrafish.

    Science.gov (United States)

    Caballero-Gallardo, Karina; Wirbisky-Hershberger, Sara E; Olivero-Verbel, Jesus; de la Rosa, Jesus; Freeman, Jennifer L

    2018-03-01

    Coal mining is one of the economic activities with the greatest impact on environmental quality. At all stages contaminants are released as particulates such as coal dust. The first aim of this study was to obtain an aqueous coal dust extract and characterize its composition in terms of trace elements by ICP-MS. In addition, the developmental toxicity of the aqueous coal extract was evaluated using zebrafish (Danio rerio) after exposure to different concentrations (0-1000 ppm; μg mL -1 ) to establish acute toxicity, morphology and transcriptome changes. Trace elements within the aqueous coal dust extract present at the highest concentrations (>10 ppb) included Sr, Zn, Ba, As, Cu and Se. In addition, Cd and Pb were found in lower concentrations. No significant difference in mortality was observed (p > 0.05), but a delay in hatching was found at 0.1 and 1000 ppm (p 0.05). Transcriptomic results of zebrafish larvae revealed alterations in 77, 61 and 1376 genes in the 1, 10, and 100 ppm groups, respectively. Gene ontology analysis identified gene alterations associated with the development and function of connective tissue and the hematological system, as well as pathways associated with apoptosis, the cell cycle, transcription, and oxidative stress including the MAPK signaling pathway. In addition, altered genes were associated with cancer; connective tissue, muscular, and skeletal disorders; and immunological and inflammatory diseases. Overall, this is the first study to characterize gene expression alterations in response to developmental exposure to aqueous coal dust residue from coal mining with transcriptome results signifying functions and systems to target in future studies.

  15. Dietary (n-6 : n-3 Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Amira Abdulbari Kassem

    2012-01-01

    Full Text Available The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO: 50% cod liver oil (CLO (1 : 1, 84% SBO: 16% CLO (6 : 1, 96% SBO: 4% CLO (30 : 1. Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.

  16. Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue

    NARCIS (Netherlands)

    Geurts, L.; Vos, de W.M.

    2011-01-01

    Growing evidence supports the role of gut microbiota in the development of obesity, type 2 diabetes, and low-grade inflammation. The endocrine activity of adipose tissue has been found to contribute to the regulation of glucose homeostasis and low-grade inflammation. Among the key hormones produced

  17. Dietary (n-6 : n-3) fatty acids alter plasma and tissue fatty acid composition in pregnant Sprague Dawley rats.

    Science.gov (United States)

    Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

    2012-01-01

    The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.

  18. Dietary fat source affects metabolism of fatty acids in pigs as evaluated by altered expression of lipogenic genes in liver and adipose tissues

    DEFF Research Database (Denmark)

    Duran-Montge, P; Theil, Peter Kappel; Lauridsen, Charlotte

    2009-01-01

    Little is known about pig gene expressions related to dietary fatty acids (FAs) and most work have been conducted in rodents. The aim of this study was to investigate how dietary fats regulate fat metabolism of pigs in different tissues. Fifty-six crossbred gilts (62 ± 5.2 kg BW) were fed one of ...

  19. Dietary (n-6 : n-3) Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

    Science.gov (United States)

    Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

    2012-01-01

    The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat. PMID:22489205

  20. Alterations of tissue metallothionein and vitellogenin concentrations in tropical cup oysters (Saccostrea sp.) following short-term (96 h) exposure to cadmium

    International Nuclear Information System (INIS)

    Moncaleano-Niño, Angela M.; Barrios-Latorre, Sergio A.; Poloche-Hernández, Javier F.; Becquet, Vanessa; Huet, Valérie; Villamil, Luisa; Thomas-Guyon, Hélène; Ahrens, Michael J.; Luna-Acosta, Andrea

    2017-01-01

    Highlights: • The cup oyster Saccostrea sp. is present in Santa Marta, Colombian Caribbean. • 96 h exposure of oysters to Cd increased metallothionein concentrations in digestive glands up to 2-fold. • 96 h exposure of oysters to Cd decreased vitellogenin concentrations in gonads up to 6-fold. • Metallothionein and vitellogenin tissue concentrations correlated with whole tissue Cd concentrations. • Significant changes in metallothionein and vitellogenin levels were only evident at Cd concentrations above 100 μg/L. - Abstract: Metallothioneins and vitellogenins are low molecular weight proteins that have been used widely in environmental monitoring as biomarkers of exposure and damage to metals and estrogenic compounds, respectively. In the present study, the responses of metallothionein and vitellogenin tissue concentrations were measured following acute (96 h) aqueous exposures to cadmium in Saccostrea sp., a tropical cup oyster native to the Western Pacific Ocean that has recently established itself in the Caribbean Sea. Adult oysters (1.5–5.0 cm shell length) collected from the municipal marina of Santa Marta, Colombia (Caribbean Sea) and acclimated for 5 days in the laboratory, were exposed to Cd at five concentrations (0, 1, 10, 100 and 1000 μg/L) and their tissues (gills, digestive gland and adductor muscle) were analyzed in pools of 5 individuals (3 replicates per concentration). Metallothioneins in digestive glands of oysters exposed to Cd concentrations ≥ 100 μg/L showed a significant increase, from 8.0 to 14.8 μg MT/mg total protein, whereas metallothionein concentrations in gills increased to lesser extent, and no differences were observed in adductor muscle. Metallothionein concentrations in digestive gland and gills correlated directly with whole soft tissue Cd concentrations (ranging from 2 to 297 μg/g dw Cd). Vitellogenin in homogenates of oyster gonad tissue, after 96 h of exposure to 1000 μg/L Cd, were significantly lower (0

  1. Alterations of tissue metallothionein and vitellogenin concentrations in tropical cup oysters (Saccostrea sp.) following short-term (96 h) exposure to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Moncaleano-Niño, Angela M.; Barrios-Latorre, Sergio A.; Poloche-Hernández, Javier F. [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Becquet, Vanessa; Huet, Valérie [Littoral Environnement et Sociétés (LIENSs) – UMR 7266, CNRS-Université de La Rochelle, Bâtiment ILE 2, rue Olympe de Gouges, 17 000 La Rochelle (France); Villamil, Luisa [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Thomas-Guyon, Hélène [Littoral Environnement et Sociétés (LIENSs) – UMR 7266, CNRS-Université de La Rochelle, Bâtiment ILE 2, rue Olympe de Gouges, 17 000 La Rochelle (France); Ahrens, Michael J., E-mail: michael.ahrens@utadeo.edu.co [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Luna-Acosta, Andrea [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia)

    2017-04-15

    Highlights: • The cup oyster Saccostrea sp. is present in Santa Marta, Colombian Caribbean. • 96 h exposure of oysters to Cd increased metallothionein concentrations in digestive glands up to 2-fold. • 96 h exposure of oysters to Cd decreased vitellogenin concentrations in gonads up to 6-fold. • Metallothionein and vitellogenin tissue concentrations correlated with whole tissue Cd concentrations. • Significant changes in metallothionein and vitellogenin levels were only evident at Cd concentrations above 100 μg/L. - Abstract: Metallothioneins and vitellogenins are low molecular weight proteins that have been used widely in environmental monitoring as biomarkers of exposure and damage to metals and estrogenic compounds, respectively. In the present study, the responses of metallothionein and vitellogenin tissue concentrations were measured following acute (96 h) aqueous exposures to cadmium in Saccostrea sp., a tropical cup oyster native to the Western Pacific Ocean that has recently established itself in the Caribbean Sea. Adult oysters (1.5–5.0 cm shell length) collected from the municipal marina of Santa Marta, Colombia (Caribbean Sea) and acclimated for 5 days in the laboratory, were exposed to Cd at five concentrations (0, 1, 10, 100 and 1000 μg/L) and their tissues (gills, digestive gland and adductor muscle) were analyzed in pools of 5 individuals (3 replicates per concentration). Metallothioneins in digestive glands of oysters exposed to Cd concentrations ≥ 100 μg/L showed a significant increase, from 8.0 to 14.8 μg MT/mg total protein, whereas metallothionein concentrations in gills increased to lesser extent, and no differences were observed in adductor muscle. Metallothionein concentrations in digestive gland and gills correlated directly with whole soft tissue Cd concentrations (ranging from 2 to 297 μg/g dw Cd). Vitellogenin in homogenates of oyster gonad tissue, after 96 h of exposure to 1000 μg/L Cd, were significantly lower (0

  2. Microradiographic investigations on experimentally provoked structural alterations in hard tooth tissues after sealing with plastic material in places where caries is apt to develop

    International Nuclear Information System (INIS)

    Falten, E.

    1981-01-01

    The aim of the present investigation was, after sealing three areas in extracted human teeth: fissures, dental necksand approximate areas and subsequent exposure to experimentally produced cariogenous noxae, to establish possible alterations in the area of transition between sealed and unsealed dental enamal. This would provide a further decision-taking aid with regard to the question whether also the remaining parts where caries is apt to develop should be sealed. (orig./MG) [de

  3. Acerola (Malpighia emarginata DC.) juice intake protects against alterations to proteins involved in inflammatory and lipolysis pathways in the adipose tissue of obese mice fed a cafeteria diet.

    Science.gov (United States)

    Dias, Fernando Milanez; Leffa, Daniela Dimer; Daumann, Francine; Marques, Schérolin de Oliveira; Luciano, Thais F; Possato, Jonathan Correa; de Santana, Aline Alves; Neves, Rodrigo Xavier; Rosa, José Cesar; Oyama, Lila Missae; Rodrigues, Bruno; de Andrade, Vanessa Moraes; de Souza, Cláudio Teodoro; de Lira, Fabio Santos

    2014-02-04

    Obesity has been studied as a metabolic and an inflammatory disease and is characterized by increases in the production of pro-inflammatory adipokines in the adipose tissue.To elucidate the effects of natural dietary components on the inflammatory and metabolic consequences of obesity, we examined the effects of unripe, ripe and industrial acerola juice (Malpighia emarginata DC.) on the relevant inflammatory and lipolysis proteins in the adipose tissue of mice with cafeteria diet-induced obesity. Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13 weeks. Afterwards, the CAF-fed animals were divided into five subgroups, each of which received a different supplement for one further month (water, unripe acerola juice, ripe acerola juice, industrial acerola juice, or vitamin C) by gavage. Enzyme-linked immunosorbent assays, Western blotting, a colorimetric method and histology were utilized to assess the observed data. The CAF water (control obese) group showed a significant increase in their adiposity indices and triacylglycerol levels, in addition to a reduced IL-10/TNF-α ratio in the adipose tissue, compared with the control lean group. In contrast, acerola juice and Vitamin C intake ameliorated the weight gain, reducing the TAG levels and increasing the IL-10/TNF-α ratio in adipose tissue. In addition, acerola juice intake led to reductions both in the level of phosphorylated JNK and to increases in the phosphorylation of IκBα and HSLser660 in adipose tissue. Taken together, these results suggest that acerola juice reduces low-grade inflammation and ameliorates obesity-associated defects in the lipolytic processes.

  4. Stimulation of Transforming Growth Factor-β1-Induced Endothelial-To-Mesenchymal Transition and Tissue Fibrosis by Endothelin-1 (ET-1): A Novel Profibrotic Effect of ET-1.

    Science.gov (United States)

    Wermuth, Peter J; Li, Zhaodong; Mendoza, Fabian A; Jimenez, Sergio A

    2016-01-01

    TGF-β-induced endothelial-to-mesenchymal transition (EndoMT) is a newly recognized source of profibrotic activated myofibroblasts and has been suggested to play a role in the pathogenesis of various fibrotic processes. Endothelin-1 (ET-1) has been implicated in the development of tissue fibrosis but its participation in TGF-β-induced EndoMT has not been studied. Here we evaluated the role of ET-1 on TGF-β1-induced EndoMT in immunopurified CD31+/CD102+ murine lung microvascular endothelial cells. The expression levels of α-smooth muscle actin (α-SMA), of relevant profibrotic genes, and of various transcription factors involved in the EndoMT process were assessed employing quantitative RT-PCR, immunofluorescence histology and Western blot analysis. TGF-β1 caused potent induction of EndoMT whereas ET-1 alone had a minimal effect. However, ET-1 potentiated TGF-β1-induced EndoMT and TGF-β1-stimulated expression of mesenchymal cell specific and profibrotic genes and proteins. ET-1 also induced expression of the TGF-β receptor 1 and 2 genes, suggesting a plausible autocrine mechanism to potentiate TGF-β-mediated EndoMT and fibrosis. Stimulation of TGF-β1-induced skin and lung fibrosis by ET-1 was confirmed in vivo in an animal model of TGF-β1-induced tissue fibrosis. These results suggest a novel role for ET-1 in the establishment and progression of tissue fibrosis.

  5. Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue

    Directory of Open Access Journals (Sweden)

    Lucie eGeurts

    2011-07-01

    Full Text Available Growing evidence supports the role of gut microbiota in the development of obesity, type 2 diabetes and low-grade inflammation. The endocrine activity of adipose tissue has been found to contribute to the regulation of glucose homeostasis and low-grade inflammation. Among the key hormones produced by this tissue, apelin has been shown to regulate glucose homeostasis. Recently, it has been proposed that gut microbiota participate in adipose tissue metabolism via the endocannabinoid system and gut microbiota-derived compounds, namely lipopolysaccharide (LPS. We have investigated gut microbiota composition in obese and diabetic leptin-resistant mice (db/db by combining pyrosequencing and phylogenetic microarray analysis of 16S ribosomal RNA gene sequences. We observed a significant higher abundance of Firmicutes, Proteobacteria and Fibrobacteres phyla in db/db mice compared to lean mice. The abundance of 10 genera was significantly affected by the genotype. We identified the roles of the endocannabinoid system and LPS in the regulation of apelinergic system tone (apelin and APJ mRNA expression in genetic obese and diabetic mice. By using in vivo and in vitro models, we have demonstrated that both the endocannabinoid system and low-grade inflammation differentially regulate apelin and APJ mRNA expression in adipose tissue. Finally, deep-gut microbiota profiling revealed that the gut microbial community of type 2 diabetic mice is significantly different from that of their lean counterparts. This indicates specific relationships between the gut microbiota and the regulation of the apelinergic system. However, the exact roles of specific bacteria in shaping the phenotype of db/db mice remain to be determined.

  6. Flavanol-Enriched Cocoa Powder Alters the Intestinal Microbiota, Tissue and Fluid Metabolite Profiles, and Intestinal Gene Expression in Pigs1234

    Science.gov (United States)

    Jang, Saebyeol; Sun, Jianghao; Chen, Pei; Lakshman, Sukla; Molokin, Aleksey; Harnly, James M; Vinyard, Bryan T; Urban, Joseph F; Davis, Cindy D; Solano-Aguilar, Gloria

    2016-01-01

    Background: Consumption of cocoa-derived polyphenols has been associated with several health benefits; however, their effects on the intestinal microbiome and related features of host intestinal health are not adequately understood. Objective: The objective of this study was to determine the effects of eating flavanol-enriched cocoa powder on the composition of the gut microbiota, tissue metabolite profiles, and intestinal immune status. Methods: Male pigs (5 mo old, 28 kg mean body weight) were supplemented with 0, 2.5, 10, or 20 g flavanol-enriched cocoa powder/d for 27 d. Metabolites in serum, urine, the proximal colon contents, liver, and adipose tissue; bacterial abundance in the intestinal contents and feces; and intestinal tissue gene expression of inflammatory markers and Toll-like receptors (TLRs) were then determined. Results: O-methyl-epicatechin-glucuronide conjugates dose-dependently increased (P cocoa powder. The concentration of 3-hydroxyphenylpropionic acid isomers in urine decreased as the dose of cocoa powder fed to pigs increased (75–85%, P cocoa powder/d, respectively. Moreover, consumption of cocoa powder reduced TLR9 gene expression in ileal Peyer’s patches (67–80%, P cocoa powder/d compared with pigs not supplemented with cocoa powder. Conclusion: This study demonstrates that consumption of cocoa powder by pigs can contribute to gut health by enhancing the abundance of Lactobacillus and Bifidobacterium species and modulating markers of localized intestinal immunity. PMID:26936136

  7. Expression patterns of porcine Toll-like receptors family set of genes (TLR1-10) in gut-associated lymphoid tissues alter with age.

    Science.gov (United States)

    Uddin, Muhammad Jasim; Kaewmala, Kanokwan; Tesfaye, Dawit; Tholen, Ernst; Looft, Christian; Hoelker, Michael; Schellander, Karl; Cinar, Mehmet Ulas

    2013-08-01

    The aim was to study the expression pattern of the porcine TLR family (TLR1-10) genes in gut-associated lymphoid tissues (GALT) of varying ages. A total of nine clinically healthy pigs of three ages group (1 day, 2 months and 5 months old) were selected for this experiment (three pigs in each group). Tissues from intestinal mucosa in stomach, duodenum, jejunum and ileum and mesenteric lymph node (MLN) were used. mRNA expression of TLRs (1-10) was detectable in all tissues and TLR3 showed the highest mRNA abundance among TLRs. TLR3 expression in stomach, and TLR1 and TLR6 expression in MLN were higher in adult than newborn pigs. The western blot results of TLR2, 3 and 9 in some cases, did not coincide with the mRNA expression results. The protein localization of TLR2, 3 and 9 showed that TLR expressing cells were abundant in the lamina propria, Peyer's patches in intestine, and around and within the lymphoid follicles in the MLN. This expressions study sheds the first light on the expression patterns of all TLR genes in GALT at different ages of pigs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Influence of low-intensity pulsed ultrasound on osteogenic tissue regeneration in a periodontal injury model: X-ray image alterations assessed by micro-computed tomography.

    Science.gov (United States)

    Wang, Yunji; Chai, Zhaowu; Zhang, Yuanyuan; Deng, Feng; Wang, Zhibiao; Song, Jinlin

    2014-08-01

    This study was conducted to evaluate, with micro-computed tomography, the influence of low-intensity pulsed ultrasound on wound-healing in periodontal tissues. Periodontal disease with Class II furcation involvement was surgically produced at the bilateral mandibular premolars in 8 adult male beagle dogs. Twenty-four teeth were randomly assigned among 4 groups (G): G1, periodontal flap surgery; G2, periodontal flap surgery+low-intensity pulsed ultrasound (LIPUS); G3, guided tissue regeneration (GTR) surgery; G4, GTR surgery plus LIPUS. The affected area in the experimental group was exposed to LIPUS. At 6 and 8weeks, the X-ray images of regenerated teeth were referred to micro-CT scanning for 3-D measurement. Bone volume (BV), bone surface (BS), and number of trabeculae (Tb) in G2 and G4 were higher than in G1 and G3 (pperiodontal flap surgery group. LIPUS irradiation increased the number, volume, and area of new alveolar bone trabeculae. LIPUS has the potential to promote the repair of periodontal tissue, and may work effectively if combined with GTR. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Metabolomic Analyses of Brain Tissue in Sepsis Induced by Cecal Ligation Reveal Specific Redox Alterations-Protective Effects of the Oxygen Radical Scavenger Edaravone

    DEFF Research Database (Denmark)

    Hara, Naomi; Chijiiwa, Miyuki; Yara, Miki

    2015-01-01

    at analyzing the preventive effect of the free radical scavenger edaravone on sepsis-induced brain alterations. Sepsis was induced by cecal ligation and puncture (CLP) and the mice were divided into three groups-CLP vehicle (CLPV), CLP and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one) (CLPE......), and sham-operated (Sham). Mice in CLPV and CLPE were injected with saline or edaravone intraperitoneally at a dose of 10 mg/kg twice daily. The treatments were initiated 4 days prior to the surgical procedure. Mortality, histological changes, electron microscopy (EM), and expression of Bcl-2 family genes...

  10. 11-Hydroxy-β-steroid dehydrogenase gene expression in canine adipose tissue and adipocytes: stimulation by lipopolysaccharide and tumor necrosis factor α.

    Science.gov (United States)

    Ryan, V H; Trayhurn, P; Hunter, L; Morris, P J; German, A J

    2011-10-01

    The enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD-1) is expressed in a number of tissues in rodents and humans and is responsible for the reactivation of inert cortisone into cortisol. Its gene expression and activity are increased in white adipose tissue (WAT) from obese humans and may contribute to the adverse metabolic consequences of obesity and the metabolic syndrome. The extent to which 11β-HSD-1 contributes to adipose tissue function in dogs is unknown; the aim of the present study was to examine 11β-HSD-1 gene expression and its regulation by proinflammatory and anti-inflammatory agents in canine adipocytes. Real-time PCR was used to examine the expression of 11β-HSD-1 in canine adipose tissue and canine adipocytes differentiated in culture. The mRNA encoding 11β-HSD-1 was identified in all the major WAT depots in dogs and also in liver, kidney, and spleen. Quantification by real-time PCR showed that 11β-HSD-1 mRNA was least in perirenal and falciform depots and greatest in subcutaneous, omental, and gonadal depots. Greater expression was seen in the omental depot in female than in male dogs (P=0.05). Gene expression for 11β-HSD-1 was also seen in adipocytes, from both subcutaneous and visceral depots, differentiated in culture; expression was evident throughout differentiation but was generally greatest in preadipocytes and during early differentiation, declining as cells progressed to maturity. The inflammatory mediators lipopolysaccharide and tumor necrosis factor α had a main stimulatory effect on 11β-HSD-1 gene expression in canine subcutaneous adipocytes, but IL-6 had no significant effect. Treatment with dexamethasone resulted in a significant time- and dose-dependent increase in 11β-HSD-1 gene expression, with greatest effects seen at 24 h (2 nM: approximately 4-fold; 20 nM: approximately 14-fold; P=0.010 for both). When subcutaneous adipocytes were treated with the peroxisome proliferator activated receptor γ agonist rosiglitazone

  11. Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

    Directory of Open Access Journals (Sweden)

    Jialin Xu

    Full Text Available AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD, regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting. METHODS AND RESULTS: Male C57BL/6 (WT and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36 and Fatty acid transport protein (FATP 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

  12. Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome

    KAUST Repository

    Blackburn, Patrick R.; Xu, Zhi; Tumelty, Kathleen E.; Zhao, Rose W.; Monis, William J.; Harris, Kimberly G.; Gass, Jennifer M.; Cousin, Margot A.; Boczek, Nicole J.; Mitkov, Mario V.; Cappel, Mark A.; Francomano, Clair A.; Parisi, Joseph E.; Klee, Eric W.; Faqeih, Eissa; Alkuraya, Fowzan S.; Layne, Matthew D.; McDonnell, Nazli B.; Atwal, Paldeep S.

    2018-01-01

    AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1 mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC [p.Asn490_Met495delins(40)] and c.1743C>A [p.Cys581]) in the first individual, a homozygous variant (c.1320_1326del [p.Arg440Serfs3]) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that biallelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype.

  13. Mosquito bottlenecks alter viral mutant swarm in a tissue and time-dependent manner with contraction and expansion of variant positions and diversity.

    Science.gov (United States)

    Patterson, Edward I; Khanipov, Kamil; Rojas, Mark M; Kautz, Tiffany F; Rockx-Brouwer, Dedeke; Golovko, Georgiy; Albayrak, Levent; Fofanov, Yuriy; Forrester, Naomi L

    2018-01-01

    Viral diversity is theorized to play a significant role during virus infections, particularly for arthropod-borne viruses (arboviruses) that must infect both vertebrate and invertebrate hosts. To determine how viral diversity influences mosquito infection and dissemination Culex taeniopus mosquitoes were infected with the Venezuelan equine encephalitis virus endemic strain 68U201. Bodies and legs/wings of the mosquitoes were collected individually and subjected to multi-parallel sequencing. Virus sequence diversity was calculated for each tissue. Greater diversity was seen in mosquitoes with successful dissemination versus those with no dissemination. Diversity across time revealed that bottlenecks influence diversity following dissemination to the legs/wings, but levels of diversity are restored by Day 12 post-dissemination. Specific minority variants were repeatedly identified across the mosquito cohort, some in nearly every tissue and time point, suggesting that certain variants are important in mosquito infection and dissemination. This study demonstrates that the interaction between the mosquito and the virus results in changes in diversity and the mutational spectrum and may be essential for successful transition of the bottlenecks associated with arbovirus infection.

  14. Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome

    KAUST Repository

    Blackburn, Patrick R.

    2018-03-29

    AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1 mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC [p.Asn490_Met495delins(40)] and c.1743C>A [p.Cys581]) in the first individual, a homozygous variant (c.1320_1326del [p.Arg440Serfs3]) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that biallelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype.

  15. Conformational alterations in the CD4 binding cavity of HIV-1 gp120 influencing gp120-CD4 interactions and fusogenicity of HIV-1 envelopes derived from brain and other tissues

    Directory of Open Access Journals (Sweden)

    Ramsland Paul A

    2011-06-01

    Full Text Available Abstract Background CD4-binding site (CD4bs alterations in gp120 contribute to HIV-1 envelope (Env mediated fusogenicity and the ability of gp120 to utilize low levels of cell-surface CD4. In a recent study, we constructed three-dimensional models of gp120 to illustrate CD4bs conformations associated with enhanced fusogenicity and enhanced CD4-usage of a modestly-sized panel of blood-derived HIV-1 Envs (n = 16. These conformations were characterized by a wider aperture of the CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop. Here, we sought to provide further validation of the utility of these models for understanding mechanisms that influence Env function, by characterizing the structure-function relationships of a larger panel of Envs derived from brain and other tissues (n = 81. Findings Three-dimensional models of gp120 were generated by our recently validated homology modelling protocol. Analysis of predicted CD4bs structures showed correlations between the aperture width of the CD4bs cavity and ability of the Envs to mediate cell-cell fusion, scavenge low-levels of cell-surface CD4, bind directly to soluble CD4, and bind to the Env mAb IgG1b12 whose epitope overlaps the gp120 CD4bs. These structural alterations in the CD4bs cavity were associated with repositioning of the V5 loop. Conclusions Using a large, independent panel of Envs, we can confirm the utility of three-dimensional gp120 structural models for illustrating CD4bs alterations that can affect Env function. Furthermore, we now provide new evidence that these CD4bs alterations augment the ability of gp120 to interact with CD4 by increasing the exposure of the CD4bs.

  16. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

    -depth understanding of the mechanism regulating blood flow and perfusion is necessary if we are to come up with new ideas for intervention and treatment. Method: From fresh born placentas stem villi arteries were carefully dissected. The artery branches were divided. The surrounding tissue was removed from one end...... and was left untouched in the other end. Then using wire myography they were investigated in terms of contractility and sensitivity to physiological relevant human-like agonists. Results: Sensitivity to PGF2α, Tx-analog, 5-HT and endothelin-1 was significantly lower in arteries with intact surrounding tissue...... compared to arteries stripped of the tissue. The maximal force development was also significantly lower in arteries with surrounding tissue, when they were depolarized high extracellular [K+] or stimulated with PGF2α or endotheline-1. Conclusion: The perivascular tissue significantly alters stem villi...

  17. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

    . Materials and methods. From fresh born placentas, stem villi arteries were carefully dissected. The artery branches were divided. The surrounding tissue was removed from one end and was left untouched in the other end.Then, using wire myography, they were investigated in terms of contractility...... and sensitivity to physiological relevant human-like agonists. Results. Sensitivity to PGF2α, Tx-analog, 5-HT and endothelin-1 was significantly lower in arteries with intact surrounding tissue compared to arteries stripped of the tissue. The maximal force development was also significantly lower in arteries...... with surrounding tissue when they were depolarized high extracellular [K+] or stimulated with PGF2α or endotheline-1. Conclusion. The perivascular tissue significantly alters stem villi arteries' sensitivity and force development in a suppressive way. This implicates a new aspect of blood flow regulation...

  18. Diet and diet combined with chronic aerobic exercise decreases body fat mass and alters plasma and adipose tissue inflammatory markers in obese women.

    Science.gov (United States)

    Lakhdar, Nadia; Denguezli, Myriam; Zaouali, Monia; Zbidi, Abdelkrim; Tabka, Zouhair; Bouassida, Anissa

    2013-12-01

    The purpose of this study was to investigate the effect of 6 months aerobic exercise and diet alone or in combination on markers of inflammation (MOI) in circulation and in adipose abdominal tissue (AT) in obese women. Thirty obese subjects were randomized into a 24-week intervention: (1) exercise (EX), (2) diet (DI), and (3) exercise and diet (EXD). Blood samples were collected at baseline, after 12 and 24 weeks. AT biopsies were obtained only at baseline and after 24 weeks. In the EXD and DI groups, the fat loss was after 12 weeks was -13.74 and -7.8 % (P exercise was found to have no effects on circulating and AT MOI despite an increased VO2max. Rather important body composition modifications were found to have beneficial effects on circulating and AT MOI in these obese women.

  19. Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

    DEFF Research Database (Denmark)

    Sørensen, C.M.; Holmskov, U.; Aalbæk, B.

    2005-01-01

    , the absence of macrophage marker immunoreactivity and the presence of dendritic cell marker immunoreactivity. Increased expression of pSP-D in the surfactant coincided with presence of pSP-D-positive dendritic cells in bronchus-associated lymphoid tissue (BALT), indicating a possible transport of p...... and with dendritic cells in microbial-induced BALT. The function of the interaction between pSP-D and dendritic cells in BALT remain unclear, but pSP-D could represent a link between the innate and adaptive immune system, facilitating the bacterial antigen presentation by dendritic cells in BALT.......Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic...

  20. Six months training alone or combined with diet alters HOMA-AD, HOMA-IR and plasma and adipose tissue adiponectin in obese women.

    Science.gov (United States)

    Lakhdar, Nadia; Denguezli, Myriam; Zaouali, Monia; Zbidi, Abdelkrim; Tabka, Zouhair; Bouassida, Anissa

    2014-01-01

    We investigate the effect of 6 months aerobic training alone or in combination with diet on adiponectin in circulation and in adipose abdominal tissue (AT) in obese women. Twenty obese subjects were randomized into a 24 weeks intervention: 1) training (TR) and 2) training and diet (TRD). Blood samples were collected at baseline, after 12 wk and 24 wk. AT biopsies were obtained only at baseline and after 24 wk. In the TRD group the fat loss was after 12 wk -13.74% (pHOMA-IR and HOMA-AD for assessing insulin resistance were strongly affected by protocols. HOMA-IR decreased (pHOMA-AD increased in both groups after 12 (pHOMA-IR.

  1. Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome.

    Science.gov (United States)

    Blackburn, Patrick R; Xu, Zhi; Tumelty, Kathleen E; Zhao, Rose W; Monis, William J; Harris, Kimberly G; Gass, Jennifer M; Cousin, Margot A; Boczek, Nicole J; Mitkov, Mario V; Cappel, Mark A; Francomano, Clair A; Parisi, Joseph E; Klee, Eric W; Faqeih, Eissa; Alkuraya, Fowzan S; Layne, Matthew D; McDonnell, Nazli B; Atwal, Paldeep S

    2018-04-05

    AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1 -/- mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC [p.Asn490_Met495delins(40)] and c.1743C>A [p.Cys581 ∗ ]) in the first individual, a homozygous variant (c.1320_1326del [p.Arg440Serfs ∗ 3]) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that bi-allelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  2. Insulin, IGF-1, and GH Receptors Are Altered in an Adipose Tissue Depot-Specific Manner in Male Mice With Modified GH Action.

    Science.gov (United States)

    Hjortebjerg, Rikke; Berryman, Darlene E; Comisford, Ross; Frank, Stuart J; List, Edward O; Bjerre, Mette; Frystyk, Jan; Kopchick, John J

    2017-05-01

    Growth hormone (GH) is a determinant of glucose homeostasis and adipose tissue (AT) function. Using 7-month-old transgenic mice expressing the bovine growth hormone (bGH) gene and growth hormone receptor knockout (GHR-/-) mice, we examined whether changes in GH action affect glucose, insulin, and pyruvate tolerance and AT expression of proteins involved in the interrelated signaling pathways of GH, insulinlike growth factor 1 (IGF-1), and insulin. Furthermore, we searched for AT depot-specific differences in control mice. Glycated hemoglobin levels were reduced in bGH and GHR-/- mice, and bGH mice displayed impaired gluconeogenesis as judged by pyruvate tolerance testing. Serum IGF-1 was elevated by 90% in bGH mice, whereas IGF-1 and insulin were reduced by 97% and 61% in GHR-/- mice, respectively. Igf1 RNA was increased in subcutaneous, epididymal, retroperitoneal, and brown adipose tissue (BAT) depots in bGH mice (mean increase ± standard error of the mean in all five depots, 153% ± 27%) and decreased in all depots in GHR-/- mice (mean decrease, 62% ± 4%). IGF-1 receptor expression was decreased in all AT depots of bGH mice (mean decrease, 49% ± 6%) and increased in all AT depots of GHR-/- mice (mean increase, 94% ± 8%). Insulin receptor expression was reduced in retroperitoneal, mesenteric, and BAT depots in bGH mice (mean decrease in all depots, 56% ± 4%) and augmented in subcutaneous, retroperitoneal, mesenteric, and BAT depots in GHR-/- mice (mean increase: 51% ± 1%). Collectively, our findings indicate a role for GH in influencing hormone signaling in AT in a depot-dependent manner. Copyright © 2017 Endocrine Society.

  3. Expression of S-adenosylmethionine Hydrolase in Tissues Synthesizing Secondary Cell Walls Alters Specific Methylated Cell Wall Fractions and Improves Biomass Digestibility

    Directory of Open Access Journals (Sweden)

    Aymerick Eudes

    2016-07-01

    Full Text Available Plant biomass is a large source of fermentable sugars for the synthesis of bioproducts using engineered microbes. These sugars are stored as cell wall polymers, mainly cellulose and hemicellulose, and are embedded with lignin, which makes their enzymatic hydrolysis challenging. One of the strategies to reduce cell wall recalcitrance is the modification of lignin content and composition. Lignin is a phenolic polymer of methylated aromatic alcohols and its synthesis in tissues developing secondary cell walls is a significant sink for the consumption of the methyl donor S-adenosylmethionine (AdoMet. In this study, we demonstrate in Arabidopsis stems that targeted expression of S-adenosylmethionine hydrolase (AdoMetase, E.C. 3.3.1.2 in secondary cell-wall synthesizing tissues reduces the AdoMet pool and impacts lignin content and composition. In particular, both NMR analysis and pyrolysis gas chromatography mass spectrometry of lignin in engineered biomass showed relative enrichment of non-methylated p-hydroxycinnamyl (H units and a reduction of dimethylated syringyl (S units. This indicates a lower degree of methylation compared to that in wild-type lignin. Quantification of cell wall-bound hydroxycinnamates revealed a reduction of ferulate in AdoMetase transgenic lines. Biomass from transgenic lines, in contrast to that in control plants, exhibits an enrichment of glucose content and a reduction in the degree of hemicellulose glucuronoxylan methylation. We also show that these modifications resulted in a reduction of cell wall recalcitrance, because sugar yield generated by enzymatic biomass saccharification was greater than that of wild type plants. Considering that transgenic plants show no important diminution of biomass yields, and that heterologous expression of AdoMetase protein can be spatiotemporally optimized, this novel approach provides a valuable option for the improvement of lignocellulosic biomass feedstock.

  4. Aluminium-Induced Oxidative Stress, Apoptosis and Alterations in Testicular Tissue and Sperm Quality in Wistar Rats: Ameliorative Effects of Curcumin

    Directory of Open Access Journals (Sweden)

    Ebrahim Cheraghi

    2017-09-01

    Full Text Available Background Reproductive toxicity is a major challenge associated with aluminum (Al exposure. No studies have evaluated the possible effects of curcumin (CUR on Al-induced reproductive dysfunction. Therefore, this study investigated the effects of CUR treatment on Al-induced reproductive damage. Materials and Methods In this experimental study, 40 male Wistar rats were allocated to the five groups (n=8 based on the treatment they received: no treatment (control, solvent [dimethyl sulfoxide (DMSO or distilled water], CUR 10 mg/kg body weight (BW, Al chloride 10 mg/kg BW, and CUR+Al chloride (10 mg/kg BW/each alone. Treatments were performed by intraperitoneal (IP injections for 28 days. The left testis was assessed for histopathological analysis as well as the incidence of germ cell apoptosis. One-way analysis of variance (ANOVA followed by the Tukey’s test was used. P<0.05 was considered significant. A value of P<0.05 was considered significant. Results Significant reductions in body and testis weight; plasma testosterone and luteinizing hormone levels; sperm count, motility, morphology, and viability; germinal epithelium thickness; seminiferous tubules diameter; as well as, superoxide dismutase activity were observed in rats treated with Al. Moreover, Al exposure caused significant increments in the lumen diameter of tubules, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL-positive cells and malondialdehyde (MDA levels compared to the control group. However, in rats receiving CUR+Al, CUR significantly reversed the adverse effects of Al on testis and sperm quality. No significant differences in follicle-stimulating hormone (FSH levels and nuclear diameter of spermatogonia were detected among all groups. Conclusion It can be concluded that Al causes reproductive dysfunction by creating oxidative damage. CUR, on the other hand, reduces the toxic effects of Al and improves the antioxidant status and sperm quality in male rats.

  5. Water diffusion reveals networks that modulate multiregional morphological plasticity after repetitive brain stimulation.

    Science.gov (United States)

    Abe, Mitsunari; Fukuyama, Hidenao; Mima, Tatsuya

    2014-03-25

    Repetitive brain stimulation protocols induce plasticity in the stimulated site in brain slice models. Recent evidence from network models has indicated that additional plasticity-related changes occur in nonstimulated remote regions. Despite increasing use of brain stimulation protocols in experimental and clinical settings, the neural substrates underlying the additional effects in remote regions are unknown. Diffusion-weighted MRI (DWI) probes water diffusion and can be used to estimate morphological changes in cortical tissue that occur with the induction of plasticity. Using DWI techniques, we estimated morphological changes induced by application of repetitive transcranial magnetic stimulation (rTMS) over the left primary motor cortex (M1). We found that rTMS altered water diffusion in multiple regions including the left M1. Notably, the change in water diffusion was retained longest in the left M1 and remote regions that had a correlation of baseline fluctuations in water diffusion before rTMS. We conclude that synchronization of water diffusion at rest between stimulated and remote regions ensures retention of rTMS-induced changes in water diffusion in remote regions. Synchronized fluctuations in the morphology of cortical microstructures between stimulated and remote regions might identify networks that allow retention of plasticity-related morphological changes in multiple regions after brain stimulation protocols. These results increase our understanding of the effects of brain stimulation-induced plasticity on multiregional brain networks. DWI techniques could provide a tool to evaluate treatment effects of brain stimulation protocols in patients with brain disorders.

  6. Thyroid Stimulating Hormone Receptor

    Directory of Open Access Journals (Sweden)

    Murat Tuncel

    2017-02-01

    Full Text Available Thyroid stimulating hormone receptor (TSHR plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  7. EFFECT OF INFLIXIMAB ON DYNAMICS OF FUNCTIONAL CLASS AND RADIOLOGICAL SIGN OF BONE AND CARTILAGINOUS TISSUES ALTERATION OF JOINTS IN PATIENTS WITH DIFFERENT TYPES OF JUVENILE ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E.I. Alexeeva

    2008-01-01

    Full Text Available An objective of this trial was evaluation of effect of treatment with blocker of tumor necrosis factor infliximab on dynamics of functional class and radiological changes of bone and cartilaginous tissue of joints in children with different clinical types of juvenile arthritis (JA. Infliximab was used according to standard scheme on 0, 2, 6 and then every 8 week by intravenous infusion. Mean single dose of infliximab was 6,8 ± 2,3 mg/kg. All children were treated with immunosuppressive agents (ciclosporin in 6% of patients, methotrexate in 60%, ciclosporin combined with methotrexate — 20%, ciclosporin with leflunomide — 5%, leflunomide with methotreate — 4% combined with anti cytokine treatment. 7 children were treated with oral glucocorticoids in mean dose 0,37 mg/kg daily. disorders in joint function and structural changes of joints of different severity (radiological sign were discovered in all patients before starting of treatment with infliximab. Duration of observation was 6 week — 2 years. Authors made a conclusion that treatment with infliximab prevents progressing of bone and cartilaginous destruction in all types of AJ, not depending on intensity of its clinical activity. This medication provides for full functional recovery of joints and elimination of features of disablement in patients with good clinical activity.Key words: children, juvenile arthritis, infliximab, treatment.

  8. Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus

    Directory of Open Access Journals (Sweden)

    Mittra Arjun

    2011-03-01

    Full Text Available Abstract Introduction Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. Methods GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET utilizing carrier-free 124I radiotracer. Results GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P 124I-PET. Conclusion Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.

  9. Evaluation of high-perimeter electrode designs for deep brain stimulation

    Science.gov (United States)

    Howell, Bryan; Grill, Warren M.

    2014-08-01

    Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, complications including infections and mis-programing following surgical replacement of the battery-powered implantable pulse generator adversely impact the safety profile of this therapy. We sought to decrease power consumption and extend battery life by modifying the electrode geometry to increase stimulation efficiency. The specific goal of this study was to determine whether electrode contact perimeter or area had a greater effect on increasing stimulation efficiency. Approach. Finite-element method (FEM) models of eight prototype electrode designs were used to calculate the electrode access resistance, and the FEM models were coupled with cable models of passing axons to quantify stimulation efficiency. We also measured in vitro the electrical properties of the prototype electrode designs and measured in vivo the stimulation efficiency following acute implantation in anesthetized cats. Main results. Area had a greater effect than perimeter on altering the electrode access resistance; electrode (access or dynamic) resistance alone did not predict stimulation efficiency because efficiency was dependent on the shape of the potential distribution in the tissue; and, quantitative assessment of stimulation efficiency required consideration of the effects of the electrode-tissue interface impedance. Significance. These results advance understanding of the features of electrode geometry that are important for designing the next generation of efficient DBS electrodes.

  10. Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Ding, Xian-Fei; Sun, Mou; Guan, Fang-Xia; Guo, Li-Na; Zhang, Yan-Yan; Wan, You-Dong; Zhang, Xiao-Juan; Yu, Yan-Wu; Ma, Shan-Shan; Yao, Hai-Mu; Yao, Rui; Zhang, Rui-Fang; Sun, Tong-Wen; Kan, Quan-Cheng

    2017-11-06

    Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0.79 mg/kg LPS, respectively, on the 8th, 10th, and 12th days of gestation; an ADSCs group, which was intravenously injected with 1.8 × 107 ADSCs on the 8th, 10th, and 12th days of gestation; and an LPS + ADSCs group, which received a combination of the treatments administered to the LPS and ADSCs groups. Prenatal LPS exposure increased blood pressure, Ang II expression, Ang II-positive, monocyte and lymphocyte, apoptotic cells in the kidney, and induced renal histological changes in offspring; however, the LPS and control groups did not differ significantly with respect to plasma renin activity levels, Ang II levels, or renal function. ADSCs treatment attenuated the blood pressure and also ameliorated the other effects of LPS-treated adult offspring. Prenatal exposure to LPS activates the intrarenal RAS but not the circulating RAS and thus induces increases in blood pressure in adult offspring; however, ADSCs treatment attenuates the blood pressure increases resulting from LPS exposure and also ameliorates the other phenotypic changes induced by LPS treatment by inhibiting intrarenal RAS activation. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  11. Tissue alterations in the pirarucu, Arapaima gigas, infected by Goezia spinulosa (Nematoda Alterações teciduais em pirarucu, Arapaima gigas, infectado por Goezia spinulosa (Nematoda

    Directory of Open Access Journals (Sweden)

    Rodrigo Caldas Menezes

    2011-09-01

    Full Text Available Five specimens of Arapaima gigas caught in the Araguaia River (State of Mato Grosso, Brazil were investigated for helminths in 2004. Numerous adult specimens of the rhapidascarid nematode Goezia spinulosa were found in stomach ulcers in all the specimens of A. gigas and were surrounded by thickening of the mucosa. The gastric glands of all the fish were necrotic and there was a severe and diffuse inflammatory reaction composed of eosinophils (which were predominant, lymphocytes and rare macrophages in the mucosa, submucosa and muscle layer. This is the first report of tissue lesion occurrences in this host, in the presence of G. spinulosa, and it confirms the high pathogenicity of this parasite species.Cinco espécimens de Arapaima gigas capturados no Rio Araguaia (Estado do Mato Grosso, Brasil foram investigados para diagnóstico de infecção por helmintos em 2004. Numerosos espécimes adultos do nematóide rafidascarídeo Goezia spinulosa foram encontrados em úlceras do estômago circundadas por um espessamento da mucosa em todos os exemplares de A. gigas. As glândulas gástricas de todos encontravam-se necróticas e havia um acentuado e difuso infiltrado inflamatório composto por eosinófilos, que eram predominantes, linfócitos e raros macrófagos na mucosa, submucosa e camada muscular. As lesões teciduais na presença de nematóide G. spinulosa são relatadas pela primeira vez nesse hospedeiro e confirmam a alta patogenicidade dessa esp��cie de parasito.

  12. growth stimulant

    African Journals Online (AJOL)

    Effects of timing and duration of supplementation of LIVFIT VET ® (growth stimulant) as substitute for fish meal on the growth performance, haematology and clinical enzymes concentration of growing pigs.

  13. Receptor for advanced glycation end products - membrane type1 matrix metalloproteinase axis regulates tissue factor expression via RhoA and Rac1 activation in high-mobility group box-1 stimulated endothelial cells.

    Directory of Open Access Journals (Sweden)

    Koichi Sugimoto

    Full Text Available BACKGROUND: Atherosclerosis is understood to be a blood vessel inflammation. High-mobility group box-1 (HMGB-1 plays a key role in the systemic inflammation. Tissue factor (TF is known to lead to inflammation which promotes thrombus formation. Membrane type1 matrix metalloprotease (MT1-MMP associates with advanced glycation endproducts (AGE triggered-TF protein expression and phosphorylation of NF-κB. However, it is still unclear about the correlation of MT1-MMP and HMBG-1-mediated TF expression. In this study, we investigated the molecular mechanisms of TF expression in response to HMGB-1 stimulation and the involvement of MT1-MMP in endothelial cells. METHODS AND RESULTS: Pull-down assays and Western blotting revealed that HMGB-1 induced RhoA/Rac1 activation and NF-kB phosphorylation in cultured human aortic endothelial cells. HMGB-1 increased the activity of MT1-MMP, and inhibition of RAGE or MT1-MMP by siRNA suppressed HMGB-1-induced TF upregulation as well as HMGB-1-triggered RhoA/Rac1 activation and NF-kB phosphorylation. CONCLUSIONS: The present study showed that RAGE/MT1-MMP axis modified HMBG-1-mediated TF expression through RhoA and Rac1 activation and NF-κB phosphorylation in endothelial cells. These results suggested that MT1-MMP was involved in vascular inflammation and might be a good target for treating atherosclerosis.

  14. Studies the alterations of biochemical and mineral contents in bone tissue of mus musculus due to aluminum toxicity and the protective action of desferrioxamine and deferiprone by FTIR, ICP-OES, SEM and XRD techniques.

    Science.gov (United States)

    Sivakumar, S; Khatiwada, Chandra Prasad; Sivasubramanian, J

    2014-05-21

    The present study has attempt to analyze the changes in the biochemical and mineral contents of aluminum intoxicated bone and determine the protective action of desferrioxamine (DFO) and deferiprone (DFP) by using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), inductively coupled plasma optical emission spectroscopy (ICP-OES), and scanning electron microscopy (SEM) techniques for four groups of animals such as control (Group I), aluminum intoxicated (Group II), Al+DFP (Group III) and Al+DFO+DFP (Group IV) treated groups respectively. The FTIR spectra of the aluminum intoxicated bone showed significant alteration in the biochemical constituents. The bands ratio at I1400/I877 significantly decreased from control to aluminum, but enhanced it by Al+DFP to Al+DFO+DFP treated bone tissue for treatments of 16 weeks. This result suggests that DFO and DFP are the carbonate inhibitor, recovered from chronic growth of bone diseases and pathologies. The alteration of proteins profile indicated by Amide I and Amide II, where peak area values decreased from control to aluminum respectively, but enhanced by treated with DFP (p.o.) and DFO+DFP (i.p.) respectively. The XRD analysis showed a decrease in crystallinity due to aluminum toxicity. Further, the Ca, Mg, and P contents of the aluminum exposed bone were less than those of the control group, and enhanced by treatments with DFO and DFP. The concentrations of trace elements were found by ICP-OES. Therefore, present study suggests that due to aluminum toxicity severe loss of bone minerals, decrease in the biochemical constituents and changes in the surface morphology. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Proteomic approaches for the study of tissue specific effects of 3,5,3’-triiodo-L-thyronine and 3,5-diiodo-L-thyronine in conditions of altered energy metabolism.

    Directory of Open Access Journals (Sweden)

    Elena eSilvestri

    2014-12-01

    Full Text Available In vertebrates and, specifically, in mammals, energy homeostasis is achieved by the integration of metabolic and neuroendocrine signals linked to one another in an intricate network hierarchically responding to the tight modulating action of hormones among which thyroid hormones (THs play a central role. At the cellular level, 3,5,3’-triiodo-L-thyronine (T3 acts mainly by binding to specific nuclear receptors (TRs but actually it is becoming more and more evident that some T3- actions are independent of TRs and that other iodothyronines, such as 3,5-diiodo-L-thyronine (T2, affect energy metabolism and adiposity. In the postgenomic era, clinical and basic biological researches are increasingly benefiting from the recently developed new omics approaches including, among the others, proteomics. Considering the recognized value of proteins as excellent targets in physiology, the functional and simultaneous analysis of the expression level and the cellular localization of multiple proteins can actually be considered fundamental in the understanding of complex mechanisms such as those involved in thyroid control of metabolism. Here, we will discuss new leads (i.e. target proteins and metabolic pathways emerging in applying proteomics to the actions of T3 and T2 in conditions of altered energy metabolism in animal tissues having a central role in the control of energy balance.

  16. Brain Stimulation Therapies

    Science.gov (United States)

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  17. Comportamento da impedância elétrica dos tecidos biológicos durante estimulação elétrica transcutânea Electrical impedance behavior of biological tissues during transcutaneous electrical stimulation

    Directory of Open Access Journals (Sweden)

    VJ Bolfe

    2007-04-01

    Full Text Available OBJETIVO: Analisar a impedância elétrica dos tecidos biológicos durante estimulação elétrica em diferentes segmentos, faces e freqüências da corrente, aumentando-se a distância intereletrodos. MÉTODO: 20 voluntárias, idade média 23 ± 2,25anos e índice de massa corporal 20,65 ± 1,44kg/m², permaneceram em decúbito, sendo um eletrodo posicionado proximalmente às interlinhas articulares do punho e tornozelo, anterior e posteriormente, ou à espinha ilíaca póstero-superior, e outro eletrodo distanciado seqüencialmente em 10, 20, 30 e 40cm. Foram aplicadas duas correntes (100us e 10mA, uma de 100Hz (BF e outra de 2000Hz modulada em 100% da amplitude para 100Hz (MF, com intervalo mínimo de 7 dias. A impedância foi calculada, indiretamente, pela Lei de Ohm, a partir da intensidade aplicada e da tensão elétrica captada em sistema composto por osciloscópio digital (TDS 210, Tektronix® e gerador de corrente constante (Dualpex 961, Quark®. Para análise estatística, aplicou-se Anova-F e Kruskal-Wallis com post hoc (SNK, teste de Friedman e coeficiente de correlação de Spearman, considerando pOBJECTIVE: To analyze the electrical impedance of biological tissues during electrical stimulation in relation to different segments, surfaces and current frequencies, with increasing distance between electrodes. METHOD: 20 female volunteers of mean age 23 ± 2.25 years and mean body mass index 20.65 ± 1.44 kg/m² were positioned in decubitus with one electrode placed proximally to the wrist and ankle joint lines, anteriorly and posteriorly, or on the posterosuperior iliac spine, and the other electrode was placed at distance of 10, 20, 30 and 40 cm, sequentially. Two currents (100 us and 10 mA were applied: one at 100 Hz (LF and the other at 2000 Hz modulated at 100% of the amplitude for 100 Hz (MF, with a minimum interval of seven days. The impedance was calculated indirectly using Ohm's Law, from the applied intensity and the

  18. Radiation-induced changes in production of prostaglandins Fsub(2α), E, and thromboxane B2 in guinea pig parenchymal lung tissues

    International Nuclear Information System (INIS)

    Steel, L.K.; Catravas, G.N.

    1982-01-01

    At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2α), PGE, and thromboxane B 2 were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB 2 synthesis at 24 hours and for PGFsub(2α) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur

  19. Radiation-induced changes in production of prostaglandins Fsub(2. cap alpha. ), E, and thromboxane B/sub 2/ in guinea pig parenchymal lung tissues

    Energy Technology Data Exchange (ETDEWEB)

    Steel, L K; Catravas, G N [Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)

    1982-11-01

    At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2..cap alpha..), PGE, and thromboxane B/sub 2/ were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB/sub 2/ synthesis at 24 hours and for PGFsub(2..cap alpha..) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur.

  20. Computational analysis of transcranial magnetic stimulation in the presence of deep brain stimulation probes

    Science.gov (United States)

    Syeda, F.; Holloway, K.; El-Gendy, A. A.; Hadimani, R. L.

    2017-05-01

    Transcranial Magnetic Stimulation is an emerging non-invasive treatment for depression, Parkinson's disease, and a variety of other neurological disorders. Many Parkinson's patients receive the treatment known as Deep Brain Stimulation, but often require additional therapy for speech and swallowing impairment. Transcranial Magnetic Stimulation has been explored as a possible treatment by stimulating the mouth motor area of the brain. We have calculated induced electric field, magnetic field, and temperature distributions in the brain using finite element analysis and anatomically realistic heterogeneous head models fitted with Deep Brain Stimulation leads. A Figure of 8 coil, current of 5000 A, and frequency of 2.5 kHz are used as simulation parameters. Results suggest that Deep Brain Stimulation leads cause surrounding tissues to experience slightly increased E-field (Δ Emax =30 V/m), but not exceeding the nominal values induced in brain tissue by Transcranial Magnetic Stimulation without leads (215 V/m). The maximum temperature in the brain tissues surrounding leads did not change significantly from the normal human body temperature of 37 °C. Therefore, we ascertain that Transcranial Magnetic Stimulation in the mouth motor area may stimulate brain tissue surrounding Deep Brain Stimulation leads, but will not cause tissue damage.

  1. Against Strong Ethical Parity: Situated Cognition Theses and Transcranial Brain Stimulation.

    Science.gov (United States)

    Heinrichs, Jan-Hendrik

    2017-01-01

    According to a prominent suggestion in the ethics of transcranial neurostimulation the effects of such devices can be treated as ethically on par with established, pre-neurotechnological alterations of the mind. This parity allegedly is supported by situated cognition theories showing how external devices can be part of a cognitive system. This article will evaluate this suggestion. It will reject the claim, that situated cognition theories support ethical parity. It will however point out another reason, why external carriers or modifications of the mental might come to be considered ethically on par with internal carriers. Section "Why Could There Be Ethical Parity between Neural Tissue and External Tools?" presents the ethical parity theses between external and internal carriers of the mind as well as neurotechnological alterations and established alterations. Section "Extended, Embodied, Embedded: Situated Cognition as a Relational Thesis" will elaborate the different situated cognition approaches and their relevance for ethics. It will evaluate, whether transcranial stimulation technologies are plausible candidates for situated cognition theses. Section "On the Ethical Relevance of Situated Cognition Theses" will discuss criteria for evaluating whether a cognitive tool is deeply embedded with a cognitive system and apply these criteria to transcranial brain stimulation technologies. Finally it will discuss the role diverse versions of situated cognition theory can play in the ethics of altering mental states, especially the ethics of transcranial brain stimulation technologies.

  2. Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns.

    Science.gov (United States)

    Getzenberg, R H; Coffey, D S

    1990-09-01

    The DNA of interphase nuclei have very specific three-dimensional organizations that are different in different cell types, and it is possible that this varying DNA organization is responsible for the tissue specificity of gene expression. The nuclear matrix organizes the three-dimensional structure of the DNA and is believed to be involved in the control of gene expression. This study compares the nuclear structural proteins between two sex accessory tissues in the same animal responding to the same androgen stimulation by the differential expression of major tissue-specific secretory proteins. We demonstrate here that the nuclear matrix is tissue specific in the rat ventral prostate and seminal vesicle, and undergoes characteristic alterations in its protein composition upon androgen withdrawal. Three types of nuclear matrix proteins were observed: 1) nuclear matrix proteins that are different and tissue specific in the rat ventral prostate and seminal vesicle, 2) a set of nuclear matrix proteins that either appear or disappear upon androgen withdrawal, and 3) a set of proteins that are common to both the ventral prostate and seminal vesicle and do not change with the hormonal state of the animal. Since the nuclear matrix is known to bind androgen receptors in a tissue- and steroid-specific manner, we propose that the tissue specificity of the nuclear matrix arranges the DNA in a unique conformation, which may be involved in the specific interaction of transcription factors with DNA sequences, resulting in tissue-specific patterns of secretory protein expression.

  3. Functional and morphological alterations of the stomach in case of irradiation of the para-aortic area

    Energy Technology Data Exchange (ETDEWEB)

    Beyer-Enke, S.A.; Gladisch, R.; Heine, M.; Georgi, M.

    1987-12-01

    Six assays were conducted in order to determine some functional and morphological parameters of the gastric mucosa in patients who underwent Co/sup 60/ irradiations of the para-aortic area. Slight as well as marked morphological alterations were observed whereas the functional alterations were found to be marked in all cases. Basal gastric secretion and serum gastrin level showed a continous reduction, however, in case of severe gastritis the stimulated secretion was increased. A possible correlation with increased tissue histamine levels is discussed.

  4. Cardiac tissue engineering

    Directory of Open Access Journals (Sweden)

    MILICA RADISIC

    2005-03-01

    Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

  5. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  6. Alteraciones en el eje hipotálamo-tejido adiposo y su relación con el riesgo para la aterosclerosis coronaria Alterations in hypothalamus-adipose tissue axis in relation with the risk of coronary atherosclerosis

    Directory of Open Access Journals (Sweden)

    Raúl I. Coniglio

    2004-04-01

    complex mechanisms. Genetics or acquired alterations in these regulation systems can be the origin of obesity and specially of central obesity. The visceral adipose tissue can be considered a secretor organ and its mass increment could generate insulin-resistance (IR state, which directly or indirectly, could develop into endothelial dysfunction and coronary atherosclerosis. Although some studies estimate that 40% of IR are of genetic origin, a high proportion of these are acquired by inadequate habits in life style (specially excess of food intake and low physical activity. Finally, a better knowledge of the central and peripheric regulations in alimentation habits and energetic balance could help to develop treatments to decrease the incidence of these metabolic alterations and, consequently the morbidity and mortality due to coronary atherosclerosis.

  7. Can the human lumbar posterior columns be stimulated by transcutaneous spinal cord stimulation? A modeling study

    OpenAIRE

    Danner, Simon M.; Hofstoetter, Ursula S.; Ladenbauer, Josef; Rattay, Frank; Minassian, Karen

    2011-01-01

    Stimulation of different spinal cord segments in humans is a widely developed clinical practice for modification of pain, altered sensation and movement. The human lumbar cord has become a target for modification of motor control by epidural and more recently by transcutaneous spinal cord stimulation. Posterior columns of the lumbar spinal cord represent a vertical system of axons and when activated can add other inputs to the motor control of the spinal cord than stimulated posterior roots. ...

  8. Sensory processing of deep tissue nociception in the rat spinal cord and thalamic ventrobasal complex.

    Science.gov (United States)

    Sikandar, Shafaq; West, Steven J; McMahon, Stephen B; Bennett, David L; Dickenson, Anthony H

    2017-07-01

    Sensory processing of deep somatic tissue constitutes an important component of the nociceptive system, yet associated central processing pathways remain poorly understood. Here, we provide a novel electrophysiological characterization and immunohistochemical analysis of neural activation in the lateral spinal nucleus (LSN). These neurons show evoked activity to deep, but not cutaneous, stimulation. The evoked responses of neurons in the LSN can be sensitized to somatosensory stimulation following intramuscular hypertonic saline, an acute model of muscle pain, suggesting this is an important spinal relay site for the processing of deep tissue nociceptive inputs. Neurons of the thalamic ventrobasal complex (VBC) mediate both cutaneous and deep tissue sensory processing, but in contrast to the lateral spinal nucleus our electrophysiological studies do not suggest the existence of a subgroup of cells that selectively process deep tissue inputs. The sensitization of polymodal and thermospecific VBC neurons to mechanical somatosensory stimulation following acute muscle stimulation with hypertonic saline suggests differential roles of thalamic subpopulations in mediating cutaneous and deep tissue nociception in pathological states. Overall, our studies at both the spinal (lateral spinal nucleus) and supraspinal (thalamic ventrobasal complex) levels suggest a convergence of cutaneous and deep somatosensory inputs onto spinothalamic pathways, which are unmasked by activation of muscle nociceptive afferents to produce consequent phenotypic alterations in spinal and thalamic neural coding of somatosensory stimulation. A better understanding of the sensory pathways involved in deep tissue nociception, as well as the degree of labeled line and convergent pathways for cutaneous and deep somatosensory inputs, is fundamental to developing targeted analgesic therapies for deep pain syndromes. © 2017 University College London. Physiological Reports published by Wiley Periodicals

  9. Smectite alteration

    International Nuclear Information System (INIS)

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  10. Piezoelectric materials for tissue regeneration: A review.

    Science.gov (United States)

    Rajabi, Amir Hossein; Jaffe, Michael; Arinzeh, Treena Livingston

    2015-09-01

    The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues raised the question whether or not electric fields play an important role in cell function. It has kindled research and the development of technologies in emulating biological electricity for tissue regeneration. Promising effects of electrical stimulation on cell growth and differentiation and tissue growth has led to interest in using piezoelectric scaffolds for tissue repair. Piezoelectric materials can generate electrical activity when deformed. Hence, an external source to apply electrical stimulation or implantation of electrodes is not needed. Various piezoelectric materials have been employed for different tissue repair applications, particularly in bone repair, where charges induced by mechanical stress can enhance bone formation; and in neural tissue engineering, in which electric pulses can stimulate neurite directional outgrowth to fill gaps in nervous tissue injuries. In this review, a summary of piezoelectricity in different biological tissues, mechanisms through which electrical stimulation may affect cellular response, and recent advances in the fabrication and application of piezoelectric scaffolds will be discussed. The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues has kindled research and the development of technologies using electrical stimulation for tissue regeneration. Piezoelectric materials generate electrical activity in response to deformations and allow for the delivery of an electrical stimulus without the need for an external power source. As a scaffold for tissue engineering, growing interest exists due to its potential of providing electrical stimulation to cells to promote tissue formation. In this review, we cover the discovery of piezoelectricity in biological tissues, its connection to streaming potentials, biological response to electrical stimulation and

  11. Treatment of movement disorders using deep brain stimulation – illustrative case reports and technical notes

    Directory of Open Access Journals (Sweden)

    Tadej Strojnik

    2012-05-01

    Full Text Available Operative neuromodulation is the field of electrically or chemically altering the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks to produce therapeutic effects. Deep brain stimulation (DBS is an important component of the therapy of movement disorders and has almost completely replaced high-frequency coagulation of brain tissue in stereotactic neurosurgery. This article presents the first DBS cases in Slovenia. In the article the technical features and adjustments of magnetic resonance (MR imaging and development of a new microdrive, which was clinically successfully tested, are described and discussed.

  12. Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type I to Type II: Oscillation Onset and Wave Propagation.

    Directory of Open Access Journals (Sweden)

    Stewart Heitmann

    2017-01-01

    Full Text Available Constant optogenetic stimulation targeting both pyramidal cells and inhibitory interneurons has recently been shown to elicit propagating waves of gamma-band (40-80 Hz oscillations in the local field potential of non-human primate motor cortex. The oscillations emerge with non-zero frequency and small amplitude-the hallmark of a type II excitable medium-yet they also propagate far beyond the stimulation site in the manner of a type I excitable medium. How can neural tissue exhibit both type I and type II excitability? We investigated the apparent contradiction by modeling the cortex as a Wilson-Cowan neural field in which optogenetic stimulation was represented by an external current source. In the absence of any external current, the model operated as a type I excitable medium that supported propagating waves of gamma oscillations similar to those observed in vivo. Applying an external current to the population of inhibitory neurons transformed the model into a type II excitable medium. The findings suggest that cortical tissue normally operates as a type I excitable medium but it is locally transformed into a type II medium by optogenetic stimulation which predominantly targets inhibitory neurons. The proposed mechanism accounts for the graded emergence of gamma oscillations at the stimulation site while retaining propagating waves of gamma oscillations in the non-stimulated tissue. It also predicts that gamma waves can be emitted on every second cycle of a 100 Hz oscillation. That prediction was subsequently confirmed by re-analysis of the neurophysiological data. The model thus offers a theoretical account of how optogenetic stimulation alters the excitability of cortical neural fields.

  13. Effects of cocaine on norepinephrine stimulated phosphoinositide hydrolysis and locomotor activity in rat

    International Nuclear Information System (INIS)

    Mosaddeghi, M.

    1989-01-01

    The function of α 1 -adrenoceptors was determined by stimulating cortical tissue slices, which were pre-labeled with [ 3 H]inositol, with norepinephrine (NE) in the presence of 8 mM LiCl. Results of in vitro studies showed that cocaine 10 μM potentiated maximal NE-stimulated PI hydrolysis by 30%. In addition, the EC 50 was decreased from 3.93 ± 0.42 to 1.91 ± 0.31 μM NE. Concentrations of 0.1-100 μM and 0.1-10 μM cocaine enhanced PI hydrolysis stimulated by 0.3 and 3 μM NE, respectively. The concentration-effect curves for NE-stimulated PI hydrolysis were shifted to the right 100-fold in the presence of 0.1 μM prazosin. Cocaine (10 μM) did not potentiate NE-stimulated PI hydrolysis in the presence of 0.1 μM prazosin. [ 3 H]Prazosin saturation and NE [ 3 H]prazosin competition binding studies using crude membrane preparations showed that 10 μM cocaine did not alter binding parameters B max , K d , Hill slope, and IC 50 . Together, these results implied that cocaine in vitro potentiated NE-stimulated PI hydrolysis by blocking NE reuptake. For in vivo studies, the locomotor activity was determined after an acute or chronic injections of either cocaine or saline. Cocaine or saline-treated rats were killed after measurement of the locomotor activity, and NE-stimulated PI hydrolysis was measured. Acute administration of cocaine 3.2-42 mg/kg (i.p.) produced an inverted U shaped dose-response curve on locomotor activity. The peak increase in locomotor activity was at 32 mg/kg cocaine. A dose of 42 mg/kg cocaine produced a significant depression of maximal NE-stimulated PI hydrolysis

  14. Transforming growth factor beta 1 increases collagen content, and stimulates procollagen I and tissue inhibitor of metalloproteinase-1 production of dental pulp cells: Role of MEK/ERK and activin receptor-like kinase-5/Smad signaling

    Directory of Open Access Journals (Sweden)

    Po-Shuen Lin

    2017-05-01

    Conclusion: These results indicate that TGF-β1 may be involved in the healing/regeneration processes of dental pulp in response to injury by stimulation of collagen and TIMP-1 production. These events are associated with activin receptor-like kinase-5/Smad2/3 and MEK/ERK signaling.

  15. Variations in maternal care alter corticosterone and 17beta-estradiol levels, estrous cycle and folliculogenesis and stimulate the expression of estrogen receptors alpha and beta in the ovaries of UCh rats

    Directory of Open Access Journals (Sweden)

    Amorim João PA

    2011-12-01

    Full Text Available Abstract Background Variations in maternal care are associated with neonatal stress, hormonal disturbances and reproductive injuries during adulthood. However, the effects of these variations on sex hormones and steroid receptors during ovary development remain undetermined. This study aimed to investigate whether variations in maternal care are able to influence the hormonal profile, follicular dynamics and expression of AR, ER-alpha and ER-beta in the ovaries of UCh rat offspring. Methods Twenty-four adult UCh rats, aged 120 days, were randomly divided into two groups (UChA and UChB and mated. Maternal care was assessed from birth (day 0 to the 10th postnatal day (PND. In adulthood, twenty adult female rats (UChA and UChB offspring; n = 10/group, aged 120 days, were euthanized by decapitation during the morning estrus. Results UChA females (providing high maternal care more frequently displayed the behaviors of carrying pups, as well as licking/grooming and arched back nursing cares. Also, mothers providing high care had elevated corticosterone levels. Additionally, offspring receiving low maternal care showed the highest estrous cycle duration, increased corticosterone and 17beta-estradiol levels, overexpression of receptors ER-alpha and ER-beta, increased numbers of primordial, antral and mature follicles and accentuated granulosa cell proliferation. Conclusions Our study suggests that low maternal care alters corticosterone and 17beta-estradiol levels, disrupting the estrous cycle and folliculogenesis and differentially regulating the expression of ER-alpha and ER-beta in the ovaries of adult rats.

  16. Transcranial magnetic stimulation and the human brain

    Science.gov (United States)

    Hallett, Mark

    2000-07-01

    Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.

  17. Bone Marrow Aspirate Concentrate-Enhanced Marrow Stimulation of Chondral Defects

    Science.gov (United States)

    Eichler, Hermann; Orth, Patrick

    2017-01-01

    Mesenchymal stem cells (MSCs) from bone marrow play a critical role in osteochondral repair. A bone marrow clot forms within the cartilage defect either as a result of marrow stimulation or during the course of the spontaneous repair of osteochondral defects. Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. The additional application of a bone marrow aspirate (BMA) to the procedure of marrow stimulation is thought to enhance cartilage repair as it may provide both an additional cell population capable of chondrogenesis and a source of growth factors stimulating cartilage repair. Moreover, the BMA clot provides a three-dimensional environment, possibly further supporting chondrogenesis and protecting the subchondral bone from structural alterations. The purpose of this review is to bridge the gap in our understanding between the basic science knowledge on MSCs and BMA and the clinical and technical aspects of marrow stimulation-based cartilage repair by examining available data on the role and mechanisms of MSCs and BMA in osteochondral repair. Implications of findings from both translational and clinical studies using BMA concentrate-enhanced marrow stimulation are discussed. PMID:28607559

  18. iTRAQ quantitative proteomics-based identification of cell adhesion as a dominant phenotypic modulation in thrombin-stimulated human aortic endothelial cells.

    Science.gov (United States)

    Wang, Huang-Joe; Chen, Sung-Fang; Lo, Wan-Yu

    2015-05-01

    The phenotypic changes in thrombin-stimulated endothelial cells include alterations in permeability, cell shape, vasomotor tone, leukocyte trafficking, migration, proliferation, and angiogenesis. Previous studies regarding the pleotropic effects of thrombin on the endothelium used human umbilical vein endothelial cells (HUVECs)-cells derived from fetal tissue that does not exist in adults. Only a few groups have used screening approaches such as microarrays to profile the global effects of thrombin on endothelial cells. Moreover, the proteomic changes of thrombin-stimulated human aortic endothelial cells (HAECs) have not been elucidated. HAECs were stimulated with 2 units/mL thrombin for 5h and their proteome was investigated using isobaric tags for the relative and absolute quantification (iTRAQ) and the MetaCore(TM) software. A total of 627 (experiment A) and 622 proteins (experiment B) were quantified in the duplicated iTRAQ analyses. MetaCore(TM) pathway analysis identified cell adhesion as a dominant phenotype in thrombin-stimulated HAECs. Replicated iTRAQ data revealed that "Cell adhesion_Chemokines and adhesion," "Cell adhesion_Histamine H1 receptor signaling in the interruption of cell barrier integrity," and "Cell adhesion_Integrin-mediated cell adhesion and migration" were among the top 10 statistically significant pathways. The cell adhesion phenotype was verified by increased THP-1 adhesion to thrombin-stimulated HAECs. In addition, the expression of ICAM-1, VCAM-1, and SELE was significantly upregulated in thrombin-stimulated HAECs. Several regulatory pathways are altered in thrombin-stimulated HAECs, with cell adhesion being the dominant altered phenotype. Our findings show the feasibility of the iTRAQ technique for evaluating cellular responses to acute stimulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Molecular and cellular mechanisms of muscle aging and sarcopenia and effects of electrical stimulation in seniors

    Directory of Open Access Journals (Sweden)

    Laura Barberi

    2015-08-01

    Full Text Available The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers, alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors.

  20. The short-circuit current of the ileum, but not the colon, is altered in the streptozotocin diabetic rat.

    Science.gov (United States)

    Forrest, Abigail; Makwana, Rajesh; Parsons, Mike

    2006-02-01

    Ion transport in control and streptozotocin-diabetic rat colon and ileum was studied using the Ussing chamber technique. No differences were observed between control and diabetic colonic mucosal short-circuit current under either basal or carbachol (100 nmol/L-1 micromol/L)-stimulated or prostaglandin E2 (100 nmol/L-1 micromol/L)-stimulated conditions. Similarly to colonic tissues, no differences in the short circuit current in either carbachol-stimulated or prostaglandin E2-stimulated tissues were observed between control and diabetic ileal mucosa. The basal diabetic ileal short circuit current (99.58 +/- 22.67 microA) was significantly greater than that of control ileal tissues (29.67 +/- 4.45 microA). This difference was abolished by the sodium-glucose-cotransporter inhibitor, phloridzin (50 micromol/L) (118.00 +/- 28.09 microA vs. 25.60 +/- 4.59 microA) and was also prevented by the replacement of glucose with mannitol in the buffer bathing the apical side of the tissue (control: 17.05 +/- 5.85 microA vs. 17.90 +/- 3.10 microA). Acetazolamide (450 micromol/L; a carbonic anhydrase inhibitor), amiloride, and bumetanide (100 micromol/L each; Na+-channel blockers), piroxicam (50 micromol/L; a COX1 cyclooxygenase inhibitor), and ouabain (1 mmol/L; a K+ transport inhibitor) had no effect on the basal short circuit current of either control or diabetic ileal tissues. This indicated that the alteration in the basal short circuit current of diabetic ileal tissues was due to a change in cellular glucose transport, whereas the evoked changes in short circuit current were unaffected by the diabetic state.

  1. Methamphetamine Administration Modifies Leukocyte Proliferation and Cytokine Production in Murine Tissues

    Science.gov (United States)

    Peerzada, Habibullah; Ghandi, Jay A.; Guimaraes, Allan J.; Nosanchuk, Joshua D.; Martinez, Luis R.

    2013-01-01

    Methamphetamine (METH) is a potent and highly addictive central nervous system (CNS) stimulant. Additionally, METH adversely impacts immunological responses, which might contribute to the higher rate and more rapid progression of certain infections in drug abusers. However no studies have shown the impact of METH on inflammation within specific organs, cellular participation and cytokine production. Using a murine model of METH administration, we demonstrated that METH modifies, with variable degrees, leukocyte recruitment and alters cellular m