Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia.

Science.gov (United States)

Salade, Laurent; Wauthoz, Nathalie; Deleu, Magali; Vermeersch, Marjorie; De Vriese, Carine; Amighi, Karim; Goole, Jonathan

2017-01-01

The aim of the present study was to develop a ghrelin-containing formulation based on liposomes coated with chitosan intended for nose-brain delivery for the treatment of cachexia. Among the three types of liposomes developed, anionic liposomes provided the best results in terms of encapsulation efficiency (56%) and enzymatic protection against trypsin (20.6% vs 0% for ghrelin alone) and carboxylesterase (81.6% vs 17.2% for ghrelin alone). Ghrelin presented both electrostatic and hydrophobic interactions with the anionic lipid bilayer, as demonstrated by isothermal titration calorimetry. Then, anionic liposomes were coated with N -(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride. The coating involved a size increment from 146.9±2.7 to 194±6.1 nm, for uncoated and coated liposomes, respectively. The ζ-potential was similarly increased from -0.3±1.2 mV to 6±0.4 mV before and after coating, respectively. Chitosan provided mucoadhesion, with an increase in mucin adsorption of 22.9%. Enhancement of permeation through the Calu3 epithelial monolayer was also observed with 10.8% of ghrelin recovered in the basal compartment in comparison to 0% for ghrelin alone. Finally, aerosols generated from two nasal devices (VP3 and SP270) intended for aqueous dispersion were characterized with either coated or uncoated liposomes. Contrarily to the SP270 device, VP3 device showed minor changes between coated and uncoated liposome aerosols, as shown by their median volume diameters of 38.4±5.76 and 37.6±5.74 µm, respectively. Overall, the results obtained in this study show that the developed formulation delivered by the VP3 device can be considered as a potential candidate for nose-brain delivery of ghrelin.

Mechanisms to explain the reverse perivascular transport of solutes out of the brain.

Science.gov (United States)

Schley, D; Carare-Nnadi, R; Please, C P; Perry, V H; Weller, R O

2006-02-21

Experimental studies and observations in the human brain indicate that interstitial fluid and solutes, such as amyloid-beta (Abeta), are eliminated from grey matter of the brain along pericapillary and periarterial pathways. It is unclear, however, what constitutes the motive force for such transport within blood vessel walls, which is in the opposite direction to blood flow. In this paper the potential for global pressure differences to achieve such transport are considered. A mathematical model is constructed in order to test the hypothesis that perivascular drainage of interstitial fluid and solutes out of brain tissue is driven by pulsations of the blood vessel walls. Here it is assumed that drainage occurs through a thin layer between astrocytes and endothelial cells or between smooth muscle cells. The model suggests that, during each pulse cycle, there are periods when fluid and solutes are driven along perivascular spaces in the reverse direction to the flow of blood. It is shown that successful drainage may depend upon some attachment of solutes to the lining of the perivascular space, in order to produce a valve-like effect, although an alternative without this requirement is also postulated. Reduction in pulse amplitude, as in ageing cerebral vessels, would prolong the attachment time, encourage precipitation of Abeta peptides in vessel walls, and impair elimination of Abeta from the brain. These factors may play a role in the pathogenesis of cerebral amyloid angiopathy and in the accumulation of Abeta in the brain in Alzheimer's disease.

In vitro evidence for the brain glutamate efflux hypothesis: brain endothelial cells cocultured with astrocytes display a polarized brain-to-blood transport of glutamate.

Science.gov (United States)

Helms, Hans Christian; Madelung, Rasmus; Waagepetersen, Helle Sønderby; Nielsen, Carsten Uhd; Brodin, Birger

2012-05-01

The concentration of the excitotoxic amino acid, L-glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood-brain barrier endothelium in brain L-glutamate homeostasis. Transendothelial transport- and accumulation studies of (3) H-L-glutamate, (3) H-L-aspartate, and (3) H-D-aspartate in an electrically tight bovine endothelial/rat astrocyte blood-brain barrier coculture model were performed. After 6 days in culture, the endothelium displayed transendothelial resistance values of 1014 ± 70 Ω cm(2) , and (14) C-D-mannitol permeability values of 0.88 ± 0.13 × 10(-6) cm s(-1) . Unidirectional flux studies showed that L-aspartate and L-glutamate, but not D-aspartate, displayed polarized transport in the brain-to-blood direction, however, all three amino acids accumulated in the cocultures when applied from the abluminal side. The transcellular transport kinetics were characterized with a K(m) of 69 ± 15 μM and a J(max) of 44 ± 3.1 pmol min(-1) cm(-2) for L-aspartate and a K(m) of 138 ± 49 μM and J(max) of 28 ± 3.1 pmol min(-1) cm(-2) for L-glutamate. The EAAT inhibitor, DL-threo-ß-Benzyloxyaspartate, inhibited transendothelial brain-to-blood fluxes of L-glutamate and L-aspartate. Expression of EAAT-1 (Slc1a3), -2 (Slc1a2), and -3 (Slc1a1) mRNA in the endothelial cells was confirmed by conventional PCR and localization of EAAT-1 and -3 in endothelial cells was shown with immunofluorescence. Overall, the findings suggest that the blood-brain barrier itself may participate in regulating brain L-glutamate concentrations. Copyright © 2012 Wiley Periodicals, Inc.

Nano carriers for drug transport across the blood-brain barrier.

Science.gov (United States)

Li, Xinming; Tsibouklis, John; Weng, Tingting; Zhang, Buning; Yin, Guoqiang; Feng, Guangzhu; Cui, Yingde; Savina, Irina N; Mikhalovska, Lyuba I; Sandeman, Susan R; Howel, Carol A; Mikhalovsky, Sergey V

2017-01-01

Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully

Strain Behavior of Concrete Panels Subjected to Different Nose Shapes of Projectile Impact.

Science.gov (United States)

Lee, Sangkyu; Kim, Gyuyong; Kim, Hongseop; Son, Minjae; Choe, Gyeongcheol; Nam, Jeongsoo

2018-03-09

This study evaluates the fracture properties and rear-face strain distribution of nonreinforced and hooked steel fiber-reinforced concrete panels penetrated by projectiles of three different nose shapes: sharp, hemispherical, and flat. The sharp projectile nose resulted in a deeper penetration because of the concentration of the impact force. Conversely, the flat projectile nose resulted in shallower penetrations. The penetration based on different projectile nose shapes is directly related to the impact force transmitted to the rear face. Scabbing can be more accurately predicted by the tensile strain on the rear face of concrete due to the projectile nose shape. The tensile strain on the rear face of the concrete was reduced by the hooked steel fiber reinforcement because the hooked steel fiber absorbed some of the impact stress transmitted to the rear face of the concrete. Consequently, the strain behavior on the rear face of concrete according to the projectile nose shape was confirmed.

Strain Behavior of Concrete Panels Subjected to Different Nose Shapes of Projectile Impact

Directory of Open Access Journals (Sweden)

Sangkyu Lee

2018-03-01

Full Text Available This study evaluates the fracture properties and rear-face strain distribution of nonreinforced and hooked steel fiber-reinforced concrete panels penetrated by projectiles of three different nose shapes: sharp, hemispherical, and flat. The sharp projectile nose resulted in a deeper penetration because of the concentration of the impact force. Conversely, the flat projectile nose resulted in shallower penetrations. The penetration based on different projectile nose shapes is directly related to the impact force transmitted to the rear face. Scabbing can be more accurately predicted by the tensile strain on the rear face of concrete due to the projectile nose shape. The tensile strain on the rear face of the concrete was reduced by the hooked steel fiber reinforcement because the hooked steel fiber absorbed some of the impact stress transmitted to the rear face of the concrete. Consequently, the strain behavior on the rear face of concrete according to the projectile nose shape was confirmed.

Nose micro-blowing for asymmetric vortices control on blunt-nose slender body at high angle of attack

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Lei Wang

2017-11-01

Full Text Available The asymmetric vortices over blunt-nose slender body at high angles of attack result in random side force. In this paper, a nose micro-blowing technology is used to control the asymmetric flow. Pressure measurement and particle image velocimetry (PIV experiments are conducted in a low-speed wind tunnel to research effects of jet flow rate on asymmetric vortices over blunt-nose slender body. The angle of attack of the model is fixed at 50° and the Reynolds number for the experiments is 1.6×10 5 based on diameter of aftbody. A blow hole (5 mm in diameter on the nose is processed at circumferential angle θb= 90° and meridian angle γb= 20° with jet momentum ratio Cμ ranging from 5.30×10-7 to 1.19×10−4. Tests are made under two kinds of perturbations. One is called single perturbation with only blow hole and the other is called combined perturbation consists of blow hole and additional granules set on nose. The results show that whether the model has the single perturbation or the combined one, the sectional side force of x/D = 3 varies in the same direction with the increasement of Cμ and remains stable when Cμ is greater than 3.29×10−6. But the stable force values are different according to various perturbations. The fact proves that the size and direction of the side force of blunt-nose slender body can be controlled by the nose micro-blowing.

Does menaquinone participate in brain astrocyte electron transport?

Science.gov (United States)

Lovern, Douglas; Marbois, Beth

2013-10-01

Quinone compounds act as membrane resident carriers of electrons between components of the electron transport chain in the periplasmic space of prokaryotes and in the mitochondria of eukaryotes. Vitamin K is a quinone compound in the human body in a storage form as menaquinone (MK); distribution includes regulated amounts in mitochondrial membranes. The human brain, which has low amounts of typical vitamin K dependent function (e.g., gamma carboxylase) has relatively high levels of MK, and different regions of brain have different amounts. Coenzyme Q (Q), is a quinone synthesized de novo, and the levels of synthesis decline with age. The levels of MK are dependent on dietary intake and generally increase with age. MK has a characterized role in the transfer of electrons to fumarate in prokaryotes. A newly recognized fumarate cycle has been identified in brain astrocytes. The MK precursor menadione has been shown to donate electrons directly to mitochondrial complex III. Vitamin K compounds function in the electron transport chain of human brain astrocytes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dendrimer D5 is a vector for peptide transport to brain cells.

Science.gov (United States)

Sarantseva, S V; Bolshakova, O I; Timoshenko, S I; Kolobov, A A; Schwarzman, A L

2011-02-01

Dendrimers are a new class of nonviral vectors for gene or drug transport. Dendrimer capacity to penetrate through the blood-brain barrier remaines little studied. Biotinylated polylysine dendrimer D5, similarly to human growth hormone biotinylated fragment covalently bound to D5 dendrimer, penetrates through the blood-brain barrier and accumulates in Drosophila brain after injection into the abdomen. Hence, D5 dendrimer can serve as a vector for peptide transport to brain cells.

Tracking Dynamic Source Direction with a Novel Stationary Electronic Nose System

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David C. Levy

2006-11-01

Full Text Available Arrays of chemical sensors, usually called electronic noses (ENose, are widelyused in industry for classifying and identifying odours. They may also be used to locate theposition and detect the direction of an emission source. Usually this task is performed by anENose cooperating with a mobile vehicle, but when a source is instantaneous, or thesurrounding terrain is hard for vehicles to traverse, an alternative approach is needed. Thus athree-step method for a stationary ENose with a novel structure to detect the direction of adynamic source is presented in this paper. The method uses the ratio of measuredconcentration from different sensors (Cn /C1 where n=2, 4 as a discriminator. In addition,this method could easily be adapted to robotics as an optimized algorithm for path trackingto a source location. The paper presents the results of a simulation of the method.

"Facilitated" amino acid transport is upregulated in brain tumors.

Science.gov (United States)

Miyagawa, T; Oku, T; Uehara, H; Desai, R; Beattie, B; Tjuvajev, J; Blasberg, R

1998-05-01

surface area between RG2 tumors and contralateral cortex. K1ACPC, deltaK1ACPC, and K DTPA were directly related to tumor cell density, were higher in regions of "impending" necrosis, and the tumor/contralateral brain ACPC radio-activity ratios (0 to 10 minutes) were very similar to that obtained with 0 to 60 minutes experiments. These results indicate that facilitated transport of ACPC is upregulated across C6 and RG2 glioma capillaries, and that tumors can induce upregulation of amino acid transporter expression in their supporting vasculature. They also suggest that early imaging (e.g., 0 to 20 minutes) with radiolabeled amino acids in a clinical setting may be optimal for defining brain tumors.

Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: implications for neuropsychopharmacology.

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Tournier, Nicolas; Declèves, Xavier; Saubaméa, Bruno; Scherrmann, Jean-Michel; Cisternino, Salvatore

2011-01-01

Some of the ATP-binding cassette (ABC) transporters like P-glycoprotein (P-gp; ABCB1, MDR1), BCRP (ABCG2) and MRPs (ABCCs) that are present at the blood-brain barrier (BBB) influence the brain pharmacokinetics (PK) of their substrates by restricting their uptake or enhancing their clearance from the brain into the blood, which has consequences for their CNS pharmacodynamics (PD). Opioid drugs have been invaluable tools for understanding the PK-PD relationships of these ABC-transporters. The effects of morphine, methadone and loperamide on the CNS are modulated by P-gp. This review examines the ways in which other opioid drugs and some of their active metabolites interact with ABC transporters and suggests new mechanisms that may be involved in the variability of the response of the CNS to these drugs like carrier-mediated system belonging to the solute carrier (SLC) superfamily. Exposure to opioids may also alter the expression of ABC transporters. P-gp can be overproduced during morphine treatment, suggesting that the drug has a direct or, more likely, an indirect action. Variations in cerebral neurotransmitters during exposure to opioids and the release of cytokines during pain could be new endogenous stimuli affecting transporter synthesis. This review concludes with an analysis of the pharmacotherapeutic and clinical impacts of the interactions between ABC transporters and opioids.

Glucose transport in brain - effect of inflammation.

Science.gov (United States)

Jurcovicova, J

2014-01-01

Glucose is transported across the cell membrane by specific saturable transport system, which includes two types of glucose transporters: 1) sodium dependent glucose transporters (SGLTs) which transport glucose against its concentration gradient and 2) sodium independent glucose transporters (GLUTs), which transport glucose by facilitative diffusion in its concentration gradient. In the brain, both types of transporters are present with different function, affinity, capacity, and tissue distribution. GLUT1 occurs in brain in two isoforms. The more glycosylated GLUT1 is produced in brain microvasculature and ensures glucose transport across the blood brain barrier (BBB). The less glycosylated form is localized in astrocytic end-feet and cell bodies and is not present in axons, neuronal synapses or microglia. Glucose transported to astrocytes by GLUT1 is metabolized to lactate serving to neurons as energy source. Proinflammatory cytokine interleukin (IL)-1β upregulates GLUT1 in endothelial cells and astrocytes, whereas it induces neuronal death in neuronal cell culture. GLUT2 is present in hypothalamic neurons and serves as a glucose sensor in regulation of food intake. In neurons of the hippocampus, GLUT2 is supposed to regulate synaptic activity and neurotransmitter release. GLUT3 is the most abundant glucose transporter in the brain having five times higher transport capacity than GLUT1. It is present in neuropil, mostly in axons and dendrites. Its density and distribution correlate well with the local cerebral glucose demands. GLUT5 is predominantly fructose transporter. In brain, GLUT5 is the only hexose transporter in microglia, whose regulation is not yet clear. It is not present in neurons. GLUT4 and GLUT8 are insulin-regulated glucose transporters in neuronal cell bodies in the cortex and cerebellum, but mainly in the hippocampus and amygdala, where they maintain hippocampus-dependent cognitive functions. Insulin translocates GLUT4 from cytosol to plasma

Neurosteroid Transport in the Brain: Role of ABC and SLC Transporters

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Markus Grube

2018-04-01

Full Text Available Neurosteroids, comprising pregnane, androstane, and sulfated steroids can alter neuronal excitability through interaction with ligand-gated ion channels and other receptors and have therefore a therapeutic potential in several brain disorders. They can be formed in brain cells or are synthesized by an endocrine gland and reach the brain by penetrating the blood–brain barrier (BBB. Especially sulfated steroids such as pregnenolone sulfate (PregS and dehydroepiandrosterone sulfate (DHEAS depend on transporter proteins to cross membranes. In this review, we discuss the involvement of ATP-binding cassette (ABC- and solute carrier (SLC-type membrane proteins in the transport of these compounds at the BBB and in the choroid plexus (CP, but also in the secretion from neurons and glial cells. Among the ABC transporters, especially BCRP (ABCG2 and several MRP/ABCC subfamily members (MRP1, MRP4, MRP8 are expressed in the brain and known to efflux conjugated steroids. Furthermore, several SLC transporters have been shown to mediate cellular uptake of steroid sulfates. These include members of the OATP/SLCO subfamily, namely OATP1A2 and OATP2B1, as well as OAT3 (SLC22A3, which have been reported to be expressed at the BBB, in the CP and in part in neurons. Furthermore, a role of the organic solute transporter OSTα-OSTβ (SLC51A/B in brain DHEAS/PregS homeostasis has been proposed. This transporter was reported to be localized especially in steroidogenic cells of the cerebellum and hippocampus. To date, the impact of transporters on neurosteroid homeostasis is still poorly understood. Further insights are desirable also with regard to the therapeutic potential of these compounds.

Glucose transporter of the human brain and blood-brain barrier

International Nuclear Information System (INIS)

Kalaria, R.N.; Gravina, S.A.; Schmidley, J.W.; Perry, G.; Harik, S.I.

1988-01-01

We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable [3H]cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific [3H]cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with [3H]cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species

Iron uptake and transport at the blood-brain barrier

DEFF Research Database (Denmark)

Larsen, Annette Burkhart; Thomsen, Louiza Bohn; Moos, Torben

The mechanism by which iron is transported across the blood-brain barrier (BBB) remains controversial, and in this study we aimed to further clarify mechanisms by which iron is transported into the brain. We analyzed and compared the mRNA and protein expression of a variety of proteins involved...... in the transport of iron (transferrin receptor, divalent metal transporter I (DMT1), steap 2, steap 3, ceruloplasmin, hephaestin and ferroportin) in both primary rat brain capillary endothelial cells (BCEC) and immortalized rat brain capillary endothelial cell line (RBE4) grown in co-culture with defined polarity....... The mRNA expression of the iron-related molecules was also investigated in isolated brain capillaries from iron deficiency, iron reversible and normal rats. We also performed iron transport studies to analyze the routes by which iron is transported through the brain capillary endothelial cells: i) We...

Glutamate Transporters in the Blood-Brain Barrier

DEFF Research Database (Denmark)

Helms, Hans Christian Cederberg; Nielsen, Carsten Uhd; Waagepetersen, Helle S

2017-01-01

concentration of L-glutamate causes excitotoxicity. A tight control of the brain interstitial fluid L-glutamate levels is therefore imperative, in order to maintain optimal neurotransmission and to avoid such excitotoxicity. The blood-brain barrier, i.e., the endothelial lining of the brain capillaries...... cells. The mechanisms underlying transendothelial L-glutamate transport are however still not well understood. The present chapter summarizes the current knowledge on blood-brain barrier L-glutamate transporters and the suggested pathways for the brain-to-blood L-glutamate efflux......., regulates the exchange of nutrients, gases, and metabolic waste products between plasma and brain interstitial fluid. It has been suggested that brain capillary endothelial cells could play an important role in L-glutamate homeostasis by mediating brain-to-blood L-glutamate efflux. Both in vitro and in vivo...

Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?

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Alessandro Dalpiaz

2018-03-01

Full Text Available Although several viruses can easily infect the central nervous system (CNS, antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs. These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1, multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5, and breast cancer resistance protein (ABCG2 or BCRP. Inhibitors of AETs may be considered, but their co-administration causes serious unwanted effects. Nasal administration of antiviral drugs is therefore proposed in order to overcome the aforementioned problems, but innovative devices, formulations (thermoreversible gels, polymeric micro- and nano-particles, solid lipid microparticles, nanoemulsions, absorption enhancers (chitosan, papaverine, and mucoadhesive agents (chitosan, polyvinilpyrrolidone are required in order to selectively target the antiviral drugs and, possibly, the AET inhibitors in the CNS. Moreover, several prodrugs of antiretroviral agents can inhibit or elude the AET systems, appearing as interesting substrates for innovative nasal formulations able to target anti-Human Immunodeficiency Virus (HIV agents into macrophages of the CNS, which are one of the most important HIV Sanctuaries of the body.

Progress and perspectives on targeting nanoparticles for brain drug delivery

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Huile Gao

2016-07-01

Full Text Available Due to the ability of the blood–brain barrier (BBB to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier (BBTB, and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.

Progress and perspectives on targeting nanoparticles for brain drug delivery

Institute of Scientific and Technical Information of China (English)

Huile Gao

2016-01-01

Due to the ability of the blood–brain barrier(BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier(BBTB), and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.

The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport.

Science.gov (United States)

Ochiai, Yusuke; Uchida, Yasuo; Ohtsuki, Sumio; Tachikawa, Masanori; Aizawa, Sanshiro; Terasaki, Tetsuya

2017-05-01

We purposed to clarify the contribution of fatty acid transport protein 1 (FATP1/SLC 27A1) to the supply of docosahexaenoic acid (DHA) to the brain across the blood-brain barrier in this study. Transport experiments showed that the uptake rate of [ 14 C]-DHA in human FATP1-expressing HEK293 cells was significantly greater than that in empty vector-transfected (mock) HEK293 cells. The steady-state intracellular DHA concentration was nearly 2-fold smaller in FATP1-expressing than in mock cells, suggesting that FATP1 works as not only an influx, but also an efflux transporter for DHA. [ 14 C]-DHA uptake by a human cerebral microvascular endothelial cell line (hCMEC/D3) increased in a time-dependent manner, and was inhibited by unlabeled DHA and a known FATP1 substrate, oleic acid. Knock-down of FATP1 in hCMEC/D3 cells with specific siRNA showed that FATP1-mediated uptake accounts for 59.2-73.0% of total [ 14 C]-DHA uptake by the cells. Insulin treatment for 30 min induced translocation of FATP1 protein to the plasma membrane in hCMEC/D3 cells and enhanced [ 14 C]-DHA uptake. Immunohistochemical analysis of mouse brain sections showed that FATP1 protein is preferentially localized at the basal membrane of brain microvessel endothelial cells. We found that two neuroprotective substances, taurine and biotin, in addition to DHA, undergo FATP1-mediated efflux. Overall, our results suggest that FATP1 localized at the basal membrane of brain microvessels contributes to the transport of DHA, taurine and biotin into the brain, and insulin rapidly increases DHA supply to the brain by promoting translocation of FATP1 to the membrane. Read the Editorial Comment for this article on page 324. © 2016 International Society for Neurochemistry.

Depletion of liver glutathione levels in rats: a potential confound of nose-only inhalation.

Science.gov (United States)

Fechter, Laurence D; Nelson-Miller, Alisa; Gearhart, Caroline

2008-07-01

Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.

From the "little brain" gastrointestinal infection to the "big brain" neuroinflammation: a proposed fast axonal transport pathway involved in multiple sclerosis.

Science.gov (United States)

Deretzi, Georgia; Kountouras, Jannis; Grigoriadis, Nikolaos; Zavos, Christos; Chatzigeorgiou, Stavros; Koutlas, Evangelos; Tsiptsios, Iakovos

2009-11-01

The human central nervous system (CNS) is targeted by different pathogens which, apart from pathogens' intranasal inoculation or trafficking into the brain through infected blood cells, may use a distinct pathway to bypass the blood-brain barrier by using the gastrointestinal tract (GIT) retrograde axonal transport through sensory or motor fibres. The recent findings regarding the enteric nervous system (often called the "little brain") similarities with CNS and GIT axonal transport of infections resulting in CNS neuroinflammation are mainly reviewed in this article. We herein propose that the GIT is the vulnerable area through which pathogens (such as Helicobacter pylori) may influence the brain and induce multiple sclerosis pathologies, mainly via the fast axonal transport by the afferent neurones connecting the GIT to brain.

Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study

Directory of Open Access Journals (Sweden)

Alam S

2012-11-01

-loaded nanoparticles (TQ-NP1 proved more effective in brain targeting compared to intravenous and intranasal TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the mucoadhesive properties of TQ-NP1.Keywords: thymoquinone, chitosan, nanoparticles, nose-to-brain targeting, gamma scintigraphy

Container transport direct call – logistic solution to container transport via Estonia

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A. Tolli

2007-12-01

Full Text Available Container transport in the world grows up to 12 % every year. Chinese container transport contributes majority of container flows in international container transport. Many world seaports compete for Chinese container flows and make eff orts to get investments and direct calls from China to their ports. Estonia has a possibility to decrease its large dependence and risks due to the transit of oil and oil products and coal with the help of container flows from China. In addition to a favorable geographical location Estonia has several other important arguments, like suffi cient land in the harbours for developing a container terminal to launch extensive container transport transit from China. Port of St. Petersburg, container transport port closest to Estonia by the Baltic Sea, is overloaded. Estonia can compete for container flows directed to Moscow, Nizhniy Novgorod, Kazan and Kaluga. Construction of an international high-tech container terminal in Port of Tallinn serves as one important precondition for directing Russian transit container flows through Estonia. Such a container terminal could service also larger vessels and container flows from China. Container lines and container terminals operating as alliances are jointly able to substantially increase container flows through countries.

Determination of Ignitable Liquids in Fire Debris: Direct Analysis by Electronic Nose

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Marta Ferreiro-González

2016-05-01

Full Text Available Arsonists usually use an accelerant in order to start or accelerate a fire. The most widely used analytical method to determine the presence of such accelerants consists of a pre-concentration step of the ignitable liquid residues followed by chromatographic analysis. A rapid analytical method based on headspace-mass spectrometry electronic nose (E-Nose has been developed for the analysis of Ignitable Liquid Residues (ILRs. The working conditions for the E-Nose analytical procedure were optimized by studying different fire debris samples. The optimized experimental variables were related to headspace generation, specifically, incubation temperature and incubation time. The optimal conditions were 115 °C and 10 min for these two parameters. Chemometric tools such as hierarchical cluster analysis (HCA and linear discriminant analysis (LDA were applied to the MS data (45–200 m/z to establish the most suitable spectroscopic signals for the discrimination of several ignitable liquids. The optimized method was applied to a set of fire debris samples. In order to simulate post-burn samples several ignitable liquids (gasoline, diesel, citronella, kerosene, paraffin were used to ignite different substrates (wood, cotton, cork, paper and paperboard. A full discrimination was obtained on using discriminant analysis. This method reported here can be considered as a green technique for fire debris analyses.

Determination of Ignitable Liquids in Fire Debris: Direct Analysis by Electronic Nose

Science.gov (United States)

Ferreiro-González, Marta; Barbero, Gerardo F.; Palma, Miguel; Ayuso, Jesús; Álvarez, José A.; Barroso, Carmelo G.

2016-01-01

Arsonists usually use an accelerant in order to start or accelerate a fire. The most widely used analytical method to determine the presence of such accelerants consists of a pre-concentration step of the ignitable liquid residues followed by chromatographic analysis. A rapid analytical method based on headspace-mass spectrometry electronic nose (E-Nose) has been developed for the analysis of Ignitable Liquid Residues (ILRs). The working conditions for the E-Nose analytical procedure were optimized by studying different fire debris samples. The optimized experimental variables were related to headspace generation, specifically, incubation temperature and incubation time. The optimal conditions were 115 °C and 10 min for these two parameters. Chemometric tools such as hierarchical cluster analysis (HCA) and linear discriminant analysis (LDA) were applied to the MS data (45–200 m/z) to establish the most suitable spectroscopic signals for the discrimination of several ignitable liquids. The optimized method was applied to a set of fire debris samples. In order to simulate post-burn samples several ignitable liquids (gasoline, diesel, citronella, kerosene, paraffin) were used to ignite different substrates (wood, cotton, cork, paper and paperboard). A full discrimination was obtained on using discriminant analysis. This method reported here can be considered as a green technique for fire debris analyses. PMID:27187407

Regulatory mechanisms for iron transport across the blood-brain barrier.

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Duck, Kari A; Simpson, Ian A; Connor, James R

2017-12-09

Many critical metabolic functions in the brain require adequate and timely delivery of iron. However, most studies when considering brain iron uptake have ignored the iron requirements of the endothelial cells that form the blood-brain barrier (BBB). Moreover, current models of BBB iron transport do not address regional regulation of brain iron uptake or how neurons, when adapting to metabolic demands, can acquire more iron. In this study, we demonstrate that both iron-poor transferrin (apo-Tf) and the iron chelator, deferoxamine, stimulate release of iron from iron-loaded endothelial cells in an in vitro BBB model. The role of the endosomal divalent metal transporter 1 (DMT1) in BBB iron acquisition and transport has been questioned. Here, we show that inhibition of DMT1 alters the transport of iron and Tf across the endothelial cells. These data support an endosome-mediated model of Tf-bound iron uptake into the brain and identifies mechanisms for local regional regulation of brain iron uptake. Moreover, our data provide an explanation for the disparity in the ratio of Tf to iron transport into the brain that has confounded the field. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimal-mass-transfer-based estimation of glymphatic transport in living brain

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Ratner, Vadim; Zhu, Liangjia; Kolesov, Ivan; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

2015-03-01

It was recently shown that the brain-wide cerebrospinal fluid (CSF) and interstitial fluid exchange system designated the `glymphatic pathway' plays a key role in removing waste products from the brain, similarly to the lymphatic system in other body organs . It is therefore important to study the flow patterns of glymphatic transport through the live brain in order to better understand its functionality in normal and pathological states. Unlike blood, the CSF does not flow rapidly through a network of dedicated vessels, but rather through para-vascular channels and brain parenchyma in a slower time-domain, and thus conventional fMRI or other blood-flow sensitive MRI sequences do not provide much useful information about the desired flow patterns. We have accordingly analyzed a series of MRI images, taken at different times, of the brain of a live rat, which was injected with a paramagnetic tracer into the CSF via the lumbar intrathecal space of the spine. Our goal is twofold: (a) find glymphatic (tracer) flow directions in the live rodent brain; and (b) provide a model of a (healthy) brain that will allow the prediction of tracer concentrations given initial conditions. We model the liquid flow through the brain by the diffusion equation. We then use the Optimal Mass Transfer (OMT) approach to derive the glymphatic flow vector field, and estimate the diffusion tensors by analyzing the (changes in the) flow. Simulations show that the resulting model successfully reproduces the dominant features of the experimental data. Keywords: inverse problem, optimal mass transport, diffusion equation, cerebrospinal fluid flow in brain, optical flow, liquid flow modeling, Monge Kantorovich problem, diffusion tensor estimation

The average Indian female nose.

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Patil, Surendra B; Kale, Satish M; Jaiswal, Sumeet; Khare, Nishant; Math, Mahantesh

2011-12-01

This study aimed to delineate the anthropometric measurements of the noses of young women of an Indian population and to compare them with the published ideals and average measurements for white women. This anthropometric survey included a volunteer sample of 100 young Indian women ages 18 to 35 years with Indian parents and no history of previous surgery or trauma to the nose. Standardized frontal, lateral, oblique, and basal photographs of the subjects' noses were taken, and 12 standard anthropometric measurements of the nose were determined. The results were compared with published standards for North American white women. In addition, nine nasal indices were calculated and compared with the standards for North American white women. The nose of Indian women differs significantly from the white nose. All the nasal measurements for the Indian women were found to be significantly different from those for North American white women. Seven of the nine nasal indices also differed significantly. Anthropometric analysis suggests differences between the Indian female nose and the North American white nose. Thus, a single aesthetic ideal is inadequate. Noses of Indian women are smaller and wider, with a less projected and rounded tip than the noses of white women. This study established the nasal anthropometric norms for nasal parameters, which will serve as a guide for cosmetic and reconstructive surgery in Indian women.

Blood-brain barrier transport of drugs for the treatment of brain diseases.

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Gabathuler, Reinhard

2009-06-01

The central nervous system is a sanctuary protected by barriers that regulate brain homeostasis and control the transport of endogenous compounds into the brain. The blood-brain barrier, formed by endothelial cells of the brain capillaries, restricts access to brain cells allowing entry only to amino acids, glucose and hormones needed for normal brain cell function and metabolism. This very tight regulation of brain cell access is essential for the survival of neurons which do not have a significant capacity to regenerate, but also prevents therapeutic compounds, small and large, from reaching the brain. As a result, various strategies are being developed to enhance access of drugs to the brain parenchyma at therapeutically meaningful concentrations to effectively manage disease.

Telesne spremembe med nosečnostjo

OpenAIRE

Predikaka, Sandra

2014-01-01

POVZETEK Nosečnost spremljajo obsežne fiziološke spremembe, ki se pojavijo že zgodaj po zanositvi. Pogosto se to zgodi, še preden se ženska zave, da je noseča. Nosečnost ni bolezen, ampak je »drugo stanje«, na to stanje se je potrebno pripraviti, saj le zdrava nosečnost prinese zdravega in primerno razvitega otroka. Namen raziskave je bil ugotoviti, kako nosečnice gledajo na telesne spremembe v nosečnosti in kako to vpliva na njihovo zadovoljstvo. Anketirali smo 100 nosečnic, ki so obi...

Steady-state cerebral glucose concentrations and transport in the human brain

OpenAIRE

Gruetter, R.; Ugurbil, K.; Seaquist, E. R.

1998-01-01

Understanding the mechanism of brain glucose transport across the blood- brain barrier is of importance to understanding brain energy metabolism. The specific kinetics of glucose transport nave been generally described using standard Michaelis-Menten kinetics. These models predict that the steady- state glucose concentration approaches an upper limit in the human brain when the plasma glucose level is well above the Michaelis-Menten constant for half-maximal transport, K(t). In experiments wh...

The virtual nose: a 3-dimensional virtual reality model of the human nose.

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Vartanian, A John; Holcomb, Joi; Ai, Zhuming; Rasmussen, Mary; Tardy, M Eugene; Thomas, J Regan

2004-01-01

The 3-dimensionally complex interplay of soft tissue, cartilaginous, and bony elements makes the mastery of nasal anatomy difficult. Conventional methods of learning nasal anatomy exist, but they often involve a steep learning curve. Computerized models and virtual reality applications have been used to facilitate teaching in a number of other complex anatomical regions, such as the human temporal bone and pelvic floor. We present a 3-dimensional (3-D) virtual reality model of the human nose. Human cadaveric axial cross-sectional (0.33-mm cuts) photographic data of the head and neck were used. With 460 digitized images, individual structures were traced and programmed to create a computerized polygonal model of the nose. Further refinements to this model were made using a number of specialized computer programs. This 3-D computer model of the nose was then programmed to operate as a virtual reality model. Anatomically correct 3-D model of the nose was produced. High-resolution images of the "virtual nose" demonstrate the nasal septum, lower lateral cartilages, middle vault, bony dorsum, and other structural details of the nose. Also, the model can be combined with a separate virtual reality model of the face and its skin cover as well as the skull. The user can manipulate the model in space, examine 3-D anatomical relationships, and fade superficial structures to reveal deeper ones. The virtual nose is a 3-D virtual reality model of the nose that is accurate and easy to use. It can be run on a personal computer or in a specialized virtual reality environment. It can serve as an effective teaching tool. As the first virtual reality model of the nose, it establishes a virtual reality platform from which future applications can be launched.

Complication of nose and paranasal sinus disease

International Nuclear Information System (INIS)

Kazmi, H.S.; Ali, S.; Ali, Z.

2012-01-01

Diseases of nose and paranasal sinuses can complicate to involve the orbit and other surrounding structures because of their close proximity. These diseases are usually infective or can be neoplastic in origin. Method: All the patients presenting in ENT or Eye Departments of Ayub Teaching Hospital during the one year study period who had complicated nose or paranasal sinus disease were included in the study. A detailed history and examination followed by CT scanning and laboratory investigations to assess the type and extent of the disease, was carried out. Results: Infections were the most common cause of complicated sinus disease 11 (75%). The rest of the 4 (25%) cases were tumours. 12 (80%) of the cases presented with proptosis. In 1 of these 12 cases, there was complete blindness. In 2 (13%) of the cases there was only orbital cellulitis. Two of these patients had facial swelling and 2 had nasal obstruction and presented as snoring. Two patients presented with history of weight loss and these patients had malignant tumour of the paranasal sinuses. One patient presented with early signs of meningitis. In 1 case sub periosteal scalp abscess (Pott's puffy tumour) was the only complication noted. Conclusion: Nose and paranasal sinus diseases can complicate to involve mostly the orbit, but sometimes brain, meninges and skull bones can also get involved. (author)

Brain targeted nanoparticulate drug delivery system of rasagiline via intranasal route.

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Mittal, Deepti; Md, Shadab; Hasan, Quamrul; Fazil, Mohammad; Ali, Asgar; Baboota, Sanjula; Ali, Javed

2016-01-01

The aim of the present study was to prepare and evaluate a rasagiline-loaded chitosan glutamate nanoparticles (RAS-CG-NPs) by ionic gelation of CG with tripolyphosphate anions (TPP). RAS-loaded CG-NPs were characterized for particle size, size distribution, encapsulation efficiency and in vitro drug release. The mean particles size, polydispersity index (PDI) and encapsulation efficiency was found to be 151.1 ± 10.31, 0.380 ± 0.01 and 96.43 ± 4.23, respectively. Biodistribution of RAS formulations in the brain and blood of mice following intranasal (i.n.) and intravenous (i.v.) administration was performed using HPLC analytical method. The drug concentrations in brain following the i.n. of CG-NPs were found to be significantly higher at all the time points compared to both drug (i.n.) and drug CG-NPs (i.v.). The Cmax (999.25 ng/ml) and AUC (2086.60 ng h/ml) of formulation CG-NPs (i.n) were found to be significantly higher than CG-NPs (i.v.) and RAS solution (i.n.). The direct transport percentage (DTP%) values of RAS-loaded CG-NPs (i.n.) as compared to drug solution (i.n.) increased from 66.27 ± 1.8 to 69.27 ± 2.1%. The results showed significant enhancement of bioavailability in brain, after administration of the RAS-loaded CG-NPs which could be a substantial achievement of direct nose to brain targeting in Parkinson's disease therapy.

Estrogen and insulin transport through the blood-brain barrier.

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May, Aaron A; Bedel, Nicholas D; Shen, Ling; Woods, Stephen C; Liu, Min

2016-09-01

Obesity is associated with insulin resistance and reduced transport of insulin through the blood-brain barrier (BBB). Reversal of high-fat diet-induced obesity (HFD-DIO) by dietary intervention improves the transport of insulin through the BBB and the sensitivity of insulin in the brain. Although both insulin and estrogen (E2), when given alone, reduce food intake and body weight via the brain, E2 actually renders the brain relatively insensitive to insulin's catabolic action. The objective of these studies was to determine if E2 influences the ability of insulin to be transported into the brain, since the receptors for both E2 and insulin are found in BBB endothelial cells. E2 (acute or chronic) was systemically administered to ovariectomized (OVX) female rats and male rats fed a chow or a high-fat diet. Food intake, body weight and other metabolic parameters were assessed along with insulin entry into the cerebrospinal fluid (CSF). Acute E2 treatment in OVX female and male rats reduced body weight and food intake, and chronic E2 treatment prevented or partially reversed high-fat diet-induced obesity. However, none of these conditions increased insulin transport into the CNS; rather, chronic E2 treatment was associated less-effective insulin transport into the CNS relative to weight-matched controls. Thus, the reduction of brain insulin sensitivity by E2 is unlikely to be mediated by increasing the amount of insulin entering the CNS. Copyright © 2016 Elsevier Inc. All rights reserved.

Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders

Directory of Open Access Journals (Sweden)

Tachikawa Masanori

2011-02-01

Full Text Available Abstract Guanidino compounds (GCs, such as creatine, phosphocreatine, guanidinoacetic acid, creatinine, methylguanidine, guanidinosuccinic acid, γ-guanidinobutyric acid, β-guanidinopropionic acid, guanidinoethane sulfonic acid and α-guanidinoglutaric acid, are present in the mammalian brain. Although creatine and phosphocreatine play important roles in energy homeostasis in the brain, accumulation of GCs may induce epileptic discharges and convulsions. This review focuses on how physiologically important and/or neurotoxic GCs are distributed in the brain under physiological and pathological conditions. Transporters for GCs at the blood-brain barrier (BBB and the blood-cerebrospinal fluid (CSF barrier (BCSFB have emerged as substantial contributors to GCs distribution in the brain. Creatine transporter (CRT/solute carrier (SLC 6A8 expressed at the BBB regulates creatine concentration in the brain, and represents a major pathway for supply of creatine from the circulating blood to the brain. CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6 and organic cation transporter (OCT3/SLC22A3 expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters. Instead, the BCSFB functions as a major cerebral clearance system for GCs. In conclusion, transport of GCs at the BBB and BCSFB appears to be the key determinant of the cerebral levels of GCs, and changes in the transport characteristics may cause the abnormal distribution of GCs in the brain seen

The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

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Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

2012-01-01

The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s disease patients, changes in glucose transporter function and expression have been observed, but a possible link between the altered glucose transporter function and disease progress is missing. Future recognition of the role of new glucose transporter isoforms in the brain may provide a better understanding of brain glucose metabolism in normal and disease states. Elucidation of clinical pathological mechanisms related to glucose transport and metabolism may provide common links to the etiology of these two diseases. Considering these facts, in this review we provide a current understanding of the vital roles of a variety of glucose transporters in the normal, diabetic and Alzheimer’s disease brain. PMID:23202918

Altered blood-brain barrier transport in neuro-inflammatory disorders.

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Schenk, Geert J; de Vries, Helga E

2016-06-01

During neurodegenerative and neuroinflammatory disorders of the central nervous system (CNS), such as Alzheimer's disease (AD) and multiple sclerosis (MS), the protective function of the blood-brain barrier (BBB) may be severely impaired. The general neuro-inflammatory response, ranging from activation of glial cells to immune cell infiltration that is frequently associated with such brain diseases may underlie the loss of the integrity and function of the BBB. Consequentially, the delivery and disposition of drugs to the brain will be altered and may influence the treatment efficiency of such diseases. Altered BBB transport of drugs into the CNS during diseases may be the result of changes in both specific transport and non-specific transport pathways. Potential alterations in transport routes like adsorptive mediated endocytosis and receptor-mediated endocytosis may affect drug delivery to the brain. As such, drugs that normally are unable to traverse the BBB may reach their target in the diseased brain due to increased permeability. In contrast, the delivery of (targeted) drugs could be hampered during inflammatory conditions due to disturbed transport mechanisms. Therefore, the inventory of the neuro-inflammatory status of the neurovasculature (or recovery thereof) is of utmost importance in choosing and designing an adequate drug targeting strategy under disease conditions. Within this review we will briefly discuss how the function of the BBB can be affected during disease and how this may influence the delivery of drugs into the diseased CNS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hyperammonaemia, plasma aminoacid imbalance, and blood-brain aminoacid transport: a unified theory of portal-systemic encephalopathy.

Science.gov (United States)

James, J H; Ziparo, V; Jeppsson, B; Fischer, J E

1979-10-13

It is proposed that hyperammonaemia in liver cirrhosis or after portacaval shunt contributes to plasma neutral aminoacid imbalance and to increased activity of the blood-brain neutral amino-acid transport system. Plasma neutral aminoacid concentrations are deranged, partly, but not completely, because ammonia stimulates glucagon secretion; a high rate of gluconeogenesis and hyperinsulinaemia follow. Brain uptake of neutral aminoacids rises because ammonia stimulates brain-glutamine synthesis, which results in rapid exchange of brain glutamine for plasma neutral aminoacids. Hyperammonaemia therefore contributes to encephalopathy indirectly, by raising the brain concentration of neutral aminoacids which after neurotransmitter metabolism, rather than directly, by toxic effects on neuronal metabolism.

Insulin transport into the brain and cerebrospinal fluid.

Science.gov (United States)

Begg, Denovan P

2015-01-01

The pancreatic hormone insulin plays a well-described role in the periphery, based principally on its ability to lower circulating glucose levels via activation of glucose transporters. However, insulin also acts within the central nervous system (CNS) to alter a number of physiological outcomes ranging from energy balance and glucose homeostasis to cognitive performance. Insulin is transported into the CNS by a saturable receptor-mediated process that is proposed to be dependent on the insulin receptor. Transport of insulin into the brain is dependent on numerous factors including diet, glycemia, a diabetic state and notably, obesity. Obesity leads to a marked decrease in insulin transport from the periphery into the CNS and the biological basis of this reduction of transport remains unresolved. Despite decades of research into the effects of central insulin on a wide range of physiological functions and its transport from the periphery to the CNS, numerous questions remain unanswered including which receptor is responsible for transport and the precise mechanisms of action of insulin within the brain. © 2015 Elsevier Inc. All rights reserved.

Simultaneous measurement of glucose transport and utilization in the human brain

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Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.

2011-01-01

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMRglc) obtained from other tracer studies, such as 13C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state 1H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMRglc, this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain. PMID:21791622

Rapid transport of CCL11 across the blood-brain barrier: regional variation and importance of blood cells.

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Erickson, Michelle A; Morofuji, Yoichi; Owen, Joshua B; Banks, William A

2014-06-01

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.

Brain Transport Profiles of Ginsenoside Rb1 by Glucose Transporter 1: In Vitro and in Vivo

Directory of Open Access Journals (Sweden)

Yu-Zhu Wang

2018-04-01

Full Text Available Ginsenoside Rb1 (Rb1 has been demonstrated its protection for central nervous system and is apparently highly distributed to the brain. The objective of this study was to characterize Rb1 transport at the blood–brain barrier (BBB using primary cultured rat brain microvascular endothelial cells (rBMEC, an in vitro BBB model. The initial uptake velocity of Rb1 in rBMEC was temperature- and concentration-dependent, and was significantly reduced by phloretin, an inhibitor of GLUT1 transporter, but was independent of metabolic inhibitor. Furthermore, the transport of Rb1 into rBMEC was significantly diminished in the presence of natural substrate α-D-glucose, suggesting a facilitated transport of Rb1 via GLUT1 transporter. The impact of GLUT1 on the distribution of Rb1 between brain and plasma was studied experimentally in rats. Administration of phloretin (5 mg/kg, i.v. to normal rats for consecutive 1 week before Rb1 (10 mg/kg, i.v. at 0.5, 2, and 6 h did not alter Rb1 concentrations in plasma, but resulted in significant decreased brain concentrations of Rb1 compared to in the phloretin-untreated normal rats (489.6 ± 58.3 versus 105.1 ± 15.1 ng/g, 193.8 ± 11.1 versus 84.8 ± 4.1 ng/g, and 114.2 ± 24.0 versus 39.9 ± 4.9 ng/g, respectively. The expression of GLUT1 in the phloretin-treated group by western blotting analysis in vitro and in vivo experiments was significantly decreased, indicating that the decreased transport of Rb1 in brain was well related to the down-regulated function and level of GLUT1. Therefore, our in vitro and in vivo results indicate that the transport of Rb1 at the BBB is at least partly mediated by GLUT1 transporter.

Caudal Septal Stabilization Suturing Technique to Treat Crooked Noses.

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Baykal, Bahadir; Erdim, Ibrahim; Guvey, Ali; Oghan, Fatih; Kayhan, Fatma Tulin

2016-10-01

To rotate the nasal axis and septum to the midline using an L-strut graft and a novel caudal septal stabilization suturing technique to treat crooked noses. Thirty-six patients were included in the study. First, an L-strut graft was prepared by excising the deviated cartilage site in all patients. Second, multiple stabilization suturing, which we describe as a caudal septal stabilization suturing technique with a "fishing net"-like appearance, was applied between the anterior nasal spine and caudal septum in all patients. This new surgical technique, used to rotate the caudal septum, was applied to 22 I-type and 14 C-type crooked noses. Correction rates for the crooked noses were compared between the 2 inclination types with angular estimations. Deviation angles were measured using the AutoCAD 2012 software package and frontal (anterior) views, with the Frankfurt horizontal line parallel to the ground. Nasal axis angles showing angle improvement graded 4 categories as excellent, good, acceptable, and unsuccessful for evaluations at 6 months after surgery in the study. The success rate in the C-type nasal inclination was 86.7% (±21.9) and 88% (±16.7) in the I-type. The overall success rate of L-strut grafting and caudal septal stabilization suturing in crooked nose surgeries was 87.5% (±18.6). "Unsuccessful" results were not reported in any of the patients. L-strut grafting and caudal septal stabilization suturing techniques are efficacious in crooked noses according to objective measurement analysis results. However, a longer follow-up duration in a larger patient population is needed.

Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.

Science.gov (United States)

Plog, Benjamin A; Dashnaw, Matthew L; Hitomi, Emi; Peng, Weiguo; Liao, Yonghong; Lou, Nanhong; Deane, Rashid; Nedergaard, Maiken

2015-01-14

The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity. Copyright © 2015 the authors 0270-6474/15/350518-09$15.00/0.

Transport of /sup 99m/Tc complexes through the blood-brain barrier

International Nuclear Information System (INIS)

Loberg, M.D.; Corder, E.H.; Fields, A.T.; Callery, P.S.

1979-01-01

Thirteen /sup 99m/Tc complexes have been synthesized and used to determine the relationships between protein binding, lipophilicity and membrane transport. The lipophilicity of the /sup 99m/Tc complexes was altered by adding substituents to either IDA, EDTA, DTPA or oxine; membrane transport was estimated using the brain uptake index (BUI) method. The BUI of the /sup 99m/Tc complexes was found to vary directly with lipophilicity and inversely with protein binding. These results demonstrated that /sup 99m/Tc-oxine derivatives are better suited for use in the development of intracellular tracers than are the /sup 99m/Tc derivatives of aminopolycarboxylates

Direct detection of fungal siderophores on bats with white-nose syndrome via fluorescence microscopy-guided ambient ionization mass spectrometry.

Science.gov (United States)

Mascuch, Samantha J; Moree, Wilna J; Hsu, Cheng-Chih; Turner, Gregory G; Cheng, Tina L; Blehert, David S; Kilpatrick, A Marm; Frick, Winifred F; Meehan, Michael J; Dorrestein, Pieter C; Gerwick, Lena

2015-01-01

White-nose syndrome (WNS) caused by the pathogenic fungus Pseudogymnoascus destructans is decimating the populations of several hibernating North American bat species. Little is known about the molecular interplay between pathogen and host in this disease. Fluorescence microscopy ambient ionization mass spectrometry was used to generate metabolic profiles from the wings of both healthy and diseased bats of the genus Myotis. Fungal siderophores, molecules that scavenge iron from the environment, were detected on the wings of bats with WNS, but not on healthy bats. This work is among the first examples in which microbial molecules are directly detected from an infected host and highlights the ability of atmospheric ionization methodologies to provide direct molecular insight into infection.

Potential Applications and Limitations of Electronic Nose Devices for Plant Disease Diagnosis

Directory of Open Access Journals (Sweden)

Antonio Cellini

2017-11-01

Full Text Available Electronic nose technology has recently been applied to the detection of several plant diseases and pests, with promising results. However, in spite of its numerous advantages, including operational simplicity, non-destructivity, and bulk sampling, drawbacks include a low sensitivity and specificity in comparison with microbiological and molecular methods. A critical review of the use of an electronic nose for plant disease diagnosis and pest detection is presented, describing the instrumental and procedural advances of sensorial analysis, for the improvement of discrimination between healthy and infected or infested plants. In conclusion, the use of electronic nose technology is suggested to assist, direct, and optimise traditionally adopted diagnostic techniques.

Quantification of Transporter and Receptor Proteins in Dog Brain Capillaries and Choroid Plexus: Relevance for the Distribution in Brain and CSF of Selected BCRP and P-gp Substrates.

Science.gov (United States)

Braun, Clemens; Sakamoto, Atsushi; Fuchs, Holger; Ishiguro, Naoki; Suzuki, Shinobu; Cui, Yunhai; Klinder, Klaus; Watanabe, Michitoshi; Terasaki, Tetsuya; Sauer, Achim

2017-10-02

Transporters at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) play a pivotal role as gatekeepers for efflux or uptake of endogenous and exogenous molecules. The protein expression of a number of them has already been determined in the brains of rodents, nonhuman primates, and humans using quantitative targeted absolute proteomics (QTAP). The dog is an important animal model for drug discovery and development, especially for safety evaluations. The purpose of the present study was to clarify the relevance of the transporter protein expression for drug distribution in the dog brain and CSF. We used QTAP to examine the protein expression of 17 selected transporters and receptors at the dog BBB and BCSFB. For the first time, we directly linked the expression of two efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), to regional brain and CSF distribution using specific substrates. Two cocktails, each containing one P-gp substrate (quinidine or apafant) and one BCRP substrate (dantrolene or daidzein) were infused intravenously prior to collection of the brain. Transporter expression varied only slightly between the capillaries of different brain regions and did not result in region-specific distribution of the investigated substrates. There were, however, distinct differences between brain capillaries and choroid plexus. Largest differences were observed for BCRP and P-gp: both were highly expressed in brain capillaries, but no BCRP and only low amounts of P-gp were detected in the choroid plexus. K p,uu,brain and K p,uu,CSF of both P-gp substrates were indicative of drug efflux. Also, K p,uu,brain for the BCRP substrates was low. In contrast, K p,uu,CSF for both BCRP substrates was close to unity, resulting in K p,uu,CSF /K p,uu,brain ratios of 7 and 8, respectively. We conclude that the drug transporter expression profiles differ between the BBB and BCSFB in dogs, that there are species differences

Application of nose smear method to the assessment of internal contamination

International Nuclear Information System (INIS)

Miyabe, K.; Ishiguro, H.; Nakata, K.; Fukuda, S.

1985-01-01

At PNC Tokai Works, the plutonium fuel fabrication facility has been operating since 1967. Lung counting and bioassay for urine are performed routinely for internal radiation dosimetry in this facility. The nose smear method is used for assessing the significance of intake whenever an incident involving inhalation of radioactive material occurs. It was found empirically on the basis of 22 inhalation cases that nose smear samples were useful for assessing tentatively the intake in an incidental inhalation of plutonium aerosol. In 80% of the cases of plutonium inhalation, the amount in the early faecal excretion (5 days after inhalation) is less than 10 times the plutonium in the nose smear samples over the activity region from 0.074 to 28 Bq of nose smear samples. It is suggested that the amount of plutonium in early excreted faeces be estimated by applying the factor of 10 to the activity in nose smear samples. As an example, when PuO 2 (class Y, AMAD 1 μm) 0.074 Bq corresponding to the minimum detectable amount is measured in the nose smear samples, the early faecal excretion and the total intake can be estimated approximately to be 0.74 Bq and 1.55 Bq, respectively, applying the clearance model of ICRP 30, and the committed dose equivalent of bone surface is estimated as 1.6 mSv. (author)

Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery.

Science.gov (United States)

Patching, Simon G

2017-03-01

Glucose transporters (GLUTs) at the blood-brain barrier maintain the continuous high glucose and energy demands of the brain. They also act as therapeutic targets and provide routes of entry for drug delivery to the brain and central nervous system for treatment of neurological and neurovascular conditions and brain tumours. This article first describes the distribution, function and regulation of glucose transporters at the blood-brain barrier, the major ones being the sodium-independent facilitative transporters GLUT1 and GLUT3. Other GLUTs and sodium-dependent transporters (SGLTs) have also been identified at lower levels and under various physiological conditions. It then considers the effects on glucose transporter expression and distribution of hypoglycemia and hyperglycemia associated with diabetes and oxygen/glucose deprivation associated with cerebral ischemia. A reduction in glucose transporters at the blood-brain barrier that occurs before the onset of the main pathophysiological changes and symptoms of Alzheimer's disease is a potential causative effect in the vascular hypothesis of the disease. Mutations in glucose transporters, notably those identified in GLUT1 deficiency syndrome, and some recreational drug compounds also alter the expression and/or activity of glucose transporters at the blood-brain barrier. Approaches for drug delivery across the blood-brain barrier include the pro-drug strategy whereby drug molecules are conjugated to glucose transporter substrates or encapsulated in nano-enabled delivery systems (e.g. liposomes, micelles, nanoparticles) that are functionalised to target glucose transporters. Finally, the continuous development of blood-brain barrier in vitro models is important for studying glucose transporter function, effects of disease conditions and interactions with drugs and xenobiotics.

Carbogen inhalation increases oxygen transport to hypoperfused brain tissue in patients with occlusive carotid artery disease: increased oxygen transport to hypoperfused brain

DEFF Research Database (Denmark)

Ashkanian, Mahmoud; Gjedde, Albert; Mouridsen, Kim

2009-01-01

to inhaled oxygen (the mixture known as carbogen). In the present study, we measured CBF by positron emission tomography (PET) during inhalation of test gases (O(2), carbogen, and atmospheric air) in healthy volunteers (n = 10) and in patients with occlusive carotid artery disease (n = 6). Statistical...... and Sa(O2) are readily obtained with carbogen, while oxygen increases only Sa(O2). Thus, carbogen improves oxygen transport to brain tissue more efficiently than oxygen alone. Further studies with more subjects are, however, needed to investigate the applicability of carbogen for long-term inhalation...

The Effect of Body Posture on Brain Glymphatic Transport.

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Lee, Hedok; Xie, Lulu; Yu, Mei; Kang, Hongyi; Feng, Tian; Deane, Rashid; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2015-08-05

The glymphatic pathway expedites clearance of waste, including soluble amyloid β (Aβ) from the brain. Transport through this pathway is controlled by the brain's arousal level because, during sleep or anesthesia, the brain's interstitial space volume expands (compared with wakefulness), resulting in faster waste removal. Humans, as well as animals, exhibit different body postures during sleep, which may also affect waste removal. Therefore, not only the level of consciousness, but also body posture, might affect CSF-interstitial fluid (ISF) exchange efficiency. We used dynamic-contrast-enhanced MRI and kinetic modeling to quantify CSF-ISF exchange rates in anesthetized rodents' brains in supine, prone, or lateral positions. To validate the MRI data and to assess specifically the influence of body posture on clearance of Aβ, we used fluorescence microscopy and radioactive tracers, respectively. The analysis showed that glymphatic transport was most efficient in the lateral position compared with the supine or prone positions. In the prone position, in which the rat's head was in the most upright position (mimicking posture during the awake state), transport was characterized by "retention" of the tracer, slower clearance, and more CSF efflux along larger caliber cervical vessels. The optical imaging and radiotracer studies confirmed that glymphatic transport and Aβ clearance were superior in the lateral and supine positions. We propose that the most popular sleep posture (lateral) has evolved to optimize waste removal during sleep and that posture must be considered in diagnostic imaging procedures developed in the future to assess CSF-ISF transport in humans. The rodent brain removes waste better during sleep or anesthesia compared with the awake state. Animals exhibit different body posture during the awake and sleep states, which might affect the brain's waste removal efficiency. We investigated the influence of body posture on brainwide transport of inert

Nose: Applied aspects in dermatology

Directory of Open Access Journals (Sweden)

Dammaningala Venkataramaiah Lakshmi

2016-01-01

Full Text Available Nose is the most prominent part of the mid-face and has important physiological, aesthetic and psychological functions. Skin diseases on the nose are commonly seen by dermatologists, otorhinolaryngologists, and plastic surgeons. Because of its exposed, highly visible localization, lesions on the skin of the nose are often noticed by patients themselves, typically very early in the course of the disease. Similarly, the dermatological lexicon is well known with descriptive terminologies, synonyms, acronyms, eponyms, toponyms, misnomers. We have tried to compile the anatomical applications of nose in cosmetology and dermatosurgery subspecialities with nasal eponyms and signs encountered in clinical dermatology that would be helpful for residents.

Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?

Science.gov (United States)

Abdullahi, Wazir; Davis, Thomas P; Ronaldson, Patrick T

2017-07-01

Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain. With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. Therefore, our laboratory has proposed that optimization of CNS drug delivery, particularly for treatment of diseases with an H/R component, can be achieved by targeting Oatp isoforms at the BBB. As the major drug transporting Oatp isoform, Oatp1a4 has demonstrated blood-to-brain transport of substrate drugs with neuroprotective properties. Furthermore, our laboratory has shown that targeting Oatp1a4 regulation (i.e., TGF-β signaling mediated via the ALK-1 and ALK-5 transmembrane receptors) represents an opportunity to control Oatp1a4 functional expression for the purpose of delivering therapeutics to the CNS. In this review, we will discuss limitations of targeting P-gp-mediated transport activity and the advantages of targeting Oatp-mediated transport. Through this discussion, we will also provide critical information on novel approaches to improve CNS drug delivery by targeting endogenous uptake transporters expressed at the BBB.

GLP-1 analog raises glucose transport capacity of blood-brain barrier in Alzheimer's disease

DEFF Research Database (Denmark)

Gejl, M.; Brock, B.; Egefjord, L.

2017-01-01

transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P cerebral cortex as a whole compared...... and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here...

Lactate transport and signaling in the brain

DEFF Research Database (Denmark)

Bergersen, Linda Hildegard

2015-01-01

AMP. The localization and function of HCAR1 and the three MCTs (MCT1, MCT2, and MCT4) expressed in brain constitute the focus of this review. They are possible targets for new therapeutic drugs and interventions. The author proposes that lactate actions in the brain through MCTs and the lactate receptor underlie part......Lactate acts as a ‘buffer’ between glycolysis and oxidative metabolism. In addition to being exchanged as a fuel by the monocarboxylate transporters (MCTs) between cells and tissues with different glycolytic and oxidative rates, lactate may be a ‘volume transmitter’ of brain signals. According...... to some, lactate is a preferred fuel for brain metabolism. Immediately after brain activation, the rate of glycolysis exceeds oxidation, leading to net production of lactate. At physical rest, there is a net efflux of lactate from the brain into the blood stream. But when blood lactate levels rise...

Direct detection of fungal siderophores on bats with white-nose syndrome via fluorescence microscopy-guided ambient ionization mass spectrometry

Science.gov (United States)

Mascuch, Samantha J.; Moree, Wilna J.; Cheng-Chih Hsu, Cheng-Chih; Turner, Gregory G.; Cheng, Tina L.; Blehert, David S.; Kilpatrick, A. Marm; Frick, Winifred F.; Meehan, Michael J.; Dorrestein, Pieter C.; Gerwick, Lena

2015-01-01

White-nose syndrome (WNS) caused by the pathogenic fungus Pseudogymnoascus destructans is decimating the populations of several hibernating North American bat species. Little is known about the molecular interplay between pathogen and host in this disease. Fluorescence microscopy ambient ionization mass spectrometry was used to generate metabolic profiles from the wings of both healthy and diseased bats of the genus Myotis. Fungal siderophores, molecules that scavenge iron from the environment, were detected on the wings of bats with WNS, but not on healthy bats. This work is among the first examples in which microbial molecules are directly detected from an infected host and highlights the ability of atmospheric ionization methodologies to provide direct molecular insight into infection.

Direct detection of fungal siderophores on bats with white-nose syndrome via fluorescence microscopy-guided ambient ionization mass spectrometry.

Directory of Open Access Journals (Sweden)

Samantha J Mascuch

Full Text Available White-nose syndrome (WNS caused by the pathogenic fungus Pseudogymnoascus destructans is decimating the populations of several hibernating North American bat species. Little is known about the molecular interplay between pathogen and host in this disease. Fluorescence microscopy ambient ionization mass spectrometry was used to generate metabolic profiles from the wings of both healthy and diseased bats of the genus Myotis. Fungal siderophores, molecules that scavenge iron from the environment, were detected on the wings of bats with WNS, but not on healthy bats. This work is among the first examples in which microbial molecules are directly detected from an infected host and highlights the ability of atmospheric ionization methodologies to provide direct molecular insight into infection.

The Gendered Nose and its Lack: "Medieval" Nose-Cutting and its Modern Manifestations.

Science.gov (United States)

Skinner, Patricia

2014-01-01

Time magazine's cover photograph in August 2010 of a noseless Afghan woman beside the emotive strap line, "What happens if we leave Afghanistan," fuelled debate about the "medieval" practices of the Taliban, whose local commander had instructed her husband to take her nose and ears. Press reports attributed the violence to the Pashtun tradition that a dishonored husband "lost his nose." This equation of nose-cutting with tradition begs questions not only about the Orientalist lens of the western press when viewing Afghanistan, but also about the assumption that the word "medieval" can function as a label for such practices. A study of medieval nose-cutting suggests that its identification as an "eastern" practice should be challenged. Rather clearer is its connection with patriarchal values of authority and honor: the victims of such punishment have not always been women, but this is nevertheless a gendered punishment of the powerless by the powerful.

The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

OpenAIRE

Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

2012-01-01

The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s dis...

Transport across the blood-brain barrier of pluronic leptin.

Science.gov (United States)

Price, Tulin O; Farr, Susan A; Yi, Xiang; Vinogradov, Serguei; Batrakova, Elena; Banks, William A; Kabanov, Alexander V

2010-04-01

Leptin is a peptide hormone produced primarily by adipose tissue that acts as a major regulator of food intake and energy homeostasis. Impaired transport of leptin across the blood-brain barrier (BBB) contributes to leptin resistance, which is a cause of obesity. Leptin as a candidate for the treatment of this obesity is limited because of the short half-life in circulation and the decreased BBB transport that arises in obesity. Chemical modification of polypeptides with amphiphilic poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) is a promising technology to improve efficiency of delivery of polypeptides to the brain. In the present study, we determined the effects of Pluronic P85 (P85) with intermediate hydrophilic-lipophilic balance conjugated with leptin via a degradable SS bond [leptin(ss)-P85] on food intake, clearance, stability, and BBB uptake. The leptin(ss)-P85 exhibited biological activity when injected intracerebroventricularly after overnight food deprivation and 125I-leptin(ss)-P85 was stable in blood, with a half-time clearance of 32.3 min (versus 5.46 min for leptin). 125I-Leptin(ss)-P85 crossed the BBB [blood-to-brain unidirectional influx rate (K(i)) = 0.272 +/- 0.037 microl/g x min] by a nonsaturable mechanism unrelated to the leptin transporter. Capillary depletion showed that most of the 125I-leptin(ss)-P85 taken up by the brain reached the brain parenchyma. Food intake was reduced when 3 mg of leptin(ss)-P85 was administered via tail vein in normal body weight mice [0-30 min, p penetration by a mechanism-independent BBB leptin transporter.

Foreign body in the nose

Science.gov (United States)

... page: //medlineplus.gov/ency/article/000037.htm Foreign body in the nose To use the sharing features ... in a normal attempt to explore their own bodies. Objects placed in the nose may include food, ...

Using the Electronic Nose to Identify Airway Infection during COPD Exacerbations.

Directory of Open Access Journals (Sweden)

Hanaa Shafiek

Full Text Available The electronic nose (e-nose detects volatile organic compounds (VOCs in exhaled air. We hypothesized that the exhaled VOCs print is different in stable vs. exacerbated patients with chronic obstructive pulmonary disease (COPD, particularly if the latter is associated with airway bacterial infection, and that the e-nose can distinguish them.Smell-prints of the bacteria most commonly involved in exacerbations of COPD (ECOPD were identified in vitro. Subsequently, we tested our hypothesis in 93 patients with ECOPD, 19 of them with pneumonia, 50 with stable COPD and 30 healthy controls in a cross-sectional case-controlled study. Secondly, ECOPD patients were re-studied after 2 months if clinically stable. Exhaled air was collected within a Tedlar bag and processed by a Cynarose 320 e-nose. Breath-prints were analyzed by Linear Discriminant Analysis (LDA with "One Out" technique and Sensor logic Relations (SLR. Sputum samples were collected for culture.ECOPD with evidence of infection were significantly distinguishable from non-infected ECOPD (p = 0.018, with better accuracy when ECOPD was associated to pneumonia. The same patients with ECOPD were significantly distinguishable from stable COPD during follow-up (p = 0.018, unless the patient was colonized. Additionally, breath-prints from COPD patients were significantly distinguished from healthy controls. Various bacteria species were identified in culture but the e-nose was unable to identify accurately the bacteria smell-print in infected patients.E-nose can identify ECOPD, especially if associated with airway bacterial infection or pneumonia.

Prehrana in telesna aktivnost nosečnice

OpenAIRE

Ciglar, Ksenija

2012-01-01

V diplomskem delu smo predstavili nosečnost kot stanje fizioloških in psiholoških sprememb ter prehrano in telesno aktivnost nosečnice. Zdrava in uravnotežena prehrana je pomembna v vseh življenjskih obdobjih ženske, še posebej pa pred nosečnostjo, v nosečnosti in v času laktacije. Telesna ali športna dejavnost pa vpliva pozitivno na nosečničino zdravje in dobro počutje. Diplomsko delo je sestavljeno iz dveh delov. V prvem (teoretičnem) delu je predstavljena fiziologija nosečnosti, prehrana ...

Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

Science.gov (United States)

Tong, Wenyong; Dwyer, Chrissa A; Thacker, Bryan E; Glass, Charles A; Brown, Jillian R; Hamill, Kristina; Moremen, Kelley W; Sarrazin, Stéphane; Gordts, Philip L S M; Dozier, Lara E; Patrick, Gentry N; Tor, Yitzhak; Esko, Jeffrey D

2017-12-06

Iduronidase (IDUA)-deficient mice accumulate glycosaminoglycans in cells and tissues and exhibit many of the same neuropathological symptoms of patients suffering from Mucopolysaccharidosis I. Intravenous enzyme-replacement therapy for Mucopolysaccharidosis I ameliorates glycosaminoglycan storage and many of the somatic aspects of the disease but fails to treat neurological symptoms due to poor transport across the blood-brain barrier. In this study, we examined the delivery of IDUA conjugated to guanidinoneomycin (GNeo), a molecular transporter. GNeo-IDUA and IDUA injected intravenously resulted in reduced hepatic glycosaminoglycan accumulation but had no effect in the brain due to fast clearance from the circulation. In contrast, intranasally administered GNeo-IDUA entered the brain rapidly. Repetitive intranasal treatment with GNeo-IDUA reduced glycosaminoglycan storage, lysosome size and number, and neurodegenerative astrogliosis in the olfactory bulb and primary somatosensory cortex, whereas IDUA was less effective. The enhanced efficacy of GNeo-IDUA was not the result of increased nose-to-brain delivery or enzyme stability, but rather due to more efficient uptake into neurons and astrocytes. GNeo conjugation also enhanced glycosaminoglycan clearance by intranasally delivered sulfamidase to the brain of sulfamidase-deficient mice, a model of Mucopolysaccharidosis IIIA. These findings suggest the general utility of the guanidinoglycoside-based delivery system for restoring missing lysosomal enzymes in the brain. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Puerarin transport across rat nasal epithelial cells and the influence of compatibility with paeoniflorin and menthol

Directory of Open Access Journals (Sweden)

Zhang L

2017-09-01

Full Text Available Lin Zhang, Shou-Ying Du, Yang Lu, Chang Liu, Hui-Chao Wu, Zhi-Hao Tian, Min Wang, Chang Yang School of Chinese Materia Medica, Beijing University of Chinese Medicine, Chaoyang District, Beijing, People’s Republic of China Abstract: Nose-to-brain transport can provide an excellent pathway for drugs of the central nervous system. Consequently, how to make full use of this pathway in practical applications has become a focus of drug design. However, many aspects affecting drug delivery from the nose to the brain remain unclear. This study aimed to more deeply investigate the transport of puerarin and to explore the mechanism underlying the influence of compatible drugs on puerarin permeability in a primary cell model simulating the nasal mucosa. In this research, based on rat nasal epithelial cells (RNECs cultured in vitro and cytotoxicity assays, the bidirectional transport of puerarin across RNEC monolayers and the effect of its compatibility with peoniflorin and menthol were analyzed. The apparent permeability coefficient was <1.5×10–6 cm/s, and the efflux ratio of puerarin was <2, indicating that puerarin had poor absorption and that menthol but not peoniflorin significantly improved puerarin transport. Simultaneously, through experiments, such as immunofluorescence staining, transepithelial electrical resistance measurement, rhodamine 123 efflux evaluation, the cell membrane fluorescence recovery after photobleaching test, and ATPase activity determination, the permeability promoting mechanism of menthol was confirmed to be closely related to disruption of the tight junction protein structure, to the P-glycoprotein inhibitory effect, to increased membrane fluidity, and to the promotion of enzyme activity. These results provide reliable data on nasal administration of the studied drugs and lay the foundation for a deeper investigation of the nose–brain pathway and nasal administration. Keywords: Chinese herbal compound

Methylmercury transport across the blood-brain barrier by molecular mimicry

International Nuclear Information System (INIS)

Kerper, L.E.; Ballatori, N.; Clarkson, T.W.

1990-01-01

The mechanism by which methylmercury (MeHg) crosses the blood-brain barrier is not known. Co-administration of MeHg with L-cysteine by intravenous injection has been shown to accelerate MeHg uptake into brain tissue in rats. Since the complex of MeHg with L-cysteine is structurally similar to L-methionine, a substrate for the L (leucine-preferring) neutral amino acid transport system, this amino acid carrier may be involved in MeHg uptake into brain. To examine this hypothesis, the rapid carotid infusion technique was used in the rat. The concentration-dependence of initial rates of Me 203 Hg uptake into rat brains following injection of Me 203 Hg-L-cysteine complex was non-linear, exhibiting characteristics of saturable transport (K m 250 μM, V max 700 pmol·g -1 ·15 s -1 ). A slower, nonsaturable uptake was seen following MeHg-D-cysteine injection. MeHg-L-cysteine uptake was inhibited by co-injection of L-methionine (K i 200 μM), D-methionine (K i 600 μM), and amino acid analog 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (K i 1.4 mM), but not by amino acid analog α-methylaminoisobutyric acid. Transport of 14 C-L-phenylalanine was inhibited by MeHg-L-cysteine, but not by MeHgCl. The results suggest that MeHg may enter brain capillary endothelial cells as a cysteine complex, via amino acid transport system L

First Steps to Develop and Validate a CFPD Model in Order to Support the Design of Nose-to-Brain Delivered Biopharmaceuticals.

Science.gov (United States)

Engelhardt, Lucas; Röhm, Martina; Mavoungou, Chrystelle; Schindowski, Katharina; Schafmeister, Annette; Simon, Ulrich

2016-06-01

Aerosol particle deposition in the human nasal cavity is of high interest in particular for intranasal central nervous system (CNS) drug delivery via the olfactory cleft. The objective of this study was the development and comparison of a numerical and experimental model to investigate various parameters for olfactory particle deposition within the complex anatomical nasal geometry. Based on a standardized nasal cavity, a computational fluid and particle dynamics (CFPD) model was developed that enables the variation and optimization of different parameters, which were validated by in vitro experiments using a constructed rapid-prototyped human nose model. For various flow rates (5 to 40 l/min) and particle sizes (1 to 10 μm), the airflow velocities, the calculated particle airflow patterns and the particle deposition correlated very well with the experiment. Particle deposition was investigated numerically by varying particle sizes at constant flow rate and vice versa assuming the particle size distribution of the used nebulizer. The developed CFPD model could be directly translated to the in vitro results. Hence, it can be applied for parameter screening and will contribute to the improvement of aerosol particle deposition at the olfactory cleft for CNS drug delivery in particular for biopharmaceuticals.

[Blood-brain barrier part III: therapeutic approaches to cross the blood-brain barrier and target the brain].

Science.gov (United States)

Weiss, N; Miller, F; Cazaubon, S; Couraud, P-O

2010-03-01

Over the last few years, the blood-brain barrier has come to be considered as the main limitation for the treatment of neurological diseases caused by inflammatory, tumor or neurodegenerative disorders. In the blood-brain barrier, the close intercellular contact between cerebral endothelial cells due to tight junctions prevents the passive diffusion of hydrophilic components from the bloodstream into the brain. Several specific transport systems (via transporters expressed on cerebral endothelial cells) are implicated in the delivery of nutriments, ions and vitamins to the brain; other transporters expressed on cerebral endothelial cells extrude endogenous substances or xenobiotics, which have crossed the cerebral endothelium, out of the brain and into the bloodstream. Recently, several strategies have been proposed to target the brain, (i) by by-passing the blood-brain barrier by central drug administration, (ii) by increasing permeability of the blood-brain barrier, (iii) by modulating the expression and/or the activity of efflux transporters, (iv) by using the physiological receptor-dependent blood-brain barrier transport, and (v) by creating new viral or chemical vectors to cross the blood-brain barrier. This review focuses on the illustration of these different approaches. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

Ultrasound effects on brain-targeting mannosylated liposomes: in vitro and blood-brain barrier transport investigations.

Science.gov (United States)

Zidan, Ahmed S; Aldawsari, Hibah

2015-01-01

Delivering drugs to intracerebral regions can be accomplished by improving the capacity of transport through blood-brain barrier. Using sertraline as model drug for brain targeting, the current study aimed at modifying its liposomal vesicles with mannopyranoside. Box-Behnken design was employed to statistically optimize the ultrasound parameters, namely ultrasound amplitude, time, and temperature, for maximum mannosylation capacity, sertraline entrapment, and surface charge while minimizing vesicular size. Moreover, in vitro blood-brain barrier transport model was established to assess the transendothelial capacity of the optimized mannosylated vesicles. Results showed a dependence of vesicular size, mannosylation capacity, and sertraline entrapment on cavitation and bubble implosion events that were related to ultrasound power amplitude, temperature. However, short ultrasound duration was required to achieve >90% mannosylation with nanosized vesicles (ultrasound parameters of 65°C, 27%, and 59 seconds for ultrasound temperature, amplitude, and time were elucidated to produce 81.1%, 46.6 nm, and 77.6% sertraline entrapment, vesicular size, and mannosylation capacity, respectively. Moreover, the transendothelial ability was significantly increased by 2.5-fold by mannosylation through binding with glucose transporters. Hence, mannosylated liposomes processed by ultrasound could be a promising approach for manufacturing and scale-up of brain-targeting liposomes.

Bioinspired one-dimensional materials for directional liquid transport.

Science.gov (United States)

Ju, Jie; Zheng, Yongmei; Jiang, Lei

2014-08-19

One-dimensional materials (1D) capable of transporting liquid droplets directionally, such as spider silks and cactus spines, have recently been gathering scientists' attention due to their potential applications in microfluidics, textile dyeing, filtration, and smog removal. This remarkable property comes from the arrangement of the micro- and nanostructures on these organisms' surfaces, which have inspired chemists to develop methods to prepare surfaces with similar directional liquid transport ability. In this Account, we report our recent progress in understanding how this directional transport works, as well our advances in the design and fabrication of bioinspired 1D materials capable of transporting liquid droplets directionally. To begin, we first discuss some basic theories on droplet directional movement. Then, we discuss the mechanism of directional transport of water droplets on natural spider silks. Upon contact with water droplets, the spider silk undergoes what is known as a wet-rebuilt, which forms periodic spindle-knots and joints. We found that the resulting gradient of Laplace pressure and surface free energy between the spindle-knots and joints account for the cooperative driving forces to transport water droplets directionally. Next, we discuss the directional transport of water droplets on desert cactus. The integration of multilevel structures of the cactus and the resulting integration of multiple functions together allow the cactus spine to transport water droplets continuously from tip to base. Based on our studies of natural spider silks and cactus spines, we have prepared a series of artificial spider silks (A-SSs) and artificial cactus spines (A-CSs) with various methods. By changing the surface roughness and chemical compositions of the artificial spider silks' spindle-knots, or by introducing stimulus-responsive molecules, such as thermal-responsive and photoresponsive molecules, onto the spindle-knots, we can reversibly manipulate

Developmental changes of l-arginine transport at the blood-brain barrier in rats.

Science.gov (United States)

Tachikawa, Masanori; Hirose, Shirou; Akanuma, Shin-Ichi; Matsuyama, Ryo; Hosoya, Ken-Ichi

2018-05-01

l-Arginine is required for regulating synapse formation/patterning and angiogenesis in the developing brain. We hypothesized that this requirement would be met by increased transporter-mediated supply across the blood-brain barrier (BBB). Thus, the purpose of this work was to test the idea that elevation of blood-to-brain l-arginine transport across the BBB in the postnatal period coincides with up-regulation of cationic acid transporter 1 (CAT1) expression in developing brain capillaries. We found that the apparent brain-to-plasma concentration ratio (Kp, app) of l-arginine after intravenous administration during the first and second postnatal weeks was 2-fold greater than that at the adult stage. Kp, app of l-serine was also increased at the first postnatal week. In contrast, Kp, app of d-mannitol, a passively BBB-permeable molecule, did not change, indicating that increased transport of l-arginine and l-serine is not due to BBB immaturity. Double immunohistochemical staining of CAT1 and a marker protein, glucose transporter 1, revealed that CAT1 was localized on both luminal and abluminal membranes of brain capillary endothelial cells during the developmental and adult stages. A dramatic increase in CAT1 expression in the brain was seen at postnatal day 7 (P7) and day 14 (P14) and the expression subsequently decreased as the brain matured. In accordance with this, intense immunostaining of CAT1 was observed in brain capillaries at P7 and P14. These findings strongly support our hypothesis and suggest that the supply of blood-born l-arginine to the brain via CAT1 at the BBB plays a key role in meeting the elevated demand for l-arginine in postnatal brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain barriers and functional interfaces with sequential appearance of ABC efflux transporters during human development

DEFF Research Database (Denmark)

Møllgård, Kjeld; Dziegielewska, Katarzyna M.; Holst, Camilla B.

2017-01-01

Adult brain is protected from entry of drugs and toxins by specific mechanisms such as ABC (ATP-binding Cassette) efflux transporters. Little is known when these appear in human brain during development. Cellular distribution of three main ABC transporters (ABCC1, ABCG2, ABCB1) was determined...... at blood-brain barriers and interfaces in human embryos and fetuses in first half of gestation. Antibodies against claudin-5 and-11 and antibodies to α-fetoprotein were used to describe morphological and functional aspects of brain barriers. First exchange interfaces to be established, probably at 4...... three transporters. Results provide evidence for sequential establishment of brain exchange interfaces and spatial and temporal timetable for three main ABC transporters in early human brain....

The Gendered Nose and its Lack: “Medieval” Nose-Cutting and its Modern Manifestations

Science.gov (United States)

Skinner, Patricia

2014-01-01

Time magazine’s cover photograph in August 2010 of a noseless Afghan woman beside the emotive strap line, “What happens if we leave Afghanistan,” fuelled debate about the “medieval” practices of the Taliban, whose local commander had instructed her husband to take her nose and ears. Press reports attributed the violence to the Pashtun tradition that a dishonored husband “lost his nose.” This equation of nose-cutting with tradition begs questions not only about the Orientalist lens of the western press when viewing Afghanistan, but also about the assumption that the word “medieval” can function as a label for such practices. A study of medieval nose-cutting suggests that its identification as an “eastern” practice should be challenged. Rather clearer is its connection with patriarchal values of authority and honor: the victims of such punishment have not always been women, but this is nevertheless a gendered punishment of the powerless by the powerful. PMID:24790391

Chitosan Glutamate-Coated Niosomes: A Proposal for Nose-to-Brain Delivery

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Federica Rinaldi

2018-03-01

Full Text Available The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS, while size and morphology were also studied by atomic force microscopy (AFM. Bilayer properties and mucoadhesive behavior were investigated by fluorescence studies and DLS analyses, respectively. Changes in vesicle size and ζ-potential values were shown after addition of chitosan glutamate to niosomes, and when in contact with mucin solution. In particular, interactions with mucin were observed in both drug free and pentamidine loaded niosomes regardless of the presence of the coating. The characteristics of the proposed systems, such as pentamidine entrapment and mucin interaction, show promising results to deliver pentamidine or other possible drugs to the brain via nasal administration.

Electronic Nose Technology and its Applications

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Esmaeil MAHMOUDI

2009-08-01

Full Text Available In the past decade, Electronic Nose instrumentation has generated much interest internationally for its potential to solve a wide variety of problems in fragrance and cosmetics production, food and beverages manufacturing, chemical engineering, environmental monitoring and more recently medical diagnostic, bioprocesses and clinical diagnostic plant diseases. This instrument measure electrical resistance changes generated by adsorption of volatiles to the surface of electro active- polymer coated sensor- unique digital electronic fingerprint of aroma derived from multi-sensor- responses to distinct mixture of microbial volatiles. Major advances in information and gas sensor technology could enhance the diagnostic power of future bio-electronic nose and facilitate global surveillance mode of disease control and management. Several dozen companies are now designed and selling electronic nose units globally for a wide variety of expending markets. The present review includes principles of electronic nose technology, biosensor structure and applications of electronic nose in many fields.

Applications of electronic noses in meat analysis

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Elżbieta GÓRSKA-HORCZYCZAK

2016-01-01

Full Text Available Abstract Electronic noses are devices able to characterize and differentiate the aroma profiles of various food, especially meat and meat products. During recent years e-noses have been widely used in food analysis and proved to provide a fast, simple, non-expensive and non-destructive method of food assessment and quality control. The aim of this study is to summarize the most important features of this analytic tool and to present basic fields and typical areas of e-nose use as well as most commonly used sensor types and patterns for e-nose design. Prospects for the future development of this technique are presented. Methods and research results presented in this manuscript may be a guideline for practical e-nose use.

Beta-endorphin chimeric peptides: Transport through the blood-brain barrier in vivo and cleavage of disulfide linkage by brain

International Nuclear Information System (INIS)

Pardridge, W.M.; Triguero, D.; Buciak, J.L.

1990-01-01

Water soluble peptides are normally not transported through the blood-brain barrier (BBB). Chimeric peptides may be transportable through the BBB and are formed by the covalent coupling of a nontransportable peptide to a transportable peptide vector, e.g. cationized albumin, using disulfide-based coupling reagents such as N-succinimidyl 3-[2-pyridyldithio(propionate)] (SPDP). The transcytosis of peptide into brain parenchyma, as opposed to vascular sequestration of blood-borne peptide, was quantified using an internal carotid artery perfusion/capillary depletion method. It is shown that [125I]beta-endorphin is not transported through the BBB, but is rapidly cleaved to free [125I] tyrosine via capillary peptidase. Therefore, chimeric peptide was prepared using [125I] [D-Ala2]beta-endorphin (DABE), owing to the resistance of this analogue to peptidase degradation. The [125I] DABE-cationized albumin chimeric peptide is shown to enter brain parenchyma at a rate comparable to that reported previously for unconjugated cationized albumin. When the [125I] DABE-cationized albumin chimeric peptide was incubated with rat brain homogenate at 37 C, the free [125I] DABE was liberated from the cationized albumin conjugate prior to its subsequent degradation into free [125I] tyrosine. Approximately 50% of the chimeric peptide was cleaved within 60 sec of incubation at 37 C. These studies demonstrate that (1) [125I]beta-endorphin is not transported through the BBB in its unconjugated form, (2) a [125I] DABE-cationized albumin chimeric peptide is transported through the BBB into brain parenchyma at a rate comparable to the unconjugated cationized albumin, and (3) brain contains the necessary disulfide reductases for rapid cleavage of the chimeric peptide into free beta-endorphin and this cleavage occurs before degradation of the [125I] DABE into [125I] tyrosine

Beta-endorphin chimeric peptides: Transport through the blood-brain barrier in vivo and cleavage of disulfide linkage by brain

Energy Technology Data Exchange (ETDEWEB)

Pardridge, W.M.; Triguero, D.; Buciak, J.L. (UCLA School of Medicine (USA))

1990-02-01

Water soluble peptides are normally not transported through the blood-brain barrier (BBB). Chimeric peptides may be transportable through the BBB and are formed by the covalent coupling of a nontransportable peptide to a transportable peptide vector, e.g. cationized albumin, using disulfide-based coupling reagents such as N-succinimidyl 3-(2-pyridyldithio(propionate)) (SPDP). The transcytosis of peptide into brain parenchyma, as opposed to vascular sequestration of blood-borne peptide, was quantified using an internal carotid artery perfusion/capillary depletion method. It is shown that (125I)beta-endorphin is not transported through the BBB, but is rapidly cleaved to free (125I) tyrosine via capillary peptidase. Therefore, chimeric peptide was prepared using (125I) (D-Ala2)beta-endorphin (DABE), owing to the resistance of this analogue to peptidase degradation. The (125I) DABE-cationized albumin chimeric peptide is shown to enter brain parenchyma at a rate comparable to that reported previously for unconjugated cationized albumin. When the (125I) DABE-cationized albumin chimeric peptide was incubated with rat brain homogenate at 37 C, the free (125I) DABE was liberated from the cationized albumin conjugate prior to its subsequent degradation into free (125I) tyrosine. Approximately 50% of the chimeric peptide was cleaved within 60 sec of incubation at 37 C. These studies demonstrate that (1) (125I)beta-endorphin is not transported through the BBB in its unconjugated form, (2) a (125I) DABE-cationized albumin chimeric peptide is transported through the BBB into brain parenchyma at a rate comparable to the unconjugated cationized albumin, and (3) brain contains the necessary disulfide reductases for rapid cleavage of the chimeric peptide into free beta-endorphin and this cleavage occurs before degradation of the (125I) DABE into (125I) tyrosine.

Selective binding of 2-[125I]iodo-nisoxetine to norepinephrine transporters in the brain

International Nuclear Information System (INIS)

Kung, M.-P.; Choi, Seok-Rye; Hou, Catherine; Zhuang, Z.-P.; Foulon, Catherine; Kung, Hank F.

2004-01-01

A radioiodinated ligand, (R)-N-methyl-(2-[ 125 I]iodo-phenoxy)-3-phenylpropylamine, [ 125 I]2-INXT, targeting norepinephrine transporters (NET), was successfully prepared. A no-carrier-added product, [ 125 I]2-INXT, displayed a saturable binding with a high affinity (K d =0.06 nM) in the homogenates prepared from rat cortical tissues as well as from LLC-PK 1 cells expressing NET. A relatively low number of binding sties (B max =55 fmol/mg protein) measured with [ 125 I]2-INXT in rat cortical homogenates is consistent with the value reported for a known NET ligand, [ 3 H]nisoxetine. Competition studies with various compounds on [ 125 I]2-INXT binding clearly confirmed the pharmacological specificity and selectivity for NET binding sites. Following a tail-vein injection of [ 125 I]2-INXT in rats, a good initial brain uptake was observed (0.56% dose at 2 min) followed by a slow washout from the brain (0.2% remained at 3 hours post-injection). The hypothalamus (a NET-rich region) to striatum (a region devoid of NET) ratio was 1.5 at 3 hours post-i.v. injection. Pretreatment of rats with nisoxetine significantly inhibited the uptake of [ 125 I]2-INXT (70-100% inhibition) in locus coeruleus, hypothalamus and raphe nuclei, regions known to have a high density of NET; whereas escitalopram, a serotonin transporter ligand, did not show a similar effect. Ex vivo autoradiography of rat brain sections of [ 125 I]2-INXT (at 3 hours after an i.v. injection) displayed an excellent regional brain localization pattern corroborated to the specific NET distribution in the brain. The specific brain localization was significantly reduced by a dose of nisoxetine pretreatment. Taken together, the data suggest that [ 123 I]2-INXT may be useful for mapping NET binding sites in the brain

Navigating a 2D Virtual World using Direct Brain Stimulation

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Darby M. Losey

2016-11-01

Full Text Available Can the human brain learn to interpret inputs from a virtual world delivered directly through brain stimulation? We answer this question by describing the first demonstration of humans playing a computer game utilizing only direct brain stimulation and no other sensory inputs. The demonstration also provides the first instance of artificial sensory information, in this case depth, being delivered directly to the human brain through noninvasive methods. Our approach utilizes transcranial magnetic stimulation (TMS of the human visual cortex to convey binary information about obstacles in a virtual maze. At certain intensities, TMS elicits visual percepts known as phosphenes, which transmits information to the subject about their current location within the maze. Using this computer-brain interface (CBI, five subjects successfully navigated an average of 92% of all the steps in a variety of virtual maze worlds. They also became more accurate in solving the task over time. These results suggest that humans can learn to utilize information delivered directly and noninvasively to their brains to solve tasks that cannot be solved using their natural senses, opening the door to human sensory augmentation and novel modes of human-computer interaction.

Efflux of drugs and solutes from brain: the interactive roles of diffusional transcapillary transport, bulk flow and capillary transporters.

Science.gov (United States)

Groothuis, Dennis R; Vavra, Michael W; Schlageter, Kurt E; Kang, Eric W-Y; Itskovich, Andrea C; Hertzler, Shannon; Allen, Cathleen V; Lipton, Howard L

2007-01-01

We examined the roles of diffusion, convection and capillary transporters in solute removal from extracellular space (ECS) of the brain. Radiolabeled solutes (eight with passive distribution and four with capillary or cell transporters) were injected into the brains of rats (n=497) and multiple-time point experiments measured the amount remaining in brain as a function of time. For passively distributed compounds, there was a relationship between lipid:water solubility and total brain efflux:diffusional efflux, which dominated when k(p), the transcapillary efflux rate constant, was >10(0) h(-1); when 10(-1)transporters. The total efflux rate constant, k(eff), was the sum of a passive component (k(p)=0.0018 h(-1)), a convective component (k(csf)=0.2 h(-1)), and a variable, concentration-dependent component (k(x)=0 to 0.45 h(-1)). Compounds with cell membrane transporters had longer clearance half times as did an oligonucleotide, which interacted with cell surface receptors. Manipulation of physiologic state (n=35) did not affect efflux, but sucrose efflux half time was longer with pentobarbital anesthesia (24 h) than with no anesthesia or ketamine-xylazine anesthesia (2 to 3 h). These results show that solute clearance from normal brain ECS may involve multiple physiologic pathways, may be affected by anesthesia, and suggests that convection-mediated efflux may be manipulated to increase or decrease drug clearance from brain.

Close-To-Practice Assessment Of Meat Freshness With Metal Oxide Sensor Microarray Electronic Nose

International Nuclear Information System (INIS)

Musatov, V. Yu.; Sysoev, V. V.; Sommer, M.; Kiselev, I.

2009-01-01

In this report we estimate the ability of KAMINA e-nose, based on a metal oxide sensor (MOS) microarray and Linear Discriminant Analysis (LDA) pattern recognition, to evaluate meat freshness. The received results show that, 1) one or two exposures of standard meat samples to the e-nose are enough for the instrument to recognize the fresh meat prepared by the same supplier with 100% probability; 2) the meat samples of two kinds, stored at 4 deg. C and 25 deg. C, are mutually recognized at early stages of decay with the help of the LDA model built independently under the e-nose training to each kind of meat; 3) the 3-4 training cycles of exposure to meat from different suppliers are necessary for the e-nose to build a reliable LDA model accounting for the supplier factor. This study approves that the MOS e-nose is ready to be currently utilised in food industry for evaluation of product freshness. The e-nose performance is characterized by low training cost, a confident recognition power of various product decay conditions and easy adjustment to changing conditions.

Electronic Nose Technology to Measure Soil Microbial Activity and Classify Soil Metabolic Status

OpenAIRE

Fabrizio De Cesare; Elena Di Mattia; Simone Pantalei; Emiliano Zampetti; Vittorio Vinciguerra; Antonella Macagnano

2011-01-01

The electronic nose (E-nose) is a sensing technology that has been widely used to monitor environments in the last decade. In the present study, the capability of an E-nose, in combination with biochemical and microbiological techniques, of both detecting the microbial activity and estimating the metabolic status of soil ecosystems, was tested by measuring on one side respiration, enzyme activities and growth of bacteria in natural but simplified soil ecosystems over 23 days of incubation thr...

Distribution of vesicular glutamate transporters in the human brain

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Erika eVigneault

2015-03-01

Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

Altered neurocircuitry in the dopamine transporter knockout mouse brain.

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Xiaowei Zhang

2010-07-01

Full Text Available The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI. Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn(2+ into the prefrontal cortex indicated that DAT KO mice have a truncated Mn(2+ distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn(2+ transport into more posterior midbrain nuclei and contralateral

Estimating direction in brain-behavior interactions: Proactive and reactive brain states in driving.

Science.gov (United States)

Garcia, Javier O; Brooks, Justin; Kerick, Scott; Johnson, Tony; Mullen, Tim R; Vettel, Jean M

2017-04-15

Conventional neuroimaging analyses have ascribed function to particular brain regions, exploiting the power of the subtraction technique in fMRI and event-related potential analyses in EEG. Moving beyond this convention, many researchers have begun exploring network-based neurodynamics and coordination between brain regions as a function of behavioral parameters or environmental statistics; however, most approaches average evoked activity across the experimental session to study task-dependent networks. Here, we examined on-going oscillatory activity as measured with EEG and use a methodology to estimate directionality in brain-behavior interactions. After source reconstruction, activity within specific frequency bands (delta: 2-3Hz; theta: 4-7Hz; alpha: 8-12Hz; beta: 13-25Hz) in a priori regions of interest was linked to continuous behavioral measurements, and we used a predictive filtering scheme to estimate the asymmetry between brain-to-behavior and behavior-to-brain prediction using a variant of Granger causality. We applied this approach to a simulated driving task and examined directed relationships between brain activity and continuous driving performance (steering behavior or vehicle heading error). Our results indicated that two neuro-behavioral states may be explored with this methodology: a Proactive brain state that actively plans the response to the sensory information and is characterized by delta-beta activity, and a Reactive brain state that processes incoming information and reacts to environmental statistics primarily within the alpha band. Published by Elsevier Inc.

Comparative investigations of anatomy and physiology in mammalian noses (Homo sapiens--Artiodactyla).

Science.gov (United States)

Grützenmacher, S; Robinson, D M; Sevecke, J; Mlynski, G; Beule, A G

2011-03-01

Knowledge of airflow in animal noses is sparse. Such knowledge could be important for selection of animal models used in environmental studies. From the phylogenetic and ontogenetic point of view, a comparison between the animal and human nose is interesting. Nose models of 5 even-toed ungulate species (he-goat, sheep, cow, roebuck, wild boar) and two humans (new born infant and adult) were examined. Anatomical and physiological features of the nasal cavities of all species were compared. All models were rinsed with water and the flow was visualized for observation. Geometric and rhinoresistometric measurements were then performed. Even-toed ungulates have two turbinates directly in the main part of the nasal airflow (respiratory turbinates) and a different number of turbinates in a so-called dead space of the nasal airflow above the nasopharyngeal duct (ethmoidal turbinates). The latter correspond with the upper and middle turbinate in analogy to the human nose. Respiratory turbinates of even-toed ungulates insert immediately behind the external nasal ostium. Thus, the whole nasal cavity acts as a functional area with the exception of a small area acting as dead space only detectable in ruminants, possibly indicating a small evolutionary progress from suinae to bovidae. The shape of the animal nasal cavity is stretched and flat. The airflow runs nearly completely turbulent through the nose. The nasal cavity in the adult human is relatively short and high. The area between the external nasal ostium and the head of the inferior turbinate is called inflow area. It distributes the airflow over the whole nasal cross section and generates a turbulent flow. So the airflow is prepared to contact the mucosa in the functional area (turbinate area). The morphology of the inflow area is approximately formed by the shape of the external nose. The nasal cavity of a newborn child is also stretched and flat and more similar to the nasal shape of the investigated animals. The

Simultaneous measurement of glucose blood–brain transport constants and metabolic rate in rat brain using in-vivo 1H MRS

Science.gov (United States)

Du, Fei; Zhang, Yi; Zhu, Xiao-Hong; Chen, Wei

2012-01-01

Cerebral glucose consumption and glucose transport across the blood–brain barrier are crucial to brain function since glucose is the major energy fuel for supporting intense electrophysiological activity associated with neuronal firing and signaling. Therefore, the development of noninvasive methods to measure the cerebral metabolic rate of glucose (CMRglc) and glucose transport constants (KT: half-saturation constant; Tmax: maximum transport rate) are of importance for understanding glucose transport mechanism and neuroenergetics under various physiological and pathological conditions. In this study, a novel approach able to simultaneously measure CMRglc, KT, and Tmax via monitoring the dynamic glucose concentration changes in the brain tissue using in-vivo 1H magnetic resonance spectroscopy (MRS) and in plasma after a brief glucose infusion was proposed and tested using an animal model. The values of CMRglc, Tmax, and KT were determined to be 0.44±0.17 μmol/g per minute, 1.35±0.47 μmol/g per minute, and 13.4±6.8 mmol/L in the rat brain anesthetized with 2% isoflurane. The Monte-Carlo simulations suggest that the measurements of CMRglc and Tmax are more reliable than that of KT. The overall results indicate that the new approach is robust and reliable for in-vivo measurements of both brain glucose metabolic rate and transport constants, and has potential for human application. PMID:22714049

Qualification Approach for the CMC Nose Cap of X-38

Science.gov (United States)

Weihs, H.; Gülhan, A.

2002-01-01

In October 2001 the flight hardware of the TPS nose assembly of X-38 has been installed at the main structure of the X-38 V201 vehicle at NASA's Johnson Space Center, Houston Texas. X-38 is a test vehicle for the planned Crew Return Vehicle CRV for the International Space Station ISS. Currently the flight of the X-38 is scheduled for 2005. Besides the Body flaps (MAN-T) and the nose skirt system (ASTRIUM, MAN-T) the nose cap system is one of the essential hot structure components that were developed within Germany's national TETRA (Technologies for future space transportation systems) programme. The integration of the hardware was an important milestone for the nose cap development which started approx. 5 years ago. DLR-Stuttgart is responsible for the design and manufacturing of the CMC based nose cap system, which has to withstand the extreme thermal loads during re-entry which will induce a maximum temperature up to 1750 °C on the surface of the cap. Thus, the shell of the cap system is designed and manufactured using DLR's C/C-SiC material which is a special kind of carbon based ceramic matrix composite (CMC) material produced via the in house liquid silicon infiltration process of DLR. This material has demonstrated its good temperature resistance during FOTON and EXPRESS re-entry capsule missions. Besides the design and manufacturing of the nose cap system, the qualification approach was an important effort of the development work. Missing a test facility which is able to simulate all loading conditions from lift off to re-entry and landing, is was necessary to separate the loads and to use different test facilities. Considering the limitations of the facilities, the budget and time constraints, an optimized test philosophy has been established. The goal was to use a full scale qualification unit including all TPS components of the nose area for most of the tests. These were the simulation of ascent loads given by the shuttle requirements and descent loads

Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

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Murrin L Charles

2011-03-01

Full Text Available Abstract Background Methamphetamine (METH, an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial cell activation. Here we hypothesized that METH-induced interference of glucose uptake and transport at the endothelium can disrupt the energy requirement of the blood-brain barrier (BBB function and integrity. We undertake this study because there is no report of METH effects on glucose uptake and transport across the blood-brain barrier (BBB to date. Results In this study, we demonstrate that METH-induced disruption of glucose uptake by endothelium lead to BBB dysfunction. Our data indicate that a low concentration of METH (20 μM increased the expression of glucose transporter protein-1 (GLUT1 in primary human brain endothelial cell (hBEC, main component of BBB without affecting the glucose uptake. A high concentration of 200 μM of METH decreased both the glucose uptake and GLUT1 protein levels in hBEC culture. Transcription process appeared to regulate the changes in METH-induced GLUT1 expression. METH-induced decrease in GLUT1 protein level was associated with reduction in BBB tight junction protein occludin and zonula occludens-1. Functional assessment of the trans-endothelial electrical resistance of the cell monolayers and permeability of dye tracers in animal model validated the pharmacokinetics and molecular findings that inhibition of glucose uptake by GLUT1 inhibitor cytochalasin B (CB aggravated the METH-induced disruption of the BBB integrity. Application of acetyl-L-carnitine suppressed the effects of METH on glucose uptake and BBB function. Conclusion Our findings suggest that impairment of GLUT1 at the brain endothelium by METH may contribute to energy-associated disruption of tight junction assembly and loss of BBB integrity.

Regional amino acid transport into brain during diabetes: Effect of plasma amino acids

International Nuclear Information System (INIS)

Mans, A.M.; DeJoseph, M.R.; Davis, D.W.; Hawkins, R.A.

1987-01-01

Transport of phenylalanine and lysine into the brain was measured in 4-wk streptozotocin-diabetic rats to assess the effect on the neutral and basic amino acid transport systems at the blood-brain barrier. Amino acid concentrations in plasma and brain were also measured. Regional permeability-times-surface area (PS) products and influx were determined using a continuous infusion method and quantitative autoradiography. The PS of phenylalanine was decreased by an average of 40% throughout the entire brain. Influx was depressed by 35%. The PS of lysine was increased by an average of 44%, but the influx was decreased by 27%. Several plasma neutral amino acids (branched chain) were increased, whereas all basic amino acids were decreased. Brain tryptophan, phenylalanine, tyrosine, methionine, and lysine contents were markedly decreased. The transport changes were almost entirely accounted for by the alterations in the concentrations of the plasma amino acids that compete for the neutral and basic amino acid carriers. The reduced influx could be responsible for the low brain content of some essential amino acids, with possibly deleterious consequences for brain functions

Applications and Advances in Electronic-Nose Technologies

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Manuela Baietto

2009-06-01

Full Text Available Electronic-nose devices have received considerable attention in the field of sensor technology during the past twenty years, largely due to the discovery of numerous applications derived from research in diverse fields of applied sciences. Recent applications of electronic nose technologies have come through advances in sensor design, material improvements, software innovations and progress in microcircuitry design and systems integration. The invention of many new e-nose sensor types and arrays, based on different detection principles and mechanisms, is closely correlated with the expansion of new applications. Electronic noses have provided a plethora of benefits to a variety of commercial industries, including the agricultural, biomedical, cosmetics, environmental, food, manufacturing, military, pharmaceutical, regulatory, and various scientific research fields. Advances have improved product attributes, uniformity, and consistency as a result of increases in quality control capabilities afforded by electronic-nose monitoring of all phases of industrial manufacturing processes. This paper is a review of the major electronic-nose technologies, developed since this specialized field was born and became prominent in the mid 1980s, and a summarization of some of the more important and useful applications that have been of greatest benefit to man.

Prediction of brain target site concentrations on the basis of CSF PK : impact of mechanisms of blood-to-brain transport and within brain distribution

OpenAIRE

Westerhout, J.

2014-01-01

In the development of drugs for the treatment of central nervous system (CNS) disorders, the prediction of human CNS drug action is a big challenge. Direct measurement of brain extracellular fluid (brainECF) concentrations is highly restricted in human. Therefore, unbound drug concentrations in human cerebrospinal fluid (CSF) are used as a surrogate for human brainECF concentrations. Due to qualitative and quantitative differences in processes that govern the pharmacokinetics (PK) of drugs in...

Different alterations in brain functional networks according to direct and indirect topological connections in patients with schizophrenia.

Science.gov (United States)

Park, Chang-Hyun; Lee, Seungyup; Kim, Taewon; Won, Wang Yeon; Lee, Kyoung-Uk

2017-10-01

Schizophrenia displays connectivity deficits in the brain, but the literature has shown inconsistent findings about alterations in global efficiency of brain functional networks. We supposed that such inconsistency at the whole brain level may be due to a mixture of different portions of global efficiency at sub-brain levels. Accordingly, we considered measuring portions of global efficiency in two aspects: spatial portions by considering sub-brain networks and topological portions by considering contributions to global efficiency according to direct and indirect topological connections. We proposed adjacency and indirect adjacency as new network parameters attributable to direct and indirect topological connections, respectively, and applied them to graph-theoretical analysis of brain functional networks constructed from resting state fMRI data of 22 patients with schizophrenia and 22 healthy controls. Group differences in the network parameters were observed not for whole brain and hemispheric networks, but for regional networks. Alterations in adjacency and indirect adjacency were in opposite directions, such that adjacency increased, but indirect adjacency decreased in patients with schizophrenia. Furthermore, over connections in frontal and parietal regions, increased adjacency was associated with more severe negative symptoms, while decreased adjacency was associated with more severe positive symptoms of schizophrenia. This finding indicates that connectivity deficits associated with positive and negative symptoms of schizophrenia may involve topologically different paths in the brain. In patients with schizophrenia, although changes in global efficiency may not be clearly shown, different alterations in brain functional networks according to direct and indirect topological connections could be revealed at the regional level. Copyright © 2017 Elsevier B.V. All rights reserved.

Review of electronic-nose technologies and algorithms to detect hazardous chemicals in the environment

Science.gov (United States)

Alphus D. Wilson

2012-01-01

Novel mobile electronic-nose (e-nose) devices and algorithms capable of real-time detection of industrial and municipal pollutants, released from point-sources, recently have been developed by scientists worldwide that are useful for monitoring specific environmental-pollutant levels for enforcement and implementation of effective pollution-abatement programs. E-nose...

Bioavailability and transport of peptides and peptide drugs into the brain.

Science.gov (United States)

Egleton, R D; Davis, T P

1997-01-01

Rational drug design and the targeting of specific organs has become a reality in modern drug development, with the emergence of molecular biology and receptor chemistry as powerful tools for the pharmacologist. A greater understanding of peptide function as one of the major extracellular message systems has made neuropeptides an important target in neuropharmaceutical drug design. The major obstacle to targeting the brain with therapeutics is the presence of the blood-brain barrier (BBB), which controls the concentration and entry of solutes into the central nervous system. Peptides are generally polar in nature, do not easily cross the blood-brain barrier by diffusion, and except for a small number do not have specific transport systems. Peptides can also undergo metabolic deactivation by peptidases of the blood, brain and the endothelial cells that comprise the BBB. In this review, we discuss a number of the recent strategies which have been used to promote peptide stability and peptide entry into the brain. In addition, we approach the subject of targeting specific transport systems that can be found on the brain endothelial cells, and describe the limitations of the methodologies that are currently used to study brain entry of neuropharmaceuticals.

Simultaneous measurement of glucose transport and utilization in the human brain

OpenAIRE

Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.; Öz, Gülin

2011-01-01

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose tra...

Test of the 'glymphatic' hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma.

Science.gov (United States)

Smith, Alex J; Yao, Xiaoming; Dix, James A; Jin, Byung-Ju; Verkman, Alan S

2017-08-21

Transport of solutes through brain involves diffusion and convection. The importance of convective flow in the subarachnoid and paravascular spaces has long been recognized; a recently proposed 'glymphatic' clearance mechanism additionally suggests that aquaporin-4 (AQP4) water channels facilitate convective transport through brain parenchyma. Here, the major experimental underpinnings of the glymphatic mechanism were re-examined by measurements of solute movement in mouse brain following intracisternal or intraparenchymal solute injection. We found that: (i) transport of fluorescent dextrans in brain parenchyma depended on dextran size in a manner consistent with diffusive rather than convective transport; (ii) transport of dextrans in the parenchymal extracellular space, measured by 2-photon fluorescence recovery after photobleaching, was not affected just after cardiorespiratory arrest; and (iii) Aqp4 gene deletion did not impair transport of fluorescent solutes from sub-arachnoid space to brain in mice or rats. Our results do not support the proposed glymphatic mechanism of convective solute transport in brain parenchyma.

Serotonin transporter and dopamine transporter imaging in the canine brain

International Nuclear Information System (INIS)

Peremans, Kathelijne; Goethals, Ingeborg; De Vos, Filip; Dobbeleir, A.; Ham, Hamphrey; Van Bree, Henri; Heeringen, Cees van; Audenaert, Kurt

2006-01-01

The serotonergic and dopaminergic systems are involved in a wide range of emotional and behavioral aspects of animals and humans and are involved in many neuropsychiatric disorders. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are designed to block the 5-HT transporter (SERT), thereby increasing the available 5-HT in the brain. Functional imaging with specific SERT and dopamine transporter (DAT) ligands contributes to the study of the SSRI-transporter interaction. First, we evaluated the feasibility of a canine model in the study of the SERT and DAT with the radioligands [ 123 I]-β-CIT and [ 123 I]-FP-CIT as well as single-photon emission computed tomography imaging. Second, we studied the effect of SSRIs (sertraline, citalopram and escitalopram) on the SERT and DAT in two dogs. The position of the canine model in the study of the SERT and DAT is discussed and compared with other animal models

PPAR-α, a lipid-sensing transcription factor, regulates blood-brain barrier efflux transporter expression.

Science.gov (United States)

More, Vijay R; Campos, Christopher R; Evans, Rebecca A; Oliver, Keith D; Chan, Gary Ny; Miller, David S; Cannon, Ronald E

2017-04-01

Lipid sensor peroxisome proliferator-activated receptor alpha (PPAR- α) is the master regulator of lipid metabolism. Dietary release of endogenous free fatty acids, fibrates, and certain persistent environmental pollutants, e.g. perfluoroalkyl fire-fighting foam components, are peroxisome proliferator-activated receptor alpha ligands. Here, we define a role for peroxisome proliferator-activated receptor alpha in regulating the expression of three ATP-driven drug efflux transporters at the rat and mouse blood-brain barriers: P-glycoprotein (Abcb1), breast cancer resistance protein (Bcrp/Abcg2), and multidrug resistance-associated protein 2 (Mrp2/Abcc2). Exposing isolated rat brain capillaries to linoleic acid, clofibrate, or PKAs increased the transport activity and protein expression of the three ABC transporters. These effects were blocked by the PPAR- α antagonist, GW6471. Dosing rats with 20 mg/kg or 200 mg/kg of clofibrate decreased the brain accumulation of the P-glycoprotein substrate, verapamil, by 50% (in situ brain perfusion; effects blocked by GW6471) and increased P-glycoprotein expression and activity in capillaries ex vivo. Fasting C57Bl/6 wild-type mice for 24 h increased both serum lipids and brain capillary P-glycoprotein transport activity. Fasting did not alter P-glycoprotein activity in PPAR- α knockout mice. These results indicate that hyperlipidemia, lipid-lowering fibrates and exposure to certain fire-fighting foam components activate blood-brain barrier peroxisome proliferator-activated receptor alpha, increase drug efflux transporter expression and reduce drug delivery to the brain.

Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior

Directory of Open Access Journals (Sweden)

Samantha J. Hindle

2017-10-01

Full Text Available Summary: Central nervous system (CNS chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB. Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice. Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. : Hindle et al. shed light on the curious finding that some drugs cause behavioral side-effects despite negligible access into the brain. These authors propose a unifying hypothesis that links blood-brain barrier drug transporter function and brain access of circulating steroids to common CNS adverse drug responses. Keywords: drug side effect mechanisms, central nervous system, blood brain barrier, behavior, toxicology, drug transporters, endobiotics, steroid hormones

An improved approach to identify irradiated spices using electronic nose, FTIR, and EPR spectroscopy.

Science.gov (United States)

Sanyal, Bhaskar; Ahn, Jae-Jun; Maeng, Jeong-Hwan; Kyung, Hyun-Kyu; Lim, Ha-Kyeong; Sharma, Arun; Kwon, Joong-Ho

2014-09-01

Changes in cumin and chili powder from India resulting from electron-beam irradiation were investigated using 3 analytical methods: electronic nose (E-nose), Fourier transform infrared (FTIR) spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy. The spices had been exposed to 6 to 14 kGy doses recommended for microbial decontamination. E-nose measured a clear difference in flavor patterns of the irradiated spices in comparison with the nonirradiated samples. Principal component analysis further showed a dose-dependent variation. FTIR spectra of the samples showed strong absorption bands at 3425, 3007 to 2854, and 1746 cm(-1). However, both nonirradiated and irradiated spice samples had comparable patterns without any noteworthy changes in functional groups. EPR spectroscopy of the irradiated samples showed a radiation-specific triplet signal at g = 2.006 with a hyper-fine coupling constant of 3 mT confirming the results obtained with the E-nose technique. Thus, E-nose was found to be a potential tool to identify irradiated spices. © 2014 Institute of Food Technologists®

Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma

DEFF Research Database (Denmark)

Johnsen, Kasper B.; Burkhart, Annette; Melander, Fredrik

2017-01-01

Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibi...... cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain....... investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does...... not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased...

On trans-parenchymal transport after blood brain barrier opening: pump-diffuse-pump hypothesis

Science.gov (United States)

Postnov, D. E.; Postnikov, E. B.; Karavaev, A. S.; Glushkovskaya-Semyachkina, O. V.

2018-04-01

Transparenchymal transport attracted the attention of many research groups after the discovery of glymphatic mechanism for the brain drainage in 2012. While the main facts of rapid transport of substances across the parenchyma are well established experimentally, specific mechanisms that drive this drainage are just hypothezised but not proved yed. Moreover, the number of modeling studies show that the pulse wave powered mechanism is unlikely able to perform pumping as suggested. Thus, the problem is still open. In addition, new data obtained under the conditions of intensionally opened blood brain barrier shows the presence of equally fast transport in opposite durection. In our study we investigate the possible physical mechanisms for rapid transport of substances after the opening of blood-brain barrier under the conditions of zero net flow.

Facilitated transport of glucose from blood to brain in man and the effect of moderate hypoglycaemia on cerebral glucose utilization

International Nuclear Information System (INIS)

Blomqvist, G.; Widen, L.; Hellstrand, E.; Gutniak, M.; Grill, V.

1991-01-01

The effect of steady-state moderate hypoglycaemia on human brain homeostasis has been studied with positron emission tomography using D-glucose 11 C(ul) as tracer. To rule out any effects of insulin, the plasma insulin concentration was maintained at the same level under normo- and hypoglycaemic conditions. Reduction of blood glucose by 55% increased the glucose clearance through the blood-brain barrier by 50% and reduced brain glucose consumption by 40%. Blood flow was not affected. The results are consistent with facilitated transport of glucose from blood to brain in humans. The maximal transport rate of glucose from blood to brain was found to be 62±19 (mean±SEM) μmol hg -1 min -1 , and the half-saturation constant was found to be 4.1±3.2 mM. (orig.)

21 CFR 868.6225 - Nose clip.

Science.gov (United States)

2010-04-01

... ANESTHESIOLOGY DEVICES Miscellaneous § 868.6225 Nose clip. (a) Identification. A nose clip is a device intended to close a patient's external nares (nostrils) during diagnostic or therapeutic procedures. (b... from the current good manufacturing practice requirements of the quality system regulation in part 820...

Prediction of brain target site concentrations on the basis of CSF PK : impact of mechanisms of blood-to-brain transport and within brain distribution

NARCIS (Netherlands)

Westerhout, J.

2014-01-01

In the development of drugs for the treatment of central nervous system (CNS) disorders, the prediction of human CNS drug action is a big challenge. Direct measurement of brain extracellular fluid (brainECF) concentrations is highly restricted in human. Therefore, unbound drug concentrations in

Early Decline in Glucose Transport and Metabolism Precedes Shift to Ketogenic System in Female Aging and Alzheimer's Mouse Brain: Implication for Bioenergetic Intervention

Science.gov (United States)

Ding, Fan; Yao, Jia; Rettberg, Jamaica R.; Chen, Shuhua; Brinton, Roberta Diaz

2013-01-01

We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3–15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6–9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention.

Science.gov (United States)

Ding, Fan; Yao, Jia; Rettberg, Jamaica R; Chen, Shuhua; Brinton, Roberta Diaz

2013-01-01

We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

Electronic Nose and Electronic Tongue

Science.gov (United States)

Bhattacharyya, Nabarun; Bandhopadhyay, Rajib

Human beings have five senses, namely, vision, hearing, touch, smell and taste. The sensors for vision, hearing and touch have been developed for several years. The need for sensors capable of mimicking the senses of smell and taste have been felt only recently in food industry, environmental monitoring and several industrial applications. In the ever-widening horizon of frontier research in the field of electronics and advanced computing, emergence of electronic nose (E-Nose) and electronic tongue (E-Tongue) have been drawing attention of scientists and technologists for more than a decade. By intelligent integration of multitudes of technologies like chemometrics, microelectronics and advanced soft computing, human olfaction has been successfully mimicked by such new techniques called machine olfaction (Pearce et al. 2002). But the very essence of such research and development efforts has centered on development of customized electronic nose and electronic tongue solutions specific to individual applications. In fact, research trends as of date clearly points to the fact that a machine olfaction system as versatile, universal and broadband as human nose and human tongue may not be feasible in the decades to come. But application specific solutions may definitely be demonstrated and commercialized by modulation in sensor design and fine-tuning the soft computing solutions. This chapter deals with theory, developments of E-Nose and E-Tongue technology and their applications. Also a succinct account of future trends of R&D efforts in this field with an objective of establishing co-relation between machine olfaction and human perception has been included.

Serotonin transporter and dopamine transporter imaging in the canine brain

Energy Technology Data Exchange (ETDEWEB)

Peremans, Kathelijne [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Goethals, Ingeborg [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); De Vos, Filip [Laboratory of Radiopharmacy, Pharmaceutical Sciences, Ghent University, B-9000 Ghent (Belgium); Dobbeleir, A. [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Ham, Hamphrey [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); Van Bree, Henri [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Heeringen, Cees van [Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium); Audenaert, Kurt [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium) and Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium)]. E-mail: kurt.audenaert@ugent.be

2006-10-15

The serotonergic and dopaminergic systems are involved in a wide range of emotional and behavioral aspects of animals and humans and are involved in many neuropsychiatric disorders. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are designed to block the 5-HT transporter (SERT), thereby increasing the available 5-HT in the brain. Functional imaging with specific SERT and dopamine transporter (DAT) ligands contributes to the study of the SSRI-transporter interaction. First, we evaluated the feasibility of a canine model in the study of the SERT and DAT with the radioligands [{sup 123}I]-{beta}-CIT and [{sup 123}I]-FP-CIT as well as single-photon emission computed tomography imaging. Second, we studied the effect of SSRIs (sertraline, citalopram and escitalopram) on the SERT and DAT in two dogs. The position of the canine model in the study of the SERT and DAT is discussed and compared with other animal models.

Whisker and Nose Tactile Sense Guide Rat Behavior in a Skilled Reaching Task

Directory of Open Access Journals (Sweden)

Pierantonio Parmiani

2018-02-01

Full Text Available Skilled reaching is a complex movement in which a forelimb is extended to grasp food for eating. Video-recordings analysis of control rats enables us to distinguish several components of skilled reaching: Orient, approaching the front wall of the reaching box and poking the nose into the slot to locate the food pellet; Transport, advancing the forelimb through the slot to reach-grasp the pellet; and Withdrawal of the grasped food to eat. Although food location and skilled reaching is guided by olfaction, the importance of whisker/nose tactile sense in rats suggests that this too could play a role in reaching behavior. To test this hypothesis, we studied skilled reaching in rats trained in a single-pellet reaching task before and after bilateral whisker trimming and bilateral infraorbital nerve (ION severing. During the task, bilaterally trimmed rats showed impaired Orient with respect to controls. Specifically, they detected the presence of the wall by hitting it with their nose (rather than their whiskers, and then located the slot through repetitive nose touches. The number of nose touches preceding poking was significantly higher in comparison to controls. On the other hand, macrovibrissae trimming resulted in no change in reaching/grasping or withdrawal components of skilled reaching. Bilaterally ION-severed rats, displayed a marked change in the structure of their skilled reaching. With respect to controls, in ION-severed rats: (a approaches to the front wall were significantly reduced at 3–5 and 6–8 days; (b nose pokes were significantly reduced at 3–5 days, and the slot was only located after many repetitive nose touches; (c the reaching-grasping-retracting movement never appeared at 3–5 days; (d explorative paw movements, equal to zero in controls, reached significance at 9–11 days; and (e the restored reaching-grasping-retracting sequence was globally slower than in controls, but the success rate was the same. These findings

Electronic nose in edible insects area

Directory of Open Access Journals (Sweden)

Martin Adámek

2017-01-01

Full Text Available Edible insect is appraised by many cultures as delicious and nutritionally beneficial food. In western countries this commodity is not fully appreciated, and the worries about edible insect food safety prevail. Electronic noses can become a simple and cheap way of securing the health safety of food, and they can also become a tool for evaluating the quality of certain commodities. This research is a pilot project of using an electronic nose in edible insect culinary treatment, and this manuscript describes the phases of edible insect culinary treatment and methods of distinguishing mealworm (Tenebrio molitor and giant mealworm (Zophobas morio using simple electronic nose. These species were measured in the live stage, after killing with boiling water, after drying and after inserting into the chocolate.The sensing device was based on the Arduino Mega platform with the ability to store the recorded data on the SD memory card, and with the possibility to communicate via internet. Data analysis shows that even a simple, cheap and portable electronic nose can distinguish between the different steps of culinary treatment (native samples, dried samples, samples enriched with chocolate for cooking and selected species. Another benefit of the electronic nose could be its future introduction into the control mechanisms of food security systems (e.g. HACCP.

Divalent metal transporter 1 (DMT1) in the brain: implications for a role in iron transport at the blood-brain barrier, and neuronal and glial pathology.

Science.gov (United States)

Skjørringe, Tina; Burkhart, Annette; Johnsen, Kasper Bendix; Moos, Torben

2015-01-01

Iron is required in a variety of essential processes in the body. In this review, we focus on iron transport in the brain and the role of the divalent metal transporter 1 (DMT1) vital for iron uptake in most cells. DMT1 locates to cellular membranes and endosomal membranes, where it is a key player in non-transferrin bound iron uptake and transferrin-bound iron uptake, respectively. Four isoforms of DMT1 exist, and their respective characteristics involve a complex cell-specific regulatory machinery all controlling iron transport across these membranes. This complexity reflects the fine balance required in iron homeostasis, as this metal is indispensable in many cell functions but highly toxic when appearing in excess. DMT1 expression in the brain is prominent in neurons. Of serious dispute is the expression of DMT1 in non-neuronal cells. Recent studies imply that DMT1 does exist in endosomes of brain capillary endothelial cells denoting the blood-brain barrier. This supports existing evidence that iron uptake at the BBB occurs by means of transferrin-receptor mediated endocytosis followed by detachment of iron from transferrin inside the acidic compartment of the endosome and DMT1-mediated pumping iron into the cytosol. The subsequent iron transport across the abluminal membrane into the brain likely occurs by ferroportin. The virtual absent expression of transferrin receptors and DMT1 in glial cells, i.e., astrocytes, microglia and oligodendrocytes, suggest that the steady state uptake of iron in glia is much lower than in neurons and/or other mechanisms for iron uptake in these cell types prevail.

Towards a Chemiresistive Sensor-Integrated Electronic Nose: A Review

Directory of Open Access Journals (Sweden)

Kea-Tiong Tang

2013-10-01

Full Text Available Electronic noses have potential applications in daily life, but are restricted by their bulky size and high price. This review focuses on the use of chemiresistive gas sensors, metal-oxide semiconductor gas sensors and conductive polymer gas sensors in an electronic nose for system integration to reduce size and cost. The review covers the system design considerations and the complementary metal-oxide-semiconductor integrated technology for a chemiresistive gas sensor electronic nose, including the integrated sensor array, its readout interface, and pattern recognition hardware. In addition, the state-of-the-art technology integrated in the electronic nose is also presented, such as the sensing front-end chip, electronic nose signal processing chip, and the electronic nose system-on-chip.

Nose profile morphology and accuracy study of nose profile estimation method in Scottish subadult and Indonesian adult populations.

Science.gov (United States)

Sarilita, Erli; Rynn, Christopher; Mossey, Peter A; Black, Sue; Oscandar, Fahmi

2018-05-01

This study investigated nose profile morphology and its relationship to the skull in Scottish subadult and Indonesian adult populations, with the aim of improving the accuracy of forensic craniofacial reconstruction. Samples of 86 lateral head cephalograms from Dundee Dental School (mean age, 11.8 years) and 335 lateral head cephalograms from the Universitas Padjadjaran Dental Hospital, Bandung, Indonesia (mean age 24.2 years), were measured. The method of nose profile estimation based on skull morphology previously proposed by Rynn and colleagues in 2010 (FSMP 6:20-34) was tested in this study. Following this method, three nasal aperture-related craniometrics and six nose profile dimensions were measured from the cephalograms. To assess the accuracy of the method, six nose profile dimensions were estimated from the three craniometric parameters using the published method and then compared to the actual nose profile dimensions.In the Scottish subadult population, no sexual dimorphism was evident in the measured dimensions. In contrast, sexual dimorphism of the Indonesian adult population was evident in all craniometric and nose profile dimensions; notably, males exhibited statistically significant larger values than females. The published method by Rynn and colleagues (FSMP 6:20-34, 2010) performed better in the Scottish subadult population (mean difference of maximum, 2.35 mm) compared to the Indonesian adult population (mean difference of maximum, 5.42 mm in males and 4.89 mm in females).In addition, regression formulae were derived to estimate nose profile dimensions based on the craniometric measurements for the Indonesian adult population. The published method is not sufficiently accurate for use on the Indonesian population, so the derived method should be used. The accuracy of the published method by Rynn and colleagues (FSMP 6:20-34, 2010) was sufficiently reliable to be applied in Scottish subadult population.

[Study of dopamine transporter imaging on the brain of children with autism].

Science.gov (United States)

Sun, Xiaomian; Yue, Jing; Zheng, Chongxun

2008-04-01

This study was conducted to evaluate the applicability of 99mTc-2beta-[ N, N'-bis (2-mercaptoethyl) ethylenediamino]methyl,3beta(4-chlorophenyl)tropane(TRODAT-1) dopamine transporter(DAT) SPECT imaging in children with autism, and thus to provide an academic basis for the etiology, mechanism and clinical therapy of autism. Ten autistic children and ten healthy controls were examined with 99mTc-TRODAT-1 DAT SPECT imaging. Striatal specific uptake of 99mTc-TRODAT-1 was calculated with region of interest analysis according to the ratics between striatum and cerebellum [(STR-BKG)/BKG]. There was no statistically significant difference in semiquantitative dopamine transporter between the bilateral striata of autistic children (P=0.562), and between those of normal controls (p=0.573); Dopamine transporter in the brain of patients with autism increased significantly as compared with that in the brain of normal controls (P=0.017). Dopaminergic nervous system is dysfunctioning in the brain of children with autism, and DAT 99mTc-TRODAT-1 SPECT imaging on the brain will help the imaging diagnosis of childhcod autism.

Understanding Colds: Anatomy of the Nose

Science.gov (United States)

... Complications Special Features References Common Cold Understanding Colds Anatomy of the Nose The nose contains shelf-like ... white). Soft tissue, such as the eye, is gray. The maxillary sinus of adults has a volume ...

Hydrophilic solute transport across the rat blood-brain barrier

International Nuclear Information System (INIS)

Lucchesi, K.J.

1987-01-01

Brain capillary permeability-surface area products (PS) of hydrophilic solutes ranging in size from 180 to 5,500 Daltons were measured in rats according to the method of Ohno, Pettigrew and Rapoport. The distribution volume of 70 KD dextran at 10 minutes after i.v. injection was also measured to determine the residual volume of blood in brain tissue at the time of sacrifice. Small test solutes were injected in pairs in order to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. This issue was examined in rats whose blood-brain barrier (BBB) was presumed to be intact (untreated) and in rats that received intracarotid infusions to open the BBB (isosmotic salt (ISS) and hyperosmolar arabinose). Ohno PS values of 3 H-inulin and 14 C-L-glucose in untreated rats were found to decrease as the labelling time was lengthened. This was evidence that a rapidly equilibrating compartment exists between blood and brain that renders the Ohno two-compartment model inadequate for computing true transfer rate constants. When the data were reanalyzed using a multi-compartment graphical analysis, solutes with different molecular radii were found to enter the brain at approximately equal rates. Furthermore, unidirectional transport is likely to be initiated by solute adsorption to a glycocalyx coat on the luminal surface of brain capillary endothelium. Apparently, more inulin than L-glucose was adsorbed, which may account for its slightly faster transfer across the BBB. After rats were treated with intracarotid infusions of ISS or hyperosmolar arabinose, solute PS values were significantly increased, but the ratio of PS for each of the solute pairs approached that of their free-diffusion coefficients

Enhancement of transport of curcumin to brain in mice by poly(n-butylcyanoacrylate) nanoparticle

Energy Technology Data Exchange (ETDEWEB)

Sun Min; Gao Yan; Guo Chenyu; Cao Fengliang; Song Zhimei; Xi Yanwei; Yu Aihua; Li Aiguo; Zhai Guangxi, E-mail: professorzhai@yeah.ne [Shandong University, Department of Pharmaceutics, College of Pharmacy (China)

2010-10-15

Curcumin, a widely used coloring agent and spice in food, has a potential in blocking brain tumor formation and curing Alzheimer's disease. Due to the specific properties of blood-brain barrier (BBB), only traces of curcumin were transported across BBB. The aim of the present study was to design and characterize curcumin loaded polybutylcyanoacrylate nanoparticles (PBCN) coated with polysorbate 80, and to evaluate the effect of PBCN as a delivery system on carrying curcumin across BBB. Curcumin loaded nanoparticles were prepared by an anionic polymerization method, and they presented in a core-shell spherical shape under transmission electron microscopy, with an average diameter of 152.0 nm. The average drug loading was 21.1%. Physicochemical status of curcumin in the nanoparticles was confirmed with differential scanning colorimetry and Fourier transform infrared spectroscopy. The in vitro release behavior of drug from the nanoparticles was fitted to a double phase kinetics model. The studies of pharmacokinetic and bio-distribution to brain were conducted in mice after intravenous administration of the nanoparticle formulation at the dose of 5 mg/kg and curcumin solution at the dose of 10 mg/kg via the tail vein. The results showed that in plasma, the area under concentration-time curve (AUC{sub 0-{infinity}}) for curcumin loaded nanoparticles was greater than that for the control solution, moreover, the mean residence time of curcumin loaded nanoparticles was 14-fold that of the control solution. In brain, AUC{sub 0-{infinity}} for curcumin loaded nanoparticles was 2.53-fold that for the control solution. In conclusion, the present study demonstrated that PBCN could enhance the transport of curcumin to brain and have a potential as a delivery system to cross the BBB.

Enhancement of transport of curcumin to brain in mice by poly( n-butylcyanoacrylate) nanoparticle

Science.gov (United States)

Sun, Min; Gao, Yan; Guo, Chenyu; Cao, Fengliang; Song, Zhimei; Xi, Yanwei; Yu, Aihua; Li, Aiguo; Zhai, Guangxi

2010-10-01

Curcumin, a widely used coloring agent and spice in food, has a potential in blocking brain tumor formation and curing Alzheimer's disease. Due to the specific properties of blood-brain barrier (BBB), only traces of curcumin were transported across BBB. The aim of the present study was to design and characterize curcumin loaded polybutylcyanoacrylate nanoparticles (PBCN) coated with polysorbate 80, and to evaluate the effect of PBCN as a delivery system on carrying curcumin across BBB. Curcumin loaded nanoparticles were prepared by an anionic polymerization method, and they presented in a core-shell spherical shape under transmission electron microscopy, with an average diameter of 152.0 nm. The average drug loading was 21.1%. Physicochemical status of curcumin in the nanoparticles was confirmed with differential scanning colorimetry and Fourier transform infrared spectroscopy. The in vitro release behavior of drug from the nanoparticles was fitted to a double phase kinetics model. The studies of pharmacokinetic and bio-distribution to brain were conducted in mice after intravenous administration of the nanoparticle formulation at the dose of 5 mg/kg and curcumin solution at the dose of 10 mg/kg via the tail vein. The results showed that in plasma, the area under concentration-time curve (AUC0-∞) for curcumin loaded nanoparticles was greater than that for the control solution, moreover, the mean residence time of curcumin loaded nanoparticles was 14-fold that of the control solution. In brain, AUC0-∞ for curcumin loaded nanoparticles was 2.53-fold that for the control solution. In conclusion, the present study demonstrated that PBCN could enhance the transport of curcumin to brain and have a potential as a delivery system to cross the BBB.

Enhancement of transport of curcumin to brain in mice by poly(n-butylcyanoacrylate) nanoparticle

International Nuclear Information System (INIS)

Sun Min; Gao Yan; Guo Chenyu; Cao Fengliang; Song Zhimei; Xi Yanwei; Yu Aihua; Li Aiguo; Zhai Guangxi

2010-01-01

Curcumin, a widely used coloring agent and spice in food, has a potential in blocking brain tumor formation and curing Alzheimer's disease. Due to the specific properties of blood-brain barrier (BBB), only traces of curcumin were transported across BBB. The aim of the present study was to design and characterize curcumin loaded polybutylcyanoacrylate nanoparticles (PBCN) coated with polysorbate 80, and to evaluate the effect of PBCN as a delivery system on carrying curcumin across BBB. Curcumin loaded nanoparticles were prepared by an anionic polymerization method, and they presented in a core-shell spherical shape under transmission electron microscopy, with an average diameter of 152.0 nm. The average drug loading was 21.1%. Physicochemical status of curcumin in the nanoparticles was confirmed with differential scanning colorimetry and Fourier transform infrared spectroscopy. The in vitro release behavior of drug from the nanoparticles was fitted to a double phase kinetics model. The studies of pharmacokinetic and bio-distribution to brain were conducted in mice after intravenous administration of the nanoparticle formulation at the dose of 5 mg/kg and curcumin solution at the dose of 10 mg/kg via the tail vein. The results showed that in plasma, the area under concentration-time curve (AUC 0-∞ ) for curcumin loaded nanoparticles was greater than that for the control solution, moreover, the mean residence time of curcumin loaded nanoparticles was 14-fold that of the control solution. In brain, AUC 0-∞ for curcumin loaded nanoparticles was 2.53-fold that for the control solution. In conclusion, the present study demonstrated that PBCN could enhance the transport of curcumin to brain and have a potential as a delivery system to cross the BBB.

Heat Transfer in Directional Water Transport Fabrics

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Chao Zeng

2016-10-01

Full Text Available Directional water transport fabrics can proactively transfer moisture from the body. They show great potential in making sportswear and summer clothing. While moisture transfer has been previously reported, heat transfer in directional water transport fabrics has been little reported in research literature. In this study, a directional water transport fabric was prepared using an electrospraying technique and its heat transfer properties under dry and wet states were evaluated, and compared with untreated control fabric and the one pre-treated with NaOH. All the fabric samples showed similar heat transfer features in the dry state, and the equilibrium temperature in the dry state was higher than for the wet state. Wetting considerably enhanced the thermal conductivity of the fabrics. Our studies indicate that directional water transport treatment assists in moving water toward one side of the fabric, but has little effect on thermal transfer performance. This study may be useful for development of “smart” textiles for various applications.

CCK increases the transport of insulin into the brain.

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May, Aaron A; Liu, Min; Woods, Stephen C; Begg, Denovan P

2016-10-15

Food intake occurs in bouts or meals, and numerous meal-generated signals have been identified that act to limit the size of ongoing meals. Hormones such as cholecystokinin (CCK) are secreted from the intestine as ingested food is being processed, and in addition to aiding the digestive process, they provide a signal to the brain that contributes to satiation, limiting the size of the meal. The potency of CCK to elicit satiation is enhanced by elevated levels of adiposity signals such as insulin. In the present experiments we asked whether CCK and insulin interact at the level of the blood-brain barrier (BBB). We first isolated rat brain capillary endothelial cells that comprise the BBB and found that they express the mRNA for both the CCK1R and the insulin receptor, providing a basis for a possible interaction. We then administered insulin intraperitoneally to another group of rats and 15min later administered CCK-8 intraperitoneally to half of those rats. After another 15min, CSF and blood samples were obtained and assayed for immunoreactive insulin. Plasma insulin was comparably elevated above baseline in both the CCK-8 and control groups, indicating that the CCK had no effect on circulating insulin levels given these parameters. In contrast, rats administered CCK had CSF-insulin levels that were more than twice as high as those of control rats. We conclude that circulating CCK greatly facilitates the transport of insulin into the brain, likely by acting directly at the BBB. These findings imply that in circumstances in which the plasma levels of both CCK and insulin are elevated, such as during and soon after meals, satiation is likely to be due, in part, to this newly-discovered synergy between CCK and insulin. Copyright © 2016 Elsevier Inc. All rights reserved.

The Fabrication of Non-Implant 3D Printed Nose

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Chuan Yong Leng

2018-01-01

Full Text Available Non-surgical rhinoplasty procedures which involves the use of injectable derma fillers are highly risky as patients are susceptible to side effects and complications that may cause unwanted changes in their appearance. This research explores an alternative method of non-surgical rhinoplasty for patients seeking augmentation of the nose with the use of three-dimensional (3D printing. Most rhinoplasty procedures are conducted with the intention of enhancing the aesthetical features of the nose, a 3D model nose was designed based on the combination of the average and the ideal aesthetic parameters of the Northern European Caucasians and South Asia Chinese nose. The modelling of nose is done using the SolidWorks CAD software. An initial design was sketched in a polygon mesh form and further improved on. Different printing materials and infill densities were compared to determine the suitable printing technique. The final nose model is then printed using the Ultimaker 3D printer using Polylactic acid (PLA with an infill density of 100% at a thickness of 1.4 mm. An inner layer to the 3D printed nose was developed for comfortable attachment of the nose model to human skin. The inner layer was fabricated using agar gelatine. Experiments were carried out to increase the strength and adhesiveness of the gelatine so that it could adhere to the human skin and the PLA surface. Tensile and adhesive strength tests were carried out to determine the suitable gel composition for the attachment of the nose to the user’s face. The key outcome from the experiments using natural gelatine was capability of gel to act as an inner layer for the temporary attachment of the 3D nose model to the human skin

Role of Transporters in Central Nervous System Drug Delivery and Blood-Brain Barrier Protection: Relevance to Treatment of Stroke

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Hrvoje Brzica

2017-03-01

Full Text Available Ischemic stroke is a leading cause of morbidity and mortality in the United States. The only approved pharmacologic treatment for ischemic stroke is thrombolysis via recombinant tissue plasminogen activator (r-tPA. A short therapeutic window and serious adverse events (ie, hemorrhage, excitotoxicity greatly limit r-tPA therapy, which indicates an essential need to develop novel stroke treatment paradigms. Transporters expressed at the blood-brain barrier (BBB provide a significant opportunity to advance stroke therapy via central nervous system delivery of drugs that have neuroprotective properties. Examples of such transporters include organic anion–transporting polypeptides (Oatps and organic cation transporters (Octs. In addition, multidrug resistance proteins (Mrps are transporter targets in brain microvascular endothelial cells that can be exploited to preserve BBB integrity in the setting of stroke. Here, we review current knowledge on stroke pharmacotherapy and demonstrate how endogenous BBB transporters can be targeted for improvement of ischemic stroke treatment.

Classification of human pathogen bacteria for early screening using electronic nose

Science.gov (United States)

Zulkifli, Syahida Amani; Mohamad, Che Wan Syarifah Robiah; Abdullah, Abu Hassan

2017-10-01

This paper present human pathogen bacteria for early screening using electronic nose. Electronic nose (E-nose) known as gas sensor array is a device that analyze the odor measurement give the fast response and less time consuming for clinical diagnosis. Many bacterial pathogens could lead to life threatening infections. Accurate and rapid diagnosis is crucial for the successful management of these infections disease. The conventional method need more time to detect the growth of bacterial. Alternatively, the bacteria are Pseudomonas aeruginosa and Shigella cultured on different media agar can be detected and classifies according to the volatile compound in shorter time using electronic nose (E-nose). Then, the data from electronic nose (E-nose) is processed using statistical method which is principal component analysis (PCA). The study shows the capability of electronic nose (E-nose) for early screening for bacterial infection in human stomach.

Development of an electronic nose for environmental odour monitoring.

Science.gov (United States)

Dentoni, Licinia; Capelli, Laura; Sironi, Selena; Del Rosso, Renato; Zanetti, Sonia; Della Torre, Matteo

2012-10-25

Exhaustive odour impact assessment should involve the evaluation of the impact of odours directly on citizens. For this purpose it might be useful to have an instrument capable of continuously monitoring ambient air quality, detecting the presence of odours and also recognizing their provenance. This paper discusses the laboratory and field tests conducted in order to evaluate the performance of a new electronic nose, specifically developed for monitoring environmental odours. The laboratory tests proved the instrument was able to discriminate between the different pure substances being tested, and to estimate the odour concentrations giving correlation indexes (R2) of 0.99 and errors below 15%. Finally, the experimental monitoring tests conducted in the field, allowed us to verify the effectiveness of this electronic nose for the continuous detection of odours in ambient air, proving its stability to variable atmospheric conditions and its capability to detect odour peaks.

Ultrasound effects on brain-targeting mannosylated liposomes: in vitro and blood–brain barrier transport investigations

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Zidan AS

2015-07-01

Full Text Available Ahmed S Zidan,1,2 Hibah Aldawsari1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt Abstract: Delivering drugs to intracerebral regions can be accomplished by improving the capacity of transport through blood–brain barrier. Using sertraline as model drug for brain targeting, the current study aimed at modifying its liposomal vesicles with mannopyranoside. Box-Behnken design was employed to statistically optimize the ultrasound parameters, namely ultrasound amplitude, time, and temperature, for maximum mannosylation capacity, sertraline entrapment, and surface charge while minimizing vesicular size. Moreover, in vitro blood–brain barrier transport model was established to assess the transendothelial capacity of the optimized mannosylated vesicles. Results showed a dependence of vesicular size, mannosylation capacity, and sertraline entrapment on cavitation and bubble implosion events that were related to ultrasound power amplitude, temperature. However, short ultrasound duration was required to achieve >90% mannosylation with nanosized vesicles (<200 nm of narrow size distribution. Optimized ultrasound parameters of 65°C, 27%, and 59 seconds for ultrasound temperature, amplitude, and time were elucidated to produce 81.1%, 46.6 nm, and 77.6% sertraline entrapment, vesicular size, and mannosylation capacity, respectively. Moreover, the transendothelial ability was significantly increased by 2.5-fold by mannosylation through binding with glucose transporters. Hence, mannosylated liposomes processed by ultrasound could be a promising approach for manufacturing and scale-up of brain-targeting liposomes. Keywords: CNS delivery, sizing, lipid based formulations, quality by design, sertraline hydrochloride

Future applications of electronic-nose technologies in healthcare and biomedicine

Science.gov (United States)

Alphus D. Wilson

2011-01-01

The development and utilization of many new electronic-nose (e-nose) applications in the healthcare and biomedical fields have continued to rapidly accelerate over the past 20 years. Innovative e-nose technologies are providing unique solutions to a diversity of complex problems in biomedicine that are now coming to fruition. A wide range of electronic-nose instrument...

Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies.

Science.gov (United States)

El-Zaafarany, Ghada M; Soliman, Mahmoud E; Mansour, Samar; Awad, Gehanne A S

2016-04-30

Lipid-based nanovectors offer effective carriers for brain delivery by improving drug potency and reducing off-target effects. Emulsomes are nano-triglyceride (TG) carriers formed of lipid cores supported by at least one phospholipid (PC) sheath. Due to their surface active properties, PC forms bilayers at the aqueous interface, thereby enabling encapsulated drug to benefit from better bioavailability and stability. Emulsomes of oxcarbazepine (OX) were prepared, aimed to offer nanocarriers for nasal delivery for brain targeting. Different TG cores (Compritol(®), tripalmitin, tristearin and triolein) and soya phosphatidylcholine in different amounts and ratios were used for emulsomal preparation. Particles were modulated to generate nanocarriers with suitable size, charge, encapsulation efficiency and prolonged release. Cytotoxicity and pharmacokinetic studies were also implemented. Nano-spherical OX-emulsomes with maximal encapsulation of 96.75% were generated. Stability studies showed changes within 30.6% and 11.2% in the size and EE% after 3 months. MTT assay proved a decrease in drug toxicity by its encapsulation in emulsomes. Incorporation of OX into emulsomes resulted in stable nanoformulations. Tailoring emulsomes properties by modulating the surface charge and particle size produced a stable system for the lipophilic drug with a prolonged release profile and mean residence time and proved direct nose-to-brain transport in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Driving and driven architectures of directed small-world human brain functional networks.

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Chaogan Yan

Full Text Available Recently, increasing attention has been focused on the investigation of the human brain connectome that describes the patterns of structural and functional connectivity networks of the human brain. Many studies of the human connectome have demonstrated that the brain network follows a small-world topology with an intrinsically cohesive modular structure and includes several network hubs in the medial parietal regions. However, most of these studies have only focused on undirected connections between regions in which the directions of information flow are not taken into account. How the brain regions causally influence each other and how the directed network of human brain is topologically organized remain largely unknown. Here, we applied linear multivariate Granger causality analysis (GCA and graph theoretical approaches to a resting-state functional MRI dataset with a large cohort of young healthy participants (n = 86 to explore connectivity patterns of the population-based whole-brain functional directed network. This directed brain network exhibited prominent small-world properties, which obviously improved previous results of functional MRI studies showing weak small-world properties in the directed brain networks in terms of a kernel-based GCA and individual analysis. This brain network also showed significant modular structures associated with 5 well known subsystems: fronto-parietal, visual, paralimbic/limbic, subcortical and primary systems. Importantly, we identified several driving hubs predominantly located in the components of the attentional network (e.g., the inferior frontal gyrus, supplementary motor area, insula and fusiform gyrus and several driven hubs predominantly located in the components of the default mode network (e.g., the precuneus, posterior cingulate gyrus, medial prefrontal cortex and inferior parietal lobule. Further split-half analyses indicated that our results were highly reproducible between two

Dual and Direction-Selective Mechanisms of Phosphate Transport by the Vesicular Glutamate Transporter

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Julia Preobraschenski

2018-04-01

Full Text Available Summary: Vesicular glutamate transporters (VGLUTs fill synaptic vesicles with glutamate and are thus essential for glutamatergic neurotransmission. However, VGLUTs were originally discovered as members of a transporter subfamily specific for inorganic phosphate (Pi. It is still unclear how VGLUTs accommodate glutamate transport coupled to an electrochemical proton gradient ΔμH+ with inversely directed Pi transport coupled to the Na+ gradient and the membrane potential. Using both functional reconstitution and heterologous expression, we show that VGLUT transports glutamate and Pi using a single substrate binding site but different coupling to cation gradients. When facing the cytoplasm, both ions are transported into synaptic vesicles in a ΔμH+-dependent fashion, with glutamate preferred over Pi. When facing the extracellular space, Pi is transported in a Na+-coupled manner, with glutamate competing for binding but at lower affinity. We conclude that VGLUTs have dual functions in both vesicle transmitter loading and Pi homeostasis within glutamatergic neurons. : Preobraschenski et al. show that the vesicular glutamate transporter functions as a bi-directional phosphate transporter that is coupled with different cations in each direction and hence may play a key role in neuronal phosphate homeostasis. Keywords: VGLUT, SLC17 family, type I Na+-dependent inorganic phosphate transporter, ATPase, proteoliposomes, hybrid vesicles, anti-VGLUT1 nanobody

Alpha Adrenergic Induction of Transport of Lysosomal Enzyme across the Blood-Brain Barrier.

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Akihiko Urayama

Full Text Available The impermeability of the adult blood-brain barrier (BBB to lysosomal enzymes impedes the ability to treat the central nervous system manifestations of lysosomal storage diseases. Here, we found that simultaneous stimulation of the alpha1 and alpha2 adrenoreceptor restores in adult mice the high rate of transport for the lysosomal enzyme P-GUS that is seen in neonates but lost with development. Beta adrenergics, other monoamines, and acetylcholine did not restore this transport. A high dose (500 microg/mouse of clonidine, a strong alpha2 and weak alpha1 agonist, was able to act as monotherapy in the stimulation of P-GUS transport. Neither use of alpha1 plus alpha2 agonists nor the high dose clonidine disrupted the BBB to albumin. In situ brain perfusion and immunohistochemistry studies indicated that adrengerics act on transporters already at the luminal surface of brain endothelial cells. These results show that adrenergic stimulation, including monotherapy with clonidine, could be key for CNS enzyme replacement therapy.

After irradiation of the throat or nose area: pay attention to the eye

International Nuclear Information System (INIS)

Balen, A.Th.M. van

1984-01-01

Radiotherapy of carcinomas in the nose can give delayed side effects on the visual system. In this article four cases are described, in which a neuropathy of the optical nerve, caused by vascular damaging, developed one to three years after radiotherapy of nose-neoplasms, with total irradiation doses of 7000 rad. (Auth.)

Discovery of unique and ENM— specific pathophysiologic pathways: Comparison of the translocation of inhaled iridium nanoparticles from nasal epithelium versus alveolar epithelium towards the brain of rats

Energy Technology Data Exchange (ETDEWEB)

Kreyling, Wolfgang G., E-mail: kreyling@helmholtz-muenchen.de

2016-05-15

The biokinetics of inhaled nanoparticles (NP) is more complex than that of larger particles since NP may NP deposited on the nasal mucosa of the upper respiratory tract (URT) may translocate to the olfactory bulb of the brain and also via the trigeminus (URT neuronal route); and (b) NP deposited in the lower respiratory tract (LRT) may cross the ABB into blood and enter the brain across the blood-brain-barrier (BBB) or take a neuronal route from enervated tracheo-bronchial epithelia via the vagus nerve. Translocation from both - the URT and the LRT - are quantified during the first 24 h after a 1-hour aerosol inhalation of 20 nm-sized, {sup 192}Ir radiolabeled iridium NP by healthy adult rats using differential exposures: (I) nose-only exposure of the entire respiratory tract or (II) intratracheal (IT) inhalation of intubated and ventilated rats, thereby bypassing the URT and extrathoracic nasal passages. After nose-only exposure brain accumulation (BrAcc) is significantly nine-fold higher than after IT inhalation since the former results from both pathways (a + b) while the latter exposure comes only from pathway (b). Interestingly, there are significantly more circulating NP in blood 24 h after nose-only inhalation than after IT inhalation. Distinguishing translocation from URT versus LRT estimated from the differential inhalation exposures, the former is significantly higher (8-fold) than from the LRT. Although the BrAcc fraction is rather low compared to total NP deposition after this short-term exposure, this study proofs that inhaled insoluble NP can accumulate in the brain from both – URT and LRT which may trigger and/or modulate adverse health effects in the central nervous system (CNS) during chronic exposure. - Highlights: • Nanoparticle (NP) translocation from nose versus lungs to brain is differentiated. • Differential exposure of 20 nm radio-NP:nose-only versus intratracheal inhalation • The nose-brain path precedes via nerves, the lungs-brain

Regional distribution of serotonin transporter protein in postmortem human brain

International Nuclear Information System (INIS)

Kish, Stephen J.; Furukawa, Yoshiaki; Chang Lijan; Tong Junchao; Ginovart, Nathalie; Wilson, Alan; Houle, Sylvain; Meyer, Jeffrey H.

2005-01-01

Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met

Regional distribution of serotonin transporter protein in postmortem human brain

Energy Technology Data Exchange (ETDEWEB)

Kish, Stephen J. [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)]. E-mail: Stephen_Kish@CAMH.net; Furukawa, Yoshiaki [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Chang Lijan [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Tong Junchao [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Ginovart, Nathalie [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Wilson, Alan [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Meyer, Jeffrey H. [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

2005-02-01

Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.

Acoustic rhinometry of the Indian and Anglo-Saxon nose.

Science.gov (United States)

Gurr, P; Diver, J; Morgan, N; MacGregor, F; Lund, V

1996-09-01

The internal and external geometry of the nose has previously been shown to differ between Anglo-Saxon, Chinese, and Negro noses. It is therefore important to define the normal geometric nasal parameters of a given race, so as to detect the abnormal nose. We present acoustic rhinometric data, with height-adjusted figures, examining the nasal minimum cross-sectional area (MCA), the distance to the nostril from the MCA, and the MCA between 0-6 cm. These data show no significant differences between Indian and Anglo-Saxon noses.

The Blood-Brain Barrier: Connecting the Gut and the Brain

OpenAIRE

Banks, William A.

2008-01-01

The BBB prevents the unrestricted exchange of substances between the central nervous system (CNS) and the blood. The blood-brain barrier (BBB) also conveys information between the CNS and the gastrointestinal (GI) tract through several mechanisms. Here, we review three of those mechanisms. First, the BBB selectively transports some peptides and regulatory proteins in the blood-to-brain or the brain-to-blood direction. The ability of GI hormones to affect functions of the BBB, as illustrated b...

A Novel Semi-Supervised Electronic Nose Learning Technique: M-Training

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Pengfei Jia

2016-03-01

Full Text Available When an electronic nose (E-nose is used to distinguish different kinds of gases, the label information of the target gas could be lost due to some fault of the operators or some other reason, although this is not expected. Another fact is that the cost of getting the labeled samples is usually higher than for unlabeled ones. In most cases, the classification accuracy of an E-nose trained using labeled samples is higher than that of the E-nose trained by unlabeled ones, so gases without label information should not be used to train an E-nose, however, this wastes resources and can even delay the progress of research. In this work a novel multi-class semi-supervised learning technique called M-training is proposed to train E-noses with both labeled and unlabeled samples. We employ M-training to train the E-nose which is used to distinguish three indoor pollutant gases (benzene, toluene and formaldehyde. Data processing results prove that the classification accuracy of E-nose trained by semi-supervised techniques (tri-training and M-training is higher than that of an E-nose trained only with labeled samples, and the performance of M-training is better than that of tri-training because more base classifiers can be employed by M-training.

Selective binding of 2-[{sup 125}I]iodo-nisoxetine to norepinephrine transporters in the brain

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Kung, M.-P.; Choi, Seok-Rye; Hou, Catherine; Zhuang, Z.-P.; Foulon, Catherine; Kung, Hank F. E-mail: kunghf@sunmac.spect.upenn.edu

2004-07-01

A radioiodinated ligand, (R)-N-methyl-(2-[{sup 125}I]iodo-phenoxy)-3-phenylpropylamine, [{sup 125}I]2-INXT, targeting norepinephrine transporters (NET), was successfully prepared. A no-carrier-added product, [{sup 125}I]2-INXT, displayed a saturable binding with a high affinity (K{sub d}=0.06 nM) in the homogenates prepared from rat cortical tissues as well as from LLC-PK{sub 1} cells expressing NET. A relatively low number of binding sties (B{sub max}=55 fmol/mg protein) measured with [{sup 125}I]2-INXT in rat cortical homogenates is consistent with the value reported for a known NET ligand, [{sup 3}H]nisoxetine. Competition studies with various compounds on [{sup 125}I]2-INXT binding clearly confirmed the pharmacological specificity and selectivity for NET binding sites. Following a tail-vein injection of [{sup 125}I]2-INXT in rats, a good initial brain uptake was observed (0.56% dose at 2 min) followed by a slow washout from the brain (0.2% remained at 3 hours post-injection). The hypothalamus (a NET-rich region) to striatum (a region devoid of NET) ratio was 1.5 at 3 hours post-i.v. injection. Pretreatment of rats with nisoxetine significantly inhibited the uptake of [{sup 125}I]2-INXT (70-100% inhibition) in locus coeruleus, hypothalamus and raphe nuclei, regions known to have a high density of NET; whereas escitalopram, a serotonin transporter ligand, did not show a similar effect. Ex vivo autoradiography of rat brain sections of [{sup 125}I]2-INXT (at 3 hours after an i.v. injection) displayed an excellent regional brain localization pattern corroborated to the specific NET distribution in the brain. The specific brain localization was significantly reduced by a dose of nisoxetine pretreatment. Taken together, the data suggest that [{sup 123}I]2-INXT may be useful for mapping NET binding sites in the brain.

Advances in electronic-nose technologies developed for biomedical applications.

Science.gov (United States)

Wilson, Alphus D; Baietto, Manuela

2011-01-01

The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and recent biomedical research findings and developments of electronic-nose sensor technologies, and to identify current and future potential e-nose applications that will continue to advance the effectiveness and efficiency of biomedical treatments and healthcare services for many years. An abundance of electronic-nose applications has been developed for a variety of healthcare sectors including diagnostics, immunology, pathology, patient recovery, pharmacology, physical therapy, physiology, preventative medicine, remote healthcare, and wound and graft healing. Specific biomedical e-nose applications range from uses in biochemical testing, blood-compatibility evaluations, disease diagnoses, and drug delivery to monitoring of metabolic levels, organ dysfunctions, and patient conditions through telemedicine. This paper summarizes the major electronic-nose technologies developed for healthcare and biomedical applications since the late 1980s when electronic aroma detection technologies were first recognized to be potentially useful in providing effective solutions to problems in the healthcare industry.

Advances in Electronic-Nose Technologies Developed for Biomedical Applications

Directory of Open Access Journals (Sweden)

Alphus D. Wilson

2011-01-01

Full Text Available The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and recent biomedical research findings and developments of electronic-nose sensor technologies, and to identify current and future potential e-nose applications that will continue to advance the effectiveness and efficiency of biomedical treatments and healthcare services for many years. An abundance of electronic-nose applications has been developed for a variety of healthcare sectors including diagnostics, immunology, pathology, patient recovery, pharmacology, physical therapy, physiology, preventative medicine, remote healthcare, and wound and graft healing. Specific biomedical e-nose applications range from uses in biochemical testing, blood-compatibility evaluations, disease diagnoses, and drug delivery to monitoring of metabolic levels, organ dysfunctions, and patient conditions through telemedicine. This paper summarizes the major electronic-nose technologies developed for healthcare and biomedical applications since the late 1980s when electronic aroma detection technologies were first recognized to be potentially useful in providing effective solutions to problems in the healthcare industry.

Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma.

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Johnsen, Kasper Bendix; Burkhart, Annette; Melander, Fredrik; Kempen, Paul Joseph; Vejlebo, Jonas Bruun; Siupka, Piotr; Nielsen, Morten Schallburg; Andresen, Thomas Lars; Moos, Torben

2017-09-04

Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain.

14 CFR 67.105 - Ear, nose, throat, and equilibrium.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Ear, nose, throat, and equilibrium. 67.105..., nose, throat, and equilibrium. Ear, nose, throat, and equilibrium standards for a first-class airman... may reasonably be expected to be manifested by, vertigo or a disturbance of equilibrium. ...

Pharmacokinetics, brain distribution, release and blood-brain barrier transport of Shunaoxin pills.

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Wu, Kai; Wang, Zhan-Zhang; Liu, Dan; Qi, Xian-Rong

2014-02-12

Shunaoxin pills, a traditional Chinese medicine (TCM) product, have been used to treat cerebrovascular diseases in China since 2005. The main active components of Shunaoxin pills are ferulic acid and ligustilide from Chuanxiong (Ligusticum chuanxiong Hort, Umbelliferae) and Danggui (Angelica sinensis radix, Umbelliferae). As Shunaoxin shows excellent activity in the central nervous system (CNS), the extent to which the major constituents of Shunaoxin reach the CNS should be investigated. Moreover, the in vivo-in vitro correlations (IVIVC) of the formulation should be studied to elucidate the mechanisms of action of TCM in the CNS. However, these data have not previously been available. Thus we intended to investigate what the extent when these constituents of Shunaoxin pills reach the CNS, and evaluate the IVIVC of release and pharmacokinetics. In this study, we evaluated the release of ferulic acid and ligustilide from Shunaoxin pills, and their transport across an in vitro model of the BBB. We also evaluated their pharmacokinetics and brain distribution in vivo. High-performance liquid chromatography (HPLC) was used to quantify both compounds simultaneously. Based on the release in vitro and absorption of ferulic acid and ligustilide in vivo, IVIVC permitted prediction of the pharmacokinetics of these compounds. The release of ferulic acid and ligustilide reached a platform phase within 1h. Ferulic acid and ligustilide rapidly crossed the BBB in different patterns; the transport ratio increased over time. After intragastric (i.g.) administration of Shunaoxin pills, ferulic acid and ligustilide were rapidly absorbed and distributed into brain, which may result in a rapid onset of action. Ferulic acid and ligustilide were transported across a model BBB. After i.g. administration of Shunaoxin pills, ferulic acid and ligustilide were rapidly absorbed and distributed in brain; this may lead to rapid pharmacological onset. The IVIVC can be used to predict in vivo

14 CFR 67.305 - Ear, nose, throat, and equilibrium.

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2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Ear, nose, throat, and equilibrium. 67.305..., nose, throat, and equilibrium. Ear, nose, throat, and equilibrium standards for a third-class airman... by, or that may reasonably be expected to be manifested by, vertigo or a disturbance of equilibrium. ...

Effects of insulin on hexose transport across blood-brain barrier in normoglycemia

International Nuclear Information System (INIS)

Namba, H.; Lucignani, G.; Nehlig, A.; Patlak, C.; Pettigrew, K.; Kennedy, C.; Sokoloff, L.

1987-01-01

The effects of insulin on 3-O-[ 14 C] methylglucose transport across the blood-brain barrier (BBB) were studied in conscious rats under steady-state normoglycemic conditions. The [ 14 C]methylglucose was infused intravenously at a constant rate, and animals were killed at various times between 5 and 30 min after the initiation of the infusion. The time course of the arterial plasma concentration of [ 14 C]methylglucose was determined in timed arterial blood samples taken during the infusion. Local cerebral tissue concentrations of [ 14 C]methylglucose at the time of killing were determined by quantitative autoradiography of brain sections. The rate constants for inward and outward transport of [ 14 C]methylglucose across the BBB, K 1 , and k 2 , respectively, were estimated by a least-squares, best-fit of a kinetic equation to the measured time courses of plasma and tissue concentrations. The equilibrium distribution ration, K 1 /k 2 , for [ 14 C]methylglucose in brain increased by ∼ 10-11% in the hyperinsulinemic animals. Because 3-O-[ 14 C]methylglucose shares the same carrier that transports glucose and other hexoses across the BBB, these results suggest that hyperinsulinemia decreases the rate constants for transport but increases the distribution space for hexoses in brain. These effects are, however, quite small and are probably minor or negligible when compared with the major effects of insulin in other tissues

Influence of histidine on zinc transport into rat brain

International Nuclear Information System (INIS)

Takeda, Atsushi; Suzuki, Mai; Okada, Shoji; Oku, Naoto

2000-01-01

The brain of rats injected intravenously with 65 Zn-His or 65 ZnCl 2 was subjected to autoradiography to study the role of histidine on zinc transport into the brain. One hour after injection, the radioactivity from 65 Zn-His was largely concentrated in the choroid plexus in the ventricles. Six days after injection, the radioactivity from 65 Zn-His was relatively concentrated in the hippocampal CA3 and dentate gyrus and the amygdala. The relative distribution of 65 Zn-His in the brain was similar to that of 65 ZnCl 2 group at both 1 h and 6 days, suggesting that histidine may participate in zinc uptake in the brain. On the other hand, the clearance of the 65 Zn-His group from the blood was higher than that of the 65 ZnCl 2 group. Brain uptake of the former was lower than that of the latter both 1 h and 6 days after injection. These results suggest that zinc uptake in the brain is influenced by histidine levels in the bloodstream. (author)

Nanoparticle transport across the blood brain barrier.

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Grabrucker, Andreas M; Ruozi, Barbara; Belletti, Daniela; Pederzoli, Francesca; Forni, Flavio; Vandelli, Maria Angela; Tosi, Giovanni

2016-01-01

While the role of the blood-brain barrier (BBB) is increasingly recognized in the (development of treatments targeting neurodegenerative disorders, to date, few strategies exist that enable drug delivery of non-BBB crossing molecules directly to their site of action, the brain. However, the recent advent of Nanomedicines may provide a potent tool to implement CNS targeted delivery of active compounds. Approaches for BBB crossing are deeply investigated in relation to the pathology: among the main important diseases of the CNS, this review focuses on the application of nanomedicines to neurodegenerative disorders (Alzheimer, Parkinson and Huntington's Disease) and to other brain pathologies as epilepsy, infectious diseases, multiple sclerosis, lysosomal storage disorders, strokes.

The use and reliability of SymNose for quantitative measurement of the nose and lip in unilateral cleft lip and palate patients.

Science.gov (United States)

Mosmuller, David; Tan, Robin; Mulder, Frans; Bachour, Yara; de Vet, Henrica; Don Griot, Peter

2016-10-01

It is essential to have a reliable assessment method in order to compare the results of cleft lip and palate surgery. In this study the computer-based program SymNose, a method for quantitative assessment of the nose and lip, will be assessed on usability and reliability. The symmetry of the nose and lip was measured twice in 50 six-year-old complete and incomplete unilateral cleft lip and palate patients by four observers. For the frontal view the asymmetry level of the nose and upper lip were evaluated and for the basal view the asymmetry level of the nose and nostrils were evaluated. A mean inter-observer reliability when tracing each image once or twice was 0.70 and 0.75, respectively. Tracing the photographs with 2 observers and 4 observers gave a mean inter-observer score of 0.86 and 0.92, respectively. The mean intra-observer reliability varied between 0.80 and 0.84. SymNose is a practical and reliable tool for the retrospective assessment of large caseloads of 2D photographs of cleft patients for research purposes. Moderate to high single inter-observer reliability was found. For future research with SymNose reliable outcomes can be achieved by using the average outcomes of single tracings of two observers. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Brain serotonin and dopamine transporter bindings in adults with high-functioning autism.

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Nakamura, Kazuhiko; Sekine, Yoshimoto; Ouchi, Yasuomi; Tsujii, Masatsugu; Yoshikawa, Etsuji; Futatsubashi, Masami; Tsuchiya, Kenji J; Sugihara, Genichi; Iwata, Yasuhide; Suzuki, Katsuaki; Matsuzaki, Hideo; Suda, Shiro; Sugiyama, Toshiro; Takei, Nori; Mori, Norio

2010-01-01

Autism is a neurodevelopmental disorder that is characterized by repetitive and/or obsessive interests and behavior and by deficits in sociability and communication. Although its neurobiological underpinnings are postulated to lie in abnormalities of the serotoninergic and dopaminergic systems, the details remain unknown. To determine the occurrence of changes in the binding of serotonin and dopamine transporters, which are highly selective markers for their respective neuronal systems. Using positron emission tomography, we measured the binding of brain serotonin and dopamine transporters in each individual with the radioligands carbon 11 ((11)C)-labeled trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652) and 2beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane ([(11)C]WIN-35,428), respectively. Statistical parametric mapping was used for between-subject analysis and within-subject correlation analysis with respect to clinical variables. Participants recruited from the community. Twenty men (age range, 18-26 years; mean [SD] IQ, 99.3 [18.1]) with autism and 20 age- and IQ-matched control subjects. Serotonin transporter binding was significantly lower throughout the brain in autistic individuals compared with controls (P dopamine transporter binding was significantly higher in the orbitofrontal cortex of the autistic group (P dopamine transporter binding was significantly inversely correlated with serotonin transporter binding (r = -0.61; P = .004). The brains of autistic individuals have abnormalities in both serotonin transporter and dopamine transporter binding. The present findings indicate that the gross abnormalities in these neurotransmitter systems may underpin the neurophysiologic mechanism of autism. Our sample was not characteristic or representative of a typical sample of adults with autism in the community.

Optimal-mass-transfer-based estimation of glymphatic transport in living brain

OpenAIRE

Ratner, Vadim; Zhu, Liangjia; Kolesov, Ivan; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

2015-01-01

It was recently shown that the brain-wide cerebrospinal fluid (CSF) and interstitial fluid exchange system designated the ‘glymphatic pathway’ plays a key role in removing waste products from the brain, similarly to the lymphatic system in other body organs1,2. It is therefore important to study the flow patterns of glymphatic transport through the live brain in order to better understand its functionality in normal and pathological states. Unlike blood, the CSF does not flow rapidly through ...

Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells

Science.gov (United States)

Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K.

2012-01-01

Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-Riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with Km and Vmax values of 19 ± 3 µM and 0.235 ± 0.012 picomoles/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca++/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-Riboflavin. Apical and baso-lateral uptake of [3H]-Riboflavin clearly indicate that riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. Blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. PMID:22683359

14 CFR 67.205 - Ear, nose, throat, and equilibrium.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Ear, nose, throat, and equilibrium. 67.205..., nose, throat, and equilibrium. Ear, nose, throat, and equilibrium standards for a second-class airman..., vertigo or a disturbance of equilibrium. ...

Conceptual Design of Deployment Structure of Morphing Nose Cone

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Junlan Li

2013-01-01

Full Text Available For a reusable space vehicle or a missile, the shape of the nose cone has a significant effect on the drag of the vehicle. In this paper, the concept of morphing nose cone is proposed to reduce the drag when the reentry vehicle flies back into the atmosphere. The conceptual design of the structure of morphing nose cone is conducted. Mechanical design and optimization approach are developed by employing genetic algorithm to find the optimal geometric parameters of the morphing structure. An example is analyzed by using the proposed method. The results show that optimal solution supplies the minimum position error. The concept of morphing nose cone will provide a novel way for the drag reduction of reentry vehicle. The proposed method could be practically used for the design and optimization of the deployable structure of morphing nose cone.

Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism.

Science.gov (United States)

Jin, Byung-Ju; Smith, Alex J; Verkman, Alan S

2016-12-01

A "glymphatic system," which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier-Stokes and convection-diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS. © 2016 Jin et al.

Nose swabs and urinalysis as indicators of exposure to I-131

Energy Technology Data Exchange (ETDEWEB)

Barrall, R. C.

1963-06-15

During a maintenance operation on the Aromour Research Reactor, a heat lamp, which was drying a valve, caused a small quantity of I/sup 131/ become airborne. A continuous air monitor sampling in the area gave the alarm and the area ntified by the use of a 256 channel analyzer. Nose swabs of the personnel involved were taken and 24 hour urine samples were obtained. A single channel analyzer was set up, calibrated for I/sup 131/ and thyroid counts were started several hours after the incident. The thyroid count rose during the first 24 hour period and then declined closely following the 8 day half life of I/sup 131/. The urine Samples were analyzed by two different gamma counting techniques. Portions of the 24 hour urine sample were also sent to a commercial urinalysis service and analysis for I/sup 131/specifically requested. The results of the commercial service in this instance appeared to be poor. Nose swabs taken immediately after the incident were analyzed using a NaI well crystal. The average value of the ratio mu c on nose swabs to mu c in thyroid was found to be 2.6 x 1-/sup -1/ with all values within a factor of 6. The average value of the ratio mu c in 24 hour urine sample to mu c in thyroid was 5.7 with all values within a factor of 2. It would appear that at short times after a suspected exposure to I/sup 131/ nose swabs and urine samples are both useful in making a rapid assessment of exposure. The data presented are based on 10 subjects. (auth)

Aquaporin-11: A channel protein lacking apparent transport function expressed in brain

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Tsunenari Takashi

2006-05-01

Full Text Available Abstract Background The aquaporins are a family of integral membrane proteins composed of two subfamilies: the orthodox aquaporins, which transport only water, and the aquaglyceroporins, which transport glycerol, urea, or other small solutes. Two recently described aquaporins, numbers 11 and 12, appear to be more distantly related to the other mammalian aquaporins and aquaglyceroporins. Results We report on the characterization of Aquaporin-11 (AQP11. AQP11 RNA and protein is found in multiple rat tissues, including kidney, liver, testes and brain. AQP11 has a unique distribution in brain, appearing in Purkinje cell dendrites, hippocampal neurons of CA1 and CA2, and cerebral cortical neurons. Immunofluorescent staining of Purkinje cells indicates that AQP11 is intracellular. Unlike other aquaporins, Xenopus oocytes expressing AQP11 in the plasma membrane failed to transport water, glycerol, urea, or ions. Conclusion AQP11 is functionally distinct from other proteins of the aquaporin superfamily and could represent a new aquaporin subfamily. Further studies are necessary to elucidate the role of AQP11 in the brain.

Transport and metabolism at blood-brain interfaces and in neural cells: relevance to bilirubin-induced encephalopathy

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Silvia eGazzin

2012-05-01

Full Text Available Bilirubin, the end-product of heme catabolism, circulates in non pathological plasma mostly as a protein-bound species. When bilirubin concentration builds up, the free fraction of the molecule increases. Unbound bilirubin then diffuses across blood-brain interfaces into the brain, where it accumulates and exerts neurotoxic effects. In this classical view of bilirubin neurotoxicity, blood-brain interfaces act merely as structural barriers impeding the penetration of the pigment-bound carrier protein, and neural cells are considered as passive targets of its toxicity. Yet, the role of blood-brain interfaces in the occurrence of bilirubin encephalopathy appears more complex than being simple barriers to the diffusion of bilirubin, and neural cells such as astrocytes and neurons can play an active role in controlling the balance between the neuroprotective and neurotoxic effects of bilirubin. This article reviews the emerging in vivo and in vitro data showing that transport and metabolic detoxification mechanisms at the blood-brain and blood-CSF barriers may modulate bilirubin flux across both cellular interfaces, and that these protective functions can be affected in chronic hyperbilirubinemia. Then the in vivo and in vitro arguments in favor of the physiological antioxidant function of intracerebral bilirubin are presented, as well as with the potential role of transporters such as ABCC-1 and metabolizing enzymes such as cytochromes P-450 in setting the cerebral cell- and structure-specific toxicity of bilirubin following hyperbilirubinemia. The relevance of these data to the pathophysiology of bilirubin-induced neurological diseases is discussed.

The study on transport of brain-derived neurotrophic factor in facial nerve

International Nuclear Information System (INIS)

Li Yunchun; Li Lin; Wang Quanlin; Yang Xiaochuan; He Gang; Gao Bingqing; Lin Daicheng; Liang Chuanyu

2000-01-01

The transport information of brain-derived neurotrophic factor (BDNF) in facial nerve is studied using 125 I-BDNF or 131 I-BDNF. After one lateral facial nerve trunk of adult rabbit is transected, a silicone chamber is inserted between the stumps, and labelled compounds are administered into the chamber. Bilateral facial nerve trunk and facial nerve motor neurone of brain-stem of rabbits are collected and counted respectively, and imaged at coronary position of head in live rabbit. The results show that BDNF has a retrograde transport in facial nerve, and the transport of 131 I-BDNF is marked restrained by BDNF in facial nerve

Kinetics of Transferrin and Transferrin-Receptor during Iron Transport through Blood Brain Barrier

Science.gov (United States)

Khan, Aminul; Liu, Jin; Dutta, Prashanta

2017-11-01

Transferrin and its receptors play an important role during the uptake and transcytosis of iron by blood brain barrier (BBB) endothelial cells to maintain iron homeostasis in BBB endothelium and brain. In the blood side of BBB, ferric iron binds with the apo-transferrin to form holo-transferrin which enters the endothelial cell via transferrin receptor mediated endocytosis. Depending on the initial concentration of iron inside the cell endocytosed holo-transferrin can either be acidified in the endosome or exocytosed through the basolateral membrane. Acidification of holo-transferrin in the endosome releases ferrous irons which may either be stored and used by the cell or transported into brain side. Exocytosis of the holo-transferrin through basolateral membrane leads to transport of iron bound to transferrin into brain side. In this work, kinetics of internalization, recycling and exocytosis of transferrin and its receptors are modeled by laws of mass action during iron transport in BBB endothelial cell. Kinetic parameters for the model are determined by least square analysis. Our results suggest that the cell's initial iron content determines the extent of the two possible iron transport pathways, which will be presented in this talk Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

Electronic Noses and Tongues: Applications for the Food and Pharmaceutical Industries

Directory of Open Access Journals (Sweden)

Sharon Dea

2011-05-01

Full Text Available The electronic nose (e-nose is designed to crudely mimic the mammalian nose in that most contain sensors that non-selectively interact with odor molecules to produce some sort of signal that is then sent to a computer that uses multivariate statistics to determine patterns in the data. This pattern recognition is used to determine that one sample is similar or different from another based on headspace volatiles. There are different types of e-nose sensors including organic polymers, metal oxides, quartz crystal microbalance and even gas-chromatography (GC or combined with mass spectroscopy (MS can be used in a non-selective manner using chemical mass or patterns from a short GC column as an e-nose or “Z” nose. The electronic tongue reacts similarly to non-volatile compounds in a liquid. This review will concentrate on applications of e-nose and e-tongue technology for edible products and pharmaceutical uses.

Applications and advances in electronic-nose technologies

Science.gov (United States)

A. D. Wilson; M. Baietto

2009-01-01

Electronic-nose devices have received considerable attention in the field of sensor technology during the past twenty years, largely due to the discovery of numerous applications derived from research in diverse fields of applied sciences. Recent applications of electronic nose technologies have come through advances in sensor design, material improvements, software...

Glucose transporter 1 and monocarboxylate transporters 1, 2, and 4 localization within the glial cells of shark blood-brain-barriers.

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Carolina Balmaceda-Aguilera

Full Text Available Although previous studies showed that glucose is used to support the metabolic activity of the cartilaginous fish brain, the distribution and expression levels of glucose transporter (GLUT isoforms remained undetermined. Optic/ultrastructural immunohistochemistry approaches were used to determine the expression of GLUT1 in the glial blood-brain barrier (gBBB. GLUT1 was observed solely in glial cells; it was primarily located in end-feet processes of the gBBB. Western blot analysis showed a protein with a molecular mass of 50 kDa, and partial sequencing confirmed GLUT1 identity. Similar approaches were used to demonstrate increased GLUT1 polarization to both apical and basolateral membranes in choroid plexus epithelial cells. To explore monocarboxylate transporter (MCT involvement in shark brain metabolism, the expression of MCTs was analyzed. MCT1, 2 and 4 were expressed in endothelial cells; however, only MCT1 and MCT4 were present in glial cells. In neurons, MCT2 was localized at the cell membrane whereas MCT1 was detected within mitochondria. Previous studies demonstrated that hypoxia modified GLUT and MCT expression in mammalian brain cells, which was mediated by the transcription factor, hypoxia inducible factor-1. Similarly, we observed that hypoxia modified MCT1 cellular distribution and MCT4 expression in shark telencephalic area and brain stem, confirming the role of these transporters in hypoxia adaptation. Finally, using three-dimensional ultrastructural microscopy, the interaction between glial end-feet and leaky blood vessels of shark brain was assessed in the present study. These data suggested that the brains of shark may take up glucose from blood using a different mechanism than that used by mammalian brains, which may induce astrocyte-neuron lactate shuttling and metabolic coupling as observed in mammalian brain. Our data suggested that the structural conditions and expression patterns of GLUT1, MCT1, MCT2 and MCT4 in shark

Influence of histidine on zinc transport into rat brain

Energy Technology Data Exchange (ETDEWEB)

Takeda, Atsushi; Suzuki, Mai; Okada, Shoji; Oku, Naoto [Shizuoka Univ. (Japan). School of Pharmaceutical Sciences

2000-06-01

The brain of rats injected intravenously with {sup 65}Zn-His or {sup 65}ZnCl{sub 2} was subjected to autoradiography to study the role of histidine on zinc transport into the brain. One hour after injection, the radioactivity from {sup 65}Zn-His was largely concentrated in the choroid plexus in the ventricles. Six days after injection, the radioactivity from {sup 65}Zn-His was relatively concentrated in the hippocampal CA3 and dentate gyrus and the amygdala. The relative distribution of {sup 65}Zn-His in the brain was similar to that of {sup 65}ZnCl{sub 2} group at both 1 h and 6 days, suggesting that histidine may participate in zinc uptake in the brain. On the other hand, the clearance of the {sup 65}Zn-His group from the blood was higher than that of the {sup 65}ZnCl{sub 2} group. Brain uptake of the former was lower than that of the latter both 1 h and 6 days after injection. These results suggest that zinc uptake in the brain is influenced by histidine levels in the bloodstream. (author)

Assessment of compost maturity by using an electronic nose.

Science.gov (United States)

López, Rafael; Giráldez, Inmaculada; Palma, Alberto; Jesús Díaz, M

2016-02-01

The composting process produces and emits hundreds of different gases. Volatile organic compounds (VOCs) can provide information about progress of composting process. This paper is focused on the qualitative and quantitative relationships between compost age, as sign of compost maturity, electronic-nose (e-nose) patterns and composition of compost and composting gas at an industrial scale plant. Gas and compost samples were taken at different depths from composting windrows of different ages. Temperature, classical chemical parameters, O2, CO, combustible gases, VOCs and e-nose profiles were determined and related using principal component analysis (PCA). Factor analysis carried out to a data set including compost physical-chemical properties, pile pore gas composition and composting time led to few factors, each one grouping together standard composting parameters in an easy to understand way. PCA obtained from e-nose profiles allowed the classifying of piles, their aerobic-anaerobic condition, and a rough estimation of the composting time. That would allow for immediate and in-situ assessment of compost quality and maturity by using an on-line e-nose. The e-nose patterns required only 3-4 sensor signals to account for a great percentage (97-98%) of data variance. The achieved patterns both from compost (chemical analysis) and gas (e-nose analysis) samples are robust despite the high variability in feedstock characteristics (3 different materials), composting conditions and long composting time. GC-MS chromatograms supported the patterns. Copyright © 2015 Elsevier Ltd. All rights reserved.

Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity.

Science.gov (United States)

Matsui, Takashi; Omuro, Hideki; Liu, Yu-Fan; Soya, Mariko; Shima, Takeru; McEwen, Bruce S; Soya, Hideaki

2017-06-13

Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry-based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain.

Handbook of Machine Olfaction: Electronic Nose Technology

Science.gov (United States)

Pearce, Tim C.; Schiffman, Susan S.; Nagle, H. Troy; Gardner, Julian W.

2003-02-01

"Electronic noses" are instruments which mimic the sense of smell. Consisting of olfactory sensors and a suitable signal processing unit, they are able to detect and distinguish odors precisely and at low cost. This makes them very useful for a remarkable variety of applications in the food and pharmaceutical industry, in environmental control or clinical diagnostics and more. The scope covers biological and technical fundamentals and up-to-date research. Contributions by renowned international scientists as well as application-oriented news from successful "e-nose" manufacturers give a well-rounded account of the topic, and this coverage from R&D to applications makes this book a must-have read for e-nose researchers, designers and users alike.

Histopathology confirms white-nose syndrome in bats in Europe.

Science.gov (United States)

Pikula, Jiri; Bandouchova, Hana; Novotny, Ladislav; Meteyer, Carol U; Zukal, Jan; Irwin, Nancy R; Zima, Jan; Martínková, Natália

2012-01-01

White-nose syndrome, associated with the fungal skin infection geomycosis, caused regional population collapse in bats in North America. Our results, based on histopathology, show the presence of white-nose syndrome in Europe. Dermatohistopathology on two bats (Myotis myotis) found dead in March 2010 with geomycosis in the Czech Republic had characteristics resembling Geomyces destructans infection in bats confirmed with white-nose syndrome in US hibernacula. In addition, a live M. myotis, biopsied for histopathology during hibernation in April 2011, had typical fungal infection with cupping erosion and invasion of muzzle skin diagnostic for white-nose syndrome and conidiospores identical to G. destructans that were genetically confirmed as G. destructans.

Advances of electronic nose and its application in fresh foods: A review.

Science.gov (United States)

Shi, Hao; Zhang, Min; Adhikari, Benu

2017-06-30

The science and technology aspects of electronic nose (E-nose) has been developed rapidly in last decade (2006-2016). This paper reviews of the publications that that cover the developments in science and technological aspects of electronic nose together with its application in fresh foods. The first part of this review covers the sensing and pattern recognition system (PR) of E-nose. The second part covers the application of E-nose in classification, flavor detection, and evaluation of spoilage in fresh foods area. With more new sensor materials to be found and more combination between E-nose and other analysis technologies, the usages of E-nose in fresh foods will have wider prospects.

Plant Pest Detection Using an Artificial Nose System: A Review

Directory of Open Access Journals (Sweden)

Shaoqing Cui

2018-01-01

Full Text Available This paper reviews artificial intelligent noses (or electronic noses as a fast and noninvasive approach for the diagnosis of insects and diseases that attack vegetables and fruit trees. The particular focus is on bacterial, fungal, and viral infections, and insect damage. Volatile organic compounds (VOCs emitted from plants, which provide functional information about the plant’s growth, defense, and health status, allow for the possibility of using noninvasive detection to monitor plants status. Electronic noses are comprised of a sensor array, signal conditioning circuit, and pattern recognition algorithms. Compared with traditional gas chromatography–mass spectrometry (GC-MS techniques, electronic noses are noninvasive and can be a rapid, cost-effective option for several applications. However, using electronic noses for plant pest diagnosis is still in its early stages, and there are challenges regarding sensor performance, sampling and detection in open areas, and scaling up measurements. This review paper introduces each element of electronic nose systems, especially commonly used sensors and pattern recognition methods, along with their advantages and limitations. It includes a comprehensive comparison and summary of applications, possible challenges, and potential improvements of electronic nose systems for different plant pest diagnoses.

Plant Pest Detection Using an Artificial Nose System: A Review.

Science.gov (United States)

Cui, Shaoqing; Ling, Peter; Zhu, Heping; Keener, Harold M

2018-01-28

This paper reviews artificial intelligent noses (or electronic noses) as a fast and noninvasive approach for the diagnosis of insects and diseases that attack vegetables and fruit trees. The particular focus is on bacterial, fungal, and viral infections, and insect damage. Volatile organic compounds (VOCs) emitted from plants, which provide functional information about the plant's growth, defense, and health status, allow for the possibility of using noninvasive detection to monitor plants status. Electronic noses are comprised of a sensor array, signal conditioning circuit, and pattern recognition algorithms. Compared with traditional gas chromatography-mass spectrometry (GC-MS) techniques, electronic noses are noninvasive and can be a rapid, cost-effective option for several applications. However, using electronic noses for plant pest diagnosis is still in its early stages, and there are challenges regarding sensor performance, sampling and detection in open areas, and scaling up measurements. This review paper introduces each element of electronic nose systems, especially commonly used sensors and pattern recognition methods, along with their advantages and limitations. It includes a comprehensive comparison and summary of applications, possible challenges, and potential improvements of electronic nose systems for different plant pest diagnoses.

A new kernel discriminant analysis framework for electronic nose recognition

International Nuclear Information System (INIS)

Zhang, Lei; Tian, Feng-Chun

2014-01-01

Graphical abstract: - Highlights: • This paper proposes a new discriminant analysis framework for feature extraction and recognition. • The principle of the proposed NDA is derived mathematically. • The NDA framework is coupled with kernel PCA for classification. • The proposed KNDA is compared with state of the art e-Nose recognition methods. • The proposed KNDA shows the best performance in e-Nose experiments. - Abstract: Electronic nose (e-Nose) technology based on metal oxide semiconductor gas sensor array is widely studied for detection of gas components. This paper proposes a new discriminant analysis framework (NDA) for dimension reduction and e-Nose recognition. In a NDA, the between-class and the within-class Laplacian scatter matrix are designed from sample to sample, respectively, to characterize the between-class separability and the within-class compactness by seeking for discriminant matrix to simultaneously maximize the between-class Laplacian scatter and minimize the within-class Laplacian scatter. In terms of the linear separability in high dimensional kernel mapping space and the dimension reduction of principal component analysis (PCA), an effective kernel PCA plus NDA method (KNDA) is proposed for rapid detection of gas mixture components by an e-Nose. The NDA framework is derived in this paper as well as the specific implementations of the proposed KNDA method in training and recognition process. The KNDA is examined on the e-Nose datasets of six kinds of gas components, and compared with state of the art e-Nose classification methods. Experimental results demonstrate that the proposed KNDA method shows the best performance with average recognition rate and total recognition rate as 94.14% and 95.06% which leads to a promising feature extraction and multi-class recognition in e-Nose

Application of direct discrete method (DDM) to multigroup neutron transport problems

International Nuclear Information System (INIS)

Vosoughi, Naser; Salehi, Ali Akbar; Shahriari, Majid

2003-01-01

The Direct Discrete Method (DDM), which produced excellent results for one-group neutron transport problems, has been developed for multigroup energy. A multigroup neutron transport discrete equation has been produced for a cylindrical shape fuel element with and without associated coolant regions with two boundary conditions. The calculations are illustrated for two-group energy by graphs showing the fast and thermal fluxes. The validity of the results are tested against the results obtained by the ANISN code. (author)

Histopathology confirms white-nose syndrome in bats in Europe

Science.gov (United States)

Pikula, J.; Bandouchova, H.; Novotny, L.; Meteyer, C.U.; Zukal, J.; Irwin, N.R.; Zima, J.; Martinkova, N.

2012-01-01

White-nose syndrome, associated with the fungal skin infection geomycosis, caused regional population collapse in bats in North America. Our results, based on histopathology, show the presence of white-nose syndrome in Europe. Dermatohistopathology on two bats (Myotis myotis) found dead in March 2010 with geomycosis in the Czech Republic had characteristics resembling Geomyces destructans infection in bats confirmed with white-nose syndrome in US hibernacula. In addition, a live M. myotis, biopsied for histopathology during hibernation in April 2011, had typical fungal infection with cupping erosion and invasion of muzzle skin diagnostic for white-nose syndrome and conidiospores identical to G. destructans that were genetically confirmed as G. destructans. ?? Wildlife Disease Association 2012.

Spatial model of convective solute transport in brain extracellular space does not support a “glymphatic” mechanism

Science.gov (United States)

Jin, Byung-Ju; Smith, Alex J.

2016-01-01

A “glymphatic system,” which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier–Stokes and convection–diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS. PMID:27836940

The spectacular human nose: an amplifier of individual quality?

Directory of Open Access Journals (Sweden)

Åse Kristine Rognmo Mikalsen

2014-04-01

Full Text Available Amplifiers are signals that improve the perception of underlying differences in quality. They are cost free and advantageous to high quality individuals, but disadvantageous to low quality individuals, as poor quality is easier perceived because of the amplifier. For an amplifier to evolve, the average fitness benefit to the high quality individuals should be higher than the average cost for the low quality individuals. The human nose is, compared to the nose of most other primates, extraordinary large, fragile and easily broken—especially in male–male interactions. May it have evolved as an amplifier among high quality individuals, allowing easy assessment of individual quality and influencing the perception of attractiveness? We tested the latter by manipulating the position of the nose tip or, as a control, the mouth in facial pictures and had the pictures rated for attractiveness. Our results show that facial attractiveness failed to be influenced by mouth manipulations. Yet, facial attractiveness increased when the nose tip was artificially centered according to other facial features. Conversely, attractiveness decreased when the nose tip was displaced away from its central position. Our results suggest that our evaluation of attractiveness is clearly sensitive to the centering of the nose tip, possibly because it affects our perception of the face’s symmetry and/or averageness. However, whether such centering is related to individual quality remains unclear.

Mechanism and developmental changes in iron transport across the blood-brain barrier.

Science.gov (United States)

Morgan, Evan H; Moos, Torben

2002-01-01

Transferrin and iron uptake by the brain were measured using [(59)Fe-(125)I]transferrin injected intravenously in rats aged from 15 days to 22 weeks. The values for both decreased with age. In rats aged 18 and 70 days the uptake was measured at short time intervals after the injection. When expressed as the volume of distribution (Vd), which represents the volume of plasma from which the transferrin and iron were derived, the results for iron were greater than those of transferrin as early as 7 min after injection and the difference increased rapidly with time, especially in the younger animals. A very similar time course was found for uptake by bone marrow (femurs) where iron uptake involves receptor-mediated endocytosis of Fe-transferrin, release of iron in the cell and recycling of apo-transferrin to the blood. It is concluded that, during transport of transferrin-bound plasma iron into the brain, a similar process occurs in brain capillary endothelial cells (BCECs) and that transcytosis of transferrin into the brain interstitium is only a minor pathway. Also, the high rate of iron transport into the brain in young animals, when iron requirements are high due to rapid growth of the brain, is a consequence of the level of expression and rate of recycling of transferrin receptors on BCECs. As the animal and brain mature both decrease. Copyright 2002 S. Karger AG, Basel

Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior.

Science.gov (United States)

Hindle, Samantha J; Munji, Roeben N; Dolghih, Elena; Gaskins, Garrett; Orng, Souvinh; Ishimoto, Hiroshi; Soung, Allison; DeSalvo, Michael; Kitamoto, Toshihiro; Keiser, Michael J; Jacobson, Matthew P; Daneman, Richard; Bainton, Roland J

2017-10-31

Central nervous system (CNS) chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB). Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice). Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Sensors: From Biosensors to the Electronic Nose

OpenAIRE

García-González, Diego L.; Aparicio López, Ramón

2002-01-01

The recent advances in sensor devices have allowed the developing of new applications in many technological fields. This review describes the current state-of-the-art of this sensor technology, placing special emphasis on the food applications. The design, technology and sensing mechanism of each type of sensor are analysed. A description of the main characteristics of the electronic nose and electronic tongue (taste sensors) is also given. Finally, the applications of some statistical pro...

Sensors: From biosensors to the electronic nose

OpenAIRE

Aparicio, Ramón; García-González, Diego L.

2002-01-01

The recent advances in sensor devices have allowed the developing of new applications in many technological fields. This review describes the current state-of-the-art of this sensor technology, placing special emphasis on the food applications. The design, technology and sensing mechanism of each type of sensor are analysed. A description of the main characteristics of the electronic nose and electronic tongue (taste sensors) is also given. Finally, the applications of some statistical proced...

Similar Fracture Patterns in Human Nose and Gothic Cathedral.

Science.gov (United States)

Lee, Shu Jin; Tse, Kwong Ming; Lee, Heow Pueh

2015-10-01

This study proposes that the bony anatomy of the human nose and masonry structure of the Gothic cathedral are geometrically similar, and have common fracture patterns. We also aim to correlate the fracture patterns observed in patients' midface structures with those seen in the Gothic cathedral using computational approach. CT scans of 33 patients with facial fractures were examined and compared with computer simulations of both the Gothic cathedral and human nose. Three similar patterns were found: (1) Cracks of the nasal arch with crumpling of the vertical buttresses akin to the damage seen during minor earthquakes; (2) lateral deviation of the central nasal arch and collapse of the vertical buttresses akin to those due to lateral forces from wind and in major earthquakes; and (3) Central arch collapse seen as a result of collapse under excessive dead weight. Interestingly, the finding of occult nasal and septal fractures in the mandible fractures with absence of direct nasal trauma highlights the possibility of transmission of forces from the foundation to the arch leading to structural failure. It was also found that the structural buttresses of the Gothic cathedral delineate the vertical buttresses in the human midface structure. These morphologic similarities between the human nose and Gothic cathedral will serve as a basis to study the biomechanics of nasal fractures. Identification of structural buttresses in a skeletal structure has important implications for reconstruction as reestablishment of structural continuity restores normal anatomy and architectural stability of the human midface structure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Mapping directionality specific volume changes using tensor based morphometry: an application to the study of gyrogenesis and lateralization of the human fetal brain.

Science.gov (United States)

Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A; Kim, Kio; Rousseau, Francois; Glenn, Orit A; Barkovich, A James; Studholme, Colin

2012-11-01

Tensor based morphometry (TBM) is a powerful approach to analyze local structural changes in brain anatomy. However, conventional scalar TBM methods do not completely capture all direction specific volume changes required to model complex changes such as those during brain growth. In this paper, we describe novel TBM descriptors for studying direction-specific changes in a subject population which can be used in conjunction with scalar TBM to analyze local patterns in directionality of volume change during brain development. We also extend the methodology to provide a new approach to mapping directional asymmetry in deformation tensors associated with the emergence of structural asymmetry in the developing brain. We illustrate the use of these methods by studying developmental patterns in the human fetal brain, in vivo. Results show that fetal brain development exhibits a distinct spatial pattern of anisotropic growth. The most significant changes in the directionality of growth occur in the cortical plate at major sulci. Our analysis also detected directional growth asymmetry in the peri-Sylvian region and the medial frontal lobe of the fetal brain. Copyright © 2012 Elsevier Inc. All rights reserved.

Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.

Science.gov (United States)

Heni, Martin; Schöpfer, Patricia; Peter, Andreas; Sartorius, Tina; Fritsche, Andreas; Synofzik, Matthis; Häring, Hans-Ulrich; Maetzler, Walter; Hennige, Anita M

2014-08-01

Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.

Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

Science.gov (United States)

Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

2015-02-01

Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Graphene-Based Chemical Vapor Sensors for Electronic Nose Applications

Science.gov (United States)

Nallon, Eric C.

An electronic nose (e-nose) is a biologically inspired device designed to mimic the operation of the olfactory system. The e-nose utilizes a chemical sensor array consisting of broadly responsive vapor sensors, whose combined response produces a unique pattern for a given compound or mixture. The sensor array is inspired by the biological function of the receptor neurons found in the human olfactory system, which are inherently cross-reactive and respond to many different compounds. The use of an e-nose is an attractive approach to predict unknown odors and is used in many fields for quantitative and qualitative analysis. If properly designed, an e-nose has the potential to adapt to new odors it was not originally designed for through laboratory training and algorithm updates. This would eliminate the lengthy and costly R&D costs associated with materiel and product development. Although e-nose technology has been around for over two decades, much research is still being undertaken in order to find new and more diverse types of sensors. Graphene is a single-layer, 2D material comprised of carbon atoms arranged in a hexagonal lattice, with extraordinary electrical, mechanical, thermal and optical properties due to its 2D, sp2-bonded structure. Graphene has much potential as a chemical sensing material due to its 2D structure, which provides a surface entirely exposed to its surrounding environment. In this configuration, every carbon atom in graphene is a surface atom, providing the greatest possible surface area per unit volume, so that electron transport is highly sensitive to adsorbed molecular species. Graphene has gained much attention since its discovery in 2004, but has not been realized in many commercial electronics. It has the potential to be a revolutionary material for use in chemical sensors due to its excellent conductivity, large surface area, low noise, and versatile surface for functionalization. In this work, graphene is incorporated into a

Monocarboxylate transporters in the brain and in cancer.

Science.gov (United States)

Pérez-Escuredo, Jhudit; Van Hée, Vincent F; Sboarina, Martina; Falces, Jorge; Payen, Valéry L; Pellerin, Luc; Sonveaux, Pierre

2016-10-01

Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1-4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Pediatric Obesity and Ear, Nose, and Throat Disorders

Science.gov (United States)

... Marketplace Find an ENT Doctor Near You Pediatric Obesity and Ear, Nose, and Throat Disorders Pediatric Obesity ... self-esteem, and isolation from their peers. Pediatric obesity and otolaryngic problems Otolaryngologists, or ear, nose, and ...

Pediatric Obesity and Ear, Nose, and Throat Disorders

Science.gov (United States)

... ENTCareers Marketplace Find an ENT Doctor Near You Pediatric Obesity and Ear, Nose, and Throat Disorders Pediatric ... of self-esteem, and isolation from their peers. Pediatric obesity and otolaryngic problems Otolaryngologists, or ear, nose, ...

The serotonin transporter in rhesus monkey brain: comparison of DASB and citalopram binding sites

International Nuclear Information System (INIS)

Zeng Zhizhen; Chen, T.-B.; Miller, Patricia J.; Dean, Dennis; Tang, Y.S.; Sur, Cyrille; Williams, David L.

2006-01-01

We have characterized the interaction of the serotonin transporter ligand [ 3 H]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine (DASB) with rhesus monkey brain in vitro using tissue homogenate binding and autoradiographic mapping. [ 3 H]-DASB, a tritiated version of the widely used [ 11 C] positron emission tomography tracer, was found to selectively bind to a single population of sites with high affinity (K d =0.20±0.04 nM). The serotonin transporter density (B max ) obtained for rhesus frontal cortex was found to be 66±8 fmol/mg protein using [ 3 H]-DASB, similar to the B max value obtained using the reference radioligand [ 3 H]-citalopram, a well-characterized and highly selective serotonin reuptake inhibitor (83±22 fmol/mg protein). Specific binding sites of both [ 3 H]-DASB and [ 3 H]-citalopram were similarly and nonuniformly distributed throughout the rhesus central nervous system, in a pattern consistent with serotonin transporter localization reported for human brain. Regional serotonin transporter densities, estimated from optical densities of the autoradiographic images, were well correlated between the two radioligands. Finally, DASB and fluoxetine showed dose-dependent full inhibition of [ 3 H]-citalopram binding in a competition autoradiographic study, with K i values in close agreement with those obtained from rhesus brain homogenates. This side-by-side comparison of [ 3 H]-DASB and [ 3 H]-citalopram binding sites in rhesus tissue homogenates and in adjacent rhesus brain slices provides additional support for the use of [ 11 C]-DASB to assess the availability and distribution of serotonin transporters in nonhuman primates

Application Of Electronic Nose And Ion Mobility Spectrometer To Quality Control Of Spice Mixtures

International Nuclear Information System (INIS)

Banach, U.; Tiebe, C.; Huebert, Th.

2009-01-01

The aim of the paper is to demonstrate the application of electronic nose (e-nose) and ion mobility spectrometry (IMS) to quality control and to find out product adulteration of spice mixtures. Therefore the gaseous head space phase of four different spice mixtures (spices for sausages and saveloy) was differed from original composition and product adulteration. In this set of experiments metal-oxide type e-nose (KAMINA-type) has been used, and characteristic patterns of data corresponding to various complex odors of the four different spice mixtures were generated. Simultaneously an ion mobility spectrometer was coupled also to an emission chamber for the detection of gaseous components of spice mixtures. The two main methods that have been used show a clear discrimination between the original spice mixtures and product adulteration could be distinguished from original spice mixtures.

Ectoparasites may serve as vectors for the white-nose syndrome fungus.

Science.gov (United States)

Lučan, Radek K; Bandouchova, Hana; Bartonička, Tomáš; Pikula, Jiri; Zahradníková, Alexandra; Zukal, Jan; Martínková, Natália

2016-01-13

Vertebrate ectoparasites frequently play a role in transmission of infectious agents. Pseudogymnoascus destructans is a psychrophilic fungus known to cause white-nose syndrome (WNS), an emerging infectious disease of bats. It is transmitted with direct contact between bats or with contaminated environment. The aim of this study was to examine wing mites from the family Spinturnicidae parasitizing hibernating bats for the presence of P. destructans propagules as another possible transmission route. Wing mites collected from 33 bats at four hibernation sites in the Czech Republic were inspected for the presence and load of pathogen's DNA using quantitative PCR. Simultaneously, wing damage of inspected bats caused by WNS was quantified using ultraviolet light (UV) transillumination and the relationship between fungal load on wing mites and intensity of infection was subjected to correlation analysis. All samples of wing mites were positive for the presence of DNA of P. destructans, indicating a high probability of their role in the transmission of the pathogen's propagules between bats. Mechanical transport of adhesive P. destructans spores and mycelium fragments on the body of spinturnicid mites is highly feasible. The specialised lifestyle of mites, i.e., living on bat wing membranes, the sites most typically affected by fungal growth, enables pathogen transport. Moreover, P. destructans metabolic traits suggest an ability to grow and sporulate on a range of organic substrates, including insects, which supports the possibility of growth on bat ectoparasites, at least in periods when bats roost in cold environments and enter torpor. In addition to transport of fungal propagules, mites may facilitate entry of fungal hyphae into the epidermis through injuries caused by biting.

Directing energy transport in organic photovoltaic cells using interfacial exciton gates.

Science.gov (United States)

Menke, S Matthew; Mullenbach, Tyler K; Holmes, Russell J

2015-04-28

Exciton transport in organic semiconductors is a critical, mediating process in many optoelectronic devices. Often, the diffusive and subdiffusive nature of excitons in these systems can limit device performance, motivating the development of strategies to direct exciton transport. In this work, directed exciton transport is achieved with the incorporation of exciton permeable interfaces. These interfaces introduce a symmetry-breaking imbalance in exciton energy transfer, leading to directed motion. Despite their obvious utility for enhanced exciton harvesting in organic photovoltaic cells (OPVs), the emergent properties of these interfaces are as yet uncharacterized. Here, directed exciton transport is conclusively demonstrated in both dilute donor and energy-cascade OPVs where judicious optimization of the interface allows exciton transport to the donor-acceptor heterojunction to occur considerably faster than when relying on simple diffusion. Generalized systems incorporating multiple exciton permeable interfaces are also explored, demonstrating the ability to further harness this phenomenon and expeditiously direct exciton motion, overcoming the diffusive limit.

Stereospecific transport of Tyr-MIF-1 across the blood-brain barrier by peptide transport system-1

Energy Technology Data Exchange (ETDEWEB)

Banks, W.A.; Kastin, A.J.; Michals, E.A.; Barrera, C.M. (Veterans Affairs Medical Center, New Orleans, LA (USA))

1990-10-01

Previous studies have suggested that peptide transport system-1 (PTS-1), the saturable system that transports Tyr-MIF-1, the enkephalins, and related peptides out of the central nervous system (CNS), exhibits stereospecificity. In the present studies, we showed that {sup 125}I-L-Tyr-MIF-1, but not {sup 131}I-D-Tyr-MIF-1, was cleared from the CNS more rapidly than could be accounted for by nonspecific mechanisms. Such clearance was inhibited by a 1.0 nmol dose of L-Tyr-MIF-1, but not by D-Tyr-MIF-1. Neither L- nor D-Tyr-MIF-1 altered the much lower clearance of I-D-Tyr-MIF-1 from the brain. Radioactivity recovered from the vascular space after the injection of {sup 125}I-Tyr-MIF-1 into the lateral ventricle of the brain eluted by HPLC primarily as intact peptide, demonstrating that most of the Tyr-MIF-1 was not degraded during transport. By contrast, the nonsaturable unidirectional influx of Tyr-MIF-1 into the CNS did not distinguish between the isomers. These studies confirm and extend the observations that Tyr-MIF-1 is transported out of the CNS by a saturable, stereospecific transport system as an intact peptide while the influx into the CNS is by a nonsaturable mechanism that does not distinguish between the isomers.

Effect of nose bluntness and afterbody shape on aerodynamic characteristics of a monoplanar missile concept with bodies of circular and elliptical cross sections at a Mach number of 2.50

Science.gov (United States)

Graves, E. B.; Fournier, R. H.

1979-01-01

The tests were performed at a Mach number of 2.50 and at angles of attack from about -4 deg to 32 deg. The results indicate that increasing nose bluntness increases zero lift drag and decreases both the maximum lift-drag ratio and the level of directional stability. The center of pressure generally moves forward with increasing nose size; however, small nose radii on the modified elliptical configurations move the center of pressure rearward. The circular bodied configurations exhibit the greatest longitudinal stability and the least directional stability. Concepts with the variable geometry afterbody contour display the most directional stability and the greatest zero lift drag.

Prospective Study of the Surgical Techniques Used in Primary Rhinoplasty on the Caucasian Nose and Comparison of the Preoperative and Postoperative Anthropometric Nose Measurements

Science.gov (United States)

Berger, Cezar Augusto Sarraf; Freitas, Renato da Silva; Malafaia, Osvaldo; Pinto, José Simão de Paula; Macedo Filho, Evaldo Dacheux; Mocellin, Marcos; Fagundes, Marina Serrato Coelho

2014-01-01

Introduction The knowledge and study of surgical techniques and anthropometric measurements of the nose make possible a qualitative and quantitative analysis of surgical results. Objective Study the main technique used in rhinoplasty on Caucasian noses and compare preoperative and postoperative anthropometric measurements of the nose. Methods A prospective study with 170 patients was performed at a private hospital. Data were collected using the Electronic System Integrated of Protocols software (Sistema Integrado de Protocolos Eletrônicos, SINPE©). The surgical techniques used in the nasal dorsum and tip were evaluated. Preoperative and 12-month follow-up photos as well as the measurements compared with the ideal aesthetic standard of a Caucasian nose were analyzed objectively. Student t test and standard deviation test were applied. Results There was a predominance of endonasal access (94.4%). The most common dorsum technique was hump removal (33.33%), and the predominance of sutures (24.76%) was observed on the nasal tip, with the lateral intercrural the most frequent (32.39%). Comparison between preoperative and postoperative photos found statistically significant alterations on the anthropometric measurements of the noses. Conclusion The main surgical techniques on Caucasian noses were evaluated, and a great variety was found. The evaluation of anthropometric measurements of the nose proved the efficiency of the performed procedures. PMID:25992149

Identifying Septal Support Reconstructions for Saddle Nose Deformity: The Cakmak Algorithm.

Science.gov (United States)

Cakmak, Ozcan; Emre, Ismet Emrah; Ozkurt, Fazil Emre

2015-01-01

The saddle nose deformity is one of the most challenging problems in nasal surgery with a less predictable and reproducible result than other nasal procedures. The main feature of this deformity is loss of septal support with both functional and aesthetic implications. Most reports on saddle nose have focused on aesthetic improvement and neglected the reestablishment of septal support to improve airway. To explain how the Cakmak algorithm, an algorithm that describes various fixation techniques and grafts in different types of saddle nose deformities, aids in identifying saddle nose reconstructions that restore supportive nasal framework and provide the aesthetic improvements typically associated with procedures to correct saddle nose deformities. This algorithm presents septal support reconstruction of patients with saddle nose deformity based on the experience of the senior author in 206 patients with saddle nose deformity. Preoperative examination, intraoperative assessment, reconstruction techniques, graft materials, and patient evaluation of aesthetic success were documented, and 4 different types of saddle nose deformities were defined. The Cakmak algorithm classifies varying degrees of saddle nose deformity from type 0 to type 4 and helps identify the most appropriate surgical procedure to restore the supportive nasal framework and aesthetic dorsum. Among the 206 patients, 110 women and 96 men, mean (range) age was 39.7 years (15-68 years), and mean (range) of follow-up was 32 months (6-148 months). All but 12 patients had a history of previous nasal surgeries. Application of the Cakmak algorithm resulted in 36 patients categorized with type 0 saddle nose deformities; 79, type 1; 50, type 2; 20, type 3a; 7, type 3b; and 14, type 4. Postoperative photographs showed improvement of deformities, and patient surveys revealed aesthetic improvement in 201 patients and improvement in nasal breathing in 195 patients. Three patients developed postoperative infection

A Solid Trap and Thermal Desorption System with Application to a Medical Electronic Nose

Directory of Open Access Journals (Sweden)

Xuntao Xu

2008-11-01

Full Text Available In this paper, a solid trap/thermal desorption-based odorant gas condensation system has been designed and implemented for measuring low concentration odorant gas. The technique was successfully applied to a medical electronic nose system. The developed system consists of a flow control unit, a temperature control unit and a sorbent tube. The theoretical analysis and experimental results indicate that gas condensation, together with the medical electronic nose system can significantly reduce the detection limit of the nose system and increase the system’s ability to distinguish low concentration gas samples. In addition, the integrated system can remove the influence of background components and fluctuation of operational environment. Even with strong disturbances such as water vapour and ethanol gas, the developed system can classify the test samples accurately.

Quantitative autoradiography of ligands for dopamine receptors and transporters in brain of Göttingen minipig

DEFF Research Database (Denmark)

Minuzzi, Luciano; Olsen, Aage Kristian; Bender, Dirk

2006-01-01

The pig has been used as animal model for positron emission tomography (PET) studies of dopamine (DA) receptors and pharmacological perturbations of DA neurotransmission. However, the binding properties of DA receptors and transporters in pig brain have not been characterized in vitro. Therefore...... in young and old pigs, and were close to those reported for rat and human brain. Furthermore, gradients in the concentrations of D1 and D2/3 sites in striatum measured in vitro agreed with earlier findings in PET studies. However, the dopamine transporter (DAT) ligand [3H]GBR12935 did not bind in pig brain...

A new therapeutic strategy for lengthening severe short nose.

Science.gov (United States)

Rikimaru, Hideaki; Kiyokawa, Kensuke; Watanabe, Koichi; Koga, Noriyuki; Nishi, Yukiko

2010-03-01

Correction of severe short nose is a distressing problem for plastic surgeons. It is difficult to simultaneously lengthen the 3 components of the nose, which are the outer skin envelope, the framework, and the mucosal lining. We developed a new method to lengthen the nose more than 10 mm definitively and safely, which was performed using the technique of distraction osteogenesis. The procedure involves a 2-stage operation. At the first stage, boat-shaped iliac bone is grafted on the dorsum. More than 6 months later, the second-stage operation is performed. The grafted bone is cut horizontally in the center, and the distraction device is applied to it. Distraction osteogenesis is started after a latency period of 14 days and performed at a rate of 0.6 mm once daily. The distraction device is replaced by a special attachment (Ribbond; Ribbond Inc) during the 3-month consolidation period. Our method was applied for 2 patients with congenitally and posttraumatic severe short nose, respectively. The total amount of distraction osteogenesis was 12.6 and 13.8 mm, respectively. The profiles of both of the patients improved, and they were satisfied with the results. The method we developed is an entirely new approach to the correction of severe short nose. Furthermore, it was determined that nonvascularized grafted iliac bone could be lengthened by distraction osteogenesis. Our new method was a very effective and definitive technique and could become a mainstream procedure for the correction of severe short nose.

Targeted drug delivery to the brain using magnetic nanoparticles.

Science.gov (United States)

Thomsen, Louiza Bohn; Thomsen, Maj Schneider; Moos, Torben

2015-01-01

Brain capillary endothelial cells denote the blood-brain barrier (BBB), and conjugation of nanoparticles with antibodies that target molecules expressed by these endothelial cells may facilitate their uptake and transport into the brain. Magnetic nanoparticles can be encapsulated in liposomes and carry large molecules with therapeutic potential, for example, siRNA, cDNA and polypeptides. An additional approach to enhance the transport of magnetic nanoparticles across the BBB is the application of extracranially applied magnetic force. Stepwise targeting of magnetic nanoparticles to brain capillary endothelial cells followed by transport through the BBB using magnetic force may prove a novel mechanism for targeted therapy of macromolecules to the brain.

Identification of Chinese Herbal Medicines with Electronic Nose Technology: Applications and Challenges.

Science.gov (United States)

Zhou, Huaying; Luo, Dehan; GholamHosseini, Hamid; Li, Zhong; He, Jiafeng

2017-05-09

This paper provides a review of the most recent works in machine olfaction as applied to the identification of Chinese Herbal Medicines (CHMs). Due to the wide variety of CHMs, the complexity of growing sources and the diverse specifications of herb components, the quality control of CHMs is a challenging issue. Much research has demonstrated that an electronic nose (E-nose) as an advanced machine olfaction system, can overcome this challenge through identification of the complex odors of CHMs. E-nose technology, with better usability, high sensitivity, real-time detection and non-destructive features has shown better performance in comparison with other analytical techniques such as gas chromatography-mass spectrometry (GC-MS). Although there has been immense development of E-nose techniques in other applications, there are limited reports on the application of E-noses for the quality control of CHMs. The aim of current study is to review practical implementation and advantages of E-noses for robust and effective odor identification of CHMs. It covers the use of E-nose technology to study the effects of growing regions, identification methods, production procedures and storage time on CHMs. Moreover, the challenges and applications of E-nose for CHM identification are investigated. Based on the advancement in E-nose technology, odor may become a new quantitative index for quality control of CHMs and drug discovery. It was also found that more research could be done in the area of odor standardization and odor reproduction for remote sensing.

Prospective Study of the Surgical Techniques Used in Primary Rhinoplasty on the Caucasian Nose and Comparison of the Preoperative and Postoperative Anthropometric Nose Measurements

Directory of Open Access Journals (Sweden)

Berger, Cezar Augusto Sarraf

2014-12-01

Full Text Available Introduction The knowledge and study of surgical techniques and anthropometric measurements of the nose make possible a qualitative and quantitative analysis of surgical results. Objective Study the main technique used in rhinoplasty on Caucasian noses and compare preoperative and postoperative anthropometric measurements of the nose. Methods A prospective study with 170 patients was performed at a private hospital. Data were collected using the Electronic System Integrated of Protocols software (Sistema Integrado de Protocolos Eletrônicos, SINPE©. The surgical techniques used in the nasal dorsum and tip were evaluated. Preoperative and 12-month follow-up photos as well as the measurements compared with the ideal aesthetic standard of a Caucasian nose were analyzed objectively. Student t test and standard deviation test were applied. Results There was a predominance of endonasal access (94.4%. The most common dorsum technique was hump removal (33.33%, and the predominance of sutures (24.76% was observed on the nasal tip, with the lateral intercrural the most frequent (32.39%. Comparison between preoperative and postoperative photos found statistically significant alterations on the anthropometric measurements of the noses. Conclusion The main surgical techniques on Caucasian noses were evaluated, and a great variety was found. The evaluation of anthropometric measurements of the nose proved the efficiency of the performed procedures.

The serotonin transporter in rhesus monkey brain: comparison of DASB and citalopram binding sites

Energy Technology Data Exchange (ETDEWEB)

Zeng Zhizhen [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)]. E-mail: zhizhen_zeng@merck.com; Chen, T.-B. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Miller, Patricia J. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Dean, Dennis [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Tang, Y.S. [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Sur, Cyrille [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Williams, David L. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)

2006-05-15

We have characterized the interaction of the serotonin transporter ligand [{sup 3}H]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine (DASB) with rhesus monkey brain in vitro using tissue homogenate binding and autoradiographic mapping. [{sup 3}H]-DASB, a tritiated version of the widely used [{sup 11}C] positron emission tomography tracer, was found to selectively bind to a single population of sites with high affinity (K {sub d}=0.20{+-}0.04 nM). The serotonin transporter density (B {sub max}) obtained for rhesus frontal cortex was found to be 66{+-}8 fmol/mg protein using [{sup 3}H]-DASB, similar to the B {sub max} value obtained using the reference radioligand [{sup 3}H]-citalopram, a well-characterized and highly selective serotonin reuptake inhibitor (83{+-}22 fmol/mg protein). Specific binding sites of both [{sup 3}H]-DASB and [{sup 3}H]-citalopram were similarly and nonuniformly distributed throughout the rhesus central nervous system, in a pattern consistent with serotonin transporter localization reported for human brain. Regional serotonin transporter densities, estimated from optical densities of the autoradiographic images, were well correlated between the two radioligands. Finally, DASB and fluoxetine showed dose-dependent full inhibition of [{sup 3}H]-citalopram binding in a competition autoradiographic study, with K {sub i} values in close agreement with those obtained from rhesus brain homogenates. This side-by-side comparison of [{sup 3}H]-DASB and [{sup 3}H]-citalopram binding sites in rhesus tissue homogenates and in adjacent rhesus brain slices provides additional support for the use of [{sup 11}C]-DASB to assess the availability and distribution of serotonin transporters in nonhuman primates.

Načrtovani preventivni hišni obisk pri nosečnici

OpenAIRE

Hofinger Mihelič, Špela

2009-01-01

Rojstvo zdravega otroka je nedvomno eden izmed najpomembnejših dogodkov v življenju posameznika in družine. Namen diplomske naloge je bil ugotoviti v kolikšni meri se pri nosečnicah vključuje v preventivo patronažna medicinska sestra (PMS) in kaj nosečnice pričakujejo od njenega hišnega obiska. Cilj je bil oceniti želje nosečnic po hišnem obisku PMS in ugotoviti kje dobijo nosečnice največ informacij o nosečnosti in zdravem načinu življenja ter ugotoviti koliko so nosečnice poučene o pravicah...

Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin-Producing Cells

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Gérard Manière

2016-09-01

Full Text Available Dietary leucine has been suspected to play an important role in insulin release, a hormone that controls satiety and metabolism. The mechanism by which insulin-producing cells (IPCs sense leucine and regulate insulin secretion is still poorly understood. In Drosophila, insulin-like peptides (DILP2 and DILP5 are produced by brain IPCs and are released in the hemolymph after leucine ingestion. Using Ca2+-imaging and ex vivo cultured larval brains, we demonstrate that IPCs can directly sense extracellular leucine levels via minidiscs (MND, a leucine transporter. MND knockdown in IPCs abolished leucine-dependent changes, including loss of DILP2 and DILP5 in IPC bodies, consistent with the idea that MND is necessary for leucine-dependent DILP release. This, in turn, leads to a strong increase in hemolymph sugar levels and reduced growth. GDH knockdown in IPCs also reduced leucine-dependent DILP release, suggesting that nutrient sensing is coupled to the glutamate dehydrogenase pathway.

St. John's Wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier.

NARCIS (Netherlands)

Ott, M.; Huls, M.; Cornelius, M.G.; Fricker, G.

2010-01-01

PURPOSE: The purpose of this study was to investigate the short-term signaling effects of St. John's Wort (SJW) extract and selected SJW constituents on the blood-brain barrier transporter P-glycoprotein and to describe the role of PKC in the signaling. METHODS: Cultured porcine brain capillary

Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain

Science.gov (United States)

Murlidharan, Giridhar; Crowther, Andrew; Reardon, Rebecca A.; Song, Juan

2016-01-01

Adeno-associated viruses (AAV) are currently being evaluated in clinical trials for gene therapy of CNS disorders. However, host factors that influence the spread, clearance, and transduction efficiency of AAV vectors in the brain are not well understood. Recent studies have demonstrated that fluid flow mediated by aquaporin-4 (AQP4) channels located on astroglial end feet is essential for exchange of solutes between interstitial and cerebrospinal fluid. This phenomenon, which is essential for interstitial clearance of solutes from the CNS, has been termed glial-associated lymphatic transport or glymphatic transport. In the current study, we demonstrate that glymphatic transport profoundly affects various aspects of AAV gene transfer in the CNS. Altered localization of AQP4 in aged mouse brains correlated with significantly increased retention of AAV vectors in the parenchyma and reduced systemic leakage following ventricular administration. We observed a similar increase in AAV retention and transgene expression upon i.c.v. administration in AQP4–/– mice. Consistent with this observation, fluorophore-labeled AAV vectors showed markedly reduced flux from the ventricles of AQP4–/– mice compared with WT mice. These results were further corroborated by reduced AAV clearance from the AQP4-null brain, as demonstrated by reduced transgene expression and vector genome accumulation in systemic organs. We postulate that deregulation of glymphatic transport in aged and diseased brains could markedly affect the parenchymal spread, clearance, and gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the kinetics of CSF flux in prospective gene therapy patients might inform variable treatment outcomes and guide future clinical trial design. PMID:27699236

Detection and Classification of Human Body Odor Using an Electronic Nose

Directory of Open Access Journals (Sweden)

Teerakiat Kerdcharoen

2009-09-01

Full Text Available An electronic nose (E-nose has been designed and equipped with software that can detect and classify human armpit body odor. An array of metal oxide sensors was used for detecting volatile organic compounds. The measurement circuit employs a voltage divider resistor to measure the sensitivity of each sensor. This E-nose was controlled by in-house developed software through a portable USB data acquisition card with a principle component analysis (PCA algorithm implemented for pattern recognition and classification. Because gas sensor sensitivity in the detection of armpit odor samples is affected by humidity, we propose a new method and algorithms combining hardware/software for the correction of the humidity noise. After the humidity correction, the E-nose showed the capability of detecting human body odor and distinguishing the body odors from two persons in a relative manner. The E-nose is still able to recognize people, even after application of deodorant. In conclusion, this is the first report of the application of an E-nose for armpit odor recognition.

Detection and classification of human body odor using an electronic nose.

Science.gov (United States)

Wongchoosuk, Chatchawal; Lutz, Mario; Kerdcharoen, Teerakiat

2009-01-01

An electronic nose (E-nose) has been designed and equipped with software that can detect and classify human armpit body odor. An array of metal oxide sensors was used for detecting volatile organic compounds. The measurement circuit employs a voltage divider resistor to measure the sensitivity of each sensor. This E-nose was controlled by in-house developed software through a portable USB data acquisition card with a principle component analysis (PCA) algorithm implemented for pattern recognition and classification. Because gas sensor sensitivity in the detection of armpit odor samples is affected by humidity, we propose a new method and algorithms combining hardware/software for the correction of the humidity noise. After the humidity correction, the E-nose showed the capability of detecting human body odor and distinguishing the body odors from two persons in a relative manner. The E-nose is still able to recognize people, even after application of deodorant. In conclusion, this is the first report of the application of an E-nose for armpit odor recognition.

Bat white-nose syndrome: An emerging fungal pathogen?

Science.gov (United States)

Blehert, D.S.; Hicks, A.C.; Behr, M.; Meteyer, C.U.; Berlowski-Zier, B. M.; Buckles, E.L.; Coleman, J.T.H.; Darling, S.R.; Gargas, A.; Niver, R.; Okoniewski, J.C.; Rudd, R.J.; Stone, W.B.

2009-01-01

White-nose syndrome (WNS) is a condition associated with an unprecedented bat mortality event in the northeastern United States. Since the winter of 2006*2007, bat declines exceeding 75% have been observed at surveyed hibernacula. Affected bats often present with visually striking white fungal growth on their muzzles, ears, and/or wing membranes. Direct microscopy and culture analyses demonstrated that the skin of WNS-affected bats is colonized by a psychro-philic fungus that is phylogenetically related to Geomyces spp. but with a conidial morphology distinct from characterized members of this genus. This report characterizes the cutaneous fungal infection associated with WNS.

Directed Fluid Transport with Biomimetic ``Silia'' Arrays

Science.gov (United States)

Shields, A. R.; Evans, B. A.; Carstens, B. L.; Falvo, M. R.; Washburn, S.; Superfine, R.

2008-10-01

We present results on the long-range, directed fluid transport produced by the collective beating of arrays of biomimetic ``silia.'' Silia are arrays of free-standing nanorods roughly the size of biological cilia, which we fabricate from a polymer-magnetic nanoparticle composite material. With external permanent magnets we actuate our silia such that their motion mimics the beating of biological cilia. Biological cilia have evolved to produce microscale fluid transport and are increasingly being recognized as critical components in a wide range of biological systems. However, despite much effort cilia generated fluid flows remain an area of active study. In the last decade, cilia-driven fluid flow in the embryonic node of vertebrates has been implicated as the initial left-right symmetry breaking event in these embryos. With silia we generate directional fluid transport by mimicking the tilted conical beating of these nodal cilia and seek to answer open questions about the nature of particle advection in such a system. By seeding fluorescent microparticles into the fluid we have noted the existence of two distinct flow regimes. The fluid flow is directional and coherent above the tips of the silia, while between the silia tips and floor particle motion is complicated and suggestive of chaotic advection.

Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma

DEFF Research Database (Denmark)

Johnsen, Kasper B.; Burkhart, Annette; Melander, Fredrik

2017-01-01

Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing...... the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we...... investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does...

Transport rankings of non-steroidal antiinflammatory drugs across blood-brain barrier in vitro models.

Directory of Open Access Journals (Sweden)

Iveta Novakova

Full Text Available The aim of this work was to conduct a comprehensive study about the transport properties of NSAIDs across the blood-brain barrier (BBB in vitro. Transport studies with celecoxib, diclofenac, ibuprofen, meloxicam, piroxicam and tenoxicam were accomplished across Transwell models based on cell line PBMEC/C1-2, ECV304 or primary rat brain endothelial cells. Single as well as group substance studies were carried out. In group studies substance group compositions, transport medium and serum content were varied, transport inhibitors verapamil and probenecid were added. Resulted permeability coefficients were compared and normalized to internal standards diazepam and carboxyfluorescein. Transport rankings of NSAIDs across each model were obtained. Single substance studies showed similar rankings as corresponding group studies across PBMEC/C1-2 or ECV304 cell layers. Serum content, glioma conditioned medium and inhibitors probenecid and verapamil influenced resulted permeability significantly. Basic differences of transport properties of the investigated NSAIDs were similar comparing all three in vitro BBB models. Different substance combinations in the group studies and addition of probenecid and verapamil suggested that transporter proteins are involved in the transport of every tested NSAID. Results especially underlined the importance of same experimental conditions (transport medium, serum content, species origin, cell line for proper data comparison.

Electronic nose in edible insects area

OpenAIRE

Martin Adámek; Anna Adámková; Marie Borkovcová; Jiří Mlček; Martina Bednářová; Lenka Kouřimská; Josef Skácel; Michal Řezníček

2017-01-01

Edible insect is appraised by many cultures as delicious and nutritionally beneficial food. In western countries this commodity is not fully appreciated, and the worries about edible insect food safety prevail. Electronic noses can become a simple and cheap way of securing the health safety of food, and they can also become a tool for evaluating the quality of certain commodities. This research is a pilot project of using an electronic nose in edible insect culinary treatment, and this manusc...

Identification of Chinese Herbal Medicines with Electronic Nose Technology: Applications and Challenges

Directory of Open Access Journals (Sweden)

Huaying Zhou

2017-05-01

Full Text Available This paper provides a review of the most recent works in machine olfaction as applied to the identification of Chinese Herbal Medicines (CHMs. Due to the wide variety of CHMs, the complexity of growing sources and the diverse specifications of herb components, the quality control of CHMs is a challenging issue. Much research has demonstrated that an electronic nose (E-nose as an advanced machine olfaction system, can overcome this challenge through identification of the complex odors of CHMs. E-nose technology, with better usability, high sensitivity, real-time detection and non-destructive features has shown better performance in comparison with other analytical techniques such as gas chromatography-mass spectrometry (GC-MS. Although there has been immense development of E-nose techniques in other applications, there are limited reports on the application of E-noses for the quality control of CHMs. The aim of current study is to review practical implementation and advantages of E-noses for robust and effective odor identification of CHMs. It covers the use of E-nose technology to study the effects of growing regions, identification methods, production procedures and storage time on CHMs. Moreover, the challenges and applications of E-nose for CHM identification are investigated. Based on the advancement in E-nose technology, odor may become a new quantitative index for quality control of CHMs and drug discovery. It was also found that more research could be done in the area of odor standardization and odor reproduction for remote sensing.

Impacts of Deflection Nose on Ballistic Trajectory Control Law

Directory of Open Access Journals (Sweden)

Bo Zhang

2014-01-01

Full Text Available The deflection of projectile nose is aimed at changing the motion of the projectile in flight with the theory of motion control and changing the exterior ballistics so as to change its range and increase its accuracy. The law of external ballistics with the deflectable nose is considered as the basis of the design of a flight control system and an important part in the process of projectile development. Based on the existing rigid external ballistic model, this paper establishes an external ballistic calculation model for deflectable nose projectile and further establishes the solving programs accordingly. Different angle of attack, velocity, coefficients of lift, resistance, and moment under the deflection can be obtained in this paper based on the previous experiments and emulation researches. In the end, the author pointed out the laws on the impaction of external ballistic trajectory by the deflection of nose of the missile.

Electronic Nose Odor Classification with Advanced Decision Tree Structures

Directory of Open Access Journals (Sweden)

S. Guney

2013-09-01

Full Text Available Electronic nose (e-nose is an electronic device which can measure chemical compounds in air and consequently classify different odors. In this paper, an e-nose device consisting of 8 different gas sensors was designed and constructed. Using this device, 104 different experiments involving 11 different odor classes (moth, angelica root, rose, mint, polis, lemon, rotten egg, egg, garlic, grass, and acetone were performed. The main contribution of this paper is the finding that using the chemical domain knowledge it is possible to train an accurate odor classification system. The domain knowledge about chemical compounds is represented by a decision tree whose nodes are composed of classifiers such as Support Vector Machines and k-Nearest Neighbor. The overall accuracy achieved with the proposed algorithm and the constructed e-nose device was 97.18 %. Training and testing data sets used in this paper are published online.

Organic cation transporter 1 (OCT1 is involved in pentamidine transport at the human and mouse blood-brain barrier (BBB.

Directory of Open Access Journals (Sweden)

Gayathri N Sekhar

Full Text Available Pentamidine is an effective trypanocidal drug used against stage 1 Human African Trypanosomiasis (HAT. At the blood-brain barrier (BBB, it accumulates inside the endothelial cells but has limited entry into the brain. This study examined transporters involved in pentamidine transport at the human and mouse BBB using hCMEC/D3 and bEnd.3 cell lines, respectively. Results revealed that both cell lines expressed the organic cation transporters (OCT1, OCT2 and OCT3, however, P-gp was only expressed in hCMEC/D3 cells. Polarised expression of OCT1 was also observed. Functional assays found that ATP depletion significantly increased [3H]pentamidine accumulation in hCMEC/D3 cells (***p<0.001 but not in bEnd.3 cells. Incubation with unlabelled pentamidine significantly decreased accumulation in hCMEC/D3 and bEnd.3 cells after 120 minutes (***p<0.001. Treating both cell lines with haloperidol and amantadine also decreased [3H]pentamidine accumulation significantly (***p<0.001 and **p<0.01 respectively. However, prazosin treatment decreased [3H]pentamidine accumulation only in hCMEC/D3 cells (*p<0.05, and not bEnd.3 cells. Furthermore, the presence of OCTN, MATE, PMAT, ENT or CNT inhibitors/substrates had no significant effect on the accumulation of [3H]pentamidine in both cell lines. From the data, we conclude that pentamidine interacts with multiple transporters, is taken into brain endothelial cells by OCT1 transporter and is extruded into the blood by ATP-dependent mechanisms. These interactions along with the predominant presence of OCT1 in the luminal membrane of the BBB contribute to the limited entry of pentamidine into the brain. This information is of key importance to the development of pentamidine based combination therapies which could be used to treat CNS stage HAT by improving CNS delivery, efficacy against trypanosomes and safety profile of pentamidine.

Design and validation of a microfluidic device for blood-brain barrier monitoring and transport studies

Science.gov (United States)

Ugolini, Giovanni Stefano; Occhetta, Paola; Saccani, Alessandra; Re, Francesca; Krol, Silke; Rasponi, Marco; Redaelli, Alberto

2018-04-01

In vitro blood-brain barrier models are highly relevant for drug screening and drug development studies, due to the challenging task of understanding the transport mechanism of drug molecules through the blood-brain barrier towards the brain tissue. In this respect, microfluidics holds potential for providing microsystems that require low amounts of cells and reagent and can be potentially multiplexed for increasing the ease and throughput of the drug screening process. We here describe the design, development and validation of a microfluidic device for endothelial blood-brain barrier cell transport studies. The device comprises of two microstructured layers (top culture chamber and bottom collection chamber) sandwiching a porous membrane for the cell culture. Microstructured layers include two pairs of physical electrodes, embedded into the device layers by geometrically defined guiding channels with computationally optimized positions. These electrodes allow the use of commercial electrical measurement systems for monitoring trans-endothelial electrical resistance (TEER). We employed the designed device for performing preliminary assessment of endothelial barrier formation with murine brain endothelial cells (Br-bEnd5). Results demonstrate that cellular junctional complexes effectively form in the cultures (expression of VE-Cadherin and ZO-1) and that the TEER monitoring systems effectively detects an increase of resistance of the cultured cell layers indicative of tight junction formation. Finally, we validate the use of the described microsystem for drug transport studies demonstrating that Br-bEnd5 cells significantly hinder the transport of molecules (40 kDa and 4 kDa dextran) from the top culture chamber to the bottom collection chamber.

Technical basis for using nose swab bioassay data for early internal dose assessment

International Nuclear Information System (INIS)

Guilmette, Raymond A.; Bertelli, Luiz; Miller, Guthrie; Little, Tom T.

2007-01-01

One of the challenges to the dose assessment team in response to an inhalation incident in the workplace is to provide the occupational physicians, operational radiation protection personnel and line managers with early estimates of radionuclide intakes so that appropriate consequence management and mitigation can be done. For radionuclides such as Pu, where in vivo counting is not adequately sensitive, other techniques such as the measurement of removable radionuclide from the nasal airway passages can be used. At Los Alamos National Laboratory (LANL), nose swabs of the ET 1 region have been used routinely as a first response to airborne Pu releases in the workplace, as well as for other radionuclides. This paper presents the results of analysing over 15 years of nose swab data, comparing these with dose assessments performed using the Bayesian methods developed at LANL. The results provide empirical support for using nose swab data for early dose assessments. For Pu, a rule of thumb is a dose factor of 0.8 mSv Bq -1 , assuming a linear relationship between nasal swab activity and committed effective dose equivalent. However, this value is specific to the methods and models used at LANL, and should not be applied directly without considering possible differences in measurement and calculation methods. (authors)

Design of a portable electronic nose for real-fake detection of liquors

Science.gov (United States)

Qi, Pei-Feng; Zeng, Ming; Li, Zhi-Hua; Sun, Biao; Meng, Qing-Hao

2017-09-01

Portability is a major issue that influences the practical application of electronic noses (e-noses). For liquors detection, an e-nose must preprocess the liquid samples (e.g., using evaporation and thermal desorption), which makes the portable design even more difficult. To realize convenient and rapid detection of liquors, we designed a portable e-nose platform that consists of hardware and software systems. The hardware system contains an evaporation/sampling module, a reaction module, a control/data acquisition and analysis module, and a power module. The software system provides a user-friendly interface and can achieve automatic sampling and data processing. This e-nose platform has been applied to the real-fake recognition of Chinese liquors. Through parameter optimization of a one-class support vector machine classifier, the error rate of the negative samples is greatly reduced, and the overall recognition accuracy is improved. The results validated the feasibility of the designed portable e-nose platform.

Strategies to improve drug delivery across the blood-brain barrier.

Science.gov (United States)

de Boer, Albertus G; Gaillard, Pieter J

2007-01-01

The blood-brain barrier (BBB), together with the blood-cerebrospinal-fluid barrier, protects and regulates the homeostasis of the brain. However, these barriers also limit the transport of small-molecule and, particularly, biopharmaceutical drugs such as proteins, genes and interference RNA to the brain, thereby limiting the treatment of many brain diseases. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. In this review, we discuss briefly the biology and physiology of the BBB as the most important barrier for drug transport to the brain and, in more detail, the possibilities for delivering large-molecule drugs, particularly genes, by receptor-mediated nonviral drug delivery to the (human) brain. In addition, the systemic and intracellular pharmacokinetics of nonviral gene delivery, together with targeted brain imaging, are reviewed briefly.

An analysis of parameters affecting slapdown of transportation packages

International Nuclear Information System (INIS)

Bergmann, V.L.; Ammerman, D.J.

1991-06-01

In the certification of packages for transport of radioactive material, the issue of slapdown must be addressed. Slapdown is a secondary impact of the body caused by rotational accelerations induced during eccentric primary impact. In this report, several parameters are evaluated that affect slapdown severity of packages for the transport of nuclear material. The nose and tail accelerations in a slapdown event are compared to those experienced by the same cask in a side-drop configuration, in which there is no rotation, for a range of initial impact angles, impact limiter models, and friction coefficients for two existing cask geometries. In some cases, the rotation induced during a shallow-angle impact is sufficient to cause accelerations at the tail during secondary impact to be greater than those at the nose during initial impact. Furthermore, both nose and tail accelerations are often greater than the side-on accelerations. The results described here have been calculated using the code SLAPDOWN, which approximates the impact response of deformable bodies. Finally, SLAPDOWN has been used to estimate the coefficient of friction acting at the nose and tail for one particular cask during one specific slapdown drop test by comparison of results with experimental data. 2 refs., 16 figs., 3 tabs

Evidence for a role of transporter-mediated currents in the depletion of brain serotonin induced by serotonin transporter substrates.

Science.gov (United States)

Baumann, Michael H; Bulling, Simon; Benaderet, Tova S; Saha, Kusumika; Ayestas, Mario A; Partilla, John S; Ali, Syed F; Stockner, Thomas; Rothman, Richard B; Sandtner, Walter; Sitte, Harald H

2014-05-01

Serotonin (5-HT) transporter (SERT) substrates like fenfluramine and 3,4-methylenedioxymethamphetamine cause long-term depletion of brain 5-HT, while certain other substrates do not. The 5-HT deficits produced by SERT substrates are dependent upon transporter proteins, but the exact mechanisms responsible are unclear. Here, we compared the pharmacology of several SERT substrates: fenfluramine, d-fenfluramine, 1-(m-chlorophenyl)piperazine (mCPP) and 1-(m-trifluoromethylphenyl)piperainze (TFMPP), to establish relationships between acute drug mechanisms and the propensity for long-term 5-HT depletions. In vivo microdialysis was carried out in rat nucleus accumbens to examine acute 5-HT release and long-term depletion in the same subjects. In vitro assays were performed to measure efflux of [(3)H]5-HT in rat brain synaptosomes and transporter-mediated ionic currents in SERT-expressing Xenopus oocytes. When administered repeatedly to rats (6 mg/kg, i.p., four doses), all drugs produce large sustained elevations in extracellular 5-HT (>5-fold) with minimal effects on dopamine. Importantly, 2 weeks after dosing, only rats exposed to fenfluramine and d-fenfluramine display depletion of brain 5-HT. All test drugs evoke fluoxetine-sensitive efflux of [(3)H]5-HT from synaptosomes, but d-fenfluramine and its bioactive metabolite d-norfenfluramine induce significantly greater SERT-mediated currents than phenylpiperazines. Our data confirm that drug-induced 5-HT release probably does not mediate 5-HT depletion. However, the magnitude of transporter-mediated inward current may be a critical factor in the cascade of events leading to 5-HT deficits. This hypothesis warrants further study, especially given the growing popularity of designer drugs that target SERT.

THE EFFECT OF TRANSPORTATION INFRASTRUCTURE ONFOREIGN DIRECT INVESTMENT ATTRACTION IN IRAN

Directory of Open Access Journals (Sweden)

Manijeh Taghilou Barzelaghi

2012-07-01

Full Text Available Weak transportation infrastructure in developing countries, e.g. Iran, presents abig obstacle to foreign direct investment attraction. One way of increasing theflow of foreign direct investment into a country is decreasing the production coststhrough expanding facilities as well as employing higher technology level. Thus,transportation cost usually is high in these countries and industries are oftenconcentrated in regions with more improved transportation system. The presentstudy aimed to investigate the effect of transportation infrastructure in Iran onforeign direct investment attraction. Hence, the researchers employed JohansenJuselius econometrics method to quantify the short run and long run effect oftransportation infrastructure, trade intensity, and market size on foreign directinvestment attraction during 1974-2007. The results emerging from the presentstudy indicated that transportationinfrastructure did not affect foreign directinvestment attraction in short run, but in long run, it had positive and significanteffect on foreign direct investment attraction.

A Compact and Low Cost Electronic Nose for Aroma Detection

Directory of Open Access Journals (Sweden)

Ramón Gallardo Caballero

2013-04-01

Full Text Available This article explains the development of a prototype of a portable and a very low-cost electronic nose based on an mbed microcontroller. Mbeds are a series of ARM microcontroller development boards designed for fast, flexible and rapid prototyping. The electronic nose is comprised of an mbed, an LCD display, two small pumps, two electro-valves and a sensor chamber with four TGS Figaro gas sensors. The performance of the electronic nose has been tested by measuring the ethanol content of wine synthetic matrices and special attention has been paid to the reproducibility and repeatability of the measurements taken on different days. Results show that the electronic nose with a neural network classifier is able to discriminate wine samples with 10, 12 and 14% V/V alcohol content with a classification error of less than 1%.

Enterobius vermicularis in the nose: A rare entity

OpenAIRE

Kaniyur, Vishnu; Chandra Prasad, Kishore H.; Devan, P. P.; Doddamani, S. S.; Balachandran, Bharati; Kulkarni, Vikram

2005-01-01

A rare case of enterobius vermicularis pin-worm is reported in the nose. An 11-year-old girl presented with the vague symptoms of crawling sensation in the nose for few weeks, who had received treatment for allergic rhinitis. The nasal secretions were examined and confirmed the diagnosis of pinworm infection and treated by albendazole.

In vitro evidence for the brain glutamate efflux hypothesis

DEFF Research Database (Denmark)

Helms, Hans Christian; Madelung, Rasmus; Waagepetersen, Helle Sønderby

2012-01-01

resistance values of 1014 ± 70 O cm(2) , and (14) C-D-mannitol permeability values of 0.88 ± 0.13 × 10(-6) cm s(-1) . Unidirectional flux studies showed that L-aspartate and L-glutamate, but not D-aspartate, displayed polarized transport in the brain-to-blood direction, however, all three amino acids......The concentration of the excitotoxic amino acid, L-glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood-brain barrier endothelium in brain L......-glutamate homeostasis. Transendothelial transport- and accumulation studies of (3) H-L-glutamate, (3) H-L-aspartate, and (3) H-D-aspartate in an electrically tight bovine endothelial/rat astrocyte blood-brain barrier coculture model were performed. After 6 days in culture, the endothelium displayed transendothelial...

The Role of P-Glycoprotein in Transport of Danshensu across the Blood-Brain Barrier

Directory of Open Access Journals (Sweden)

Peng-Fei Yu

2011-01-01

Full Text Available Danshensu (3-(3, 4-dihydroxyphenyl lactic acid, a water-soluble active component isolated from the root of Salvia miltiorrhiza Bunge, is widely used for the treatment of cerebrovascular diseases. The present study aims to investigate the role of P-glycoprotein in transport of Danshensu across the blood-brain barrier. Sprague-Dawley rats were pretreated with verapamil at a dose of 20 mg kg−1 (verapamil group or the same volume of normal saline (control group. Ninety minutes later, the animals were administrated with Danshensu (15 mg kg−1 by intravenous injection. At 15 min, 30 min, and 60 min after Danshensu administration, the levels of Danshensu in the blood and brain were detected by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS. The results showed that Danshensu concentrations in the brain of the rats pretreated with verapamil were significantly increased. In addition, the brain-plasma ratios of the group pretreated with verapamil were much higher than that of the control group. There was no difference in Danshensu level in plasma between the verapamil group and control group. The findings indicated that Danshensu can pass the blood-brain barrier, and P-glycoprotein plays an important role in Danshensu transportation in brain.

On the impact of a concave nosed axisymmetric body on a free surface

Science.gov (United States)

Mathai, Varghese; Govardhan, Raghuraman N.; Arakeri, Vijay H.

2015-02-01

We report on an experimental study of the vertical impact of a concave nosed axisymmetric body on a free surface. Previous studies have shown that bodies with a convex nose, like a sphere, produce a well defined splash with a relatively large cavity behind the model. In contrast, we find that with a concave nose, there is hardly a splash and the cavity extent is greatly reduced. This may be explained by the fact that in the concave nosed case, the initial impact is between a confined air pocket and the free surface unlike in the convex nosed case. From measurements of the unsteady pressure in the concave nose portion, we show that in this case, the maximum pressures are significantly lower than the classically expected "water hammer" pressures and also lower than those generally measured on other geometries. Thus, the presence of an air pocket in the case of a concave nosed body adds an interesting dimension to the classical problem of impact of solid bodies on to a free surface.

Nose muscular dynamics: the tip trigonum.

Science.gov (United States)

Figallo, E E; Acosta, J A

2001-10-01

In 1995, the senior author (E.E.F.) published an article in which he described the musculus digastricus septi nasi labialis. In the article presented here, work carried out by anatomists and other researchers who, over the last two centuries, studied nose muscular dynamics is described. The present study is based on Gray's Anatomy, which, in 1858, first described the nasal tip muscles, along with the other nasal muscles. Later works not only used different terminology for these muscles but also ignored some, creating tremendous confusion. The study presented here provides an update of the exact terms, location, insertions, and muscle functions of the muscles of the nose. Each nose muscle is described with regard to the two portions able to produce separate contractions. In this study, the term "dual function" is used and characterizes the nasal mimetic muscles that do not have well-defined fascia. Therefore, there is doubt about the existence of a real nasal superficial muscle aponeurotic system. The musculus myrtiformis seems to have a dual function, inserting in the canine fosse and in the periosteum of the central incisors, forming two portions-one to the septum and the other to the nostril-each of which has specific functions. This study has been based on research in physiognomy, the science of expression. With regard to the basis for nose expressions, common anatomical research is excluded because it provides a different view of the dynamics studied to date. The term trigonum musculare apicis nasi defines the interaction of the musculi compressor narium minor and dilator naris anterior, connecting with the columellar bundle of the musculus digastricus and levering the nasal spine. This muscular trigone creates circular concentric and eccentric movements of the nasal tip.

Aging alters mRNA expression of amyloid transporter genes at the blood-brain barrier.

Science.gov (United States)

Osgood, Doreen; Miller, Miles C; Messier, Arthur A; Gonzalez, Liliana; Silverberg, Gerald D

2017-09-01

Decreased clearance of potentially toxic metabolites, due to aging changes, likely plays a significant role in the accumulation of amyloid-beta (Aβ) peptides and other macromolecules in the brain of the elderly and in the patients with Alzheimer's disease (AD). Aging is the single most important risk factor for AD development. Aβ transport receptor proteins expressed at the blood-brain barrier are significantly altered with age: the efflux transporters lipoprotein receptor-related protein 1 and P-glycoprotein are reduced, whereas the influx transporter receptor for advanced glycation end products is increased. These receptors play an important role in maintaining brain biochemical homeostasis. We now report that, in a rat model of aging, gene transcription is altered in aging, as measured by Aβ receptor gene messenger RNA (mRNA) at 3, 6, 9, 12, 15, 20, 30, and 36 months. Gene mRNA expression from isolated cerebral microvessels was measured by quantitative polymerase chain reaction. Lipoprotein receptor-related protein 1 and P-glycoprotein mRNA were significantly reduced in aging, and receptor for advanced glycation end products was increased, in parallel with the changes seen in receptor protein expression. Transcriptional changes appear to play a role in aging alterations in blood-brain barrier receptor expression and Aβ accumulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood-Brain Barrier.

Science.gov (United States)

Georgieva, Julia V; Hoekstra, Dick; Zuhorn, Inge S

2014-11-17

The blood-brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood-brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier-drug system ("Trojan horse complex") is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain.

Diagnostic imaging of the nose and paranasal sinuses

International Nuclear Information System (INIS)

Lloyd, G.A.S.

1988-01-01

This book offers extensively illustrated and comprehensive coverage of diagnostic imaging techniques of the nose and paranasal sinuses. The important feature of the work is the way it correlates histology with CT and MRI and includes magnetic resonance contrast studies using Gadolinium DTPA. Furthermore, it is the first text to treat the imaging of the various types of tumors of the nose and paranasal sinuses on an individual basis

Present and potential distribution of Snub-nosed Monkey

DEFF Research Database (Denmark)

Nüchel, Jonas; Bøcher, Peder Klith; Svenning, Jens-Christian

are the Snub-nosed Monkeys (Rhinopithecus), a temperate-subtropical East Asian genus. We use species distribution modeling to assess the following question of key relevancy for conservation management of Rhinopithecus; 1. Which climatic factors determine the present distribution of Rhinopithecus within...... distribution of Rhinopithecus within the region, considering climate, habitat availability and the locations of nature reserves. Keywords: biodiversity, biogeography, conservation, China, snub-nosed monkey, rhinopithecus, primates, species distribution modeling...

Advances in electronic-nose technologies developed for biomedical applications

Science.gov (United States)

Dan Wilson; Manuela. Baietto

2011-01-01

The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and...

Controlling chaos-assisted directed transport via quantum resonance.

Science.gov (United States)

Tan, Jintao; Zou, Mingliang; Luo, Yunrong; Hai, Wenhua

2016-06-01

We report on the first demonstration of chaos-assisted directed transport of a quantum particle held in an amplitude-modulated and tilted optical lattice, through a resonance-induced double-mean displacement relating to the true classically chaotic orbits. The transport velocity is controlled by the driving amplitude and the sign of tilt, and also depends on the phase of the initial state. The chaos-assisted transport feature can be verified experimentally by using a source of single atoms to detect the double-mean displacement one by one, and can be extended to different scientific fields.

Controlling chaos-assisted directed transport via quantum resonance

Energy Technology Data Exchange (ETDEWEB)

Tan, Jintao; Zou, Mingliang; Luo, Yunrong; Hai, Wenhua, E-mail: whhai2005@aliyun.com [Department of Physics and Key Laboratory of Low-dimensional Quantum Structures and Quantum Control of Ministry of Education, Hunan Normal University, Changsha 410081, China and Synergetic Innovation Center for Quantum Effects and Applications, Hunan Normal University, Changsha 410081 (China)

2016-06-15

We report on the first demonstration of chaos-assisted directed transport of a quantum particle held in an amplitude-modulated and tilted optical lattice, through a resonance-induced double-mean displacement relating to the true classically chaotic orbits. The transport velocity is controlled by the driving amplitude and the sign of tilt, and also depends on the phase of the initial state. The chaos-assisted transport feature can be verified experimentally by using a source of single atoms to detect the double-mean displacement one by one, and can be extended to different scientific fields.

[On the "Brain is the House of Yuanshen" in "Bencao Gangmu"; from Li Shizhen to Zhang Xichun].

Science.gov (United States)

Okuno, Shigeo

2011-03-01

The phrase the "Brain is the House of Yuanshen" is used in "Bencao Gangmu" in order to explain the reason why magnolia flower is good for sinus problems; however, the ideas on the relationship between the brain and the nose originate from "Huangdi Neijing" and those on the relationship between the brain and Yuanshen come from Taoism. It was "Bencao Beiyao" that combined the theory with the Western idea that "someone's memory is in the brain". The idea of the brain staying on as memory had great impact on "Leizheng Zhicai" and "Yilin Gaicuo", but again in "Yixue Zhongzhong Sanxilu" it claimed that "Yuanshen is in the brain" from Taoism's point of view, and it criticized the theory of the brain derived from the Western world. In this paper, the meaning of "Brain is the House of Yuanshen" in "Bencao Gangmu" is examined, along with the influence this idea had on the subsequent theories of medicine.

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

OpenAIRE

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers non...

Surgical Considerations in the Management of Tumours of the Nose ...

African Journals Online (AJOL)

BACKGROUND: Tumours of the nose and paranasal sinuses in sub-Saharan Africa are generally characterised by late presentation posing management challenges to the otorhinolaryngologists in the sub-region. OBJECTIVES: To appraise surgical considerations in the management of tumours of the nose and paranasal ...

[Comparison of ability to humidification of inspired air through the nose and oral cavity using dew point hygrometer].

Science.gov (United States)

Paczesny, Daniel; Rapiejko, Piotr; Weremczuk, Jerzy; Jachowicz, Ryszard; Jurkiewicz, Dariusz

2007-01-01

Aim of this study was to check at the hospital the dew point hygrometer for fast measurement of air humidity in upper airways. The nose ability to humidification of inspired air and partially recover moisture from expired air was evaluated. Measurements from respiration through the nose and oral cavity were compared. The study was carried out in a group of 30 people (8 female and 22 male), age group 18 to 70 (mean age: 37 years old). In 22 of the participants there were no deviation from normal state in laryngologic examination, while in 4 participants nasal septum deviation without imaired nasal; oatency was found, in other 3--nasal vonchae hyperthrophy and in 1--nasal polips (grade I). The measurements of air humidity in upper air ways was done using specially designed and constructed measurement system. The air inspired through the nose and oral cavity is humidified. For typical external conditions (T = 22 degrees C i RH = 50%) the nose humidifies inspired air two times better then oral cavity (short time range of measurement approximately 1 min). Moisture from expired air through the nose is partially recovered (for patients with regular patency is 25% of the value of humidifying of inspired air). The oral cavity does not have ability to partially recovery moisture form expired air. The paper presented fast dew point hygrometer based on semiconductor microsystems for measurement humidity in inspired and expired air through the nose and oral cavity. Presented system can be a proper instrument for evaluation of nasal functions.

Different Ways to Apply a Measurement Instrument of E-Nose Type to Evaluate Ambient Air Quality with Respect to Odour Nuisance in a Vicinity of Municipal Processing Plants

Directory of Open Access Journals (Sweden)

Bartosz Szulczyński

2017-11-01

Full Text Available This review paper presents different ways to apply a measurement instrument of e-nose type to evaluate ambient air with respect to detection of the odorants characterized by unpleasant odour in a vicinity of municipal processing plants. An emphasis was put on the following applications of the electronic nose instruments: monitoring networks, remote controlled robots and drones as well as portable devices. Moreover, this paper presents commercially available sensors utilized in the electronic noses and characterized by the limit of quantification below 1 ppm v/v, which is close to the odour threshold of some odorants. Additionally, information about bioelectronic noses being a possible alternative to electronic noses and their principle of operation and application potential in the field of air evaluation with respect to detection of the odorants characterized by unpleasant odour was provided.

Macroscopic Modeling of Transport Phenomena in Direct Methanol Fuel Cells

DEFF Research Database (Denmark)

Olesen, Anders Christian

An increasing need for energy efficiency and high energy density has sparked a growing interest in direct methanol fuel cells for portable power applications. This type of fuel cell directly generates electricity from a fuel mixture consisting of methanol and water. Although this technology...... surpasses batteries in important areas, fundamental research is still required to improve durability and performance. Particularly the transport of methanol and water within the cell structure is difficult to study in-situ. A demand therefore exist for the fundamental development of mathematical models...... for studying their transport. In this PhD dissertation the macroscopic transport phenomena governing direct methanol fuel cell operation are analyzed, discussed and modeled using the two-fluid approach in the computational fluid dynamics framework of CFX 14. The overall objective of this work is to extend...

Ear, nose, and throat disorders in a nigerian rural community

Directory of Open Access Journals (Sweden)

Waheed Atilade Adegbiji

2017-01-01

Full Text Available Aims and Objectives: This study aimed at assessing the prevalence of ear, nose, and throat with head and neck diseases in a rural community in Oyo State, Nigeria. Materials and Methods: This is a prospective community-based study of ear, nose, and throat diseases. The study was carried out over a period of 3 months (January to March 2017. Verbal consent was obtained from the village head and participants. A total of 738 individuals were enrolled into the study. Interview-assisted questionnaire was administered to obtain bio data and otorhinolaryngological history from all participants, followed by examination and investigation. Data obtained were collated and statistically analyzed using SPSS version 16. Results: A total of 738 consented participants had various forms of ear, nose, and throat disorders. They constituted 435 (58.9% males and 303 (41.1% females, with a male: female ratio of 1:1. Majority of enrollee were dependent age groups. These age groups were 27.4% (1–10, 25.5% (11–20, and 14.1% (51–60. The occupational status revealed that 28.9% were employed; 9.3% were retired; 45.5% were children/students/apprenticeship; and 16.3% were artisans, homemakers, and farmers. Nasal diseases (34.4% were the most common otorhinolaryngological, head and neck disorders while ear, nose, and throat with head and neck diseases were responsible for 43.4%, 14.6%, and 7.6%, respectively. The common diseases were wax impaction (11.7%, sinusitis (14.4%, and allergic rhinitis (22.6%. Less prevalent otorhinolaryngological, head and neck diseases were vertigo/balance disorder (0.9%, cervical spondylosis (1.6%, and pharyngitis/tonsillitis (2.0%. Common procedures performed included impacted earwax removal (22.8%, aural toilet/dressing (14.4%, pure tone audiometry (32.5%, tympanometry (18.4%, endoscopy (9.8%, and antral irrigation (5.7%. Referred cases of 7.2% were recorded. The barriers experienced by these villagers in seeking otorhinolaryngological

Analog Multilayer Perceptron Circuit with On-chip Learning: Portable Electronic Nose

Science.gov (United States)

Pan, Chih-Heng; Tang, Kea-Tiong

2011-09-01

This article presents an analog multilayer perceptron (MLP) neural network circuit with on-chip back propagation learning. This low power and small area analog MLP circuit is proposed to implement as a classifier in an electronic nose (E-nose). Comparing with the E-nose using microprocessor or FPGA as a classifier, the E-nose applying analog circuit as a classifier can be faster and much smaller, demonstrate greater power efficiency and be capable of developing a portable E-nose [1]. The system contains four inputs, four hidden neurons, and only one output neuron; this simple structure allows the circuit to have a smaller area and less power consumption. The circuit is fabricated using TSMC 0.18 μm 1P6M CMOS process with 1.8 V supply voltage. The area of this chip is 1.353×1.353 mm2 and the power consumption is 0.54 mW. Post-layout simulations show that the proposed analog MLP circuit can be successively trained to identify three kinds of fruit odors.

An isotope dilution gas chromatography/mass spectrometry method for trace analysis of xylene and its metabolites in tissues following threshold limit value exposures

Energy Technology Data Exchange (ETDEWEB)

Pyon, K.H.; Kracko, D.A.; Strunk, M.R. [and others

1995-12-01

The existence of a nose-brain barrier that functions to protect the central nervous system (CNS) from inhaled toxicants has been postulated. Just as a blood-brain barrier protects the CNS from systemic toxicants, the nose-brain barrier may have similar characteristic functions. One component of interest is nasal xenobiotic metabolism and its effect on the transport of pollutants into the CNS at environmentally plausible levels of exposure. Previous results have shown that inhaled xylene are dimethyl phenol (DMP) and methyl benzyl alcohol (MBA), and the nonvolatile metabolites are toluic acid (TA) and methyl hippuric acid (MHA). The nonvolatile metabolites of xylene, along with a small quantity of volatiles, representing either parent xylene or volatile metabolites, are transported via the olfactory epithelium to the glomeruli within the olfactory bulbs of the brain. Further work will be done to establish the linearity for each analyte at the actual highest detection limit of the GC/MS.

An isotope dilution gas chromatography/mass spectrometry method for trace analysis of xylene and its metabolites in tissues following threshold limit value exposures

International Nuclear Information System (INIS)

Pyon, K.H.; Kracko, D.A.; Strunk, M.R.

1995-01-01

The existence of a nose-brain barrier that functions to protect the central nervous system (CNS) from inhaled toxicants has been postulated. Just as a blood-brain barrier protects the CNS from systemic toxicants, the nose-brain barrier may have similar characteristic functions. One component of interest is nasal xenobiotic metabolism and its effect on the transport of pollutants into the CNS at environmentally plausible levels of exposure. Previous results have shown that inhaled xylene are dimethyl phenol (DMP) and methyl benzyl alcohol (MBA), and the nonvolatile metabolites are toluic acid (TA) and methyl hippuric acid (MHA). The nonvolatile metabolites of xylene, along with a small quantity of volatiles, representing either parent xylene or volatile metabolites, are transported via the olfactory epithelium to the glomeruli within the olfactory bulbs of the brain. Further work will be done to establish the linearity for each analyte at the actual highest detection limit of the GC/MS

[18F]FDG is not transported by P-glycoprotein and breast cancer resistance protein at the rodent blood–brain barrier

International Nuclear Information System (INIS)

Wanek, Thomas; Traxl, Alexander; Bankstahl, Jens P.; Bankstahl, Marion; Sauberer, Michael; Langer, Oliver; Kuntner, Claudia

2015-01-01

Introduction: Transport of 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) by the multidrug efflux transporters P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) at the blood–brain barrier (BBB) may confound the interpretation of [ 18 F]FDG brain PET data. Aim of this study was to assess the influence of ABCB1 and ABCG2 at the BBB on brain distribution of [ 18 F]FDG in vivo by performing [ 18 F]FDG PET scans in wild-type and transporter knockout mice and by evaluating changes in [ 18 F]FDG brain distribution after transporter inhibition. Methods: Dynamic small-animal PET experiments (60 min) were performed with [ 18 F]FDG in groups of wild-type and transporter knockout mice (Abcb1a/b (−/−) , Abcg2 (−/−) and Abcb1a/b (−/−) Abcg2 (−/−) ) and in wild-type rats without and with i.v. pretreatment with the known ABCB1 inhibitor tariquidar (15 mg/kg, given at 2 h before PET). Blood was sampled from animals from the orbital sinus vein at the end of the PET scans and measured in a gamma counter. Brain uptake of [ 18 F]FDG was expressed as the brain-to-blood radioactivity concentration ratio in the last PET time frame (K b,brain ). Results: K b,brain values of [ 18 F]FDG were not significantly different between different mouse types both without and with tariquidar pretreatment. The blood-to-brain transfer rate constant of [ 18 F]FDG was significantly lower in tariquidar-treated as compared with vehicle-treated rats (0.350 ± 0.025 mL/min/g versus 0.416 ± 0.024 mL/min/g, p = 0.026, paired t-test) but K b,brain values were not significantly different between both rat groups. Conclusion: Our results show that [ 18 F]FDG is not transported by Abcb1 at the mouse and rat BBB in vivo. In addition we found no evidence for Abcg2 transport of [ 18 F]FDG at the mouse BBB. Advances in knowledge and implications for patient care: Our findings imply that functional activity of ABCB1 and ABCG2 at the BBB does not need to be taken into account when

Is it possible to rapidly and noninvasively identify different plants from Asteraceae using electronic nose with multiple mathematical algorithms?

Directory of Open Access Journals (Sweden)

Hui-Qin Zou

2015-12-01

Full Text Available Many plants originating from the Asteraceae family are applied as herbal medicines and also beverage ingredients in Asian areas, particularly in China. However, they may be confused due to their similar odor, especially when ground into powder, losing their typical macroscopic characteristics. In this paper, 11 different multiple mathematical algorithms, which are commonly used in data processing, were utilized and compared to analyze the electronic nose (E-nose response signals of different plants from Asteraceae family. Results demonstrate that three-dimensional plot scatter figure of principal component analysis with less extracted components could offer the identification results more visually; simultaneously, all nine kinds of artificial neural network could give classification accuracies at 100%. This paper presents a rapid, accurate, and effective method to distinguish Asteraceae plants based on their response signals in E-nose. It also gives insights to further studies, such as to find unique sensors that are more sensitive and exclusive to volatile components in Chinese herbal medicines and to improve the identification ability of E-nose. Screening sensors made by other novel materials would be also an interesting way to improve identification capability of E-nose.

Post-harvest Quality Evaluation of Grapes using Non-destructive Electronic Nose

Directory of Open Access Journals (Sweden)

RAJIN S. M. Ataul Karim

2015-10-01

Full Text Available Over the past decades, electronic nose has opened a variety of possibilities and is becoming one of the most important non-destructive odour inspection technologies in the food industry. The objective of this study is to determine the quality degradation of the fruit by monitoring the change in the volatile compound while kept in storage using a lab manufactured electronic nose. Here, grapes are chosen as the fruit sample for experiment. Principal component analysis (PCA is used to determine the ability of the electronic nose to distinguish the different quality of the fruit stored over an interval of time. The result shows that using PCA analysis, the electronic nose is able to identify a clear distinction between the aromas of grapes stored for different time intervals.

Transport, monitoring, and successful brain MR imaging in unsedated neonates

International Nuclear Information System (INIS)

Mathur, Amit M.; Neil, Jeffrey J.; McKinstry, Robert C.; Inder, Terrie E.

2008-01-01

Neonatal cerebral MR imaging is a sensitive technique for evaluating brain injury in the term and preterm infant. In term encephalopathic infants, MR imaging reliably detects not only the pattern of brain injury but might also provide clues about the timing of injury. In premature infants, MR imaging has surpassed US in the detection of white matter injury, a common lesion in this population. Concerns remain about the safety and transport of sedated neonates for MR examination to radiology suites, which are usually located at a distance from neonatal intensive care units. We present our own institutional experience and guidelines used to optimize the performance of cerebral MR examinations in neonates without sedation or anesthesia. (orig.)

When the Nose Doesn’t Know: Canine Olfactory Function Associated With Health, Management, and Potential Links to Microbiota

Science.gov (United States)

Jenkins, Eileen K.; DeChant, Mallory T.; Perry, Erin B.

2018-01-01

The impact of health, management, and microbiota on olfactory function in canines has not been examined in review. The most important characteristic of the detection canine is its sense of smell. Olfactory receptors are primarily located on the ethmoturbinates of the nasal cavity. The vomeronasal organ is an additional site of odor detection that detects chemical signals that stimulate behavioral and/or physiological changes. Recent advances in the genetics of olfaction suggest that genetic changes, along with the unique anatomy and airflow of the canine nose, are responsible for the macrosmia of the species. Inflammation, alterations in blood flow and hydration, and systemic diseases alter olfaction and may impact working efficiency of detection canines. The scientific literature contains abundant information on the potential impact of pharmaceuticals on olfaction in humans, but only steroids, antibiotics, and anesthetic agents have been studied in the canine. Physical stressors including exercise, lack of conditioning, and high ambient temperature impact olfaction directly or indirectly in the canine. Dietary fat content, amount of food per meal, and timing of meals have been demonstrated to impact olfaction in mice and dogs. Gastrointestinal (GI) microbiota likely impacts olfaction via bidirectional communication between the GI tract and brain, and the microbiota is impacted by exercise, diet, and stress. The objective of this literature review is to discuss the specific effects of health, management, and microbiota shifts on olfactory performance in working canines. PMID:29651421

When the Nose Doesn’t Know: Canine Olfactory Function Associated With Health, Management, and Potential Links to Microbiota

Directory of Open Access Journals (Sweden)

Eileen K. Jenkins

2018-03-01

Full Text Available The impact of health, management, and microbiota on olfactory function in canines has not been examined in review. The most important characteristic of the detection canine is its sense of smell. Olfactory receptors are primarily located on the ethmoturbinates of the nasal cavity. The vomeronasal organ is an additional site of odor detection that detects chemical signals that stimulate behavioral and/or physiological changes. Recent advances in the genetics of olfaction suggest that genetic changes, along with the unique anatomy and airflow of the canine nose, are responsible for the macrosmia of the species. Inflammation, alterations in blood flow and hydration, and systemic diseases alter olfaction and may impact working efficiency of detection canines. The scientific literature contains abundant information on the potential impact of pharmaceuticals on olfaction in humans, but only steroids, antibiotics, and anesthetic agents have been studied in the canine. Physical stressors including exercise, lack of conditioning, and high ambient temperature impact olfaction directly or indirectly in the canine. Dietary fat content, amount of food per meal, and timing of meals have been demonstrated to impact olfaction in mice and dogs. Gastrointestinal (GI microbiota likely impacts olfaction via bidirectional communication between the GI tract and brain, and the microbiota is impacted by exercise, diet, and stress. The objective of this literature review is to discuss the specific effects of health, management, and microbiota shifts on olfactory performance in working canines.

When the Nose Doesn't Know: Canine Olfactory Function Associated With Health, Management, and Potential Links to Microbiota.

Science.gov (United States)

Jenkins, Eileen K; DeChant, Mallory T; Perry, Erin B

2018-01-01

The impact of health, management, and microbiota on olfactory function in canines has not been examined in review. The most important characteristic of the detection canine is its sense of smell. Olfactory receptors are primarily located on the ethmoturbinates of the nasal cavity. The vomeronasal organ is an additional site of odor detection that detects chemical signals that stimulate behavioral and/or physiological changes. Recent advances in the genetics of olfaction suggest that genetic changes, along with the unique anatomy and airflow of the canine nose, are responsible for the macrosmia of the species. Inflammation, alterations in blood flow and hydration, and systemic diseases alter olfaction and may impact working efficiency of detection canines. The scientific literature contains abundant information on the potential impact of pharmaceuticals on olfaction in humans, but only steroids, antibiotics, and anesthetic agents have been studied in the canine. Physical stressors including exercise, lack of conditioning, and high ambient temperature impact olfaction directly or indirectly in the canine. Dietary fat content, amount of food per meal, and timing of meals have been demonstrated to impact olfaction in mice and dogs. Gastrointestinal (GI) microbiota likely impacts olfaction via bidirectional communication between the GI tract and brain, and the microbiota is impacted by exercise, diet, and stress. The objective of this literature review is to discuss the specific effects of health, management, and microbiota shifts on olfactory performance in working canines.

Comparison of a Rat Primary Cell-Based Blood-Brain Barrier Model With Epithelial and Brain Endothelial Cell Lines: Gene Expression and Drug Transport

Directory of Open Access Journals (Sweden)

Szilvia Veszelka

2018-05-01

Full Text Available Cell culture-based blood-brain barrier (BBB models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC, ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA. As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L, and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1 and influx transporters (GLUT-1, LAT-1 were present in all models at mRNA levels. The transcript of BCRP (ABCG2 was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6, -9, MCT6, -8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which

Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler.

Science.gov (United States)

Longest, P Worth; Golshahi, Laleh; Behara, Srinivas R B; Tian, Geng; Farkas, Dale R; Hindle, Michael

2015-06-01

Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy. The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region. The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5-2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%. The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy.

Diverse applications of electronic-nose technologies in agriculture and forestry.

Science.gov (United States)

Wilson, Alphus D

2013-02-08

Electronic-nose (e-nose) instruments, derived from numerous types of aroma-sensor technologies, have been developed for a diversity of applications in the broad fields of agriculture and forestry. Recent advances in e-nose technologies within the plant sciences, including improvements in gas-sensor designs, innovations in data analysis and pattern-recognition algorithms, and progress in material science and systems integration methods, have led to significant benefits to both industries. Electronic noses have been used in a variety of commercial agricultural-related industries, including the agricultural sectors of agronomy, biochemical processing, botany, cell culture, plant cultivar selections, environmental monitoring, horticulture, pesticide detection, plant physiology and pathology. Applications in forestry include uses in chemotaxonomy, log tracking, wood and paper processing, forest management, forest health protection, and waste management. These aroma-detection applications have improved plant-based product attributes, quality, uniformity, and consistency in ways that have increased the efficiency and effectiveness of production and manufacturing processes. This paper provides a comprehensive review and summary of a broad range of electronic-nose technologies and applications, developed specifically for the agriculture and forestry industries over the past thirty years, which have offered solutions that have greatly improved worldwide agricultural and agroforestry production systems.

Diverse Applications of Electronic-Nose Technologies in Agriculture and Forestry

Science.gov (United States)

Wilson, Alphus D.

2013-01-01

Electronic-nose (e-nose) instruments, derived from numerous types of aroma-sensor technologies, have been developed for a diversity of applications in the broad fields of agriculture and forestry. Recent advances in e-nose technologies within the plant sciences, including improvements in gas-sensor designs, innovations in data analysis and pattern-recognition algorithms, and progress in material science and systems integration methods, have led to significant benefits to both industries. Electronic noses have been used in a variety of commercial agricultural-related industries, including the agricultural sectors of agronomy, biochemical processing, botany, cell culture, plant cultivar selections, environmental monitoring, horticulture, pesticide detection, plant physiology and pathology. Applications in forestry include uses in chemotaxonomy, log tracking, wood and paper processing, forest management, forest health protection, and waste management. These aroma-detection applications have improved plant-based product attributes, quality, uniformity, and consistency in ways that have increased the efficiency and effectiveness of production and manufacturing processes. This paper provides a comprehensive review and summary of a broad range of electronic-nose technologies and applications, developed specifically for the agriculture and forestry industries over the past thirty years, which have offered solutions that have greatly improved worldwide agricultural and agroforestry production systems. PMID:23396191

Holdaway's analysis of the nose prominence of an adult Nigerian ...

African Journals Online (AJOL)

The nose prominence was assessed using Holdaway's analysis. Twenty radiographs randomly selected, were retraced to assess for errors. Data analysis included descriptive statistics, Student's t‑tests and analysis of variance using the Statistical Package for Social Sciences. Results: The mean value recorded for the nose ...

Ultrasound imaging of the nose in septorhinoplasty patients.

Science.gov (United States)

Stenner, Markus; Rudack, Claudia

2015-10-01

Detailed preoperative planning based on available clinical information is an essential component of determining septorhinoplasty outcome. In addition to rhinoscopy and airway measurements, preoperative photographs are the only image modalities that are regularly used in septorhinoplasty patients and contribute to the preoperative planning of the surgery. The aim of this study was to evaluate the use of high-resolution ultrasonography in septorhinoplasty patients before surgery and during follow-up. We examined 35 patients before and after open septorhinoplasty using 12- and 15-MHz B-mode, linear array transducer ultrasound in noncontact mode. The patients presented with a variety of different functional and aesthetic problems, and all underwent septorhinoplasty for septal modification, and tip and dorsum refinement. The mean follow-up time for ultrasound after surgery was 4.5 weeks. Soft tissue, cartilaginous, and bony structures of the nose could be well-visualised. In the untreated nose, functional and aesthetic characteristics as well as preoperative anatomy relevant for the planning of the surgery could be documented. Surgical modifications of the treated nose postoperatively, that is, osteotomies, inserted spreader grafts, diced cartilage in fascia, and tip sutures could be visualized and followed. Ultrasonography of the nose with a high-frequency transducer may be a helpful tool during preoperative planning and postoperative follow-up in septorhinoplasty patients and might be a reasonable completion to the common photographic and functional diagnostic.

Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters

Energy Technology Data Exchange (ETDEWEB)

Kilbourn, Michael R; Frey, Kirk A; Vander Borght, Thierry; Sherman, Phillip S

1996-05-01

The effects of various dopaminergic drug treatments on the in vivo regional brain distribution of high-affinity radioligands ([{sup 11}C]dihydrotetrabenazine and [{sup 11}C]methoxytetrabenazine) for the rat brain vesicular monoamine transporter (VMAT2) were determined. Acute treatments with reserpine (2 mg/kg i.p.), tetrabenazine (10 mg/kg i.v.) or related benzoisoquinolines significantly reduced radiotracer binding in vivo. In contrast, radiotracer distributions remained unchanged after treatments with other dopaminergic drugs, whether given by single injection (haloperidol, 1 mg/kg i.p., pargyline 80 mg/kg), repeatedly (pargyline, 80 mg/kg s.c., 14 days), or by continuous infusion (deprenyl, 10 mg/kg/day, 5 days; L-DOPA methyl ester 100 mg/kg/day, 5 days). Repeated injections of tetrabenazine (5 mg/kg i.p., twice daily, 3 days) did not alter in vivo radioligand binding measured after allowing drug washout from the brain. These studies support the proposal that in vivo PET imaging of VMAT2 radioligands in patients with extrapyramidal movement disorders will not be affected by concurrent use of L-DOPA or deprenyl.

Quantification of Wine Mixtures with an Electronic Nose and a Human Panel

Science.gov (United States)

Aleixandre, Manuel; Cabellos, Juan M.; Arroyo, Teresa; Horrillo, M. C.

2018-01-01

In this work, an electronic nose and a human panel were used for the quantification of wines formed by binary mixtures of four white grape varieties and two varieties of red wines at different percentages (from 0 to 100% in 10% steps for the electronic nose and from 0 to 100% in 25% steps for the human panel). The wines were prepared using the traditional method with commercial yeasts. Both techniques were able to quantify the mixtures tested, but it is important to note that the technology of the electronic nose is faster, simpler, and more objective than the human panel. In addition, better results of quantification were also obtained using the electronic nose. PMID:29484296

21 CFR 874.4500 - Ear, nose, and throat microsurgical carbon dioxide laser.

Science.gov (United States)

2010-04-01

... laser. 874.4500 Section 874.4500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND..., nose, and throat microsurgical carbon dioxide laser. (a) Identification. An ear, nose, and throat microsurgical carbon dioxide laser is a device intended for the surgical excision of tissue from the ear, nose...

Economic Evaluation pf Antibacterial Usage in Ear, Nose and Throat ...

African Journals Online (AJOL)

Purpose: To carry out economic evaluation of antibacterial usage for Ear, Nose and Throat infections in a tertiary health care facility in Nigeria. Methods: Antibacterial utilisation evaluation was carried out retrospectively over one year period by reviewing 122 case notes containing 182 prescriptions of patient with Ear Nose ...

White-nose syndrome in bats: a primer for resource managers

Science.gov (United States)

Castle, K.T.; Cryan, P.M.

2010-01-01

White-nose syndrome emerged as a devastating new disease of North American hibernating bats over the past four winters. The disease has spread more than 1,600 kilometers (1,000 mi) since it was first observed in a small area of upstate New York, and has affected six species of bats in the caves and mines they rely on for winter survival. A newly discovered, cold-loving fungus (Geomyces destructans) causes the characteristic skin infection of white-nose syndrome and can infect presumably healthy bats when they hibernate. Although clear links between skin infection by G. destructans and death have not yet been established, the fungus is the most plausible cause of the disease. Thousands of caves and mines are administered by the National Park Service. Although bats testing positive for white-nose syndrome have been detected only at two sites in the National Park System thus far, the National Park Service (NPS) has been preparing for the spread and effects of white-nose syndrome through a proactive national program of response coordination, research support and interpretation, and education. National park areas across the nation are uniquely situated to help understand white-nose syndrome and its ecosystem impacts, and assist in the conservation and recovery of affected bat species.

What will this do to me and my brain? Ethical issues in brain-to-brain interfacing

Directory of Open Access Journals (Sweden)

Elisabeth eHildt

2015-02-01

Full Text Available For several years now, brain-computer interfaces (BCIs in which brain signals are used to navigate a computer, a prostheses or a technical device, have been developed in various experimental contexts (Wolpaw & Wolpaw 2012; Grübler & Hildt 2014. Researchers have recently taken the next step and run experiments based on connections between two brains. These so-called brain-to-brain interfaces (abbreviation: BBIs or BTBIs involve not only a BCI component deriving information from a brain and sending it to a computer, but also a computer-brain interface (CBI component delivering information to another brain. What results is technology-mediated brain-to-brain communication (B2B communication, i.e. direct communication between two brains that does not involve any activity of the peripheral nervous system. In what follows, ethical issues that arise in neural interfacing will be discussed after a short introduction to recent BBI experiments. In this, the focus will be on the implications BBIs may have on the individual at the CBI side of the BBI, i.e. on the recipient.

Stuffy or runny nose - adult

Science.gov (United States)

... than 10 days, or produces yellow-green or gray mucus Nasal discharge following a head injury Symptoms ... nose; Postnasal drip; Rhinorrhea; Nasal congestion Images Throat anatomy References Bachert C, Calus L, Gevaert P. Rhinosinusitis ...

Electrokinetic Particle Transport in Micro-Nanofluidics Direct Numerical Simulation Analysis

CERN Document Server

Qian, Shizhi

2012-01-01

Numerous applications of micro-/nanofluidics are related to particle transport in micro-/nanoscale channels, and electrokinetics has proved to be one of the most promising tools to manipulate particles in micro/nanofluidics. Therefore, a comprehensive understanding of electrokinetic particle transport in micro-/nanoscale channels is crucial to the development of micro/nano-fluidic devices. Electrokinetic Particle Transport in Micro-/Nanofluidics: Direct Numerical Simulation Analysis provides a fundamental understanding of electrokinetic particle transport in micro-/nanofluidics involving elect

Circadian Regulation of Glutamate Transporters

Directory of Open Access Journals (Sweden)

Donají Chi-Castañeda

2018-06-01

Full Text Available L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS. This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation of glutamate transport in neuronal and glial cells, and their consequence in brain function.

White-Nose Syndrome of bats

Science.gov (United States)

Jessie A. Glaeser; Martin J. Pfeiffer; Daniel L. Lindner

2016-01-01

Devastating. Catastrophic. Unprecedented. This is how white-nose syndrome of bats (WNS) is characterized. It is one of the deadliest wildlife diseases ever observed and could have significant impacts on outdoor recreation, agriculture and wildlife management.

Stuffy or runny nose - children

Science.gov (United States)

... than 10 days, or produces yellow-green or gray mucus Symptoms that last more than 3 weeks ... baby or infant has a fever Images Throat anatomy Runny and stuffy nose References McGann KA, Long SS. ...

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies.

Science.gov (United States)

Nour, Samia A; Abdelmalak, Nevine S; Naguib, Marianne J; Rashed, Hassan M; Ibrahim, Ahmed B

2016-11-01

Clonazepam (CZ) is an anti-epileptic drug used mainly in status epilepticus (SE). The drug belongs to Class II according to BCS classification with very limited solubility and high permeability and it suffers from extensive first-pass metabolism. The aim of the present study was to develop CZ-loaded polymeric micelles (PM) for direct brain delivery allowing immediate control of SE. PM were prepared via thin film hydration (TFH) technique adopting a central composite face-centered design (CCFD). The seventeen developed formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro release. For evaluating the in vivo behavior of the optimized formula, both biodistrbution using 99m Tc-radiolabeled CZ and pharmacodynamics studies were done in addition to ex vivo cytotoxicty. At a drug:Pluronic® P123:Pluronic® L121 ratio of 1:20:20 (PM7), a high EE, ZP, Q8h, and a low PDI was achieved. The biodistribution studies revealed that the optimized formula had significantly higher drug targeting efficiency (DTE = 242.3%), drug targeting index (DTI = 144.25), and nose-to-brain direct transport percentage (DTP = 99.30%) and a significant prolongation of protection from seizures in comparison to the intranasally administered solution with minor histopathological changes. The declared results reveal the ability of the developed PM to be a strong potential candidate for the emergency treatment of SE.

Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood–Brain Barrier

Directory of Open Access Journals (Sweden)

Julia V. Georgieva

2014-11-01

Full Text Available The blood–brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood–brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier–drug system (“Trojan horse complex” is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain.

Ionic charge transport between blockages: Sodium cation conduction in freshly excised bulk brain tissue

Energy Technology Data Exchange (ETDEWEB)

Emin, David, E-mail: emin@unm.edu [Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131 (United States); Akhtari, Massoud [Semple Institutes for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States); Ellingson, B. M. [Department of Radiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States); Mathern, G. W. [Department of Neurosurgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States)

2015-08-15

We analyze the transient-dc and frequency-dependent electrical conductivities between blocking electrodes. We extend this analysis to measurements of ions’ transport in freshly excised bulk samples of human brain tissue whose complex cellular structure produces blockages. The associated ionic charge-carrier density and diffusivity are consistent with local values for sodium cations determined non-invasively in brain tissue by MRI (NMR) and diffusion-MRI (spin-echo NMR). The characteristic separation between blockages, about 450 microns, is very much shorter than that found for sodium-doped gel proxies for brain tissue, >1 cm.

Angioendotheliosarcoma of the nose--a case report

DEFF Research Database (Denmark)

Waersted, A; Andersen, Klaus Ejner; Hansen, J P

1984-01-01

Angioendotheliosarcoma of the face or scalp is regarded as a highly malignant tumor. We present a case with onset as a purple macule on the nose, suspected to be rosacea, and emphasize the use of early skin biopsy when a red or purple discoloration is seen in the face of elderly people.......Angioendotheliosarcoma of the face or scalp is regarded as a highly malignant tumor. We present a case with onset as a purple macule on the nose, suspected to be rosacea, and emphasize the use of early skin biopsy when a red or purple discoloration is seen in the face of elderly people....

Directions of development of transport infrastructure of Ukraine

Directory of Open Access Journals (Sweden)

V.I. Kopytko

2012-08-01

Full Text Available The trends of the transport infrastructure development as a basic factor of national security, the stable and dynamic economic growth, its integration into the European and world economic space are considered. The most important element of the transport infrastructure in the modern economy is a network of logistic providers, which reduce transaction costs and improve the quality of transport service. And the main direction of government policy according to infrastructure should be a gradual transition of activities for establishing and operating the infrastructure objects, that is a burden for the State, from a cost sphere to an efficient business based on the state-private partnership.

An empirical study of direct rebound effect for passenger transport in urban China

International Nuclear Information System (INIS)

Wang, H.; Zhou, P.; Zhou, D.Q.

2012-01-01

Transport sector accounts for about 8% of total energy consumption in China and this share will likely increase in the visible future. Improving energy efficiency has been considered as a major way for reducing transport energy use, whereas its effectiveness might be affected by the rebound effect. This paper estimates the direct rebound effect for passenger transport in urban China by using the linear approximation of the Almost Ideal Demand System model and simulation analysis. Our empirical results reveal the existence of direct rebound effect for passenger transport in urban China. A majority of the expected reduction in transport energy consumption from efficiency improvement could be offset due to the existence of rebound effect. We have further investigated the relationship between the magnitude of direct rebound effect and households' expenditure. It was found that the direct rebound effect for passenger transport tends to decline with the increase of per capita household consumption expenditure. - Highlights: ► The magnitude of direct rebound effect for urban passenger transport in China is 96%. ► The rebound effect in China could be larger than that in developed countries. ► The rebound effect in China declined with the increase of per capita expenditure.

Quality Evaluation of Agricultural Distillates Using an Electronic Nose

OpenAIRE

Dymerski, Tomasz; Gębicki, Jacek; Wardencki, Waldemar; Namieśnik, Jacek

2013-01-01

The paper presents the application of an electronic nose instrument to fast evaluation of agricultural distillates differing in quality. The investigations were carried out using a prototype of electronic nose equipped with a set of six semiconductor sensors by FIGARO Co., an electronic circuit converting signal into digital form and a set of thermostats able to provide gradient temperature characteristics to a gas mixture. A volatile fraction of the agricultural distillate samples differing ...

Identification of insecticide residues with a conducting-polymer electronic nose

Science.gov (United States)

A.D. Wilson

2014-01-01

The identification of insecticide residues on crop foliage is needed to make periodic pest management decisions. Electronic-nose (e-nose) methods were developed and tested as a means of acquiring rapid identifications of insecticide residue types at relatively low cost by detection of headspace volatiles released from inert surfaces in vitro. Detection methods were...

White-Nose Syndrome Fungus (Geomyces destructans) in Bats, Europe

OpenAIRE

Wibbelt, Gudrun; Kurth, Andreas; Hellmann, David; Weishaar, Manfred; Barlow, Alex; Veith, Michael; Prüger, Julia; Görföl, Tamás; Grosche, Lena; Bontadina, Fabio; Zöphel, Ulrich; Seidl, Hans-Peter; Cryan, Paul M.; Blehert, David S.

2010-01-01

White-nose syndrome is an emerging disease in North America that has caused substantial declines in hibernating bats. A recently identified fungus (Geomyces destructans) causes skin lesions that are characteristic of this disease. Typical signs of this infection were not observed in bats in North America before white-nose syndrome was detected. However, unconfirmed reports from Europe indicated white fungal growth on hibernating bats without associated deaths. To investigate these differences...

Animal models for studying transport across the blood-brain barrier.

Science.gov (United States)

Bonate, P L

1995-01-01

There are many reasons for wishing to determine the rate of uptake of a drug from blood into brain parenchyma. However, when faced with doing so for the first time, choosing a method can be a formidable task. There are at least 7 methods from which to choose: indicator dilution, brain uptake index, microdialysis, external registration, PET scanning, in situ perfusion, and compartmental modeling. Each method has advantages and disadvantages. Some methods require very little equipment while others require equipment that can cost millions of dollars. Some methods require very little technical experience whereas others require complex surgical manipulation. The mathematics alone for the various methods range from simple algebra to complex integral calculus and differential equations. Like most things in science, as the complexity of the technique increases, so does the quantity of information it provides. This review is meant to serve as a starting point for the researcher who wishes to study transport and uptake across the blood-brain barrier in animal models. An overview of the mathematical theory, as well as an introduction to the techniques, is presented.

Discrimination of chicken seasonings and beef seasonings using electronic nose and sensory evaluation.

Science.gov (United States)

Tian, Huaixiang; Li, Fenghua; Qin, Lan; Yu, Haiyan; Ma, Xia

2014-11-01

This study examines the feasibility of electronic nose as a method to discriminate chicken and beef seasonings and to predict sensory attributes. Sensory evaluation showed that 8 chicken seasonings and 4 beef seasonings could be well discriminated and classified based on 8 sensory attributes. The sensory attributes including chicken/beef, gamey, garlic, spicy, onion, soy sauce, retention, and overall aroma intensity were generated by a trained evaluation panel. Principal component analysis (PCA), discriminant factor analysis (DFA), and cluster analysis (CA) combined with electronic nose were used to discriminate seasoning samples based on the difference of the sensor response signals of chicken and beef seasonings. The correlation between sensory attributes and electronic nose sensors signal was established using partial least squares regression (PLSR) method. The results showed that the seasoning samples were all correctly classified by the electronic nose combined with PCA, DFA, and CA. The electronic nose gave good prediction results for all the sensory attributes with correlation coefficient (r) higher than 0.8. The work indicated that electronic nose is an effective method for discriminating different seasonings and predicting sensory attributes. © 2014 Institute of Food Technologists®

[Malignant diseases of the inner nose--epidemiology and occupational medicine aspects].

Science.gov (United States)

Hartung, M

1989-06-01

Squamous cell carcinomas are the most frequent malignancies of the inner nose, followed by adenocarcinomas, adenoid cystic carcinomas, and other malignant neoplasms. Carcinomas of the nose can be recognized as occupational diseases if there has been a professional exposition to ionizing rays, certain arsenic compounds, hexavalent chrome compounds, nickel, oak or beech wood dust. The sources of danger relevant in industrial medicine are indicated. At present, adenocarcinomas induced by dust of wood are of special significance: 16 out of 22 carcinomas of the nose recognized as occupational diseases between 1978 and 1986 are due to oak and beech wood dust.

Quantitative Analysis of Nanoparticle Transport through in Vitro Blood-Brain Barrier Models

NARCIS (Netherlands)

Åberg, Christoffer

2016-01-01

Nanoparticle transport through the blood-brain barrier has received much attention of late, both from the point of view of nano-enabled drug delivery, as well as due to concerns about unintended exposure of nanomaterials to humans and other organisms. In vitro models play a lead role in efforts to

Mathematical interpretation of Brownian motor model: Limit cycles and directed transport phenomena

Science.gov (United States)

Yang, Jianqiang; Ma, Hong; Zhong, Suchuang

2018-03-01

In this article, we first suggest that the attractor of Brownian motor model is one of the reasons for the directed transport phenomenon of Brownian particle. We take the classical Smoluchowski-Feynman (SF) ratchet model as an example to investigate the relationship between limit cycles and directed transport phenomenon of the Brownian particle. We study the existence and variation rule of limit cycles of SF ratchet model at changing parameters through mathematical methods. The influences of these parameters on the directed transport phenomenon of a Brownian particle are then analyzed through numerical simulations. Reasonable mathematical explanations for the directed transport phenomenon of Brownian particle in SF ratchet model are also formulated on the basis of the existence and variation rule of the limit cycles and numerical simulations. These mathematical explanations provide a theoretical basis for applying these theories in physics, biology, chemistry, and engineering.

Monitoring storage time and quality attribute of egg based on electronic nose

International Nuclear Information System (INIS)

Wang Yongwei; Jun Wang; Bo Zhou; Qiujun Lu

2009-01-01

The objective of this study was to investigate the potential of an electronic nose (E-nose) technique for monitoring egg storage time and quality attributes. An electronic nose was used to distinguish eggs under cool and room-temperature storage by means of principal component analysis (PCA), linear discriminant analysis (LDA), BP neural network (BPNN) and the combination of a genetic algorithm and BP neural network (GANN). Results showed that the E-nose could distinguish eggs of different storage time under cool and room-temperature storage by LDA, PCA, BPNN and GANN; better prediction values were obtained by GANN than by BPNN. Relationships were established between the E-nose signal and egg quality indices (Haugh unit and yolk factor) by quadratic polynomial step regression (QPSR). The prediction models for Haugh unit and yolk factor indicated a good prediction performance. The Haugh unit model had a standard error of prediction of 3.74 and correlation coefficient 0.91; the yolk factor model had a 0.02 SEP and 0.93 correlation coefficient between predicted and measured values respectively.

Directed Fluid Transport and Mixing with Biomimetic Cilia Arrays

Science.gov (United States)

Shields, A. R.; Evans, B. A.; Carstens, B. L.; Falvo, M. R.; Washburn, S.; Superfine, R.

2009-03-01

We present results on the long-range, directed fluid transport and fluidic mixing produced by the collective beating of arrays of biomimetic cilia. These artificial cilia are arrays of free-standing nanorods roughly the size of biological cilia, which we fabricate from a polymer-magnetic nanoparticle composite material and actuate with permanent magnets to mimic biological cilia. Biological cilia have evolved to produce microscale fluid transport and are increasingly being recognized as critical components in a wide range of biological systems. However, despite much effort cilia generated fluid flows remain an area of active study. In the last decade, cilia-driven fluid flow in the embryonic node of vertebrates has been implicated as the initial left-right symmetry breaking event in these embryos. With silia we generate directional fluid transport by mimicking the tilted conical beating of these nodal cilia. By seeding fluorescent microparticles into the fluid we have noted the existence of two distinct flow regimes. The fluid flow is directional and coherent above the cilia tips, while between the cilia tips and the floor particle motion is complicated and suggestive of chaotic advection.

Analysis of New Aerodynamic Design of the Nose Cone Section Using CFD and SPH

Directory of Open Access Journals (Sweden)

Bogdan-Alexandru BELEGA

2015-06-01

Full Text Available A new nose cones concept that promises a gain in performance over existing conventional nose cones is discussed in this paper. It is shown that significant performance gains result from the adaptation of the exhaust flow to the ambient pressure. For this complex work, it was necessary to collect and study the various nose cone shapes and the equations describing them? The paper objective was to identify the types of nose cones with ejector channels and specific aerodynamic characteristics of different types of nose cones. The scope of this paper is to develop some prototype profiles with outstanding aerodynamic qualities and low cost for use in construction projects for missile increasing their range and effect on target. The motivation for such a work is caused by a lack of data on aerodynamics for profiles of some nose cones and especially improved aerodynamic qualities that can be used in designing missiles/ rockets. This design method consists of a geometry creation step in which a three-dimensional geometry is generated, a mathematical model presented and a simple flow analysis (FLUENT Simulation from SolidWorks2012 and ANSYS Simulation with SPH for fluid-structure interaction, step which predicts the air intake mass flow rate. Flow phenomena observed in numerical simulations during different nose cone operations are highlighted, critical design aspects and operation conditions are discussed, and performance characteristics of the selected nose cone are presented.

Peptide carrier-mediated non-covalent delivery of unmodified cisplatin, methotrexate and other agents via intravenous route to the brain.

Directory of Open Access Journals (Sweden)

Gobinda Sarkar

Full Text Available BACKGROUND: Rapid pre-clinical evaluation of chemotherapeutic agents against brain cancers and other neurological disorders remains largely unattained due to the presence of the blood-brain barrier (BBB, which limits transport of most therapeutic compounds to the brain. A synthetic peptide carrier, K16ApoE, was previously developed that enabled transport of target proteins to the brain by mimicking a ligand-receptor system. The peptide carrier was found to generate transient BBB permeability, which was utilized for non-covalent delivery of cisplatin, methotrexate and other compounds to the brain. APPROACH: Brain delivery of the chemotherapeutics and other agents was achieved either by injecting the carrier peptide and the drugs separately or as a mixture, to the femoral vein. A modification of the method comprised injection of K16ApoE pre-mixed with cetuximab, followed by injection of a 'small-molecule' drug. PRINCIPAL FINDINGS: Seven-of-seven different small molecules were successfully delivered to the brain via K16ApoE. Depending on the method, brain uptake with K16ApoE was 0.72-1.1% for cisplatin and 0.58-0.92% for methotrexate (34-50-fold and 54-92 fold greater for cisplatin and methotrexate, respectively, with K16ApoE than without. Visually intense brain-uptake of Evans Blue, Light Green SF and Crocein scarlet was also achieved. Direct intracranial injection of EB show locally restricted distribution of the dye in the brain, whereas K16ApoE-mediated intravenous injection of EB resulted in the distribution of the dye throughout the brain. Experiments with insulin suggest that ligand-receptor signaling intrinsic to the BBB provides a natural means for passive transport of some molecules across the BBB. SIGNIFICANCE: The results suggest that the carrier peptide can non-covalently transport various chemotherapeutic agents to the brain. Thus, the method offers an avenue for pre-clinical evaluation of various small and large therapeutic molecules

Permeabilization of the blood-brain barrier via mucosal engrafting: implications for drug delivery to the brain.

Science.gov (United States)

Bleier, Benjamin S; Kohman, Richie E; Feldman, Rachel E; Ramanlal, Shreshtha; Han, Xue

2013-01-01

Utilization of neuropharmaceuticals for central nervous system(CNS) disease is highly limited due to the blood-brain barrier(BBB) which restricts molecules larger than 500Da from reaching the CNS. The development of a reliable method to bypass the BBB would represent an enormous advance in neuropharmacology enabling the use of many potential disease modifying therapies. Previous attempts such as transcranial catheter implantation have proven to be temporary and associated with multiple complications. Here we describe a novel method of creating a semipermeable window in the BBB using purely autologous tissues to allow for high molecular weight(HMW) drug delivery to the CNS. This approach is inspired by recent advances in human endoscopic transnasal skull base surgical techniques and involves engrafting semipermeable nasal mucosa within a surgical defect in the BBB. The mucosal graft thereby creates a permanent transmucosal conduit for drugs to access the CNS. The main objective of this study was to develop a murine model of this technique and use it to evaluate transmucosal permeability for the purpose of direct drug delivery to the brain. Using this model we demonstrate that mucosal grafts allow for the transport of molecules up to 500 kDa directly to the brain in both a time and molecular weight dependent fashion. Markers up to 40 kDa were found within the striatum suggesting a potential role for this technique in the treatment of Parkinson's disease. This proof of principle study demonstrates that mucosal engrafting represents the first permanent and stable method of bypassing the BBB thereby providing a pathway for HMW therapeutics directly into the CNS.

Roles and regulation of brain glutamate transporters in normal and pathological brain function

International Nuclear Information System (INIS)

O'Shea, R.D.

2001-01-01

Full text: Glutamate (Glu) is the major excitatory neurotransmitter in the mammalian CNS. Synaptically released Glu acts on both ionotropic (iGluR) and metabotropic receptors, and excessive iGluR activation results in neuronal death (termed excitotoxicity). Removal of Glu from the synapse is thus critical for normal transmission and to prevent excitotoxicity, and is performed exclusively by a family of excitatory amino acid transporters (EAATs, also known as glutamate transporters). Disregulation of Glu transport may contribute to the pathogenesis of many neurodegenerative conditions, and altered expression or function of EAATs has been identified in a number of these pathologies. These studies investigated the functional and pathological effects of EAAT inhibitors in vitro, and developed a novel screening assay for compounds with activity at EAATs. Astrocytic EAATs are responsible for the majority of Glu uptake in brain, so preparations containing both astrocytes and neurones are required to analyse the contribution of EAATs to neuroprotection. Organotypic hippocampal cultures (OHCs), which exhibit many of the features of the intact CNS, were prepared from 11-14 day old Sprague Dawley rats (anaesthetised with halothane). Hippocampal slices (350 μm thick) were maintained on culture well inserts in chemically defined medium. After 2 weeks, cultures were treated with EAAT inhibitors for 3-7 days in the presence or absence of 300 μM Glu. Treatment with most EAAT inhibitors resulted in cell death that was proportional to the Glu concentration in the medium. In contrast, (2S,3S,4R)-2-(carboxycyclopropyl)glycine (L-CCG-III), a competitive substrate at EAATs (and possibly an antagonist at the kainate subtype of iGluR), appeared to be neuroprotective: increased Glu was not toxic in the presence of this drug. These results demonstrate the sensitivity of OHCs to inhibition of Glu uptake, highlighting the importance of EAATs in preventing excitotoxicity. Since modulation of

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain.

Science.gov (United States)

Jensen, Vivi F H; Mølck, Anne-Marie; Chapman, Melissa; Alifrangis, Lene; Andersen, Lene; Lykkesfeldt, Jens; Bøgh, Ingrid B

2017-01-01

The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30-50% (4-6 mM versus 7-9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

Direct transport to a PCI-capable hospital is associated with improved survival after adult out-of-hospital cardiac arrest of medical aetiology.

Science.gov (United States)

McKenzie, Nicole; Williams, Teresa A; Ho, Kwok M; Inoue, Madoka; Bailey, Paul; Celenza, Antonio; Fatovich, Daniel; Jenkins, Ian; Finn, Judith

2018-05-02

To compare survival outcomes of adults with out-of-hospital cardiac arrest (OHCA) of medical aetiology directly transported to a percutaneous-coronary-intervention capable (PCI-capable) hospital (direct transport) with patients transferred to a PCI-capable hospital via another hospital without PCI services available (indirect transport) by emergency medical services (EMS). This retrospective cohort study used the St John Ambulance Western Australia OHCA Database and medical chart review. We included OHCA patients (≥18 years) admitted to any one of five PCI-capable hospitals in Perth between January 2012 and December 2015. Survival to hospital discharge (STHD) and survival up to 12-months after OHCA were compared between the direct and indirect transport groups using multivariable logistic and Cox-proportional hazards regression, respectively, while adjusting for so-called "Utstein variables" and other potential confounders. Of the 509 included patients, 404 (79.4%) were directly transported to a PCI-capable hospital and 105 (20.6%) transferred via another hospital to a PCI-capable hospital; 274/509 (53.8%) patients STHD and 253/509 (49.7%) survived to 12-months after OHCA. Direct transport patients were twice as likely to STHD (adjusted odds ratio 1.97, 95% confidence interval [CI] 1.13-3.43) than those transferred via another hospital. Indirect transport was also associated with a possible increased risk of death, up to 12-months, compared to direct transport (adjusted hazard ratio 1.36, 95% CI 1.00-1.84). Direct transport to a PCI-capable hospital for post-resuscitation care is associated with a survival advantage for adults with OHCA of medical aetiology. This has implications for EMS transport protocols for patients with OHCA. Copyright © 2018 Elsevier B.V. All rights reserved.

[Targeting the brain through the nose. Effects of intranasally administered insulin].

Science.gov (United States)

Brünner, Y F; Benedict, C; Freiherr, J

2013-08-01

The assumption that the human brain is an insulin-independent organ was disproved with the discovery of insulin receptors in the central nervous system in the year 1978. Evidence has been provided for a high density of insulin receptors in brain regions responsible for cognitive memory processes (hippocampus) and for the regulation of appetite (hypothalamus). Accordingly, in animal studies an increased insulin level in the central nervous system leads to an improvement of hippocampal memory function and a decrease of food intake. Similar results were obtained in humans using the method of intranasal administration of insulin. Intranasal insulin reaches the brain and the cerebrospinal fluid via the olfactory epithelium and olfactory nerve fiber bundles leading through the lamina cribrosa to the olfactory bulb. Thus, this method renders the investigation of specific insulin effects in humans possible. The therapeutic potential of an intranasal insulin administration for the treatment of diseases for which an imbalance of the central nervous insulin metabolism is discussed (e.g. Alzheimer's disease, diabetes mellitus and obesity) can only be estimated with the help of further clinical studies.

Continuous monitoring of odours from a composting plant using electronic noses.

Science.gov (United States)

Sironi, Selena; Capelli, Laura; Céntola, Paolo; Del Rosso, Renato; Il Grande, Massimiliano

2007-01-01

The odour impact of a composting plant situated in an urbanized area was evaluated by continuously monitoring the ambient air close to the plant during a period of about 4 days using two electronic noses. One electronic nose was installed in a nearby house, and the other one inside the perimeter of the composting plant in order to compare the response of both instruments. The results of the monitoring are represented by tables that report the olfactory class and the odour concentration value attributed to the analyzed air for each of the 370 measurements carried out during the monitoring period. The electronic nose installed at the house detected the presence of odours coming from the composting plant for about 7.8% of the monitoring total duration. Of the odour detections, 86% (25 of 29 measurements) were classified as belonging to the olfactory class corresponding to the open air storage of the waste screening overflows heaps, which was therefore identified to be the major odour source of the monitored composting plant. In correspondence of the measurements during which the electronic nose inside the house detected the presence of odours from the composting plant, the olfactory classes recognized by both instruments coincide. Moreover, the electronic nose at the house detected the presence of odours from the composting plant at issue in correspondence of each odour perception of the house occupants. The results of the study show the possibility of using an electronic nose for environmental odours monitoring, which enables the classification of the quality of the air and to quantify the olfactory nuisance from an industrial source in terms of duration and odour concentration.

Development and evaluation of Desvenlafaxine loaded PLGA-chitosan nanoparticles for brain delivery

Directory of Open Access Journals (Sweden)

Gui-Feng Tong

2017-09-01

Full Text Available Depression is a debilitating psychiatric condition that remains the second most common cause of disability worldwide. Currently, depression affects more than 4 per cent of the world’s population. Most of the drugs intended for clinical management of depression augment the availability of neurotransmitters at the synapse by inhibiting their neuronal reuptake. However, the therapeutic efficacy of antidepressants is often compromised as they are unable to reach brain by the conventional routes of administration. The purpose of the present study was to reconnoiter the potential of mucoadhesive PLGA-chitosan nanoparticles for the delivery of encapsulated Desvenlafaxine to the brain by nose to brain delivery route for superior pharmacokinetic and pharmacodynamic profile of Desvenlafaxine. Desvenlafaxine loaded PLGA-chitosan nanoparticles were prepared by solvent emulsion evaporation technique and optimized for various physiochemical characteristics. The antidepressant efficacy of optimized Desvenlafaxine was evaluated in various rodent depression models together with the biochemical estimation of monoamines in their brain. Further, the levels of Desvenlafaxine in brain and blood plasma were determined at various time intervals for calculation of different pharmacokinetic parameters. The optimized Desvenlafaxine loaded PLGA-chitosan nanoparticles (∼172 nm/+35 mV on intranasal administration significantly reduced the symptoms of depression and enhanced the level of monoamines in the brain in comparison with orally administered Desvenlafaxine. Nose to brain delivery of Desvenlafaxine PLGA-chitosan nanoparticles also enhanced the pharmacokinetic profile of Desvenlafaxine in brain together with their brain/blood ratio at different time points. Thus, intranasal mucoadhesive Desvenlafaxine PLGA-chitosan nanoparticles could be potentially used for the treatment of depression.

Brain activation during direct and indirect processing of positive and negative words.

Science.gov (United States)

Straube, Thomas; Sauer, Andreas; Miltner, Wolfgang H R

2011-09-12

The effects of task conditions on brain activation to emotional stimuli are poorly understood. In this event-related fMRI study, brain activation to negative and positive words (matched for arousal) and neutral words was investigated under two task conditions. Subjects either had to attend to the emotional meaning (direct task) or to non-emotional features of the words (indirect task). Regardless of task, positive vs. negative words led to increased activation in the ventral medial prefrontal cortex, while negative vs. positive words induced increased activation of the insula. Compared to neutral words, all emotional words were associated with increased activation of the amygdala. Finally, the direct condition, as compared to the indirect condition, led to enhanced activation to emotional vs. neutral words in the dorsomedial prefrontal cortex and the anterior cingulate cortex. These results suggest valence and arousal dependent brain activation patterns that are partially modulated by participants' processing mode of the emotional stimuli. Copyright © 2011 Elsevier B.V. All rights reserved.

Chocolate Classification by an Electronic Nose with Pressure Controlled Generated Stimulation

Directory of Open Access Journals (Sweden)

Luis F. Valdez

2016-10-01

Full Text Available In this work, we will analyze the response of a Metal Oxide Gas Sensor (MOGS array to a flow controlled stimulus generated in a pressure controlled canister produced by a homemade olfactometer to build an E-nose. The built E-nose is capable of chocolate identification between the 26 analyzed chocolate bar samples and four features recognition (chocolate type, extra ingredient, sweetener and expiration date status. The data analysis tools used were Principal Components Analysis (PCA and Artificial Neural Networks (ANNs. The chocolate identification E-nose average classification rate was of 81.3% with 0.99 accuracy (Acc, 0.86 precision (Prc, 0.84 sensitivity (Sen and 0.99 specificity (Spe for test. The chocolate feature recognition E-nose gives a classification rate of 85.36% with 0.96 Acc, 0.86 Prc, 0.85 Sen and 0.96 Spe. In addition, a preliminary sample aging analysis was made. The results prove the pressure controlled generated stimulus is reliable for this type of studies.

Chocolate Classification by an Electronic Nose with Pressure Controlled Generated Stimulation.

Science.gov (United States)

Valdez, Luis F; Gutiérrez, Juan Manuel

2016-10-20

In this work, we will analyze the response of a Metal Oxide Gas Sensor (MOGS) array to a flow controlled stimulus generated in a pressure controlled canister produced by a homemade olfactometer to build an E-nose. The built E-nose is capable of chocolate identification between the 26 analyzed chocolate bar samples and four features recognition (chocolate type, extra ingredient, sweetener and expiration date status). The data analysis tools used were Principal Components Analysis (PCA) and Artificial Neural Networks (ANNs). The chocolate identification E-nose average classification rate was of 81.3% with 0.99 accuracy (Acc), 0.86 precision (Prc), 0.84 sensitivity (Sen) and 0.99 specificity (Spe) for test. The chocolate feature recognition E-nose gives a classification rate of 85.36% with 0.96 Acc, 0.86 Prc, 0.85 Sen and 0.96 Spe. In addition, a preliminary sample aging analysis was made. The results prove the pressure controlled generated stimulus is reliable for this type of studies.

Using Computational Fluid Dynamics to examine airflow characteristics in Empty Nose Syndrome

Science.gov (United States)

Flint, Tim; Esmaily-Moghadam, Mahdi; Thamboo, Andrew; Velasquez, Nathalia; Nayak, Jayakar V.; Sellier, Mathieu; Moin, Parviz

2016-11-01

The enigmatic disorder, empty nose syndrome (ENS), presents with a complex subjective symptom profile despite objectively patent nasal airways, and recent reports suggest that surgical augmentation of the nasal airway can improve quality of life and ENS-related complaints. In this study, computational fluid dynamics (CFD) was performed both prior to, and following, inferior turbinate augmentation to model the resultant changes in airflow patterns and better understand the pathophysiology of ENS. An ENS patient with marked reduction in ENS symptoms following turbinate augmentation was identified, and pre- and post-operative CT imaging was collected. A Finite element framework with the variational multiscale method (Esmaily-Moghadam, Comput. Methods Appl. Mech. Engrg. 2015) was used to compute the airflow, temperature, and moisture transport through the nasal cavity. Comparison of the CFD results following corrective surgery showed higher levels of airflow turbulence. Augmentation produced 50%, 25%, and 25% increases in root mean square pressure, wall shear stress, and heat flux respectively. These results provide insight into the changes in nasal airflow characteristics attainable through surgical augmentation, and by extension, how nasal airflow patterns may be distorted in the 'overly patent' airway of ENS patients. Supported by Stanford University CTR and Fulbright New Zealand.

Prediction of egg freshness during storage using electronic nose.

Science.gov (United States)

Yimenu, Samuel M; Kim, J Y; Kim, B S

2017-10-01

The aim of the present study was to investigate the potential of a fast gas chromatography (GC) e-nose for freshness discrimination and for prediction of storage time as well as sensory and internal quality changes during storage of hen eggs. All samples were obtained from the same egg production farm and stored at 20 °C for 20 d. Egg sampling was conducted every 0, 3, 6, 9, 12, 16, and 20 d. During each sampling time, 4 egg cartons (each containing 10 eggs) were randomly selected: one carton for Haugh units, one carton for sensory evaluation and 2 cartons for the e-nose experiment. The e-nose study included 2 independent test sets; calibration (35 samples) and validation (28 samples). Every sampling time, 5 replicates were prepared from one egg carton for calibration samples and 4 replicates were prepared from the remaining egg carton for validation samples. Sensors (peaks) were selected prior to multivariate chemometric analysis; qualitative sensors for principal component analysis (PCA) and discriminant factor analysis (DFA) and quantitative sensors for partial least square (PLS) modeling. PCA and DFA confirmed the difference in volatile profiles of egg samples from 7 different storage times accounting for a total variance of 95.7% and 93.71%, respectively. Models for predicting storage time, Haugh units, odor score, and overall acceptability score from e-nose data were developed using calibration samples by PLS regression. The results showed that these quality indices were well predicted from the e- nose signals, with correlation coefficients of R2 = 0.9441, R2 = 0.9511, R2 = 0.9725, and R2 = 0.9530 and with training errors of 0.887, 1.24, 0.626, and 0.629, respectively. As a result of ANOVA, most of the PLS model results were not significantly (P > 0.05) different from the corresponding reference values. These results proved that the fast GC electronic nose has the potential to assess egg freshness and feasibility to predict multiple egg freshness indices

On the impact of a concave nosed axisymmetric body on a free surface

OpenAIRE

Mathai, Varghese; Govardhan, Raghuraman N.; Arakeri, Vijay H.

2017-01-01

We report on an experimental study of the vertical impact of a concave nosed axisymmetric body on a free surface. Previous studies have shown that bodies with a convex nose, like a sphere, produce a well defined splash with a relatively large cavity behind the model. In contrast, we find that with a concave nose, there is hardly a splash and the cavity extent is greatly reduced. This may be explained by the fact that in the concave nosed case, the initial impact is between a confined air pock...

[The crooked nose: correction of dorsal and caudal septal deviations].

Science.gov (United States)

Foda, H M T

2010-09-01

The deviated nose represents a complex cosmetic and functional problem. Septal surgery plays a central role in the successful management of the externally deviated nose. This study included 800 patients seeking rhinoplasty to correct external nasal deviations; 71% of these suffered from variable degrees of nasal obstruction. Septal surgery was necessary in 736 (92%) patients, not only to improve breathing, but also to achieve a straight, symmetric external nose. A graduated surgical approach was adopted to allow correction of the dorsal and caudal deviations of the nasal septum without weakening its structural support to the nasal dorsum or nasal tip. The approach depended on full mobilization of deviated cartilage, followed by straightening of the cartilage and its fixation in the corrected position by using bony splinting grafts through an external rhinoplasty approach.

Recent advances in electronic nose techniques for monitoring of fermentation process.

Science.gov (United States)

Jiang, Hui; Zhang, Hang; Chen, Quansheng; Mei, Congli; Liu, Guohai

2015-12-01

Microbial fermentation process is often sensitive to even slight changes of conditions that may result in unacceptable end-product quality. Thus, the monitoring of the process is critical for discovering unfavorable deviations as early as possible and taking the appropriate measures. However, the use of traditional analytical techniques is often time-consuming and labor-intensive. In this sense, the most effective way of developing rapid, accurate and relatively economical method for quality assurance in microbial fermentation process is the use of novel chemical sensor systems. Electronic nose techniques have particular advantages in non-invasive monitoring of microbial fermentation process. Therefore, in this review, we present an overview of the most important contributions dealing with the quality control in microbial fermentation process using the electronic nose techniques. After a brief description of the fundamentals of the sensor techniques, some examples of potential applications of electronic nose techniques monitoring are provided, including the implementation of control strategies and the combination with other monitoring tools (i.e. sensor fusion). Finally, on the basis of the review, the electronic nose techniques are critically commented, and its strengths and weaknesses being highlighted. In addition, on the basis of the observed trends, we also propose the technical challenges and future outlook for the electronic nose techniques.

SPECT imaging with the serotonin transporter radiotracer [123I]p ZIENT in nonhuman primate brain

International Nuclear Information System (INIS)

Cosgrove, Kelly P.; Staley, Julie K.; Baldwin, Ronald M.; Bois, Frederic; Plisson, Christophe; Al-Tikriti, Mohammed S.; Seibyl, John P.; Goodman, Mark M.; Tamagnan, Gilles D.

2010-01-01

Introduction: Serotonin dysfunction has been linked to a variety of psychiatric diseases; however, an adequate SPECT radioligand to probe the serotonin transporter system has not been successfully developed. The purpose of this study was to characterize and determine the in vivo selectivity of iodine-123-labeled 2β-carbomethoxy-3β-(4'-((Z)-2-iodoethenyl)phenyl)nortropane, [ 123 I]p ZIENT, in nonhuman primate brain. Methods: Two ovariohysterectomized female baboons participated in nine studies (one bolus and eight bolus to constant infusion at a ratio of 9.0 h) to evaluate [ 123 I]p ZIENT. To evaluate the selectivity of [ 123 I]p ZIENT, the serotonin transporter blockers fenfluramine (1.5, 2.5 mg/kg) and citalopram (5 mg/kg), the dopamine transporter blocker methylphenidate (0.5 mg/kg) and the norepinephrine transporter blocker nisoxetine (1 mg/kg) were given at 8 h post-radiotracer injection. Results: In the bolus to constant infusion studies, equilibrium was established by 4-8 h. [ 123 I]p ZIENT was 93% and 90% protein bound in the two baboons and there was no detection of lipophilic radiolabeled metabolites entering the brain. In the high-density serotonin transporter regions (diencephalon and brainstem), fenfluramine and citalopram resulted in 35-71% and 129-151% displacement, respectively, whereas methylphenidate and nisoxetine did not produce significant changes ( 123 I]p ZIENT is a favorable compound for in vivo SPECT imaging of serotonin transporters with negligible binding to norepinephrine and dopamine transporters.

Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

Directory of Open Access Journals (Sweden)

Nicolas Diotel

2018-02-01

Full Text Available Sex steroid hormones are synthesized from cholesterol and exert pleiotropic effects notably in the central nervous system. Pioneering studies from Baulieu and colleagues have suggested that steroids are also locally-synthesized in the brain. Such steroids, called neurosteroids, can rapidly modulate neuronal excitability and functions, brain plasticity, and behavior. Accumulating data obtained on a wide variety of species demonstrate that neurosteroidogenesis is an evolutionary conserved feature across fish, birds, and mammals. In this review, we will first document neurosteroidogenesis and steroid signaling for estrogens, progestagens, and androgens in the brain of teleost fish, birds, and mammals. We will next consider the effects of sex steroids in homeostatic and regenerative neurogenesis, in neuroprotection, and in sexual behaviors. In a last part, we will discuss the transport of steroids and lipoproteins from the periphery within the brain (and vice-versa and document their effects on the blood-brain barrier (BBB permeability and on neuroprotection. We will emphasize the potential interaction between lipoproteins and sex steroids, addressing the beneficial effects of steroids and lipoproteins, particularly HDL-cholesterol, against the breakdown of the BBB reported to occur during brain ischemic stroke. We will consequently highlight the potential anti-inflammatory, anti-oxidant, and neuroprotective properties of sex steroid and lipoproteins, these latest improving cholesterol and steroid ester transport within the brain after insults.

Short-cut transport path for Asian dust directly to the Arctic: a case study

International Nuclear Information System (INIS)

Huang, Zhongwei; Huang, Jianping; Wang, Shanshan; Zhou, Tian; Jin, Hongchun; Hayasaka, Tadahiro

2015-01-01

Asian dust can be transported long distances from the Taklimakan or Gobi desert to North America across the Pacific Ocean, and it has been found to have a significant impact on ecosystems, climate, and human health. Although it is well known that Asian dust is transported all over the globe, there are limited observations reporting Asian dust transported to the Arctic. We report a case study of a large-scale heavy dust storm over East Asia on 19 March 2010, as shown by ground-based and space-borne multi-sensor observations, as well as NCEP/NCAR reanalysis data and HYSPLIT trajectories. Our analysis suggests that Asian dust aerosols were transported from northwest China to the Arctic within 5 days, crossing eastern China, Japan and Siberia before reaching the Arctic. The results indicate that Asian dust can be transported for long distances along a previously unreported transport path. Evidence from other dust events over the past decade (2001–2010) also supports our results, indicating that dust from 25.2% of Asian dust events has potentially been transported directly to the Arctic. The transport of Asian dust to the Arctic is due to cyclones and the enhanced East Asia Trough (EAT), which are very common synoptic systems over East Asia. This suggests that many other large dust events would have generated long-range transport of dust to the Arctic along this path in the past. Thus, Asian dust potentially affects the Arctic climate and ecosystem, making climate change in the Arctic much more complex to be fully understood. (letter)

Rhinoplasty for the multiply revised nose.

Science.gov (United States)

Foda, Hossam M T

2005-01-01

To evaluate the problems encountered on revising a multiply operated nose and the methods used in correcting such problems. The study included 50 cases presenting for revision rhinoplasty after having had 2 or more previous rhinoplasties. An external rhinoplasty approach was used in all cases. Simultaneous septal surgery was done whenever indicated. All cases were followed for a mean period of 32 months (range, 1.5-8 years). Evaluation of the surgical result depended on clinical examination, comparison of pre- and postoperative photographs, and degree of patients' satisfaction with their aesthetic and functional outcome. Functionally, 68% suffered nasal obstruction that was mainly caused by septal deviations and nasal valve problems. Aesthetically, the most common deformities of the upper two thirds of the nose included pollybeak (64%), dorsal irregularities (54%), dorsal saddle (44%), and open roof deformity (42%), whereas the deformities of lower third included depressed tip (68%), tip contour irregularities (60%), and overrotated tip (42%). Nasal grafting was necessary in all cases; usually more than 1 type of graft was used in each case. Postoperatively, 79% of the patients, with preoperative nasal obstruction, reported improved breathing; 84% were satisfied with their aesthetic result; and only 8 cases (16%) requested further revision to correct minor deformities. Revision of a multiply operated nose is a complex and technically demanding task, yet, in a good percentage of cases, aesthetic as well as functional improvement are still possible.

An Electrically Tight In Vitro Blood-Brain Barrier Model Displays Net Brain-to-Blood Efflux of Substrates for the ABC Transporters, P-gp, Bcrp and Mrp-1

DEFF Research Database (Denmark)

Helms, Hans Christian; Hersom, Maria; Kuhlmann, Louise Borella

2014-01-01

Efflux transporters of the ATP-binding cassette superfamily including breast cancer resistance protein (Bcrp/Abcg2), P-glycoprotein (P-gp/Abcb1) and multidrug resistance-associated proteins (Mrp's/Abcc's) are expressed in the blood-brain barrier (BBB). The aim of this study was to investigate......, zosuquidar, reversan and MK 571 alone or in combinations. Digoxin was mainly transported via P-gp, estrone-3-sulphate via Bcrp and Mrp's and etoposide via P-gp and Mrp's. The expression of P-gp, Bcrp and Mrp-1 was confirmed using immunocytochemistry. The findings indicate that P-gp, Bcrp and at least one...... isoform of Mrp are functionally expressed in our bovine/rat co-culture model and that the model is suitable for investigations of small molecule transport....

Electrolyte depletion in white-nose syndrome bats.

Science.gov (United States)

Cryan, Paul M; Meteyer, Carol Uphoff; Blehert, David S; Lorch, Jeffrey M; Reeder, DeeAnn M; Turner, Gregory G; Webb, Julie; Behr, Melissa; Verant, Michelle; Russell, Robin E; Castle, Kevin T

2013-04-01

The emerging wildlife disease white-nose syndrome is causing widespread mortality in hibernating North American bats. White-nose syndrome occurs when the fungus Geomyces destructans infects the living skin of bats during hibernation, but links between infection and mortality are underexplored. We analyzed blood from hibernating bats and compared blood electrolyte levels to wing damage caused by the fungus. Sodium and chloride tended to decrease as wing damage increased in severity. Depletion of these electrolytes suggests that infected bats may become hypotonically dehydrated during winter. Although bats regularly arouse from hibernation to drink during winter, water available in hibernacula may not contain sufficient electrolytes to offset winter losses caused by disease. Damage to bat wings from G. destructans may cause life-threatening electrolyte imbalances.

Electrolyte depletion in white-nose syndrome bats

Science.gov (United States)

Cryan, Paul M.; Meteyer, Carol Uphoff; Blehert, David S.; Lorch, Jeffrey M.; Reeder, DeeAnn M.; Turner, Gregory G.; Webb, Julie; Behr, Melissa; Verant, Michelle L.; Russell, Robin E.; Castle, Kevin T.

2013-01-01

The emerging wildlife disease white-nose syndrome is causing widespread mortality in hibernating North American bats. White-nose syndrome occurs when the fungus Geomyces destructans infects the living skin of bats during hibernation, but links between infection and mortality are underexplored. We analyzed blood from hibernating bats and compared blood electrolyte levels to wing damage caused by the fungus. Sodium and chloride tended to decrease as wing damage increased in severity. Depletion of these electrolytes suggests that infected bats may become hypotonically dehydrated during winter. Although bats regularly arouse from hibernation to drink during winter, water available in hibernacula may not contain sufficient electrolytes to offset winter losses caused by disease. Damage to bat wings from G. destructans may cause life-threatening electrolyte imbalances.

Transferrin-conjugated magnetic dextran-spermine nanoparticles for targeted drug transport across blood-brain barrier.

Science.gov (United States)

Ghadiri, Maryam; Vasheghani-Farahani, Ebrahim; Atyabi, Fatemeh; Kobarfard, Farzad; Mohamadyar-Toupkanlou, Farzaneh; Hosseinkhani, Hossein

2017-10-01

Application of many vital hydrophilic medicines have been restricted by blood-brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran-spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS-NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested. The superparamagnetic characteristic of TDS-NPs was verified by vibration simple magnetometer. Capecitabine loaded TDS-NPs exhibited pH-sensitive release behavior with enhanced cytotoxicity against U87MG cells, compared to DS-NPs and free capecitabine. Prussian-blue staining and TEM-imaging showed the significant cellular uptake of TDS-NPs. Furthermore, a remarkable increase of Fe concentrations in brain was observed following their biodistribution and histological studies in vivo, after 1 and 7 days of post-injection. Enhanced drug transport across BBB and pH-triggered cellular uptake of TDS-NPs indicated that these theranostic nanocarriers are promising candidate for the brain malignance treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2851-2864, 2017. © 2017 Wiley Periodicals, Inc.