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Sample records for rapid brain uptake

  1. Selective and rapid uptake of adeno-associated virus type 2 in brain.

    Science.gov (United States)

    Bartlett, J S; Samulski, R J; McCown, T J

    1998-05-20

    Recombinant adeno-associated virus (AAV) vectors effectively transfer and express foreign genes in the brain. The transferred genes, however, are selectively expressed in neurons, and the cause of this specificity is not understood. To address this question, wild-type AAV-2 capsids were covalently labeled with the fluorophore, Cy3, and infused into the inferior colliculus or the hippocampus. Using antibodies to identify neurons (NeuN), astrocytes (GFAP), or oligodendrocytes (OX-42), clear neuron-specific uptake of the virus was observed as early as 6 min after the start of the infusion. By 30 min postinfusion, AAV particles were present in the nucleus of neurons, yet in both the inferior colliculus and hippocampus, a subset of neurons did not take up the virus particles. No AAV particles were found in astrocytes 1.5 min or 24 hr after virus infusion. Interestingly, 1 hr postinfusion, no AAV particles were found in microglia, yet by 24 hr postinfusion, a punctate pattern of AAV particles was found in microglia. To test whether virus uptake correlated with vector-transduced cells, an rAAV-CMV-GFP virus was infused. By 3 days postinfusion, GFP was localized to neuronal populations with no expression in astrocytes or microglia, similar to that of fluorescent virus uptake. These findings demonstrate that in brain, AAV particles rapidly bind and enter primarily neurons with a pattern similar to that of in vivo vector transduction. In addition, these studies indicate that viral binding and uptake, independent of promoter tropism, can explain the specificity of AAV brain transduction. Thus, this first description of AAV kinetic disposition in vivo should facilitate targeted application of this vector for human brain gene therapy.

  2. Blood-brain barrier permeability and brain uptake mechanism of kainic Acid and dihydrokainic Acid

    DEFF Research Database (Denmark)

    Gynther, Mikko; Petsalo, Aleksanteri; Hansen, Steen Honoré

    2015-01-01

    tools in various in vivo central nervous system disease models in rodents, as well as being templates in the design of novel ligands affecting the glutamatergic system. Both molecules are highly polar but yet capable of crossing the blood-brain barrier (BBB). We used an in situ rat brain perfusion...... technique to determine the brain uptake mechanism and permeability across the BBB. To determine KA and DHK concentrations in the rat brain, simple and rapid sample preparation and liquid chromatography mass spectrometer methods were developed. According to our results the BBB permeability of KA and DHK...... is low, 0.25 × 10(-6) and 0.28 × 10(-6) cm/s for KA and DHK, respectively. In addition, the brain uptake is mediated by passive diffusion, and not by active transport. Furthermore, the non-specific plasma and brain protein binding of KA and DHK was determined to be low, which means that the unbound drug...

  3. Brain Glucose Transporter (Glut3) Haploinsufficiency Does Not Impair Mouse Brain Glucose Uptake

    Science.gov (United States)

    Stuart, Charles A.; Ross, Ian R.; Howell, Mary E. A.; McCurry, Melanie P.; Wood, Thomas G.; Ceci, Jeffrey D.; Kennel, Stephen J.; Wall, Jonathan

    2011-01-01

    Mouse brain expresses three principle glucose transporters. Glut1 is an endothelial marker and is the principal glucose transporter of the blood-brain barrier. Glut3 and Glut6 are expressed in glial cells and neural cells. A mouse line with a null allele for Glut3 has been developed. The Glut3−/− genotype is intrauterine lethal by seven days post-coitis, but the heterozygous (Glut3+/−) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberrations. At twelve weeks of age, brain uptake of tail vein-injected 3H-2-deoxy glucose in Glut3+/− mice was not different from Glut3+/+ littermates, despite 50% less Glut3 protein expression in the brain. The brain uptake of injected 18F-2-fluoro-2-deoxy glucose was similarly not different from Glut3+/− littermates in the total amount, time course, or brain imaging in the Glut3+/− mice. Glut1 and Glut6 protein expressions evaluated by immunoblots were not affected by the diminished Glut3 expression in the Glut3+/− mice. We conclude that a 50% decrease in Glut3 is not limiting for the uptake of glucose into the mouse brain, since Glut3 haploinsufficiency does not impair brain glucose uptake or utilization. PMID:21316350

  4. Brain uptake of nonsteroidal anti-inflammatory drugs: ibuprofen, flurbiprofen, and indomethacin.

    Science.gov (United States)

    Parepally, Jagan Mohan R; Mandula, Haritha; Smith, Quentin R

    2006-05-01

    To determine the roles of blood-brain barrier (BBB) transport and plasma protein binding in brain uptake of nonsteroidal anti-inflammatory drugs (NSAIDs)-ibuprofen, flurbiprofen, and indomethacin. Brain uptake was measured using in situ rat brain perfusion technique. [14C]Ibuprofen, [3H]flurbiprofen, and [14C]indomethacin were rapidly taken up into the brain in the absence of plasma protein with BBB permeability-surface area products (PS(u)) to free drug of (2.63 +/- 0.11) x 10(-2), (1.60 +/- 0.08) x 10(-2), and (0.64 +/- 0.05) x 10(-2) mL s(-1) g(-1) (n = 9-11), respectively. BBB [14C]ibuprofen uptake was inhibited by unlabeled ibuprofen (Km = 0.85 +/- 0.02 mM, Vmax = 13.5 +/- 0.4 nmol s(-1) g(-1)) and indomethacin, but not by pyruvate, probenecid, digoxin, or valproate. No evidence was found for saturable BBB uptake of [3H]flurbiprofen or [14C]indomethacin. Initial brain uptake for all three NSAIDs was reduced by the addition of albumin to the perfusion buffer. The magnitude of the brain uptake reduction correlated with the NSAID free fraction in the perfusate. Free ibuprofen, flurbiprofen, and indomethacin rapidly cross the BBB, with ibuprofen exhibiting a saturable component of transport. Plasma protein binding limits brain NSAID uptake by reducing the free fraction of NSAID in the circulation.

  5. Fluorescent Nanoparticle Uptake for Brain Tumor Visualization

    Directory of Open Access Journals (Sweden)

    Rachel Tréhin

    2006-04-01

    Full Text Available Accurate delineation of tumor margins is vital to the successful surgical resection of brain tumors. We have previously developed a multimodal nanoparticle CLIO-Cy5.5, which is detectable by both magnetic resonance imaging and fluorescence, to assist in intraoperatively visualizing tumor boundaries. Here we examined the accuracy of tumor margin determination of orthotopic tumors implanted in hosts with differing immune responses to the tumor. Using a nonuser-based signal intensity method applied to fluorescent micrographs of 9L gliosarcoma green fluorescent protein (GFP tumors, mean overestimations of 2 and 24 µm were obtained using Cy5.5 fluorescence, compared to the true tumor margin determined by GFP fluorescence, in nude mice and rats, respectively. To resolve which cells internalized the nanoparticle and to quantitate degree of uptake, tumors were disaggregated and cells were analyzed by flow cytometry and fluorescence microscopy. Nanoparticle uptake was seen in both CD11b+ cells (representing activated microglia and macrophages and tumor cells in both animal models by both methods. CD11b+ cells were predominantly found at the tumor margin in both hosts, but were more pronounced at the margin in the rat model. Additional metastatic (CT26 colon and primary (Gli36 glioma brain tumor models likewise demonstrated that the nanoparticle was internalized both by tumor cells and by host cells. Together, these observations suggest that fluorescent nanoparticles provide an accurate method of tumor margin estimation based on a combination of tumor cell and host cell uptake for primary and metastatic tumors in animal model systems and offer potential for clinical translation.

  6. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  7. Thallium uptake and biological behaviour in childhood brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, E.J.; Howman-Giles, R.; Kellie, S.; Uren, R.F. [Royal Alexandra Hospital for Children, Sydney, NSW (Australia)

    1998-03-01

    Full text: The histopathological grade and radiological appearance of the diverse cerebral neoplasms in childhood frequently poorly reflect their biological behaviour. We examined thallium accumulation prior to treatment (and in several cases, at intervals there after) in 13 children to determine its usefulness as a tumour marker. 23 SPECT studies were acquired 20 minutes after the injection of 1-3 mCi of {sup 201}TI. Thallium index (TI), the ratio of counts in tumour/normal brain, was calculated. No uptake was seen in two patients (pts) with a Grade 1 cerebellar astrocytomas (disease free at 4/12 f/u). Three pts with medulloblastomas were studied. One pt showed intense uptake (Tl =12). His tumour (proliferative antigen stain Ki67 = 50%) recurred early after debulking surgery (Tl +ve prior to CT or MRI changes). The second pt was imaged at relapse (Ki67 = 60%) and showed intense uptake, Tl = 17. The third pt showed lower level uptake (Tl = 2), Ki67 = 5%, and is disease-free at 5/12 (as per {sup 201}TI and MRI). One pt with a Grade 1 brainstem glioma showed Tl = 5 and has progressed rapidly despite low grade histology. Four pts with chiasmatic-hypothalamic gliomas have been studied. Although these neoplasms are usually low grade histologically, their growth properties vary greatly. Two pts with Tl<2.5 have been conservatively managed because of slow tumour growth. The other two pts have Tl>3.5 and have required aggressive treatment for rapid disease progression. One pt with a large pilocytic astrocytoma of the optic chiasm showed Tl = 9.5. Active treatment was not undertaken. One pt with a pineal germ cell tumour showed avid {sup 201}TI uptake (Tl not performed) and has had two normal studies, and is clinically well, since BMT. Avid {sup 201}TI uptake also seen in one pt with cerebral neuroblastoma. (Died at 8/12 after Dx.) Thus, {sup 201}TI accumulates in histologically diverse paediatric neoplasms. The Tl appears to reflect biological behaviour in the limited

  8. Brain abscess uptake at TI-201 brain SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Hyoung; Han, Eun Ji; Yoo, Ie Ryung; Chung, Yong An; Sohn, Hyung Sun; Kim, Sung Hoon; Chung, Soo Kyo; Choi, Yeong Jin [The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-08-15

    A 22-year-old woman with a history of acute lymphoblastic leukemia was hospitalized for headache and vomiting CT scan showed a well-defined, ring like enhancing mass in the left frontal lobe with surrounding edema and midline shift. Magnetic resonance imaging demonstrated a round homogeneous mass with a ring of enhancement in the left frontal lobe. TI-201 brain SPECT showed increased focal uptake coinciding with the CT and MRI abnormality. Aspiration of the lesion performed through a burr hole yielded many neutrophils, a few lymphocytes and histiocytes with some strands of filamentous microorganism-like material. Modified AFB stained negative for norcardia. Gram stain showed a few white blood cells and no microorganism. Antibiotics were started and produced a good clinical response. After one month, CT scan showed markedly reduction in size and extent was observed.

  9. Calcium uptake in brain synaptosomes: a pharmacologic study

    Energy Technology Data Exchange (ETDEWEB)

    Rampe, D.E.

    1986-01-01

    Pinched-off nerve endings (synaptosomes) from rat and guinea pig brain were used as a model to study Ca/sup 2 +/ entry mechanisms in neuronal tissue. Synaptosomes contain high affinity binding sites for both, 1,4-dihydropyridine Ca/sup 2 +/ channel antagonists, and activators. The thermodynamic characteristics of (/sup 3/H)nitrendipine building in synaptosomes were similar to those seen in both cardiac and smooth muscle preparations. Synaptosomes display two distinct K/sup +/-induced Ca/sup 2 +/ entry mechanisms. These are kinetically distinct with the faster of the two terminating in approx. 1 second while the slower persists for approx. minute. The slow phase uptake process is abolished in Na/sup +/-free media, is sensitive to antagonism by 3,4-dichlorobenzamil and displays a more rapid ontogenic appearance relative to the fast phase. It is likely that the slow phase represents Ca/sup 2 +/ entry via Na/sup +//Ca/sup 2 +/ exchange. The rapid inactivation of the fast phase coupled with its voltage dependence suggest that it represents Ca/sup 2 +/ entry via one or more types of voltage dependent Ca/sup 2 +/ channels. These channels may not be dihydropyridin sensitive since neither nitrendipine nor Bay K 8644 were shown to modulate synaptosomal Ca/sup 2 +/ uptake. The benzodiazepine receptor ligands Ro 5-4864, PK 11195 and diazepam all selectively inhibited fast phase Ca/sup 2 +/ entry relative to slow phase entry. In addition, these compounds altered (/sup 3/H)nitrendipine binding affinity. It is concluded that certain benzodiazepine receptor ligands can interact specifically with voltage dependent Ca/sup 2 +/ channels.

  10. Evaluation of factors influencing 18 F-FET uptake in the brain

    OpenAIRE

    Verger, Antoine; Stegmayr, Carina; Eickhoff, Simon; Galldiks, Norbert; Van Der Gucht, Axel; Lohmann, Philipp; Stoffels, Gabriele; Shah, Nadim J.; Fink, Gereon R.; Guedj, Eric; Langen, Karl-Josef

    2018-01-01

    PET using the amino-acid O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) is gaining increasing interest for brain tumour management. Semi-quantitative analysis of tracer uptake in brain tumours is based on the standardized uptake value (SUV) and the tumour-to-brain ratio (TBR). The aim of this study was to explore physiological factors that might influence the relationship of SUV of 18F-FET uptake in various brain areas, and thus affect quantification of 18F-FET uptake in brain tumours. Negative 1...

  11. Inhibitors of glutamate dehydrogenase block sodium-dependent glutamate uptake in rat brain membranes

    Directory of Open Access Journals (Sweden)

    Brendan S Whitelaw

    2013-09-01

    Full Text Available We recently found evidence for anatomic and physical linkages between the astroglial Na+-dependent glutamate transporters (GLT-1/EAAT2 and GLAST/EAAT1 and mitochondria. In these same studies, we found that the glutamate dehydrogenase (GDH inhibitor, epigallocatechin-monogallate (EGCG, inhibits both glutamate oxidation and Na+-dependent glutamate uptake in astrocytes. In the present study, we extend this finding by exploring the effects of EGCG on Na+-dependent L-[3H]-glutamate (Glu uptake in crude membranes (P2 prepared from rat brain cortex. In this preparation, uptake is almost exclusively mediated by GLT-1. EGCG inhibited L-[3H]-Glu uptake in cortical membranes with an IC50 value of 230 µM. We also studied the effects of two additional inhibitors of GDH, hexachlorophene (HCP and bithionol (BTH. Both of these compounds also caused concentration-dependent inhibition of glutamate uptake in cortical membranes. Pre-incubating with HCP for up to 15 min had no greater effect than that observed with no pre-incubation, showing that the effects occur rapidly. HCP decreased the Vmax for glutamate uptake without changing the Km, consistent with a non-competitive mechanism of action. EGCG, HCP, and BTH also inhibited Na+-dependent transport of D-[3H]-aspartate (Asp, a non-metabolizable substrate, and [3H]-γ-aminobutyric acid (GABA. In contrast to the forebrain, glutamate uptake in crude cerebellar membranes (P2 is likely mediated by GLAST (EAAT1. Therefore, the effects of these compounds were examined in cerebellar membranes. In this region, none of these compounds had any effect on uptake of either L-[3H]-Glu or D-[3H]-Asp, but they all inhibited [3H]-GABA uptake. Together these studies suggest that GDH is preferentially required for glutamate uptake in forebrain as compared to cerebellum, and GDH may be required for GABA uptake as well. They also provide further evidence for a functional linkage between glutamate transport and mitochondria.

  12. Decreased brain FDG uptake in patients with extensive non-Hodgkin's lymphoma lesions.

    Science.gov (United States)

    Hanaoka, Kohei; Hosono, Makoto; Shimono, Taro; Usami, Kimio; Komeya, Yoshihiro; Tsuchiya, Norio; Yamazoe, Yuzuru; Ishii, Kazunari; Tatsumi, Youichi; Sumita, Mitsugu

    2010-12-01

    Faint brain [(18)F]fluoro-2-deoxyglucose (FDG) uptake has sporadically been reported in patients with FDG-avid large or diffusely extended tumors. The purpose of this study was to investigate whether there is a correlation between massive tumor uptake and decreased brain uptake on FDG positron emission tomography/computed tomography (PET/CT). Sixty-five patients with histologically confirmed non-Hodgkin's lymphoma who underwent FDG-PET/CT were enrolled. Thirty control subjects were also included to evaluate normal brain FDG uptake. PET/CT examinations were retrospectively reviewed. The volumetric regions of interest were placed over lesions by referring to CT and PET/CT fusion images to measure mean standardized uptake value (SUVavg). The products of SUVavg and tumor volume were calculated as total glycolytic volume (TGV). The maximum SUV (SUVmax) and SUVavg were measured in the cerebrum and cerebellum. The values of TGV and brain FDG uptake were plotted and analyzed with a linear regression method. In the lymphoma patients, there were statistically significant negative correlations between TGV and brain SUVs. Demonstrating a significant negative correlation between TGV and brain uptake validated the phenomenon of decreased brain FDG uptake. Diversion of FDG from the brain to the lymphoma tissue may occur during the FDG accumulation process. Recognition of this phenomenon prevents unnecessary further neurological examinations in such cases.

  13. Uptake and metabolism of iron and iron oxide nanoparticles in brain astrocytes.

    Science.gov (United States)

    Hohnholt, Michaela C; Dringen, Ralf

    2013-12-01

    Astrocytes are considered key regulators of the iron metabolism of the brain. These cells are able to rapidly accumulate iron ions and various iron-containing compounds, store iron efficiently in ferritin and also export iron. The present short review summarizes our current knowledge of the molecular mechanisms involved in the handling of iron by astrocytes. Cultured astrocytes efficiently take up iron as ferrous or ferric iron ions or as haem by specific iron transport proteins in their cell membrane. In addition, astrocytes accumulate large amounts of iron oxide nanoparticles by endocytotic mechanisms. Despite the rapid accumulation of high amounts of iron from various iron-containing sources, the viability of astrocytes is hardly affected. A rather slow liberation of iron from accumulated haem or iron oxide nanoparticles as well as the strong up-regulation of the synthesis of the iron storage protein ferritin are likely to contribute to the high resistance of astrocytes to iron toxicity. The efficient uptake of extracellular iron by cultured astrocytes as well as their strong up-regulation of ferritin after iron exposure also suggests that brain astrocytes deal well with an excess of iron and protect the brain against iron-mediated toxicity.

  14. Reductions in Calcium Uptake Induced in Rat Brain Synaptosomes by Ionizing Radiation

    Science.gov (United States)

    1991-01-01

    located in the brain and heart using nimodipine and Reductions in Calcium Uptake Induced in Rat Brain Synapto- nifedipine (I1-13). Nimodipine binding...was also reduced by radiation exposure. Nimodipine binding to dihydropyridine (DHP) L-type calcium uptake after irradiation in wh31e-brain, cortical...resistant to the direct effects of MATERIALS AND METHODS ionizing radiation, exposure to ionizing radiation can have Materials. Bay K 8644 and nimodipine

  15. Evaluation of factors influencing 18F-FET uptake in the brain.

    Science.gov (United States)

    Verger, Antoine; Stegmayr, Carina; Galldiks, Norbert; Van Der Gucht, Axel; Lohmann, Philipp; Stoffels, Gabriele; Shah, Nadim J; Fink, Gereon R; Eickhoff, Simon B; Guedj, Eric; Langen, Karl-Josef

    2018-01-01

    PET using the amino-acid O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) is gaining increasing interest for brain tumour management. Semi-quantitative analysis of tracer uptake in brain tumours is based on the standardized uptake value (SUV) and the tumour-to-brain ratio (TBR). The aim of this study was to explore physiological factors that might influence the relationship of SUV of 18F-FET uptake in various brain areas, and thus affect quantification of 18F-FET uptake in brain tumours. Negative 18F-FET PET scans of 107 subjects, showing an inconspicuous brain distribution of 18F-FET, were evaluated retrospectively. Whole-brain quantitative analysis with Statistical Parametric Mapping (SPM) using parametric SUV PET images, and volumes of interest (VOIs) analysis with fronto-parietal, temporal, occipital, and cerebellar SUV background areas were performed to study the effect of age, gender, height, weight, injected activity, body mass index (BMI), and body surface area (BSA). After multivariate analysis, female gender and high BMI were found to be two independent factors associated with increased SUV of 18F-FET uptake in the brain. In women, SUVmean of 18F-FET uptake in the brain was 23% higher than in men (p < 0.01). SUVmean of 18F-FET uptake in the brain was positively correlated with BMI (r = 0.29; p < 0.01). The influence of these factors on SUV of 18F-FET was similar in all brain areas. In conclusion, SUV of 18F-FET in the normal brain is influenced by gender and weakly by BMI, but changes are similar in all brain areas.

  16. Stimulated Raman scattering microscopy for rapid brain tumor histology

    Directory of Open Access Journals (Sweden)

    Yifan Yang

    2017-09-01

    Full Text Available Rapid histology of brain tissues with sufficient diagnostic information has the great potential to aid neurosurgeons during operations. Stimulated Raman Scattering (SRS microscopy is an emerging label-free imaging technique, with the intrinsic chemical resolutions to delineate brain tumors from normal tissues without the need of time-consuming tissue processing. Growing number of studies have shown SRS as a “virtual histology” tool for rapid diagnosis of various types of brain tumors. In this review, we focus on the basic principles and current developments of SRS microscopy, as well as its applications for brain tumor imaging.

  17. Are rapid changes in brain elasticity possible?

    Science.gov (United States)

    Parker, K. J.

    2017-09-01

    Elastography of the brain is a topic of clinical and preclinical research, motivated by the potential for viscoelastic measures of the brain to provide sensitive indicators of pathological processes, and to assist in early diagnosis. To date, studies of the normal brain and of those with confirmed neurological disorders have reported a wide range of shear stiffness and shear wave speeds, even within similar categories. A range of factors including the shear wave frequency, and the age of the individual are thought to have a possible influence. However, it may be that short term dynamics within the brain may have an influence on the measured stiffness. This hypothesis is addressed quantitatively using the framework of the microchannel flow model, which derives the tissue stiffness, complex modulus, and shear wave speed as a function of the vascular and fluid network in combination with the elastic matrix that comprise the brain. Transformation rules are applied so that any changes in the fluid channels or the elastic matrix can be mapped to changes in observed elastic properties on a macroscopic scale. The results are preliminary but demonstrate that measureable, time varying changes in brain stiffness are possible simply by accounting for vasodynamic or electrochemical changes in the state of any region of the brain. The value of this preliminary exploration is to identify possible mechanisms and order-of-magnitude changes that may be testable in vivo by specialized protocols.

  18. Brain Glucose Transporter (Glut3) Haploinsufficiency Does Not Impair Mouse Brain Glucose Uptake

    OpenAIRE

    Stuart, Charles A.; Ross, Ian R.; Howell, Mary E. A.; McCurry, Melanie P.; Wood, Thomas G.; Ceci, Jeffrey D.; Kennel, Stephen J.; Wall, Jonathan

    2011-01-01

    Mouse brain expresses three principle glucose transporters. Glut1 is an endothelial marker and is the principal glucose transporter of the blood-brain barrier. Glut3 and Glut6 are expressed in glial cells and neural cells. A mouse line with a null allele for Glut3 has been developed. The Glut3−/− genotype is intrauterine lethal by seven days post-coitis, but the heterozygous (Glut3+/−) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberration...

  19. Reductions in calcium uptake induced in rat brain synaptosomes by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Howerton, T.C.; Hunt, W.A. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1991-02-01

    Gamma irradiation (60Co) reduced KCl-stimulated voltage-dependent 45Ca2+ uptake in whole-brain, cortical, and striatal synaptosomes. The time course (3, 10, 30, and 60 s) of calcium uptake by irradiated (3 Gy) and nonirradiated synaptosomes, as well as the effect of KCl (15-65 mM), was measured in whole-brain synaptosomes. The fastest and highest rate of depolarization-dependent calcium uptake occurred at 3 s with 65 mM KCl. Irradiation reduced calcium uptake at all incubation times and KCl concentrations. Bay K 8644 enhancement of KCl-stimulated calcium influx was also reduced by radiation exposure. Nimodipine binding to dihydropyridine (DHP) L-type calcium channel receptors was not altered following radiation exposure. These results demonstrate an inhibitory effect of ionizing radiation on the voltage-sensitive calcium channels in rat brain synaptosomes that are not mediated by DHP receptors.

  20. Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.

    Science.gov (United States)

    Wagner, Sylvia; Zensi, Anja; Wien, Sascha L; Tschickardt, Sabrina E; Maier, Wladislaw; Vogel, Tikva; Worek, Franz; Pietrzik, Claus U; Kreuter, Jörg; von Briesen, Hagen

    2012-01-01

    The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.

  1. Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat.

    Science.gov (United States)

    Qaiser, M Zeeshan; Dolman, Diana E M; Begley, David J; Abbott, N Joan; Cazacu-Davidescu, Mihaela; Corol, Delia I; Fry, Jonathan P

    2017-09-01

    Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found (3) H-PregS to enter more rapidly than (3) H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes. Although permeability measurements suggested a net efflux, addition of the efflux inhibitors GF120918 and/or MK571 to the perfusate reduced rather than enhanced the uptake of (3) H-DHEAS and (3) H-PregS; a further reduction was seen upon the addition of unlabelled steroid sulphate, suggesting a saturable uptake transporter. Analysis of brain fractions after 0.5 min perfusion with the (3) H-steroid sulphates showed no further metabolism of PregS beyond the liberation of free steroid pregnenolone. By contrast, DHEAS underwent 17-hydroxylation to form androstenediol in both the steroid sulphate and the free steroid fractions, with some additional formation of androstenedione in the latter. Our results indicate a gain of free steroid from circulating steroid sulphates as hormone precursors at the blood-brain barrier, with implications for ageing, neurogenesis, neuronal survival, learning and memory. © 2017 International Society for Neurochemistry.

  2. 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...

  3. Concurrent low brain and high liver uptake on FDG PET are associated with cardiovascular risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Hyun Yeol [Dept. of Nuclear Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon (Korea, Republic of); Jun, Sung Min [Dept. of Nuclear Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan (Korea, Republic of); Pak, Kyoung June; Kim, In Joo [Dept. of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of)

    2017-04-15

    Concurrent low brain and high liver uptake are sometimes observed on fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We investigated the potential clinical significance of this uptake pattern related to metabolic syndrome (MS). We retrospectively reviewed data from 264 consecutive males who had undergone general health check-ups, including FDG PET/CT scans. After an overnight fast, the men had their peripheral blood drawn and the levels of various laboratory parameters measured; an FDG PET/CT scan was performed on the same day. We measured the maximum standardized uptake values of the brain and liver from regions of interest manually placed over the frontal cortex at the level of the centrum semiovale and the right lobe of the liver parenchyma, respectively. Fasting blood glucose (FBG; odds ratio [OR] = 1.063, p < 0.001) and glycated hemoglobin (HbA1c; OR = 3.634, p = 0.010) were the strongest predictive factors for low brain FDG uptake, whereas waist circumference (OR = 1.200, p < 0.001) and γ-glutamyl transpeptidase (OR = 1.012, p = 0.001) were the strongest predictive factors for high liver uptake. Eleven subjects (4.2%) showed concurrent low brain and high liver FDG uptake, and all but one of these subjects (90.9%) had MS. Systolic blood pressure, waist circumference, FBG, triglyceride, alanine aminotransferase, insulin resistance (measured by homeostasis model assessment), insulin, HbA1c, and body mass index were higher in subjects with this FDG uptake pattern than in those without (all, p < 0.001). Concurrent low brain and high liver FDG uptake were closely associated with MS. Moreover, subjects with this pattern had higher values for various cardiovascular risk factors than did those without.

  4. Semi-Mechanistic Population Pharmacokinetic Modeling of L-Histidine Disposition and Brain Uptake in Wildtype and Pht1 Null Mice.

    Science.gov (United States)

    Wang, Xiao-Xing; Li, Yang-Bing; Feng, Meihua R; Smith, David E

    2018-01-05

    To develop a semi-mechanistic population pharmacokinetic (PK) model to quantitate the disposition kinetics of L-histidine, a peptide-histidine transporter 1 (PHT1) substrate, in the plasma, cerebrospinal fluid and brain parenchyma of wildtype (WT) and Pht1 knockout (KO) mice. L-[ 14 C]Hisidine (L-His) was administrated to WT and KO mice via tail vein injection, after which plasma, cerebrospinal fluid (CSF) and brain parenchyma samples were collected. A PK model was developed using non-linear mixed effects modeling (NONMEM). The disposition of L-His between the plasma, brain, and CSF was described by a combination of PHT1-mediated uptake, CSF bulk flow and first-order micro-rate constants. The PK profile of L-His was best described by a four-compartment model. A more rapid uptake of L-His in brain parenchyma was observed in WT mice due to PHT1-mediated uptake, a process characterized by a Michaelis-Menten component (V max  = 0.051 nmoL/min and K m  = 34.94 μM). A semi-mechanistic population PK model was successfully developed, for the first time, to quantitatively characterize the disposition kinetics of L-His in brain under in vivo conditions. This model may prove a useful tool in predicting the uptake of L-His, and possibly other PHT1 peptide/mimetic substrates, for drug delivery to the brain.

  5. Uptake of 3-hydroxykynurenine measured in rat brain slices and in a neuronal cell line.

    Science.gov (United States)

    Eastman, C L; Guilarte, T R; Lever, J R

    1992-07-03

    The uptake of 3-hydroxykynurenine (3HK), a tryptophan metabolite with reported convulsant and cytotoxic properties, has been investigated in a neuronally derived hybrid cell line and in tissue slices prepared from rat brain. In both systems, the observed uptake was temperature-dependent and inhibited in the presence of large neutral amino acids. The apparent Km and Vmax determined for 3HK uptake into N18-RE-105 cells were 1.65 mM and 25.5 nmol/(min x mg protein), respectively. The uptake of 3HK into rat brain slices could be resolved into two components on the basis of their requirements for sodium. Kinetic analyses performed using hippocampal slices revealed a Km of 1.1 mM and Vmax of 18.8 nmol/(h x mg protein) for the sodium-independent process and a Km of 4.8 mM and Vmax of 54.5 nmol/(h x mg protein) for the sodium-dependent process. While sodium-dependent uptake was abolished following treatment with metabolic inhibitors, sodium-independent uptake was only slightly impaired. Sodium-independent uptake was inhibited in the presence of the non-metabolizable amino acids, aminoisobutyric acid (AIB) and aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH), but not by N-methylated amino acid substrates. Sodium-dependent uptake was insensitive to AIB and was completely abolished by BCH. These results indicate that an uptake process for 3HK is present in the mammalian brain, and suggest that the sodium-dependent component of 3HK transport may be mediated by a system which has not previously been described in CNS tissue.

  6. [Pharmacological influences on the brain level and transport of GABA. II) Effect of various psychoactive drugs on brain level and uptake of GABA].

    Science.gov (United States)

    Gabana, M A; Varotto, M; Saladini, M; Zanchin, G; Battistin, L

    1981-04-30

    The effects of some psychoactive drugs on the level and uptake of GABA in the mouse brain was studied using well standardized procedures, mainely the silica-gel cromatography for determining the GABA content and the brain slices for measuring GABA uptake. It was found that levomepromazine, sulpiride, haloperidol and amytryptiline were without effects on the cerebral level of GABA; it was also found that these drugs do not influence the rates of uptake of GABA by mouse brain slices. Such results do indicate that the psychoactive drugs studied are without effects on the level and uptake of GABA in the brain.

  7. Bivalent Brain Shuttle Increases Antibody Uptake by Monovalent Binding to the Transferrin Receptor

    Science.gov (United States)

    Hultqvist, Greta; Syvänen, Stina; Fang, Xiaotian T; Lannfelt, Lars; Sehlin, Dag

    2017-01-01

    The blood-brain barrier (BBB) is an obstacle for antibody passage into the brain, impeding the development of immunotherapy and antibody-based diagnostics for brain disorders. In the present study, we have developed a brain shuttle for active transport of antibodies across the BBB by receptor-mediated transcytosis. We have thus recombinantly fused two single-chain variable fragments (scFv) of the transferrin receptor (TfR) antibody 8D3 to the light chains of mAb158, an antibody selectively binding to Aβ protofibrils, which are involved in the pathogenesis of Alzheimer's disease (AD). Despite the two TfR binders, a monovalent interaction with TfR was achieved due to the short linkers that sterically hinder bivalent binding to the TfR dimer. The design enabled efficient receptor-mediated brain uptake of the fusion protein. Two hours after administration, brain concentrations were 2-3% of the injected dose per gram brain, comparable to small molecular drugs and 80-fold higher than unmodified mAb158. After three days, fusion protein concentrations in AD transgenic mouse brains were 9-fold higher than in wild type mice, demonstrating high in vivo specificity. Thus, our innovative recombinant design markedly increases mAb158 brain uptake, which makes it a strong candidate for improved Aβ immunotherapy and as a PET radioligand for early diagnosis and evaluation of treatment effect in AD. Moreover, this approach could be applied to any target within the brain. PMID:28042336

  8. Monoaminergic uptake in synaptosomes prepared from frozen brain tissue samples of normal and narcoleptic canines.

    Science.gov (United States)

    Valtier, D; Dement, W C; Mignot, E

    1992-08-14

    Canine narcolepsy, a model of the human disorder, is associated with altered catecholamine but not serotonin (5-HT) metabolism in some brain areas, particularly the amygdala. A possible explanation for these global changes could be the existence of specific defects in monoamine uptake processes. We have studied the uptake of [3H]norepinephrine (NE), [3H]dopamine (DA) and [3H]5-HT in synaptosomes prepared from cortex and amygdala of narcoleptic and control Doberman pinscher brains. Since narcoleptic canines are relatively few in number, we have used a specific brain freezing procedure that has been reported to allow restoration of metabolically functional tissue upon thawing. Preliminary studies comparing monoamine uptake in fresh and frozen brain samples of both groups of dogs were carried out and demonstrated that this procedure significantly altered serotoninergic but not noradrenergic and dopaminergic uptake. All further investigations were then done on synaptosomes prepared from frozen samples. Our results demonstrate that synaptosomal uptake of [3H]NE, [3H]DA and [3H]5-HT in cortex and amygdala are not altered in narcolepsy.

  9. Biotin and biocytin uptake into cultured primary calf brain microvessel endothelial cells of the blood-brain barrier.

    Science.gov (United States)

    Baur, B; Baumgartner, E R

    2000-03-10

    The uptake of biotin and the closely related biocytin was characterized in primary cultures of calf brain microvessel endothelial (CBME) cells. Biotin uptake was found to be Na(+)-gradient dependent and independent of changes in the membrane potential. Concentration dependence revealed a single saturation mechanism with a K(m) of 47 microM and a V(max) of 101 pmol/min/mg. Inhibition studies demonstrated dependence on metabolic energy and the necessity for a free carboxyl group for transport activity. The anticonvulsants primidone and carbamazepine had no inhibitory effect. Biotin uptake into CBME cells is a secondary active, electroneutral, saturable and specific process. Biocytin which accumulates in biotinidase deficiency, a human congenital disorder, did not inhibit biotin uptake and was not transported into these cells. The presence of human serum with normal biotinidase activity significantly reduced biotin uptake by about 50%. Further, added biocytin was hydrolyzed to biotin, which accumulated intracellularly but to a lesser extent than added free biotin. Biotin uptake after addition of plasma of biotinidase-deficient patients was not different from that in the presence of normal serum. These results indicate that the absence of biotinidase activity in serum does not reduce blood-brain barrier transport of biotin.

  10. Blood-brain barrier molecular trojan horse enables imaging of brain uptake of radioiodinated recombinant protein in the rhesus monkey.

    Science.gov (United States)

    Boado, Ruben J; Hui, Eric K-W; Lu, Jeff Zhiqiang; Sumbria, Rachita K; Pardridge, William M

    2013-10-16

    Recombinant proteins are large molecule drugs that do not cross the blood-brain barrier (BBB). However, BBB-penetration of protein therapeutics is enabled by re-engineering the recombinant protein as IgG fusion proteins. The IgG domain is a monoclonal antibody (mAb) against an endogenous BBB receptor-mediated transport system, such as the human insulin receptor (HIR), and acts as a molecular Trojan horse to ferry the fused protein across the BBB. In the present study, a recombinant lysosomal enzyme, iduronate 2-sulfatase (IDS), is fused to the HIRMAb, and BBB penetration of the IDS alone vs the HIRMAb-IDS fusion protein is compared in the Rhesus monkey. Recombinant IDS and the HIRMAb-IDS fusion protein were radiolabeled with indirect iodination with the [(125)I]-Bolton-Hunter reagent and with direct iodination with Iodogen/[(125)I]-idodine. IDS and the HIRMAb-IDS fusion protein have comparable plasma pharmacokinetics and uptake by peripheral organs. IDS does not cross the BBB. The HIRMAb-IDS fusion protein crosses the BBB and the brain uptake is 1% of injected dose/brain. Brain imaging shows HIRMAb-IDS penetration to all parts of brain, and immunoprecipitation of brain radioactivity shows intact fusion protein in brain. The use of BBB molecular Trojan horses enables brain imaging of recombinant proteins that are re-engineered for BBB transport.

  11. In situ deformations in the immature brain during rapid rotations.

    Science.gov (United States)

    Ibrahim, Nicole G; Natesh, Rahul; Szczesny, Spencer E; Ryall, Karen; Eucker, Stephanie A; Coats, Brittany; Margulies, Susan S

    2010-04-01

    Head trauma is the leading cause of death and debilitating injury in children. Computational models are important tools used to understand head injury mechanisms but they must be validated with experimental data. In this communication we present in situ measurements of brain deformation during rapid, nonimpact head rotation in juvenile pigs of different ages. These data will be used to validate computational models identifying age-dependent thresholds of axonal injury. Fresh 5 days (n=3) and 4 weeks (n=2) old piglet heads were transected horizontally and secured in a container. The cut surface of each brain was marked and covered with a transparent, lubricated plate that allowed the brain to move freely in the plane of rotation. For each brain, a rapid (20-28 ms) 65 deg rotation was applied sequentially at 50 rad/s, 75 rad/s, and 75 rad/s. Each rotation was digitally captured at 2500 frames/s (480x320 pixels) and mark locations were tracked and used to compute strain using an in-house program in MATLAB. Peak values of principal strain (E(peak)) were significantly larger during deceleration than during acceleration of the head rotation (p<0.05), and doubled with a 50% increase in velocity. E(peak) was also significantly higher during the second 75 rad/s rotation than during the first 75 rad/s rotation (p<0.0001), suggesting structural alteration at 75 rad/s and the possibility that similar changes may have occurred at 50 rad/s. Analyzing only lower velocity (50 rad/s) rotations, E(peak) significantly increased with age (16.5% versus 12.4%, p<0.003), which was likely due to the larger brain mass and smaller viscoelastic modulus of the 4 weeks old pig brain compared with those of the 5 days old. Strain measurement error for the overall methodology was estimated to be 1%. Brain tissue strain during rapid, nonimpact head rotation in the juvenile pig varies significantly with age. The empirical data presented will be used to validate computational model predictions of

  12. Is brain uptake of leptin in vivo saturable and reduced by fasting?

    Energy Technology Data Exchange (ETDEWEB)

    Karonen, S.L.; Nikkinen, P. [Department of Clinical Chemistry, Helsinki University Central Hospital, FIN-00290 Helsinki (Finland); Koistinen, H.A.; Koivisto, V.A. [Department of Medicine, Helsinki University Central Hospital, FIN-00290 Helsinki (Finland)

    1998-06-01

    Leptin is a peptide hormone produced by adipocytes which provides a negative feedback signal to control the amount of body fat. The action of leptin on food intake and weight loss is thought to be mediated by interaction with its hypothalamic receptor. We examined the biodistribution and brain uptake of radioiodinated leptin ({sup 123}I-leptin) by dynamic gamma imaging in six anaesthetized New Zealand white rabbits. Leptin uptake was seen in the brain, lungs, liver and kidneys. In the brain, increase in radioactivity as a function of time was seen in the choroid plexus area. The choroid plexus to brain radioactivity ratio (CP/BR) was used as the target to background ratio. The CP/BR ratio increased up to approximately 40-60 min, after which a steady state in CP/BR was achieved. The steady state uptake ratio was higher in the rabbits that had fasted for only 6-8 h before the experiment (CP/BR approximately 2.5) than in those that had fasted for 25-27 h before the experiment (CP/BR approximately 1.8). Thus, leptin uptake in vivo occurs in the choroid plexus region of the brain and in the lungs, kidney and the liver. The uptake of leptin in the choroid plexus appears to be saturable, as indicated by the achieved steady state in the CP/BR radioactivity curve 40-60 min following {sup 123}I-leptin injection. The lower steady state CP/BR after prolonged fasting may be the result of the downregulation of leptin receptors in the choroid plexus. (orig.) With 4 figs., 36 refs.

  13. Preferred stereoselective brain uptake of d-serine--a modulator of glutamatergic neurotransmission.

    Science.gov (United States)

    Bauer, Dagmar; Hamacher, Kurt; Bröer, Stefan; Pauleit, Dirk; Palm, Christoph; Zilles, Karl; Coenen, Heinz H; Langen, Karl-Josef

    2005-11-01

    Although it has long been presumed that d-amino acids are uncommon in mammalians, substantial amounts of free d-serine have been detected in the mammalian brain. d-Serine has been demonstrated to be an important modulator of glutamatergic neurotransmission and acts as an agonist at the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors. The blood-to-brain transfer of d-serine is thought to be extremely low, and it is assumed that d-serine is generated by isomerization of l-serine in the brain. Stimulated by the observation of a preferred transport of the d-isomer of proline at the blood-brain barrier, we investigated the differential uptake of [3H]-d-serine and [3H]-l-serine in the rat brain 1 h after intravenous injection using quantitative autoradiography. Surprisingly, brain uptake of [3H]-d-serine was significantly higher than that of [3H]-l-serine, indicating a preferred transport of the d-enantiomer of serine at the blood-brain barrier. This finding indicates that exogenous d-serine may have a direct influence on glutamatergic neurotransmission and associated diseases.

  14. Brain Tumor Initiating Cells Adapt to Restricted Nutrition through Preferential Glucose Uptake

    Science.gov (United States)

    Flavahan, William A.; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E.; Weil, Robert J.; Nakano, Ichiro; Sarkaria, Jann N.; Stringer, Brett W.; Day, Bryan W.; Li, Meizhang; Lathia, Justin D.; Rich, Jeremy N.; Hjelmeland, Anita B.

    2013-01-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) due to preferential BTIC survival and adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3 and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, TICs may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may instruct the tumor hierarchy and portend poor prognosis. PMID:23995067

  15. A minimal model for the mitochondrial rapid mode of Ca²+ uptake mechanism.

    Directory of Open Access Journals (Sweden)

    Jason N Bazil

    Full Text Available Mitochondria possess a remarkable ability to rapidly accumulate and sequester Ca²⁺. One of the mechanisms responsible for this ability is believed to be the rapid mode (RaM of Ca²⁺ uptake. Despite the existence of many models of mitochondrial Ca²⁺ dynamics, very few consider RaM as a potential mechanism that regulates mitochondrial Ca²⁺ dynamics. To fill this gap, a novel mathematical model of the RaM mechanism is developed herein. The model is able to simulate the available experimental data of rapid Ca²⁺ uptake in isolated mitochondria from both chicken heart and rat liver tissues with good fidelity. The mechanism is based on Ca²⁺ binding to an external trigger site(s and initiating a brief transient of high Ca²⁺ conductivity. It then quickly switches to an inhibited, zero-conductive state until the external Ca²⁺ level is dropped below a critical value (∼100-150 nM. RaM's Ca²⁺- and time-dependent properties make it a unique Ca²⁺ transporter that may be an important means by which mitochondria take up Ca²⁺ in situ and help enable mitochondria to decode cytosolic Ca²⁺ signals. Integrating the developed RaM model into existing models of mitochondrial Ca²⁺ dynamics will help elucidate the physiological role that this unique mechanism plays in mitochondrial Ca²⁺-homeostasis and bioenergetics.

  16. A 24-hour temporal profile of in vivo brain and heart pet imaging reveals a nocturnal peak in brain 18F-fluorodeoxyglucose uptake.

    Directory of Open Access Journals (Sweden)

    Daan R van der Veen

    Full Text Available Using positron emission tomography, we measured in vivo uptake of (18F-fluorodeoxyglucose (FDG in the brain and heart of C57Bl/6 mice at intervals across a 24-hour light-dark cycle. Our data describe a significant, high amplitude rhythm in FDG uptake throughout the whole brain, peaking at the mid-dark phase of the light-dark cycle, which is the active phase for nocturnal mice. Under these conditions, heart FDG uptake did not vary with time of day, but did show biological variation throughout the 24-hour period for measurements within the same mice. FDG uptake was scanned at different times of day within an individual mouse, and also compared to different times of day between individuals, showing both biological and technical reproducibility of the 24-hour pattern in FDG uptake. Regional analysis of brain FDG uptake revealed especially high amplitude rhythms in the olfactory bulb and cortex, while low amplitude rhythms were observed in the amygdala, brain stem and hypothalamus. Low amplitude 24-hour rhythms in regional FDG uptake may be due to multiple rhythms with different phases in a single brain structure, quenching some of the amplitude. Our data show that the whole brain exhibits significant, high amplitude daily variation in glucose uptake in living mice. Reports applying the 2-deoxy-D[(14C]-glucose method for the quantitative determination of the rates of local cerebral glucose utilization indicate only a small number of brain regions exhibiting a day versus night variation in glucose utilization. In contrast, our data show 24-hour patterns in glucose uptake in most of the brain regions examined, including several regions that do not show a difference in glucose utilization. Our data also emphasizes a methodological requirement of controlling for the time of day of scanning FDG uptake in the brain in both clinical and pre-clinical settings, and suggests waveform normalization of FDG measurements at different times of the day.

  17. Evaluation of anesthesia effects on [{sup 18}F]FDG uptake in mouse brain and heart using small animal PET

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Hiroshi E-mail: htoyama@fujita-hu.ac.jp; Ichise, Masanori; Liow, Jeih-San; Vines, Douglass C.; Seneca, Nicholas M.; Modell, Kendra J.; Seidel, Jurgen; Green, Michael V.; Innis, Robert B

    2004-02-01

    This study evaluates effects of anesthesia on {sup 18}F-FDG (FDG) uptake in mouse brain and heart to establish the basic conditions of small animal PET imaging. Prior to FDG injection, 12 mice were anesthetized with isoflurane gas; 11 mice were anesthetized with an intraperitoneal injection of a ketamine/xylazine mixture; and 11 mice were awake. In isoflurane and ketamine/xylazine conditions, FDG brain uptake (%ID/g) was significantly lower than in controls. Conversely, in the isoflurane condition, %ID/g in heart was significantly higher than in controls, whereas heart uptake in ketamine/xylazine mice was significantly lower. Results suggest that anesthesia impedes FDG uptake in mouse brain and affects FDG uptake in heart; however, the effects in the brain and heart differ depending on the type of anesthesia used.

  18. Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors.

    Science.gov (United States)

    Kangasniemi, Marko; Stafford, R Jason; Price, Roger E; Jackson, Edward F; Hazle, John D

    2003-02-01

    Thermal coagulation of cerebral tumors induces reactive changes within adjacent brain tissue, which appear as Gd-DTPA enhancement in MR images. This makes assessment of therapeutic success difficult to establish radiographically because the reactive changes can mimic residual tumor. Dynamic Gd-DTPA uptake curves in reactive tissue and tumor were investigated to assess the utility of contrast enhanced (CE)-dynamic MRI to distinguish reactive changes from residual tumor in a canine model. Cerebral thermal necrosis was induced using a 980 nm laser in 11 dogs with intracerebral transmissible venereal tumors (TVTs). A fast spin-echo T1-weighted imaging sequence was used for CE-dynamic MRI. Gd-DTPA uptake data were acquired with 10-second temporal resolution and for untreated TVTs for reactive tissue using a sigmoidal-exponential model. Characteristic gadolinium uptake curves were measured and characterized for reactive brain tissue, and untreated and treated TVTs. Both early and delayed dynamic responses were significantly different in reactive brain tissue compared with TVT. Reactive thermal changes in otherwise normal brain tissue can be distinguished from residual tumor after cerebral thermal therapy using CE-dynamic MRI.

  19. Drought Rapidly Diminishes the Large Net CO2 Uptake in 2011 Over Semi-Arid Australia

    Science.gov (United States)

    Ma, Xuanlong; Huete, Alfredo; Cleverly, James; Eamus, Derek; Chevallier, Frederic; Joiner, Joanna; Poulter, Benjamin; Zhang, Yongguang; Guanter, Luis; Meyer, Wayne; hide

    2016-01-01

    Each year, terrestrial ecosystems absorb more than a quarter of the anthropogenic carbon emissions, termed as land carbon sink. An exceptionally large land carbon sink anomaly was recorded in 2011, of which more than half was attributed to Australia. However, the persistence and spatially attribution of this carbon sink remain largely unknown. Here we conducted an observation-based study to characterize the Australian land carbon sink through the novel coupling of satellite retrievals of atmospheric CO2 and photosynthesis and in-situ flux tower measures. We show the 2010-11 carbon sink was primarily ascribed to savannas and grasslands. When all biomes were normalized by rainfall, shrublands however, were most efficient in absorbing carbon. We found the 2010-11 net CO2 uptake was highly transient with rapid dissipation through drought. The size of the 2010-11 carbon sink over Australia (0.97 Pg) was reduced to 0.48 Pg in 2011-12, and was nearly eliminated in 2012-13 (0.08 Pg). We further report evidence of an earlier 2000-01 large net CO2 uptake, demonstrating a repetitive nature of this land carbon sink. Given a significant increasing trend in extreme wet year precipitation over Australia, we suggest that carbon sink episodes will exert greater future impacts on global carbon cycle.

  20. Drought rapidly diminishes the large net CO2 uptake in 2011 over semi-arid Australia

    Science.gov (United States)

    Ma, Xuanlong; Huete, Alfredo; Cleverly, James; Eamus, Derek; Chevallier, Frédéric; Joiner, Joanna; Poulter, Benjamin; Zhang, Yongguang; Guanter, Luis; Meyer, Wayne; Xie, Zunyi; Ponce-Campos, Guillermo

    2016-01-01

    Each year, terrestrial ecosystems absorb more than a quarter of the anthropogenic carbon emissions, termed as land carbon sink. An exceptionally large land carbon sink anomaly was recorded in 2011, of which more than half was attributed to Australia. However, the persistence and spatially attribution of this carbon sink remain largely unknown. Here we conducted an observation-based study to characterize the Australian land carbon sink through the novel coupling of satellite retrievals of atmospheric CO2 and photosynthesis and in-situ flux tower measures. We show the 2010–11 carbon sink was primarily ascribed to savannas and grasslands. When all biomes were normalized by rainfall, shrublands however, were most efficient in absorbing carbon. We found the 2010–11 net CO2 uptake was highly transient with rapid dissipation through drought. The size of the 2010–11 carbon sink over Australia (0.97 Pg) was reduced to 0.48 Pg in 2011–12, and was nearly eliminated in 2012–13 (0.08 Pg). We further report evidence of an earlier 2000–01 large net CO2 uptake, demonstrating a repetitive nature of this land carbon sink. Given a significant increasing trend in extreme wet year precipitation over Australia, we suggest that carbon sink episodes will exert greater future impacts on global carbon cycle. PMID:27886216

  1. Nanofiber Ion-Exchange Membranes for the Rapid Uptake and Recovery of Heavy Metals from Water

    Directory of Open Access Journals (Sweden)

    Nithinart Chitpong

    2016-12-01

    Full Text Available An evaluation of the performance of polyelectrolyte-modified nanofiber membranes was undertaken to determine their efficacy in the rapid uptake and recovery of heavy metals from impaired waters. The membranes were prepared by grafting poly(acrylic acid (PAA and poly(itaconic acid (PIA to cellulose nanofiber mats. Performance measurements quantified the dynamic ion-exchange capacity for cadmium (Cd, productivity, and recovery of Cd(II from the membranes by regeneration. The dynamic binding capacities of Cd(II on both types of nanofiber membrane were independent of the linear flow velocity, with a residence time of as low as 2 s. Analysis of breakthrough curves indicated that the mass flow rate increased rapidly at constant applied pressure after membranes approached equilibrium load capacity for Cd(II, apparently due to a collapse of the polymer chains on the membrane surface, leading to an increased porosity. This mechanism is supported by hydrodynamic radius (Rh measurements for PAA and PIA obtained from dynamic light scattering, which show that Rh values decrease upon Cd(II binding. Volumetric productivity was high for the nanofiber membranes, and reached 0.55 mg Cd/g/min. The use of ethylenediaminetetraacetic acid as regeneration reagent was effective in fully recovering Cd(II from the membranes. Ion-exchange capacities were constant over five cycles of binding-regeneration.

  2. Nanofiber Ion-Exchange Membranes for the Rapid Uptake and Recovery of Heavy Metals from Water

    Science.gov (United States)

    Chitpong, Nithinart; Husson, Scott M.

    2016-01-01

    An evaluation of the performance of polyelectrolyte-modified nanofiber membranes was undertaken to determine their efficacy in the rapid uptake and recovery of heavy metals from impaired waters. The membranes were prepared by grafting poly(acrylic acid) (PAA) and poly(itaconic acid) (PIA) to cellulose nanofiber mats. Performance measurements quantified the dynamic ion-exchange capacity for cadmium (Cd), productivity, and recovery of Cd(II) from the membranes by regeneration. The dynamic binding capacities of Cd(II) on both types of nanofiber membrane were independent of the linear flow velocity, with a residence time of as low as 2 s. Analysis of breakthrough curves indicated that the mass flow rate increased rapidly at constant applied pressure after membranes approached equilibrium load capacity for Cd(II), apparently due to a collapse of the polymer chains on the membrane surface, leading to an increased porosity. This mechanism is supported by hydrodynamic radius (Rh) measurements for PAA and PIA obtained from dynamic light scattering, which show that Rh values decrease upon Cd(II) binding. Volumetric productivity was high for the nanofiber membranes, and reached 0.55 mg Cd/g/min. The use of ethylenediaminetetraacetic acid as regeneration reagent was effective in fully recovering Cd(II) from the membranes. Ion-exchange capacities were constant over five cycles of binding-regeneration. PMID:27999394

  3. Enhanced cerebral uptake of receptor ligands by modulation of P-glycoprotein function in the blood-brain barrier

    NARCIS (Netherlands)

    Doze, P; Van Waarde, A; Elsinga, P H; Hendrikse, N H; Vaalburg, W

    Low cerebral uptake of some therapeutic drugs can be enhanced by modulation of P-glycoprotein (P-gp), an ATP-driven drug efflux pump at the blood-brain barrier (BBB). We investigated the possibility of increasing cerebral uptake of the beta-adrenergic ligands S-1'-[(18)F]-fluorocarazolol (FCAR) and

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

    Science.gov (United States)

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

    2017-04-01

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

  5. Piperine Decreases Binding of Drugs to Human Plasma and Increases Uptake by Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Dubey, Raghvendra K; Leeners, Brigitte; Imthurn, Bruno; Merki-Feld, Gabriele Susanne; Rosselli, Marinella

    2017-09-26

    We previously reported that piperine, an active alkaloidal principal of black and long peppers, enhances drug bioavailability by inhibiting drug metabolism. Another mechanism influencing drug availability/uptake is its free fraction. Since piperine is highly lipophilic, we hypothesize that it could also interact with drugs through binding displacement and influence their bioavailability. Accordingly, using equilibrium dialysis, we investigated whether piperine alters the binding of model drug ligands, that is flunitrazepam, diazepam, warfarin, salicylic acid, propranolol, lidocaine, and disopyramide to human plasma (n = 4). Since alterations in binding influence drug disposition, we also studied the effects of piperine on the uptake of plasma bound (3) H-propranolol and (14) C-warfarin by cultured bovine brain microvascular endothelial cells (BMECs). Piperine (1-1000 μM) increased the free fraction (fu) of both albumin and alpha-acid glycoprotein bound drugs in a concentration-dependent manner (p piperine (10 μM) increased the uptake of (3) H-propranolol and (14) C-warfarin by BMECs (p piperine displaces plasma bound drugs from both albumin and alpha-acid glycoprotein and facilitates drug uptake across biological membranes (e.g. BMEC). Moreover, it is feasible that piperine may similarly facilitate the transport of drugs into tissues, in vivo, and alter both pharmacokinetics and pharmacodynamics of administered drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Rapidly profiling blood-brain barrier penetration with liposome EKC.

    Science.gov (United States)

    Wang, Yongjun; Sun, Jin; Liu, Hongzhuo; He, Zhonggui

    2007-07-01

    This report intended to study the potential of liposome EKC (LEKC) as a convenient and high-throughput screening tool to assess drug penetration across the blood-brain barrier (BBB). The retention factors (k) of 24 structurally diverse compounds were determined with LEKC and vesicle EKC (VEKC), respectively. Principal component analysis of the steady-state concentrations ratio of compounds in the brain and in the blood expressed as log BB, log k(LEKC), log k(VEKC), and other lipophilic descriptors including octanol/water partition coefficient (Clog P), octanol/water distribution coefficients (log D(7.4)), and polar surface area (PSA), showed the maximum similarity of partitioning processes in LEKC to drug penetration across the BBB. Furthermore, the log BB were correlated with the above five lipophilic descriptors, and the results showed that log k(LEKC) gave the better correlation coefficient (r(2) = 0.811, p <0.0001) than those of log D(7.4), Clog P, PSA, and log k(VEKC) (r(2) = 0.730, 0.672, 0.627, and 0.620, p <0.0001). This is the first report of the use of LEKC as a promising rapid tool to profile drug penetration across the BBB.

  7. Rapid discrimination of visual scene content in the human brain.

    Science.gov (United States)

    Anokhin, Andrey P; Golosheykin, Simon; Sirevaag, Erik; Kristjansson, Sean; Rohrbaugh, John W; Heath, Andrew C

    2006-06-06

    The rapid evaluation of complex visual environments is critical for an organism's adaptation and survival. Previous studies have shown that emotionally significant visual scenes, both pleasant and unpleasant, elicit a larger late positive wave in the event-related brain potential (ERP) than emotionally neutral pictures. The purpose of the present study was to examine whether neuroelectric responses elicited by complex pictures discriminate between specific, biologically relevant contents of the visual scene and to determine how early in the picture processing this discrimination occurs. Subjects (n = 264) viewed 55 color slides differing in both scene content and emotional significance. No categorical judgments or responses were required. Consistent with previous studies, we found that emotionally arousing pictures, regardless of their content, produce a larger late positive wave than neutral pictures. However, when pictures were further categorized by content, anterior ERP components in a time window between 200 and 600 ms following stimulus onset showed a high selectivity for pictures with erotic content compared to other pictures regardless of their emotional valence (pleasant, neutral, and unpleasant) or emotional arousal. The divergence of ERPs elicited by erotic and non-erotic contents started at 185 ms post-stimulus in the fronto-central midline region, with a later onset in parietal regions. This rapid, selective, and content-specific processing of erotic materials and its dissociation from other pictures (including emotionally positive pictures) suggests the existence of a specialized neural network for prioritized processing of a distinct category of biologically relevant stimuli with high adaptive and evolutionary significance.

  8. Autoradiographic localization of /sup 3/H-paroxetine-labeled serotonin uptake sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    De Souza, E.B.; Kuyatt, B.L.

    1987-01-01

    Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin.

  9. [C-11]{beta}CNT: A new monoamine uptake ligand for studying serotonin and dopamine transporter sites in the living brain with PET

    Energy Technology Data Exchange (ETDEWEB)

    Mulholland, G.K.; Zheng, Q.H.; Zhou, F.C. [Indiana Univ. Medical Center, Indianapolis, IN (United States)] [and others

    1996-05-01

    There is considerable interest in measuring serotonin (5HT) and dopamine (DA) function in the human brain. Altered levels of 5HT and DA are recognized in drug abuse, neurotoxicities, psychiatric disorders, and neurodegenerative conditions including Alzheimer`s and Parkinson`s disease. Several phenyltropane analogs of cocaine bind tightly to both DA and 5HT uptake proteins. We have made a new agent from this class called {beta}CNT, 2{beta}-carboxymethyl-3{beta}-(2-naphthyl)-tropane, the isosteric O-for-CH{sub 2} analog of a compound reported to have among the highest measured affinities for DA and 5HT transporters and studied its in vivo brain distributions in animals for the first time. Optically pure {beta}CNT was made from cocaine, and labeled at the O-methyl position by esterification of {beta}CNT-acid with [C-11]CH{sub 3}OTfl under conditions similar to Wilson`s. HPLC-purified (99+%) final products (15-50% eob yield from CO{sub 2}, 40 min synth) had specific activities 0.1-1.2 Ci/{mu}mol at the time of injection. Preliminary [C-11]{beta}{beta}CNT rodent distribution showed very high brain uptake (3% ID at 60 min) and localization (striat: fr cort: hypo: cer: blood, 11: 5: 4: 1: 06). {beta}CNT-PET studies in juvenile pigs (5-20 mCi, 20-35 kg) found rapid brain uptake, and prominent retention (85 min) in midbrain, anterior brainstem and striatum, followed by cortex and olfactory bulb. Paroxetine pretreatment (5HT uptake blocker, 2mg/kg), diminished retention in most brain areas; nomifensine (DA/NE uptake blocker, 6 mg/kg) reduced striatum selectively. Direct comparisons of [C-11]{beta}CNT with other PET transporter radioligands {beta}CFT, {beta}CIT, and {beta}CTT (RTI-32) in the same pig found {beta}CNT had highest overall brain uptake among the agents. These initial results suggest {beta}CNT has favorable properties for imaging both 5HT and DA transporters in vivo, and further evaluation of its potential as a human PET agent is warranted.

  10. Manganese distribution across the blood-brain barrier III. The divalent metal transporter-1 is not the major mechanism mediating brain manganese uptake.

    Science.gov (United States)

    Crossgrove, Janelle S; Yokel, Robert A

    2004-03-01

    Manganese (Mn) is essential for and toxic to the brain. Brain Mn uptake utilizes both diffusion and transporter-mediated pathways. The divalent metal transporter-1 (DMT-1) has been suggested to mediate brain Mn uptake. The b/b Belgrade rat does not express significant amounts of functional DMT-1. In the present work, brain influx transfer coefficients of (54) Mn ion and (54) Mn transferrin (Mn Tf) were determined in b/b and +/b Belgrade and Wistar rats using the in situ brain perfusion technique. Brain Mn uptake was not significantly different among the three rat strains for either Mn species. We hypothesized that Mn may enter brain endothelial cells by a DMT-1-independent process but not be able to distribute across those cells into brain tissue due to the absence of DMT-1 activity. To test this hypothesis the brain capillary endothelial cells were isolated from b/b and +/b Belgrade rats and Wistar rats after in situ brain perfusion. Some animals received cerebrovascular washout after in situ brain perfusion to ascertain any affect of genotype on (54) Mn adsorption to the endothelial cell luminal surface. Less than 30% of the brain (54) Mn after (54) Mn ion or (54) Mn Tf perfusion remained associated with endothelial cells, suggesting the majority had distributed into brain extracellular fluid (ECF) and/or brain cells. Mn appears to distribute across the rat blood-brain barrier (BBB) into the brain by one or more carrier-mediated processes other than the DMT-1.

  11. Uptake in brain and neurophysiological activity of two lipid esters of gamma-aminobutyric acid.

    Science.gov (United States)

    Hesse, G W; Jacob, J N; Shashoua, V E

    1988-06-01

    Two lipid esters of gamma-aminobutyric acid (GABA), 1-linolenoyl-2,3-bis(4-aminobutyryl)propane-1,2,3-triol and 1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol, were found to have brain uptake indices of greater than 30% using the single-pass carotid artery injection technique. Both compounds produced dose-dependent inhibition of the evoked population spike in slices of rat hippocampus maintained in vitro. This effect was blocked reversibly by picrotoxin. The magnitude of the inhibition produced by the lipid esters of GABA was comparable to that of similar doses of GABA, but for both compounds the duration of the effect was at least 10 times longer than that produced by GABA. These data are consistent with the idea that the lipid esters of GABA can effectively penetrate the blood-brain barrier and act as prodrugs for the delivery of GABA to the central nervous system.

  12. Rapid uptake, metabolism, and elimination of inhaled sulfuryl fluoride fumigant by rats.

    Science.gov (United States)

    Mendrala, A L; Markham, D A; Eisenbrandt, D L

    2005-08-01

    Sulfuryl fluoride (SO(2)F(2)) is a structural fumigant gas used to control drywood termites and wood-boring beetles. The pharmacokinetics and metabolism of inhaled SO(2)F(2) were evaluated in male Fischer-344 rats exposed to 30 or 300 ppm (35)S-labeled SO(2)F(2) for 4 h. Blood, urine and feces were collected during and after the exposures and analyzed for radioactivity, (35)S-labeled fluorosulfate and sulfate, and fluoride (urine and feces only). Selected tissues were collected 7 days post-exposure and analyzed for radioactivity. During and after unlabeled SO(2)F(2) exposures, blood, brain, and kidney were collected and analyzed for fluoride ion. SO(2)F(2) was rapidly absorbed, achieving maximum concentrations of radioactivity in both plasma and red blood cells (RBC) near the end of the 4-h exposure period. Radioactivity was rapidly excreted, mostly via the urine. Seven days post-exposure, small amounts of radioactivity were distributed among several tissues, with the highest concentration detected in respiratory tissues. Radioactivity associated with the RBC remained elevated 7 days post-exposure, and highly perfused tissues had higher levels of radioactivity than other non-respiratory tissues. Radioactivity cleared from plasma and RBC with initial half-lives of 2.5 h after 30 ppm and 1-2.5 h after 300 ppm exposures. The terminal half-life of radioactivity was 2.5-fold longer in RBC than plasma. Based on the radiochemical profiles, there was no evidence of parent (35)SO(2)F(2) in blood. Identification of fluorosulfate and sulfate in blood and urine suggests that SO(2)F(2) is hydrolyzed to fluorosulfate, with release of fluoride, followed by further hydrolysis to sulfate and release of the remaining fluoride.

  13. Rapid treatment-induced brain changes in pediatric CRPS.

    Science.gov (United States)

    Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

    2016-03-01

    To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.

  14. Rapid Treatment-Induced Brain Changes in Pediatric CRPS

    Science.gov (United States)

    Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

    2014-01-01

    To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex-and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray (PAG), two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation. PMID:25515312

  15. Radioiodide uptake in brain, CSF, thyroid, and salivary glands of audiogenic seizure mice

    Energy Technology Data Exchange (ETDEWEB)

    Engstrom, F.L.; Chow, S.Y.; Kemp, J.W.; Woodbury, D.M.

    1984-08-01

    DBA/2J (DBA) mice are susceptible to audiogenic seizures (ASs) in an age-dependent manner. Anion transport as measured by radioiodide uptake was determined in thyroid gland, salivary gland, skeletal muscle, cerebral cortex, cerebellum, brainstem, and CSF from these mice at various ages. Anion transport was also determined in C57BL/6J(C57) mice, an AS-resistant strain. In thyroid, DBA mice had an enhanced ability to concentrate iodide at 21 days of age when they have maximal AS susceptibility, as compared with the same-aged C57 mice. This difference in thyroid function was less marked at 40 days of age, when DBA mice are less AS susceptible, and was absent at 110 days of age, when DBA mice are AS resistant. In brain, differences in iodide uptake were also noted between these two strains of mice at 21 days of age. DBA mice had an increased concentration of iodide in CSF, an indication that they have a defect in the transport of iodide out of the CSF across the choroid plexus. In addition, DBA mice had a lower ratio of cerebral cortex to CSF iodide, which suggests that DBA mice have a defect in the transport of this anion into cerebral cortical cells from brain interstitial fluid. These differences in iodide transport in brain decreased with age as the AS susceptibility of DBA mice decreased. These results suggest a relation between anion transport in thyroid gland, cerebral cortex, and choroid plexus and AS susceptibility in DBA mice at 21 days of age.

  16. Effect of cyclosporin A on the uptake of D{sub 3}-selective PET radiotracers in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Tu Zhude; Li Shihong; Xu Jinbin; Chu Wenhua; Jones, Lynne A. [Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Luedtke, Robert R. [Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States); Mach, Robert H., E-mail: rhmach@mir.wustl.edu [Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110 (United States)

    2011-07-15

    Introduction: Four benzamide analogs having a high affinity and selectivity for D{sub 3} versus D{sub 2} receptors were radiolabeled with {sup 11}C or {sup 18}F for in vivo evaluation. Methods: Precursors were synthesized, and the four D{sub 3} selective benzamide analogs were radiolabeled. The tissue distribution and brain uptake of the four compounds were evaluated in control rats and rats pretreated with cyclosporin A, a modulator of P-glycoprotein and an inhibitor of other ABC efflux transporters that contribute to the blood brain barrier. Micro-positron emission tomographic (PET) imaging was carried out for [{sup 11}C]6 in a control and a cyclosporin A pretreated rat. Results: All four compounds showed low brain uptake in control rats at 5 and 30 min post-injection; despite recently reported rat behavioral studies conducted on analogs 6 (WC-10) and 7 (WC-44). Following administration of cyclosporin A, increased brain uptake was observed with all four PET radiotracers at both 5 and 30 min post-intravenous injection. An increase in brain uptake following modulation/inhibition of the ABC transporters was also observed in the microPET study. Conclusions: These data suggest that D3 selective conformationally-flexible benzamide analogs which contain a N-2-methoxyphenylpiperazine moiety are substrates for P-glycoprotein or other adenosine triphosphate (ATP)-binding cassette transporters expressed at the blood-brain barrier, and that PET radiotracers containing this pharmacophore may display low brain uptake in rodents due to the action of these efflux transporters.

  17. Synthesis and regional mouse brain distribution of [11C]nisoxetine, a norepinephrine uptake inhibitor.

    Science.gov (United States)

    Haka, M S; Kilbourn, M R

    1989-01-01

    Nisoxetine, a selective and high affinity (IC50 = 1 nM) inhibitor of NE reuptake, has been radiolabeled in high specific activity (greater than 600 Ci/mmol) by the alkylation of the nor-methyl precursor with [11C]CH3I. Synthetic yields are good (40-60% from [11C]methyl iodide, corrected for decay, 20 min synthesis), with the product purified by HPLC. In vivo studies of regional brain distribution in CD-1 mice show uptake and retention of tracer in the cortex, striatum, hypothalamus and thalamus, with the highest levels in the hypothalamus and cortex. Specific binding in the cortex and hypothalamus can be reduced by preadministration of 7 mg/kg i.v. unlabeled nisoxetine. The possible value of [11C]nisoxetine as a PET imaging agent is discussed.

  18. Oxygen uptake efficiency slope correlates with brain natriuretic peptide in patients with heart failure.

    Science.gov (United States)

    Straburzyńska-Migaj, Ewa; Gwizdała, Adrian; Siniawski, Andrzej; Ochotny, Romuald; Grajek, Stefan

    2010-01-01

    Cardiopulmonary exercise testing is a well-established tool for clinical and prognostic assessment of patients with chronic heart failure (CHF). Recently, a new parameter of this examination--oxygen uptake efficiency slope (OUES)--has been described and proposed as a new prognostic factor in patients with CHF. Brain natriuretic peptide (BNP) is an established prognostic factor in CHF. The purpose of the study was to assess OUES in patients with CHF in relation to other cardiopulmonary parameters and BNP levels. The study group consisted of 42 patients with CHF and left ventricular ejection fraction (LVEF) slope (35.7 +/- 7.8 vs 25.7 +/- 2.7). In patients, OUES was significantly (p slope (r = -0.59). BNP was independently related to OUES in multivariate regression analysis. Oxygen uptake efficiency slope is significantly reduced in patients with CHF and correlates with peak VO(2) and other parameters of cardiopulmonary exercise treadmill test. It is not related to age. BNP is an independent marker of OUES in patients with CHF.

  19. Fatty Acid-Binding Protein 5 Mediates the Uptake of Fatty Acids, but not Drugs, Into Human Brain Endothelial Cells.

    Science.gov (United States)

    Lee, Gordon S; Pan, Yijun; Scanlon, Martin J; Porter, Christopher J H; Nicolazzo, Joseph A

    2017-12-14

    The purpose of this study was to examine the involvement of fatty acid-binding protein 5 (FABP5), a lipid-binding protein expressed at the blood-brain barrier (BBB), in fatty acid and drug uptake into human brain endothelial cells. Following transfection with siRNA against hFABP5, human brain endothelial cell (hCMEC/D3) uptake of lipophilic ligands with varying affinity to FABP5 was assessed with intracellular concentrations quantified by liquid scintillation counting, HPLC, or LCMS/MS. The in situ BBB transport of [3H]-diazepam was also assessed in wild type and FABP5-deficient mice. hFABP5 siRNA reduced FABP5 expression in hCMEC/D3 cells by 39.9 ± 3.8% (mRNA) and 38.8 ± 6.6% (protein; mean ± SEM), leading to a reduction in uptake of [14C]-lauric acid, [3H]-oleic acid, and [14C]-stearic acid by 37.5 ± 8.8%, 41.7 ± 11.6%, and 50.7 ± 13.6%, respectively, over 1 min. No significant changes in [14C]-diazepam, pioglitazone, and troglitazone uptake were detected following FABP5 knockdown in hCMEC/D3 cells. Similarly, no difference in BBB transport of [3H]-diazepam was observed between wild type and FABP5-deficient mice. Therefore, although FABP5 facilitates brain endothelial cell uptake of fatty acids, it has limited effects on brain endothelial cell uptake and BBB transport of drugs with lower affinity for FABP5. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  20. Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults.

    Science.gov (United States)

    Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran

    2018-01-01

    Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease.

  1. Laminated adsorbents with very rapid CO2 uptake by freeze-casting of zeolites.

    Science.gov (United States)

    Ojuva, Arto; Akhtar, Farid; Tomsia, Antoni P; Bergström, Lennart

    2013-04-10

    Structured zeolite 13X monoliths with a laminated structure and hierarchical macro-/microporosity were prepared by freeze-casting aqueous suspensions of zeolite 13X powder, bentonite, and polyethylene glycol. Colloidally stable suspensions with a low viscosity at both room temperature and near freezing could be prepared at alkaline conditions where both the zeolite 13X powder and bentonite carry a negative surface charge. Slow directional freezing of the suspensions led to the formation of well-defined and thin lamellar pores and pore walls while fast freezing resulted in more cylindrical pores. The wall thickness, which varied between 8 and 35 μm, increased with increasing solids loading of the suspension. Thermal treatment at 1053 K of the freeze-cast bodies containing between 9 and 17 wt % bentonite resulted in mechanically stable zeolite 13X monoliths. The monoliths displayed a carbon dioxide uptake capacity of 4-5 mmol/g and an uptake kinetics characterized by a very fast initial uptake where more than 50% of the maximum uptake was reached within 15 s. Freeze-cast laminated zeolite monoliths could be used to improve the volumetric efficiency and reduce the cycle time, of importance in, for example, biogas upgrading and CO2 separation from flue gas.

  2. Rapid successions affect microbial N-acetyl-glucosamine uptake patterns during a lacustrine spring phytoplankton bloom.

    Science.gov (United States)

    Eckert, Ester M; Salcher, Michaela M; Posch, Thomas; Eugster, Bettina; Pernthaler, Jakob

    2012-03-01

    The vernal successions of phytoplankton, heterotrophic nanoflagellates (HNF) and viruses in temperate lakes result in alternating dominance of top-down and bottom-up factors on the bacterial community. This may lead to asynchronous blooms of bacteria with different life strategies and affect the channelling of particular components of the dissolved organic matter (DOM) through microbial food webs. We followed the dynamics of several bacterial populations and of other components of the microbial food web throughout the spring phytoplankton bloom period in a pre-alpine lake, and we assessed bacterial uptake patterns of two constituents of the labile DOM pool (N-acetyl-glucosamine [NAG] and leucine). There was a clear genotypic shift within the bacterial assemblage, from fast growing Cytophaga-Flavobacteria (CF) affiliated with Fluviicola and from Betaproteobacteria (BET) of the Limnohabitans cluster to more grazing resistant AcI Actinobacteria (ACT) and to filamentous morphotypes. This was paralleled by successive blooms of viruses and HNF. We also noted the transient rise of other CF (related to Cyclobacteriaceae and Sphingobacteriaceae) that are not detected by fluorescence in situ hybridization with the general CF probe. Both, the average uptake rates of leucine and the fractions of leucine incorporating bacteria were approximately five to sixfold higher than of NAG. However, the composition of the NAG-active community was much more prone to genotypic successions, in particular of bacteria with different life strategies: While 'opportunistically' growing BET and CF dominated NAG uptake in the initial period ruled by bottom-up factors, ACT constituted the major fraction of NAG active cells during the subsequent phase of high predation pressure. This indicates that some ACT could profit from a substrate that might in parts have originated from the grazing of protists on their bacterial competitors. © 2011 Society for Applied Microbiology and Blackwell Publishing

  3. 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

    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....

  4. Inflammation-induced brain endothelial activation leads to uptake of electrostatically stabilized iron oxide nanoparticles via sulfated glycosaminoglycans.

    Science.gov (United States)

    Berndt, Dominique; Millward, Jason M; Schnorr, Jörg; Taupitz, Matthias; Stangl, Verena; Paul, Friedemann; Wagner, Susanne; Wuerfel, Jens T; Sack, Ingolf; Ludwig, Antje; Infante-Duarte, Carmen

    2017-05-01

    Based on our previous data on the presence of very small superparamagnetic iron oxide nanoparticles (VSOP) on brain endothelial structures during experimental autoimmune encephalomyelitis (EAE), we investigated the mechanisms of VSOP binding on inflamed brain endothelial cells in vivo and in vitro. After intravenous application, VSOP were detected in brain endothelial cells of EAE animals at peak disease and prior to clinical onset. In vitro, inflammatory stimuli increased VSOP uptake by brain endothelial bEnd.3 cells, which we confirmed in primary endothelial cells and in bEnd.3 cells cultured under shear stress. Transmission electron microscopy and blocking experiments revealed that during inflammation VSOP were endocytosed by bEnd.3. Modified sulfated glycosaminoglycans (GAG) on inflamed brain endothelial cells were the primary binding site for VSOP, as GAG degradation and inhibition of GAG sulfation reduced VSOP uptake. Thus, VSOP-based MRI is sensitive to visualize early neuroinflammatory processes such as GAG modifications on brain endothelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. [Effect of psychotropic substances on the uptake of [H3]-gamma-aminobutyric acid by rat brain synaptosomes].

    Science.gov (United States)

    Maĭsov, N I; Tolmacheva, N S; Raevskiĭ, K S

    1975-01-01

    The in vitro effects of some neuroleptics and antidepressants on the accumulation of [3H]/-GABA by the synaprosomes of the rat brain cortex were studied. Chloropromazine, trifluoperazine, fluphenazine, perphenazine, thioproperazine, haloperidol, trifluperidol, droperidol, imipramine, haloanison and phthoracyzine were found (in order of a decreasing activity) to inhibit the [3H]/-GABA uptake of synaptosomes. Neuroleptics, except for a new drug carbidine, proved to be more potent inhibitors than antidepressants are. The tranquilized diazepan failed to have any effect on the [3H]/-GABA uptake. The rats synaptosomes treated with chlorpromazine and imipramine were found to display a decreased ability to accumulate [3H]/-GABA. The suppressive effect of psychotropic agents on the [3H]/-GABA uptake by synaptosomes is suggested to be due, at least partly, to their known inhibitory influence on the Na+, K+-dependent ATPase.

  6. Rapid Analytical Methods for On-Site Triage for Traumatic Brain Injury

    Science.gov (United States)

    North, Stella H.; Shriver-Lake, Lisa C.; Taitt, Chris R.; Ligler, Frances S.

    2012-07-01

    Traumatic brain injury (TBI) results from an event that causes rapid acceleration and deceleration of the brain or penetration of the skull with an object. Responses to stimuli and questions, loss of consciousness, and altered behavior are symptoms currently used to justify brain imaging for diagnosis and therapeutic guidance. Tests based on such symptoms are susceptible to false-positive and false-negative results due to stress, fatigue, and medications. Biochemical markers of neuronal damage and the physiological response to that damage are being identified. Biosensors capable of rapid measurement of such markers in the circulation offer a solution for on-site triage, as long as three criteria are met: (a) Recognition reagents can be identified that are sufficiently sensitive and specific, (b) the biosensor can provide quantitative assessment of multiple markers rapidly and simultaneously, and (c) both the sensor and reagents are designed for use outside the laboratory.

  7. Effects of high-dose fenfluramine treatment on monoamine uptake sites in rat brain: Assessment using quantitative autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Appel, N.M.; Mitchell, W.M.; Contrera, J.F.; De Souza, E.B. (NIDA Addiction Research Center, Baltimore, MD (USA))

    1990-01-01

    Fenfluramine is an amphetamine derivative that in humans is used primarily as an anorectic agent in the treatment of obesity. In rats, subchronic high-dose d,l-fenfluramine treatment (24 mg/kg subcutaneously, twice daily for 4 days) causes long-lasting decreases in brain serotonin (5HT), its metabolite 5-hydroxyindoleacetic acid, and high-affinity 5HT uptake sites. Moreover, this high-dose treatment regimen causes both selective long-lasting decreases in fine-caliber 5HT-immunoreactive axons and appearance of other 5HT-immunoreactive axons with morphology characteristic of degenerating axons. Determination of the potential neurotoxic effects of fenfluramine treatment using immunohistochemistry is limited from the perspectives that staining is difficult to quantify and that it relies on presence of the antigen (in this case 5HT), and the 5HT-depleting effects of fenfluramine are well known. In the present study, we used quantitative in vitro autoradiography to assess, in detail, the density and regional distribution of (3H)paroxetine-labeled 5HT and (3H)mazindol-labeled catecholamine uptake sites in response to the high-dose fenfluramine treatment described above. Because monoamine uptake sites are concentrated on monoamine-containing nerve terminals, decreases in uptake site density would provide a quantitative assessment of potential neurotoxicity resulting from this fenfluramine treatment regimen. Marked decreases in densities of (3H)paroxetine-labeled 5HT uptake sites occurred in brain regions in which fenfluramine treatment decreased the density of 5HT-like immunostaining when compared to saline-treated control rats. These included cerebral cortex, caudate putamen, hippocampus, thalamus, and medial hypothalamus.

  8. Soluble Aβ oligomers are rapidly sequestered from brain ISF in vivo and bind GM1 ganglioside on cellular membranes

    National Research Council Canada - National Science Library

    Hong, Soyon; Ostaszewski, Beth L; Yang, Ting; O'Malley, Tiernan T; Jin, Ming; Yanagisawa, Katsuhiko; Li, Shaomin; Bartels, Tim; Selkoe, Dennis J

    2014-01-01

    .... Here, we found that soluble Aβ oligomers were sequestered from brain interstitial fluid onto brain membranes much more rapidly than nontoxic monomers and were recovered in part as bound to GM1 ganglioside on membranes. Aβ...

  9. FDG-PET in healthy and epileptic Lagotto Romagnolo dogs and changes in brain glucose uptake with age.

    Science.gov (United States)

    Jokinen, Tarja S; Haaparanta-Solin, Merja; Viitmaa, Ranno; Grönroos, Tove J; Johansson, Jarkko; Bergamasco, Luciana; Snellman, Marjatta; Metsähonkala, Liisa

    2014-01-01

    Regional cerebral metabolism and blood flow can be measured noninvasively with positron emission tomography (PET). 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG) widely serves as a PET tracer in human patients with epilepsy to identify the seizure focus. The goal of this prospective study was to determine whether juvenile or adult dogs with focal-onset epilepsy exhibit abnormal cerebral glucose uptake interictally and whether glucose uptake changes with age. We used FDG-PET to examine six Lagotto Romagnolo dogs with juvenile epilepsy, two dogs with adult-onset epilepsy, and five control dogs of the same breed at different ages. Three researchers unaware of dog clinical status visually analyzed co-registered PET and magnetic resonance imaging (MRI) images. Results of the visual PET analyses were compared with electroencephalography (EEG) results. In semiquantitative analysis, relative standard uptake values (SUV) of regions of interest (ROI) drawn to different brain regions were compared between epileptic and control dogs. Visual analysis revealed areas of hypometabolism interictally in five out of six dogs with juvenile epilepsy in the occipital, temporal, and parietal cortex. Changes in EEG occurred in three of these dogs in the same areas where PET showed cortical hypometabolism. Visual analysis showed no abnormalities in cerebral glucose uptake in dogs with adult-onset epilepsy. Semiquantitative analysis detected no differences between epileptic and control dogs. This result emphasizes the importance of visual analysis in FDG-PET studies of epileptic dogs. A change in glucose uptake was also detected with age. Glucose uptake values increased between dog ages of 8 and 28 weeks and then remained constant. © 2013 American College of Veterinary Radiology.

  10. Biogenic monoamine uptake by rat brain synaptosomes during aging. Effects of nootropic drugs.

    Science.gov (United States)

    Stancheva, S L; Alova, L G

    1994-09-01

    1. In experiments on young (3-5-month-old), adult (10-11-month-old) and old (21-22-month-old) rats, it was found that significant age-related changes occurred in the high-affinity uptake of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) by cortical and striatal synaptosomes. 2. Changes in DA, NA and 5-HT uptake during aging are suggested to be neurochemical correlates of cognition and memory deficits that develops in senescence. 3. The in vitro effects of the nootropic drugs piracetam, aniracetam, meclofenoxate and adafenoxate on the DA, NA and 5-HT uptake by cortical and striatal synaptosomes from young rats were studied. Administered in increasing concentrations (1 x 10(-4) to 5 x 10(-3) M) these drugs inhibited monoamine uptake. 4. Adafenoxate proved to be a more potent monoamine uptake inhibitor than the other three drugs; it inhibited the uptake in the frontal cortex and striatum without selectivity for either monoaminergic system. It is suggested that adafenoxate affects cognition through the involvement of central neurotransmission and particularly through the inhibition of monoamine uptake systems.

  11. The new PET imaging agent [{sup 11}C]AFE is a selective serotonin transporter ligand with fast brain uptake kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Zhihong [Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032 (United States); Guo Ningning [Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032 (United States); Narendran, Raj [Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032 (United States)] [and others

    2004-11-01

    A new positron emission tomography (PET) radioligand for the serotonin transporter (SERT), [{sup 11}C]2-[2-[[(dimethylamino)methyl]phenyl]thio]-5-(2-fluoroethyl)phenylamine ([{sup 11}C]AFE, 12), was synthesized and evaluated in vivo in rats and baboons. [{sup 11}C]AFE (12) was prepared from its monomethylamino precursor 11 by reaction with high specific activity [{sup 11}C]methyl triflate. Radiochemical yield was 32{+-}17% based on [{sup 11}C]methyl triflate (n=6) and specific activity was 1670{+-}864 Ci/mmol at end of synthesis (EOS, n=6). Binding assays indicated that AFE displays high affinity for SERT (K{sub i}=1.80 nM for hSERT) and lower affinity for norepinephrine transporter (K{sub i}=946 nM for hNET) or dopamine transporter (K{sub i}>10,000 nM for hDAT). In addition, AFE displays negligible binding affinities for other serotonin and dopamine receptors, indicating an excellent binding selectivity in vitro. Biodistribution studies in rats indicated that [{sup 11}C]AFE enters the brain readily and localizes in regions known to contain high concentrations of SERT, such as the thalamus, hypothalamus, frontal cortex and striatum. Moreover, such binding in SERT-rich brain regions is reduced significantly by pretreatment with either citalopram or the cold compound itself, but not by nisoxetine or GBR 12935, thus demonstrating that [{sup 11}C]AFE binding in the rat brain is saturable, specific and selective for the SERT. Imaging experiments in baboons indicated that the uptake pattern of [{sup 11}C]AFE is consistent with the known distribution of SERT in the baboon brain, with high levels of radioactivity detected in the midbrain and thalamus, moderate levels in the hippocampus and striatum and low levels in the cortical regions. The uptake kinetics of [{sup 11}C]AFE in the baboon brain is rapid, with activity in the midbrain and thalamus peaking at 15-40 min postinjection. Pretreatment of the baboon with citalopram (4 mg/kg) 20 min before radioactivity injection

  12. Imaging the dopamine uptake site with ex vivo [18F]GBR 13119 binding autoradiography in rat brain.

    Science.gov (United States)

    Ciliax, B J; Kilbourn, M R; Haka, M S; Penney, J B

    1990-08-01

    We studied the binding of [18F]GBR 13119 (1-[[(4-[18F]fluorophenyl) (phenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine) to rat brain with autoradiography after intravenous injection. The rank order of binding was dorsal striatum greater than nucleus accumbens = olfactory tubercle greater than substantia nigra = ventral tegmental area greater than other areas. Binding was blocked by prior injection of dopamine uptake blockers but not by injection of dopamine receptor antagonists or drugs that bind to the dialkylpiperazine site. Unilateral 6-hydroxy-dopamine lesions of dopamine neurons caused a marked decrease in striatal and nigral binding on the side of the lesion. We conclude that intravenous injection of [18F]GBR 13119 provides a useful marker of presynaptic dopamine uptake sites.

  13. Functional Brain Activation Differences in Stuttering Identified with a Rapid fMRI Sequence

    Science.gov (United States)

    Loucks, Torrey; Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech…

  14. Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.

    Science.gov (United States)

    Clark, Andrew J; Davis, Mark E

    2015-10-06

    Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.

  15. Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer's disease dementia.

    Science.gov (United States)

    Castellano, Christian-Alexandre; Nugent, Scott; Paquet, Nancy; Tremblay, Sébastien; Bocti, Christian; Lacombe, Guy; Imbeault, Hélène; Turcotte, Éric; Fulop, Tamas; Cunnane, Stephen C

    2015-01-01

    The cerebral metabolic rate of glucose (CMRg) is lower in specific brain regions in Alzheimer's disease (AD). The ketones, acetoacetate and β-hydroxybutyrate, are the brain's main alternative energy substrates to glucose. To gain insight into brain fuel metabolism in mild AD dementia by determining whether the regional CMR and the rate constant of acetoacetate (CMRa and Ka, respectively) reflect the same metabolic deficit reported for cerebral glucose uptake (CMRg and Kg). Mild AD dementia (Mild AD; n = 10, age 76 y) patients were compared with gender- and age-matched cognitively normal older adults (Controls; n = 29, age 75 y) using a PET/MRI protocol and analyzed with both ROI- and voxel-based methods. ROI-based analysis showed 13% lower global CMRg in the gray matter of mild AD dementia versus Controls (34.2 ± 5.0 versus 38.3 ± 4.7 μmol/100 g/min, respectively; p = 0.015), with CMRg and Kg in the parietal cortex, posterior cingulate, and thalamus being the most affected (p ≤ 0.022). Neither global nor regional CMRa or Ka differed between the two groups (all p ≥ 0.188). Voxel-based analysis showed a similar metabolic pattern to ROI-based analysis with seven clusters of significantly lower CMRg in the mild AD dementia group (uncorrected p ≤ 0.005) but with no difference in CMRa. Regional brain energy substrate hypometabolism in mild AD dementia may be specific to impaired glucose uptake and/or utilization. This suggests a potential avenue for compensating brain energy deficit in AD dementia with ketones.

  16. Rapid control of male typical behaviors by brain-derived estrogens

    Science.gov (United States)

    Cornil, Charlotte A.; Ball, Gregory F.; Balthazart, Jacques

    2012-01-01

    Beside their genomic mode of action, estrogens also activate a variety of cellular signaling pathways through non-genomic mechanisms. Until recently, little was known regarding the functional significance of such actions in males and the mechanism that control local estrogen concentration with a spatial and time resolution compatible with these non-genomic actions had rarely been examined. Here, we review evidence that estrogens rapidly modulate a variety of behaviors in male vertebrates. Then, we present in vitro work supporting the existence of a control mechanism of local brain estrogen synthesis by aromatase along with in vivo evidence that rapid changes in aromatase activity also occur in a region-specific manner in response to changes in the social or environmental context. Finally, we suggest that the brain estrogen provision may also play a significant role in females. Together these data bolster the hypothesis that brain-derived estrogens should be considered as neuromodulators. PMID:22983088

  17. PET studies on P-glycoprotein function in the blood-brain barrier : How it affects uptake and binding of drugs within the CNS

    NARCIS (Netherlands)

    Elsinga, PH; Hendrikse, Nelis; Bart, J; Vaalburg, W; van Waarde, A

    2004-01-01

    Permeability of the blood-brain barrier (BBB) is one of the factors determining the bioavailability of therapeutic drugs. The BBB only allows entry of lipophilic compounds with low molecular weights by passive diffusion. However, many lipophilic drugs show negligible brain uptake. They are

  18. gamma-Aminobutyric acid esters. 2. Synthesis, brain uptake, and pharmacological properties of lipid esters of gamma-aminobutyric acid.

    Science.gov (United States)

    Jacob, J N; Shashoua, V E; Campbell, A; Baldessarini, R J

    1985-01-01

    Two lipid esters of U-14C-labeled and unlabeled gamma-aminobutyric acid (GABA) were synthesized to test the possibility that natural lipid analogues, which resemble normal components of lipid bilayer membranes, can penetrate the blood-brain barrier and transport exogenous GABA to the brain. The uptake of 1-linolenoyl-2,3-bis(4-aminobutyryl)propane-1,2,3-triol and 1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol into mouse brain relative to liver was found to be, respectively, 75- and 127-fold greater than that of free GABA. The results indicate that there is little or no blood-brain barrier for the GABA ester molecules at doses up to 0.36 mmol/kg. Both ester compounds, but neither free GABA nor the lipid components delivered systemically, demonstrated central nervous system depressant properties by inhibiting the general motor activity of mice. Brain tissue has esterase activity which can release GABA from these compounds. This suggests that these compounds function as "prodrugs" to release GABA in the CNS.

  19. Response of canopy nitrogen uptake to a rapid decrease in bulk nitrate deposition in two eastern Canadian boreal forests.

    Science.gov (United States)

    Houle, D; Marty, C; Duchesne, L

    2015-01-01

    A few studies have reported a recent and rapid decline in NO3(-) deposition in eastern North America. Whether this trend can be observed at remote boreal sites with low rates of N deposition and how it could impact canopy uptake (CU) of N remain unknown. Here we report trends between 1997/1999 and 2012 for precipitation, throughfall N deposition as well as inorganic N CU for two boreal forest sites of Quebec, Canada, with contrasted N deposition rates and tree species composition. NO3(-) bulk deposition declined by approximately 50% at both sites over the studied period while no change was observed for NH4(+). As a result, the contribution of NH4(+) to inorganic N deposition changed from ~33% to more than 50% during the study period. On average, 52-59% of N deposition was intercepted by the canopy, the retention being higher for NH4(+) (60-67%) than for NO3(-) (45-54%). The decrease in NO3(-) bulk deposition and the increase in the NH4(+):NO3(-) ratio had important impacts on N-canopy interactions. The contribution of NH4(+) CU to that of total inorganic N CU increased at both sites but the trend was significant only at Tirasse (lowest N deposition). At this site, absolute NO3(-) CU significantly decreased (as did total N CU) during the study period, a consequence of the strong relationship (r(2) = 0.88) between NO3(-) bulk deposition and NO3(-) CU. Our data suggest that N interactions with forest canopies may change rapidly with changes in N deposition as well as with tree species composition.

  20. Alpha-synuclein gene deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of alpha-synuclein palmitate binding

    DEFF Research Database (Denmark)

    Golovko, Mikhail Y; Færgeman, Nils J.; Cole, Nelson B

    2005-01-01

    Alpha-synuclein is an abundant protein in the central nervous system that is associated with a number of neurodegenerative disorders, including Parkinson's disease. Its physiological function is poorly understood, although recently it was proposed to function as a fatty acid binding protein....... To better define a role for alpha-synuclein in brain fatty acid uptake and metabolism, we infused awake, wild-type, or alpha-synuclein gene-ablated mice with [1-(14)C]palmitic acid (16:0) and assessed fatty acid uptake and turnover kinetics in brain phospholipids. Alpha-synuclein deficiency decreased brain...

  1. Rapid changes in brain structure predict improvements induced by perceptual learning.

    Science.gov (United States)

    Ditye, Thomas; Kanai, Ryota; Bahrami, Bahador; Muggleton, Neil G; Rees, Geraint; Walsh, Vincent

    2013-11-01

    Practice-dependent changes in brain structure can occur in task relevant brain regions as a result of extensive training in complex motor tasks and long-term cognitive training but little is known about the impact of visual perceptual learning on brain structure. Here we studied the effect of five days of visual perceptual learning in a motion-color conjunction search task using anatomical MRI. We found rapid changes in gray matter volume in the right posterior superior temporal sulcus, an area sensitive to coherently moving stimuli, that predicted the degree to which an individual's performance improved with training. Furthermore, behavioral improvements were also predicted by volumetric changes in an extended white matter region underlying the visual cortex. These findings point towards quick and efficient plastic neural mechanisms that enable the visual brain to deal effectively with changing environmental demands. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Mapping metals in Parkinson's and normal brain using rapid-scanning x-ray fluorescence

    Science.gov (United States)

    Popescu, Bogdan F. Gh; George, Martin J.; Bergmann, Uwe; Garachtchenko, Alex V.; Kelly, Michael E.; McCrea, Richard P. E.; Lüning, Katharina; Devon, Richard M.; George, Graham N.; Hanson, Akela D.; Harder, Sheri M.; Chapman, L. Dean; Pickering, Ingrid J.; Nichol, Helen

    2009-02-01

    Rapid-scanning x-ray fluorescence (RS-XRF) is a synchrotron technology that maps multiple metals in tissues by employing unique hardware and software to increase scanning speed. RS-XRF was validated by mapping and quantifying iron, zinc and copper in brain slices from Parkinson's disease (PD) and unaffected subjects. Regions and structures in the brain were readily identified by their metal complement and each metal had a unique distribution. Many zinc-rich brain regions were low in iron and vice versa. The location and amount of iron in brain regions known to be affected in PD agreed with analyses using other methods. Sample preparation is simple and standard formalin-fixed autopsy slices are suitable. RS-XRF can simultaneously and non-destructively map and quantify multiple metals and holds great promise to reveal metal pathologies associated with PD and other neurodegenerative diseases as well as diseases of metal metabolism.

  3. The bus rapid transit system: A service quality dimension of commuter uptake in Cape Town, South Africa

    Directory of Open Access Journals (Sweden)

    Prince D. Ugo

    2014-03-01

    Full Text Available This study evaluated commuter uptake of the bus rapid transit (BRT system in Cape Town,South Africa. As a stated preference survey was not carried out prior to the launch of the new BRT system in the City of Cape Town, it became difficult to assess commuters’ preferences,which would have provided City policymakers and planners with an understanding of customer satisfaction of the proposed bus service. The commuting trend of the BRT system in the City indicates that tickets sales and utilisation by commuters is gradually picking up, but one would have expected high commuter engagement in terms of the modernity profile of the BRT system. This study investigated commuters’ (n = 260 satisfaction levels with 30 service quality variables on a self-rated questionnaire, using quantitative research methodology.The study result showed that passengers were not satisfied with the transport fare and the availability or accessibility of ticket sales outlets. In the context of this study, this result implies that the ‘responsiveness and affordability’ variable of the service quality dimensions should be an area of interest and review to City of Cape Town policymakers and planners. Service quality trends in public transport were also highlighted.

  4. Functional brain activation differences in stuttering identified with a rapid fMRI sequence

    Science.gov (United States)

    Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech motor and auditory brain activity in children who stutter closer to the age at which recovery from stuttering is documented. Rapid sequences may be preferred for individuals or populations who do not tolerate long scanning sessions. In this report, we document the application of a picture naming and phoneme monitoring task in three minute fMRI sequences with adults who stutter (AWS). If relevant brain differences are found in AWS with these approaches that conform to previous reports, then these approaches can be extended to younger populations. Pairwise contrasts of brain BOLD activity between AWS and normally fluent adults indicated the AWS showed higher BOLD activity in the right inferior frontal gyrus (IFG), right temporal lobe and sensorimotor cortices during picture naming and and higher activity in the right IFG during phoneme monitoring. The right lateralized pattern of BOLD activity together with higher activity in sensorimotor cortices is consistent with previous reports, which indicates rapid fMRI sequences can be considered for investigating stuttering in younger participants. PMID:22133409

  5. Differential uptake of O-(2-18F-fluoroethyl)-L-tyrosine, L-3H-methionine, and 3H-deoxyglucose in brain abscesses.

    Science.gov (United States)

    Salber, Dagmar; Stoffels, Gabriele; Pauleit, Dirk; Oros-Peusquens, Anna-Maria; Shah, Nadim Jon; Klauth, Peter; Hamacher, Kurt; Coenen, Heinz Hubert; Langen, Karl-Josef

    2007-12-01

    The amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) has been shown to be a useful tracer for brain tumor imaging. Experimental studies demonstrated no uptake of (18)F-FET in inflammatory cells but increased uptake has been reported in single cases of human brain abscesses. To explore this inconsistency, we investigated the uptake of (18)F-FET in comparison with that of L-[methyl-(3)H]methionine ((3)H-MET) and D-(3)H-deoxyglucose ((3)H-DG) in brain and calf abscesses in rats. Abscesses were induced in the brain (n = 9) and calf (n = 5) of Fisher CDF rats after inoculation of Staphylococcus aureus. Five days later, (18)F-FET and (3)H-MET (n = 10) or (18)F-FET and (3)H-DG (n = 4) were injected intravenously. One hour after injection the rats were sacrificed, and the brain or calf muscle was investigated using dual-tracer autoradiography. Lesion-to-background ratios (L/B) and standardized uptake values (SUVs) were calculated. The autoradiograms were compared with histology and immunostaining for glial fibrillary acidic protein (GFAP), CD68 for macrophages, and CD11b for microglia. (18)F-FET uptake in the area of macrophage infiltration and activated microglia at the rim of the brain abscesses was low (L/B, 1.5 +/- 0.4). In contrast, high uptake was observed for (3)H-MET as well as for (3)H-DG (L/B, 4.1 +/- 1.1 for (3)H-MET vs. 3.1 +/- 1.5 for (3)H-DG; P < 0.01 vs. (18)F-FET). Results for calf abscesses were similar. In the vicinity of the brain abscesses, slightly increased uptake was noted for (18)F-FET (L/B, 1.8 +/- 0.3) and (3)H-MET (L/B, 1.8 +/- 0.4), whereas (3)H-DG distribution was normal (L/B, 1.2 +/- 0.2). Anti-GFAP immunofluorescence showed a diffuse astrocytosis in those areas. Our results demonstrate that there is no accumulation of (18)F-FET in macrophages and activated microglia in experimental brain abscesses, whereas (3)H-MET and (3)H-DG exhibit high uptake in these cells. Thus, the specificity of (18)F-FET for gliomas may be superior to that

  6. Uptake of silica nanoparticles in the brain and effects on neuronal differentiation using different in vitro models.

    Science.gov (United States)

    Ducray, Angélique D; Stojiljkovic, Ana; Möller, Anja; Stoffel, Michael H; Widmer, Hans-Rudolf; Frenz, Martin; Mevissen, Meike

    2017-04-01

    Nanomedicine offers a promising tool for therapies of brain diseases, but they may be associated with potential adverse effects. The aim of this study was to investigate the uptake of silica-nanoparticles engineered for laser-tissue soldering in the brain using SH-SY5Y cells, dissociated and organotypic slice cultures from rat hippocampus. Nanoparticles were predominantly taken up by microglial cells in the hippocampal cultures but nanoparticles were also found in differentiated SH-SY5Y cells. The uptake was time- and concentration-dependent in primary hippocampal cells. Transmission electron microscopy experiments demonstrated nanoparticle aggregates and single particles in the cytoplasm. Nanoparticles were found in the endoplasmic reticulum, but not in other cellular compartments. Nanoparticle exposure did not impair cell viability and neuroinflammation in primary hippocampal cultures at all times investigated. Neurite outgrowth was not significantly altered in SH-SY5Y cells, but the neuronal differentiation markers indicated a reduction in neuronal differentiation induction after nanoparticle exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Prevention and treatment of traumatic brain injury due to rapid-onset natural disasters

    Directory of Open Access Journals (Sweden)

    James L. Regens

    2014-04-01

    Full Text Available The prevention and treatment of traumatic brain injury (TBI attributable to rapid-onset natural disasters is a major challenge confronting disaster preparedness planners and emergency medical personnel responding to those incidents. The kinetic energy released by rapid-onset natural disasters such as earthquakes, hurricanes or typhoons, and tornadoes can cause mild, moderate or severe TBIs. As a result, neurotrauma is a major risk factor for mortality and morbidity outcomes within the spatial domain impacted by a rapid-onset natural disaster. This review article elucidates major challenges associated with immediate emergency medical response, long-term care, and prevention of post-event increases in pediatric TBIs because of child abuse when rapid-onset natural disasters occur.

  8. Efficient Brain Uptake of Piperine and Its Pharmacokinetics Characterization after Oral Administration.

    Science.gov (United States)

    Ren, Tianjing; Wang, Qianwen; Li, Chenrui; Yang, Mengbi; Zuo, Zhong

    2017-11-21

    1. Piperine, the major biological active component in black pepper has been associated with miscellaneous pharmacological effects, especially on central nervous system. To correlates with its neurological activity, a comprehensive pharmacokinetic profile of piperine in brain, plasma and cerebrospinal fluid after oral administration in rats was investigated in the current study. 2. It was noted that piperine could efficiently penetrate and homogeneously distribute into brain with similar pharmacokinetics profiles in each region. In addition, piperine concentrations in brain and plasma were found to be comparable with brain to plasma AUC0→∞ ratios of 0.95 and 1.10 for total concentration and unbound concentrations, respectively. Piperine also demonstrated high affinity towards brain tissue (98.4-98.5%) and plasma protein (96.2-97.8%) leading to a brain distribution volume of 36.32±1.40 ml/g brain. Moreover, its efficient membrane permeability (Papp values of 5.41±0.40 × 10(-5) cm/sec and 4.78±0.16 × 10(-5) cm/sec for basolateral to apical and apical to basolateral transport in Caco-2 monolayer model) and limited hepatic metabolism (Clint of 8.15 μl/min/mg) could also contribute to its quick and high extent brain exposure. 3. In summary, the present study for the first time demonstrated high brain penetration potency of piperine could be resulted from its high brain tissue affinity and membrane permeability together with its limited liver metabolism.

  9. Selective intra-arterial administration of {sup 18}F-FDG to the rat brain - effects on hemispheric uptake

    Energy Technology Data Exchange (ETDEWEB)

    Arnberg, Fabian; Samen, Erik; Lundberg, Johan; Grafstroem, Jonas; Soederman, Michael; Stone-Elander, Sharon; Holmin, Staffan [Karolinska Institutet, Department of Clinical Neuroscience, Stockholm (Sweden); Karolinska University Hospital-Solna, Department of Neuroradiology, Stockholm (Sweden); Lu, Li [Karolinska University Hospital-Solna, KERIC, Stockholm (Sweden)

    2014-05-15

    The purpose of this study was to investigate the radioligand uptake and iodine contrast distribution in the intra- and extracranial circulation of the rat, after intra-arterial injections to the common carotid artery and different parts of the internal carotid artery. All animal experiments were carried out in accordance with Karolinska Institutet's guidelines and were approved by the local laboratory animal ethics committee. We used clinical neurointerventional systems to place microcatheters in the extra- or intracranial carotid artery of 15 Sprague-Dawley rats. Here, injection dynamics of iodine contrast was assessed using digital subtraction angiography. Maintaining the catheter position, the animals were placed in a micro PET and small-animal positron emission tomography (PET) was used to analyze injections [2-{sup 18}F]-2-fluoro-2-deoxy-d-glucose ({sup 18}F-FDG). Microcatheters had to be placed in the intracranial carotid artery (iICA) for the infusate to distribute to the brain. Selective injection via the iICA resulted in a 9-fold higher uptake of {sup 18}F-FDG in the injected hemisphere (p < 0.005) compared to both intravenous and more proximal carotid artery injections. Furthermore, selective injection gave a dramatically improved contrast between the brain and extracranial tissue. Intra-arterial injection increases the cerebral uptake of a radiotracer dramatically compared to systemic injection. This technique has potential applications for endovascular treatment of malignancies allowing intra-interventional modifications of injection strategy, based on information on tumor perfusion and risk to surrounding normal parenchyma. Furthermore the technique may increase diagnostic sensitivity and avoid problems due to peripheral pharmacological barriers and first passage metabolism of labile tracers. (orig.)

  10. Characterization of GABA/sub A/ receptor-mediated /sup 36/chloride uptake in rat brain synaptoneurosomes

    Energy Technology Data Exchange (ETDEWEB)

    Luu, M.D.; Morrow, A.L.; Paul, S.M.; Schwartz, R.D.

    1987-09-07

    ..gamma..-Aminobutyric acid (GABA) receptor-mediated /sup 36/chloride (/sup 36/Cl/sup -/) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated /sup 36/Cl/sup -/ uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated /sup 36/Cl/sup -/ uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated /sup 36/Cl/sup -/ uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br/sup -/>Cl/sup -/greater than or equal toNO/sub 3//sup -/>I/sup -/greater than or equal toSCN/sup -/>>C/sub 3/H/sub 5/OO/sup -/greater than or equal toClO/sub 4//sup -/>F/sup -/, consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl/sup -/ channel. 43 references, 4 figures, 3 tables.

  11. Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants.

    Science.gov (United States)

    Bien-Ly, Nga; Yu, Y Joy; Bumbaca, Daniela; Elstrott, Justin; Boswell, C Andrew; Zhang, Yin; Luk, Wilman; Lu, Yanmei; Dennis, Mark S; Weimer, Robby M; Chung, Inhee; Watts, Ryan J

    2014-02-10

    Antibodies to transferrin receptor (TfR) have potential use for therapeutic entry into the brain. We have shown that bispecific antibodies against TfR and β-secretase (BACE1 [β-amyloid cleaving enzyme-1]) traverse the blood-brain barrier (BBB) and effectively reduce brain amyloid β levels. We found that optimizing anti-TfR affinity improves brain exposure and BACE1 inhibition. Here we probe the cellular basis of this improvement and explore whether TfR antibody affinity alters the intracellular trafficking of TfR. Comparing high- and low-affinity TfR bispecific antibodies in vivo, we found that high-affinity binding to TfR caused a dose-dependent reduction of brain TfR levels. In vitro live imaging and colocalization experiments revealed that high-affinity TfR bispecific antibodies facilitated the trafficking of TfR to lysosomes and thus induced the degradation of TfR, an observation which was further confirmed in vivo. Importantly, high-affinity anti-TfR dosing induced reductions in brain TfR levels, which significantly decreased brain exposure to a second dose of low-affinity anti-TfR bispecific. Thus, high-affinity anti-TfR alters TfR trafficking, which dramatically impacts the capacity for TfR to mediate BBB transcytosis.

  12. Specific uptake of DHA by the brain from a structured phospholipid, AceDoPC®

    Directory of Open Access Journals (Sweden)

    Bernoud-Hubac Nathalie

    2017-03-01

    Full Text Available Docosahexaenoic acid (DHA; 22:6 ω-3 is highly enriched in the brain and is required for proper brain development and function. Its deficiency has been shown to be linked with the emergence of neurological diseases. Dietary ω-3 fatty acid supplements including DHA have been suggested to improve neuronal development and enhance cognitive functions. Findings suggested that DHA is better incorporated into the brain when esterified at the sn-2 position of a lysophosphatidylcholine (LysoPC-DHA. AceDoPC® is a structured phospholipid or acetyl-LysoPC-DHA. As previously shown for LysoPC-DHA, AceDoPC® is a specific and preferred carrier of DHA to the brain. When AceDoPC® was injected to rats that were subjected to an ischemic stroke, it prevents the extension of brain lesions. Regarding the essential role of DHA for cerebral functions, targeting the brain with specific carriers of DHA might provide novel therapeutic approaches to neurodegenerative diseases.

  13. Whole body synthesis rates of DHA from α-linolenic acid are greater than brain DHA accretion and uptake rates in adult rats[S

    Science.gov (United States)

    Domenichiello, Anthony F.; Chen, Chuck T.; Trepanier, Marc-Olivier; Stavro, P. Mark; Bazinet, Richard P.

    2014-01-01

    Docosahexaenoic acid (DHA) is important for brain function, however, the exact amount required for the brain is not agreed upon. While it is believed that the synthesis rate of DHA from α-linolenic acid (ALA) is low, how this synthesis rate compares with the amount of DHA required to maintain brain DHA levels is unknown. The objective of this work was to assess whether DHA synthesis from ALA is sufficient for the brain. To test this, rats consumed a diet low in n-3 PUFAs, or a diet containing ALA or DHA for 15 weeks. Over the 15 weeks, whole body and brain DHA accretion was measured, while at the end of the study, whole body DHA synthesis rates, brain gene expression, and DHA uptake rates were measured. Despite large differences in body DHA accretion, there was no difference in brain DHA accretion between rats fed ALA and DHA. In rats fed ALA, DHA synthesis and accretion was 100-fold higher than brain DHA accretion of rats fed DHA. Also, ALA-fed rats synthesized approximately 3-fold more DHA than the DHA uptake rate into the brain. This work indicates that DHA synthesis from ALA may be sufficient to supply the brain. PMID:24212299

  14. Survival in Out-of-hospital Rapid Sequence Intubation of Non-Traumatic Brain Pathologies.

    Science.gov (United States)

    Fouche, Pieter Francsois; Jennings, Paul Andrew; Smith, Karen; Boyle, Malcolm; Blecher, Gabriel; Knott, Jonathan; Raji, Mani; Rosengarten, Pamela; Augello, Michael Roberto; Bernard, Stephen

    2017-01-01

    Rapid sequence intubation (RSI) is not only used in traumatic brain injuries in the out-of-hospital setting, but also for non-traumatic brain pathologies (NTBP) such as brain tumors, meningitis, encephalitis, hypoxic/anoxic brain injury, stroke, arteriovenous malformations, tumors, aneurysms, brain hemorrhage, as well as brain injury due to diabetes, seizures and toxicity, metabolic conditions, and alcohol and drug overdose. Previous research suggests that RSI is common in non-traumatic coma, but with an unknown prevalence of NTBP in those that receive RSI. If NTBP is common and if brain trauma RSI evidence is not valid for NTBP then a sizable proportion of NTBP receive this treatment without evidence of benefit. This study calculated the out-of-hospital NTBP prevalence in patients that had received RSI and explored factors that predicted survival. A retrospective cohort study based on data collected from an ambulance service and seven hospitals based in Melbourne, Australia. Non-traumatic brain pathologies were defined using ICD10-AM codes for the calculation of NTBP prevalence. Logistic regression modelled out-of-hospital predictors of survival to hospital discharge after adjustment for comorbidities. The seven participating hospitals treated 2,277 patients that received paramedic RSI for all illnesses and indications from January 1, 2008 to December 31, 2015, with survival data available for 1,940 (85%). Of the 1,940, 1,125 (58%) patients had at least one hospital-diagnosed NTBP. Sixty-nine percent all of NTBP survived to hospital discharge, compared to 65% for traumatic intracranial injury. Strokes were the most common and had poor survival to discharge (37%) compared to the second most common NTBP toxicity/toxic encephalopathy that had very high survival (98%). No out-of-hospital clinical intervention or prehospital time interval predicted survival. Factors that did predict survival include Glasgow Coma Scale (GCS), duration of mechanical ventilation, age, ICU

  15. Uptake characteristics of pinocembrin and its effect on p-glycoprotein at the blood-brain barrier in in vitro cell experiments.

    Science.gov (United States)

    Yang, Zhi-Hong; Sun, Xiao; Qi, Yun; Mei, Chao; Sun, Xiao-Bo; Du, Guan-Hua

    2012-01-01

    One purpose of the present study was to investigate the uptake characteristics of pinocembrin (PCB) and its effect on p-glycoprotein (P-gp) at the blood-brain barrier (BBB). Cultured rat brain microvascular endothelial cells (rBMECs) were used as an in vitro BBB model. Experiments were conducted to examine time-, concentration-, and temperature-dependent elements of PCB uptake, and the effect of classical P-gp inhibitors, cyclosporin A (CsA) and verapamil (Ver), on the steady-state uptake of PCB. Uptake of rhodamine 123 (Rho123), the typical P-gp substance, was measured with or without PCB. Meanwhile, the protein level of P-gp after incubation with PCB was detected by Western blot assay. The results demonstrated that PCB uptake by rBMECs was in a time- and concentration-dependent manner. CsA and Ver slightly increased PCB steady-state uptake by less than 10% (p>0.05). Similar results were observed in Rho123 uptake by co-administration of PCB. Further results were obtained by Western blot assay. PCB might not affect P-gp expression in rBMECs. Overall, the findings demonstrate that the passive transport process may be the main process for PCB to pass through the BBB, and P-gp is likely to have a little effect on the PCB transport process. Furthermore, PCB may not affect the functional activity and the protein expression of the P-gp transporter at the BBB.

  16. Improved brain uptake of peptide-based CNS drugs via alternative routes of administrations of its nanocarrier delivery systems: a promising strategy for CNS targeting delivery of peptides.

    Science.gov (United States)

    Qian, Shuai; Wang, Qianwen; Zuo, Zhong

    2014-11-01

    Recently, developing peptide-based drugs to treat CNS diseases has gained increasing attention in both academics and pharmaceutical industry. However, targeting delivery of peptides to brain is one of the most challenging problems faced in the treatment of CNS diseases. After explaining the brain barriers limiting the delivery of peptides, the current review focuses on summarizing the most promising approaches for the enhancement of peptide and brain uptake, including delivery via alternative routes of administrations or using nanocarriers or intranasal administration of nanocarriers loaded with peptide. In addition, the biopharmaceutic, pharmacokinetic and pharmacodynamic details of several successful peptide-based CNS drugs are highlighted. Although using nanocarriers or delivery via alternative routes could improve to a certain extent the brain uptake of peptides, the magnitude of changes remains moderate. Alternatively, intranasal administration of nanocarriers loaded with peptide has been demonstrated to be an effective approach for CNS-targeted delivery of peptides.

  17. Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

    Directory of Open Access Journals (Sweden)

    Wenda Xue

    2013-01-01

    Full Text Available The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2, leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression.

  18. A rapid, non-destructive methodology to monitor activity of sulfide-induced corrosion of concrete based on H2S uptake rate.

    Science.gov (United States)

    Sun, Xiaoyan; Jiang, Guangming; Bond, Philip L; Wells, Tony; Keller, Jurg

    2014-08-01

    Many existing methods to monitor the corrosion of concrete in sewers are either very slow or destructive measurements. To overcome these limitations, a rapid, non-invasive methodology was developed to monitor the sulfide-induced corrosion process on concrete through the measurement of the H2S uptake rates of concrete at various corrosion stages. The H2S uptake rate for a concrete coupon was determined by measuring the gaseous H2S concentrations over time in a temperature- and humidity-controlled gas-tight reactor. The reliability of this method was evaluated by carrying out repeated tests on different concrete coupons previously exposed to 50 ppm of H2S, at 30 °C and 100% relative humidity for over 32 months. The H2S uptake measurements showed good reproducibility. It was also shown that a severely corroded coupon exhibited higher sulfide uptake rates than a less corroded coupon. This could be explained by the corrosion layer in the more corroded coupon having a higher biological sulfide oxidation activity than the less corroded coupon. Additionally, temperature changes had a stronger effect on the uptake rate of the heavily corroded coupon compared to the less corroded coupon. A corrosion rate of 8.9 ± 0.5 mm/year, estimated from the H2S uptake results, agreed well with the corrosion rate observed in real sewers under similar conditions. The method could be applied to investigate important factors affecting sulfide-induced concrete corrosion, particularly temperature, fluctuating gaseous H2S concentrations, oxygen concentrations, surface pH and relative humidity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Rapid responses to reverse T₃ hormone in immature rat Sertoli cells: calcium uptake and exocytosis mediated by integrin.

    Directory of Open Access Journals (Sweden)

    Ana Paula Zanatta

    Full Text Available There is increasing experimental evidence of the nongenomic action of thyroid hormones mediated by receptors located in the plasma membrane or inside cells. The aim of this work was to characterize the reverse T₃ (rT₃ action on calcium uptake and its involvement in immature rat Sertoli cell secretion. The results presented herein show that very low concentrations of rT₃ are able to increase calcium uptake after 1 min of exposure. The implication of T-type voltage-dependent calcium channels and chloride channels in the effect of rT₃ was evidenced using flunarizine and 9-anthracene, respectively. Also, the rT₃-induced calcium uptake was blocked in the presence of the RGD peptide (an inhibitor of integrin-ligand interactions. Therefore, our findings suggest that calcium uptake stimulated by rT₃ may be mediated by integrin αvβ₃. In addition, it was demonstrated that calcium uptake stimulated by rT₃ is PKC and ERK-dependent. Furthermore, the outcomes indicate that rT₃ also stimulates cellular secretion since the cells manifested a loss of fluorescence after 4 min incubation, indicating an exocytic quinacrine release that seems to be mediated by the integrin receptor. These findings indicate that rT₃ modulates the calcium entry and cellular secretion, which might play a role in the regulation of a plethora of intracellular processes involved in male reproductive physiology.

  20. Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain

    Directory of Open Access Journals (Sweden)

    Katharine Askew

    2017-01-01

    Full Text Available Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing the whole population to be renewed several times during a lifetime. The number of microglial cells remains steady from late postnatal stages until aging and is maintained by the spatial and temporal coupling of proliferation and apoptosis, as shown by pulse-chase studies, chronic in vivo imaging of microglia, and the use of mouse models of dysregulated apoptosis. Our results reveal that the microglial population is constantly and rapidly remodeled, expanding our understanding of its role in the maintenance of brain homeostasis.

  1. Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel

    2014-01-01

    Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case-control desi......Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case...... were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF and NT-3 were evaluated in various affective states in bipolar disorder...

  2. A novel brain-computer interface based on the rapid serial visual presentation paradigm.

    Science.gov (United States)

    Acqualagna, Laura; Treder, Matthias Sebastian; Schreuder, Martijn; Blankertz, Benjamin

    2010-01-01

    Most present-day visual brain computer interfaces (BCIs) suffer from the fact that they rely on eye movements, are slow-paced, or feature a small vocabulary. As a potential remedy, we explored a novel BCI paradigm consisting of a central rapid serial visual presentation (RSVP) of the stimuli. It has a large vocabulary and realizes a BCI system based on covert non-spatial selective visual attention. In an offline study, eight participants were presented sequences of rapid bursts of symbols. Two different speeds and two different color conditions were investigated. Robust early visual and P300 components were elicited time-locked to the presentation of the target. Offline classification revealed a mean accuracy of up to 90% for selecting the correct symbol out of 30 possibilities. The results suggest that RSVP-BCI is a promising new paradigm, also for patients with oculomotor impairments.

  3. Evaluation of sup 3 H-paroxetine as a radioligand for in vivo study of 5-hydroxytryptamine uptake sites in mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kenji; Goromaru, Tsuyoshi (Fukuyama Univ., Hiroshima (Japan). Faculty of Pharmacy and Pharmaceutical Sciences)

    1990-08-01

    The distribution of radioactivity in the mouse brain after intravenous administration of {sup 3}H-paroxetine was in descending order hypothalamus > cerebral cortex > cerebellum. The radioactivity in the hypothalamus and cerebral cortex after injection of {sup 3}H-paroxetine was significantly decreased by treatment with 6-nitroquipazine or paroxetine. HPLC and TLC analyses show that no radioactive metabolites were found in the mouse brain 3 h after intravenous administration of {sup 3}H-paroxetine. The present results indicate that {sup 3}H-paroxetine would be a suitable radioligand for in vivo study of 5-HT uptake sites in mouse brain.

  4. A population-based cross-sectional study of barriers to uptake of eye care services in South India: the Rapid Assessment of Visual Impairment (RAVI) project.

    Science.gov (United States)

    Marmamula, Srinivas; Khanna, Rohit C; Shekhar, Konegari; Rao, Gullapalli N

    2014-06-12

    To assess the barriers to uptake of eye care services among those with avoidable impairment in the population aged ≥40 years in the South Indian state of Andhra Pradesh. Cross-sectional study. Community setting. Of 7800 participants recruited from one urban and two rural locations using a two-stage cluster random sampling methodology, 7378 (95%) were examined. Eye examinations were conducted using a rapid assessment protocol. Visual impairment (VI) was defined as presenting visual acuity attitude and 'felt need' to improve vision, newer and much intensive awareness campaigns are needed to bring about an attitudinal/behavioural change among individuals to improve the uptake of services. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Gene transfer-applied BNCT (g-BNCT) for amelanotic melanoma in brain. Further upregulation of {sup 10}B uptake by cell modulation

    Energy Technology Data Exchange (ETDEWEB)

    Iwakura, M.; Tamaki, N. [Kobe Univ. (Japan). School of Medicine; Kondoh, H.; Mishima, Y. [Mishima Inst. for Dermatol. Res., Kobe, Hyogo (Japan); Hiratsuka, J. [Kawasaki Medical School, Dept. Radiation Oncol., Kurashiki, Okayama (Japan)

    2000-10-01

    Our success in eradicating melanoma by single BNCT with BPA led to the next urgent theme, i.e. application of such BNCT for currently uncurable melanoma metastasis in brain. In order to establish {sup 10}B-BPA-BNCT for melanoma in brain, we have investigated the pharmacokinetics of BPA which is most critical factor for successful BNCT, in melanotic and amelanotic and further tyrosinase gene-transfected amelanotic melanoma proliferating in brain having blood-brain-barrier, as compared to melanoma proliferating in skin. We have established three implanted models for melanoma in brain: 1) A1059 cells, amelanotic melanoma, 2) B16B15b cells, melanotic melanoma cells, highly metastatic to brain, and 3) TA1059 cells, with active melanogenesis induced by tyrosinase gene transfection. We would like to report the results of comparative analysis of the BPA uptake ability in these melanoma cells in both brain and skin. Based on these findings, we are further investigating to enhance {sup 10}B-BPA uptake by not only g-BNCT but also by additional melanogenesis upregulating cell modulation. (author)

  6. Rapid prototyping of an EEG-based brain-computer interface (BCI).

    Science.gov (United States)

    Guger, C; Schlögl, A; Neuper, C; Walterspacher, D; Strein, T; Pfurtscheller, G

    2001-03-01

    The electroencephalogram (EEG) is modified by motor imagery and can be used by patients with severe motor impairments (e.g., late stage of amyotrophic lateral sclerosis) to communicate with their environment. Such a direct connection between the brain and the computer is known as an EEG-based brain-computer interface (BCI). This paper describes a new type of BCI system that uses rapid prototyping to enable a fast transition of various types of parameter estimation and classification algorithms to real-time implementation and testing. Rapid prototyping is possible by using Matlab, Simulink, and the Real-Time Workshop. It is shown how to automate real-time experiments and perform the interplay between on-line experiments and offline analysis. The system is able to process multiple EEG channels on-line and operates under Windows 95 in real-time on a standard PC without an additional digital signal processor (DSP) board. The BCI can be controlled over the Internet, LAN or modem. This BCI was tested on 3 subjects whose task it was to imagine either left or right hand movement. A classification accuracy between 70% and 95% could be achieved with two EEG channels after some sessions with feedback using an adaptive autoregressive (AAR) model and linear discriminant analysis (LDA).

  7. Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Heon; Lee, Kyu Chan; Choi, Jin Ho; Kim, Hye Young; Lee, Seok Ho; Sung, Ki Hoon; Kim, Yun Mi [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2012-06-15

    To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Nine patients with multiple ({>=}4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10- 12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

  8. Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells.

    Science.gov (United States)

    Uchida, Yasuo; Ito, Katsuaki; Ohtsuki, Sumio; Kubo, Yoshiyuki; Suzuki, Takashi; Terasaki, Tetsuya

    2015-07-01

    The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [(3) H]biotin and [(3) H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier. In humans, it was unclear (not concluded) about what transport system at the blood-brain barrier (BBB) is responsible for the brain uptakes of two vitamins, biotin and pantothenic acid, which are necessary for brain proper function. This study clarified for the first time that the solute carrier 5A6/Na(+) -dependent multivitamin transporter SLC5A6/SMVT is responsible for the supplies of biotin and pantothenic acid into brain across the BBB in humans. DHA, docosahexaenoic acid; NSAID, non-steroidal anti-inflammatory drug; PGE2, prostaglandin E2. © 2015

  9. Brain activity-based image classification from rapid serial visual presentation.

    Science.gov (United States)

    Bigdely-Shamlo, Nima; Vankov, Andrey; Ramirez, Rey R; Makeig, Scott

    2008-10-01

    We report the design and performance of a brain-computer interface (BCI) system for real-time single-trial binary classification of viewed images based on participant-specific dynamic brain response signatures in high-density (128-channel) electroencephalographic (EEG) data acquired during a rapid serial visual presentation (RSVP) task. Image clips were selected from a broad area image and presented in rapid succession (12/s) in 4.1-s bursts. Participants indicated by subsequent button press whether or not each burst of images included a target airplane feature. Image clip creation and search path selection were designed to maximize user comfort and maintain user awareness of spatial context. Independent component analysis (ICA) was used to extract a set of independent source time-courses and their minimally-redundant low-dimensional informative features in the time and time-frequency amplitude domains from 128-channel EEG data recorded during clip burst presentations in a training session. The naive Bayes fusion of two Fisher discriminant classifiers, computed from the 100 most discriminative time and time-frequency features, respectively, was used to estimate the likelihood that each clip contained a target feature. This estimator was applied online in a subsequent test session. Across eight training/test session pairs from seven participants, median area under the receiver operator characteristic curve, by tenfold cross validation, was 0.97 for within-session and 0.87 for between-session estimates, and was nearly as high (0.83) for targets presented in bursts that participants mistakenly reported to include no target features.

  10. Radiosynthesis of [{sup 18}F] N-(3-Fluoropropyl)-2-{beta}-Carbomethoxy-3-{beta}-(4-Bromophenyl) Nortropane and the regional brain uptake in non human primate using PET

    Energy Technology Data Exchange (ETDEWEB)

    Chaly, Thomas E-mail: tchaly@nshs.edu; Baldwin, R.M.; Neumeyer, John L.; Hellman, Matthew J.; Dhawan, Vijay; Garg, Pradeep K.; Tamagnan, Gilles; Staley, Julie K.; Al-Tikriti, Mohammed S.; Hou, Yankun; Zoghbi, Sami S.; Gu Xiaohui; Zong, R.; Eidelberg, David

    2004-01-01

    A synthetic procedure for the preparation of [{sup 18}F]FPCBT, an imaging agent for the dopamine transporter (DAT), has been developed. The radiosynthesis was carried out in a two step procedure. Even though the yield was low, we were able to prepare 20 to 30mCi of the product, which was enough for two or three studies. The radiochemical purity was greater than 96%. The in vivo properties of this radiotracer were evaluated using baboon and it showed highest uptake in the striatum. The studies also revealed that the maximum uptake was reached within 7 to 10 minutes post injection. Plasma metabolite analysis indicated that there is only one metabolite and it is less lipophilic than the parent compound. [{sup 18}F]FPCBT displayed good brain uptake and its high target to non target ratio indicate that it is a potential candidate for DAT imaging.

  11. Iron and copper interact during their uptake and deposition in the brain and other organs of developing rats exposed to dietary excess of the two metals.

    Science.gov (United States)

    Crowe, A; Morgan, E H

    1996-01-01

    This study examined the effect of iron and copper loading on rat brain, liver, kidney, femur, blood and plasma concentrations of these metals and iron transport into the organs during development. Dams were fed control diets or iron-loaded diets (20 g/kg carbonyl iron) with either distilled water or copper-loaded water (350 mg/L) beginning at d 20 of pregnancy. The weanlings also had access to the diets and water supply and were examined at 15, 21 and 63 d of age. The iron content of the liver was 17- to 30-fold greater in iron-loaded rats than in controls, whereas liver, kidney and plasma copper levels generally were lower. Iron loading alone did not increase brain iron concentrations, suggesting the blood-brain barrier is already developed at birth. However, dual loading of iron and copper resulted in elevated concentrations of brain non-heme iron and copper in 15- and 63-d-old rats compared with animals loaded with iron alone. These results suggest that brain iron uptake mechanisms may be different when excess copper is present. Liver non-heme iron was also greater in copper-loaded rats, irrespective of iron status. However, kidney iron concentrations generally were not affected by dietary copper. In rats fed the copper-containing diet, the uptake of iron into brain and liver was significantly lower than in those fed the control diet, suggesting that copper loading can decrease iron uptake into organs. It is concluded that combined dietary supplementation with iron and copper can alter the metabolism of each metal. These changes are age and organ dependent. Developing rats may be very susceptible to these combined overload states because significant effects are seen in early adulthood.

  12. Anesthetics rapidly promote synaptogenesis during a critical period of brain development.

    Directory of Open Access Journals (Sweden)

    Mathias De Roo

    Full Text Available Experience-driven activity plays an essential role in the development of brain circuitry during critical periods of early postnatal life, a process that depends upon a dynamic balance between excitatory and inhibitory signals. Since general anesthetics are powerful pharmacological modulators of neuronal activity, an important question is whether and how these drugs can affect the development of synaptic networks. To address this issue, we examined here the impact of anesthetics on synapse growth and dynamics. We show that exposure of young rodents to anesthetics that either enhance GABAergic inhibition or block NMDA receptors rapidly induce a significant increase in dendritic spine density in the somatosensory cortex and hippocampus. This effect is developmentally regulated; it is transient but lasts for several days and is also reproduced by selective antagonists of excitatory receptors. Analyses of spine dynamics in hippocampal slice cultures reveals that this effect is mediated through an increased rate of protrusions formation, a better stabilization of newly formed spines, and leads to the formation of functional synapses. Altogether, these findings point to anesthesia as an important modulator of spine dynamics in the developing brain and suggest the existence of a homeostatic process regulating spine formation as a function of neural activity. Importantly, they also raise concern about the potential impact of these drugs on human practice, when applied during critical periods of development in infants.

  13. Rapid and Accurate MRI Segmentation of Peritumoral Brain Edema in Meningiomas.

    Science.gov (United States)

    Latini, F; Larsson, E-M; Ryttlefors, M

    2017-06-01

    The extent of peritumoral brain edema (PTBE) in meningiomas commonly affects the clinical outcome. Despite its importance, edema volume is usually highly inaccurately approximated to a spheroid shape. We tested the accuracy and the reproducibility of semiautomatic lesion management software for the analysis of PTBE in a homogeneous case series of surgically confirmed intracranial meningiomas. PTBE volume was calculated on magnetic resonance images in 50 patients with intracranial meningiomas using commercial lesion management software (Vue PACS Livewire, Carestream, Rochester, NY, USA). Inter and intraobserver agreement evaluation and a comparison between manual volume calculation, the semiautomatic software and spheroid approximation were performed in 22 randomly selected patients. The calculation of edema volume was possible in all cases irrespective of the extent of the signal changes. The median time for each calculation was 3 min. Interobserver and intraobserver agreement confirmed the reproducibility of the method. Comparison with standard (fully manual) calculation confirmed the accuracy of this software. Our study showed a high level of reproducibility of this semiautomatic computational method for peritumoral brain edema. It is rapid and easy to use after relatively short training and is suitable for implementation in clinical practice.

  14. Acute Lesioning and Rapid Repair of Hypothalamic Neurons outside the Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    Ernie Yulyaningsih

    2017-06-01

    Full Text Available Neurons expressing agouti-related protein (AgRP are essential for feeding. The majority of these neurons are located outside the blood-brain barrier (BBB, allowing them to directly sense circulating metabolic factors. Here, we show that, in adult mice, AgRP neurons outside the BBB (AgRPOBBB were rapidly ablated by peripheral administration of monosodium glutamate (MSG, whereas AgRP neurons inside the BBB and most proopiomelanocortin (POMC neurons were spared. MSG treatment induced proliferation of tanycytes, the putative hypothalamic neural progenitor cells, but the newly proliferated tanycytes did not become neurons. Intriguingly, AgRPOBBB neuronal number increased within a week after MSG treatment, and newly emerging AgRP neurons were derived from post-mitotic cells, including some from the Pomc-expressing cell lineage. Our study reveals that the lack of protection by the BBB renders AgRPOBBB vulnerable to lesioning by circulating toxins but that the rapid re-emergence of AgRPOBBB is part of a reparative process to maintain energy balance.

  15. Different uptake of 99mTc-ECD adn 99mTc-HMPAO in the same brains: analysis by statistical parametric mapping.

    Science.gov (United States)

    Hyun, Y; Lee, J S; Rha, J H; Lee, I K; Ha, C K; Lee, D S

    2001-02-01

    The purpose of this study was to investigate the differences between technetium-99m ethyl cysteinate dimer (99mTc-ECD) and technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) uptake in the same brains by means of statistical parametric mapping (SPM) analysis. We examined 20 patients (9 male, 11 female, mean age 62+/-12 years) using 99mTc-ECD and 99mTc-HMPAO single-photon emission tomography (SPET) and magnetic resonance imaging (MRI) of the brain less than 7 days after onset of stroke. MRI showed no cortical infarctions. Infarctions in the pons (6 patients) and medulla (1), ischaemic periventricular white matter lesions (13) and lacunar infarction (7) were found on MRI. Split-dose and sequential SPET techniques were used for 99mTc-ECD and 99mTc-HMPAO brain SPET, without repositioning of the patient. All of the SPET images were spatially transformed to standard space, smoothed and globally normalized. The differences between the 99mTc-ECD and 99mTc-HMPAO SPET images were statistically analysed using statistical parametric mapping (SPM) 96 software. The difference between two groups was considered significant at a threshold of uncorrected P values less than 0.01. Visual analysis showed no hypoperfused areas on either 99mTc-ECD or 99mTc-HMPAO SPET images. SPM analysis revealed significantly different uptake of 99mTc-ECD and 99mTc-HMPAO in the same brains. On the 99mTc-ECD SPET images, relatively higher uptake was observed in the frontal, parietal and occipital lobes, in the left superior temporal lobe and in the superior region of the cerebellum. On the 99mTc-HMPAO SPET images, relatively higher uptake was observed in the medial temporal lobes, thalami, periventricular white matter and brain stem. These differences in uptake of the two tracers in the same brains on SPM analysis suggest that interpretation of cerebral perfusion is possible using SPET with 99mTc-ECD and 99mTc-HMPAO.

  16. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice

    Directory of Open Access Journals (Sweden)

    Natalia Brzozowska

    2016-05-01

    Full Text Available Cannabidiol (CBD is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp and breast cancer resistance protein (Bcrp mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b−∕−, Bcrp knockout (Abcg2−∕−, combined P-gp/Bcrp knockout (Abcb1a/b−∕−Abcg2−∕− and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders.

  17. A Process Evaluation to Assess Contextual Factors Associated With the Uptake of a Rapid Response Service to Support Health Systems’ Decision-Making in Uganda

    Directory of Open Access Journals (Sweden)

    Rhona Mijumbi-Deve

    2017-10-01

    Full Text Available Background Although proven feasible, rapid response services (RRSs to support urgent decision and policymaking are still a fairly new and innovative strategy in several health systems, more especially in low-income countries. There are several information gaps about these RRSs that exist including the factors that make them work in different contexts and in addition what affects their uptake by potential end users. Methods We used a case study employing process evaluation methods to determine what contextual factors affect the utilization of a RRS in Uganda. We held in-depth interviews with researchers, knowledge translation (KT specialists and policy-makers from several research and policy-making institutions in Uganda’s health sector. We analyzed the data using thematic analysis to develop categories and themes about activities and structures under given program components that affected uptake of the service. Results We identified several factors under three themes that have both overlapping relations and also reinforcing loops amplifying each other: Internal factors (those factors that were identified as over which the RRS had full [or almost full] control; external factors (factors over which the service had only partial influence, a second party holds part of this influence; and environmental factors (factors over which the service had no or only remote control if at all. Internal factors were the design of the service and resources available for it, while the external factors were the service’s visibility, integrity and relationships. Environmental factors were political will and health system policy and decision-making infrastructure. Conclusion For health systems practitioners considering RRSs, knowing what factors will affect uptake and therefore modifying them within their contexts is important to ensure efficient use and successful utilization of the mechanisms.

  18. Enhanced Brain Delivery of Dimethyl Fumarate Employing Tocopherol-Acetate-Based Nanolipidic Carriers: Evidence from Pharmacokinetic, Biodistribution, and Cellular Uptake Studies.

    Science.gov (United States)

    Kumar, Pramod; Sharma, Gajanand; Kumar, Rajendra; Malik, Ruchi; Singh, Bhupinder; Katare, O P; Raza, Kaisar

    2017-04-19

    Dimethyl fumarate (DMF) is an approved drug for the management of relapsing multiple sclerosis. Despite efficacy, DMF is also reported to be a challenging drug owing to concerns like gastrointestinal tract flushing, multiple dosing, lower brain permeability, less patient compliance, and economic hurdles. The present study aims to develop DMF-tocopherol acetate nanolipidic carrier (NLCs) to enhance brain permeability and improve the gastric tolerance. The developed DMF-tocopherol acetate NLCs offered an average size of 69.70 nm, PDI of 0.317, and a zeta potential of -9.71 mV. Higher drug entrapment (90.12%) and drug loading (20.13%) assured controlled drug release behavior both in gastric and intestinal pH. Cellular uptake studies on Caco-2 and SH-SY5Y monolayers confirmed better intestinal absorption and neuronal uptake of the developed system, which was further corroborated by the pharmacokinetic and biodistribution studies. The oral bioavailability was enhanced by 4.09 times and brain availability was substantially improved vis-à-vis plain drug. The findings are promising and offer preclinical evidence for better brain availability of DMF, which can be exploited in the better management of diseases like multiple sclerosis.

  19. Differentiation of Glioblastomas from Metastatic Brain Tumors by Tryptophan Uptake and Kinetic Analysis: A Positron Emission Tomographic Study with Magnetic Resonance Imaging Comparison

    Directory of Open Access Journals (Sweden)

    David O. Kamson

    2013-07-01

    Full Text Available Differentiating high-grade gliomas from solitary brain metastases is often difficult by conventional magnetic resonance imaging (MRI; molecular imaging may facilitate such discrimination. We tested the accuracy of α[11C]methyl-L-tryptophan (AMT–positron emission tomography (PET to differentiate newly diagnosed glioblastomas from brain metastases. AMT-PET was performed in 36 adults with suspected brain malignancy. Tumoral AMT accumulation was measured by standardized uptake values (SUVs. Tracer kinetic analysis was also performed to separate tumoral net tryptophan transport (by AMT volume of distribution [VD] from unidirectional uptake rates using dynamic PET and blood input function. Differentiating the accuracy of these PET variables was evaluated and compared to conventional MRI. For glioblastoma/metastasis differentiation, tumoral AMT SUV showed the highest accuracy (74% and the tumor/cortex VD ratio had the highest positive predictive value (82%. The combined accuracy of MRI (size of contrast-enhancing lesion and AMT-PET reached up to 93%. For ring-enhancing lesions, tumor/cortex SUV ratios were higher in glioblastomas than in metastatic tumors and could differentiate these two tumor types with > 90% accuracy. These results demonstrate that evaluation of tryptophan accumulation by PET can enhance pretreatment differentiation of glioblastomas and metastatic brain tumors. This approach may be particularly useful in patients with a newly diagnosed solitary ring-enhancing mass.

  20. Rapid acquisition strategy for functional T1ρ mapping of the brain.

    Science.gov (United States)

    Johnson, Casey P; Heo, Hye-Young; Thedens, Daniel R; Wemmie, John A; Magnotta, Vincent A

    2014-11-01

    Functional T1ρ mapping has been proposed as a method to assess pH and metabolism dynamics in the brain with high spatial and temporal resolution. The purpose of this work is to describe and evaluate a variant of the spin-locked echo-planar imaging sequence for functional T1ρ mapping at 3T. The proposed sequence rapidly acquires a time series of T1ρ maps with 4.0second temporal resolution and 10 slices of volumetric coverage. Simulation, phantom, and in vivo experiments are used to evaluate many aspects of the sequence and its implementation including fidelity of measured T1ρ dynamics, potential confounds to the T1ρ response, imaging parameter tradeoffs, time series analysis approaches, and differences compared to blood oxygen level dependent functional magnetic resonance imaging. It is shown that the high temporal resolution and volumetric coverage of the sequence are obtained with some expense including underestimation of the T1ρ response, sensitivity to T1 dynamics, and reduced signal-to-noise ratio. In vivo studies using a flashing checkerboard functional magnetic resonance imaging paradigm suggest differences between T1ρ and blood oxygen level dependent activation patterns. Possible sources of the functional T1ρ response and potential sequence improvements are discussed. The capability of T1ρ to map whole-brain pH and metabolism dynamics with high temporal and spatial resolution is potentially unique and warrants further investigation and development. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Rapid vascular uptake of contrast during a retrograde urethro-cystogram in a cat with chronic lower urinary tract disease

    Directory of Open Access Journals (Sweden)

    Xander Huizing

    2015-05-01

    Full Text Available Case summary A 9-year male neutered domestic longhair cat was referred to our hospital for investigation of recurrent urinary tract obstruction. The clinical signs had started 12 months earlier and the cat had been catheterised on multiple occasions. Clinical examination and abdominal ultrasound of the abdomen was unremarkable but examination of the penis revealed it to be prolapsed and extremely erythematous and friable. A retrograde contrast urethrocystogram was performed, showing extravasation of the contrast medium and establishing the presence of partial leakage or a tear of the urethra. In subsequent radiographs, the contrast was seen being rapidly absorbed into the pelvic and systemic vasculature via the penile veins, internal and external pudendal veins, internal and external iliac veins, and, ultimately, the caudal vena cava. Later, the contrast medium was seen within the renal pelves. Retrograde urethrocystography revealed stenosis and irregularities of the caudal urethral mucosa consistent with strictures. A routine perineal urethrostomy was performed and the cat recovered well. Conclusions and relevance Rapid vascular absorption of extravasated contrast medium has not been reported before. In this case, the increased blood supply to the distal urethra and penis is likely secondary to (chronic inflammation, as demonstrated by the urethral strictures and the friable, oedematous nature of the penis. Whether the inflammation was caused by chronic obstruction or repeated iatrogenic trauma, or a combination of these factors, will remain debatable. Nonetheless, this case demonstrates that when a retrograde contrast urethrocystogram is considered, it is imperative that a contrast medium (or other intraurethral medication such as local anaesthesia is chosen that is safe for intravascular use. Equally, an absolute aseptic technique is essential considering the potential for contaminants to be absorbed quite rapidly into the systemic

  2. Normal cerebral FDG uptake during childhood

    Energy Technology Data Exchange (ETDEWEB)

    London, Kevin [The Children' s Hospital at Westmead, Department of Nuclear Medicine, Sydney, NSW (Australia); University of Sydney, Discipline of Paediatrics and Child Health, Sydney Medical School, Sydney, NSW (Australia); Howman-Giles, Robert [The Children' s Hospital at Westmead, Department of Nuclear Medicine, Sydney, NSW (Australia); University of Sydney, Disciplines of Imaging and Paediatrics and Child Health, Sydney Medical School, Sydney, NSW (Australia)

    2014-04-15

    Current understanding of cerebral FDG uptake during childhood originates from a small number of studies in patients with neurological abnormalities. Our aim was to describe cerebral FDG uptake in a dataset of FDG PET scans in children more likely to represent a normal population. We reviewed cerebral FDG PET scans in children up to 16 years of age with suspected/proven extracranial malignancies and the following exclusions: central nervous system metastases, previous malignancies, previous chemotherapy or radiotherapy, development of cerebral metastases during therapy, neurological conditions, taking antiepileptic medication or medications likely to interfere with cerebral metabolism, and general anaesthesia within 24 h. White matter, basal ganglia, thalamus and the cerebellar cortex were analysed using regional SUV{sub max}, and the cerebral cortex, basal ganglia, thalamus and cerebellum were analysed using a regional relative uptake analysis in comparison to maximal cortical uptake. Scans from 30 patients (age range 11 months to 16 years, mean age 10 years 5 months) were included. All regions showed increasing SUV{sub max} with age. The parietal, occipital, lateral temporal and medial temporal lobes showed lower rates of increasing FDG uptake causing changing patterns of regional FDG uptake during childhood. The cortical regions showing the most intense uptake in early childhood were the parietal and occipital lobes. At approximately 7 years of age these regions had relatively less uptake than the frontal lobes and at approximately 10 years of age these regions had relatively less uptake than the thalamus. Relative FDG uptake in the brain has not reached an adult pattern by 1 year of age, but continues to change up to 16 years of age. The changing pattern is due to different regional rates of increasing cortical FDG uptake, which is less rapid in the parietal, occipital and temporal lobes than in the frontal lobes. (orig.)

  3. Synthesis of new fluorinated analogs of GABA, Pregabalin bioisosteres, and their effects on [(3)H]GABA uptake by rat brain nerve terminals.

    Science.gov (United States)

    Borisova, T; Pozdnyakova, N; Shaitanova, E; Gerus, I; Dudarenko, M; Mironets, R; Haufe, G; Kukhar, V

    2015-08-01

    Fluorinated analogs of natural substances take an essential place in the design of new biologically active compounds. New fluorinated analogs of γ-aminobutyric acid, that is, β-polyfluoroalkyl-GABAs (FGABAs), were synthesized with substituents: β-CF3-β-OH (1), β-CF3 (2); β-CF2CF2H (3). FGABAs are bioisosteres of Pregabalin (Lyrica®, Pfizer's blockbuster drug, β-i-Bu-GABA), and have lipophilicity close to this medicine. The effects of synthesized FGABAs on [(3)H]GABA uptake by isolated rat brain nerve terminals (synaptosomes) were assessed and compared with those of Pregabalin. FGABAs 1-3 (100μM) did not influence the initial velocity of [(3)H]GABA uptake when applied acutely, whereas an increase in this parameter was found after preliminary incubation of FGABAs with synaptosomes. Pregabalin after preliminary incubation with synaptosomes caused unidirectional changes in the initial velocity of [(3)H]GABA uptake. Using specific inhibitors of GAT1 and GAT3, NO-711 and SNAP5114, respectively, the ability of FGABAs 1-3 to influence non-GAT1 and non-GAT3 uptake activity of nerve terminals was analyzed, but no specificity was found. Therefore, new synthesized FGABAs are structural but not functional analogs of GABA (because they did not inhibit synaptosomal [(3)H]GABA uptake). Moreover, FGABAs are able to increase the initial velocity of [(3)H]GABA uptake by synaptosomes, and this effect is higher than that of Pregabalin. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Influence of blood-brain barrier permeability on O-(2-{sup 18}F-fluoroethyl)-L-tyrosine uptake in rat gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Stegmayr, Carina; Bandelow, Ulrike; Oliveira, Dennis; Lohmann, Philipp; Willuweit, Antje; Galldiks, Norbert; Luebke, Joachim H.R. [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, Juelich (Germany); Filss, Christian; Ermert, Johannes; Langen, Karl-Josef [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, Juelich (Germany); RWTH/University Hospital Aachen, Department of Nuclear Medicine and Neurology, Aachen (Germany); Shah, N. Jon [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, Juelich (Germany); RWTH/University Hospital Aachen, Department of Nuclear Medicine and Neurology, Aachen (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Aachen (Germany)

    2017-03-15

    O-(2-{sup 18}F-fluoroethyl)-L-tyrosine ({sup 18}F-FET) is an established tracer for the diagnosis of brain tumors with PET. This study investigates the influence of blood-brain barrier (BBB) permeability on {sup 18}F-FET uptake in two rat glioma models and one human xenograft model. F98 glioma, 9L gliosarcoma or human U87 glioblastoma cells were implanted into the striatum of 56 Fischer or RNU rats. Thereafter, animals were divided into a control group and a group receiving injections of the glucocorticoid dexamethasone (Dex). After 12-13 days of tumor growth animals received injection of Evans blue dye (EBD) to visualize BBB disturbance and underwent {sup 18}F-FET PET followed by autoradiography. Time activity curves, standardized uptake values (SUV) and Tumor-to-brain ratios (TBR) of {sup 18}F-FET uptake [18-61 min post injection (p.i.)] were evaluated using a volume-of-Interest (VOI) analysis. BBB disturbance was quantitatively evaluated by EBD fluorescence. The membrane gaps of blood vessel endothelial tight junctions were measured using electron microscopy to visualize ultrastructural BBB alterations in one untreated and one Dex treated F98 glioma. Data were analyzed by two-way ANOVAs. In Dex treated animals EBD extravasation was significantly reduced in 9L (P < 0.001) and U87 (P = 0.008) models and showed a trend in F98 models (P = 0.053). In contrast, no significant differences of {sup 18}F-FET uptake were observed between Dex treated animals and control group except a decrease of the TBR in the 9L tumor model in PET (P < 0.01). Ultrastructural evaluation of tumor blood vessel endothelia revealed significant reduction of the cleft diameter between endothelial cells after Dex treatment in F98 model (P = 0.010). Despite a considerable reduction of BBB permeability in rat gliomas after Dex treatment, no relevant changes of {sup 18}F-FET uptake were noted in this experimental study. Thus, {sup 18}F-FET uptake in gliomas appears to be widely independent of the

  5. Phencyclidine rapidly decreases neuronal mRNA of brain-derived neurotrophic factor.

    Science.gov (United States)

    Katanuma, Yusuke; Numakawa, Tadahiro; Adachi, Naoki; Yamamoto, Noriko; Ooshima, Yoshiko; Odaka, Haruki; Inoue, Takafumi; Kunugi, Hiroshi

    2014-06-01

    Downregulation of brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, has been implicated in psychiatric diseases including schizophrenia. However, detailed mechanisms of its reduction in patients with schizophrenia remain unclear. Here, using cultured cortical neurons, we monitored BDNF mRNA levels following acute application of phencyclidine [PCP; an N-methyl-d-aspartate (NMDA) receptor blocker], which is known to produce schizophrenia-like symptoms. We found that PCP rapidly caused a reduction in total amount of BDNF transcripts without effect on cell viability, while mRNA levels of nerve growth factor was intact. Actinomycin-D (ActD), an RNA synthesis inhibitor, decreased total BDNF mRNA levels similar to PCP, and coapplication of ActD with PCP did not show further reduction in BDNF mRNA compared with solo application of each drug. Among BDNF exons I, IV, and VI, the exon IV, which is positively regulated by neuronal activity, was highly sensitive to PCP. Furthermore, PCP inactivated cAMP response element-binding protein (CREB; a regulator of transcriptional activity of exon IV). The inactivation of CREB was also achieved by an inhibitor for Ca(2+) /calmodulin kinase II (CaMKII), although coapplication with PCP induced no further inhibition on the CREB activity. It is possible that PCP decreases BDNF transcription via blocking the NMDA receptor/CaMKII/CREB signaling. Copyright © 2014 Wiley Periodicals, Inc.

  6. Regional distribution of methionine adenosyltransferase in rat brain as measured by a rapid radiochemical method

    Energy Technology Data Exchange (ETDEWEB)

    Hiemke, C.; Ghraf, R.

    1981-09-01

    The distribution of methionine adenosyltransferase (MAT) in the CNS of the rat was studied by use of a rapid, sensitive and specific radiochemical method. The S-adenosyl-(methyl-/sup 14/C)L-methionine ((/sup 14/C)SAM) generated by adenosyl transfer from ATP to (methyl-/sup 14/C)L-methionine is quantitated by use of a SAM-consuming transmethylation reaction. Catechol O-methyltransferase (COMT), prepared from rat liver, transfers the methyl-/sup 14/C group of SAM to 3,4-dihydroxybenzoic acid. The /sup 14/C-labelled methylation products, vanillic acid and isovanillic acid, are separated from unreacted methionine by solvent extraction and quantitated by liquid scintillation counting. Compared to other methods of MAT determination, which include separation of generated SAM from methionine by ion-exchange chromatography, the assay described exhibited the same high degree of specificity and sensitivity but proved to be less time consuming. MAT activity was found to be uniformly distributed between various brain regions and the pituitary gland of adult male rats. In the pineal gland the enzyme activity is about tenfold higher.

  7. Modulating antibody affinity towards the transferrin receptor to increase brain uptake of anti-transferrin receptor antibody targeted gold nanoparticles

    DEFF Research Database (Denmark)

    Johnsen, Kasper Bendix; Bak, Martin; Melander, Fredrik

    2017-01-01

    . The transferrin receptor is exclusively expressed on capillaries of the brain, which makes it an interesting target for transport of drugs towards the brain. However, the current evidence on the receptor movement in brain capillaries does not suggest transcytosis, and delivering medicines or nanoparticles using......Drug delivery to the brain is hampered by the presence of the blood-brain barrier (BBB) that under physiological conditions precludes entrance of most substances contained in the systemic circulation. Thus, this barrier must be overcome to deliver medicines into the brain parenchyma...

  8. Targeting Cells With MR Imaging Probes: Cellular Interaction And Intracellular Magnetic Iron Oxide Nanoparticles Uptake In Brain Capillary Endothelial and Choroidal Plexus Epithelial Cells

    Science.gov (United States)

    Cambianica, I.; Bossi, M.; Gasco, P.; Gonzalez, W.; Idee, J. M.; Miserocchi, G.; Rigolio, R.; Chanana, M.; Morjan, I.; Wang, D.; Sancini, G.

    2010-10-01

    Magnetic iron oxide nanoparticles (NPs) are considered for various diagnostic and therapeutic applications in brain including their use as contrast agent for magnetic resonance imaging. In delivery application, the critical step is the transport across cell layers and the internalization of NPs into specific cells, a process often limited by poor targeting specificity and low internalization efficiency. The development of the models of brain endothelial cells and choroidal plexus epithelial cells in culture has allowed us to investigate into these mechanisms. Our strategy is aimed at exploring different routes to the entrapment of iron oxide NPs in these brain related cells. Here we demonstrated that not only cells endowed with a good phagocytic activity like activated macrophages but also endothelial brain capillary and choroidal plexus epithelial cells do internalize iron oxide NPs. Our study of the intracellular trafficking of NPs by TEM, and confocal microscopy revealed that NPs are mainly internalized by the endocytic pathway. Iron oxide NPs were dispersed in water and coated with 3,4-dihydroxyl-L-phenylalanine (L-DOPA) using standard procedures. Magnetic lipid NPs were prepared by NANOVECTOR: water in oil in water (W/O/W) microemulsion process has been applied to directly coat different iron based NPs by lipid layer or to encapsulate them into Solid Lipid Nanoparticles (SLNs). By these coating/loading the colloidal stability was improved without strong alteration of the particle size distribution. Magnetic lipid NPs could be reconstituted after freeze drying without appreciable changes in stability. L-DOPA coated NPs are stable in PBS and in MEM (Modified Eagle Medium) medium. The magnetic properties of these NPs were not altered by the coating processes. We investigated the cellular uptake, cytotoxicity, and interaction of these NPs with rat brain capillary endothelial (REB4) and choroidal plexus epithelial (Z310) cells. By means of widefield, confocal

  9. Regional brain distribution of [18F]GBR 13119, a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice.

    Science.gov (United States)

    Kilbourn, M R; Haka, M S; Mulholland, G K; Sherman, P S; Pisani, T

    1989-07-18

    We have examined the regional brain distribution of [18F]GBR 13119 (18F: beta +, T1/2 = 110 min), a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice. High levels of binding are observed in the striatum of both species, with striatum/cerebellum ratios of 3-4 at 60 min after injection of the radiotracer. Striatum radioactivity and striatum/cerebellum ratios are more than 50% reduced in C57BL/6 mice treated chronically with the neurotoxin MPTP. We conclude mice are an appropriate model for the in vivo study of the dopamine uptake system, and that [18F]GBR 13119 may be a suitable in vivo marker for degeneration of striatal dopaminergic neurons.

  10. gamma-Aminobutyric acid esters. 3. Synthesis, brain uptake, and pharmacological properties of C-18 glyceryl lipid esters of GABA with varying degree of unsaturation.

    Science.gov (United States)

    Jacob, J N; Hesse, G W; Shashoua, V E

    1987-09-01

    A series of 14C-labeled and unlabeled di-gamma-aminobutyric acid esters of glyceryl lipids having zero to three double bonds (stearoyl, oleoyl, linoleoyl, and linolenoyl) were synthesized. Measurements of the octanol/water partition coefficients of the compounds showed an increase with decreasing number of double bonds (i.e., from linolenoyl to stearoyl). The brain-uptake index went up from 31.5 (linolenoyl) to 45.1 (stearoyl) and similarly the brain-penetration index went up from 15 (linolenoyl) to 28 (stearoyl). Intraperitoneal injections of these di-GABA lipid esters produced a substantial inhibition of the general motor activity in mice at a dose of 30 mg/kg; the most active molecules were those containing two and three double bonds, i.e., the linolenoyl and linolenoyl derivatives. This is in reverse order to that predicted by brain-uptake and lipid-solubility properties, suggesting that the structure of the fatty acid side chain may be an additional factor in influencing biological activity.

  11. In Vitro and In Vivo Evidence for Active Brain Uptake of the GHB Analog HOCPCA by the Monocarboxylate Transporter Subtype 1.

    Science.gov (United States)

    Thiesen, Louise; Kehler, Jan; Clausen, Rasmus P; Frølund, Bente; Bundgaard, Christoffer; Wellendorph, Petrine

    2015-08-01

    γ-Hydroxybutyric acid (GHB) is a recreational drug, a clinically prescribed drug in narcolepsy and alcohol dependence, and an endogenous substance that binds to both high- and low-affinity sites in the brain. For studying the molecular mechanisms and the biologic role of the GHB high-affinity binding sites, ligands with high and specific affinity are essential. The conformationally restricted GHB analog HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid) is one such compound. The objective of this study was to investigate the transport of HOCPCA across the blood-brain barrier in vitro and in vivo and to investigate the hypothesis that HOCPCA, like GHB, is a substrate for the monocarboxylate transporters (MCTs). For in vitro uptake studies, MCT1, -2, and -4 were recombinantly expressed in Xenopus laevis oocytes, and the previously reported radioligand [(3)H]HOCPCA was used as substrate. HOCPCA inhibited the uptake of the endogenous MCT substrate l-[(14)C]lactate, and [(3)H]HOCPCA was shown to act as substrate for MCT1 and 2 (Km values in the low- to mid-millimolar range). Introducing single-point amino acid mutations into positions essential for MCT function supported that HOCPCA binds to the endogenous substrate pocket of MCTs. MCT1-mediated brain entry of HOCPCA (10 mg/kg s.c.) was further confirmed in vivo in mice by coadministration of increasing doses of the MCT inhibitor AR-C141990 [(R)-5-(3-hydroxypyrrolidine-1-carbonyl)-1-isobutyl-3-methyl-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione], which inhibited brain penetration of HOCPCA in a dose-dependent manner (ID50 = 4.6 mg/kg). Overall, our study provides evidence that MCT1 is an important brain entry site for HOCPCA and qualifies for future in vivo studies with HOCPCA. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Reproducibility of O-(2-{sup 18}F-fluoroethyl)-L-tyrosine uptake kinetics in brain tumors and influence of corticoid therapy: an experimental study in rat gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Stegmayr, Carina; Schoeneck, Michael; Oliveira, Dennis; Willuweit, Antje [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); Filss, Christian; Coenen, Heinz H.; Langen, Karl-Josef [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); University of Aachen, Department of Nuclear Medicine and Neurology, Aachen (Germany); Galldiks, Norbert [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); University of Cologne, Department of Neurology, Cologne (Germany); Shah, N. Jon [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); University of Aachen, Department of Nuclear Medicine and Neurology, Aachen (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Juelich (Germany)

    2016-06-15

    Positron emission tomography (PET) using O-(2-{sup 18}F-fluoroethyl)-L-tyrosine ({sup 18}F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of {sup 18}F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy. F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10-11 days of tumor growth, the animals underwent dynamic PET after injection of {sup 18}F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of {sup 18}F-FET uptake (18-61 min p.i.) and the slope of the time-activity-curves (TAC) (18-61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC). The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7 ± 2.8 %; p < 0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r = 0.77; p < 0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (-8.2 ± 6.1 %; p < 0.03), but did not influence the slope of the tumor TAC. TBR of {sup 18}F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation. (orig.)

  13. Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies.

    Science.gov (United States)

    Fryer, Tim D; Ejaz, Sohail; Jensen-Kondering, Ulf; Williamson, David J; Sitnikov, Sergey; Sawiak, Stephen J; Aigbirhio, Franklin I; Hong, Young T; Baron, Jean-Claude

    2017-01-01

    Mapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO) positron emission tomography (PET) is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO) is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs), two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity. Thirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI) and tetrazolium chloride (TTC) staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9), tissue oxygen partial pressure (PtO2) was measured in the ischemic tissue during both control and NBO conditions. As expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2. Despite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging.

  14. 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...

  15. Brain-derived neurotrophic factor rapidly enhances phosphorylation of the postsynaptic N-methyl-d-aspartate receptor subunit 1

    OpenAIRE

    Suen, Piin-Chau; Wu, Kuo; Levine, Eric S; Mount, Howard T. J.; Xu, Jia-Ling; LIN, SIANG-YO; Black, Ira B.

    1997-01-01

    Although neurotrophins have traditionally been regarded as neuronal survival factors, recent work has suggested a role for these factors in synaptic plasticity. In particular, brain-derived neurotrophic factor (BDNF) rapidly enhances synaptic transmission in hippocampal neurons through trkB receptor stimulation and postsynaptic phosphorylation mechanisms. Activation of trkB also modulates hippocampal long-term potentiation, in which postsynaptic N-methyl-d-aspartate glutamate receptors play a...

  16. THE RAPID PRODUCTION OF ACUTE DISSEMINATED ENCEPHALOMYELITIS IN RHESUS MONKEYS BY INJECTION OF HETEROLOGOUS AND HOMOLOGOUS BRAIN TISSUE WITH ADJUVANTS

    Science.gov (United States)

    Kabat, Elvin A.; Wolf, Abner; Bezer, Ada E.

    1947-01-01

    1. A picture resembling acute disseminated encephalomyelitis in the human being has been regularly and rapidly produced in rhesus monkeys by injection of emulsions of adult rabbit and monkey brain administered with adjuvants. 2. No lesions of the central nervous system resulted from injection of similar emulsions of fetal rabbit brain or adult rabbit lung. 3. A description of the gross and histological findings in the central nervous system is given and compared with features of human demyelinating disease. 4. The experimental findings are in accord with the hypothesis that antibody to the injected brain emulsion reacts with the tissues of the nervous system of the animal to produce the pathological changes. PMID:19871595

  17. Rapid P300 brain-computer interface communication with a head-mounted display

    Directory of Open Access Journals (Sweden)

    Ivo eKäthner

    2015-06-01

    Full Text Available Visual ERP (P300 based brain-computer interfaces (BCIs allow for fast and reliable spelling and are intended as a muscle-independent communication channel for people with severe paralysis. However, they require the presentation of visual stimuli in the field of view of the user. A head mounted display could allow convenient presentation of visual stimuli in situations, where mounting a conventional monitor might be difficult or not feasible (e.g. at a patient’s bedside. To explore if similar accuracies can be achieved with a virtual reality (VR headset compared to a conventional flat screen monitor, we conducted an experiment with 18 healthy participants. We also evaluated it with a person in the locked-in state (LIS to verify that usage of the headset is possible for a severely paralyzed person. Healthy participants performed online spelling with three different display methods. In one condition a 5x5 letter matrix was presented on a conventional 22 inch TFT monitor. Two configurations of the VR headset were tested. In the first (glasses A, the same 5x5 matrix filled the field of view of the user. In the second (glasses B, single letters of the matrix filled the field of view of the user. The participant in the LIS tested the VR headset on 3 different occasions (glasses A condition only. For healthy participants, average online spelling accuracies were 94% (15.5 bits/min using three flash sequences for spelling with the monitor and glasses A and 96% (16.2 bits/min with glasses B. In one session, the participant in the LIS reached an online spelling accuracy of 100% (10 bits/min using the glasses A condition. We also demonstrated that spelling with one flash sequence is possible with the VR headset for healthy users (mean: 32.1 bits/min, maximum reached by one user: 71.89 bits/min at 100% accuracy. We conclude that the VR headset allows for rapid P300 BCI communication in healthy users and may be a suitable display option for severely

  18. Quantitative Gd-DOTA uptake from cerebrospinal fluid into rat brain using 3D VFA-SPGR at 9.4T

    DEFF Research Database (Denmark)

    Lee, Hedok; Mortensen, Kristian; Sanggaard, Simon

    2017-01-01

    gadolinium concentration maps are derived. METHODS: We implemented a 3D variable flip angle spoiled gradient echo (VFA-SPGR) longitudinal relaxation time (T1) technique, the accuracy of which was cross-validated by way of inversion recovery rapid acquisition with relaxation enhancement (IR-RARE) using...... phantoms. Normal Wistar rats underwent Gd-DOTA infusion into CSF via the cisterna magna and continuous MRI for approximately 130 min using T1-weighted imaging. Dynamic Gd-DOTA concentration maps were calculated and parenchymal uptake was estimated. RESULTS: In the phantom study, T1 discrepancies between...... states. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine....

  19. Pho4 Is Essential for Dissemination of Cryptococcus neoformans to the Host Brain by Promoting Phosphate Uptake and Growth at Alkaline pH.

    Science.gov (United States)

    Lev, Sophie; Kaufman-Francis, Keren; Desmarini, Desmarini; Juillard, Pierre G; Li, Cecilia; Stifter, Sebastian A; Feng, Carl G; Sorrell, Tania C; Grau, Georges E R; Bahn, Yong-Sun; Djordjevic, Julianne T

    2017-01-01

    Phosphate acquisition by fungi is regulated by the phosphate-sensing and acquisition (PHO) signaling pathway. Cryptococcus neoformans disseminates from the lung to the brain and is the commonest cause of fungal meningitis worldwide. To investigate the contribution of PHO signaling to cryptococcal dissemination, we characterized a transcription factor knockout strain (hlh3Δ/pho4Δ) defective in phosphate acquisition. Despite little similarity with other fungal Pho4 proteins, Hlh3/Pho4 functioned like a typical phosphate-responsive transcription factor in phosphate-deprived cryptococci, accumulating in nuclei and triggering expression of genes involved in phosphate acquisition. The pho4Δ mutant strain was susceptible to a number of stresses, the effect of which, except for alkaline pH, was alleviated by phosphate supplementation. Even in the presence of phosphate, the PHO pathway was activated in wild-type cryptococci at or above physiological pH, and under these conditions, the pho4Δ mutant had a growth defect and compromised phosphate uptake. The pho4Δ mutant was hypovirulent in a mouse inhalation model, where dissemination to the brain was reduced dramatically, and markedly hypovirulent in an intravenous dissemination model. The pho4Δ mutant was not detected in blood, nor did it proliferate significantly when cultured with peripheral blood monocytes. In conclusion, dissemination of infection and the pathogenesis of meningitis are dependent on cryptococcal phosphate uptake and stress tolerance at alkaline pH, both of which are Pho4 dependent. IMPORTANCE Cryptococcal meningitis is fatal without treatment and responsible for more than 500,000 deaths annually. To be a successful pathogen, C. neoformans must obtain an adequate supply of essential nutrients, including phosphate, from various host niches. Phosphate acquisition in fungi is regulated by the PHO signaling cascade, which is activated when intracellular phosphate decreases below a critical level

  20. Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation.

    Science.gov (United States)

    St John, James A; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W; Ulett, Glen C; Batzloff, Michael R; Beacham, Ifor R; Ekberg, Jenny A K

    2016-09-01

    Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of (/sup 3/H)paroxetine-labeled serotonin uptake sites

    Energy Technology Data Exchange (ETDEWEB)

    Battaglia, G.; Yeh, S.Y.; O' Hearn, E.; Molliver, M.E.; Kuhar, M.J.; De Souza, E.B.

    1987-09-01

    This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%) in the density of (/sup 3/H)paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of (/sup 3/H)mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.

  2. Rapid Water Uptake and Limited Storage Capacity at Height of Growing Season in Four Temperate Tree Species in a Central Pennsylvania Catchment

    Science.gov (United States)

    Gaines, K.; Meinzer, F. C.; Duffy, C.; Thomas, E.; Eissenstat, D. M.

    2014-12-01

    rapid water uptake and tree water storage limited to about a month in duration. These findings are necessary for modeling of hydrologic parameters that are influenced by tree water age. They also indicate that trees on shallow soil in this catchment may be at risk if droughts lasting over a month occur more frequently in future years.

  3. Plan Quality and Treatment Efficiency for Radiosurgery to Multiple Brain Metastases: Non-Coplanar RapidArc vs Gamma Knife

    Directory of Open Access Journals (Sweden)

    Haisong eLiu

    2016-02-01

    Full Text Available Objectives: This study compares the dosimetry and efficiency of two modern radiosurgery (SRS modalities for multiple brain metastases (Gamma Knife and LINAC-based RapidArc/volumetric modulated arc therapy, with a special focus on the comparison of low dose spread.Methods: Six patients with three or four small brain metastases were used in this study. The size of targets varied from 0.1 ~ 10.5 cc. SRS doses were prescribed according to size of lesions. SRS plans were made using both Gamma Knife® Perfexion and a single-isocenter, multiple non-coplanar RapidArc®. Dosimetric parameters analyzed included RTOG conformity index (CI, gradient index (GI, 12 Gy isodose volume (V12Gy for each target, and the dose spread (Dspread for each plan. Dspread reflects SRS plan’s capability of confining radiation to within the local vicinity of the lesion and to not spread out to the surrounding normal brain tissues. Each plan has a dose (Dspread, such that once dose decreases below Dspread (on total tissue DVH, isodose volume starts increasing dramatically. Dspread is defined as that dose when volume increase first exceeds 20 cc per 0.1 Gy dose decrease. Results: RapidArc SRS has smaller CI (1.19 ±0.14 vs. 1.50 ± 0.16, p<0.001 and larger GI (4.77 ± 1.49 vs. 3.65 ± 0.98, p <0.01. V12Gy results were comparable (2.73 ± 1.38 cc vs. 3.06 ± 2.20 cc, p = 0.58. Moderate to lower dose spread, V6, V4.5, and V3, were also equivalent. Gamma Knife plans achieved better very low dose spread (≤3 Gy and also had slightly smaller Dspread, 1.9 Gy vs 2.5 Gy. Total treatment time for Gamma Knife is estimated between 60~100 min. Gamma Knife treatments are between 3~5 times longer compared to RapidArc treatment techniques.Conclusion: Dosimetric parameters reflecting prescription dose conformality (CI, dose fall off (GI, radiation necrosis indicator (V12Gy, and dose spread (Dspread were compared between Gamma Knife SRS and RapidArc SRS for multi-mets. RapidArc plans have

  4. DHA brain uptake and APOE4 status: a PET study with [1-11C]-DHA.

    Science.gov (United States)

    Yassine, Hussein N; Croteau, Etienne; Rawat, Varun; Hibbeln, Joseph R; Rapoport, Stanley I; Cunnane, Stephen C; Umhau, John C

    2017-03-23

    The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer's disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influence both brain DHA metabolism and cognitive outcomes. Using positron emission tomography, regional incorporation coefficients (k*), rates of DHA incorporation from plasma into the brain using [1-11C]-DHA (J in), and regional cerebral blood flow using [15O]-water were measured in 22 middle-aged healthy adults (mean age 35 years, range 19-65 years). Data were partially volume error-corrected for brain atrophy. APOE4 phenotype was determined by protein expression, and unesterified DHA concentrations were quantified in plasma. An exploratory post hoc analysis of the effect of APOE4 on DHA brain kinetics was performed. The mean global gray matter DHA incorporation coefficient, k*, was significantly higher (16%) among APOE4 carriers (n = 9) than among noncarriers (n = 13, p = 0.046). Higher DHA incorporation coefficients were observed in several brain regions, particularly in the entorhinal subregion, an area affected early in AD pathogenesis. Cerebral blood flow, unesterified plasma DHA, and whole brain DHA incorporation rate (J in) did not differ significantly between the APOE groups. Our findings suggest an increase in the DHA incorporation coefficient in several brain regions in APOE4 carriers. These findings may contribute to understanding how APOE4 genotypes affect AD risk.

  5. Rapid and Quantitative Assay of Amyloid-Seeding Activity in Human Brains Affected with Prion Diseases.

    Directory of Open Access Journals (Sweden)

    Hanae Takatsuki

    Full Text Available The infectious agents of the transmissible spongiform encephalopathies are composed of amyloidogenic prion protein, PrPSc. Real-time quaking-induced conversion can amplify very small amounts of PrPSc seeds in tissues/body fluids of patients or animals. Using this in vitro PrP-amyloid amplification assay, we quantitated the seeding activity of affected human brains. End-point assay using serially diluted brain homogenates of sporadic Creutzfeldt-Jakob disease patients demonstrated that 50% seeding dose (SD50 is reached approximately 10(10/g brain (values varies 10(8.79-10.63/g. A genetic case (GSS-P102L yielded a similar level of seeding activity in an autopsy brain sample. The range of PrPSc concentrations in the samples, determined by dot-blot assay, was 0.6-5.4 μg/g brain; therefore, we estimated that 1 SD50 unit was equivalent to 0.06-0.27 fg of PrPSc. The SD50 values of the affected brains dropped more than three orders of magnitude after autoclaving at 121°C. This new method for quantitation of human prion activity provides a new way to reduce the risk of iatrogenic prion transmission.

  6. Rapid and reversible enhancement of blood–brain barrier permeability using lysophosphatidic acid

    Science.gov (United States)

    On, Ngoc H; Savant, Sanjot; Toews, Myron; Miller, Donald W

    2013-01-01

    The present study characterizes the effects of lysophosphatidic acid (LPA) on blood–brain barrier (BBB) permeability focusing specifically on the time of onset, duration, and magnitude of LPA-induced changes in cerebrovascular permeability in the mouse using both magnetic resonance imaging (MRI) and near infrared fluorescence imaging (NIFR). Furthermore, potential application of LPA for enhanced drug delivery to the brain was also examined by measuring the brain accumulation of radiolabeled methotrexate. Exposure of primary cultured brain microvessel endothelial cells (BMECs) to LPA produced concentration-dependent increases in permeability that were completely abolished by clostridium toxin B. Administration of LPA disrupted BBB integrity and enhanced the permeability of small molecular weight marker gadolinium diethylenetriaminepentaacetate (Gd-DTPA) contrast agent, the large molecular weight permeability marker, IRdye800cwPEG, and the P-glycoprotein efflux transporter probe, Rhodamine 800 (R800). The increase in BBB permeability occurred within 3 minutes after LPA injection and barrier integrity was restored within 20 minutes. A decreased response to LPA on large macromolecule BBB permeability was observed after repeated administration. The administration of LPA also resulted in 20-fold enhancement of radiolabeled methotrexate in the brain. These studies indicate that administration of LPA in combination with therapeutic agents may increase drug delivery to the brain. PMID:24045401

  7. Extranodal NK/T-cell lymphoma, nasal type, manifesting as rapidly progressive dementia without any mass or enhancing brain lesion.

    Science.gov (United States)

    Shimatani, Yoshimitsu; Nakano, Yuta; Tsuyama, Naoko; Murayama, Shigeo; Oki, Ryosuke; Miyamoto, Ryosuke; Murakami, Nagahisa; Fujita, Koji; Watanabe, Syunsuke; Uehara, Hisanori; Abe, Takashi; Nodera, Hiroyuki; Kawarai, Toshitaka; Izumi, Yuishin; Kaji, Ryuji

    2016-10-01

    Among the many potential etiologies for rapidly progressive dementia (RPD), primary central nervous system extranodal NK/T-cell lymphoma, nasal-type (ENKL) is a rare entity. We present the first reported case of autopsy-proven RPD due to ENKL without any mass or enhancing lesion of the brain. A 54-year-old immunocompetent man presented with RPD, myoclonus and ataxia. The mini-mental state examination (MMSE) score was 22/30. His brain MRI revealed progressive brain atrophy without gadolinium enhancement or mass lesion. Five months after the initial evaluation, cognitive impairment further worsened with an MMSE score of 3/30. At the advanced stage, lumbar MRI showed swollen cauda equina with gadolinium enhancement. The number of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid had gradually increased. Twelve months after onset, the patient died of respiratory failure. Pathological findings revealed that lymphoma cells had diffusely invaded the meninges, parenchyma of the brain, spinal cord and cauda equina. Cells were positive for CD3, CD56 and EBV-encoded small RNAs and negative for CD20. No evidence of malignancy was identified in the visceral organs. This report indicates that ENKL should be recognized as one of the rare causes of RPD. Early testing for EBV-DNA in cerebrospinal fluid and imaging of cauda equina would be useful diagnostic tools. © 2016 Japanese Society of Neuropathology.

  8. Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts.

    Science.gov (United States)

    Michelhaugh, Sharon K; Muzik, Otto; Guastella, Anthony R; Klinger, Neil V; Polin, Lisa A; Cai, Hancheng; Xin, Yangchun; Mangner, Thomas J; Zhang, Shaohui; Juhász, Csaba; Mittal, Sandeep

    2017-02-01

    Abnormal tryptophan metabolism via the kynurenine pathway is involved in the pathophysiology of a variety of human diseases including cancers. α-11C-methyl-l-tryptophan (11C-AMT) PET imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of 11C limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-18F-fluoroethyl)-l-tryptophan (18F-FETrp) may be useful to assess tryptophan metabolism via the kynurenine pathway. In this study, we tested in vivo organ and tumor uptake and kinetics of 18F-FETrp in patient-derived xenograft mouse models and compared them with 11C-AMT uptake. Xenograft mouse models of glioblastoma and metastatic brain tumors (from lung and breast cancer) were developed by subcutaneous implantation of patient tumor fragments. Dynamic PET scans with 18F-FETrp and 11C-AMT were obtained for mice bearing human brain tumors 1-7 d apart. The biodistribution and tumoral SUVs for both tracers were compared. 18F-FETrp showed prominent uptake in the pancreas and no bone uptake, whereas 11C-AMT showed higher uptake in the kidneys. Both tracers showed uptake in the xenograft tumors, with a plateau of approximately 30 min after injection; however, 18F-FETrp showed higher tumoral SUV than 11C-AMT in all 3 tumor types tested. The radiation dosimetry for 18F-FETrp determined from the mouse data compared favorably with the clinical 18F-FDG PET tracer. 18F-FETrp tumoral uptake, biodistribution, and radiation dosimetry data provide strong preclinical evidence that this new radiotracer warrants further studies that may lead to a broadly applicable molecular imaging tool to examine abnormal tryptophan metabolism in human tumors. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  9. DHA supplementation during pregnancy as phospholipids or TAG produces different placental uptake but similar fetal brain accretion in neonatal piglets.

    Science.gov (United States)

    Gázquez, Antonio; Ruíz-Palacios, María; Larqué, Elvira

    2017-12-01

    The great variety of n-3 long-chain PUFA sources raises the question of the most adequate for using as a DHA supplement during pregnancy. Placental and fetal availability of different DHA sources remains unclear. We investigated DHA availability in maternal lipoproteins, placenta and fetal tissues in pregnant sows fed DHA as phospholipid (PL) or TAG to identify the best DHA source during this period. Pregnant Iberian sows were fed diets containing 0·8 % DHA of total fatty acids as PL from egg yolk or TAG from algae oil during the last third of gestation (40 d). Maternal tissues, placentas and fetal tissues were obtained at delivery and DHA quantified by GC. Major Facilitator Superfamily Domain Containing 2a (MFSD2a) carrier expression was analysed in both placenta and fetal brain by Western blotting. Sows fed the DHA-PL diet showed higher DHA incorporation in plasma LDL but not in plasma total lipids. No differences were found in DHA content between groups in maternal liver, adipose tissue or brain. Placental tissue incorporated more DHA in both total lipids and PL fraction in sows fed DHA-PL. However, this did not lead to an enhanced DHA accretion either in fetal plasma, fetal liver or fetal brain. MFSD2a expression was similar between both experimental groups. Maternal DHA supplementation during pregnancy in sow either as PL or TAG produces similar DHA accretion in fetal tissues but not in placenta. Both fat sources are equally available for fetal brain.

  10. Rapid effects of deep brain stimulation reactivation on symptoms and neuroendocrine parameters in obsessive-compulsive disorder.

    Science.gov (United States)

    de Koning, P P; Figee, M; Endert, E; van den Munckhof, P; Schuurman, P R; Storosum, J G; Denys, D; Fliers, E

    2016-01-26

    Improvement of obsessions and compulsions by deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) is often preceded by a rapid and transient mood elevation (hypomania). In a previous study we showed that improvement of mood by DBS for OCD is associated with a decreased activity of the hypothalamus-pituitary adrenal axis. The aim of our present study was to evaluate the time course of rapid clinical changes following DBS reactivation in more detail and to assess their association with additional neuroendocrine parameters. We included therapy-refractory OCD patients treated with DBS (>1 year) and performed a baseline assessment of symptoms, as well as plasma concentrations of thyroid-stimulating hormone (TSH), prolactin, growth hormone, copeptin and homovanillic acid. This was repeated after a 1-week DBS OFF condition. Next, we assessed the rapid effects of DBS reactivation by measuring psychiatric symptom changes using visual analog scales as well as repeated neuroendocrine measures after 30 min, 2 h and 6 h. OCD, anxiety and depressive symptoms markedly increased during the 1-week OFF condition and decreased again to a similar extent already 2 h after DBS reactivation. We found lower plasma prolactin (41% decrease, P=0.003) and TSH (39% decrease, P=0.003) levels during DBS OFF, which increased significantly already 30 min after DBS reactivation. The rapid and simultaneous increase in TSH and prolactin is likely to result from stimulation of hypothalamic thyrotropin-releasing hormone (TRH), which may underlie the commonly observed transient mood elevation following DBS.

  11. An in vitro transport model for rapid screening and predicting the permeability of candidate compounds at blood-brain barrier.

    Science.gov (United States)

    Yang, Zhi-Hong; Sun, Xiao; Mei, Chao; Sun, Xiao-Bo; Liu, Xiao-Dong; Chang, Qi

    2011-12-01

    The aim of this study was to design and develop a simple in vitro blood-brain barrier (BBB) permeation model for elementarily and rapidly predicting the permeability of candidate compounds at BBB and further evaluating whether P-glycoprotein (P-gp) affects them across BBB. The model was mainly composed of cultured rat brain microvascular endothelial cells (rBMECs), glass contraption, and micropore membrane. First, we evaluated the model by morphological observation. Second, the restriction effects of paracellular transport were verified by measuring marker probes transport, and monitoring transendothelial electrical resistance (TEER) and leakage. Finally, protein expression and activity of P-gp were confirmed by carrying out Western blot analysis and polarized transport of rhodamine-123 (Rho123) in rBMECs. The rBMECs retained both endothelial cells and BBB features. The rBMECs model reproducibly attained approximately 130 Ω cm² on the steady-state TEER value, and displayed a barrier function to marker probes transport by decreasing the permeability. Protein band of 170 kDa manifested the existence of P-gp in the rBMECs, and the findings of cyclosporin A-sensitive decrease of Rho123 efflux confirmed the presence of P-gp activity. A simple, rapid, and convenient in vitro BBB permeation model was successfully established and applied to evaluate the BBB transport profiles of three natural flavonoids: quercetin, naringenin, and rutin.

  12. Rapid and minimum invasive functional brain mapping by real-time visualization of high gamma activity during awake craniotomy.

    Science.gov (United States)

    Ogawa, Hiroshi; Kamada, Kyousuke; Kapeller, Christoph; Hiroshima, Satoru; Prueckl, Robert; Guger, Christoph

    2014-11-01

    Electrocortical stimulation (ECS) is the gold standard for functional brain mapping during an awake craniotomy. The critical issue is to set aside enough time to identify eloquent cortices by ECS. High gamma activity (HGA) ranging between 80 and 120 Hz on electrocorticogram is assumed to reflect localized cortical processing. In this report, we used real-time HGA mapping and functional neuronavigation integrated with functional magnetic resonance imaging (fMRI) for rapid and reliable identification of motor and language functions. Four patients with intra-axial tumors in their dominant hemisphere underwent preoperative fMRI and lesion resection with an awake craniotomy. All patients showed significant fMRI activation evoked by motor and language tasks. During the craniotomy, we recorded electrocorticogram activity by placing subdural grids directly on the exposed brain surface. Each patient performed motor and language tasks and demonstrated real-time HGA dynamics in hand motor areas and parts of the inferior frontal gyrus. Sensitivity and specificity of HGA mapping were 100% compared with ECS mapping in the frontal lobe, which suggested HGA mapping precisely indicated eloquent cortices. We found different HGA dynamics of language tasks in frontal and temporal regions. Specificities of the motor and language-fMRI did not reach 85%. The results of HGA mapping was mostly consistent with those of ECS mapping, although fMRI tended to overestimate functional areas. This novel technique enables rapid and accurate identification of motor and frontal language areas. Furthermore, real-time HGA mapping sheds light on underlying physiological mechanisms related to human brain functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Gamma-aminobutyric acid esters. 1. Synthesis, brain uptake, and pharmacological studies of aliphatic and steroid esters of gamma-aminobutyric acid

    Energy Technology Data Exchange (ETDEWEB)

    Shashoua, V.E.; Jacob, J.N.; Ridge, R.; Campbell, A.; Baldessarini, R.J.

    1984-05-01

    Labeled and unlabeled aliphatic and steroid esters of gamma-amino(U-/sup 14/C)butyric acid (GABA) were synthesized and tested for their capacity to penetrate the blood-brain barrier and for evidence of central neuropharmacological activity in rodents. The uptake of the labeled 9,12,15-octadecatrienyl (linolenyl), 3-cholesteryl, 1-butyl, and the 9-fluoro-11 beta,17-dihydroxy-16 alpha-methyl-3,20-dioxopregna -1,4-dien-21-yl (dexamethasone) esters of GABA into mouse brain increased 2-, 25-, 74-, and 81-fold over GABA, respectively. The cholesteryl ester of GABA depressed the general motor activity of mice and rats in a dose-dependent manner, whereas the 1-butyl, linolenyl, and dexamethasone esters were inactive by this test. Studies of the rates of hydrolysis, GABA receptor binding capacity, and octanol/water partition coefficients indicated that pharmacological activity of the esters after entry into the central nervous system (CNS) was dependent on their capacity to release GABA by enzymatic hydrolysis and their lipid solubility.

  14. Gamma-aminobutyric acid esters. 1. Synthesis, brain uptake, and pharmacological studies of aliphatic and steroid esters of gamma-aminobutyric acid.

    Science.gov (United States)

    Shashoua, V E; Jacob, J N; Ridge, R; Campbell, A; Baldessarini, R J

    1984-05-01

    Labeled and unlabeled aliphatic and steroid esters of gamma-amino[U-14C]butyric acid (GABA) were synthesized and tested for their capacity to penetrate the blood-brain barrier and for evidence of central neuropharmacological activity in rodents. The uptake of the labeled 9,12,15- octadecatrienyl ( linolenyl ), 3-cholesteryl, 1-butyl, and the 9-fluoro-11 beta,17-dihydroxy-16 alpha-methyl-3,20- dioxopregna -1,4-dien-21-yl (dexamethasone) esters of GABA into mouse brain increased 2-, 25-, 74-, and 81-fold over GABA, respectively. The cholesteryl ester of GABA depressed the general motor activity of mice and rats in a dose-dependent manner, whereas the 1-butyl, linolenyl , and dexamethasone esters were inactive by this test. Studies of the rates of hydrolysis, GABA receptor binding capacity, and octanol/water partition coefficients indicated that pharmacological activity of the esters after entry into the central nervous system (CNS) was dependent on their capacity to release GABA by enzymatic hydrolysis and their lipid solubility.

  15. Frightening music triggers rapid changes in brain monoamine receptors: a pilot PET study.

    Science.gov (United States)

    Zhang, Ying; Chen, Qiaozhen; Du, Fenglei; Hu, Yanni; Chao, Fangfang; Tian, Mei; Zhang, Hong

    2012-10-01

    Frightening music can rapidly arouse emotions in listeners that mimic those from actual life-threatening experiences. However, studies of the underlying mechanism for perceiving danger created by music are limited. We investigated monoamine receptor changes induced by frightening music using (11)C-N-methyl-spiperone ((11)C-NMSP) PET. Ten healthy male volunteers were included, and their psychophysiologic changes were evaluated. Compared with the baseline condition, listening to frightening music caused a significant decrease in (11)C-NMSP in the right and left caudate nuclei, right limbic region, and right paralimbic region; a particularly significant decrease in the right anterior cingulate cortex; but an increase in the right frontal occipital and left temporal lobes of the cerebral cortex. Transient fright triggers rapid changes in monoamine receptors, which decrease in the limbic and paralimbic regions but increase in the cerebral cortex.

  16. Glucose uptake by the brain on chronic high-protein weight-loss diets with either moderate or low amounts of carbohydrate.

    Science.gov (United States)

    Lobley, Gerald E; Johnstone, Alexandra M; Fyfe, Claire; Horgan, Graham W; Holtrop, Grietje; Bremner, David M; Broom, Iain; Schweiger, Lutz; Welch, Andy

    2014-02-01

    Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m², took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30% of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake. An ¹⁸fluoro-deoxyglucose positron emission tomography scan of the brain was conducted at the end of each dietary intervention period, following an overnight fast (n 4) or 4 h after consumption of a test meal (n 8). On the next day, whole-body ketone and glucose metabolism was quantified using [1,2,3,4-¹³C]acetoacetate, [2,4-¹³C]3-hydroxybutyrate and [6,6-²H₂]glucose. The composite hunger score was 14% lower (P= 0·013) for the HPLC dietary intervention than for the HPMC diet. Whole-body ketone flux was approximately 4-fold greater for the HPLC dietary intervention than for the HPMC diet (P< 0·001). The 9-fold difference in carbohydrate intakes between the HPLC and HPMC dietary interventions led to a 5% lower supply of glucose to the brain. Despite this, the uptake of glucose by the fifty-four regions of the brain analysed remained similar for the two dietary interventions. In conclusion, differences in the composite hunger score observed for the two dietary interventions are not associated with the use of alternative fuels by the brain.

  17. From Rapid to Delayed and Remote Postconditioning: the Evolving Concept of Ischemic Postconditioning in Brain Ischemia

    Science.gov (United States)

    Zhao, Heng; Ren, Chuancheng; Chen, Xingmiao; Shen, Jiangang

    2012-01-01

    Ischemic postconditioning is a concept originally defined to contrast with that of ischemic preconditioning. While both preconditioning and postconditioning confer a neuroprotective effect on brain ischemia, preconditioning is a sublethal insult performed in advance of brain ischemia, and postconditioning, which conventionally refers to a series of brief occlusions and reperfusions of the blood vessels, is conducted after ischemia/reperfusion. In this article, we first briefly review the history of preconditioning, including the experimentation that initially uncovered its neuroprotective effects and later revealed its underlying mechanisms-of-action. We then discuss how preconditioning research evolved into that of postconditioning – a concept that now represents a broad range of stimuli or triggers, including delayed postconditioning, pharmacological postconditioning, remote postconditioning – and its underlying protective mechanisms involving the Akt, MAPK, PKC and KATP channel cell-signaling pathways. Because the concept of postconditioning is so closely associated with that of preconditioning, and both share some common protective mechanisms, we also discuss whether a combination of preconditioning and postconditioning offers greater protection than preconditioning or postconditioning alone. PMID:22204317

  18. A novel and rapid method for obtaining high titre intact prion strains from mammalian brain

    Science.gov (United States)

    Wenborn, Adam; Terry, Cassandra; Gros, Nathalie; Joiner, Susan; D’Castro, Laura; Panico, Silvia; Sells, Jessica; Cronier, Sabrina; Linehan, Jacqueline M.; Brandner, Sebastian; Saibil, Helen R.; Collinge, John; Wadsworth, Jonathan D. F.

    2015-01-01

    Mammalian prions exist as multiple strains which produce characteristic and highly reproducible phenotypes in defined hosts. How this strain diversity is encoded by a protein-only agent remains one of the most interesting and challenging questions in biology with wide relevance to understanding other diseases involving the aggregation or polymerisation of misfolded host proteins. Progress in understanding mammalian prion strains has however been severely limited by the complexity and variability of the methods used for their isolation from infected tissue and no high resolution structures have yet been reported. Using high-throughput cell-based prion bioassay to re-examine prion purification from first principles we now report the isolation of prion strains to exceptional levels of purity from small quantities of infected brain and demonstrate faithful retention of biological and biochemical strain properties. The method’s effectiveness and simplicity should facilitate its wide application and expedite structural studies of prions. PMID:25950908

  19. Brain activity during bilateral rapid alternate finger tapping measured with magnetoencephalography

    Science.gov (United States)

    Fukuda, Hiroshi; Odagaki, Masato; Hiwaki, Osamu; Kodabashi, Atsushi; Fujimoto, Toshiro

    2009-04-01

    Using magnetoencephalography (MEG), brain regions involved in an alternate bimanual tapping task by index fingers triggered with spontaneous timing were investigated. The tapping mode in which both index fingers moved simultaneously was interlaced during the task. The groups of the alternate tapping (AL mode) and the simultaneous tapping (SI mode) were extracted from the successive alternating taps with a histogram of intervals between the right and left index fingers. MEG signals in each mode were averaged separately before and after the tapping initiation of the dominant index finger. The activities of the contralateral sensorimotor cortex before and after the tapping initiation in the AL mode were larger than that in the SI mode. The result indicates that the activity of the contralateral sensorimotor cortex depends on the degree of achievement in the difficult motor task such as the voluntary alternate tapping movements.

  20. Neuroactivity of detonation nanodiamonds: dose-dependent changes in transporter-mediated uptake and ambient level of excitatory/inhibitory neurotransmitters in brain nerve terminals.

    Science.gov (United States)

    Pozdnyakova, Natalia; Pastukhov, Artem; Dudarenko, Marina; Galkin, Maxim; Borysov, Arsenii; Borisova, Tatiana

    2016-03-31

    Nanodiamonds are one of the most perspective nano-sized particles with superb physical and chemical properties, which are mainly composed of carbon sp(3) structures in the core with sp(2) and disorder/defect carbons on the surface. The research team recently demonstrated neuromodulatory properties of carbon nanodots with other than nanodiamonds hybridization types, i.e., sp(2) hybridized graphene islands and diamond-like sp(3) hybridized elements. In this study, neuroactive properties of uncoated nanodiamonds produced by detonation synthesis were assessed basing on their effects on transporter-mediated uptake and the ambient level of excitatory and inhibitory neurotransmitters, glutamate and γ-aminobutyric acid (GABA), in isolated rat brain nerve terminals. It was shown that nanodiamonds in a dose-dependent manner attenuated the initial velocity of Na(+)-dependent transporter-mediated uptake and accumulation of L-[(14)C]glutamate and [(3)H]GABA by nerve terminals and increased the ambient level of these neurotransmitters. Also, nanodiamonds caused a weak reduction in acidification of synaptic vesicles and depolarization of the plasma membrane of nerve terminals. Therefore, despite different types of hybridization in nanodiamonds and carbon dots, they exhibit very similar effects on glutamate and GABA transport in nerve terminals and this common feature of both nanoparticles is presumably associated with their nanoscale size. Observed neuroactive properties of pure nanodiamonds can be used in neurotheranostics for simultaneous labeling/visualization of nerve terminals and modulation of key processes of glutamate- and GABAergic neurotransmission. In comparison with carbon dots, wider medical application involving hypo/hyperthermia, external magnetic fields, and radiolabel techniques can be perspective for nanodiamonds.

  1. Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation

    Science.gov (United States)

    Lenoir, Magalie

    2012-01-01

    Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2–6 s) increased (30–70 μM or 6–14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (−20–40 μM or 5–10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

  2. Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation.

    Science.gov (United States)

    Kiyatkin, Eugene A; Lenoir, Magalie

    2012-09-01

    Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2-6 s) increased (30-70 μM or 6-14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (-20-40 μM or 5-10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

  3. [125I]RTI-55 binding to cocaine-sensitive dopaminergic and serotonergic uptake sites in the human brain.

    Science.gov (United States)

    Little, K Y; Kirkman, J A; Carroll, F I; Breese, G R; Duncan, G E

    1993-12-01

    [125I]RTI-55 is a newly synthesized cocaine congener that may offer advantages over other ligands previously used to examine cocaine binding sites. However, the in vitro pharmacological and anatomical characterization of [125I]RTI-55 binding sites has not been previously performed in human brain. To determine the specificity, stability, and feasibility of [125I]RTI-55 for use in radioligand binding assays in postmortem human tissue, a series of experiments were performed characterizing [125I]RTI-55 binding sites in human brain using homogenized membrane preparations and quantitative autoradiography. Analysis of the association, dissociation, and saturation data favored two-phase processes. A curve-fitting analysis of the data derived in saturation experiments found a high-affinity site with KD = 66 +/- 35 pM and Bmax = 13.2 +/- 10.1 pmol/g of tissue and a low-affinity site with KD = 1.52 +/- 0.55 nM and Bmax of 47.5 +/- 11.2 pmol/g of tissue. Competition by ligands known to bind to the dopamine transporter showed a rank order of RTI-55 > GBR-12909 > maxindol > WIN 35428 > = methylphenidate > (-)-cocaine > buproprion > (+)-amphetamine. Binding to serotonergic sites was evaluated in the midbrain. Results of the saturation experiment performed autoradiographically in the midbrain showed a single site with KD = 370 +/- 84 pM. It appears that [125I]RTI-55 should be useful in further studies of the regulation of cocaine binding sites using postmortem human specimens.

  4. Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by leptin.

    Science.gov (United States)

    Pekary, A E; Sattin, Albert; Blood, James

    2010-07-23

    Leptin is not only a feedback modulator of feeding and energy expenditure but also regulates reproductive functions, CNS development and mood. Obesity and major depression are growing public health concerns which may derive, in part, from disregulation of leptin feedback at the level of the hypothalamic feeding centers and mood regulators within the limbic system. Identifying downstream mediators of leptin action may provide therapeutic opportunities. We and others have previously reported that thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) and TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) have neuroprotective, antidepressant, anti-epileptic, analeptic, anti-ataxic, and anorectic properties. For this reason, young, adult male Sprague-Dawley rats were injected ip with 1mg/kg rat leptin and peptide and protein levels were measured in brain and peripheral tissues at 0, 0.5, 1 and 2h later. Eleven brain regions: pyriform cortex (PYR), entorhinal cortex (ENT), cerebellum (CBL), nucleus accumbens (NA), frontal cortex (FCX), amygdala (AY), posterior cingulate (PCNG), striatum (STR), hippocampus (HC), medulla oblongata (MED) and anterior cingulate (ACNG) and five peripheral tissues (adrenals, testes, epididymis, pancreas and prostate) were analyzed. TRH and six TRH-like peptide levels in STR fell by 0.5h consistent with leptin-induced release of these peptides: STR (7 downward arrow). Significant changes in TRH and TRH-like peptide levels for other brain regions were: CBL (5 downward arrow), ENT (5 downward arrow), HC (4 downward arrow), AY (4 downward arrow), FCX (3 downward arrow), and ACNG (1 downward arrow). The rapid modulation of TRH and TRH-like peptide release combined with their similarity in behavioral, neuroendocrine, immunomodulatory, metabolic and steroidogenic effects to that of leptin is consistent with these peptides participating in downstream signaling. Published by Elsevier B.V.

  5. Rapid Changes in Cortical and Subcortical Brain Regions after Early Bilateral Enucleation in the Mouse.

    Directory of Open Access Journals (Sweden)

    Olga O Kozanian

    Full Text Available Functional sensory and motor areas in the developing mammalian neocortex are formed through a complex interaction of cortically intrinsic mechanisms, such as gene expression, and cortically extrinsic mechanisms such as those mediated by thalamic input from the senses. Both intrinsic and extrinsic mechanisms are believed to be involved in cortical patterning and the establishment of areal boundaries in early development; however, the nature of the interaction between intrinsic and extrinsic processes is not well understood. In a previous study, we used a perinatal bilateral enucleation mouse model to test some aspects of this interaction by reweighting sensory input to the developing cortex. Visual deprivation at birth resulted in a shift of intraneocortical connections (INCs that aligned with ectopic ephrin A5 expression in the same location ten days later at postnatal day (P 10. A prevailing question remained: Does visual deprivation first induce a change in gene expression, followed by a shift in INCs, or vice versa? In the present study, we address this question by investigating the neuroanatomy and patterns of gene expression in post-natal day (P 1 and 4 mice following bilateral enucleation at birth. Our results demonstrate a rapid reduction in dorsal lateral geniculate nucleus (dLGN size and ephrin A5 gene expression 24-hours post-enucleation, with more profound effects apparent at P4. The reduced nuclear size and diminished gene expression mirrors subtle changes in ephrin A5 expression evident in P1 and P4 enucleated neocortex, 11 and 8 days prior to natural eye opening, respectively. Somatosensory and visual INCs were indistinguishable between P1 and P4 mice bilaterally enucleated at birth, indicating that perinatal bilateral enucleation initiates a rapid change in gene expression (within one day followed by an alteration of sensory INCs later on (second postnatal week. With these results, we gain a deeper understanding of how gene

  6. Focal adhesion kinase as a mechanotransducer during rapid brain growth of the chick embryo.

    Science.gov (United States)

    Desmond, Mary E; Knepper, Janice E; DiBenedetto, Angela J; Malaugh, Elizabeth; Callejo, Sagrario; Carretero, Raquel; Alonso, Maria-Isabel; Gato, Angel

    2014-01-01

    Expansion of the hollow fluid-filled embryonic brain occurs by an increase in intraluminal pressure created by accumulation of cerebrospinal fluid (CSF). Experiments have shown a direct correlation between cavity pressure and cell proliferation within the neuroepithelium. These findings lead us to ask how mechanistically this might come about. Are there perhaps molecules on the luminal surface of the embryonic neuroepithelium, such as focal adhesion kinases (FAKs) known to respond to tension in other epithelial cells? Immunodetection using antibodies to total FAK and p-FAK was performed with subsequent confocal analysis of the pattern of their activation under normal intraluminal pressure and induced chronic pressure. Western analysis was also done to look at the amount of FAK expression, as well as its activation under these same conditions. Using immunolocalization, we have shown that FAK is present and activated on both apical and basolateral surfaces and within the cytoplasm of the neuroepithelial cells. This pattern changed profoundly when the neuroepithelium was under pressure. By Western blot, we have shown that FAK was upregulated and activated in the neuroepithelium of the embryos just after the neural tube becomes a closed pressurized system, with phosphorylation detected on the luminal instead of the basal surface, along with an increase in cell proliferation. Chronic hyper-pressure does not induce an increase in phosphorylation of FAK. In conclusion, here we show that neuroepithelial cells respond to intraluminal pressure via FAK phosphorylation on the luminal surface.

  7. A rapid lateral fluid percussion injury rodent model of traumatic brain injury and post-traumatic epilepsy.

    Science.gov (United States)

    Hameed, Mustafa Q; Goodrich, Grant S; Dhamne, Sameer C; Amandusson, Asa; Hsieh, Tsung-Hsun; Mou, Danlei; Wang, Yingpeng; Rotenberg, Alexander

    2014-05-07

    Traumatic brain injury is a leading cause of acquired epilepsy. Initially described in 1989, lateral fluid percussion injury (LFPI) has since become the most extensively used and well-characterized rodent traumatic brain injury and post-traumatic epilepsy model. Universal findings, particularly seizures that reliably develop after an initial latent period, are evident across studies from multiple laboratories. However, the LFPI procedure is a two-stage process, requiring initial surgical attachment of a skull fluid cannula and then reanesthesia for delivery of the epidural fluid pressure wave. We now describe a modification of the original technique, termed 'rapid lateral fluid percussion injury' (rLFPI), which allows for a one-stage procedure and thus shorter operating time and reduced anesthesia exposure. Anesthetized male Long-Evans rats were subjected to rLFPI through a length of plastic tubing fitted with a pipette tip cannula with a 4-mm aperture. The cannula opening was positioned over a craniectomy of slightly smaller diameter and exposed dura such that the edges of the cannula fit tightly when pressed to the skull with a micromanipulator. Fluid percussion was then delivered immediately thereafter, in the same surgery session. rLFPI resulted in nonlethal focal cortical injury in all animals. We previously demonstrated that the rLFPI procedure resulted in post-traumatic seizures and regional gliosis, but had not examined other histopathologic elements. Now, we show apoptotic cell death confined to the perilesional cortex and chronic pathologic changes such as ipsilesional ventriculomegaly that are seen in the classic model. We conclude that the rLFPI method is a viable alternative to classic LFPI, and--being a one-stage procedure--has the advantage of shorter experiment turnaround and reduced exposure to anesthetics.

  8. Positron emission tomographical studies of 1-11C-acetoacetate, 2-18F-fluoro-deoxy-D-glucose, and L-1-11C-tyrosine uptake by cat brain with an experimental lesion

    NARCIS (Netherlands)

    Prenen, G H; Go, K G; Paans, A M; Zuiderveen, F; Vaalburg, W; Kamman, R L; Molenaar, W M; Zijlstra, S; Elsinga, P H; Sebens, J B; Korf, J

    1989-01-01

    In cat brain with a freezing injury, the uptake of 1-11C-acetoacetate (11C-ACAC), 2-18F-fluorodeoxy-D-glucose (18FDG), and L-1-11C-tyrosine (11C-TYR) was monitored by positron emission tomography following intravenous administration of the tracers, at 1 day, and 1-3 weeks after the injury. The

  9. Towards the automated localisation of targets in rapid image-sifting by collaborative brain-computer interfaces.

    Directory of Open Access Journals (Sweden)

    Ana Matran-Fernandez

    Full Text Available The N2pc is a lateralised Event-Related Potential (ERP that signals a shift of attention towards the location of a potential object of interest. We propose a single-trial target-localisation collaborative Brain-Computer Interface (cBCI that exploits this ERP to automatically approximate the horizontal position of targets in aerial images. Images were presented by means of the rapid serial visual presentation technique at rates of 5, 6 and 10 Hz. We created three different cBCIs and tested a participant selection method in which groups are formed according to the similarity of participants' performance. The N2pc that is elicited in our experiments contains information about the position of the target along the horizontal axis. Moreover, combining information from multiple participants provides absolute median improvements in the area under the receiver operating characteristic curve of up to 21% (for groups of size 3 with respect to single-user BCIs. These improvements are bigger when groups are formed by participants with similar individual performance, and much of this effect can be explained using simple theoretical models. Our results suggest that BCIs for automated triaging can be improved by integrating two classification systems: one devoted to target detection and another to detect the attentional shifts associated with lateral targets.

  10. Estrogen activates rapid signaling in the brain: role of estrogen receptor alpha and estrogen receptor beta in neurons and glia.

    Science.gov (United States)

    Mhyre, A J; Dorsa, D M

    2006-01-01

    The aging process is known to coincide with a decline in circulating sex hormone levels in both men and women. Due to an increase in the average lifespan, a growing number of post-menopausal women are now receiving hormone therapy for extended periods of time. Recent findings of the Women's Health Initiative, however, have called into question the benefits of long-term hormone therapy for treating symptoms of menopause. The results of this study are still being evaluated, but it is clear that a better understanding of the molecular effects of estradiol is needed in order to develop new estrogenic compounds that activate specific mechanisms but lack adverse side effects. Traditionally, the effects of estradiol treatment have been ascribed to changes in gene expression, namely transcription at estrogen response elements. This review focuses on emerging information that estradiol can also activate a repertoire of membrane-initiated signaling pathways and that these rapid signaling events lead to functional changes at the cellular level. The various types of cells in the brain can respond differently to estradiol treatment based on the signaling properties of the cell, as well as which receptor, estrogen receptor alpha and/or estrogen receptor beta, is expressed. Taken together, these findings suggest that the estradiol-induced activation of membrane-initiated signaling pathways occurs in a cell-type specific manner and can differentially influence how the cells respond to various insults.

  11. Rapid Effects of an Aggressive Interaction on Dehydroepiandrosterone, Testosterone and Oestradiol Levels in the Male Song Sparrow Brain: a Seasonal Comparison.

    Science.gov (United States)

    Heimovics, S A; Prior, N H; Ma, C; Soma, K K

    2016-02-01

    Across vertebrates, aggression is robustly expressed during the breeding season when circulating testosterone is elevated, and testosterone activates aggression either directly or after aromatisation into 17β-oestradiol (E2 ) in the brain. In some species, such as the song sparrow, aggressive behaviour is also expressed at high levels during the nonbreeding season, when circulating testosterone is non-detectable. At this time, the androgen precursor dehydroepiandrosterone (DHEA) is metabolised within the brain into testosterone and/or E2 to promote aggression. In the present study, we used captive male song sparrows to test the hypothesis that an acute agonistic interaction during the nonbreeding season, but not during the breeding season, would alter steroid levels in the brain. Nonbreeding and breeding subjects were exposed to either a laboratory simulated territorial intrusion (L-STI) or an empty cage for only 5 min. Immediately afterwards, the brain was rapidly collected and flash frozen. The Palkovits punch technique was used to microdissect specific brain regions implicated in aggressive behaviour. Solid phase extraction followed by radioimmunoassay was used to quantify DHEA, testosterone and E2 in punches. Overall, levels of DHEA, testosterone and E2 were higher in brain tissue than in plasma. Local testosterone and E2 levels in the preoptic area, anterior hypothalamus and nucleus taeniae of the amygdala were significantly higher in the breeding season than the nonbreeding season and were not affected by the L-STI. Unexpectedly, subjects that were dominant in the L-STI had lower levels of DHEA in the anterior hypothalamus and medial striatum in both seasons and lower levels of DHEA in the nucleus taeniae of the amygdala in the breeding season only. Taken together, these data suggest that local levels of DHEA in the brain are very rapidly modulated by social interactions in a context and region-specific pattern. © 2015 British Society for

  12. Performance of a high-sensitivity dedicated cardiac SPECT scanner for striatal uptake quantification in the brain based on analysis of projection data

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi-Ae; Moore, Stephen C.; McQuaid, Sarah J.; Kijewski, Marie Foley [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts 02115 (United States); Mueller, Stefan P. [Abteilung Nuklearmedizin, Universitaetsklinikum Essen, 45147 Essen (Germany)

    2013-04-15

    Purpose: The authors have previously reported the advantages of high-sensitivity single-photon emission computed tomography (SPECT) systems for imaging structures located deep inside the brain. DaTscan (Isoflupane I-123) is a dopamine transporter (DaT) imaging agent that has shown potential for early detection of Parkinson disease (PD), as well as for monitoring progression of the disease. Realizing the full potential of DaTscan requires efficient estimation of striatal uptake from SPECT images. They have evaluated two SPECT systems, a conventional dual-head gamma camera with low-energy high-resolution collimators (conventional) and a dedicated high-sensitivity multidetector cardiac imaging system (dedicated) for imaging tasks related to PD. Methods: Cramer-Rao bounds (CRB) on precision of estimates of striatal and background activity concentrations were calculated from high-count, separate acquisitions of the compartments (right striata, left striata, background) of a striatal phantom. CRB on striatal and background activity concentration were calculated from essentially noise-free projection datasets, synthesized by scaling and summing the compartment projection datasets, for a range of total detected counts. They also calculated variances of estimates of specific-to-nonspecific binding ratios (BR) and asymmetry indices from these values using propagation of error analysis, as well as the precision of measuring changes in BR on the order of the average annual decline in early PD. Results: Under typical clinical conditions, the conventional camera detected 2 M counts while the dedicated camera detected 12 M counts. Assuming a normal BR of 5, the standard deviation of BR estimates was 0.042 and 0.021 for the conventional and dedicated system, respectively. For an 8% decrease to BR = 4.6, the signal-to-noise ratio were 6.8 (conventional) and 13.3 (dedicated); for a 5% decrease, they were 4.2 (conventional) and 8.3 (dedicated). Conclusions: This implies that PD can

  13. Barriers and Facilitators to the Uptake and Maintenance of Healthy Behaviours by People at Mid-Life: A Rapid Systematic Review

    Science.gov (United States)

    Kelly, Sarah; Martin, Steven; Kuhn, Isla; Cowan, Andy; Brayne, Carol; Lafortune, Louise

    2016-01-01

    Background With an ageing population, there is an increasing societal impact of ill health in later life. People who adopt healthy behaviours are more likely to age successfully. To engage people in health promotion initiatives in mid-life, a good understanding is needed of why people do not undertake healthy behaviours or engage in unhealthy ones. Methods Searches were conducted to identify systematic reviews and qualitative or longitudinal cohort studies that reported mid-life barriers and facilitators to healthy behaviours. Mid-life ranged from 40 to 64 years, but younger adults in disadvantaged or minority groups were also eligible to reflect potential earlier disease onset. Two reviewers independently conducted reference screening and study inclusion. Included studies were assessed for quality. Barriers and facilitators were identified and synthesised into broader themes to allow comparisons across behavioural risks. Findings From 16,426 titles reviewed, 28 qualitative studies, 11 longitudinal cohort studies and 46 systematic reviews were included. Evidence was found relating to uptake and maintenance of physical activity, diet and eating behaviours, smoking, alcohol, eye care, and other health promoting behaviours and grouped into six themes: health and quality of life, sociocultural factors, the physical environment, access, psychological factors, evidence relating to health inequalities. Most of the available evidence was from developed countries. Barriers that recur across different health behaviours include lack of time (due to family, household and occupational responsibilities), access issues (to transport, facilities and resources), financial costs, entrenched attitudes and behaviours, restrictions in the physical environment, low socioeconomic status, lack of knowledge. Facilitators include a focus on enjoyment, health benefits including healthy ageing, social support, clear messages, and integration of behaviours into lifestyle. Specific issues

  14. Barriers and Facilitators to the Uptake and Maintenance of Healthy Behaviours by People at Mid-Life: A Rapid Systematic Review.

    Directory of Open Access Journals (Sweden)

    Sarah Kelly

    Full Text Available With an ageing population, there is an increasing societal impact of ill health in later life. People who adopt healthy behaviours are more likely to age successfully. To engage people in health promotion initiatives in mid-life, a good understanding is needed of why people do not undertake healthy behaviours or engage in unhealthy ones.Searches were conducted to identify systematic reviews and qualitative or longitudinal cohort studies that reported mid-life barriers and facilitators to healthy behaviours. Mid-life ranged from 40 to 64 years, but younger adults in disadvantaged or minority groups were also eligible to reflect potential earlier disease onset. Two reviewers independently conducted reference screening and study inclusion. Included studies were assessed for quality. Barriers and facilitators were identified and synthesised into broader themes to allow comparisons across behavioural risks.From 16,426 titles reviewed, 28 qualitative studies, 11 longitudinal cohort studies and 46 systematic reviews were included. Evidence was found relating to uptake and maintenance of physical activity, diet and eating behaviours, smoking, alcohol, eye care, and other health promoting behaviours and grouped into six themes: health and quality of life, sociocultural factors, the physical environment, access, psychological factors, evidence relating to health inequalities. Most of the available evidence was from developed countries. Barriers that recur across different health behaviours include lack of time (due to family, household and occupational responsibilities, access issues (to transport, facilities and resources, financial costs, entrenched attitudes and behaviours, restrictions in the physical environment, low socioeconomic status, lack of knowledge. Facilitators include a focus on enjoyment, health benefits including healthy ageing, social support, clear messages, and integration of behaviours into lifestyle. Specific issues relating to

  15. Case report of a 28-year-old male with the rapid progression of steroid-resistant central nervous system vasculitis diagnosed by a brain biopsy.

    Science.gov (United States)

    Takahashi, Keigo; Sato, Hideki; Hattori, Hidenori; Takao, Masaki; Takahashi, Shinichi; Suzuki, Norihiro

    2017-09-30

    A 28-year-old Japanese male without a significant past medical history presented with new-onset generalized clonic seizure and headache. A brain MRI revealed multiple enhanced lesions on both cerebral hemispheres. Laboratory exams showed no evidence of systemic inflammation or auto-immune antibodies such as ANCAs. Despite four courses of high-dose methylprednisolone pulse therapy and five treatments with plasmapheresis, his symptoms worsened and the MRI lesions progressed rapidly. During these treatments, we performed a targeted brain biopsy, that revealed histological findings consistent with a predominant angiitis of parenchymal and subdural small vessels. He was provided with diagnosis of central nervous system vasculitis (CNSV). Subsequent cyclophosphamide pulse therapy enabled a progressive successful improvement of his symptoms. While diagnostic methods for CNSV remain controversial, histological findings are thought to be more useful in obtaining a more definitive diagnosis than findings in image studies, such as MRI and angiography. We suggest that a brain biopsy should be considered during the early period of cases with suspected CNSV and rapid clinical deterioration. We also detected human herpesvirus 7 (HHV-7) using PCR technology in brain biopsy specimens, however the relationship between CNSV and HHV-7 infection is unknow.

  16. Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by ghrelin and 3-TRP-ghrelin.

    Science.gov (United States)

    Pekary, A Eugene; Sattin, Albert

    2012-08-01

    Ghrelin is not only a modulator of feeding and energy expenditure but also regulates reproductive functions, CNS development and mood. Obesity and major depression are growing public health concerns which may derive, in part, from dysregulation of ghrelin feedback at brain regions regulating feeding and mood. We and others have previously reported that thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) and TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) have neuroprotective, antidepressant, anti-epileptic, analeptic, anti-ataxic, and anorectic properties. For this reason male Sprague-Dawley rats were injected ip with 0.1mg/kg rat ghrelin or 0.9mg/kg 3-Trp-rat ghrelin. Twelve brain regions: cerebellum, medulla oblongata, anterior cingulate, posterior cingulate, frontal cortex, nucleus accumbens, hypothalamus, entorhinal cortex, hippocampus, striatum, amygdala, piriform cortex and 5 peripheral tissues (adrenals, testes, epididymis, pancreas and prostate) were analyzed. Rapid and profound decreases in TRH and TRH-like peptide levels (increased release) occurred throughout brain and peripheral tissues following ip ghrelin. Because ghrelin is rapidly deacylated in vivo we also studied 3-Trp-ghrelin which cannot be deacylated. Significant increases in TRH and TRH-like peptide levels following 3-Trp-ghrelin, relative to those after ghrelin were observed in all brain regions except posterior cingulate and all peripheral tissues except prostate and testis. The rapid stimulation of TRH and TRH-like peptide release by ghrelin in contrast with the inhibition of such release by 3-Trp-TRH is consistent with TRH and TRH-like peptides modulating the downstream effects of both ghrelin and unacylated ghrelin. Published by Elsevier Inc.

  17. Coffee consumption rapidly reduces background DNA strand breaks in healthy humans: Results of a short-term repeated uptake intervention study.

    Science.gov (United States)

    Bakuradze, Tamara; Lang, Roman; Hofmann, Thomas; Schipp, Dorothea; Galan, Jens; Eisenbrand, Gerhard; Richling, Elke

    2016-03-01

    Intervention studies provide evidence that long-term coffee consumption correlates with reduced DNA background damage in healthy volunteers. Here, we report on short-term kinetics of this effect, showing a rapid onset after normal coffee intake. In a short-term human intervention study, we determined the effects of coffee intake on DNA integrity during 8 h. Healthy male subjects ingested coffee in 200 mL aliquots every second hour up to a total volume of 800 mL. Blood samples were taken at baseline, immediately before the first coffee intake and subsequently every 2 h, prior to the respective coffee intake. DNA integrity was assayed by the comet assay. The results show a significant (p coffee intake. Continued coffee intake was associated with further decrements in background DNA damage within the 8 h intervention (p coffee consumption). Repeated coffee consumption was associated with reduced background DNA strand breakage, clearly measurable as early as 2 h after first intake resulting in a cumulative overall reduction by about one-third of the baseline value. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Whole body synthesis rates of DHA from α-linolenic acid are greater than brain DHA accretion and uptake rates in adult rats[S

    OpenAIRE

    Domenichiello, Anthony F.; Chen, Chuck T; Trepanier, Marc-Olivier; Stavro, P. Mark; Richard P. Bazinet

    2014-01-01

    Docosahexaenoic acid (DHA) is important for brain function, however, the exact amount required for the brain is not agreed upon. While it is believed that the synthesis rate of DHA from α-linolenic acid (ALA) is low, how this synthesis rate compares with the amount of DHA required to maintain brain DHA levels is unknown. The objective of this work was to assess whether DHA synthesis from ALA is sufficient for the brain. To test this, rats consumed a diet low in n-3 PUFAs, or a diet containing...

  19. New rapid, accurate T2 quantification detects pathology in normal-appearing brain regions of relapsing-remitting MS patients

    Directory of Open Access Journals (Sweden)

    Timothy M. Shepherd

    2017-01-01

    Conclusions: The EMC algorithm precisely characterizes T2 values, and is able to detect subtle T2 changes in normal-appearing brain regions of RRMS patients. These presumably capture both axon and myelin changes from inflammation and neurodegeneration. Further, T2 variations between different brain regions of healthy controls may correlate with distinct nervous tissue environments that differ from one another at a mesoscopic length-scale.

  20. Cadmium uptake by the green alga Chlorella emersonii | Arikpo ...

    African Journals Online (AJOL)

    Investigations were carried out on the uptake of the heavy metal cadmium (Cd) by the green alga Chlorella emersonii with the aid of an ion selective electrode. Cadmium uptake by Chlorella was very rapid with 70% of total uptake occurring during the first 10 seconds. Uptake of cadmium by Chlorella showed a direct ...

  1. In normal rat, intraventricularly administered insulin-like growth factor-1 is rapidly cleared from CSF with limited distribution into brain

    Directory of Open Access Journals (Sweden)

    Gorevic Peter D

    2005-07-01

    Full Text Available Abstract Background Putatively active drugs are often intraventricularly administered to gain direct access to brain and circumvent the blood-brain barrier. A few studies on the normal central nervous system (CNS have shown, however, that the distribution of materials after intraventricular injections is much more limited than presumed and their exit from cerebrospinal fluid (CSF is more rapid than generally believed. In this study, we report the intracranial distribution and the clearance from CSF and adjacent CNS tissue of radiolabeled insulin-like growth factor-1 after injection into one lateral ventricle of the normal rat brain. Methods Under barbiturate anesthesia, 125I-labeled insulin-like growth factor-1 (IGF-1 was injected into one lateral ventricle of normal Sprague-Dawley rats. The subsequent distribution of IGF-1 through the cerebrospinal fluid (CSF system and into brain, cerebral blood vessels, and systemic blood was measured over time by gamma counting and quantitative autoradiography (QAR. Results Within 5 min of infusion, IGF-1 had spread from the infused lateral ventricle into and through the third and fourth ventricles. At this time, 25% of the infused IGF-1 had disappeared from the CSF-brain-meningeal system; the half time of this loss was 12 min. The plasma concentration of cleared IGF-1 was, however, very low from 2 to 9 min and only began to rise markedly after 20 min. This delay between loss and gain plus the lack of radiotracer in the cortical subarachnoid space suggested that much of the IGF-1 was cleared into blood via the cranial and/or spinal nerve roots and their associated lymphatic systems rather than periventricular tissue and arachnoid villi. Less than 10% of the injected radioactivity remained in the CSF-brain system after 180 min. The CSF and arteries and arterioles within the subarachnoid cisterns were labeled with IGF-1 within 10 min. Between 60 and 180 min, most of the radioactivity within the cranium was

  2. Kinetics of the uptake and distribution of the dopamine D{sub 2,3} agonist (R)-N-[1-{sup 11}C]n-propylnorapomorphine in brain of healthy and MPTP-treated Goettingen miniature pigs

    Energy Technology Data Exchange (ETDEWEB)

    Cumming, Paul E-mail: paul@pet.auh.dk; Gillings, Nic M.; Jensen, Svend B.; Bjarkam, Carsten; Gjedde, Albert

    2003-05-01

    The binding of radioligand agonists to dopamine receptors in living brain can be informative about the abundance of receptors which are coupled to intracellular second messenger systems. Therefore, we developed a radiosynthesis for the dopamine D{sub 2,3} partial agonist (R)-N- [1-{sup 11}C]n-propylnorapomorphine ([{sup 11}C]NPA). The uptake of this tracer in brain of anesthetized Goettingen miniature pigs was recorded by positron emission tomography (PET) and analyzed by compartmental analysis using the metabolite-corrected arterial input, and using reference tissue methods. [{sup 11}C]NPA had a blood-brain unidirectional clearance of approximately 0.35 ml g{sup -1} min{sup -1} and an apparent distribution volume of 6 ml g{sup -1} in cerebellum. The ligand had a binding potential of 1.5 in striatum, comparable to that reported previously for the receptor antagonist [{sup 11}C]raclopride in the same strain of animals. Significant binding was detected in the hypophysis, thalamus, and medial forebrain bundle. The binding in striatum was of comparable magnitude in normal pigs and in pigs with a documented 50% dopamine depletion produced by MPTP-intoxication. Deep brain stimulation of the subthalamus was without conspicuous effect on the binding of [{sup 11}C]NPA in vivo. Results of this preliminary study indicate that this tracer meets many requirements for assaying dopamine agonist binding sites by PET.

  3. Evidence for low molecular weight, non-transferrin-bound iron in rat brain and cerebrospinal fluid

    DEFF Research Database (Denmark)

    Moos, Torben; Morgan, Evan H.

    1998-01-01

    Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake......Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake...

  4. Methodology for Rapid Measures of Glutamate Release in Rat Brain Slices Using Ceramic-Based Microelectrode Arrays: Basic Characterization and Drug Pharmacology

    Science.gov (United States)

    Quintero, Jorge E.; Pomerleau, François; Huettl, Peter; Johnson, Kirk W.; Offord, James; Gerhardt, Greg A.

    2011-01-01

    Excessive excitability or hyperexcitability of glutamate-containing neurons in the brain has been proposed as a possible explanation for anxiety, stress-induced disorders, epilepsy, and some neurodegenerative diseases. However, direct measurement of glutamate on a rapid time scale has proven to be difficult. Here we adapted enzyme-based microelectrode arrays (MEA) capable of detecting glutamate in vivo, to assess the effectiveness of hyperexcitability modulators on glutamate release in brain slices of the rat neocortex. Using glutamate oxidase coated ceramic MEAs coupled with constant voltage amperometry, we measured resting glutamate levels and synaptic overflow of glutamate after K+ stimulation in brain slices. MEAs reproducibly detected glutamate on a second-by-second time scale in the brain slice preparation after depolarization with high K+ to evoke glutamate release. This stimulus-evoked glutamate release was robust, reproducible, and calcium dependent. The K+-evoked glutamate release was modulated by ligands to the a2δ subunit of voltage sensitive calcium channels (PD-0332334 and PD-0200390). Meanwhile, agonists to Group II metabotropic glutamate (mGlu) receptors (LY379268 and LY354740), which are known to alter hyperexcitability of glutamate neurons, attenuated K+-evoked glutamate release but did not alter resting glutamate levels. This new MEA technology provides a means of directly measuring the chemical messengers involved in glutamate neurotransmission and thereby helping to reveal the role multiple glutamatergic system components have on glutamate signaling. PMID:21664606

  5. EEG Bands of Wakeful Rest, Slow-Wave and Rapid-Eye-Movement Sleep at Different Brain Areas in Rats

    Directory of Open Access Journals (Sweden)

    Jing Wei

    2016-08-01

    Full Text Available Accumulating evidences have revealed that neuronal oscillations with various frequency bands in the brain have different physiological functions. However, the frequency band divisions in rats were typically based on empirical spectral distribution from limited channels information. In the present study, functionally relevant frequency bands across vigilance states and brain regions were identified using factor analysis based on 9 channels EEG signals recorded from multiple brain areas in rats. We found that frequency band divisions varied both across vigilance states and brain regions. In particular, theta oscillations during REM sleep were subdivided into two bands, 5-7 and 8-11 Hz corresponding to the tonic and phasic stages, respectively. The spindle activities of SWS are different along the anterior-posterior axis, lower oscillations (~16 Hz in frontal regions and higher in parietal (~21 Hz. The delta and theta activities were co-varied in the visual and auditory cortex during wakeful rest. In addition, power spectra of beta oscillations were significantly decreased in association cortex. These results provide us some new insights into understand the brain oscillations across vigilance states, and also indicate that the spatial factor should not be ignored when considering the frequency band divisions in rats.

  6. Rapid high-resolution three-dimensional mapping of T1 and age-dependent variations in the non-human primate brain using magnetization-prepared rapid gradient-echo (MPRAGE) sequence

    Science.gov (United States)

    Liu, Junjie V.; Bock, Nicholas A.; Silva, Afonso C.

    2011-01-01

    The use of quantitative T1 mapping in neuroscience and neurology has raised strong interest in the development of T1-mapping techniques that can measure T1 in the whole brain, with high accuracy and precision and within short imaging and computation times. Here, we present a new inversion-recovery (IR) based T1-mapping method using a standard 3D magnetization-prepared rapid gradient-echo (MPRAGE) sequence. By varying only the inversion time (TI), but keeping other parameters constant, MPRAGE image signals become linear to exp(−TI/T1), allowing for accurate T1 estimation without flip angle correction. We also show that acquiring data at just 3 TIs, with the three different TI values optimized, gives maximum T1 precision per unit time, allowing for new efficient approaches to measure and compute T1. We demonstrate the use of our method at 7 Tesla to obtain 3D T1 maps of the whole brain in common marmosets at 0.60 mm resolution and within 11 minutes. T1 maps from the same individuals were highly reproducible across different days. Across subjects, the peak of cerebral gray matter T1 distribution was 1735±52 ms, and the lower edge of cerebral white matter T1 distribution was 1270±43 ms. We found a significant decrease of T1 in both gray and white matter of the marmoset brain with age over a span of 14 years, in agreement with previous human studies. This application illustrates that MPRAGE-based 3D T1 mapping is rapid, accurate and precise, and can facilitate high-resolution anatomical studies in neuroscience and neurological diseases. PMID:21376814

  7. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  8. Thyroid Scan and Uptake

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  9. The Origins of Word Learning: Brain Responses of 3-Month-Olds Indicate Their Rapid Association of Objects and Words

    Science.gov (United States)

    Friedrich, Manuela; Friederici, Angela D.

    2017-01-01

    The present study explored the origins of word learning in early infancy. Using event-related potentials (ERP) we monitored the brain activity of 3-month-old infants when they were repeatedly exposed to several initially novel words paired consistently with each the same initially novel objects or inconsistently with different objects. Our results…

  10. A Novel Procedure for Rapid Imaging of Adult Mouse Brains with MicroCT Using Iodine-Based Contrast.

    Directory of Open Access Journals (Sweden)

    Ryan Anderson

    Full Text Available High-resolution Magnetic Resonance Imaging (MRI has been the primary modality for obtaining 3D cross-sectional anatomical information in animals for soft tissue, particularly brain. However, costs associated with MRI can be considerably high for large phenotypic screens for gross differences in the structure of the brain due to pathology and/or experimental manipulations. MicroCT (mCT, especially benchtop mCT, is becoming a common laboratory equipment with throughput rates equal or faster than any form of high-resolution MRI at lower costs. Here we explore adapting previously developed contrast based mCT to image adult mouse brains in-situ. We show that 2% weight per volume (w/v iodine-potassium iodide solution can be successfully used to image adult mouse brains within 48 hours post-mortem when a structural support matrix is used. We demonstrate that hydrogel can be effectively used as a perfusant which limits the tissue shrinkage due to iodine.

  11. New rapid, accurate T2 quantification detects pathology in normal-appearing brain regions of relapsing-remitting MS patients.

    Science.gov (United States)

    Shepherd, Timothy M; Kirov, Ivan I; Charlson, Erik; Bruno, Mary; Babb, James; Sodickson, Daniel K; Ben-Eliezer, Noam

    2017-01-01

    Quantitative T2 mapping may provide an objective biomarker for occult nervous tissue pathology in relapsing-remitting multiple sclerosis (RRMS). We applied a novel echo modulation curve (EMC) algorithm to identify T2 changes in normal-appearing brain regions of subjects with RRMS (N = 27) compared to age-matched controls (N = 38). The EMC algorithm uses Bloch simulations to model T2 decay curves in multi-spin-echo MRI sequences, independent of scanner, and scan-settings. T2 values were extracted from normal-appearing white and gray matter brain regions using both expert manual regions-of-interest and user-independent FreeSurfer segmentation. Compared to conventional exponential T2 modeling, EMC fitting provided more accurate estimations of T2 with less variance across scans, MRI systems, and healthy individuals. Thalamic T2 was increased 8.5% in RRMS subjects (p brain regions of RRMS patients. These presumably capture both axon and myelin changes from inflammation and neurodegeneration. Further, T2 variations between different brain regions of healthy controls may correlate with distinct nervous tissue environments that differ from one another at a mesoscopic length-scale.

  12. Functional characterization of mouse organic anion transporting peptide 1a4 in the uptake and efflux of drugs across the blood-brain barrier.

    Science.gov (United States)

    Ose, Atsushi; Kusuhara, Hiroyuki; Endo, Chihiro; Tohyama, Kimio; Miyajima, Mari; Kitamura, Satoshi; Sugiyama, Yuichi

    2010-01-01

    This study investigated the role of a multispecific organic anion transporter, Oatp1a4/Slco1a4, in drug transport across the blood-brain barrier. In vitro transport studies using human embryonic kidney 293 cells expressing mouse Oatp1a4 identified the following compounds as Oatp1a4 substrates: pitavastatin (K(m) = 8.3 microM), rosuvastatin (K(m) = 12 microM), pravastatin, taurocholate (K(m) = 40 microM), digoxin, ochratoxin A, and [d-penicillamine(2,5)]-enkephalin. Double immunohistochemical staining of Oatp1a4 with P-glycoprotein (P-gp) or glial fibrillary acidic protein demonstrated that Oatp1a4 signals colocalized with P-gp signals partly but not with glial fibrillary acidic protein, suggesting that Oatp1a4 is expressed in both the luminal and the abluminal membranes of mouse brain capillary endothelial cells. The brain-to-blood transport of pitavastatin, rosuvastatin, pravastatin, and taurocholate after microinjection into the cerebral cortex was significantly decreased in Oatp1a4(-/-) mice compared with that in wild-type mice. The blood-to-brain transport of pitavastatin, rosuvastatin, taurocholate, and ochratoxin A, determined by in situ brain perfusion, was significantly lower in Oatp1a4(-/-) mice than in wild-type mice, whereas transport of pravastatin and [D-penicillamine(2,5)]-enkephalin was unchanged. The blood-to-brain transport of digoxin was significantly lower in Oatp1a4(-/-) mice than in wild-type mice only when P-gp was inhibited by N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918). Taken together, these results show that Oatp1a4 can mediate the brain-to-blood and blood-to-brain transport of its substrate drugs across the blood-brain barrier. The brain-to-plasma ratio of taurocholate, pitavastatin, and rosuvastatin was close to the capillary volume in wild-type mice, and it was not affected by Oatp1a4 dysfunction. Whether Oatp1a4 can deliver drugs from the blood

  13. Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by prazosin.

    Science.gov (United States)

    Sattin, Albert; Pekary, Albert Eugene; Blood, James

    2011-08-01

    Hyperresponsiveness to norepinephrine contributes to post-traumatic stress disorder (PTSD). Prazosin, a brain-active blocker of α(1)-adrenoceptors, originally used for the treatment of hypertension, has been reported to alleviate trauma nightmares, sleep disturbance and improve global clinical status in war veterans with PTSD. Thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) may play a role in the pathophysiology and treatment of neuropsychiatric disorders such as major depression, and PTSD (an anxiety disorder). To investigate whether TRH or TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) participate in the therapeutic effects of prazosin, male rats were injected with prazosin and these peptides then measured in brain and endocrine tissues. Prazosin stimulated TRH and TRH-like peptide release in those tissues with high α(1)-adrenoceptor levels suggesting that these peptides may play a role in the therapeutic effects of prazosin. Published by Elsevier Inc.

  14. Improving uptake and use of malaria rapid diagnostic tests in the context of artemisinin drug resistance containment in eastern Myanmar: an evaluation of incentive schemes among informal private healthcare providers.

    Science.gov (United States)

    Aung, Tin; White, Christopher; Montagu, Dominic; McFarland, Willi; Hlaing, Thaung; Khin, Hnin Su Su; San, Aung Kyaw; Briegleb, Christina; Chen, Ingrid; Sudhinaraset, May

    2015-03-06

    As efforts to contain artemisinin resistance and eliminate Plasmodium falciparum intensify, the accurate diagnosis and prompt effective treatment of malaria are increasingly needed in Myanmar and the Greater Mekong Sub-region (GMS). Rapid diagnostic tests (RDTs) have been shown to be safe, feasible, and effective at promoting appropriate treatment for suspected malaria, which are of particular importance to drug resistance containment. The informal private sector is often the first point of care for fever cases in malaria endemic areas across Myanmar and the GMS, but there is little published information about informal private provider practices, quality of service provision, or potential to contribute to malaria control and elimination efforts. This study tested different incentives to increase RDT use and improve the quality of care among informal private healthcare providers in Myanmar. The study randomized six townships in the Mon and Shan states of rural Myanmar into three intervention arms: 1) RDT price subsidies, 2) price subsidies with product-related financial incentives, and 3) price subsidies with intensified information, education and counselling (IEC). The study assessed the uptake of RDT use in the communities by cross-sectional surveys of 3,150 households at baseline and six months post-intervention (6,400 households total, 832 fever cases). The study also used mystery clients among 171 providers to assess quality of service provision across intervention arms. The pilot intervention trained over 600 informal private healthcare providers. The study found a price subsidy with intensified IEC, resulted in the highest uptake of RDTs in the community, as compared to subsidies alone or merchandise-related financial incentives. Moreover, intensified IEC led to improvements in the quality of care, with mystery client surveys showing almost double the number of correct treatment following diagnostic test results as compared to a simple subsidy. Results show

  15. In vitro and in vivo evidence for active brain uptake of the GHB analogue HOCPCA by the monocarboxylate transporter subtype 1

    DEFF Research Database (Denmark)

    Thiesen, Louise; Kehler, Jan; Clausen, Rasmus P

    2015-01-01

    γ-Hydroxybutyric acid (GHB) is a recreational drug, a clinically prescribed drug in narcolepsy and alcohol dependence, and an endogenous substance which binds to both high and low affinity sites in the brain. For studying the molecular mechanisms and the biological role of the GHB high-affinity b......γ-Hydroxybutyric acid (GHB) is a recreational drug, a clinically prescribed drug in narcolepsy and alcohol dependence, and an endogenous substance which binds to both high and low affinity sites in the brain. For studying the molecular mechanisms and the biological role of the GHB high...

  16. Synthesis, brain uptake, and pharmacological properties of a glyceryl lipid containing GABA and the GABA-T inhibitor gamma-vinyl-GABA.

    Science.gov (United States)

    Jacob, J N; Hesse, G W; Shashoua, V E

    1990-02-01

    1-O-Linolenoyl-2-O-(4-aminobutyryl)-3-O-(4-vinyl-4-aminobutyryl)glycerol (LGV) was synthesized as an example of a prodrug which readily penetrates the blood-brain barrier (brain penetration index 97% +/- 15%) and releases two active substances in the central nervous system (CNS): GABA (4-aminobutanoic acid) and the GABA transaminase inhibitor (GABA-T) of GABA breakdown. In vitro studies showed that the compound can inhibit GABA-T after hydrolysis by CNS esterases and that it enhanced GABAergic inhibition when applied to rat hippocampus slices. In vivo studies indicate that LGV depresses the spontaneous locomotor activity of mice. Its activity on a molar basis was some 300 times greater than that of gamma-vinyl-GABA.

  17. Effect of prolonged 5-hydroxytryptamine uptake inhibition by paroxetine on cortical. beta. sub 1 and. beta. sub 2 -adrenoceptors in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, D.R.; Palmer, K.J.; Johnson, A.M. (SmithKline Beecham Pharmaceuticals, Essex (England))

    1990-01-01

    The effects of prolonged oral administration of the antidepressants paroxetine and amitriptyline on rat brain cortical {beta}{sub 1}- and {beta}{sub 2}-adrenoceptor numbers and affinities were investigated using ({sup 3}H)-CGP 12177. Although amitriptyline, 27 mg/kg, caused a significant 20% reduction in the number of {beta}{sub 1}-adrenoceptors, paroxetine, at does up to 8.9 mg/kg p.o., did not influence binding of ({sup 3}H)-CGP 12177 to cortical {beta}{sub 1}- or {beta}{sub 2}-adrenoceptors. This study with paroxetine provides further evidence that the down-regulation of central {beta}{sub 1}-adrenoceptors in rat brain after repeated administration is not a property of all antidepressant drugs.

  18. Induced unilateral vocal fold paralysis and recovery rapidly modulate brain areas related to phonatory behavior: a case study.

    Science.gov (United States)

    Joshi, Ashwini; Jiang, Yang; Stemple, Joseph C; Archer, Sanford M; Andreatta, Richard D

    2011-03-01

    Peripheral and behavioral effects of voice disorders are well documented in the literature; yet, there is little information regarding the central neural biomarkers and mechanisms underlying these disorders. Understanding the details of brain function changes in disordered voice production is a critical factor for developing better treatment strategies that result in more robust patient outcomes. To examine a model of induced unilateral vocal fold paralysis (iUVFP) to demonstrate and characterize the form of activity changes within central mappings of the larynx to the induced paralysis. The induced paralysis model allowed the participant to serve as his or her own control when comparing baseline results of normal voice with results during the paralysis and subsequent recovery. Prospective, case-study design. Functional magnetic resonance imaging was used to examine central laryngeal representations during three time points: pre-iUVFP, during iUVFP, and postrecovery from iUVFP. iUVFP was induced using a lidocaine with epinephrine nerve block unilaterally. Percent changes in blood oxygenation level-dependent (BOLD) activity served as the dependent variable. Results indicated an overall reduced activity level in sensorimotor, subcortical, and cerebellar regions during paralysis. Recovery from paralysis led to augmented responses, particularly in sensory, association, and cerebellar zones. The decrease in activity during iUVFP and the significantly increased activity during the recovery phase likely represent immediate neuroplastic events occurring within minutes of nerve blockade. Recovery-related changes in the BOLD response are hypothesized to be associated with a recalibration of the system after return of normal laryngeal function. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  19. [[sup 11]C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with PET

    Energy Technology Data Exchange (ETDEWEB)

    Suehiro, M.; Scheffel, U.; Ravert, H.T.; Dannals, R.F.; Wagner, H.N. Jr. (The Johns Hopkins Medical Institutions, Baltimore, MD (United States))

    1993-01-01

    The in vivo behavior of the stereoisomers of [[sup 11]C]McN5652, a highly potent serotonin (5-HT) uptake blocker, was determined to evaluate their utility as radiotracers for imaging 5-HT uptake sites by positron emission tomography (PET). After intravenous injection into mice, [[sup 11]C](+)MnN5652 showed markedly higher uptake and longer retention in regions with high density of 5-HT uptake sites than the [[sup 11]C]-labeled racemic mixture, while [[sup 11]C]([minus])McN5652 washed out rapidly. With the [[sup 11]C](+)-enantiomer, the ratio between hypothalamus and cerebellum reached 6 at 90 minutes. The binding of [[sup 11]C](+)McN5652 was inhibited by 45-73% by pre-injection of 5 mg/kg of paroxetine, a selective 5-HT uptake blocker, in all regions examined except cerebellum where no significant effect of the drug was observed. [[sup 11]C]([minus])McN5652 showed no specific binding in any of the regions. The [[sup 11]C]-labeled cis isomer, [[sup 11]C]McN5655, revealed surprisingly low brain penetration and showed no significantly higher uptake in regions of interest than cerebellum. These results suggest that [[sup 11]C](+)McN56542 is a promising candidate as a PET radiotracer for studying 5-HT uptake sites in vivo.

  20. Glycoblotting method allows for rapid and efficient glycome profiling of human Alzheimer's disease brain, serum and cerebrospinal fluid towards potential biomarker discovery.

    Science.gov (United States)

    Gizaw, Solomon T; Ohashi, Tetsu; Tanaka, Masakazu; Hinou, Hiroshi; Nishimura, Shin-Ichiro

    2016-08-01

    Understanding of the significance of posttranslational glycosylation in Alzheimer's disease (AD) is of growing importance for the investigation of the pathogenesis of AD as well as discovery research of the disease-specific serum biomarkers. We designed a standard protocol for the glycoblotting combined with MALDI-TOFMS to perform rapid and quantitative profiling of the glycan parts of glycoproteins (N-glycans) and glycosphingolipids (GSLs) using human AD's post-mortem samples such as brain tissues (dissected cerebral cortices such as frontal, parietal, occipital, and temporal domains), serum and cerebrospinal fluid (CSF). The structural profiles of the major N-glycans released from glycoproteins and the total expression levels of the glycans were found to be mostly similar between the brain tissues of the AD patients and those of the normal control group. In contrast, the expression levels of the serum and CSF protein N-glycans such as bisect-type and multiply branched glycoforms were increased significantly in AD patient group. In addition, the levels of some gangliosides such as GM1, GM2 and GM3 appeared to alter in the AD patient brain and serum samples when compared with the normal control groups. Alteration of the expression levels of major N- and GSL-glycans in human brain tissues, serum and CSF of AD patients can be monitored quantitatively by means of the glycoblotting-based standard protocols. The changes in the expression levels of the glycans derived from the human post-mortem samples uncovered by the standardized glycoblotting method provides potential serum biomarkers in central nervous system disorders and can contribute to the insight into the molecular mechanisms in the pathogenesis of neurodegenerative diseases and future drug discovery. Most importantly, the present preliminary trials using human post-mortem samples of AD patients suggest that large-scale serum glycomics cohort by means of various-types of human AD patients as well as the normal

  1. Rapid eye movement sleep loss induces neuronal apoptosis in the rat brain by noradrenaline acting on alpha 1-adrenoceptor and by triggering mitochondrial intrinsic pathway

    Directory of Open Access Journals (Sweden)

    Bindu I Somarajan

    2016-03-01

    Full Text Available Many neurodegenerative disorders are associated with rapid eye movement sleep (REMS-loss, however the mechanism was unknown. As REMS-loss elevates noradrenaline (NA level in the brain as well as induces neuronal apoptosis and degeneration, in this study we have delineated the intracellular molecular pathway involved in REMS deprivation (REMSD associated NA-induced neuronal apoptosis. Rats were REMS deprived for 6 days by the classical flower-pot method, suitable controls were conducted and the effects on apoptosis markers evaluated. Further, the role of NA was studied by one, intraperitoneal (i.p. injection of NA-ergic alpha1-adrenoceptor antagonist prazosin (PRZ and two, by down-regulation of NA synthesis in locus coeruleus (LC neurons by local microinjection of tyrosine hydroxylase siRNA (TH-siRNA. Immunoblot estimates showed that the expressions of pro-apoptotic proteins viz. Bcl2-associated death promoter (BAD protein, apoptotic protease activating factor-1 (Apaf-1, cytochrome c, caspase9, caspase3 were elevated in the REMS-deprived rat brains, while caspase8 level remained unaffected; PRZ treatment did not allow elevation of these pro-apoptotic factors. Further, REMSD increased cytochrome c expression, which was prevented if the NA synthesis from the LC neurons was blocked by microinjection of TH-siRNA in vivo into the LC during REMSD in freely moving normal rats. Mitochondrial damage was re-confirmed by transmission electron microscopy (TEM, which showed distinctly swollen mitochondria with disintegrated cristae, chromosomal condensation and clumping along the nuclear membrane and all these changes were prevented in PRZ treated rats. Combining findings of this study along with earlier reports we propose that upon REMSD NA level increases in the brain as the LC NA-ergic REM-OFF neurons do not cease firing and TH is up-regulated in those neurons. This elevated NA acting on alpha1-adrenoceptors damages mitochondria causing release of

  2. Correlation of 18F-fluoroethyl tyrosine positron-emission tomography uptake values and histomorphological findings by stereotactic serial biopsy in newly diagnosed brain tumors using a refined software tool

    Directory of Open Access Journals (Sweden)

    Lopez WO

    2015-12-01

    Full Text Available William Omar Contreras Lopez,1,2 Joacir Graciolli Cordeiro,1 Ulrich Albicker,3 Soroush Doostkam,4 Guido Nikkhah,1,5 Robert D Kirch,6 Michael Trippel,1 Thomas Reithmeier1,7 1Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Freiburg im Breisgau, Germany; 2Division of Functional Neurosurgery, Department of Neurology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil; 3Inomed, Emmendingen, 4Department of Neuropathology, University Medical Center Freiburg, Freiburg im Breisgau, 5Department of Neurosurgery, University Clinic Erlangen, Erlangen, 6Neuroelectronic Systems, Department of Neurosurgery, University Medical Center Freiburg, Freiburg im Breisgau, 7Department of Neurosurgery, Schwabing Academic Teaching Hospital of Technical University and Ludwig Maximilian University of Munich, Munich, Germany Background: Magnetic resonance imaging (MRI is the standard neuroimaging method to diagnose neoplastic brain lesions, as well as to perform stereotactic biopsy surgical planning. MRI has the advantage of providing structural anatomical details with high sensitivity, though histological specificity is limited. Although combining MRI with other imaging modalities, such as positron-emission tomography (PET, has proven to increment specificity, exact correlation between PET threshold uptake ratios (URs and histological diagnosis and grading has not yet been described.Objectives: The aim of this study was to correlate exactly the histopathological criteria of the biopsy site to its PET uptake value with high spatial resolution (mm3, and to analyze the diagnostic value of PET using the amino acid O-(2-[18F]fluoroethyl-L-tyrosine (18F-FET PET in patients with newly diagnosed brain lesions in comparison to histological findings obtained from stereotactic serial biopsy.Patients and methods: A total of 23 adult patients with newly diagnosed brain tumors on MRI were enrolled in this study

  3. Tc-99m-bicisate (ECD)-brain-SPECT in rapidly progressive dementia; Hirn-SPECT mit Tc-99m-Bicisat (ECD) bei rasch progredientem dementiellen Syndrom

    Energy Technology Data Exchange (ETDEWEB)

    Marienhagen, J.; Eilles, C. [Regensburg Univ. (Germany). Abt. fuer Nuklearmedizin; Weingaertner, U.; Blaha, L. [Bezirkskrankenhaus Mainkofen (Germany). Psychiatrische Klinik; Zerr, I.; Poser, S. [Goettingen Univ. (Germany). Klinik und Poliklinik fuer Neurologie

    1999-07-01

    We present a 61-year-old male patient with progressive dementia. A brain SPECT with Tc-99m-bicisate was performed for confirmation of clinically suspected Alzheimer-dementia. At the time of the SPECT-investigation marked apraxia and aphasia besides severe dementia were present. Electrophysiological as well as anatomical neuroimaging findings showed non-diagnostic alterations. SPECT revealed distinct perfusion defects, which made Alzheimer Dementia unlikely. The further course of the patient was determined by rapidly progressive deterioration with development of akinetic mutism. Thereafter, increased levels of neuron-specific enolase as well as 14-3-3 proteins were found in the cerebro-spinal fluid (CSF). The patient finally died with signs of cerebral decortication. Due to the clinical course and the CSF-findings the patient's final diagnosis was Creutzfeld-Jakob-disease, nevertheless no autopsy was performed. The presented case report underscores the clinical utility of perfusion brain SPECT in the differential diagnosis of dementias. (orig.) [German] Wir berichten ueber einen 61jaehrigen Patienten mit progredientem dementiellen Syndrom, der unter der Verdachtsdiagnose einer Demenz vom Alzheimer-Typ (DAT) zur Hirn-SPECT-Untersuchung mit TC-99m-Bicisat (ECD) vorgestellt wurde. Zum Untersuchungszeitpunkt bestanden neben dem Vollbild einer Demenz eine ausgepraegte Apraxie und Aphasie bei unspezifischen Veraenderungen im EEG sowie der neuroradiologischen Bildgebung. In der Hirn-SPECT-Untersuchung fanden sich fuer eine DAT untypische ausgedehnte, vorwiegend rechtshemisphaerische Perfusionsstoerungen. Im weiteren Verlauf rasche Progredienz des Krankheitsbildes mit Entwicklung eines akinetischen Mutismus sowie Nachweis erhoehter Werte der neuronspezifischen Enolase und des 14-3-3-Proteins im Liquor. Der Patient verstarb schliesslich unter dem Bild einer Decortication. Aufgrund des klinischen Verlaufs sowie der Liquorbefunde wurde, da eine autoptische Befundsicherung

  4. Kinetics of 11C-labeled opiates in the brain of rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Hartvig, P.; Bergstroem, K.; Lindberg, B.; Lundberg, P.O.; Lundqvist, H.; Langstroem, B.; Svaerd, H.; Rane, A.

    1984-07-01

    The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.

  5. Brain perfusion studies in the evaluation of acute neurologic abnormalities.

    Science.gov (United States)

    Zuckier, Lionel S; Sogbein, O O

    2013-03-01

    Two categories of single-photon radiopharmaceuticals for brain perfusion exist, nonlipophilic and lipophilic compounds. The former are useful in performing simple flow examinations which today have application primarily in the determination of brain death. The latter also exhibit a parenchymal uptake phase that allows for evaluation of the distribution of blood flow within the brain. The lipophilic radiopharmaceuticals, therefore, have application in the evaluation of patients following catastrophic brain injury and traumatic brain injury (TBI) and in prognosticating the outcome following cerebral vascular accidents. Use of these agents to monitor therapy with thrombolytic agents, although theoretically helpful, is technically difficult due to the need to institute treatment rapidly, without undue delay. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Teilum, Maria; Wieloch, Tadeusz

    2007-01-01

    The genomic response following brain ischemia is very complex and involves activation of both protective and detrimental signaling pathways. Immediate early genes (IEGs) represent the first wave of gene expression following ischemia and are induced in extensive regions of the ischemic brain...... including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated...... at 0-6 h of reperfusion for Neuritin and 0-12 h of reperfusion for Arc while BDNF was induced 0-9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part...

  7. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... code: Phone no: Thank you! Do you have a personal story about radiology? Share your patient story ...

  8. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... known as a thyroid uptake. It is a measurement of thyroid function, but does not involve imaging. ... eating can affect the accuracy of the uptake measurement. Jewelry and other metallic accessories should be left ...

  9. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... limitations of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... top of page What are some common uses of the procedure? The thyroid scan is used to ...

  10. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... of page What are some common uses of the procedure? The thyroid scan is used to determine ...

  11. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... taking our brief survey: Survey Do you have a personal story about radiology? Share your patient story ...

  12. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... the limitations of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid ... body converts food to energy. top of page What are some common uses of the procedure? The ...

  13. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... Uptake? A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) ... of thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that ...

  14. Labeled Putrescine as a Probe in Brain Tumors

    Science.gov (United States)

    Volkow, Nora; Goldman, Stephen S.; Flamm, Eugene S.; Cravioto, Humberto; Wolf, Alfred P.; Brodie, Jonathan D.

    1983-08-01

    The polyamine metabolism of transplanted N-nitrosomethylurea-derived rat glioma was determined with radiolabeled putrescine used as a marker for malignancy. The uptake of putrescine in vivo was complete within 5 minutes and was specific for tumor tissue. The conversion of putrescine to spermine and other metabolites by the tumor was rapid, in contrast to the case for adjacent normal brain. These results suggest that putrescine labeled with carbon-11 may be used as a positron-emission tomographic tracer for the selective metabolic imaging of brain tumor and may be used in an appropriate model as a marker for tumor growth rate.

  15. Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function

    Directory of Open Access Journals (Sweden)

    Zhang Rui

    2011-10-01

    Full Text Available Abstract Background Homeobox genes are the key regulators during development, and they are in general highly conserved with only a few reported cases of rapid evolution. RHOXF2 is an X-linked homeobox gene in primates. It is highly expressed in the testicle and may play an important role in spermatogenesis. As male reproductive system is often the target of natural and/or sexual selection during evolution, in this study, we aim to dissect the pattern of molecular evolution of RHOXF2 in primates and its potential functional consequence. Results We studied sequences and copy number variation of RHOXF2 in humans and 16 nonhuman primate species as well as the expression patterns in human, chimpanzee, white-browed gibbon and rhesus macaque. The gene copy number analysis showed that there had been parallel gene duplications/losses in multiple primate lineages. Our evidence suggests that 11 nonhuman primate species have one RHOXF2 copy, and two copies are present in humans and four Old World monkey species, and at least 6 copies in chimpanzees. Further analysis indicated that the gene duplications in primates had likely been mediated by endogenous retrovirus (ERV sequences flanking the gene regions. In striking contrast to non-human primates, humans appear to have homogenized their two RHOXF2 copies by the ERV-mediated non-allelic recombination mechanism. Coding sequence and phylogenetic analysis suggested multi-lineage strong positive selection on RHOXF2 during primate evolution, especially during the origins of humans and chimpanzees. All the 8 coding region polymorphic sites in human populations are non-synonymous, implying on-going selection. Gene expression analysis demonstrated that besides the preferential expression in the reproductive system, RHOXF2 is also expressed in the brain. The quantitative data suggests expression pattern divergence among primate species. Conclusions RHOXF2 is a fast-evolving homeobox gene in primates. The rapid

  16. Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function.

    Science.gov (United States)

    Niu, Ao-lei; Wang, Yin-qiu; Zhang, Hui; Liao, Cheng-hong; Wang, Jin-kai; Zhang, Rui; Che, Jun; Su, Bing

    2011-10-12

    Homeobox genes are the key regulators during development, and they are in general highly conserved with only a few reported cases of rapid evolution. RHOXF2 is an X-linked homeobox gene in primates. It is highly expressed in the testicle and may play an important role in spermatogenesis. As male reproductive system is often the target of natural and/or sexual selection during evolution, in this study, we aim to dissect the pattern of molecular evolution of RHOXF2 in primates and its potential functional consequence. We studied sequences and copy number variation of RHOXF2 in humans and 16 nonhuman primate species as well as the expression patterns in human, chimpanzee, white-browed gibbon and rhesus macaque. The gene copy number analysis showed that there had been parallel gene duplications/losses in multiple primate lineages. Our evidence suggests that 11 nonhuman primate species have one RHOXF2 copy, and two copies are present in humans and four Old World monkey species, and at least 6 copies in chimpanzees. Further analysis indicated that the gene duplications in primates had likely been mediated by endogenous retrovirus (ERV) sequences flanking the gene regions. In striking contrast to non-human primates, humans appear to have homogenized their two RHOXF2 copies by the ERV-mediated non-allelic recombination mechanism. Coding sequence and phylogenetic analysis suggested multi-lineage strong positive selection on RHOXF2 during primate evolution, especially during the origins of humans and chimpanzees. All the 8 coding region polymorphic sites in human populations are non-synonymous, implying on-going selection. Gene expression analysis demonstrated that besides the preferential expression in the reproductive system, RHOXF2 is also expressed in the brain. The quantitative data suggests expression pattern divergence among primate species. RHOXF2 is a fast-evolving homeobox gene in primates. The rapid evolution and copy number changes of RHOXF2 had been driven by

  17. Lactate uptake against a concentration gradient

    DEFF Research Database (Denmark)

    Nordström, Carl-Henrik; Nielsen, Troels Halfeld; Nielsen, Hans Boye

    2014-01-01

    The recently published article by Jalloh et al (Jalloh I, Helmy A, Shannon RJ, Gallagher CN, Menon D, Carpenter K, Hutchinson P. Lactate uptake by the injured human brain - evidence from an arterio-venous gradient and cerebral microdialysis study. J Neurotrauma. 2013 Aug 22. [Epub ahead of print...

  18. Measuring the serotonin uptake site using (/sup 3/H)paroxetine--a new serotonin uptake inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Gleiter, C.H.; Nutt, D.J.

    1988-01-01

    Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand.

  19. The inflammatory molecules IL-1β and HMGB1 can rapidly enhance focal seizure generation in a brain slice model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Angela eChiavegato

    2014-06-01

    Full Text Available Epilepsy is a neurological disorder characterized by a hyperexcitable brain tissue and unpredictable seizures, i.e., aberrant firing discharges in large neuronal populations. It is well established that proinflammatory cytokines, in addition to their canonical involvement in the immune response, have a crucial role in the mechanism of seizure generation. The purpose of the present study was to investigate the role of interleukin-1β (IL-1β and high mobility group B1 (HMGB1 in the generation of seizure-like discharges using two models of focal epilepsy in a rat entorhinal cortex slice preparation. Seizure like-discharges were evoked by either slice perfusion with low Mg2+ and picrotoxin or with a double NMDA local stimulation in the presence of the proconvulsant 4-amino-pyridine. The effects of IL-1β or HMGB1 were evaluated by monitoring seizure discharge generation through laser scanning microscope imaging of Ca2+ signals from neurons and astrocytes. In the picrotoxin model, we revealed that both cytokines increased the mean frequency of spontaneous ictal-like discharges, whereas only IL-1β reduced the latency and prolonged the duration of the first ictal-like event. In the second model, a single NMDA pulse, per se ineffective, became successful when it was performed after IL-β or HMGB1 local applications. These findings demonstrate that both IL-1β and HMGB1 can rapidly lower focal ictal event threshold and strengthen the possibility that targeting these inflammatory pathways may represent an effective therapeutic strategy to prevent seizures.

  20. Study on the relation of brain functional connectivity to movement disorders and cognitive impairment in patients with rapid eye movement sleep behavior disorder

    Directory of Open Access Journals (Sweden)

    Hong-ju ZHANG

    2017-09-01

    Full Text Available Objective To explore the relation between abnormal functional connectivity of substantia nigra and impairment of movement and cognition in patients with rapid eye movement sleep behavior disorder (RBD. Methods A total of 22 subjects, including 14 patients with RBD and 8 sex, age, education-matched healthy controls, were enrolled in this study according to international diagnostic criteria. Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ and Hoehn-Yahr Stage were used to evaluate motor function. Digit Ordering Test - Attention (DOT - A, Symbol Digit Modalities Test (SDMT, Stroop Color-Word Test (SCWT, Trail Making Test (TMT, Rey-Osterrieth Complex Figure Test (ROCFT, Clock Drawing Test (CDT, Boston Naming Test (BNT and Auditory Verbal Learning Test (AVLT were used to evaluate cognitive function. The functional connectivity from left and right substantia nigra to brain region were examined. Results There were no statistical differences of UPDRSⅢ and Hoehn?Yahr Stage between 2 groups (P > 0.05, for all. In comparison with control group, SDMT (P = 0.001, ROCFT-copy (P = 0.013 and AVLT-N2 (P = 0.032 were significantly lower, while TMT-B test was significantly higher (P =0.005 in RBD group. Compared with control group, the functional connectivity of right substantia nigra to left precentral gyrus (P < 0.005 and right angular gyrus (P < 0.005 were all decreased in RBD group. Conclusions The results suggest that cognitive impairment occurs earlier than movement disorders in RBD, and there are abnormal functional connectivity from right substantia nigra to left precentral gyrus and right angular gyrus, proving that abnormal functional connectivity is the base of behavior disorders in RBD. DOI: 10.3969/j.issn.1672-6731.2017.09.005

  1. Phosphate Uptake by Phosphate-Starved Euglena

    Science.gov (United States)

    BLUM, J. J.

    1966-01-01

    Phosphate-deprived Euglena acquire the ability to rapidly in-corporate added phosphate and, also, synthesize an induced acid phosphatase localized in the pellicle. The phosphate uptake system is saturated at low concentrations of phosphate and is inhibited by dinitrophenol, by low temperature, by K+, Li+, and Na+ ions, and competitively by arsenate. The orthophosphate incorporated into the cell is rapidly converted into organic forms but enough remains unesterified to suggest that the uptake is an active transport process. The data do not rule out the possibility that the induced phosphatase is involved in the transport process. PMID:5924104

  2. Brain pharmacokinetics of ganciclovir in rats with orthotopic BT4C glioma.

    Science.gov (United States)

    Gynther, Mikko; Kääriäinen, Tiina M; Hakkarainen, Jenni J; Jalkanen, Aaro J; Petsalo, Aleksanteri; Lehtonen, Marko; Peura, Lauri; Kurkipuro, Jere; Samaranayake, Haritha; Ylä-Herttuala, Seppo; Rautio, Jarkko; Forsberg, Markus M

    2015-01-01

    Ganciclovir (GCV) is an essential part of the Herpes simplex virus thymidine kinase (HSV-tk) gene therapy of malignant gliomas. The purpose of this study was to investigate the brain pharmacokinetics and tumor uptake of GCV in the BT4C rat glioma model. GCV's brain and tumor uptakes were investigated by in vivo microdialysis in rats with orthotopic BT4C glioma. In addition, the ability of GCV to cross the blood-brain barrier and tumor vasculature was assessed with in situ rat brain perfusion. Finally, the extent to which GCV could permeate across the BT4C glioma cell membrane was assessed in vitro. The areas under the concentration curve of unbound GCV in blood, brain extracellular fluid (ECF), and tumor ECF were 6157, 1658, and 4834 μM⋅min, respectively. The apparent maximum unbound concentrations achieved within 60 minutes were 46.9, 11.8, and 25.8 μM in blood, brain, and tumor, respectively. The unbound GCV concentrations in brain and tumor after in situ rat brain perfusion were 0.41 and 1.39 nmol/g, respectively. The highly polar GCV likely crosses the fenestrated tumor vasculature by paracellular diffusion. Thus, GCV is able to reach the extracellular space around the tumor at higher concentrations than that in healthy brain. However, GCV uptake into BT4C cells at 100 μM was only 2.1 pmol/mg of protein, and no active transporter-mediated disposition of GCV could be detected in vitro. In conclusion, the limited efficacy of HSV-tk/GCV gene therapy may be due to the poor cellular uptake and rapid elimination of GCV. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Effects of transport inhibitors on the cellular uptake of carboxylated polystyrene nanoparticles in different cell lines.

    Directory of Open Access Journals (Sweden)

    Tiago dos Santos

    Full Text Available Nanotechnology is expected to play a vital role in the rapidly developing field of nanomedicine, creating innovative solutions and therapies for currently untreatable diseases, and providing new tools for various biomedical applications, such as drug delivery and gene therapy. In order to optimize the efficacy of nanoparticle (NP delivery to cells, it is necessary to understand the mechanisms by which NPs are internalized by cells, as this will likely determine their ultimate sub-cellular fate and localisation. Here we have used pharmacological inhibitors of some of the major endocytic pathways to investigate nanoparticle uptake mechanisms in a range of representative human cell lines, including HeLa (cervical cancer, A549 (lung carcinoma and 1321N1 (brain astrocytoma. Chlorpromazine and genistein were used to inhibit clathrin and caveolin mediated endocytosis, respectively. Cytochalasin A and nocodazole were used to inhibit, respectively, the polymerisation of actin and microtubule cytoskeleton. Uptake experiments were performed systematically across the different cell lines, using carboxylated polystyrene NPs of 40 nm and 200 nm diameters, as model NPs of sizes comparable to typical endocytic cargoes. The results clearly indicated that, in all cases and cell types, NPs entered cells via active energy dependent processes. NP uptake in HeLa and 1321N1 cells was strongly affected by actin depolymerisation, while A549 cells showed a stronger inhibition of NP uptake (in comparison to the other cell types after microtubule disruption and treatment with genistein. A strong reduction of NP uptake was observed after chlorpromazine treatment only in the case of 1321N1 cells. These outcomes suggested that the same NP might exploit different uptake mechanisms to enter different cell types.

  4. Uptake of 4-Toluene Sulfonate by Comamonas testosteroni T-2

    NARCIS (Netherlands)

    LOCHER, HH; POOLMAN, B; COOK, AM; KONINGS, WN

    The mechanism of transport of the xenobiotic 4-toluene sulfonate (TS) in Comamonas testosteroni T-2 was investigated. Rapid uptake of TS was observed only in cells grown with TS or 4-methylbenzoate as a carbon and energy source. Initial uptake rates under aerobic conditions showed substrate

  5. Thyroid Scan and Uptake

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    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician ... of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is also known as a thyroid uptake. ...

  6. Thyroid Scan and Uptake

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    Full Text Available ... A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is also known as a thyroid uptake. ... a patient’s immediate response to therapeutic interventions. Nuclear ... medical tests that help physicians diagnose and evaluate medical conditions. ...

  7. Thyroid Scan and Uptake

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    Full Text Available ... 24 hours later. Often, two separate uptake measurements are obtained at different times. For example, you may have uptake measurements at ... of exposing the fetus to radiation. These tests are also not recommended for ... medicine procedures can be time consuming. It can take several hours to days ...

  8. Actin filament-associated protein 1 (AFAP-1) is a key mediator in inflammatory signaling-induced rapid attenuation of intrinsic P-gp function in human brain capillary endothelial cells.

    Science.gov (United States)

    Hoshi, Yutaro; Uchida, Yasuo; Tachikawa, Masanori; Ohtsuki, Sumio; Terasaki, Tetsuya

    2017-04-01

    The purpose of this study was to identify regulatory molecule(s) involved in the inflammatory signaling-induced decrease in P-glycoprotein (P-gp) efflux function at the blood-brain barrier (BBB) that may occur in brain diseases. We confirmed that in vivo P-gp efflux activity at the BBB was decreased without any change in P-gp protein expression level in a mouse model of acute inflammation induced by 3 mg/kg lipopolysaccharide. In a human BBB model cell line (human brain capillary endothelial cells; hCMEC/D3), 1-h treatment with 10 ng/mL tumor necrosis factor-α (TNF-α; an inflammatory mediator) rapidly reduced P-gp efflux activity, but had no effect on P-gp protein expression level. To clarify the non-transcriptional mechanism that causes the decrease in intrinsic efflux activity of P-gp in acute inflammation, we applied comprehensive quantitative phosphoproteomics to compare hCMEC/D3 cells treated with TNF-α and vehicle (control). Actin filament-associated protein-1 (AFAP-1), MAPK1, and transcription factor AP-1 (AP-1) were significantly phosphorylated in TNF-α-treated cells, and were selected as candidate proteins. In validation experiments, knockdown of AFAP-1 expression blocked the reduction in P-gp efflux activity by TNF-α treatment, whereas inhibition of MAPK function or knockdown of AP-1 expression did not. Quantitative targeted absolute proteomics revealed that the reduction in P-gp activity by TNF-α did not require any change in P-gp protein expression levels in the plasma membrane. Our results demonstrate that AFAP-1 is a key mediator in the inflammatory signaling-induced, translocation-independent rapid attenuation of P-gp efflux activity in human brain capillary endothelial cells. © 2017 International Society for Neurochemistry.

  9. Lactate fuels the human brain during exercise

    DEFF Research Database (Denmark)

    Quistorff, Bjørn; Secher, Niels H; Van Lieshout, Johannes J

    2008-01-01

    lactate in proportion to the arterial concentration. Cerebral lactate uptake, together with glucose uptake, is larger than the uptake accounted for by the concomitant O(2) uptake, as reflected by the decrease in cerebral metabolic ratio (CMR) [the cerebral molar uptake ratio O(2)/(glucose+(1/2) lactate...... blockade but not with beta(1)-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a beta(2)-adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood-brain barrier. The pattern of CMR decrease under various forms of brain activation...

  10. [Axolemmal transporters for neurotransmitter uptake].

    Science.gov (United States)

    García-López, M

    Neurotransmission is a fundamental process in interneuronal communication. It starts with the release of the neurotransmitter following a nerve impulse and ends either by uptake by specific specific transporters or by metabolization to an inactive compound. In this review we will consider the molecular, ion dependence and electrogenic properties of the axolemal transporters for neurotransmitters and also the pathological consequences of their impairment as well as the drugs that can interact with them. Most axolemmal transporters have been cloned and grouped into two large families according to their molecular characteristics and electrogenic properties: 1. Those dependent on Na+/Cl- include transporters of GABA, noradrenaline, dopamine, serotonin, choline, proline, betaine, glycine and taurine, and 2. Those dependent on Na+/K+, which include the transporters of glutamate, alanine, serine and cysteine. The clonation of transporters has permitted (and will continue to permit) the correlation of molecular alterations of transporters with different neuro-degenerative disorders (e.g. multiple sclerosis, Parkinson's disease, Alzheimer's disease), with brain lesions (e.g. cerebral ischemia, status epilepticus) and with psychiatric alterations (e.g. schizophrenia, depression). In this respect, chemical synthesis of new selective drugs which interact with the different systems for uptake of neurotransmitters will offer new approaches to the treatment of many disorders of the central nervous system which still have no satisfactory drug treatment.

  11. Thyroid Scan and Uptake

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    Full Text Available ... for the imaging to begin, you will lie down on a moveable examination table with your head ... each thyroid uptake is five minutes or less. top of page What will I experience during and ...

  12. Thyroid Scan and Uptake

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    Full Text Available ... for several hours before your exam because eating can affect the accuracy of the uptake measurement. Jewelry ... small hand-held device resembling a microphone that can detect and measure the amount of the radiotracer ...

  13. Thyroid Scan and Uptake

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    Full Text Available ... is taken by mouth, in either liquid or capsule form, it is typically swallowed up to 24 ... I-123 or I-131) in liquid or capsule form to swallow. The thyroid uptake will begin ...

  14. Thyroid Scan and Uptake

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    Full Text Available ... scan and uptake uses small amounts of radioactive materials called radiotracers, a special camera and a computer ... last two months that used iodine-based contrast material. Your doctor will instruct you on how to ...

  15. Thyroid Scan and Uptake

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    Full Text Available ... Actual scanning time for each thyroid uptake is five minutes or less. top of page What will ... diagnostic procedures have been used for more than five decades, and there are no known long-term ...

  16. Thyroid Scan and Uptake

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    Full Text Available ... A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is ... thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that uses ...

  17. Thyroid Scan and Uptake

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    Full Text Available ... several hours before your exam because eating can affect the accuracy of the uptake measurement. Jewelry and ... often unattainable using other imaging procedures. For many diseases, nuclear medicine scans yield the most useful information ...

  18. Thyroid Scan and Uptake

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    Full Text Available ... RAIU) is also known as a thyroid uptake. It is a measurement of thyroid function, but does ... they offer the potential to identify disease in its earliest stages as well as a patient’s immediate ...

  19. Thyroid Scan and Uptake

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    Full Text Available ... Because nuclear medicine procedures are able to pinpoint molecular activity within the body, they offer the potential ... or imaging device that produces pictures and provides molecular information. The thyroid scan and thyroid uptake provide ...

  20. Thyroid Scan and Uptake

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    Full Text Available ... information about your thyroid’s size, shape, position and function that is often unattainable using other imaging procedures. ... thyroid uptake. It is a measurement of thyroid function, but does not involve imaging. Nuclear medicine is ...

  1. Thyroid Scan and Uptake

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    Full Text Available ... scan and thyroid uptake provide information about the structure and function of the thyroid. The thyroid is ... computer, create pictures offering details on both the structure and function of organs and tissues in your ...

  2. Thyroid Scan and Uptake

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    Full Text Available ... procedures within the last two months that used iodine-based contrast material. Your doctor will instruct you ... a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is also known as a ...

  3. Thyroid Scan and Uptake

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    Full Text Available ... eat for several hours before your exam because eating can affect the accuracy of the uptake measurement. ... often unattainable using other imaging procedures. For many diseases, nuclear medicine scans yield the most useful information ...

  4. Thyroid Scan and Uptake

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    Full Text Available ... When radiotracer is taken by mouth, in either liquid or capsule form, it is typically swallowed up ... radioactive iodine (I-123 or I-131) in liquid or capsule form to swallow. The thyroid uptake ...

  5. Thyroid Scan and Uptake

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    Full Text Available ... nuclear medicine include the gamma camera and single-photon emission-computed tomography (SPECT). The gamma camera, also ... to 24 hours later. Often, two separate uptake measurements are obtained at different times. For example, you ...

  6. Initial fate of prions upon peripheral infection: half-life, distribution, clearance, and tissue uptake

    Science.gov (United States)

    Urayama, Akihiko; Morales, Rodrigo; Niehoff, Michael L.; Banks, William A.; Soto, Claudio

    2011-01-01

    Prion diseases are infectious neurodegenerative disorders associated with the misfolded prion protein (PrPSc), which appears to be the sole component of the infectious agent (termed prion). To produce disease, prions have to be absorbed into the body and reach sufficient quantities in the brain. Very little is known about the biological mechanisms controlling the initial fate of prions. Here, we studied the systemic pharmacokinetics and biodistribution of PrPSc in vivo. After an intravenous injection of highly purified radiolabeled or native unlabeled PrPSc, the protein was eliminated rapidly from the serum (half-life of 3.24 h), mostly through tissue uptake. The quantity of intact PrPSc reaching the brain was ∼0.2% of the injected dose per gram of brain tissue (ID/g). The highest levels were found in liver (∼20% ID/g), spleen (∼13% ID/g), and kidney (∼7.4% ID/g). Cell surface PrPC does not appear to play a role in PrPSc pharmacokinetics, since the infectious protein distributed similarly in wild-type and PrP-null mice. To measure tissue uptake kinetics and biodistribution accurately, vascular space in tissues was measured with radioactively labeled albumin coinjected with radioactively labeled PrPSc. Our results provide a fundamental pharmacokinetic characterization of PrPSc in vivo, which may be relevant to estimate tissue risks and mechanisms of prion neuroinvasion and to identify novel therapeutic strategies.—Urayama, A., Morales, R., Niehoff, M. L., Banks, W. A., Soto, C. Initial fate of prions upon peripheral infection: half-life, distribution, clearance, and tissue uptake PMID:21555356

  7. Who among patients with acquired brain injury returned to work after occupational rehabilitation? : The rapid-return-to-work-cohort-study

    NARCIS (Netherlands)

    Aas, R.W.; Haveraaen, L.A.; Brouwers, E.P.M.; Skarpaas, L.S.

    2017-01-01

    Acquired brain injury (ABI) is known to be severely disabling. On average, 40% of employeesreturn to work (RTW) within two years after injury. There is, however, limited research on what might con-tribute to successful RTW. To examine factors that might impact the time-to first RTW for patients with

  8. Dopamine D1 receptor imaging in the rodent and primate brain using the isoquinoline (+)-[{sup 11}C]A-69024 and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Besret, L.; Herard, A.S.; Guillermier, M.; Hantraye, P. [CNRS, URA 2210, F-91406 Orsay (France); Dolle, F.; Demphel, S.; Hinnen, F.; Coulon, C.; Ottaviani, M.; Bottlaender, M. [CEA, DSV, I2BM, SHFJ, Lab Imagerie Mol Expt, F-91406 Orsay (France); Herard, A.S.; Guillermier, M.; Hantraye, P. [CEA, DSV, I2BM, Mol Imaging Res Ctr, F-92265 Fontenay Aux Roses (France); Kassiou, M. [Univ Sydney, Discipline Med Radiat Sci, Sydney, NSW 2006 (Australia); Kassiou, M. [Univ Sydney, Brain and Mind Res Inst, Sydney, NSW 2050 (Australia); Kassiou, M. [Univ Sydney, Sch Chem, Sydney, NSW 2006 (Australia)

    2008-07-01

    In vivo pharmacokinetic and brain binding characteristics of (+)-[{sup 11}C]A-69024, a high-affinity-D1-selective dopamine receptor antagonist, were assessed with micro-PET and {beta}-microprobes in the rat and PET in the baboon. The biodistribution of (+)-[{sup 11}C]A-69024 in rats and baboons showed a rapid brain uptake (reaching a maximal value at 5 and 15 min postinjection in rats and baboons, respectively), followed by a slow wash out. The region/cerebellum concentration ratio was characterized by a fourfold higher uptake in striatum and a twofold higher uptake in cortical regions, consistent with in vivo specific binding of the radiotracer in these cerebral regions. Furthermore, this specific (+)-[{sup 11}C]A-69024 binding significantly correlated with the reported in vitro distribution of dopamine D1-receptors. Finally, the specific uptake of the tracer in the striatum and cortical regions was completely prevented by either a pretreatment with large doses of nonradioactive {+-}A-69024 or of the D1-selective antagonist SCH23390, resulting in a similar uptake in the reference region (cerebellum) and in other brain regions. Thus, (+)-[{sup 11}C]A-69024 appears to be a specific and enantioselective radioligand to visualize and quantify brain dopamine D1 receptors in vivo using positron emission tomography. (authors)

  9. Effect of Human Saliva on Glucose Uptake by Streptococcus mutans and Other Oral Microorganisms

    OpenAIRE

    Germaine, Greg R.; Tellefson, Lois M.

    1981-01-01

    We examined the effects of human whole salivary supernatant and parotid fluid on glucose uptake by Streptococcus mutans, Streptococcus sanguis, Streptococcus mitis, Actinomyces viscosus, Staphylococcus aureus, and Escherichia coli. The following three effects of saliva were observed: (i) inhibition of glucose uptake (S. mutans, S. sanguis), (ii) promotion of a transient, rapid (0 to 30 s) burst of glucose uptake (S. mutans, S. sanguis), and (iii) enhancement of glucose uptake (S. mitis, A. vi...

  10. Large-scale brain functional modularity is reflected in slow electroencephalographic rhythms across the human non-rapid eye movement sleep cycle.

    Science.gov (United States)

    Tagliazucchi, Enzo; von Wegner, Frederic; Morzelewski, Astrid; Brodbeck, Verena; Borisov, Sergey; Jahnke, Kolja; Laufs, Helmut

    2013-04-15

    Large-scale brain functional networks (measured with functional magnetic resonance imaging, fMRI) are organized into separated but interacting modules, an architecture supporting the integration of distinct dynamical processes. In this work we study how the aforementioned modular architecture changes with the progressive loss of vigilance occurring in the descent to deep sleep and we examine the relationship between the ensuing slow electroencephalographic rhythms and large-scale network modularity as measured with fMRI. Graph theoretical methods are used to analyze functional connectivity graphs obtained from fifty-five participants at wakefulness, light and deep sleep. Network modularity (a measure of functional segregation) was found to increase during deeper sleep stages but not in light sleep. By endowing functional networks with dynamical properties, we found a direct link between increased electroencephalographic (EEG) delta power (1-4 Hz) and a breakdown of inter-modular connectivity. Both EEG slowing and increased network modularity were found to quickly decrease during awakenings from deep sleep to wakefulness, in a highly coordinated fashion. Studying the modular structure itself by means of a permutation test, we revealed different module memberships when deep sleep was compared to wakefulness. Analysis of node roles in the modular structure revealed an increase in the number of locally well-connected nodes and a decrease in the number of globally well-connected hubs, which hinders interactions between separated functional modules. Our results reveal a well-defined sequence of changes in brain modular organization occurring during the descent to sleep and establish a close parallel between modularity alterations in large-scale functional networks (accessible through whole brain fMRI recordings) and the slowing of scalp oscillations (visible on EEG). The observed re-arrangement of connectivity might play an important role in the processes underlying loss

  11. Who among patients with acquired brain injury returned to work after occupational rehabilitation? The rapid-return-to-work-cohort-study.

    Science.gov (United States)

    Aas, Randi Wågø; Haveraaen, Lise Aasen; Brouwers, Evelien P M; Skarpaas, Lisebet Skeie

    2017-07-20

    Acquired brain injury (ABI) is known to be severely disabling. On average, 40% of employees return to work (RTW) within two years after injury. There is, however, limited research on what might contribute to successful RTW. To examine factors that might impact the time-to first RTW for patients with ABI, participating in a RTW-program. The study was designed as a cohort study of patients on sick leave due to mild or moderate ABI (n = 137). The mean age of the patients was 51 years, and 58% were men. The most common diagnoses were stroke (75%) and traumatic brain injury (12%). Data were collected through questionnaires, and combined with register data on sickness absence. Survival analyses were used to analyse the effect of different variables on time to first RTW (full or partial), at one- and two-year follow-up. Generally, women (HR = 0.447; CI: 0.239-0.283) had higher RTW-rates than men, and patients with non-comorbid impairments returned to work earlier than patients with multiple impairments. Although not statistically significant, receiving individual consultations and participating in group-sessions were generally associated with a delayed RTW at both follow-up-times. The only service-related factor significantly associated with delayed RTW was meetings with the social insurance office (HR = 0.522; CI: 0.282-0.965), and only at one-year follow-up. Women and patients with non-comorbid impairments returned to work earlier than men and patients with multiple impairments. There seems to be an association between intense and long-lasting participation in the RTW program and prolonged time-to first-RTW, even after controlling for level of cognitive impairments and comorbidity. Implications for Rehabilitation Acquired brain injury (ABI) is known to be severely disabling, and persons with ABI often experience difficulties in regard to returning to work. This study provides information on prognostic factors that might contribute to return to work (RTW

  12. Rapid modulation of TRH and TRH-like peptide release in rat brain, pancreas, and testis by a GSK-3beta inhibitor.

    Science.gov (United States)

    Pekary, Albert Eugene; Stevens, Schetema A; Blood, James D; Sattin, Albert

    2010-06-01

    Antidepressants have been shown to be neuroprotective and able to reverse damage to glia and neurons. Thyrotropin-releasing hormone (TRH) is an endogenous antidepressant-like neuropeptide that reduces the expression of glycogen synthase kinase-3beta (GSK-3beta), an enzyme that hyperphosphorylates tau and is implicated in bipolar disorder, diabetes and Alzheimer's disease. In order to understand the potential role of GSK-3beta in the modulation of depression by TRH and TRH-like peptides and the therapeutic potential of GSK-3beta inhibitors for neuropsychiatric and metabolic diseases, young adult male Sprague-Dawley (SD) rats were (a) injected ip with 1.8mg/kg of GSK-3beta inhibitor VIII (GSKI) and sacrificed 0, 2, 4, 6, and 8h later or (b) injected with 0, 0.018, 0.18 or 1.8mg/kg GSKI and bled 4h later. Levels of TRH and TRH-like peptides were measured in various brain regions involved in mood regulation, pancreas and reproductive tissues. Large, 3-15-fold, increases of TRH and TRH-like peptide levels in cerebellum, for example, as well as other brain regions were noted at 2 and 4h. In contrast, a nearly complete loss of TRH and TRH-like peptides from testis within 2h and pancreas by 4h following GSKI injection was observed. We have previously reported similar acute effects of corticosterone in brain and peripheral tissues. Incubation of a decapsulated rat testis with either GSKI or corticosterone accelerated release of TRH, and TRH-like peptides. Glucocorticoids, via inhibition of GSK3-beta activity, may thus be involved in the inhibition of TRH and TRH-like peptide release in brain, thereby contributing to the depressogenic effect of this class of steroids. Corticosterone-induced acceleration of release of these peptides from testis may contribute to the decline in reproductive function and redirection of energy needed during life-threatening emergencies. These contrasting effects of glucocorticoid on peptide release appear to be mediated by GSK-3beta. Published

  13. Thyroid Scan and Uptake

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    Full Text Available ... probe counter used for thyroid uptake exams. The patient sits with the camera directed at the neck for five minutes, and then the leg for ... Medicine Head and Neck Cancer Treatment Radioactive Iodine (I-131) Therapy Head and ...

  14. Thyroid Scan and Uptake

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    Full Text Available ... of page Additional Information and Resources RTAnswers.org Radiation Therapy for Head and Neck Cancer top of page ... and Neck Cancer Treatment Radioactive Iodine (I-131) Therapy Head and Neck Cancer X-ray, Interventional Radiology and Nuclear ... to Thyroid Scan and Uptake ...

  15. Thyroid Scan and Uptake

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    Full Text Available ... type your comment or suggestion into the following text box: Comment: E-mail: Area code: Phone no: ... of a typical probe counter used for thyroid uptake exams. The patient sits with the camera directed at the neck for five minutes, and then the leg for ...

  16. Thyroid Scan and Uptake

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    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake ...

  17. Imaging of Brain Tumors with Copper-64 Chloride: Early Experience and Results.

    Science.gov (United States)

    Panichelli, Paola; Villano, Carlo; Cistaro, Angelina; Bruno, Andrea; Barbato, Francesco; Piccardo, Arnoldo; Duatti, Adriano

    2016-06-01

    To conduct the first investigational study that is aimed at evaluating the ability of the simple salt (64)CuCl2 to diagnose cerebral tumors in patients affected by glioblastoma multiforme (GBM). Nineteen patients with a documented history and radiologic evidence of brain tumors were enrolled in the study. Eighteen patients were diagnosed with GBM, and one patient was diagnosed with grade II astrocytoma. After initial cerebral magnetic resonance imaging (MRI), patients were administered with (64)CuCl2 (13 MBq/kg) and brain positron emission tomography (PET)/computed tomography (CT) imaging was performed at 1, 3, and 24 hours after administration. Standardized uptake values (SUVs) were calculated and used to figure out the pharmacokinetic profile of the tracer. Absorbed radiation doses were estimated using OLINDA/EXM. Copper-64 chloride clearly visualized brain cancerous lesions within 1 hour after injection, with stable retention of radioactivity at 3 and 24 hours. Excellent agreement was found between PET/CT and MRI. No uptake of the tracer was observed in low-grade astrocytoma. The agent cleared rapidly from the blood and was mostly excreted through the liver, without significant kidney washout. Analysis of time variation of SUVmax values showed persistent uptake in malignant tissues with a slight increase of radioactive concentration at 24 hours. Copper-64 chloride has favorable biological properties for brain imaging and warrants further investigation as a diagnostic tracer for GBM.

  18. B and C types natriuretic peptides modulate norepinephrine uptake and release in the rat hypothalamus.

    Science.gov (United States)

    Vatta, M S; Presas, M; Bianciotti, L G; Zarrabeitia, V; Fernández, B E

    1996-09-16

    We previously reported that atrial natriuretic factor (ANF) regulates catecholamine metabolism in the central nervous system. ANF, B and C types natriuretic peptides (BNP and CNP) also play a regulatory role in body fluid homeostasis, cardiovascular activity and hormonal and neuro-hormonal secretions. The aim of the present work was to investigate BNP and CNP effects on the uptake and release of norepinephrine (NE) in rat hypothalamic slices incubated in vitro. Results showed that BNP (100 nM) and CNP (1, 10 and 100 nM) enhanced total and neuronal [3H]NE uptake but did not modify non-neuronal uptake. BNP (100 nM) and CNP (1 nM) caused a rapid increase in NE uptake (1 min), which was sustained for 60 min. BNP (100 nM) did not modify the intracellular distribution of NE; however, 1 nM CNP increased the granular store and decreased the cytosolic pool of NE. BNP (100 nM) and CNP (1, 10 and 100 nM), diminished spontaneous NE release. In addition, BNP (1, 10, 100 nM) and CNP (1, 10 and 100 pM, as well as 1, 10 and 100 nM) reduced NE output induced by 25 mM KCl. These results suggest that BNP and CNP may be involved in the regulation of several central as well as peripheral physiological functions through the modulation of noradrenergic neurotransmission at the presynaptic neuronal level. Present results provide evidence to consider CNP as the brain natriuretic peptide since physiological concentrations of this peptide (pM) diminished NE evoked release.

  19. Imaging brain development: the adolescent brain.

    Science.gov (United States)

    Blakemore, Sarah-Jayne

    2012-06-01

    The past 15 years have seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. The First Six Years of Building and Implementing a Return-to-Work Service for Patients with Acquired Brain Injury. The Rapid-Return-to-Work-Cohort-Study.

    Science.gov (United States)

    Haveraaen, L; Brouwers, E P M; Sveen, U; Skarpaas, L S; Sagvaag, H; Aas, R W

    2017-12-01

    Background and objective Despite large activity worldwide in building and implementing new return-to-work (RTW) services, few studies have focused on how such implementation processes develop. The aim of this study was to examine the development in patient and service characteristics the first six years of implementing a RTW service for persons with acquired brain injury (ABI). Methods The study was designed as a cohort study (n=189). Data were collected by questionnaires, filled out by the service providers. The material was divided into, and analyzed with, two implementation phases. Non-parametrical statistical methods and hierarchical regression analyses were applied on the material. Results The number of patients increased significantly, and the patient group became more homogeneous. Both the duration of the service, and the number of consultations and group session days were significantly reduced. Conclusion The patient group became more homogenous, but also significantly larger during the first six years of building the RTW service. At the same time, the duration of the service decreased. This study therefore questions if there is a lack of consensus on the intensity of work rehabilitation for this group.

  1. P-glycoprotein function at the blood-brain barrier imaged using 11C-N-desmethyl-loperamide in monkeys.

    Science.gov (United States)

    Liow, Jeih-San; Kreisl, William; Zoghbi, Sami S; Lazarova, Neva; Seneca, Nicholas; Gladding, Robert L; Taku, Andrew; Herscovitch, Peter; Pike, Victor W; Innis, Robert B

    2009-01-01

    11C-Loperamide is an avid substrate for P-glycoprotein (P-gp), but it is rapidly metabolized to 11C-N-desmethyl-loperamide (11C-dLop), which is also a substrate for P-gp and thereby contaminates the radioactive signal in the brain. Should further demethylation of 11C-dLop occur, radiometabolites with low entry into the brain are generated. Therefore, we evaluated the ability of 11C-dLop to quantify the function of P-gp at the blood-brain barrier in monkeys. Six monkeys underwent 12 PET scans of the brain, 5 at baseline and 7 after pharmacologic blockade of P-gp. A subset of monkeys also underwent PET scans with 15O-water to measure cerebral blood flow. To determine whether P-gp blockade affected peripheral distribution of 11C-dLop, we measured whole-body biodistribution in 4 monkeys at baseline and after P-gp blockade. The concentration of 11C-dLop in the brain was low under baseline conditions and increased 5-fold after P-gp blockade. This increase was primarily caused by an increased rate of entry into the brain rather than a decreased rate of removal from the brain. With P-gp blockade, uptake of radioactivity among brain regions correlated linearly with blood flow, suggesting a high single-pass extraction. After correction for cerebral blood flow, the uptake of 11C-dLop was fairly uniform among brain regions, suggesting that the function of P-gp is fairly uniformly distributed in the brain. On whole-body imaging, P-gp blockade significantly affected distribution of radioactivity only to the brain and not to other visually identified source organs. The effective dose estimated for humans was approximately 9 microSv/MBq. PET with 11C-dLop can quantify P-gp function at the blood-brain barrier in monkeys. The single-pass extraction of 11C-dLop is high and requires correction for blood flow to accurately measure the function of this efflux transporter. The low uptake at baseline and markedly increased uptake after P-gp blockade suggest that 11C-dLop will be useful to

  2. Brain Basics

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    Full Text Available ... About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain Brain ... called the hypothalamic-pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life— ...

  3. Putrescine uptake in saintpaulia petals.

    Science.gov (United States)

    Bagni, N; Pistocchi, R

    1985-02-01

    Putrescine uptake and the kinetics of this uptake were studied in petals of Saintpaulia ionantha Wendl. Uptake experiments of [(3)H] or [(14)C] putrescine were done on single petals at room temperature at various pH values. The results show that putrescine uptake occurs against a concentration gradient at low external putrescine concentration (0.5-100 micromolar) and follows a concentration gradient at higher external putrescine concentrations (100 micromolar to 100 millimolar). 2,4-Dinitrophenol and carbonylcyanide-m-chlorophenylhydrazone, two uncouplers, had no effect on putrescine uptake. Uptake rates were constant for 2 hours, reaching a maximum after 3 to 4 hours. Putrescine uptake depended markedly on the external pH and two maxima were observed: at low external concentrations of putrescine, the optimum was at pH 5 to 5.5; at higher concentrations the optimum was at pH 8.

  4. Evaluation of radioiodinated (R)-N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine as a ligand for brain norepinephrine transporter imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kiyono, Yasushi; Kanegawa, Naoki; Kawashima, Hidekazu; Kitamura, Yoji; Iida, Yasuhiko; Saji, Hideo E-mail: hsaji@pharm.kyoto-u.ac.jp

    2004-02-01

    (R)-N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine (MIPP) was evaluated as a radiopharmaceutical for investigating brain norepinephrine transporters (NET) by single photon emission computed tomography (SPECT). (R)-[{sup 125}I]MIPP was synthesized with high radiochemical yield (60%) and high radiochemical purity (> 98%). In biodistribution experiments, (R)-[{sup 125}I]MIPP indicated that the brain uptake of (R)-[{sup 125}I]MIPP was rapid and retained, and that the regional cerebral distribution was consistent with the density of NET. Moreover, the administration of desipramine decreased the accumulation of (R)-[{sup 125}I]MIPP in the brain. HPLC analysis of brain radioactivity showed that more than 90% was intact (R)-MIPP. These results suggested that (R)-[{sup 123}I]MIPP is a potential radiopharmaceutical for imaging brain NET.

  5. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... body. top of page How does the procedure work? With ordinary x-ray examinations, an image is ... slight pain and redness which should rapidly resolve. Women should always inform their physician or radiology technologist ...

  6. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... being recorded. Though nuclear imaging itself causes no pain, there may be some discomfort from having to ... exam. Injection of the radiotracer may cause slight pain and redness which should rapidly resolve. Women should ...

  7. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... may be allowed to wear your own clothing. Women should always inform their physician or technologist if ... slight pain and redness which should rapidly resolve. Women should always inform their physician or radiology technologist ...

  8. Exosomes: Mechanisms of Uptake

    Directory of Open Access Journals (Sweden)

    Kelly J. McKelvey

    2015-07-01

    Full Text Available Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non-immune cell types (e.g., cancer cells and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of paramount importance.

  9. Exosomes: Mechanisms of Uptake

    Directory of Open Access Journals (Sweden)

    Kelly J. McKelvey

    2015-07-01

    Full Text Available Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non- immune cell types (e.g., cancer cells and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of para‐ mount importance.

  10. Inositol uptake in rat aorta

    Energy Technology Data Exchange (ETDEWEB)

    Rapoport, R.M.; Van Gorp, C.; Chang, Ki-Churl (Univ. of Cincinnati College of Medicine, OH (USA))

    1990-01-01

    {sup 3}H-inositol uptake into deendothelialized aorta was linear for at least 2 h and was composed of both a saturable, Na{sup +}-dependent, and a nonsaturable, Na{sup +}-independent component. The Na{sup +}-dependent component of inositol uptake had a K{sub m} of 50 {mu}M and a V{sub max} of 289 pmol/mg prot/h. Exposure to LiCl, ouabain, or Ca{sup 2+} - free Krebs-Ringer bicarbonate solution inhibited uptake. Metabolic poisoning with dinitrophenol, as well as incubation with phloretin, an inhibitor of carrier-mediated hexose transport, also inhibited uptake. Exposure to norepinephrine decreased inositol uptake, while phorbol myristate acetate was without effect. Isobutylmethylxanthine significantly increased inositol uptake, while the increased uptake due to dibutyryl cyclic AMP and forskolin were not statistically significant. Sodium nitroprusside, and activator of guanylate cyclase, and 8-bromo cyclic GMP, were without effect on uptake, as was methylene blue, an inhibitor of guanylate cyclase. Inositol uptake into the aorta was increased when the endothelium was allowed to remain intact, although this effect was likely due to uptake in both the endothelial and smooth muscle cells.

  11. Simulation of the plant uptake of organophosphates and other emerging pollutants for greenhouse experiments and field conditions

    DEFF Research Database (Denmark)

    Trapp, Stefan; Eggen, Trine

    2013-01-01

    The uptake of the organophosphates tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCPP), tributyl phosphate (TBP), the insect repellant N,N-diethyl toluamide (DEET), and the plasticizer n-butyl benzenesulfonamide (NBBS) into plants was studied in greenhouse experiments...... concentrations in straw (leaves and stem). Uptake into carrot roots was high for TCPP and TBP. NBBS showed no high uptake but was rapidly degraded. Uptake into barley seeds was small. The pattern and levels of uptake could be reproduced by the model simulations, which indicates mainly passive uptake...

  12. Uptake and disposition of select pharmaceuticals by bluegill exposed at constant concentrations in a flow-through aquatic exposure system

    Science.gov (United States)

    Zhao, Jian-Liang; Furlong, Edward T.; Schoenfuss, Heiko L.; Kolpin, Dana W.; Bird, Kyle L.; Feifarek, David J.; Schwab, Eric A.; Ying, Guang-Guo

    2017-01-01

    The increasing use of pharmaceuticals has led to their subsequent input into and release from wastewater treatment plants, with corresponding discharge into surface waters that may subsequently exert adverse effects upon aquatic organisms. Although the distribution of pharmaceuticals in surface water has been extensively studied, the details of uptake, internal distribution, and kinetic processing of pharmaceuticals in exposed fish have received less attention. For this research, we investigated the uptake, disposition, and toxicokinetics of five pharmaceuticals (diclofenac, methocarbamol, rosuvastatin, sulfamethoxazole, and temazepam) in bluegill sunfish (Lepomis macrochirus) exposed to environmentally relevant concentrations (1000–4000 ng L–1) in a flow-through exposure system. Temazepam and methocarbamol were consistently detected in bluegill biological samples with the highest concentrations in bile of 4, 940, and 180 ng g–1, respectively, while sulfamethoxazole, diclofenac, and rosuvastatin were only infrequently detected. Over 30-day exposures, the relative magnitude of mean concentrations of temazepam and methocarbamol in biological samples generally followed the order: bile ≫ gut > liver and brain > muscle, plasma, and gill. Ranges of bioconcentration factors (BCFs) in different biological samples were 0.71–3960 and 0.13–48.6 for temazepam and methocarbamol, respectively. Log BCFs were statistically positively correlated to pH adjusted log Kow (that is, log Dow), with the strongest relations for liver and brain (r2 = 0.92 and 0.99, respectively), implying that bioconcentration patterns of ionizable pharmaceuticals depend on molecular status, that is, whether a pharmaceutical is un-ionized or ionized at ambient tissue pH. Methocarbamol and temazepam underwent rapid uptake and elimination in bluegill biological compartments with uptake rate constants (Ku) and elimination rate constants (Ke) at 0.0066–0.0330 h–1 and 0.0075–0.0384 h–1

  13. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Soloway, A.H.; Barth, R.F.

    1990-01-01

    Boron neutron capture therapy offers the potentiality for treating brain tumors currently resistant to treatment. The success of this form of therapy is directly dependent upon the delivery of sufficient numbers of thermal-neutrons to tumor cells which possess high concentrations of B-10. The objective of this project is to develop chemical methodology to synthesize boron-containing compounds with the potential for becoming incorporated into rapidly-dividing malignant brain tumor cells and excluded from normal components of the brain and surrounding tissues, to develope biological methods for assessing the potential of the compound by use of cell culture or intratumoral injection, to develop analytical methodology for measuring boron in cells and tissue using direct current plasma atomic emission spectroscopy (DCP-AES) and alpha track autoradiography, to develop biochemical and HPLC procedures for evaluating compound uptake and tissue half-life, and to develop procedures required to assess both in vitro and vivo efficacy of BNCT with selected compounds.

  14. Evening intake of α-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention

    NARCIS (Netherlands)

    Markus, C.R.; Jonkman, L.M.; Lammers, J.H.C.M.; Deutz, N.E.P.; Messer, M.H.; Rigtering, N.

    2005-01-01

    Background: Brain serotonin function is thought to promote sleep regulation and cognitive processes, whereas sleep abnormalities and subsequent behavioral decline are often attributed to deficient brain serotonin activity. Brain uptake of the serotonin precursor tryptophan is dependent on nutrients

  15. Characterization of water uptake and distribution in chickpea (Cicer ...

    African Journals Online (AJOL)

    Experiments were conducted to characterize the changes in water status during imbibition by nuclear magnetic resonance (NMR) spectroscopy in chickpea seeds exposed to static magnetic fields of 100 mT for 1 h. Water uptake during seed germination showed three phases with rapid initial hydration phase I, followed by ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics provides information on how the brain works, how mental illnesses ...

  17. Brain Basics

    Science.gov (United States)

    ... Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  19. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... learning more about how the brain grows and works in healthy people, and how normal brain development ...

  20. Severe symptomatic acute hyponatremia in traumatic brain injury responded very rapidly to a single 15 mg dose of oral tolvaptan; a Mayo Clinic Health System hospital experience - need for caution with tolvaptan in younger patients with preserved renal function.

    Science.gov (United States)

    Onuigbo, Macaulay Amechi Chukwukadibia; Agbasi, Nneoma

    2017-01-01

    Tolvaptan is now well established as a potent pharmaceutical agent for symptomatic hyponatremia from syndrome of inappropriate antidiuretic hormone secretion (SIADH), congestive heart failure and liver cirrhosis. Previous studies had recruited older (63-65 years) patients with mild renal impairment (serum creatinine, 1.3-1.4 mg/dl). A 2012 report in the Journal of Neurology, Neurosurgery & Psychiatry described tolvaptan as a "lifesaving drug". A major outcome concern in the treatment of chronic hyponatremia is potentially fatal pontine demyelination from over-rapid correction of serum sodium >0.5 mEq/dL/h. The maximum reported correction of serum sodium within 24 hours was 13 mEq/L in a case of SIADH. We recently experienced the dramatic correction of hyponatremia at 1 mEq/dL/h over 18 hours, following 15 mg of oral tolvaptan in a 32-year old male patient with normal kidney function (serum creatinine 0.76 mg/dL), following traumatic brain injury (TBI). Tolvaptan is indeed an effective and life-saving drug for post-TBI hyponatremia. However, we strongly recommend the use of lower doses of tolvaptan (≤15 mg/d) in younger patients with more preserved renal function to avoid the development of life-threatening pontine demyelination.

  1. The intent to exercise influences the cerebral O(2)/carbohydrate uptake ratio in humans

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Ide, Kojiro; Cai, Yan

    2002-01-01

    to 3.7 +/- 0.2 in the first minutes of the recovery (P exercise did not change the uptake ratio significantly. Yet, in a second experiment, when submaximal exercise required a maximal effort due to partial neuromuscular blockade, the ratio decreased and remained low (4.9 +/- 0.2......During and after maximal exercise there is a 15-30 % decrease in the metabolic uptake ratio (O(2)/[glucose + 1/2 lactate]) and a net lactate uptake by the human brain. This study evaluated if this cerebral metabolic uptake ratio is influenced by the intent to exercise, and whether a change could......) in the early recovery (n = 10; P 2) when the brain is activated by exhaustive exercise, and that such metabolic changes are influenced by the will to exercise. We speculate that the uptake ratio...

  2. An audit of the uptake of key PMTCT interventions in the pre and ...

    African Journals Online (AJOL)

    Prevention of vertical transmission of HIV may require the uptake of the culturally unacceptable options of cesarean delivery and formula feeding. The successful use of HAART, as enumerated by the WHO 2009 rapid advice, has the potential for facilitating the uptake of the more culturally acceptable vaginal delivery and ...

  3. Unmasking the Role of Uptake Transporters for Digoxin Uptake Across the Barriers of the Central Nervous System in Rat

    Directory of Open Access Journals (Sweden)

    Kunal S Taskar

    2017-03-01

    Full Text Available The role of uptake transporter (organic anion–transporting polypeptide [Oatp] in the disposition of a P-glycoprotein (P-gp substrate (digoxin at the barriers of central nervous system, namely, the blood-brain barrier (BBB, blood-spinal cord barrier (BSCB, and brain-cerebrospinal fluid barrier (BCSFB, was studied using rat as a preclinical species. In vivo chemical inhibition of P-gp and Oatp was achieved using elacridar and rifampicin, respectively. Our findings show that (1 digoxin had a low brain-to-plasma concentration ratio (B/P (0.07 in rat; (2 in the presence of elacridar, the B/P of digoxin increased by about 12-fold; (3 rifampicin administration alone did not change the digoxin B/P significantly when compared with digoxin B/P alone; (4 rifampicin administration along with elacridar resulted only in 6-fold increase in the B/P of digoxin; (5 similar fold changes and trends were seen with the spinal cord-to-plasma concentration ratio of digoxin, indicating the similarity between BBB and the BSCB; and (6 unlike BBB and BSCB, the presence of rifampicin further increased the cerebrospinal fluid-to-plasma concentration ratio (CSF/P for digoxin, suggesting a differential orientation of the uptake transporters at the BCSFB (CSF to blood compared with the BBB (blood to brain. The observations for digoxin uptake, at least at the BBB and the BSCB, advocate the importance of uptake transporters (Oatps. However, the activity of such uptake transporters became evident only after inhibition of the efflux transporter (P-gp.

  4. Studies of the retention mechanism of the brain perfusion imaging agent {sup 99m}{Tc}-bicisate ({sup 99m}{Tc}-ECD)

    Energy Technology Data Exchange (ETDEWEB)

    Walovitch, R.C.; Cheesman, E.H.; Maheu, L.J.; Hall, K.M. [DuPont Merck Pharmaceutical Co., North Billerica, MA (United States)

    1994-01-01

    The structure-activity relationship in a series of analogues of {sup 99m}{Tc}-bicisate ({sup 99m}{Tc}-N,N{prime}-1,2-ethylene-diylbis-L-cysteine diethyl ester dihydrochloride, RP-217) is described using in vivo studies in rodent and primate brain tissue. All analogues investigated were {sup 99m}{Tc}-diamine dithiol diesters, which were neutral and lipophilic and had modified brain uptake indexes ({ge}40) suggesting adequate first-pass extraction. All analogues were poorly retained by the rodent brain. In contrast, the stereochemistry and structure of the {sup 99m}{Tc}-complexes affected their brain retention in primates. All compounds that demonstrated selective primate brain retention were L-diesters that were metabolized in primate brain tissue to nonlypophilic complexes resulted from ester hydrolysis. Unretained complexes were not metabolized in primate brain tissue. More extensive studies were performed with {sup 99m}{Tc}-bicisate, which demonstrated poor brain retention in several nonprimate species (i.e., dogs, ferrets, pigs, and rodents). In rodent and nonhuman primate tissue, {sup 99m}{Tc}-bicisate was rapidly metabolized to a monoacid ester ({sup 99m}{Tc}-N,N{prime}-1,2-ethylenediylbis-L-cysteine monoethyl ester). Therefore, brain metabolism of {sup 99m}{Tc}-bicisate results in the formation of an acid product(s) that is selectively trapped in primate brain. 20 refs., 2 figs., 4 tabs.

  5. Uptake of nuclides by plants

    Energy Technology Data Exchange (ETDEWEB)

    Greger, Maria [Stockholm Univ. (Sweden). Dept. of Botany

    2004-04-01

    This review on plant uptake of elements has been prepared to demonstrate how plants take up different elements. The work discusses the nutrient elements, as well as the general uptake and translocation in plants, both via roots and by foliar absorption. Knowledge of the uptake by the various elements within the periodic system is then reviewed. The work also discusses transfer factors (TF) as well as difficulties using TF to understand the uptake by plants. The review also focuses on species differences. Knowledge necessary to understand and calculate plant influence on radionuclide recirculation in the environment is discussed, in which the plant uptake of a specific nuclide and the fate of that nuclide in the plant must be understood. Plants themselves determine the uptake, the soil/sediment determines the availability of the nuclides and the nuclides themselves can interact with each other, which also influences the uptake. Consequently, it is not possible to predict the nuclide uptake in plants by only analysing the nuclide concentration of the soil/substrate.

  6. Cadmium uptake by plants

    Energy Technology Data Exchange (ETDEWEB)

    Haghiri, F.

    1973-01-01

    Absorption of /sup 115m/Cd by soybean (Gylcine max l.) plants via foliar and root systems and translocation into the seed was determined. The uptake of /sup 115m/Cd by soybeans via the root system was more efficient than that of the foliar placement. Growth and Cd concentrations of soybean and wheat (Triticum aestivum l.) tops were influenced by soil-applied Cd. In both crops, the Cd concentration of plant tops increased while yield decreased with increasing levels of applied Cd. Cadmium toxicitiy began to occur in both crops at the lowest level of soil applied Cd (2.5 ppM). With soybean plants, Cd toxicity symptoms resembled fe chlorosis. For wheat plants there were no visual symptoms other than the studied growth. The relative concentration of Cd found in several vegetable crops varied depending on the plant species. The relative Cd concentration in descending order for various vegetables was lettuce (Lactuca sativa l.) > radish top (Raphanus sativus l.) > celery stalk (Apium graveolens l.) > celery leaves greater than or equal to green pepper (Capsicum frutescens l.) > radish roots.

  7. Evaluation of 6-([{sup 18}F]fluoroacetamido)-1-hexanoicanilide for PET imaging of histone deacetylase in the baboon brain

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Alicia E. [National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892 (United States); Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: areid@bnl.gov; Hooker, Jacob; Shumay, Elena; Logan, Jean; Shea, Colleen; Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Collins, Shanika [School of Science, Health and Technology Medgar Evers College, Brooklyn, NY 11225 (United States); Xu Youwen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Volkow, Nora [National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892 (United States); National Institute on Drug Abuse, Bethesda, MD 20892 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2009-04-15

    Introduction: Histone deacetylases (HDACs) are enzymes involved in epigenetic modifications that shift the balance toward chromatin condensation and silencing of gene expression. Here, we evaluate the utility of 6-([{sup 18}F]fluoroacetamido)-1-hexanoicanilide ([{sup 18}F]FAHA) for positron emission tomography imaging of HDAC activity in the baboon brain. For this purpose, we assessed its in vivo biodistribution, sensitivity to HDAC inhibition, metabolic stability and the distribution of the putative metabolite [{sup 18}F]fluoroacetate ([{sup 18}F]FAC). Methods: [{sup 18}F]FAHA and its metabolite [{sup 18}F]FAC were prepared, and their in vivo biodistribution and pharmacokinetics were determined in baboons. [{sup 18}F]FAHA metabolism and its sensitivity to HDAC inhibition using suberanilohydroxamic acid (SAHA) were assessed in arterial plasma and by in vitro incubation studies. The chemical form of F-18 in rodent brain was assessed by ex vivo studies. Distribution volumes for [{sup 18}F]FAHA in the brain were derived. Results: [{sup 18}F]FAHA was rapidly metabolized to [{sup 18}F]FAC, and both labeled compounds entered the brain. [{sup 18}F]FAHA exhibited regional differences in brain uptake and kinetics. In contrast, [{sup 18}F]FAC showed little variation in regional brain uptake and kinetics. A kinetic analysis that takes into account the uptake of peripherally produced [{sup 18}F]FAC indicated that SAHA inhibited binding of [{sup 18}F]FAHA in the baboon brain dose-dependently. In vitro studies demonstrated SAHA-sensitive metabolism of [{sup 18}F]FAHA to [{sup 18}F]FAC within the cell and diffusion of [{sup 18}F]FAC out of the cell. All radioactivity in brain homogenate from rodents was [{sup 18}F]FAC at 7 min postinjection of [{sup 18}F]FAHA. Conclusion: The rapid metabolism of [{sup 18}F]FAHA to [{sup 18}F]FAC in the periphery complicates the quantitative analysis of HDAC in the brain. However, dose-dependent blocking studies with SAHA and kinetic modeling

  8. Biodistribution, dosimetry, metabolism and monkey PET studies of [18F]GBR 13119. Imaging the dopamine uptake system in vivo.

    Science.gov (United States)

    Kilbourn, M R; Carey, J E; Koeppe, R A; Haka, M S; Hutchins, G D; Sherman, P S; Kuhl, D E

    1989-01-01

    The in vivo characteristics of a new radiotracer, [18F]GBR 13119, have been examined. Full body biodistribution in rats has been determined and the expected human dosimetry calculated. Pharmacological specificity of in vivo regional brain distribution in rats was examined. Blockage of specific binding was accomplished by dopamine reuptake inhibitors but no effect was observed for pretreatment with serotonin or norepinephrine reuptake inhibitors. Preliminary examination of rat blood shows the presence of radiolabeled metabolites, which can be rapidly identified using bonded-phase (Sep-Pak) chromatography. Finally, the striatum of living primates has been imaged using PET and i.v. administration of [18F]GBR 13119. These results represent the intermediate steps in the development of [18F]GBR 13119 as a radiotracer for the study of the dopamine uptake system in man.

  9. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  10. Organic acids enhance the uptake of lead by wheat roots.

    Science.gov (United States)

    Wang, Huanhua; Shan, Xiaoquan; Liu, Tao; Xie, Yaning; Wen, Bei; Zhang, Shuzhen; Han, Fang; van Genuchten, Martinus Th

    2007-05-01

    The uptake and bioavailability of lead (Pb) in soil-plant systems remain poorly understood. This study indicates that acetic and malic acids enhance the uptake of Pb by wheat (Triticum aestivum L.) roots under hydroponic conditions. The net concentration-dependent uptake influx of Pb in the presence and absence of organic acids was characterized by Michaelis-Menten type nonsaturating kinetic curves that could be resolved into linear and saturable components. Fitted maximum uptake rates (V (max)) of the Michaelis-Menton saturable component in the presence of acetic and malic acids were, respectively, 2.45 and 1.63 times those of the control, while the Michaelis-Menten K (m) values of 5.5, 3.7 and 2.2 microM, respectively, remained unchanged. Enhanced Pb uptake by organic acids was partially mediated by Ca(2+) and K(+) channels, and also depended upon the physiological function of the plasma membrane P-type ATPase. Uptake may have been further enhanced by an effectively thinner unstirred layer of Pb adjacent to the roots, leading to more rapid diffusion towards roots. X-ray absorption spectroscopic studies provided evidence that the coordination environment of Pb in wheat roots was similar to that of Pb(CH(3)COO)(2)x3H(2)O in that one Pb atom was coordinated to four oxygen atoms via the carboxylate group.

  11. Further advances in modeling transdermal uptake of SVOCs

    DEFF Research Database (Denmark)

    Morrison, Glenn; Weschler, Charles J.; Bekö, Gabriel

    2016-01-01

    To better simulate dermal uptake of SVOCs from air, we develop an enhanced transport model that includes skin surface lipids (SSL). As modeled, clothing can remove SSL by contact transfer and it can act as a source or sink for gas-phase transfer to and from SSL. Addition of SSL increases the over......To better simulate dermal uptake of SVOCs from air, we develop an enhanced transport model that includes skin surface lipids (SSL). As modeled, clothing can remove SSL by contact transfer and it can act as a source or sink for gas-phase transfer to and from SSL. Addition of SSL increases...... the overall resistance to uptake of SVOCs from air but also allows for more rapid release of SVOCs to sinks like clothing or clean air. We compare the model results to reported experimental uptake of di-ethyl phthalate (DEP) and di-n-butyl phthalate (DnBP), normalized by exposed skin area and the phthalate...... air concentration during exposure (Weschler et al., 2015). Overall, the model predicts total uptake values that are consistent with those observed in the experiments. The model predicts a normalized mass uptake of DEP of 3.1 (µg/m2)/(µg/m3) whereas the experimental results range from 1.0 to 4.3 (µg/m2...

  12. In Vivo Imaging of Brain Aromatase in Female Baboons: [11C]Vorozole Kinetics and Effect of the Menstrual Cycle

    Directory of Open Access Journals (Sweden)

    Deborah Pareto

    2013-11-01

    Full Text Available The aim of this work was to quantify the brain distribution of the enzyme aromatase in the female baboon with positron emission tomography and the tracer [11C]vorozole using three different quantification methods for estimating the total distribution volume (VT: a graphical method, compartment modeling, and a tissue to plasma ratio. The graphical model and the compartment modeling gave similar estimates to the data and similar values (correlation R = .988; p = .0001. [11C]Vorozole shows a rapid uptake by the brain followed by a relatively constant accumulation, suggesting the possibility of using the tissue to plasma ratio as an estimate of VT. The highest uptake of [11C]vorozole in the baboon brain was measured in the amygdala, followed by the preoptic area and hypothalamus, basal ganglia, and cortical areas. Pretreatment studies with vorozole or letrozole showed a generalized decrease in brain accumulation and VT. The results suggested that the physiologic changes in gonadal hormone levels accompanying the menstrual cycle had a significant effect on brain aromatase VT.

  13. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN......(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives...

  14. Lactate fuels the human brain during exercise

    NARCIS (Netherlands)

    Quistorff, Bjorn; Secher, Niels H.; van Lieshout, Johannes J.

    2008-01-01

    The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up

  15. Rapid Prototyping

    Science.gov (United States)

    1999-01-01

    Javelin, a Lone Peak Engineering Inc. Company has introduced the SteamRoller(TM) System as a commercial product. The system was designed by Javelin during a Phase II NASA funded small commercial product. The purpose of the invention was to allow automated-feed of flexible ceramic tapes to the Laminated Object Manufacturing rapid prototyping equipment. The ceramic material that Javelin was working with during the Phase II project is silicon nitride. This engineered ceramic material is of interest for space-based component.

  16. Lutein and Brain Function

    Directory of Open Access Journals (Sweden)

    John W. Erdman

    2015-10-01

    Full Text Available Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated as macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Recently, interest in lutein has expanded beyond the retina to its possible contributions to brain development and function. Only primates accumulate lutein within the brain, but little is known about its distribution or physiological role. Our team has begun to utilize the rhesus macaque (Macaca mulatta model to study the uptake and bio-localization of lutein in the brain. Our overall goal has been to assess the association of lutein localization with brain function. In this review, we will first cover the evolution of the non-human primate model for lutein and brain studies, discuss prior association studies of lutein with retina and brain function, and review approaches that can be used to localize brain lutein. We also describe our approach to the biosynthesis of 13C-lutein, which will allow investigation of lutein flux, localization, metabolism and pharmacokinetics. Lastly, we describe potential future research opportunities.

  17. Brain Basics

    Medline Plus

    Full Text Available ... PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, and ongoing research that helps ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... depression experience when starting treatment. Gene Studies ... medication. This information may someday make it possible to predict who ...

  19. Brain Basics

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    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... fear hub," which activates our natural "fight-or-flight" response to confront or escape from a dangerous ...

  20. Brain Lesions

    Science.gov (United States)

    Symptoms Brain lesions By Mayo Clinic Staff A brain lesion is an abnormality seen on a brain-imaging test, such as ... tomography (CT). On CT or MRI scans, brain lesions appear as dark or light spots that don' ...

  1. Brain Basics

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    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  2. Mechanisms of U87 astrocytoma cell uptake and trafficking of monomeric versus protofibril Alzheimer's disease amyloid-β proteins.

    Directory of Open Access Journals (Sweden)

    Yali Li

    Full Text Available A significant hallmark of Alzheimer's disease is the formation of senile plaques in the brain due to the unbalanced levels of amyloid-beta (Aβ. However, although how Aβ is produced from amyloid precursor proteins is well understood, little is known regarding the clearance and metabolism of various Aβ aggregates from the brain. Similarly, little is known regarding how astrocytes internalize and degrade Aβ, although astrocytes are known to play an important role in plaque maintenance and Aβ clearance. The objective of this study is to investigate the cellular mechanisms that mediate the internalization of soluble monomeric versus oligomeric Aβ by astrocytes. We used a combination of laser confocal microscopy and genetic and pharmacological experiments to dissect the internalization of sAβ42 and oAβ42 and their postendocytic transport by U87 human brain astrocytoma cell line. Both Aβ42 species were internalized by U87 cells through fluid phase macropinocytosis, which required dynamin 2. Depleting LDL receptor-related protein 1 (LRP1 decreased sAβ42 uptake more significantly than that of oAβ42. We finally show that both Aβ42 species were rapidly transported to lysosomes through an endolytic pathway and subjected to proteolysis after internalization, which had no significant toxic effects to the U87 cells under relatively low concentrations. We propose that macropinocytic sAβ42 and oAβ42 uptake and their subsequent proteolytic degradation in astroglial cells is a significant mechanism underlying Aβ clearance from the extracellular milieu. Understanding the molecular events involved in astrocytic Aβ internalization may identify potential therapeutic targets for Alzheimer's disease.

  3. Brain Basics

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    Full Text Available ... Mental Illnesses Clinical Trials Outreach Research Priorities Funding Labs at NIMH News & Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain Brain Basics in Real Life Brain Research Glossary Brain Basics (PDF, 10 pages) ...

  4. Prognostic value of 18F-fluoroethyl-L-tyrosine PET and MRI in small nonspecific incidental brain lesions.

    Science.gov (United States)

    Floeth, Frank Willi; Sabel, Michael; Stoffels, Gabriele; Pauleit, Dirk; Hamacher, Kurt; Steiger, Hans-Jakob; Langen, Karl-Josef

    2008-05-01

    Nonspecific incidental brain lesions (NILs) are being detected more frequently because of an increasing number of screening or research MRI scans of the brain, and their natural course is uncertain. In a prospective cohort study starting in 1999, we determined the outcomes of patients with incidental, nonenhancing, supratentorial, lobar, and small-volume (or=1.6 on (18)F-FET PET were rated as positive. Four different outcome groups were identified. In group A, 5 NILs regressed or vanished completely. All of these lesions were circumscribed on MRI, and (18)F-FET uptake was negative, with an L/B ratio of 1.2+/-0.2 (mean +/- SD). In group B, 10 NILs were stable, without growth. All of these lesions were circumscribed on MRI, and (18)F-FET uptake was negative (L/B ratio: 1.0+/-0.1). In group C, 2 NILs grew slowly over years, and an astrocytoma of World Health Organization (WHO) grade II was diagnosed after resection in each case. The lesions were circumscribed on MRI, and (18)F-FET uptake was negative (L/B ratios: 0.7 and 1.0). In group D, 4 NILs showed sudden and rapid growth, with clinical deterioration, and a high-grade glioma of WHO grade III or IV was diagnosed after resection in all cases. The lesions were diffuse on MRI, and (18)F-FET uptake was significantly increased (L/B ratio: 2.0+/-0.4) (P<0.01 for group D vs. group A or group B). For NILs, a circumscribed growth pattern on MRI and normal or low (18)F-FET uptake on PET are strong predictors for a benign course, with the eventual development of a low-grade glioma. In contrast, NILs with a diffuse growth pattern on MRI and increased (18)F-FET uptake indicate a high risk for the development of a high-grade glioma.

  5. Cerebral uptake of mefloquine enantiomers with and without the P-gp inhibitor elacridar (GF1210918) in mice

    OpenAIRE

    de Lagerie, Sylvie Barraud; Comets, Emmanuelle; Gautrand, Céline; Fernandez, Christine; Auchere, Daniel; Singlas, Eric; Mentre, France; Gimenez, François

    2004-01-01

    Mefloquine is a chiral neurotoxic antimalarial agent showing stereoselective brain uptake in humans and rats. It is a substrate and an inhibitor of the efflux protein P-glycoprotein.We investigated the stereoselective uptake and efflux of mefloquine in mice, and the consequences of the combination with an efflux protein inhibitor, elacridar (GF120918) on its brain transport.Racemic mefloquine (25 mg kg−1) was administered intraperitoneally with or without elacridar (10 mg kg−1). Six to seven ...

  6. Coupling of methylmercury uptake with respiration and water pumping in freshwater tilapia Oreochromis niloticus.

    Science.gov (United States)

    Wang, Rui; Wong, Ming-Hung; Wang, Wen-Xiong

    2011-09-01

    The relationships among the uptake of toxic methylmercury (MeHg) and two important fish physiological processes-respiration and water pumping--in the Nile tilapia (Oreochromis niloticus) were explored in the present study. Coupled radiotracer and respirometric techniques were applied to measure simultaneously the uptake rates of MeHg, water, and oxygen under various environmental conditions (temperature, dissolved oxygen level, and water flow). A higher temperature enhanced MeHg influx and the oxygen consumption rate but had no effect on the water uptake, indicating the influence of metabolism on MeHg uptake. The fish showed a high tolerance to hypoxia, and the oxygen consumption rate was not affected until the dissolved oxygen concentration decreased to extremely low levels (below 1 mg/L). The MeHg and water uptake rates increased simultaneously as the dissolved oxygen level decreased, suggesting the coupling of water flux and MeHg uptake. The influence of fish swimming performance on MeHg uptake was also investigated for the first time. Rapidly swimming fish showed significantly higher uptake rates of MeHg, water, and oxygen, confirming the coupling relationships among respiration, water pumping, and metal uptake. Moreover, these results support that MeHg uptake is a rate-limiting process involving energy. Our study demonstrates the importance of physiological processes in understanding mercury bioaccumulation in fluctuating aquatic environments. Copyright © 2011 SETAC.

  7. Nitrogen Uptake in Spinach

    Science.gov (United States)

    Ramirez, J.; VanBenthem, P.

    2013-12-01

    A plant's absorption of nitrogen can be encouraged by a variety of environmental factors, especially the application of fertilizers. As a common limiting factor in plant growth, not up taking enough nitrogen can be a result of an unhealthy plant. Moreover, as farmers seek out methods to increase growth of plants, fertilizers are used as a solution to the issue of nitrogen deficiency to incorporate additional nitrogen from chemical or organic sources, by not using the right fertilizer can greatly affect the plats. The point of this research project is to determine the effect of various fertilizers on the plant growth, and to correlate the measured nitrogen, water and chlorophyll content in spinach leaves. Spinach leaves were used because they are known to quickly uptake chemicals in the environment. The spinach plants were exposed to four different growing parameters, which are referred to as control, ammonium nitrate, MiracleGro , and organic. The spinach was originally placed in nitrogen deficient soil with only 2.2x10 4 weight percent (wt. %) nitrogen. The leaves in the control group were grown in this nitrogen deficient soil without any fertilizer added. Ammomium nitrate and MiracleGro were added to the spinach in the A and MG groups, respectively, and organic chicken stool was used for the O group. By using a spectral imaging system and flame combustion techniques, the chlorophyll content can be related to the nitrogen content in the spinach leaves. In these spinach leaves, nitrogen and chlorophyll content were measured, chlorophyll is a green pigment that plays a crucial role in producing nutrients for green plants. The lack of chlorophyll will allow the plant to become susceptible to diseases, so it is extremely important that the plants have a high content of chlorophyll. The role of nitrogen in chlorophyll is very important and helps in the creation of chlorophyll; therefore it is necessary that an appropriate amount of nitrogen is added for optimal growth

  8. The Influence of Nitrate and Chloride Uptake on Expressed Sap pH, Organic Acid Synthesis, and Potassium Accumulation in Higher Plants.

    Science.gov (United States)

    Blevins, D G; Hiatt, A J; Lowe, R H

    1974-07-01

    The influence of NO(3) (-) uptake and reduction on ionic balance in barley seedlings (Hordeum vulgare, cv. Compana) was studied. KNO(3) and KCl treatment solutions were used for comparison of cation and anion uptake. The rate of Cl(-) uptake was more rapid than the rate of NO(3) (-) uptake during the first 2 to 4 hours of treatment. There was an acceleration in rate of NO(3) (-) uptake after 4 hours resulting in a sustained rate of NO(3) (-) uptake which exceeded the rate of Cl(-) uptake. The initial (2 to 4 hours) rate of K(+) uptake appeared to be independent of the rate of anion uptake. After 4 hours the rate of K(+) uptake was greater with the KNO(3) treatment than with the KCl treatment, and the solution pH, cell sap pH, and organic acid levels with KNO(3) increased, relative to those with the KCl treatment. When absorption experiments were conducted in darkness, K(+) uptake from KNO(3) did not exceed K(+) uptake from KCl. We suggest that the greater uptake and accumulation of K(+) in NO(3) (-)-treated plants resulted from (a) a more rapid, sustained uptake and transport of NO(3) (-) providing a mobile counteranion for K(+) transport, and (b) the synthesis of organic acids in response to NO(3) (-) reduction increasing the capacity for K(+) accumulation by providing a source of nondiffusible organic anions.

  9. Uranium uptake and depuration in the aquatic invertebrate Chironomus tentans

    Energy Technology Data Exchange (ETDEWEB)

    Muscatello, Jorgelina R., E-mail: jorgelina_muscatello@golder.co [Toxicology Centre, 44 Campus Dr, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Liber, Karsten [Toxicology Centre, 44 Campus Dr, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada)

    2010-05-15

    Evaluation of aqueous uranium (U) uptake and depuration in larvae of the midge Chironomus tentans were investigated in two separated experiments. First, a static-renewal experiment was performed with 10-d old C. tentans larvae exposed to 300 mug U/L. The animals steadily accumulated U (K{sub u} = 20.3) approaching steady-state conditions (BAF = 56) in approximately 9-11 d. However, accumulated U was readily depurated (K{sub d} = 0.36) with U tissue concentration decreasing rapidly within 3 d of the larvae being placed in clean water (t{sub 1/2} = 1.9 d). Also, the growth of C. tentans larvae appeared to decrease after 6-11 d of U exposure, probably due to the reallocation of resources into U detoxification mechanisms. However, growth significantly increased once C. tentans were transferred to clean water. A separate short-term experiment was performed to evaluate the possible mechanism of U uptake in this invertebrate. Results suggested a passive mechanism of U uptake coupled with an active mechanism of U depuration but no details related to the type of mechanisms or pathway was investigated. - Aqueous uranium uptake and depuration in Chironomus tentans are rapid processes that appear to be associated with passive and active process of depuration.

  10. Uptake of DNA by cancer cells without a transfection reagent.

    Science.gov (United States)

    Kong, Yanping; Zhang, Xianbo; Zhao, Yongliang; Xue, Yanfang; Zhang, Ye

    2017-01-21

    Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis. Their uptake of DNAs might be different from normal cells; they may take in DNAs directly from the environment. In this report, we studied the uptake of DNAs in cancer cells without a transfection reagent. A group of DNA fragments were prepared with PCR and labeled with isotope phosphorous-32 to test their uptake by Huh 7 (liver cancer) and THLE3 (normal liver cells) after incubation overnight by counting radioactivity of the cells' genomic DNA. Multiple cell lines including breast cancer and lung cancer were tested with the same method. DNA molecules were also labeled with fluorescence to test the location in the cells using a kit of "label it fluorescence in situ hybridization (FISH)" from Mirus (USA). The data demonstrated that hepatocellular carcinoma cells possess the ability to take in large DNA fragments directly without a transfection reagent whereas normal liver cells cannot. Huh7 and MDA-MB231 cells displayed a significantly higher Rhodamine density in the cytoplasmic phagosomes and this suggests that the mechanism of uptake of large DNA by cancer cells is likely endocytosis. The efficacy of uptake is related to the DNA's size. Some cell lines of lung cancer and breast cancer also showed similar uptake of DNA. In the present study, we have revealed the evidence that some cancer cells, but not nontumorigenic cells, can take DNA fragments directly from the environment without the aid of the transfecting

  11. Presenilin promotes dietary copper uptake.

    Directory of Open Access Journals (Sweden)

    Adam Southon

    Full Text Available Dietary copper is essential for multicellular organisms. Copper is redox active and required as a cofactor for enzymes such as the antioxidant Superoxide Dismutase 1 (SOD1. Copper dyshomeostasis has been implicated in Alzheimer's disease. Mutations in the presenilin genes encoding PS1 and PS2 are major causes of early-onset familial Alzheimer's disease. PS1 and PS2 are required for efficient copper uptake in mammalian systems. Here we demonstrate a conserved role for presenilin in dietary copper uptake in the fly Drosophila melanogaster. Ubiquitous RNA interference-mediated knockdown of the single Drosophila presenilin (PSN gene is lethal. However, PSN knockdown in the midgut produces viable flies. These flies have reduced copper levels and are more tolerant to excess dietary copper. Expression of a copper-responsive EYFP construct was also lower in the midgut of these larvae, indicative of reduced dietary copper uptake. SOD activity was reduced by midgut PSN knockdown, and these flies were sensitive to the superoxide-inducing chemical paraquat. These data support presenilin being needed for dietary copper uptake in the gut and so impacting on SOD activity and tolerance to oxidative stress. These results are consistent with previous studies of mammalian presenilins, supporting a conserved role for these proteins in mediating copper uptake.

  12. l-Methionine Placental Uptake

    Science.gov (United States)

    Araújo, João R.; Correia-Branco, Ana; Ramalho, Carla; Gonçalves, Pedro; Pinho, Maria J.; Keating, Elisa

    2013-01-01

    Our aim was to investigate the influence of gestational diabetes mellitus (GDM) and GDM-associated conditions upon the placental uptake of 14C-l-methionine (14C-l-Met). The 14C-l-Met uptake by human trophoblasts (TBs) obtained from normal pregnancies (normal trophoblast [NTB] cells) is mainly system l-type amino acid transporter 1 (LAT1 [L])-mediated, although a small contribution of system y+LAT2 is also present. Comparison of 14C-l-Met uptake by NTB and by human TBs obtained from GDM pregnancies (diabetic trophoblast [DTB] cells) reveals similar kinetics, but a contribution of systems A, LAT2, and b0+ and a greater contribution of system y+LAT1 appears to exist in DTB cells. Short-term exposure to insulin and long-term exposure to high glucose, tumor necrosis factor-α, and leptin decrease 14C-l-Met uptake in a human TB (Bewo) cell line. The effect of leptin was dependent upon phosphoinositide 3-kinase, extracellular-signal-regulated kinase 1/2 (ERK/MEK 1/2), and p38 mitogen-activated protein kinase. In conclusion, GDM does not quantitatively alter 14C-l-Met placental uptake, although it changes the nature of transporters involved in that process. PMID:23653387

  13. Heterogeneous chemistry in aircraft wakes: Constraints for uptake coefficients

    Science.gov (United States)

    KäRcher, B.

    1997-08-01

    Recent in situ measurements in subsonic and supersonic aircraft plumes show the presence of high aerosol abundances. Given the large initial surface areas of the exhaust particles (volatile aerosols, soot, and ice) of 103-105 μm2 cm-3 or more, heterogeneous processing can potentially become important. Based on an analytical model to predict the temporal evolution of the surface areas, the potential for heterogeneous chemistry during the lifetime of single aircraft wakes is investigated. The model surface areas are constrained by plume observations and compared to numerical simulations of aerosol formation and growth. Efficient heterogeneous processing on volatile aerosols and soot on timescales below 1 day generally requires uptake coefficients ≳0.003-0.007, depending on the specific surface area of soot. For low available surface areas and slow reactions, the lifetime of emitted exhaust species sensitively depends on the wake mixing properties. Shutting off uptake by volatile particles inhibits heterogeneous processing unless high soot surface areas and reaction probabilities are prescribed. Depending on the lifetime of ice contrails, uptake coefficients ≳0.1 are required for rapid uptake of exhaust species on the ice particles. This lower limit becomes relaxed if contrails are long-lived or develop into persistent cirrus or polar stratospheric clouds, rendering activation of chlorine potentially important. The model is applied to investigate the uptake of gaseous HNO2 and SO2 by the observed particles in the plume of the Concorde in the lower stratosphere.

  14. A dual porosity model of nutrient uptake by root hairs

    KAUST Repository

    Zygalakis, K. C.

    2011-08-09

    Summary: • The importance of root hairs in the uptake of sparingly soluble nutrients is understood qualitatively, but not quantitatively, and this limits efforts to breed plants tolerant of nutrient-deficient soils. • Here, we develop a mathematical model of nutrient uptake by root hairs allowing for hair geometry and the details of nutrient transport through soil, including diffusion within and between soil particles. We give illustrative results for phosphate uptake. • Compared with conventional \\'single porosity\\' models, this \\'dual porosity\\' model predicts greater root uptake because more nutrient is available by slow release from within soil particles. Also the effect of soil moisture is less important with the dual porosity model because the effective volume available for diffusion in the soil is larger, and the predicted effects of hair length and density are different. • Consistent with experimental observations, with the dual porosity model, increases in hair length give greater increases in uptake than increases in hair density per unit main root length. The effect of hair density is less in dry soil because the minimum concentration in solution for net influx is reached more rapidly. The effect of hair length is much less sensitive to soil moisture. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

  15. Effects of light intensity and temperature on Cryptomonas ovata (Cryptophyceae) growth and nutrient uptake rates

    Science.gov (United States)

    Cloern, James E.

    1977-01-01

    Specific growth rate of Cryptomonas ovata var. palustris Pringsheim was measured in batch culture at 14 light-temperature combinations. Both the maximum growth rate (μm) and optimum light intensity (Iopt) fit an empirical function that increases exponentially with temperature up to an optimum (Topt), then declines rapidly as temperature exceeds Topt. Incorporation of these functions into Steele's growth equation gives a good estimate of specific growth rate over a wide range of temperature and light intensity. Rates of phosphate, ammonium and nitrate uptake were measured separately at 16 combinations of irradiance and temperature and following a spike addition of all starved cells initially took up nutrient at a rapid rate. This transitory surge was followed by a period of steady, substrate-saturated uptake that persisted until external nutrient concentration fell. Substrate-saturated NO3−-uptake proceeded at very slow rates in the dark and was stimulated by both increased temperature and irradiance; NH4+-uptake apparently proceeded at a basal rate at 8 and l4 C and was also stimulated by increased temperature and irradiance. Rates of NH4−-uptake were much higher than NO3−-uptake at all light-temperature combinations. Below 20 C, PO4−3-uptake was more rapid in dark than in light, but was light enhanced at 26 C.

  16. Differential uptake of [18F]FET and [3H]l-methionine in focal cortical ischemia.

    Science.gov (United States)

    Salber, Dagmar; Stoffels, Gabriele; Pauleit, Dirk; Reifenberger, Guido; Sabel, Michael; Shah, Nadim Jon; Hamacher, Kurt; Coenen, Heinz H; Langen, Karl-Josef

    2006-11-01

    Amino acids such as [(11)C-methyl]l-methionine are particularly useful in brain tumor diagnosis, but unspecific uptake (e.g., in cerebral ischemia) has been reported. O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) shows a clinical potential similar to that of l-methionine (MET) in brain tumor diagnosis but is applicable on a wider clinical scale. The aim of this study was to evaluate the uptake of [(18)F]FET and [(3)H]MET in focal cortical ischemia in rats by dual-tracer autoradiography. Focal cortical ischemia was induced in 25 CDF rats using the photothrombosis (PT) model. At different time points up to 6 weeks after the induction of PT, [(18)F]FET and [(3)H]MET were injected intravenously. Additionally, contrast-enhanced magnetic resonance imaging (MRI) was performed in 10 animals. One hour after tracer injection, brains were cut in coronal sections and evaluated by dual-tracer autoradiography. Lesion-to-brain (L/B) ratios were calculated by dividing the maximal uptake in the lesion by the mean uptake in the brain. An L/B ratio of >2.0 was considered indicative of pathological uptake. Histological slices were stained by cresyl violet and supplemented by immunostainings for glial fibrillary acidic protein (GFAP) and CD68 in selected cases. A variably increased uptake of both tracers was observed in the PT lesion and its demarcation zone up to 7 days after PT for [(18)F]FET and up to 6 weeks for [(3)H]MET. The cutoff level of 2.0 was exceeded in 12/25 animals for [(18)F]FET and in 18/25 animals for [(3)H]MET. Focally increased tracer uptake matched contrast enhancement in MRI in 3/10 cases for [(18)F]FET and in 5/10 cases for [(3)H]MET. Immunohistochemical staining in lesions with differential uptake of [(18)F]FET and [(3)H]MET revealed that selective uptake of [(18)F]FET was associated with GFAP-positive astrogliosis while selective [(3)H]MET uptake correlated with CD68-positive macrophage infiltration. [(18)F]FET, like [(3)H]MET, may exhibit significant uptake

  17. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  18. Brain Basics

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    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... basic, working unit of the brain and nervous system, which processes and transmits information. neurotransmitter —A chemical produced by neurons that carries ...

  19. Brain Basics

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    Full Text Available ... learning more about how the brain grows and works in healthy people, and how normal brain development and function can go awry, leading to mental illnesses. Brain Basics will introduce you to some of this science, such as: ... of the brain communicate and work with each other How changes in the brain ...

  20. [Effect of psychotropic substances and narcotic analgesics on 14C-noradrenaline uptake by rat cerebral cortex synaptosomes].

    Science.gov (United States)

    Maĭsov, N I; Tolmacheva, N S

    1980-01-01

    The effect of different groups of neurotropic substances was studied on labeled noradrenaline and gamma-aminobutyric acid (GABA) uptake by synaptosomes of the rat brain cortex. It has been shown that each group of the test compounds is characterized by specific qualitative and quantitative features of the action on the above processes. Thus, psychostimulants actively inhibit noradrenaline uptake without changing GABA uptake. On the contrary, neuroleptics exert a pronounced inhibitory effect on GABA uptake and insignificantly inhibit noradrenaline accumulation. Antidepressants are very potent while narcotic analgesic drugs are less potent inhibitors of the accumulation of both neuromediators. Morphine and nalorphine have no effect on these processes.

  1. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  2. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  3. Brain Basics

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    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... brain. DNA —The "recipe of life," containing inherited genetic information that helps to define physical and some ...

  4. Brain Basics

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    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ... grow there are differences in brain development in children who develop bipolar disorder than children who do ...

  5. Brain Basics

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    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as they grow there are differences in brain development in children who develop bipolar disorder than children ...

  6. Brain Basics

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    Full Text Available ... imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain ... imaging technique that uses magnetic fields to take pictures of the brain's structure. mutation —A change in ...

  7. Brain Basics

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    Full Text Available ... as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the brain ... specialized for the function of conducting messages. A neuron has three basic parts: Cell body which includes ...

  8. Brain Basics

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    Full Text Available ... of the brain's structure, studies show that brain growth in children with autism appears to peak early. And as they grow there are differences in brain development in children who develop bipolar disorder than children ...

  9. Brain Basics

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    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  10. Brain Basics

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    Full Text Available ... the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. She ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  11. Brain Basics

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    Full Text Available ... about how the brain grows and works in healthy people, and how normal brain development and function ... chart how the brain develops over time in healthy people and are working to compare that with ...

  12. Brain Basics

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    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... unit of the brain and nervous system, which processes and transmits information. neurotransmitter —A chemical produced by ...

  13. Brain Basics

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    Full Text Available ... Mental Illnesses Clinical Trials Outreach Outreach Home Stakeholder Engagement Outreach Partnership Program Alliance for Research Progress Coalition ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ...

  14. Brain Basics

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    Full Text Available ... in Real Life Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video ... and epigenetic changes can be passed on to future generations. Further understanding of genes and epigenetics may ...

  15. Brain Basics

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    Full Text Available ... can lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits ... tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on ...

  16. Comparative investigations on the uptake of phallotoxins, bile acids, bovine lactoperoxidase and horseradish peroxidase into rat hepatocytes in suspension and in cell cultures.

    Science.gov (United States)

    Petzinger, E; Frimmer, M

    1988-01-13

    Two alternative uptake mechanisms for phallotoxins by liver cells are debated: carrier-mediated uptake and receptor-mediated endocytosis. We have compared the properties of hepatocellular uptake of the phallotoxins, phalloidin and demethylphalloin, with the uptake of cholate as a substrate for carrier-mediated uptake and compared with iodinated bovine lactoperoxidase or iodinated horseradish peroxidase, as the latter are known to be taken up by vesicular endocytosis. Uptake of phallotoxins and [14C]cholate uptake into isolated hepatocytes is independent of extracellular calcium but inhibited by A23187 or by monensin. Uptake of bovine lactoperoxidase strictly depends on external Ca2+, was insensitive to A23197 and was not inhibited by monensin. No mutual uptake inhibition between phalloidin or cholate and peroxidases was seen, indicating independent permeation pathways in hepatocytes. However, high concentrations of cytochalasin B inhibited the uptake of either phalloidin, cholate or bovine lactoperoxidase. Horseradish peroxidase uptake, which was taken as an indicator for fluid pinocytosis, was low in isolated hepatocytes and could not account for the amount of phalloidin or cholate taken up. In cultured rat hepatocytes, uptake of phallotoxins decreased within 1 day to 10% of the uptake seen in freshly isolated hepatocytes. The results indicate different mechanisms for hepatocellular phallotoxin/bile-acid uptake and peroxidase internalization. As monolayer cultures of hepatocytes rapidly lost the carrier-mediated uptake of phallotoxins and bile acids, freshly isolated hepatocytes might be a more suitable experimental model than cultured cells for kinetic studies on this transport system.

  17. The polyphonic brain

    DEFF Research Database (Denmark)

    Sturm, Irene; Treder, Matthias S.; Dähne, Sven

    Rapid changes in the stimulus envelope (indicating tone onsets) elicit an N1-P2 ERP response, as has been shown for clicks and sine waves, musical tones and for speech. Canonical Correlation Analysis with temporal embedding (tkCCA), a multivariate correlation-based method, allows to extract brain...

  18. Octreotide Uptake in Parathyroid Adenoma

    Directory of Open Access Journals (Sweden)

    Seyhan Karaçavuş

    2012-08-01

    Full Text Available The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive parathyroid tumors. (MIRT 2012;21:77-79

  19. Dynamic SPECT of the brain using a lipophilic technetium-99m complex, PnAO

    DEFF Research Database (Denmark)

    Holm, S; Andersen, A R; Vorstrup, S

    1985-01-01

    The lipophilic 99mTc-labeled oxime propylene amine oxime (PnAO) should, according to recent reports behave like 133Xe in the human brain. This study compares SPECT images of the two tracers in six subjects: four stroke cases, one transitory ischemic attack case and one normal subject. Technetium-......AO has a high yet incomplete brain extraction yielding a flow dominated initial distribution with limitations mentioned.......The lipophilic 99mTc-labeled oxime propylene amine oxime (PnAO) should, according to recent reports behave like 133Xe in the human brain. This study compares SPECT images of the two tracers in six subjects: four stroke cases, one transitory ischemic attack case and one normal subject. Technetium-99......m PnAO was injected i.v. as a bolus of 15 to 25 mCi. The distribution was followed over 10-sec intervals using a highly sensitive, rapidly rotating SPECT (Tomomatic 64) and compared to 133Xe flow maps. Upon arrival of the PnAO bolus to the brain, a high uptake was found in brain tissue with high...

  20. Brain nonoxidative carbohydrate consumption is not explained by export of an unknown carbon source

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Nyberg, Nils; Jaroszewski, Jerzy W

    2010-01-01

    carbon species going to and from the brain. We observed a carbohydrate accumulation of 255+/-37 mumol/100 g glucose equivalents at exhaustion not accounted for by the oxygen uptake. Although the cumulated uptake was lower than earlier observed, the results show that glucose and lactate are responsible...... for the majority of the carbon exchange across the brain. Even during intense exercise associated with the largest nonoxidative carbohydrate consumption, the brain did not show significant release of any other metabolite. We conclude that during exercise, the surplus carbohydrate uptake by the brain cannot......Brain activation provokes nonoxidative carbohydrate consumption and during exercise it is dominated by the cerebral uptake of lactate resulting in that up to approximately 1 mmol/ 100 g of glucose equivalents cannot be accounted for by cerebral oxygen uptake. The fate of this 'extra' carbohydrate...

  1. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors. Technical progress report No. 1, May 1, 1990--January 31, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Soloway, A.H.; Barth, R.F.

    1990-12-31

    Boron neutron capture therapy offers the potentiality for treating brain tumors currently resistant to treatment. The success of this form of therapy is directly dependent upon the delivery of sufficient numbers of thermal-neutrons to tumor cells which possess high concentrations of B-10. The objective of this project is to develop chemical methodology to synthesize boron-containing compounds with the potential for becoming incorporated into rapidly-dividing malignant brain tumor cells and excluded from normal components of the brain and surrounding tissues, to develope biological methods for assessing the potential of the compound by use of cell culture or intratumoral injection, to develop analytical methodology for measuring boron in cells and tissue using direct current plasma atomic emission spectroscopy (DCP-AES) and alpha track autoradiography, to develop biochemical and HPLC procedures for evaluating compound uptake and tissue half-life, and to develop procedures required to assess both in vitro and vivo efficacy of BNCT with selected compounds.

  2. Brain Basics

    Medline Plus

    Full Text Available ... pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah ... axis —A brain-body circuit which plays a critical role in the body's response to stress. impulse — ...

  3. Brain Basics

    Medline Plus

    Full Text Available ... time in healthy people and are working to compare that with brain development in people mental disorders. Genes and environmental ... the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures ...

  4. Brain Basics

    Medline Plus

    Full Text Available ... of cells in the body, the results can affect many aspects of life. Scientists are continually learning more about how the brain grows and works in healthy people, and how normal brain development and function can go awry, leading ... the environment affect the brain The basic structure of the brain ...

  5. Brain Basics

    Medline Plus

    Full Text Available ... basic working unit of the brain and nervous system. These cells are highly specialized for the function of conducting messages. ... specialized brain systems. We have many specialized brain systems that work ... research are listed below. Amygdala —The brain's "fear hub," which ...

  6. Identification of multiple cellular uptake pathways of polystyrene nanoparticles and factors affecting the uptake: relevance for drug delivery systems.

    Science.gov (United States)

    Firdessa, Rebuma; Oelschlaeger, Tobias A; Moll, Heidrun

    2014-01-01

    Nanoparticles may address challenges by human diseases through improving diagnosis, vaccination and treatment. The uptake mechanism regulates the type of threat a particle poses on the host cells and how a cell responds to it. Hence, understanding the uptake mechanisms and cellular interactions of nanoparticles at the cellular and subcellular level is a prerequisite for their effective biomedical applications. The present study shows the uptake mechanisms of polystyrene nanoparticles and factors affecting their uptake in bone marrow-derived macrophages, 293T kidney epithelial cells and L929 fibroblasts. Labeling with the endocytic marker FM4-64 and transmission electron microscopy studies show that the nanoparticles were internalized rapidly via endocytosis and accumulated in intracellular vesicles. Soon after their internalizations, nanoparticles trafficked to organelles with acidic pH. Analysis of the ultrastructural morphology of the plasma membrane invaginations or extravasations provides clear evidence for the involvement of several uptake routes in parallel to internalize a given type of nanoparticles by mammalian cells, highlighting the complexity of the nanoparticle-cell interactions. Blocking the specific endocytic pathways by different pharmacological inhibitors shows similar outcomes. The potential to take up nanoparticles varies highly among different cell types in a particle sizes-, time- and energy-dependent manner. Furthermore, infection and the activation status of bone marrow-derived macrophages significantly affect the uptake potential of the cells, indicating the need to understand the diseases' pathogenesis to establish effective and rational drug-delivery systems. This study enhances our understanding of the application of nanotechnology in biomedical sciences. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. Nitrogen uptake kinetics of freshly isolated zooxanthellae

    Digital Repository Service at National Institute of Oceanography (India)

    Wafar, M.V.M.; Wafar, S.; Rajkumar, R.

    Zooxanthellae freshly isolated from the coral host Pocillopora damicornis exhibited substrate-saturable uptake kinetics for ammonium, nitrate and urea. Maximum uptake velocity for ammonium [10.1 nmol. ( mu chl-a)./1h/1] was greater than...

  8. Arsenic uptake in bacterial calcite

    Science.gov (United States)

    Catelani, Tiziano; Perito, Brunella; Bellucci, Francesco; Lee, Sang Soo; Fenter, Paul; Newville, Matthew; Rimondi, Valentina; Pratesi, Giovanni; Costagliola, Pilario

    2018-02-01

    Bio-mediated processes for arsenic (As) uptake in calcite were investigated by means of X-ray Diffraction (XRD) and X-ray Absorption Spectroscopy (XAS) coupled with X-ray Fluorescence measurements. The environmental bacterial strain Bacillus licheniformis BD5, sampled at the Bullicame Hot Springs (Viterbo, Central Italy), was used to synthesize calcite from As-enriched growth media. Both liquid and solid cultures were applied to simulate planktonic and biofilm community environments, respectively. Bacterial calcite samples cultured in liquid media had an As enrichment factor (Kd) 50 times higher than that from solid media. The XRD analysis revealed an elongation of the crystal lattice along the c axis (by 0.03 Å) for biogenic calcite, which likely resulted from the substitution of larger arsenate for carbonate in the crystal. The XAS data also showed a clear difference in the oxidation state of sorbed As between bacterial and abiotic calcite. Abiotic chemical processes yielded predominantly As(V) uptake whereas bacterial precipitation processes led to the uptake of both As(III) and As(V). The presence of As(III) in bacterial calcite is proposed to result from subsequent reduction of arsenate to arsenite by bacterial activities. To the best of our knowledge, this is the first experimental observation of the incorporation of As(III) in the calcite crystal lattice, revealing a critical role of biochemical processes for the As cycling in nature.

  9. Arsenic uptake in bacterial calcite

    Energy Technology Data Exchange (ETDEWEB)

    Catelani, Tiziano; Perito, Brunella; Bellucci, Francesco; Lee, Sang Soo; Fenter, Paul; Newville, Matthew G.; Rimondi, Valentina; Pratesi, Giovanni; Costagliola, Pilario

    2018-02-01

    Bio-mediated processes for arsenic (As) uptake in calcite were investigated by means of X-ray Diffraction (XRD) and Xray Absorption Spectroscopy (XAS) coupled with X-ray Fluorescence measurements. The environmental bacterial strain Bacillus licheniformis BD5, sampled at the Bullicame Hot Springs (Viterbo, Central Italy), was used to synthesize calcite from As-enriched growth media. Both liquid and solid cultures were applied to simulate planktonic and biofilm community environments, respectively. Bacterial calcite samples cultured in liquid media had an As enrichment factor (Kd) 50 times higher than that from solid media. The XRD analysis revealed an elongation of the crystal lattice along the c axis (by 0.03Å) for biogenic calcite, which likely resulted from the substitution of larger arsenate for carbonate in the crystal. The XAS data also showed a clear difference in the oxidation state of sorbed As between bacterial and abiotic calcite. Abiotic chemical processes yielded predominantly As(V) uptake whereas bacterial precipitation processes led to the uptake of both As(III) and As(V). The presence of As(III) in bacterial calcite is proposed to result from subsequent reduction of arsenate to arsenite by bacterial activities. To the best of our knowledge, this is the first experimental observation of the incorporation of As(III) in the calcite crystal lattice, revealing a critical role of biochemical processes for the As cycling in nature.

  10. Specific uptake of serotonin by murine lymphoid cells

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, J.C.; Walker, R.F.; Brooks, W.H.; Roszman, T.L.

    1986-03-01

    Recently the authors confirmed and extended earlier observations that serotonin (5-hydroxytryptamine, 5HT) can influence immune function. Both 5HT and its precursor, 5-hydroxytryptophan inhibit the primary, in vivo antibody response to sheep red blood cells, in mice. Here, the authors report specific in vitro association of this amine with mouse splenocytes. Spleen cells from 6-8 week old CBA/J mice incorporated /sup 3/H-5HT(10/sup -8/ to 2.5 x 10/sup -6/M) in a saturable manner, at 37/sup 0/C. Specificity of uptake was indicated by competition with excess (10/sup -5/M) unlabelled 5HT and with 10/sup -5/M fluoxetine, a selective inhibitor of active 5HT reuptake in rat brain. The 5HT receptor antagonists, methysergide and cyproheptadine, also blocked 5HT uptake. Cell lysis and displacement studies revealed largely intracellular accumulation of /sup 3/H-5HT with little membrane association, in splenocytes. Hofstee analysis of uptake kinetics yielded an apparent Km of 0.82 +/- 0.22 x 10/sup -7/M and Vmax of 501 +/- 108 pM/3 x 10/sup 6/ cells/10 min. Spleen cells fractionated on Sephadex G10 showed virtually no specific 5HT uptake while peritoneal exudate cells from thioglycollate treated mice displayed 5HT uptake kinetics similar to those of splenocytes. The site of specific /sup 3/H-5HT incorporation within a population of spleen cells and the functional significance of this phenomenon to immunomodulation by 5HT remain to be elucidated.

  11. On the relations between /sup 67/Ga uptake in tumor or liver and blood chemistry data in patients with malignant tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, Masahiro

    1988-08-01

    Gallium-67 (/sup 67/Ga) is widely used for the detection of malignant tumors in many organs. But, the mechanism for /sup 67/Ga uptake in tumor is still unclear. In this study, we have investigated the relationships between tumor uptake of /sup 67/Ga (tumor-to-brain count ratio), /sup 67/Ga uptake in liver (liver-to-brain count ratio), blood retention rate of /sup 67/Ga and blood chemistry data in 210 patients with malignant tumors. These patients in this study were divided into three groups; the first is the group that has /sup 67/Ga uptake into tumor (/sup 67/Ga uptake (+) Tumor (+) group, N = 101), second is the group that has no /sup 67/Ga uptake into tumor (/sup 67/Ga uptake (-) Tumor (-) group, N = 43), and the third is the control group, of which tumors were resected or disappeared by therapy (/sup 67/Ga uptake (-) Tumor (-) group, N = 66). Liver-to-brain count ratio was closely correlated with the levels of serum transferrin and UIBC, and negatively with serum iron level. However, tumor-to-brain count ratio was not correlated with the levels of serum transferrin, UIBC, and iron. Serum haptoglobin level was closely correlated with tumor-to-brain count ratio, and negatively with blood retention rate. These results gave the following suggestions: (1) /sup 67/Ga may be incorporated into liver as iron analogue; (2) the mechanism of tumor uptake of /sup 67/Ga may be different from that of /sup 67/Ga uptake into liver; and (3) the degree of /sup 67/Ga uptake into tumor may be related to the degree of inflammation around the tumor.

  12. 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation.

    Science.gov (United States)

    Ismail, Muhammad-Al-Mustafa; Mateos, Laura; Maioli, Silvia; Merino-Serrais, Paula; Ali, Zeina; Lodeiro, Maria; Westman, Eric; Leitersdorf, Eran; Gulyás, Balázs; Olof-Wahlund, Lars; Winblad, Bengt; Savitcheva, Irina; Björkhem, Ingemar; Cedazo-Mínguez, Angel

    2017-03-06

    Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)-mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders. © 2017 Ismail et al.

  13. Enhancement of the relative uptake of {sup 18}F-FDG in mouse fibrosarcoma by rolipram

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Kaoru; Hosoi, Rie; Momosaki, Sotaro; Inoue, Osamu [Osaka Univ., Suita (Japan). School of Allied Health Science; Koike, Sachiko; Ando, Koichi [National Inst. of Radiological Sciences, Chiba (Japan); Nishimura, Tsunehiko [Kyoto Prefectural Univ. of Medicine (Japan)

    2002-11-01

    The effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on the uptake of {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) in tumor tissue was examined in mice transplanted with NFSa fibrosarcoma. The uptake indexes of {sup 18}F-FDG in the heart, skeletal muscle and brain remarkably decreased after treatment with 3 mg/kg of rolipram (heart: 13%, skeletal muscle: 14%, brain: 31%), but fibrosarcoma tissue showed only a 50% reduction in the uptake index of {sup 18}F-FDG. The tumor/muscle ratio of radioactivity 30 min after {sup 18}F-FDG injection was consequently enhanced from 1.9 to 6.5 by rolipram. This indicates the possible use of rolipram to enhance the sensitivity of tumor detection, as well as characterization of tumors in {sup 18}F-FDG PET. (author)

  14. Mechanisms of hepatic methylmercury uptake

    Energy Technology Data Exchange (ETDEWEB)

    Ballatori, N.; Truong, A.T. [Univ. of Rochester School of Medicine, NY (United States)

    1995-11-01

    The mechanism by which methylmercury is cleared from hepatic portal blood was examined in isolated rat livers perfused single-pass with Krebs-Henseleit buffer. [{sup 203}Hg]Methylmercury (0.24-24 {mu}M) was infused over a 30-min interval, followed by a 30-min washout, as a complex with the endogenous ligands L-cysteine (CH{sub 3}Hg-L-cys), gluthathione (CH{sub 3}Hg-DTT), chloride (CH{sub 3}HgCl), and the D-enantiomer of cysteine (CH{sub 3}Hg-D-cys). The sulfhydryl-containing compounds were added at a 10-fold molar excess. When administered as the albumin complex, only a small fraction of the [{sup 203}Hg]methylmercury was cleared from perfusate ({approximately}8%) and excreted into bile (0.7%). Hepatic uptake and biliary excretion of methylmercury was considerably higher for the other complexes. For the dithiothreitol complex, hepatic extraction of methylmercury was nearly complete during single-pass perfusion. A comparison of hepatic removal of increasing doses of CH{sub 3}Hg-L-cys and CH{sub 3}Hg-L-cys and CH{sub 3}-D-cys revealed little difference. Moreover, the fraction of methylmercury removed was similar at concentrations of 0.24, 2.4, and 24 {mu}M, indicating no saturability of uptake in this dose range. Methylmercury was not hepatotoxic at concentrations up to 24 {mu}M if administered as a mercaptide; however, the chloride complex (CH{sub 3}HgCl) produced cholestasis and an increase in perfusion pressure at a concentration of only 0.24 {mu}m. These findings indicate that hepatic methylmercury uptake and toxicity are dependent on the chemical form in blood plasma. Uptake was faster when methylmercury was present as a cysteine or glutathione complex, as compared to the albumin complex; however, the lack of steroselectivity indicates that the uptake process may be relatively unselective.

  15. Large neutral amino acids: dietary effects on brain neurochemistry and function.

    Science.gov (United States)

    Fernstrom, John D

    2013-09-01

    The ingestion of large neutral amino acids (LNAA), notably tryptophan, tyrosine and the branched-chain amino acids (BCAA), modifies tryptophan and tyrosine uptake into brain and their conversion to serotonin and catecholamines, respectively. The particular effect reflects the competitive nature of the transporter for LNAA at the blood-brain barrier. For example, raising blood tryptophan or tyrosine levels raises their uptake into brain, while raising blood BCAA levels lowers tryptophan and tyrosine uptake; serotonin and catecholamine synthesis in brain parallel the tryptophan and tyrosine changes. By changing blood LNAA levels, the ingestion of particular proteins causes surprisingly large variations in brain tryptophan uptake and serotonin synthesis, with minimal effects on tyrosine uptake and catecholamine synthesis. Such variations elicit predictable effects on mood, cognition and hormone secretion (prolactin, cortisol). The ingestion of mixtures of LNAA, particularly BCAA, lowers brain tryptophan uptake and serotonin synthesis. Though argued to improve physical performance by reducing serotonin function, such effects are generally considered modest at best. However, BCAA ingestion also lowers tyrosine uptake, and dopamine synthesis in brain. Increasing dopamine function in brain improves performance, suggesting that BCAA may fail to increase performance because dopamine is reduced. Conceivably, BCAA administered with tyrosine could prevent the decline in dopamine, while still eliciting a drop in serotonin. Such an LNAA mixture might thus prove an effective enhancer of physical performance. The thoughtful development and application of dietary proteins and LNAA mixtures may thus produce treatments with predictable and useful functional effects.

  16. One month of cocaine abstinence potentiates rapid dopamine signaling in the nucleus accumbens core.

    Science.gov (United States)

    Cameron, Courtney M; Wightman, R Mark; Carelli, Regina M

    2016-12-01

    Cocaine addiction is a chronic relapsing disorder that is difficult to treat in part because addicts relapse even after extended periods of abstinence. Given the importance of the mesolimbic dopamine (DA) system in drug addiction, we sought to characterize cocaine abstinence induced changes in rapid DA signaling in the nucleus accumbens (NAc). Here, rats were trained to self-administer cocaine for 14 consecutive days, then divided into two groups. Day 1 rats (D1; n = 7) underwent 24 h of abstinence; Day 30 rats (D30; n = 7) underwent one month of abstinence. After abstinence, all rats underwent a single extinction session. Immediately after, rats were deeply anesthetized and fast scan cyclic voltammetry (FSCV) was used to measure DA release and uptake dynamics in the NAc core before and following a single cocaine injection. We show that one month of cocaine abstinence potentiates the peak concentration of electrically evoked DA in the NAc core following an acute injection of cocaine. This potentiation is not related to alterations in DA uptake parameters, which are unchanged following abstinence, but may reflect alterations in release. These results further support the abundance of literature showing that cocaine abstinence induces neuroplasticity in brain areas implicated in drug reward and relapse. The present findings also demonstrate critical differences between abstinence-induced neuroadaptations in DA signaling and those caused by drug exposure itself. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Human brain imaging and radiation dosimetry of 11C-N-desmethyl-loperamide, a PET radiotracer to measure the function of P-glycoprotein.

    Science.gov (United States)

    Seneca, Nicholas; Zoghbi, Sami S; Liow, Jeih-San; Kreisl, William; Herscovitch, Peter; Jenko, Kimberly; Gladding, Robert L; Taku, Andrew; Pike, Victor W; Innis, Robert B

    2009-05-01

    P-glycoprotein (P-gp) is a membrane-bound efflux pump that limits the distribution of drugs to several organs of the body. At the blood-brain barrier, P-gp blocks the entry of both loperamide and its metabolite, N-desmethyl-loperamide (N-dLop), and thereby prevents central opiate effects. Animal studies have shown that (11)C-dLop, compared with (11)C-loperamide, is an especially promising radiotracer because it generates negligible radiometabolites that enter the brain. The purposes of this study were to determine whether (11)C-dLop is a substrate for P-gp at the blood-brain barrier in humans and to measure the distribution of radioactivity in the entire body to estimate radiation exposure. Brain PET scans were acquired in 4 healthy subjects for 90 min and included concurrent measurements of the plasma concentration of unchanged radiotracer. Time-activity data from the whole brain were quantified using a 1-tissue-compartment model to estimate the rate of entry (K(1)) of radiotracer into the brain. Whole-body PET scans were acquired in 8 healthy subjects for 120 min. For brain imaging, after the injection of (11)C-dLop the concentration of radioactivity in the brain was low (standardized uptake value, approximately 15%) and stable after approximately 20 min. In contrast, uptake of radioactivity in the pituitary was about 50-fold higher than that in the brain. The plasma concentration of (11)C-dLop declined rapidly, but the percentage composition of plasma was unusually stable, with the parent radiotracer constituting 85% of total radioactivity after approximately 5 min. The rate of brain entry was low (K(1) = 0.009 +/- 0.002 mL.cm(-3).min(-1); n = 4). For whole-body imaging, as a measure of radiation exposure to the entire body the effective dose of (11)C-dLop was 7.8 +/- 0.6 muSv/MBq (n = 8). The low brain uptake of radioactivity is consistent with (11)C-dLop being a substrate for P-gp in humans and confirms that this radiotracer generates negligible quantities of

  18. O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications.

    Science.gov (United States)

    Langen, Karl-Josef; Hamacher, Kurt; Weckesser, Matthias; Floeth, Frank; Stoffels, Gabriele; Bauer, Dagmar; Coenen, Heinz H; Pauleit, Dirk

    2006-04-01

    O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a promising tracer for PET that has demonstrated convincing results especially in the diagnostics of brain tumors. In contrast to other radiolabeled amino acids, it can be produced with high efficiency and distributed in a satellite concept like the widely used 2-[18F]fluoro-2-deoxy-D-glucose. Although FET is not incorporated into proteins, it shows high uptake in cerebral gliomas and in extracranial squamous cell carcinomas owing to increased transport. The tracer exhibits high in vivo stability, low uptake in inflammatory tissue and suitable uptake kinetics for clinical imaging, which indicates that it may become a new standard tracer for PET. In this article, the present knowledge on the uptake mechanisms and the clinical applications of FET are reviewed and the clinical perspectives are discussed.

  19. O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Langen, Karl-Josef [Institute of Medicine, Research Center Juelich, D-52425 Juelich (Germany) and Brain Imaging Center West, Research Center Juelich, D-52425 Juelich (Germany)]. E-mail: k.j.langen@fz-juelich.de; Hamacher, Kurt [Institute of Nuclear Chemistry, Research Center Juelich, D-52425 Juelich (Germany); Brain Imaging Center West, Research Center Juelich, D-52425 Juelich (Germany); Weckesser, Matthias [Department of Nuclear Medicine, University of Muenster, D-48149 Muenster (Germany); Floeth, Frank [Department of Neurosurgery, Heinrich-Heine-University, D-40225 Duesseldorf (Germany); Stoffels, Gabriele [Institute of Medicine, Research Center Juelich, D-52425 Juelich (Germany); Brain Imaging Center West, Research Center Juelich, D-52425 Juelich (Germany); Bauer, Dagmar [Institute of Medicine, Research Center Juelich, D-52425 Juelich (Germany); Brain Imaging Center West, Research Center Juelich, D-52425 Juelich (Germany); Coenen, Heinz H. [Institute of Nuclear Chemistry, Research Center Juelich, D-52425 Juelich (Germany); Brain Imaging Center West, Research Center Juelich, D-52425 Juelich (Germany); Pauleit, Dirk [Institute of Medicine, Research Center Juelich, D-52425 Juelich (Germany); Brain Imaging Center West, Research Center Juelich, D-52425 Juelich (Germany)

    2006-04-15

    O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine (FET) is a promising tracer for PET that has demonstrated convincing results especially in the diagnostics of brain tumors. In contrast to other radiolabeled amino acids, it can be produced with high efficiency and distributed in a satellite concept like the widely used 2-[{sup 18}F]fluoro-2-deoxy-D-glucose. Although FET is not incorporated into proteins, it shows high uptake in cerebral gliomas and in extracranial squamous cell carcinomas owing to increased transport. The tracer exhibits high in vivo stability, low uptake in inflammatory tissue and suitable uptake kinetics for clinical imaging, which indicates that it may become a new standard tracer for PET. In this article, the present knowledge on the uptake mechanisms and the clinical applications of FET are reviewed and the clinical perspectives are discussed.

  20. 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

  1. Putrescine Uptake in Saintpaulia Petals 1

    Science.gov (United States)

    Bagni, Nello; Pistocchi, Rossella

    1985-01-01

    Putrescine uptake and the kinetics of this uptake were studied in petals of Saintpaulia ionantha Wendl. Uptake experiments of [3H] or [14C] putrescine were done on single petals at room temperature at various pH values. The results show that putrescine uptake occurs against a concentration gradient at low external putrescine concentration (0.5-100 micromolar) and follows a concentration gradient at higher external putrescine concentrations (100 micromolar to 100 millimolar). 2,4-Dinitrophenol and carbonylcyanide-m-chlorophenylhydrazone, two uncouplers, had no effect on putrescine uptake. Uptake rates were constant for 2 hours, reaching a maximum after 3 to 4 hours. Putrescine uptake depended markedly on the external pH and two maxima were observed: at low external concentrations of putrescine, the optimum was at pH 5 to 5.5; at higher concentrations the optimum was at pH 8. PMID:16664065

  2. Rapid geodesic mapping of brain functional connectivity: implementation of a dedicated co-processor in a field-programmable gate array (FPGA) and application to resting state functional MRI.

    Science.gov (United States)

    Minati, Ludovico; Cercignani, Mara; Chan, Dennis

    2013-10-01

    Graph theory-based analyses of brain network topology can be used to model the spatiotemporal correlations in neural activity detected through fMRI, and such approaches have wide-ranging potential, from detection of alterations in preclinical Alzheimer's disease through to command identification in brain-machine interfaces. However, due to prohibitive computational costs, graph-based analyses to date have principally focused on measuring connection density rather than mapping the topological architecture in full by exhaustive shortest-path determination. This paper outlines a solution to this problem through parallel implementation of Dijkstra's algorithm in programmable logic. The processor design is optimized for large, sparse graphs and provided in full as synthesizable VHDL code. An acceleration factor between 15 and 18 is obtained on a representative resting-state fMRI dataset, and maps of Euclidean path length reveal the anticipated heterogeneous cortical involvement in long-range integrative processing. These results enable high-resolution geodesic connectivity mapping for resting-state fMRI in patient populations and real-time geodesic mapping to support identification of imagined actions for fMRI-based brain-machine interfaces. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

  3. Elucidating the Function of Penetratin and a Static Magnetic Field in Cellular Uptake of Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    David Stirling

    2013-02-01

    Full Text Available Nanotechnology plays an increasingly important role in the biomedical arena. In particular, magnetic nanoparticles (mNPs have become important tools in molecular diagnostics, in vivo imaging and improved treatment of disease, with the ultimate aim of producing a more theranostic approach. Due to their small sizes, the nanoparticles can cross most of the biological barriers such as the blood vessels and the blood brain barrier, thus providing ubiquitous access to most tissues. In all biomedical applications maximum nanoparticle uptake into cells is required. Two promising methods employed to this end include functionalization of mNPs with cell-penetrating peptides to promote efficient translocation of cargo into the cell and the use of external magnetic fields for enhanced delivery. This study aimed to compare the effect of both penetratin and a static magnetic field with regards to the cellular uptake of 200 nm magnetic NPs and determine the route of uptake by both methods. Results demonstrated that both techniques increased particle uptake, with penetratin proving more cell specific. Clathrin- medicated endocytosis appeared to be responsible for uptake as shown via PCR and western blot, with Pitstop 2 (known to selectively block clathrin formation blocking particle uptake. Interestingly, it was further shown that a magnetic field was able to reverse or overcome the blocking, suggesting an alternative route of uptake.

  4. Rapid doubling of Alzheimer’s amyloid-β40 and 42 levels in brains of mice exposed to a nickel nanoparticle model of air pollution [v1; ref status: indexed, http://f1000r.es/T5Rxeo

    Directory of Open Access Journals (Sweden)

    Soong Ho Kim

    2012-12-01

    Full Text Available Background: Over 20 genetic risk factors have been confirmed to associate with elevated risk for Alzheimer’s disease (AD, but the identification of environmental and/or acquired risk factors has been more elusive. At present, recognized acquired risks for AD include traumatic brain injury, hypercholesterolemia, obesity, hypertension, and type 2 diabetes. Methods: Based on reports associating various inhalants with AD pathology, we investigated the possibility that air pollution might contribute to AD risk by exposing wild-type mice to a standard air pollution modeling system employing nickel nanoparticle-enriched atmosphere for 3 hr. Results: Mice exposed to air pollution showed 72-129% increases in brain levels of both amyloid-β peptides Aβ40 and Aβ42, as well as Aβ42/40 (p <0.01. Conclusions: These effects on elevation of brain Aβ exceed those associated with trisomy 21, a known risk for early onset AD pathology, raising the possibility that clinical importance might be attached. Further work is required to establish the molecular and physiological basis for these phenomena. The rapid, dramatic effect, if verified, would suggest that inhalant exposures should be evaluated for their possible roles in contributing to the environmental risk for common forms of AD.

  5. DNA Uptake by Transformable Bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Lacks, Sanford A.

    1999-03-31

    The various processes of DNA uptake by cells can be categorized as: viral DNA entry, conjugation, or transformation. Within each category, a variety of mechanisms have been found. However, considerable similarities occur among the different mechanisms of conjugation and, especially, transformation. All of these natural mechanisms of DNA transfer are quite elaborate and involve multiple protein components, as the case may be, of the virus, the donor cell, and the recipient cell. The mechanisms of viral infection and conjugation will be discussed mainly with respect to their relevance to transformation.

  6. DNA UPTAKE BY TRANSFORMABLE BACTERIA

    Energy Technology Data Exchange (ETDEWEB)

    LACKS,S.A.

    1999-09-07

    The various processes of DNA uptake by cells can be categorized as: viral DNA entry, conjugation, or transformation. Within each category, a variety of mechanisms have been found. However, considerable similarities occur among the different mechanisms of conjugation and, especially, transformation. All of these natural mechanisms of DNA transfer are quite elaborate and involve multiple protein components, as the case may be, of the virus, the donor cell, and the recipient cell. The mechanisms of viral infection and conjugation will be discussed mainly with respect to their relevance to transformation.

  7. Brain Basics

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    Full Text Available ... are sent from one neuron to another. Share Science News New BRAIN Grants BRAIN Cell Census Launched ... human volunteers PubMed Central: An archive of life sciences journals NIH Research Fact Sheets NIH Office of ...

  8. Brain Basics

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    Full Text Available ... to change the way she thinks about and reacts to things that may trigger her depression. Several ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain ...

  9. Brain Basics

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    Full Text Available ... Careers at NIMH Staff Directories Getting to NIMH Transforming the understanding and treatment of mental illnesses. Search ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  10. Brain Basics

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    Full Text Available ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain involved in creating and filing new memories. hypothalmic-pituitary-adrenal (HPA) ...

  11. Brain Diseases

    Science.gov (United States)

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  12. Brain Basics

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    Full Text Available ... may help improve treatments for anxiety disorders like phobias or post-traumatic stress disorder (PTSD) . Prefrontal cortex ( ... brain. Using MEG, some scientists have found a specific pattern of brain activity that may help predict ...

  13. Brain Basics

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    Full Text Available ... how the brain works, how mental illnesses are disorders of the brain, and ongoing research that helps us better understand and treat disorders. Mental disorders are common. You may have a ...

  14. Brain Basics

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    Full Text Available ... doctor that she had experienced long periods of deep sadness throughout her teenage years, but had never ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain ...

  15. Brain Basics

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    Full Text Available ... but can still remember past events and learned skills, and carry on a conversation, all which rely ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

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    Full Text Available ... technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's ... resonance imaging (MRI) mdash;An imaging technique that uses magnetic fields to take pictures of the brain's ...

  17. Brain Basics

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    Full Text Available ... go awry, leading to mental illnesses. Brain Basics will introduce you to some of this science, such ... released it increases the chance that the neuron will fire. This enhances the electrical flow among brain ...

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    Full Text Available ... Functional magnetic resonance imaging (fMRI) is another important research tool in understanding how the brain functions. Another type of brain scan called magnetoencephalography, or MEG, can ...

  19. Brain Basics

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    Full Text Available ... front of the brain, which is linked to thought and emotion. It is also linked to reward ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ...

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    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... symptoms and family medical history. Epigenetic changes from stress or early-life experiences may have made it ...

  1. Brain Basics

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    Full Text Available ... Evidence shows that they can be related to changes in the anatomy, physiology, and chemistry of the ... brain communicate and work with each other How changes in the brain can lead to mental disorders, ...

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    Full Text Available ... all. She was happily married and successful in business. Then, after a serious setback at work, she ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  4. Brain Basics

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    Full Text Available ... The basic structure of the brain How different parts of the brain communicate and work with each ... of conducting messages. A neuron has three basic parts: Cell body which includes the nucleus, cytoplasm, and ...

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    Full Text Available ... and the environment affect the brain The basic structure of the brain How different parts of the ... for the cell to work properly including small structures called cell organelles. Dendrites branch off from the ...

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    Full Text Available ... Opportunities & Announcements Funding Strategy for Grants Application Process Managing Grants Clinical Research Training Labs at NIMH Labs ... normal brain development and function can go awry, leading to mental illnesses. Brain Basics will introduce you ...

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    Full Text Available ... the brain How different parts of the brain communicate and work with each other How changes in ... communication signal sent between neurons by which neurons communicate with each other. magnetic resonance imaging (MRI) mdash; ...

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    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

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    Full Text Available ... disorder and to tailor the treatment for a person's specific conditions. Such brain research help increase the understanding of how the brain grows and works and the effects of genes and environment on mental health. This ...

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    Full Text Available ... the results can affect many aspects of life. Scientists are continually learning more about how the brain ... the normal brain's structure develops and matures helps scientists understand what goes wrong in mental illnesses. Scientists ...

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    Full Text Available ... works in healthy people, and how normal brain development and function can go awry, leading to mental ... and are working to compare that with brain development in people mental disorders. Genes and environmental cues ...

  13. Brain Basics

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    Full Text Available ... the anatomy, physiology, and chemistry of the nervous system. When the brain cannot effectively coordinate the billions ... basic working unit of the brain and nervous system. These cells are highly specialized for the function ...

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    Full Text Available ... normal brain development and function can go awry, leading to mental illnesses. Brain Basics will introduce you ... of DNA. Sometimes this copying process is imperfect, leading to a gene mutation that causes the gene ...

  15. Brain Basics

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    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ... depression experience when starting treatment. Gene Studies Advanced technologies are also making it faster, easier, and more ...

  16. Brain Basics

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    Full Text Available ... The brain continues maturing well into a person's early 20s. Knowing how the brain is wired and ... for mental disorders. This could greatly help in early detection, more tailored treatments, and possibly prevention of ...

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    Full Text Available ... related to changes in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot ... her feelings. Brain Research Modern research tools and techniques are giving scientists a more detailed understanding of ...

  18. Brain Basics

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    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... blues" from time to time. In contrast, major depression is a serious disorder that lasts for weeks. ...

  19. Brain Basics

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    Full Text Available ... the brain cannot effectively coordinate the billions of cells in the body, the results can affect many ... unit of the brain and nervous system. These cells are highly specialized for the function of conducting ...

  20. Brain Basics

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    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ... the body's response to stress. impulse —An electrical communication signal sent between neurons by which neurons communicate ...

  1. Brain Basics

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    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... in her life. She began to think of suicide because she felt like things weren't going ...

  2. Brain Basics

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    Full Text Available ... in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot effectively coordinate the billions ... the basic working unit of the brain and nervous system. These cells are highly specialized for the function ...

  3. Brain Basics

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    Full Text Available ... Neurons & Neural Circuits Neurons are the basic working unit of the brain and nervous system. These cells ... A nerve cell that is the basic, working unit of the brain and nervous system, which processes ...

  4. Brain Basics

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    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in ... or problems using dopamine in the thinking and feeling regions of the brain may play a role ...

  5. Brain Basics

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    Full Text Available ... brain may play a role in disorders like schizophrenia or attention deficit hyperactivity disorder (ADHD) . Glutamate —the ... mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons ...

  6. Brain Basics

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    Full Text Available ... can be related to changes in the anatomy, physiology, and chemistry of the nervous system. When the ... healthy people, and how normal brain development and function can go awry, leading to mental illnesses. Brain ...

  7. Brain Basics

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    Full Text Available ... as: How the brain develops How genes and the environment affect the brain The basic structure of the ... leaves the cell, and responds to signals from the environment; this all helps the cell maintain its balance ...

  8. Brain Basics

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    Full Text Available ... and her husband questions about Sarah's symptoms and family medical history. Epigenetic changes from stress or early- ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  9. Brain Basics

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    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle- ... and her husband questions about Sarah's symptoms and family medical history. Epigenetic changes from stress or early- ...

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    Full Text Available ... and aiding the flow of information to the front of the brain, which is linked to thought ... and aiding the flow of information to the front of the brain. DNA —The "recipe of life," ...

  11. Brain Basics

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    Full Text Available ... or problems using dopamine in the thinking and feeling regions of the brain may play a role ... depression helps Sarah to better cope with her feelings. Brain Research Modern research tools and techniques are ...

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    Full Text Available ... mainly involved in controlling movement and aiding the flow of information to the front of the brain, ... the neuron will fire. This enhances the electrical flow among brain cells required for normal function and ...

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    Full Text Available ... control specific body functions such as sleep and speech. The brain continues maturing well into a person's ... as in areas of the brain that control movement. When electrical signals are abnormal, they can cause ...

  14. Brain Basics

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    Full Text Available ... it increases the chance that the neuron will fire. This enhances the electrical flow among brain cells ... This area of the brain also helps to control the amygdala during stressful events. Some research shows ...

  15. Brain Basics

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    Full Text Available ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding how the brain functions. Another type of brain scan called magnetoencephalography, ...

  16. Brain Basics

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    Full Text Available ... depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of ... but sometimes give rise to disabilities or diseases. neural circuit —A network of neurons and their interconnections. ...

  17. Brain Basics

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    Full Text Available ... the brain How different parts of the brain communicate and work with each other How changes in ... occur when this process does not work correctly. Communication between neurons can also be electrical, such as ...

  18. Brain Basics

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    Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate ...

  19. Brain Basics

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    Full Text Available ... treatment for a person's specific conditions. Such brain research help increase the understanding of how the brain grows and works and the effects of genes and environment on mental health. This knowledge is allowing scientists ...

  20. Brain Basics

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    Full Text Available ... How the brain develops How genes and the environment affect the brain The basic structure of the ... inside contents of the cell from its surrounding environment and controls what enters and leaves the cell, ...

  1. Brain Basics

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    Full Text Available ... depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of ... of contact for receiving impulses on a neuron, branching off from the cell body. dopamine —A neurotransmitter ...

  2. Brain Basics

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    Full Text Available ... Publications Help for Mental Illnesses Clinical Trials Outreach Research Priorities Funding Labs at NIMH News & Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The ...

  3. Polyamine Uptake in Carrot Cell Cultures 1

    Science.gov (United States)

    Pistocchi, Rossella; Bagni, Nello; Creus, José A.

    1987-01-01

    Putrescine and spermidine uptake into carrot (Daucus carota L.) cells in culture was studied. The time course of uptake showed that the two polyamines were very quickly transported into the cells, reaching a maximum absorption within 1 minute. Increasing external polyamine concentrations up to 100 millimolar showed the existence of a biphasic system with different affinities at low and high polyamine concentrations. The cellular localization of absorbed polyamines was such that a greater amount of putrescine was present in the cytoplasmic soluble fraction, while spermidine was mostly present in cell walls. The absorbed polyamines were released into the medium in the presence of increasing external concentrations of the corresponding polyamine or Ca2+. The effects of Ca2+ were different for putrescine and spermidine; putrescine uptake was slightly stimulated by 10 micromolar Ca2+ and inhibited by higher concentrations, while for spermidine uptake there was an increasing stimulation in the Ca2+ concentration range between 10 micromolar and 1 millimolar. La3+ nullified the stimulatory effect of 10 micromolar Ca2+ on putrescine uptake and that of 1 millimolar Ca2+ on spermidine uptake. La3+ at 0.5 to 1 millimolar markedly inhibited the uptake of both polyamines, suggesting that it interferes with the sites of polyamine uptake. Putrescine uptake was affected to a lesser extent by metabolic inhibitors than was spermidine uptake. It is proposed that the entry of polyamines into the cells is driven by the transmembrane electrical gradient, with a possible antiport mechanism between external and internal polyamine molecule. PMID:16665446

  4. Brain Basics

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    Full Text Available ... a major mood circuit called the hypothalamic-pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain ... in creating and filing new memories. hypothalmic-pituitary-adrenal (HPA) axis —A brain-body circuit which plays ...

  5. Brain Aneurysm

    Science.gov (United States)

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  6. Brain Basics

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    Full Text Available ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate have been ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain involved in ...

  7. Brain Basics

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    Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works in healthy people, and how ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain involved in creating and filing new memories. hypothalmic- ...

  8. Brain Basics

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    Full Text Available ... including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons working together form ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman ...

  9. Brain Basics

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    Full Text Available ... pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah ... having trouble coping with the stresses in her life. She began to think of suicide because she ...

  10. Brain Basics

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    Full Text Available ... These circuits control specific body functions such as sleep and speech. The brain continues maturing well into a person's early 20s. ... that regulates many functions, including mood, appetite, and sleep. synapse —The tiny gap between neurons, where nerve impulses are sent from one neuron to ... of Deep Brain Stimulation Brain’s Alertness Circuitry Revealed New BRAIN Grants ...

  11. Brain Aneurysm

    Science.gov (United States)

    ... inside of the brain (ventricles) or surrounding your brain and spinal cord to drain the excess fluid into an external bag. Sometimes it may then be necessary to introduce a shunt system — which consists of a ... brain and ending in your abdominal cavity. Rehabilitative therapy. ...

  12. Brain Basics

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    Full Text Available ... brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism appears to peak early. And as they grow there are differences in ...

  13. Brain Basics

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    Full Text Available ... another important research tool in understanding how the brain functions. Another type of brain scan called magnetoencephalography, or ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as judgment, decision making and problem solving, ...

  14. Bleomycin treatment of brain tumors: an evaluation

    DEFF Research Database (Denmark)

    Linnert, Mette; Gehl, Julie

    2009-01-01

    Bleomycin has been used in the treatment of brain tumors for over 30 years. Currently, we are evaluating electrochemotherapy (the use of electric pulses to enhance uptake of bleomycin) for patients with secondary brain tumors. We, therefore, reviewed the literature with specific reference...... to the tolerability and toxicity of bleomycin. Using the keywords 'brain' and 'bleomycin', a database search without date restriction was performed and over 500 articles were found. Twenty-five articles were used for this study based on relevance determined by: (i) clinical studies, (ii) use of bleomycin, and (iii......) direct injection into brain tissue or cysts. There were two main indications for the use of bleomycin directly into the brain: (i) cystic tumors in the form of craniopharyngiomas and (ii) solid brain tumors such as glioblastomas and astrocytomas. The most frequent adverse effects reported were transient...

  15. Left Brain. Right Brain. Whole Brain

    Science.gov (United States)

    Farmer, Lesley S. J.

    2004-01-01

    As the United States student population is becoming more diverse, library media specialists need to find ways to address these distinctive needs. However, some of these differences transcend culture, touching on variations in the brain itself. Most people have a dominant side of the brain, which can affect their personality and learning style.…

  16. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio.

    Science.gov (United States)

    Yang, Tianzhi; Martin, Paige; Fogarty, Brittany; Brown, Alison; Schurman, Kayla; Phipps, Roger; Yin, Viravuth P; Lockman, Paul; Bai, Shuhua

    2015-06-01

    The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model. Four types of exosomes were isolated from brain cell culture media and characterized by particle size, morphology, total protein, and transmembrane protein markers. Transport mechanism, cell uptake, and cytotoxicity of optimized exosome delivery system were tested. Brain distribution of exosome delivered anticancer drugs was evaluated using transgenic zebrafish TG (fli1: GFP) embryos and efficacies of optimized formations were examined in a xenotransplanted zebrafish model of brain cancer model. Four exosomes in 30-100 diameters showed different morphologies and exosomes derived from brain endothelial cells expressed more CD63 tetraspanins transmembrane proteins. Optimized exosomes increased the uptake of fluorescent marker via receptor mediated endocytosis and cytotoxicity of anticancer drugs in cancer cells. Images of the zebrafish showed exosome delivered anticancer drugs crossed the BBB and entered into the brain. In the brain cancer model, exosome delivered anticancer drugs significantly decreased fluorescent intensity of xenotransplanted cancer cells and tumor growth marker. Brain endothelial cell derived exosomes could be potentially used as a carrier for brain delivery of anticancer drug for the treatment of brain cancer.

  17. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    , impairment of insulin action on muscle glucose transport and uptake. Thus maximal insulin-stimulated glucose uptake at 12 mM-glucose decreased from 34.8 +/- 1.9 to 11.5 +/- 1.1 mumol/h per g (mean +/- S.E.M., n = 10) during 5 h perfusion. This decrease in glucose uptake was accompanied by a similar change...... in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation....

  18. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, Henrik; Richter, Erik

    1984-01-01

    We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats...... in severe ketoacidosis were perfused with a perfusate containing insulin antiserum. After 60 min perfusion, electrical stimulation increased glucose uptake of the contracting muscles fivefold. Also, subsequent contractions increased glucose uptake in hindquarters from nondiabetic rats perfused for 1.5 h......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

  19. New findings on cerebral ammonia uptake in HE using functional (13)N-ammonia PET

    DEFF Research Database (Denmark)

    Sørensen, Michael; Keiding, Susanne

    2007-01-01

    ) analysed such data in patients with HE by a kinetic model accounting for transfer of (13)N-ammonia across the blood-brain barrier (BBB) and intracellular formation of (13)N-glutamine. Initial unidirectional (13)N-ammonia transfer across BBB was characterized by the permeability-surface area product PS...... metabolites was linearly correlated to arterial ammonia. In conclusion, basic brain ammonia kinetics was not changed significantly in patients with cirrhosis +/- HE compared to healthy controls. Blood ammonia seems to be the more important factor for increased brain ammonia uptake in HE. Udgivelsesdato: 2007......PET is a functional imaging technique suitable for studies of brain ammonia metabolism. Dynamic (13)N-ammonia PET yields time-courses of radioactivity concentrations in brain (PET camera) and blood (samples). Ahl et al. (Hepatology 40:73-79, 2004) and Keiding et al. (Hepatology 43:42-50, 2006...

  20. In vitro uptake of /sup 14/C-praziquantel by cestodes, trematodes, and a nematode

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, P.; Thomas, H.; Weber, H.

    1980-12-01

    /sup 14/C-praziquantel was rapidly taken up by Schistosoma mansoni, Fasciola hepatica, Hymenolepis nana, and isolated strobilocerci of Taenia taeniaeformis. Schistosoma mansoni lost praziquantel rapidly to drug-free medium. Chromatography of extracts prepared after incubation of S. mansoni and H. nana yielded no indication that praziquantel was metabolized. Autoradiography revealed a uniform distribution of praziquantel throughout the tissues of S. mansoni and H. nana. Uptake was considerably slower in the nematode Heterakis spumosa and apparently via the oral route.

  1. Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene-Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy.

    Science.gov (United States)

    Fang, Jen-Hung; Chiu, Tsung-Lang; Huang, Wei-Chen; Lai, Yen-Ho; Hu, Shang-Hsiu; Chen, You-Yin; Chen, San-Yuan

    2016-03-01

    Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing efficiency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fluorescence upon intracellular uptake for cell trafficking and imaging-guided tumor treatment. The magnetic Lf-modified PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain-bearing rats. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer's disease.

    Science.gov (United States)

    Poisnel, Géraldine; Hérard, Anne-Sophie; El Tannir El Tayara, Nadine; Bourrin, Emmanuel; Volk, Andreas; Kober, Frank; Delatour, Benoit; Delzescaux, Thierry; Debeir, Thomas; Rooney, Thomas; Benavides, Jésus; Hantraye, Philippe; Dhenain, Marc

    2012-09-01

    Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow-up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month-old APP(SweLon)/PS1(M146L), a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared with age-matched control mice. We then developed a method of 3-D microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganization of glucose uptake in relation to cerebral amyloidosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. In vitro models of the blood-brain barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Abbott, N Joan; Burek, Malgorzata

    2016-01-01

    components of plasma and xenobiotics. This "blood-brain barrier" function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug...

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Radioiodine uptake in inactive pulmonary tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Bakheet, S.M.; Powe, J.; Al Suhaibani, H. [Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Hammami, M.M.; Bazarbashi, M. [Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)

    1999-06-01

    Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases. (orig.) With 4 figs., 1 tab., 9 refs.

  6. Optimizing simulated fertilizer additions using a genetic algorithm with a nutrient uptake model

    Science.gov (United States)

    Wendell P. Cropper; N.B. Comerford

    2005-01-01

    Intensive management of pine plantations in the southeastern coastal plain typically involves weed and pest control, and the addition of fertilizer to meet the high nutrient demand of rapidly growing pines. In this study we coupled a mechanistic nutrient uptake model (SSAND, soil supply and nutrient demand) with a genetic algorithm (GA) in order to estimate the minimum...

  7. Effect of 8-hydroxyquinoline on the uptake of uridine and incorporation into RNA.

    Science.gov (United States)

    Grierson, D; Hemleben, V

    1977-01-01

    8-hydroxyquinoline has been previously used as an inhibitor in studies on porphyrin metabolism, where it is thought to act by chelating iron. It is shown that this compound also rapidly inhibits uridine uptake of seedlings or cotyledons of the crucifer Matthiola incana R.Br. RNA synthesis is also affected but the inhibition is not as severe as reported for fission yeast.

  8. Rapid whole-brain resting-state fMRI at 3 T: Efficiency-optimized three-dimensional EPI versus repetition time-matched simultaneous-multi-slice EPI.

    Science.gov (United States)

    Stirnberg, Rüdiger; Huijbers, Willem; Brenner, Daniel; Poser, Benedikt A; Breteler, Monique; Stöcker, Tony

    2017-09-18

    State-of-the-art simultaneous-multi-slice (SMS-)EPI and 3D-EPI share several properties that benefit functional MRI acquisition. Both sequences employ equivalent parallel imaging undersampling with controlled aliasing to achieve high temporal sampling rates. As a volumetric imaging sequence, 3D-EPI offers additional means of acceleration complementary to 2D-CAIPIRINHA sampling, such as fast water excitation and elliptical sampling. We performed an application-oriented comparison between a tailored, six-fold CAIPIRINHA-accelerated 3D-EPI protocol at 530 ms temporal and 2.4 mm isotropic spatial resolution and an SMS-EPI protocol with identical spatial and temporal resolution for whole-brain resting-state fMRI at 3 T. The latter required eight-fold slice acceleration to compensate for the lack of elliptical sampling and fast water excitation. Both sequences used vendor-supplied on-line image reconstruction. We acquired test/retest resting-state fMRI scans in ten volunteers, with simultaneous acquisition of cardiac and respiration data, subsequently used for optional physiological noise removal (nuisance regression). We found that the 3D-EPI protocol has significantly increased temporal signal-to-noise ratio throughout the brain as compared to the SMS-EPI protocol, especially when employing motion and nuisance regression. Both sequence types reliably identified known functional networks with stronger functional connectivity values for the 3D-EPI protocol. We conclude that the more time-efficient 3D-EPI primarily benefits from reduced parallel imaging noise due to a higher, actual k-space sampling density compared to SMS-EPI. The resultant BOLD sensitivity increase makes 3D-EPI a valuable alternative to SMS-EPI for whole-brain fMRI at 3 T, with voxel sizes well below 3 mm isotropic and sampling rates high enough to separate dominant cardiac signals from BOLD signals in the frequency domain. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Mechanism of cellular uptake of genotoxic silica nanoparticles.

    Science.gov (United States)

    Mu, Qingshan; Hondow, Nicole S; Krzemiński, Lukasz; Brown, Andy P; Jeuken, Lars J C; Routledge, Michael N

    2012-07-23

    Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14 nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500 nm. In HT29, HaCat and A549 cells, cytotoxicity was observed at nanoparticle concentrations ≥ 1 μg/ml, but DNA damage was evident at 0.1 μg/ml and above. Transmission electron microscopy (TEM) combined with energy-dispersive X-ray spectroscopy confirmed entry of the silica particles into A549 cells exposed to 10 μg/ml of nanoparticles. The particles were observed in the cytoplasm but not within membrane bound vesicles or in the nucleus. TEM of cells exposed to nanoparticles at 4°C for 30 minutes showed particles enter cells when activity is low, suggesting a passive mode of entry. Plasma lipid membrane models identified physical interactions between the membrane and the silica NPs. Quartz crystal microbalance experiments on tethered bilayer lipid membrane systems show that the nanoparticles strongly bind to lipid membranes, forming an adherent monolayer on the membrane. Leakage assays on large unilamellar vesicles (400 nm diameter) indicate that binding of the silica NPs transiently disrupts the vesicles which rapidly self-seal. We suggest that an adhesive interaction between silica nanoparticles and lipid membranes could cause passive cellular uptake of the particles.

  10. Mechanism of cellular uptake of genotoxic silica nanoparticles

    Directory of Open Access Journals (Sweden)

    Mu Qingshan

    2012-07-01

    Full Text Available Abstract Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14 nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500 nm. In HT29, HaCat and A549 cells, cytotoxicity was observed at nanoparticle concentrations ≥ 1 μg/ml, but DNA damage was evident at 0.1 μg/ml and above. Transmission electron microscopy (TEM combined with energy-dispersive X-ray spectroscopy confirmed entry of the silica particles into A549 cells exposed to 10 μg/ml of nanoparticles. The particles were observed in the cytoplasm but not within membrane bound vesicles or in the nucleus. TEM of cells exposed to nanoparticles at 4°C for 30 minutes showed particles enter cells when activity is low, suggesting a passive mode of entry. Plasma lipid membrane models identified physical interactions between the membrane and the silica NPs. Quartz crystal microbalance experiments on tethered bilayer lipid membrane systems show that the nanoparticles strongly bind to lipid membranes, forming an adherent monolayer on the membrane. Leakage assays on large unilamellar vesicles (400 nm diameter indicate that binding of the silica NPs transiently disrupts the vesicles which rapidly self-seal. We suggest that an adhesive interaction between silica nanoparticles and lipid membranes could cause passive cellular uptake of the particles.

  11. Plant uptake of pentachlorophenol from sludge-amended soils

    Energy Technology Data Exchange (ETDEWEB)

    Bellin, C.A.; O' Connor, G.A.

    1990-01-01

    A greenhouse study was conducted to determine the effects of sludge on plant uptake of {sup 14}C-pentachlorophenol (PCP). Plants included tall fescue (Festuca arundinacea Schreb.), lettuce (Latuca sativa L.), carrot (Daucus carota L.), and chile pepper (Capsicum annum L.). Minimal intact PCP was detected in the fescue and lettuce by gas chromatography/mass spectrometry (GC/MS) analysis. No intact PCP was detected in the carrot tissue extracts. Chile pepper was not analyzed for intact PCP because methylene chloride extracts contained minimal {sup 14}C. The GC/MS analysis of soil extracts at harvest suggests a half-life of PCP of about 10 d independent of sludge rate or PCP loading rate. Rapid degradation of PCP in the soil apparently limited PCP availability to the plant. Bioconcentration factors (dry plant wt./initial soil PCP concentration) based on intact PCP were <0.01 for all crops, suggesting little PCP uptake. Thus, food-chain crop PCP uptake in these alkaline soils should not limit land application of sludge.

  12. Plant uptake of dual-labeled organic N biased by inorganic C uptake

    DEFF Research Database (Denmark)

    Rasmussen, Jim; Sauheitl, Leopold; Eriksen, Jørgen

    2010-01-01

    labeling experiment (15N + 13C + 14C) investigating whether root uptake of labeled inorganic C can bias the results obtained in studies of organic N uptake using dual-labeled amino acids (15N, 13C). In a rhizosphere tube experiment we investigated 13C and 14C uptake by maize either supplied with labeled...... glycine or CO2-3 , but found no differences in uptake rates between these C-sources. The uptake of inorganic C to the shoot tissue was higher for maize grown in full light compared to shading, which indicates a passive uptake of inorganic C with water. We conclude that uptake of inorganic C produced...... by mineralization of amino acids can significantly bias the interpretations of organic N uptake studies using dual-labeling....

  13. 3-[(123)I]Iodo-alpha-methyl-L-tyrosine: uptake mechanisms and clinical applications.

    Science.gov (United States)

    Langen, Karl-Josef; Pauleit, Dirk; Coenen, Heinz H

    2002-08-01

    3-[(123)I]Iodo-alpha-methyl-L-tyrosine (IMT) is an artificial amino acid which has gained considerable interest in Nuclear Medicine in the last two decades. Although the tracer is not incorporated into proteins it exhibits high uptake in brain tumors and appears to be a valuable tool especially for the diagnostic evaluation and therapy planning of patients with cerebral gliomas. In this paper the present knowledge of the uptake mechanisms and the clinical applications of IMT are reviewed and the clinical perspectives discussed.

  14. Single-Stranded DNA Uptake during Gonococcal Transformation.

    Science.gov (United States)

    Hepp, Christof; Gangel, Heike; Henseler, Katja; Günther, Niklas; Maier, Berenike

    2016-09-15

    Neisseria gonorrhoeae is naturally competent for transformation. The first step of the transformation process is the uptake of DNA from the environment into the cell. This transport step is driven by a powerful molecular machine. Here, we addressed the question whether this machine imports single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) at similar rates. The fluorescence signal associated with the uptake of short DNA fragments labeled with a single fluorescent marker molecule was quantified. We found that ssDNA with a double-stranded DNA uptake sequence (DUS) was taken up with a similar efficiency as dsDNA. Imported ssDNA was degraded rapidly, and the thermonuclease Nuc was required for degradation. In a nuc deletion background, dsDNA and ssDNA with a double-stranded DUS were imported and used as the substrates for transformation, whereas the import and transformation efficiencies of ssDNA with single-stranded DUS were below the detection limits. We conclude that the DNA uptake machine requires a double-stranded DUS for efficient DNA recognition and transports ssDNA and dsDNA with comparable efficiencies. Bacterial transformation enables bacteria to exchange genetic information. It can speed up adaptive evolution and enhances the potential of DNA repair. The transport of DNA through the outer membrane is the first step of transformation in Gram-negative species. It is driven by a powerful molecular machine whose mechanism remains elusive. Here, we show for Neisseria gonorrhoeae that the machine transports single- and double-stranded DNA at comparable rates, provided that the species-specific DNA uptake sequence is double stranded. Moreover, we found that single-stranded DNA taken up into the periplasm is rapidly degraded by the thermonuclease Nuc. We conclude that the secondary structure of transforming DNA is important for the recognition of self DNA but not for the process of transport through the outer membrane. Copyright © 2016, American Society

  15. Brain hypoxia imaging

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2007-04-15

    The measurement of pathologically low levels of tissue pO{sub 2} is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowadays have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. {sup 18}F-MISO PET and {sup 99m}Tc-EC-metronidazole SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using {sup 123}I-IAZA in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

  16. Effects of dehydroepiandrosterone (DHEA) and lactate on glucose uptake in the central nervous system.

    Science.gov (United States)

    de Souza, Danielle Kaiser; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos Rios

    2012-01-17

    Dehydroepiandrosterone (DHEA) prevents brain aging, enhances the cerebral metabolism and interacts with energy substrates. The interaction between lactate and DHEA on glucose uptake and lactate oxidation by various nervous structures was investigated and results demonstrate that the 2-(14)C-deoxiglucose (2-(14)C-Dglucose) uptake was stimulated by 10mM lactate in the hypothalamus and olfactory bulb, inhibited in the cerebral cortex and cerebellum, and unaffected in the hippocampus. We also show that, in both the cerebral cortex and hypothalamus, (14)C-lactate oxidation was higher than (14)C-glucose oxidation (p≤0.001), demonstrating a relevant role for lactate as energy substrate. The interaction of lactate and 10(-8)M DHEA was tested and, although DHEA had no significant effect on uptake in the cerebellum, hippocampus, or hypothalamus, 10(-8)M DHEA increased the 2-(14)C-Dglucose uptake in the cerebral cortex in the presence of lactate (p≤0.001), and in the olfactory bulb in the absence of lactate (pDHEA had no significant effect on (14)C-lactate oxidation. We suggest that DHEA improves glucose uptake in specific conditions. Thus, DHEA may affect CNS metabolism and interact with lactate, which is the most important neuronal energy substrate, on glucose uptake. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Brain glycogen

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia....... In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic...... activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...

  18. Brain death.

    Science.gov (United States)

    Beresford, H R

    1999-05-01

    Current law in the United States authorizes physicians to diagnose brain death by applying generally accepted neurologic criteria for determining loss of function of the entire brain. This article offers a medical-legal perspective on problems that may arise with respect to the determination of brain death. These include the possibility of diagnostic error, conceptual disagreements that may constrain the use of neurologic criteria to diagnose death, and the conflation of brain death and loss of consciousness. This article also addresses legal aspects of the debate over whether to expand the definition of brain death to include permanent unconsciousness. Although existing laws draw a clear distinction between brain death and the persistent vegetative state, many courts have authorized removal of life support from individuals whose unconsciousness is believed to be permanent on proof that removal accords with preferences expressed before sentience was lost.

  19. Comparative analysis of nitrite uptake and hemoglobin-nitrite reactions in erythrocytes: sorting out uptake mechanisms and oxygenation dependencies

    DEFF Research Database (Denmark)

    Jensen, Frank Bo; Rohde, Sabina

    2010-01-01

    (hagfish and lamprey) anion exchanger-1 (AE1) in the membrane, with the aim to unravel the mechanisms and oxygenation dependencies of nitrite transport. Added nitrite rapidly diffused into the RBCs until equilibrium. The distribution ratio of nitrite across the membrane agreed with that expected from HNO2...... diffusion and AE1-mediated facilitated NO2- diffusion. Participation of HNO2 diffusion was emphasized by rapid transmembrane nitrite equilibration also in the natural AE1 knockouts. Following the equilibration, nitrite was consumed by reacting with Hb, which created a continued inward diffusion controlled....... We propose a model for RBC nitrite uptake that involves both HNO2 diffusion and AE1-mediated transport and which explains both the present and previous (sometimes puzzling) results....

  20. Determinants of pneumococcal conjugate vaccine uptake among ...

    African Journals Online (AJOL)

    Determinants of pneumococcal conjugate vaccine uptake among children attending immunisation services at Kenyatta National Hospital, Nairobi, Kenya. ... Results: The study established that the determinants of uptake of Pneumococcal Conjugate Vaccine are age(OR 5.8, CI 1.4-23.4, p=0.014), level of education (OR 5.8, ...

  1. Water-polymer interaction during water uptake

    NARCIS (Netherlands)

    Baukh, V.; Huinink, H.P.; Adan, O.C.G.; Erich, S.J.F.; Ven, L.G.J. van der

    2011-01-01

    Water uptake by multilayer films plays an important role in their performance. Individual layers may consist of different polymeric phases. Understanding the water uptake in such systems requires knowledge of the water distribution, its state in the polymer, and influence on the polymeric phases.

  2. Radio-active iodine uptake in vitiligo

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, V.; Shankar, V.; Chaudhary, S.; Bhatia, K.K.; Mehta, L.K.; Arora, D.R. (Medical College and Hospital, Rohtak-124001 (India))

    1990-01-01

    Vitiligo and thyroid disease are commonly associated disorders. Twenty-two clinically euthyroid vitiligo patients were studied for functional assessment of thyroid by radioactive iodine uptake assay. Half of them showed abnormal uptake values at 24 hours. Of these patients, 90% had lower values indicating a tendency towards developing hypothyroid state. Subclinical thyroid dysfunction in vitiligo appears to be an adaptive change. (author).

  3. Nitrogen uptake dynamics of a persistent cyanobacterium ...

    African Journals Online (AJOL)

    ... particularly salinity, which suppressed uptake rates, and temperature, which facilitated them. The long-term bloom maintenance appears to be attributed to efficient nutrient uptake rates, absence of grazers during the hypersaline phase, and the ability of Cyanothece sp. to outcompete other microalgae at temperatures >25 ...

  4. Perception, acceptance and uptake of Human papillomavirus ...

    African Journals Online (AJOL)

    Infection with Human papillomavirus (HPV) contributes to malignant changes in the cervix leading to cancer mortality among women. HPV vaccine is now available for its prevention, yet the level of uptake is low. The study aimed at determining Perception, Acceptance and Uptake of Human papillomavirus Vaccine among ...

  5. Brain Basics

    Medline Plus

    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons working together form ...

  6. Insulin resistance and maximal oxygen uptake

    DEFF Research Database (Denmark)

    Seibaek, Marie; Vestergaard, Henrik; Burchardt, Hans

    2003-01-01

    BACKGROUND: Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown. HYPOTHESIS: This study was undertaken to determine the relationship between insulin resistance, maximal oxygen uptake......, and the presence of either diabetes or ischemic heart disease. METHODS: The study population comprised 33 patients with and without diabetes and ischemic heart disease. Insulin resistance was measured by a hyperinsulinemic euglycemic clamp; maximal oxygen uptake was measured during a bicycle exercise test. RESULTS......: There was a strong correlation between maximal oxygen uptake and insulin-stimulated glucose uptake (r = 0.7, p = 0.001), and maximal oxygen uptake was the only factor of importance for determining insulin sensitivity in a model, which also included the presence of diabetes and ischemic heart disease. CONCLUSION...

  7. Uptake of ascorbic acid by freshly isolated cells and secretory granules from the intermediate lobe of ox hypophyses

    DEFF Research Database (Denmark)

    Zhou, A; Matsumoto, T; Farver, O

    1990-01-01

    Mechanically isolated cells from the intermediate lobe of ox hypophyses contained 40.6 +/- 3.7 nmol mg-1 protein (mean +/- SE, n = 5) of ascorbic acid. They accumulated radioactivity time dependently, on incubation with L-[14C]ascorbic acid in ionic medium dominated by NaCl. No definite saturation...... of uptake occurred when mechanically isolated cells were incubated with increasing ascorbic acid concentrations up to 0.6 mM. But if such cells were purified on a Percoll gradient, a clear saturation of uptake could be observed. Acetylsalicylic acid reduced the uptake markedly. When cells loaded with L-[14C]ascorbic...... sodium-dependent. Phloridzin inhibited uptake. Secretory granules from pars intermedia contained 40.0 +/- 3.8 nmol mg-1 protein of ascorbic acid (mean +/- SE, n = 3) and could accumulate L-[14C]ascorbic acid rapidly in a KCl-dominated medium. The uptake was not saturable with ascorbic acid concentration...

  8. Development of a cost-efficient novel method for rapid, concurrent genotyping of five common single nucleotide polymorphisms of the brain derived neurotrophic factor (BDNF) gene by tetra-primer amplification refractory mutation system.

    Science.gov (United States)

    Wang, Cathy K; Xu, Michael S; Ross, Colin J; Lo, Ryan; Procyshyn, Ric M; Vila-Rodriguez, Fidel; White, Randall F; Honer, William G; Barr, Alasdair M

    2015-09-01

    Brain derived neurotrophic factor (BDNF) is a molecular trophic factor that plays a key role in neuronal survival and plasticity. Single nucleotide polymorphisms (SNPs) of the BDNF gene have been associated with specific phenotypic traits in a large number of neuropsychiatric disorders and the response to psychotherapeutic medications in patient populations. Nevertheless, due to study differences and occasionally contrasting findings, substantial further research is required to understand in better detail the association between specific BDNF SNPs and these psychiatric disorders. While considerable progress has been made recently in developing advanced genotyping platforms of SNPs, many high-throughput probe- or array-based detection methods currently available are limited by high costs, slow processing times or access to advanced instrumentation. The polymerase chain reaction (PCR)-based, tetra-primer amplification refractory mutation system (T-ARMS) method is a potential alternative technique for detecting SNP genotypes efficiently, quickly, easily, and cheaply. As a tool in psychopathology research, T-ARMS was shown to be capable of detecting five common SNPs in the BDNF gene (rs6265, rs988748, rs11030104, 11757G/C and rs7103411), which are all SNPs with previously demonstrated clinical relevance to schizophrenia and depression. The present technique therefore represents a suitable protocol for many research laboratories to study the genetic correlates of BDNF in psychiatric disorders. Copyright Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  9. [{sup 11}C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis, pharmacological characterization and microPET studies in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zessin, Joerg [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany)]. E-mail: j.zessin@fz-rossendorf.de; Deuther-Conrad, Winnie [Institut fuer Interdisziplinaere Isotopenforschung, 04318 Leipzig (Germany); Kretzschmar, Marion [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany); Wuest, Frank [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany); Pawelke, Beate [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany); Brust, Peter [Institut fuer Interdisziplinaere Isotopenforschung, 04318 Leipzig (Germany); Steinbach, Joerg [Institut fuer Interdisziplinaere Isotopenforschung, 04318 Leipzig (Germany); Bergmann, Ralf [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany)

    2006-01-15

    N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (S Me-Adam, 1) is a highly potent and selective inhibitor of the serotonin transporter (SPERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [{sup 11}C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [{sup 11}C]S Me-Adam. The radiochemical yield was 27{+-}5%, and the specific radioactivity was 26-40 GBq/{mu}mol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SPERT, such as the thalamus/hypothalamus region (3.59{+-}0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74{+-}0.95 at 60 min postinjection. The [{sup 11}C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38{+-}11% of the control value. Furthermore, no metabolites of [{sup 11}C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [{sup 11}C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.

  10. Incidence of phytoplankton and environmental conditions on the bacterial ammonium uptake in a subtropical coastal lagoon

    Directory of Open Access Journals (Sweden)

    Germán Pérez

    2014-03-01

    Full Text Available We analyzed the coupling between bacterioplankton and phytoplankton in Laguna de Rocha through an experimental approach. A freshwater zone of high turbidity and macrophytes growth and a brackish zone of higher light penetration and lower macrophytes biomass characterize this coastal lagoon. It has been shown that dissolved inorganic nitrogen, especially NH4+, has decreased to undetectable levels during the last decade. One hypothesis for this trend is the rapid removal by phytoplankton and bacterioplankton uptake. In an attempt to test this, we performed incubations using lagoon water from both zones split in two treatments (pre-filtered by 1.2 µm and unfiltered water and amended with 15N-NH4+. After 4 h incubation we found that in both zones bacterioplankton showed significantly higher NH4+ uptake rates when incubated together with phytoplankton and that uptake rates of both microbial communities were higher in freshwater incubations. These results suggest that bacterial NH4+ uptake would be coupled to phytoplankton-derived exudates and hence that depletion of dissolved NH4+ in this system could be linked to rapid microbial uptake. The degree of this coupling would vary according to hydrological dynamics in this ecosystem.

  11. Teleoncology uptake in British Columbia.

    Science.gov (United States)

    Clarke, Melissa; Barnett, Jeff

    2011-01-01

    Telehealth enables the delivery of specialized health care to patients living in isolated and remote regions. The purpose of this analysis is to determine the current uptake of teleoncology in mainland British Columbia. Patient appointment data was extracted from the Cancer Agency Information System (CAIS) for the 2009 calendar year. Three types of practitioners used teleoncology in 2009: Medical Oncologists, Genetic Counsellors and Medical Geneticists. In total, 712 telehealth encounters were conducted; Medical Oncologists conducted 595 encounters (83.6%), Genetic Counsellors conducted 112 encounters (15.7%) and Medical Geneticists conducted 5 encounters (0.7%). The most common oncology appointments were Gastro-Intestinal (11.4%) and Lymphoma (11.0%) follow-up appointments with a Medical Oncologist. Telehealth encounters were conducted by 46 individual health care providers however, a single Medical Oncologist conducted 418 encounters and this accounts for more than half (58.7%) of all telehealth appointments in 2009. Radiation Oncologists on the mainland up to this point are not using the technology. The Local Health Areas with the highest number of oncology telehealth appointments were: Kamloops: 203 encounters (34.1%), Penticton: 84 encounters (14.1%), Cranbrook: 58 encounters (9.7%) and the Southern Okanagan: 33 encounter (5.5%). Use of telehealth in rural and remote areas of BC is limited and there is significant room for growth. Further research will be required to identify barriers and restrictions to the use of telehealth in order to increase teleoncology adoption in British Columbia.

  12. Semi-automated brain segmentation method applied to a SPECT study of sup 99m Tc HMPAO uptake in migraine patients. Application d'une methode de sectorisation cerebrale semi-automatique a l'etude tomographique de la fixation du sup 99m Tc-HMPAO chez des migraineux

    Energy Technology Data Exchange (ETDEWEB)

    Bessou, M.; Dupui, P; Geraud, G.; Danet, B. (Centre Hospitalier Universitaire de Rangueil, 31 - Toulouse (France)); Gantet, P. (Centre Hospitalier Universitaire Purpan, 31 - Toulouse (France))

    1992-01-01

    The segmentation method used allows a 2x16 uptake index to be calculated for each transverse section. Significant differences were found in the analogous indexes (ANOVA) between (1) migraine patients during and outside attacks (2) control subjects and migraine patients outside attacks. Highly significant asymmetries were found between posterior cerebral indexes (p<0.01 or p<0.001) in migraine patients during attacks.

  13. Association between FDG uptake, CSF biomarkers and cognitive performance in patients with probable Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Arlt, Soenke; Jahn, Holger; Eichenlaub, Martin [University Medical Center Hamburg-Eppendorf, Department of Psychiatry and Psychotherapy, Hamburg (Germany); Brassen, Stefanie [University Medical Center Hamburg-Eppendorf, Institute for Systems Neuroscience, Hamburg (Germany); Wilke, Florian; Apostolova, Ivayla; Buchert, Ralph [University Medical Center Hamburg-Eppendorf, Department of Nuclear Medicine, Hamburg (Germany); Wenzel, Fabian; Young, Stewart [Philips Research, Digital Imaging Department, Hamburg (Germany); Thiele, Frank [Philips Research, Molecular Imaging Department, Aachen (Germany)

    2009-07-15

    Brain imaging of FDG uptake and cerebrospinal fluid (CSF) concentration of amyloid-beta 1-42 (A{beta}{sub 1-42}) or tau proteins are promising biomarkers in the diagnosis of Alzheimer's disease (AD). There is still uncertainty regarding any association between decreased FDG uptake and alterations in CSF markers. The relationship between FDG uptake, CSF A{beta}{sub 1-42} and total tau (T-tau), as well as the Mini-Mental State Examination (MMSE) score was investigated in 34 subjects with probable AD using step-wise linear regression. FDG uptake was scaled to the pons. Scaled FDG uptake was significantly reduced in the probable AD subjects compared to 17 controls bilaterally in the precuneus/posterior cingulate area, angular gyrus/inferior parietal cortex, inferior temporal/midtemporal cortex, midfrontal cortex, and left caudate. Voxel-based single-subject analysis of the probable AD subjects at p < 0.001 (uncorrected) revealed a total volume of significant hypometabolism ranging from 0 to 452 ml (median 70 ml). The total hypometabolic volume was negatively correlated with the MMSE score, but it was not correlated with the CSF measures. VOI-based step-wise linear regression revealed that scaled FDG uptake in the precuneus/posterior cingulate was negatively correlated with CSF A{beta}{sub 1-42}. Scaled FDG uptake in the caudate was positively correlated with CSF T-tau. The extent and local severity of the reduction in FDG uptake in probable AD subjects are associated with cognitive impairment. In addition, there appears to be a relationship between local FDG uptake and CSF biomarkers which differs between different brain regions. (orig.)

  14. Brain Basics

    Medline Plus

    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in the brain. Problems in producing dopamine can result in Parkinson's disease, a disorder that affects a person's ability to move as they want to, resulting in ...

  15. Brain Basics

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    Full Text Available ... The brain's "fear hub," which activates our natural "fight-or-flight" response to confront or escape from a dangerous ... The brain's "fear hub," which helps activate the fight-or-flight response and is also involved in emotions and ...

  16. Brain Basics

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    Full Text Available ... will fire. This enhances the electrical flow among brain cells required for normal function and plays an important ... of neurons and their interconnections. neuron —A nerve cell that is the basic, working unit of the brain and nervous system, which processes and transmits information. ...

  17. Brain Basics

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    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding ...

  18. Brain Basics

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    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding ...

  19. Brain Basics

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    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... MSC 9663 Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS ...

  20. Brain Basics

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    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. She was happily married and successful in business. Then, after a serious setback at work, she ...

  1. Brain Basics

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    Full Text Available ... to the front of the brain, which is linked to thought and emotion. It is also linked to reward systems in the brain. Problems in ... Problems in making or using glutamate have been linked to many mental disorders, including autism , obsessive compulsive ...

  2. Brain Basics

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    Full Text Available ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ... axis —A brain-body circuit which plays a critical role in the body's response to stress. impulse — ...

  3. Brain Basics

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    Full Text Available ... And as they grow there are differences in brain development in children who develop bipolar disorder than children who do not. Studies comparing such children to those with normal brain development may help scientists to pinpoint when and where ...

  4. Brain Basics

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    Full Text Available ... These circuits control specific body functions such as sleep and speech. The brain continues maturing well into a person's early 20s. ... Basics in Real Life—How Depression affects the Brain Meet Sarah ... had problems getting to sleep and generally felt tired, listless, and had no ...

  5. Brain Basics

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    Full Text Available ... in brain development in children who develop bipolar disorder than children who do not. Studies comparing such children to those with normal brain development may help scientists to pinpoint when and where mental disorders begin and perhaps how to slow or stop ...

  6. Brain Basics

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    Full Text Available ... as they grow there are differences in brain development in children who develop bipolar disorder than children who do not. Studies comparing such children to those with normal brain development may help scientists to pinpoint when and where ...

  7. Brain Basics

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    Full Text Available ... thinking and feeling regions of the brain may play a role in disorders like schizophrenia or attention deficit hyperactivity ... the front of the brain that, in humans, plays a role in executive functions such as judgment, decision making ...

  8. Brain Basics

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    Full Text Available ... PTSD) . Prefrontal cortex (PFC) —Seat of the brain's executive functions, such as judgment, decision making, and problem solving. ... brain that, in humans, plays a role in executive functions such as judgment, decision making and problem solving, ...

  9. Brain Basics

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    Full Text Available ... our physical surroundings but also factors that can affect our bodies, such as sleep, diet, or stress. These factors may act alone ... Life Brain Basics in Real Life—How Depression affects the Brain ... had problems getting to sleep and generally felt tired, listless, and had no ...

  10. Brain Basics

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    Full Text Available ... her symptoms were not caused by a stroke, brain tumor, or similar conditions, Sarah's doctor referred her to a psychiatrist, a type of medical doctor who is an expert on mental ... of serotonin in the brain and help reduce symptoms of depression. Sarah also ...

  11. Brain Basics

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    Full Text Available ... begun to chart how the brain develops over time in healthy people and are working to compare that with brain development in ... Other medical professionals who can diagnose mental disorders are psychologists or ... gets "the blues" from time to time. In contrast, major depression is a ...

  12. Brain Basics

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    Full Text Available ... such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ... imaging (MRI) mdash;An imaging technique that uses magnetic fields to take pictures of the brain's structure. mutation — ...

  13. Energy independent uptake and release of polystyrene nanoparticles in primary mammalian cell cultures.

    Science.gov (United States)

    Fiorentino, Ilaria; Gualtieri, Roberto; Barbato, Vincenza; Mollo, Valentina; Braun, Sabrina; Angrisani, Alberto; Turano, Mimmo; Furia, Maria; Netti, Paolo A; Guarnieri, Daniela; Fusco, Sabato; Talevi, Riccardo

    2015-01-15

    Nanoparticle (NPs) delivery systems in vivo promises to overcome many obstacles associated with the administration of drugs, vaccines, plasmid DNA and RNA materials, making the study of their cellular uptake a central issue in nanomedicine. The uptake of NPs may be influenced by the cell culture stage and the NPs physical-chemical properties. So far, controversial data on NPs uptake have been derived owing to the heterogeneity of NPs and the general use of immortalized cancer cell lines that often behave differently from each other and from primary mammalian cell cultures. Main aims of the present study were to investigate the uptake, endocytosis pathways, intracellular fate and release of well standardized model particles, i.e. fluorescent 44 nm polystyrene NPs (PS-NPs), on two primary mammalian cell cultures, i.e. bovine oviductal epithelial cells (BOEC) and human colon fibroblasts (HCF) by confocal microscopy and spectrofluorimetric analysis. Different drugs and conditions that inhibit specific internalization routes were used to understand the mechanisms that mediate PS-NP uptake. Our data showed that PS-NPs are rapidly internalized by both cell types 1) with similar saturation kinetics; 2) through ATP-independent processes, and 3) quickly released in the culture medium. Our results suggest that PS-NPs are able to rapidly cross the cell membrane through passive translocation during both uptake and release, and emphasize the need to carefully design NPs for drug delivery, to ensure their selective uptake and to optimize their retainment in the targeted cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Vision - Gateway to the brain

    CERN Multimedia

    1999-01-01

    Is the brain the result of (evolutionary) tinkering, or is it governed by natural law? How can we objectively know? What is the nature of consciousness? Vision research is spear-heading the quest and is making rapid progress with the help of new experimental, computational and theoretical tools. At the same time it is about to lead to important technical applications.

  15. Light intensity affects the uptake and metabolism of glycine by pakchoi (Brassica chinensis L.)

    Science.gov (United States)

    Ma, Qingxu; Cao, Xiaochuang; Wu, Lianghuan; Mi, Wenhai; Feng, Ying

    2016-02-01

    The uptake of glycine by pakchoi (Brassica chinensis L.), when supplied as single N-source or in a mixture of glycine and inorganic N, was studied at different light intensities under sterile conditions. At the optimal intensity (414 μmol m-2 s-1) for plant growth, glycine, nitrate, and ammonium contributed 29.4%, 39.5%, and 31.1% shoot N, respectively, and light intensity altered the preferential absorption of N sources. The lower 15N-nitrate in root but higher in shoot and the higher 15N-glycine in root but lower in shoot suggested that most 15N-nitrate uptake by root transported to shoot rapidly, with the shoot being important for nitrate assimilation, and the N contribution of glycine was limited by post-uptake metabolism. The amount of glycine that was taken up by the plant was likely limited by root uptake at low light intensities and by the metabolism of ammonium produced by glycine at high light intensities. These results indicate that pakchoi has the ability to uptake a large quantity of glycine, but that uptake is strongly regulated by light intensity, with metabolism in the root inhibiting its N contribution.

  16. Natural DNA uptake by Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Sunita Sinha

    Full Text Available Escherichia coli has homologues of the competence genes other species use for DNA uptake and processing, but natural competence and transformation have never been detected. Although we previously showed that these genes are induced by the competence regulator Sxy as in other gamma-proteobacteria, no conditions are known that naturally induce sxy expression. We have now tested whether the competence gene homologues encode a functional DNA uptake machinery and whether DNA uptake leads to recombination, by investigating the effects of plasmid-borne sxy expression on natural competence in a wide variety of E. coli strains. High- and low-level sxy expression alone did not induce transformation in any of the strains tested, despite varying the transforming DNA, its concentration, and the incubation conditions used. Direct measurements of uptake of radiolabelled DNA were below the limit of detection, however transformants were readily detected when recombination functions were provided by the lambda Red recombinase. This is the first demonstration that E. coli sxy expression can induce natural DNA uptake and that E. coli's competence genes do encode a functional uptake machinery. However, the amount of transformation cells undergo is limited both by low levels of DNA uptake and by inefficient DNA processing/recombination.

  17. Rapid, generalized adaptation to asynchronous audiovisual speech.

    Science.gov (United States)

    Van der Burg, Erik; Goodbourn, Patrick T

    2015-04-07

    The brain is adaptive. The speed of propagation through air, and of low-level sensory processing, differs markedly between auditory and visual stimuli; yet the brain can adapt to compensate for the resulting cross-modal delays. Studies investigating temporal recalibration to audiovisual speech have used prolonged adaptation procedures, suggesting that adaptation is sluggish. Here, we show that adaptation to asynchronous audiovisual speech occurs rapidly. Participants viewed a brief clip of an actor pronouncing a single syllable. The voice was either advanced or delayed relative to the corresponding lip movements, and participants were asked to make a synchrony judgement. Although we did not use an explicit adaptation procedure, we demonstrate rapid recalibration based on a single audiovisual event. We find that the point of subjective simultaneity on each trial is highly contingent upon the modality order of the preceding trial. We find compelling evidence that rapid recalibration generalizes across different stimuli, and different actors. Finally, we demonstrate that rapid recalibration occurs even when auditory and visual events clearly belong to different actors. These results suggest that rapid temporal recalibration to audiovisual speech is primarily mediated by basic temporal factors, rather than higher-order factors such as perceived simultaneity and source identity. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  18. Carbon-11 labeled stilbene derivatives from natural products for the imaging of Aβ plaques in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Mengchao; Tang, Ruikun; Li, Zijing; Jia, Hongmei; Liu, Boli [Beijing Normal Univ. (China). Key Laboratory of Radiopharmaceuticals; Zhang, Jinming; Zhang, Xiaojun [Chinese PLA General Hospital, Beijing (China). Dept. of Nuclear Medicine

    2014-04-01

    Four stilbene derivatives from natural products were screened as novel β-amyloid (Aβ) imaging ligands. In vitro binding assay showed that the methylated ligand, (E)-1-methoxy-4-styrylbenzene (8) displayed high binding affinity to Aβ{sub 1-42} aggregates (K{sub i} = 19.5 nM). Moreover, the {sup 11}C-labeled ligand, [{sup 11}C]8 was prepared through an O-methylation reaction using [{sup 11}C]CH{sub 3}OTf. In vitro autoradiography with sections of transgenic mouse brain also confirmed the high and specific binding of [{sup 11}C]8 to Aβ plaques. In vivo biodistribution experiments in normal mice indicated that [{sup 11}C]8 displayed high initial uptake (9.41 ± 0.51% ID/g at 5 min post-injection) into and rapid washout from the brain, with a brain{sub 5} {sub min}/brain{sub 30} {sub min} ratio of 6.63. These preliminary results suggest that [{sup 11}C]8 may be served as a novel Aβ imaging probe for PET. (orig.)

  19. Blood-brain barrier transcytosis of insulin in developing rabbits.

    Science.gov (United States)

    Duffy, K R; Pardridge, W M

    1987-09-08

    Previous studies with isolated brain microvessels have suggested that blood insulin is selectively transported through the brain capillary, i.e. the blood-brain barrier (BBB), by receptor-mediated transcytosis. The purpose of the present study is to demonstrate in vivo the uptake of circulating 125I-insulin by brain using thaw-mount autoradiography. However, metabolism of systemic 125I-insulin to 125I-tyrosine would allow for brain uptake of 125I-tyrosine and this would preclude interpretation of the autoradiogram. Therefore, the present studies were performed in developing rabbits, since plasma protein degradation of peptides is greatly reduced in developing animals. 125I-insulin was infused via the carotid artery at a rate of 0.25 ml/min for 1, 5, or 10 min, and the mean brain uptake, relative to a [3H]albumin reference, was 99.3 +/- 5.5%, 110.1 +/- 4.3%, and 143.6 +/- 7.9%, respectively. This uptake was saturable by simultaneously infusing unlabeled insulin. Thaw-mount autoradiography of rabbit brain after a 10-min infusion of 125I-insulin revealed silver grains in the pericapillary space and well within the brain parenchyma. HPLC analysis of acid-ethanol extracts of rabbit blood after a 10-min infusion showed virtually all of the 125I-radioactivity co-migrated with a known insulin standard on a reverse-phase column, indicating minimal degradation of infused 125I-insulin. HPLC analysis of brain radioactivity showed the major peak co-migrated with 125I-insulin and this peak was precipitated by an anti-insulin antiserum. The correlation of the transport data, the autoradiography, and the HPLC analysis support the model that brain insulin originates from blood via receptor-mediated transport of the peptide at the BBB.

  20. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    -photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover......Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...