bluuebunny/crossref_metadata_2025 huggingface dataset:
Requiring remission of undue influence of weight and shape on self‐evaluation in the definition of recovery for bulimia nervosa
Authors: Cogley Catherine B. , Keel Pamela K.
Published: July 2003

Objective

The current study evaluated the concurrent validity of requiring remission of undue influence of weight and shape on self‐evaluation (undue influence) in defining recovery from bulimia nervosa (BN).

Methods

Three groups completed the Beck Depression Inventory, the Mood and Anxiety Symptom Questionnaire, the Body Shape Questionnaire, and the Social Adjustment Scale: 31 women were fully recovered from BN (FR), 28 women had no behavioral symptoms of BN (partially recovered [PR]), and 59 matched non–eating‐disordered controls (MC).

Results

The PR group had more pathologic scores on depression, anxiety, body dissatisfaction, and social adjustment compared with both the FR and MC groups, which did not differ from each other.

Discussion

These findings suggest that including remission of cognitive symptoms in a standardized definition of recovery may prove to be clinically useful in establishing reliable prognostic indicators. Future research should evaluate the role played by cognitive symptoms in triggering relapse. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 34: 200–210, 2003.
Are adolescents harmed when asked risky weight control behavior and attitude questions? Implications for consent procedures
Authors: Celio Angela A. , Bryson Susan , Killen Joel D. , Taylor C. Barr
Published: July 2003

Objectives

This study explores whether asking minors about risky weight control behaviors and attitudes increases the frequency of those behaviors and attitudes.

Methods

Participants were 115 sixth‐grade girls who responded to questions on risky weight control behaviors and attitudes at baseline and at 12‐month follow‐up. An additional 107 girls, who had not been part of the baseline, provided data only at follow‐up. The two groups were compared on risky weight control behaviors and attitudes at follow‐up using chi‐square analyses, Mann‐Whitney U tests, Cohen's effect sizes, and odds ratios.

Results

No evidence of a negative effect in the twice‐assessed group was found. All rates decreased from baseline to follow‐up.

Conclusions

There is only minimal risk and perhaps even some benefit of asking questions about risky weight control behaviors and attitudes. Implications for determining appropriate consent procedures are discussed. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 34: 251–254, 2003.
Reduced febrile response to bacterial infection in anorexia nervosa patients
Authors: Birmingham C. Laird , Hodgson Deborah M. , Fung Jonathan , Brown Rhonda , Wakefield Alison , Bartrop Roger , Beumont Pierre
Published: July 2003

Objective

To report a reduced febrile response to bacterial infections in anorexia nervosa (AN) patients.

Method

Four cases were obtained from a retrospective review of charts from the St. Paul's Hospital Eating Disorders Program (Vancouver, Canada). The patients had died or had been admitted to the hospital for treatment of a bacterial infection. In addition, one case was obtained from the Royal Prince Alfred Hospital (Sydney, Australia).

Results

All patients suffered a bacterial infection during the course of AN. None of the patients had a temperature higher than 37°C during the infectious illness.

Discussion

The absence of fever in AN may delay the diagnosis of bacterial infection and may be a marker of an impaired immune response. Therefore, alternative methods of investigation are necessary in patients with AN suspected of having a bacterial infection. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 34: 269–272, 2003.
Stress situation reveals an association between perfectionism and drive for thinness
Authors: Ruggiero Giovanni Maria , Levi Deborah , Ciuna Arcangelo , Sassaroli Sandra
Published: July 2003

Objective

Several theorists have hypothesized that stress situations may trigger abnormal eating and even eating disorders in individuals with a perfectionistic personality. The purpose of this study was to assess whether a stress situation would reveal an association between perfectionism and measures of eating disorders among female high school students.

Methods

A sample of 42 female high school students completed the Multidimensional Perfectionism Scale and the Eating Disorder Inventory three times: on an average school day, on the day of an examination, and on the day they received the evaluation of the examination. Linear regression analysis was calculated to verify whether the dimensions of perfectionism were associated with the measures of eating disorders.

Results

Body Dissatisfaction was associated with perfectionism on all the three occasions, whereas Drive for Thinness was associated with perfectionism only on the day the students received the results of the examination.

Discussion

The results suggest that among nonclinical female individuals, stress may make significant a previously absent association between perfectionism and an actual desire or plan to lose weight. Such a finding suggests that stress may stimulate behaviors related to eating disorders in individuals with a perfectionistic personality. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 34: 220–226, 2003.
Synthesis of two modified carotenoids and their behavior during light exposure
Authors: Karagiannidou Eugenia , Størseth Trond Røvik , Sliwka Hans‐Richard , Partali Vassilia , Malterud Karl Egil , Tsimidou Maria
Published: July 2003

Two modified carotenoids, β‐6‐hydroxy‐2, 5, 7, 8‐tetramethyl‐chromane carboxylic acid β‐apo‐8'‐carotenoate (Caro‐Trolox) and 3, 5‐di‐tert‐butyl‐4‐hydroxy benzoic acid β‐apo‐8'‐carotenoate (Caro‐BHT) were synthesized by esterification of β‐apo‐8'‐carotenol with Trolox and with 3, 5‐di‐tert‐butyl‐4‐hydroxy benzoic acid, respectively. Their activity under light exposure was examined comparatively to that of Trolox, α‐tocopherol, β‐carotene, β‐apo‐8'‐carotenoic acid (CA} and ethyl β‐apo‐8'‐carotenoate. The substrate used was purified sunflower oil. In the absence of a photosensitizer (240 W/m2 , 25 °C) Caro‐Trolox (200 mg/kg) behaved as an antioxidant and was quite stable (1/5 of the initial amount remained after 2‐wk storage). Caro‐BHT (200 mg/kg) showed no antioxidant activity and was quite unstable (it was destroyed within 7 d). In the presence of 5 mg/kg chlorophyll α (12000 lx, 25 °C) similar observations were made. The activity of Caro‐Trolox was concentration‐dependent. At a 100‐mg/kg level of addition its activity was similar to that of the mixture of α‐t_copherol (100 mg/kg) and β‐carotene (10 mg/kg). Its performance at the 10‐mg/kg level was slightly better than that of the other carotenoids. The antioxidant behavior of the modified carotenoids was attributed to the presence of the phenolic moiety as supported by the results of the 1, 1‐diphenyl‐2‐picrylhydrazyl test (e.g. EC50 after 15 min: 26.2, Caro‐Trolox; 35.8, Caro‐BHT; 122, CA; 22.3, Trolox).
Oxidative stability of structured lipids produced from sunflower oil and caprylic acid
Authors: Timm‐Heinrich Maike , Xu Xuebing , Skall Nielsen Nina , Jacobsen Charlotte
Published: July 2003

Traditional sunflower oil (SO), randomized lipid (RL) and specific structured lipid (SL), both produced from SO and tricaprylin/caprylic acid, respectively, were stored for up to 12 wk to compare their oxidative stabilities by chemical and sensory analyses. Furthermore, the effect of adding a commercial antioxidant blend Grindox 117 (propyl gallate/ citric acid/ascorbyl palmitate) or gallic acid to the SL was investigated. The lipid type affected the oxidative stability: SL was less stable than SO and RL. The reduced stability was most likely caused by both the structure of the lipid and differences in production/ purification, which caused lower tocopherol content and higher initial levels of primary and secondary oxidation products in SL compared with RL and SO. Grindox 117 and gallic acid did not exert a distinct antioxidative effect in the SL oil samples during storage.
Oxidative stability of milk drinks containing structured lipids produced from sunflower oil and caprylic acid
Authors: Timm‐Heinrich Maike , Xu Xuebing , Skall Nielsen Nina , Jacobsen Charlotte
Published: July 2003

Milk drinks containing 5% traditional sunflower oil (SO), randomized lipid (RL) or specific structured lipid (SL) (both produced from SO and tricaprylin/caprylic acid) were compared with respect to their particle size, viscosity and oxidative stability during storage. Furthermore, the effect of adding potential antioxidants EDTA or gallic acid to the milk drink based on SL was investigated. The lipid type significantly affected the oxidative stability of the milk drinks: Milk drink based on SL oxidized faster than milk drink based on RL or SO. The reduced oxidative stability in the SL milk drink could not be ascribed to a single factor, but was most likely influenced by the structure of the lipid and differences in the process applied to produce and purify the lipids. EDTA was a strong antioxidant, while gallic acid did not exert a distinct antioxidative effect in the milk drink based on SL.
Oxidative stability of mayonnaise containing structured lipids produced from sunflower oil and caprylic acid
Authors: Jacobsen Charlotte , Xu Xuebing , Skall Nielsen Nina , Timm‐Heinrich Maike
Published: July 2003

Mayonnaise based on enzymatically produced specific structured lipid (SL) from sunflower oil and caprylic acid was compared with mayonnaise based on traditional sunflower oil (SO) or chemically randomized lipid (RL) with respect to their oxidative stability, sensory and rheological properties. Furthermore, the potential antioxidative effect of adding lactoferrin, propyl gallate or EDTA to the mayonnaise with SL was also investigated. Mayonnaise based on SL oxidized faster than mayonnaise based on RL or SO. The reduced oxidative stability in the SL mayonnaise could not be ascribed to a single factor, but was most likely influenced by the structure of the lipid, the lower tocopherol content and the higher initial levels of lipid hydroperoxides and secondary volatile oxidation compounds in the SL itself compared with the RL and traditional sunflower oil employed. EDTA was a strong antioxidant, while propyl gallate and lactoferrin did not exert any antioxidative effect in the SL mayonnaise.
Formation of dispersed particles composed of soybean oil and phosphatidyl choline
Authors: Asai Yasuyuki
Published: July 2003

The purpose of this study was to investigate the dispersal mechanism of soybean oil (SO) in phospholipids to form a fat emulsion. SO was dispersed with soybean phosphatidyl choline (PC) using sonication. The dispersal mechanism was evaluated by characterizing the dispersed particles using dynamic light scattering, fluorescence spectroscopy and surface monolayer techniques. The dispersions in SO fractions being in the range of 0.1‐0.7 were stable at room temperature for 3 d. A limited amount of SO was incorporated into PC bilayer membranes. The excess SO separating from the PC bilayers was stabilized as emulsion particles by the PC surface monolayer. When the PC content was lower (SO more than 0.8 mol‐%), the PC monolayer did not completely cover the hydrophobic SO particle surfaces. In this case, the particle size increased drastically and the separation into oil and water occurred. Therefore, the solubility between SO and PC and the coexistence of emulsion and liposomal particles are critical parameters for the stabilization of the particles in water.
Pharmaceutical and biomedical applications of chiral capillary electrophoresis and capillary electrochromatography: An update
Authors: Scriba Gerhard K. E.
Published: July 2003

Capillary electrophoresis is often considered an ideal method for the chiral analysis of compounds due to the high separation power of the technique and has therefore found widespread acceptance for the analysis of drugs and pharmaceuticals. In contrast, capillary electrochromatography is still more or less in an infancy state searching for its place among the analytical separation techniques although interesting applications have been published. The present review summarizes recent developments and applications of chiral pharmaceutical analysis by electromigration techniques published in 2002 and early 2003.
Determination of L‐hyoscyamine in atropine and D‐hyoscyamine in L‐hyoscyamine by chiral capillary electrophoresis as an alternative to polarimetry
Authors: Heine Stephanie , Ebert Kirstin , Blaschke Gottfried
Published: July 2003

A method for the separation of atropine enantiomers, D‐ and L‐hyoscyamine by capillary electrophoresis (CE) has been developed and validated. The advantages of the CE method compared with polarimetry include smaller amounts of analytes and a lower limit of detection of the unwanted enantiomer. Moreover, the present method enables a baseline separation of the analytes and tropic acid, one of the typical impurities of atropine. The developed enantioseparation of atropine was performed using a commercially available sulfated β‐cyclodextrin and was validated for the determination of L‐hyoscyamine in atropine as well as for the enantiomeric purity of L‐hyoscyamine.
Separation of some chiral flavanones by micellar electrokinetic chromatography
Authors: Asztemborska Monika , Miśkiewicz Magdalena , Sybilska Danuta
Published: July 2003

Micellar electrokinetic chromatography (MEKC) was applied for enantioseparation of selected flavanones, including naringin, hesperidin, neohesperidin, naringenin, hesperetin, pinostrobin, isosakuranetin, eriodictyol, and homoeriodictyol. γ‐Cyclodextrin (γ‐CD) and sodium cholate (SCh) were used as chiral modifiers inducing enantioselectivity to the background electrolyte. From among many investigated selectors only these two appeared to possess the best enantioselective properties in respect to studied flavanones. The mechanisms of their action are a little different; SCh used above critical micelle point concentration forms chiral micelles itself while γ‐CD is deprived of this property and requires addition of surfactants as, e.g., sodium dodecyl sulfate. It was found that SCh enables separation of flavanone glycosides diastereomers while separation of enantiomers of flavanone aglycones may be achieved with γ‐CD. Consideration of structural relation led to the suggestion that interaction of sugar moiety of glycosides with SCh micelles give rise to chiral recognition. MEKC appeared to be a suitable and efficient analytical tool to follow enantiomeric composition of flavanones.
A high‐order finite difference method for incompressible fluid turbulence simulations
Authors: Vedy Eric , Viazzo Stephane , Schiestel Roland
Published: July 2003

A Hermitian–Fourier numerical method for solving the Navier–Stokes equations with one non‐homogeneous direction had been presented by Schiestel and Viazzo (Internat. J. Comput. Fluids 1995; 24(6):739). In the present paper, an extension of the method is devised for solving problems with two non‐homogeneous directions. This extension is indeed not trivial since new algorithms will be necessary, in particular for pressure calculation. The method uses Hermitian finite differences in the non‐periodic directions whereas Fourier pseudo‐spectral developments are used in the remaining periodic direction. Pressure–velocity coupling is solved by a simplified Poisson equation for the pressure correction using direct method of solution that preserves Hermitian accuracy for pressure. The turbulent flow after a backward facing step has been used as a test case to show the capabilities of the method. The applications in view are mainly concerning the numerical simulation of turbulent and transitional flows. Copyright © 2003 John Wiley & Sons, Ltd.
Superconvergence and H(div) projection for discontinuous Galerkin methods
Authors: Bastian Peter , Rivière Béatrice
Published: July 2003

We introduce and analyse a projection of the discontinuous Galerkin (DG) velocity approximations that preserve the local mass conservation property. The projected velocities have the additional property of continuous normal component. Both theoretical and numerical convergence rates are obtained which show that the accuracy of the DG velocity field is maintained. Superconvergence properties of the DG methods are shown. Finally, numerical simulations of complicated flow and transport problem illustrate the benefits of the projection. Copyright © 2003 John Wiley & Sons, Ltd.
Linearized and non‐linear acoustic/viscous splitting techniques for low Mach number flows
Authors: Farshchi Mohammad , Hannani Siamak K. , Ebrahimi Mohammad
Published: July 2003

Computation of the acoustic disturbances generated by unsteady low‐speed flow fields including vortices and shear layers is considered. The equations governing the generation and propagation of acoustic fluctuations are derived from a two‐step acoustic/viscous splitting technique. An optimized high order dispersion–relation–preserving scheme is used for the solution of the acoustic field. The acoustic field generated by a corotating vortex pair is obtained using the above technique. The computed sound field is compared with the existing analytic solution. Results are in good agreement with the analytic solution except near the centre of the vortices where the acoustic pressure becomes singular. The governing equations for acoustic fluctuations are then linearized and solved for the same model problem. The difference between non‐linear and linearized solutions falls below the numerical error of the simulation. However, a considerable saving in CPU time usage is achieved in solving the linearized equations. The results indicate that the linearized acoustic/viscous splitting technique for the simulation of acoustic fluctuations generation and propagation by low Mach number flow fields seems to be very promising for three‐dimensional problems involving complex geometries. Copyright © 2003 John Wiley & Sons, Ltd.
Steady/unsteady aerodynamic analysis of wings at subsonic, sonic and supersonic Mach numbers using a 3D panel method
Authors: Cho Jeonghyun , Han Cheolheui , Cho Leesang , Cho Jinsoo
Published: July 2003

This paper treats the kernel function of an integral equation that relates a known or prescribed upwash distribution to an unknown lift distribution for a finite wing. The pressure kernel functions of the singular integral equation are summarized for all speed range in the Laplace transform domain. The sonic kernel function has been reduced to a form, which can be conveniently evaluated as a finite limit from both the subsonic and supersonic sides when the Mach number tends to one. Several examples are solved including rectangular wings, swept wings, a supersonic transport wing and a harmonically oscillating wing. Present results are given with other numerical data, showing continuous results through the unit Mach number. Computed results are in good agreement with other numerical results. Copyright © 2003 John Wiley & Sons, Ltd.
Numerical simulation of time‐dependent hydrodynamic removal of a contaminated fluid from a cavity
Authors: Fang Lih‐Chuan , Nicolaou Dimitri , Cleaver John W.
Published: July 2003

The time‐dependent hydrodynamic removal of a contaminated fluid from a rectangular cavity on the floor of a duct is analysed numerically. Laminar duct flows are considered for Reynolds numbers of 50 and 1600 where the characteristic length is the duct height. Two cases are considered where: (1) the fluid density in the cavity is the same as that for the duct fluid and (2) the cavity fluid has a higher density than the duct fluid but the two fluids are miscible. The flow is solved by a numerical solution of the time‐dependent Navier–Stokes equations. Attention is focused on the convective transport of contaminated fluid out from the cavity and the effect of duct flow velocity profile on the cleaning process. Passive markers are used in the numerical simulation for the purpose of identifying the contaminated cavity fluid. The results show that the flow patterns in the cavity are influenced by the type of duct flow. From a cleaning perspective, the results suggest that it is easier for the duct flow to penetrate a cavity and to remove contaminated cavity fluid when the duct flow is of the Poiseuille type and the aspect ratio is large. Copyright © 2003 John Wiley & Sons, Ltd.
Numerical simulation of mold filling in foam reaction injection molding
Authors: Seo Dongjin , Ryoun Youn Jae , Tucker Charles L.
Published: July 2003

A numerical simulation of reaction injection molding (RIM) of polymeric foam is developed, using a finite volume method (FVM). In this study we predict mold filling with a variable‐density fluid that fills a mold by self‐expansion. We deal with two‐dimensional, isothermal cases. With the assumptions of ideal mixing and rapid bubble nucleation, the foam is modelled as a continuum with a time‐dependent density. The continuum is assumed to be a Newtonian fluid. We develop a pressure‐based FVM for unstructured meshes that includes the SIMPLE algorithm with treatment of fluid compressibility. Cell‐based, co‐located storage is used for all physical variables. To treat the moving interface, an explicit high‐resolution interface capturing method is used. Foam flow in a slit is investigated, and the numerical calculations are in good agreement with an approximate analytic solution. For fountain flow in a rectangular cavity, the shape of the flow front is flatter and the traces of the particles are more complicated for an expanding foam than for a constant‐density fluid. An example of mold filling by an expanding foam demonstrates the geometric flexibility of the method. Copyright © 2003 John Wiley & Sons, Ltd.
Solution adaptive grids applied to low Reynolds number flow
Authors: de With G. , Holdø A. E. , Huld T. A.
Published: July 2003

A numerical study has been undertaken to investigate the use of a solution adaptive grid for flow around a cylinder in the laminar flow regime. The main purpose of this work is twofold. The first aim is to investigate the suitability of a grid adaptation algorithm and the reduction in mesh size that can be obtained. Secondly, the uniform asymmetric flow structures are ideal to validate the mesh structures due to mesh refinement and consequently the selected refinement criteria. The refinement variable used in this work is a product of the rate of strain and the mesh cell size, and contains two variables Cm and Cstr which determine the order of each term. By altering the order of either one of these terms the refinement behaviour can be modified. Copyright © 2003 John Wiley & Sons, Ltd.
Differential modulation of hippocampal chemical‐induced injury response by ebselen, pentoxifylline, and TNFα‐, IL‐1α‐, and IL‐6‐neutralizing antibodies
Authors: Jean Harry G. , Bruccoleri Alessandra , Lefebvre d'Hellencourt Christian
Published: July 2003

The proinflammatory cytokines tumor necrosis factor (TNFα), interleukin‐1 (IL‐1α), and interleukin‐6 (IL‐6) have been associated with various models of hippocampal damage. To examine their role in initiation of an acute hippocampal injury response, 21‐day‐old male CD‐1 mice received an acute intraperitoneal (i.p.) injection of trimethyltin hydroxide (TMT; 2.0 mg/kg) to produce necrosis of dentate granule neurons, astrocyte, and microglia reactivity. Tremors and intermittent seizures were evident at 24 hr. Intercellular adhesion molecule‐1 (ICAM‐1), glial fibrillary acidic protein (GFAP), anti‐apoptotic TNFα‐inducible early response gene (A‐20), macrophage inflammatory protein (MIP)‐1α, TNFα, IL‐1α, IL‐6, and caspase 3 mRNA levels were significantly elevated. Pretreatment with the antioxidant, ebselen, decreased ICAM‐1, A‐20, and TNFβ elevations. Pentoxifylline blocked elevations in A‐20 and decreased elevations in GFAP mRNA levels. Neither prevented histopathology or behavioral effects. Intracisternal injection of TNFα‐neutralizing antibody significantly inhibited both behavioral effects and histopathology. RNase protection assays showed that TMT‐induced elevations in mRNA levels for ICAM‐1, A‐20, GFAP, MIP‐1α, IL‐1α, TNFα, TNFβ, and caspase 3 were blocked by anti‐TNFα. These data demonstrate a significant role for TNFα in an acute neuro‐injury in the absence of contribution from infiltrating cells. The cerebellum shows limited if any damage after TMT; however, in combination with the i.c.v. injection, elevations were seen in GFAP and in EB‐22, a murine acute‐phase response gene homologous to the alpha (1)‐antichymotrypsin gene. Elevations were similar for artificial cerebral spinal fluid and anti‐IL‐1α, and significantly increased with anti‐TNFα, anti‐IL‐6, or the combination of antibodies. Responses seen in the cerebellum suggest synergistic interactions between the baseline state of the cell and manipulations in the cytokine environment. Data suggests a role for TNFα in the pathogenesis of hippocampal injury induced by TMT. Published 2003 Wiley‐Liss, Inc.
Spatiotemporal changes of apolipoprotein E immunoreactivity and apolipoprotein E mRNA expression after transient middle cerebral artery occlusion in rat brain
Authors: Kamada Hiroshi , Sato Keiko , Zhang Wen Ri , Omori Nobuhiko , Nagano Isao , Shoji Mikio , Abe Koji
Published: July 2003

Apolipoprotein E (ApoE) is a constituent of lipoprotein and plays an important role in the maintenance of neural networks. However, spatiotemporal differences in ApoE expression and its long‐term role in neural process after brain ischemia have not been studied. We investigated changes of ApoE immunoreactivity and ApoE mRNA expression both in the core and in the periischemic area at 1, 7, 21, or 56 days after 90 min of transient middle cerebral artery occlusion. Double stainings for ApoE plus NeuN or plus ED1 were performed in order to identify cell type of ApoE‐positive stainings. The maximal increase of ApoE expression was observed at 7 days in the core and at 7 and 21 days in the periischemic area. In the core, ApoE plus NeuN double‐positive cells increased at 1 and 7 days, without ApoE mRNA expression, whereas they increased in the periischemic area, with a peak at 21 days, with ApoE mRNA expression in glial cells but not in neurons. On the other hand, ApoE plus ED1 double‐positive cells increased only in the core, with a peak in number at 7 and 21 days and marked ApoE mRNA expression in macrophages. The present study suggests that ApoE plays various important roles in different type of cells, reflecting spatiotemporal dissociation between degenerative and regenerative processes after brain ischemia, and that ApoE is profoundly involved in pathological conditions, such as brain ischemia. © 2003 Wiley‐Liss, Inc.
Potential roles of Alzheimer precursor protein A4 and β‐amyloid in survival and function of aged spinal motor neurons after axonal injury
Authors: Xie Yuanyun , Yao Zhibin , Chai Hong , Wong Wai‐Man , Wu Wutian
Published: July 2003

To study the potential role of Alzheimer precursor protein A4 (APP) and β‐amyloid (A/β) on aging motor neuron survival, expression of APP, A/β, and choline acetyltransferase (ChaT) were investigated in aged rats after either distal axotomy or root avulsion injury. Approximately 45% in number of total aged spinal motor neuron were normally APP‐positive. A/β‐positive neurites were observed normally in the spinal ventral horn of aged rats. After distal axotomy, without apparent neurodegeneration such as cell loss and decreased ChaT‐immunoreactivity, increased levels of APP expression were observed in the spinal cords of aged rats post‐injury. In contrast, after avulsion, expression of APP and A/β were downregulated in the spinal ventral horn of aged rats, and marked loss of spinal motor neurons and downregulated ChaT expression were observed. Our data indicate that APP and A/β might play beneficial roles in neuronal survival of aged spinal motor neurons after axonal injury. © 2003 Wiley‐Liss, Inc.
Administration of the p38 MAPK inhibitor SB203580 affords brain protection with a wide therapeutic window against focal ischemic insult
Authors: Piao Chun Shu , Kim Jung‐Bin , Han Pyung‐Lim , Lee Ja‐Kyeong
Published: July 2003

We have reported previously the delayed and differential induction of p38α and p38β mitogen‐activated protein kinases (MAPKs) in microglia and astrocytes, respectively, in brain after transient global ischemia. We report here the sustained induction and activation of p38α MAPK in activating microglia in rat brain after transient middle cerebral artery occlusion (MCAO). The intraventricular administration of SB203580, a p38 MAPK inhibitor, 30 min before MCAO reduced the infarct volume to 50% of the control, which was accompanied by the significant improvement of neurological deficits. More interestingly, the infarct volume was reduced to 72% and 77% when SB203580 was administered 6 hr and 12 hr after MCAO, respectively. The induction of various factors involved in inflammatory processes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β) and cyclooxygenase‐2 (COX‐2), was suppressed by the administration of SB203580 at 6 hr after MCAO. These results suggest that sustained activation of p38 MAPK pathway and p38 MAPK‐associated inflammatory processes play a crucial role in postischemic brain. © 2003 Wiley‐Liss, Inc.
FGF‐2 modulates expression and distribution of GAP‐43 in frog retinal ganglion cells after optic nerve injury
Authors: Soto Ileana , Marie Bruno , Baro Deborah J. , Blanco Rosa E.
Published: July 2003

Basic fibroblast growth factor (bFGF or FGF‐2) has been implicated as a trophic factor that promotes survival and neurite outgrowth of neurons. We found previously that application of FGF‐2 to the proximal stump of the injured axon increases retinal ganglion cell (RGC) survival. We determine here the effect of FGF‐2 on expression of the axonal growth‐associated phosphoprotein (GAP)‐43 in retinal ganglion cells and tectum of Rana pipiens during regeneration of the optic nerve. In control retinas, GAP‐43 protein was found in the optic fiber layer and in optic nerve; mRNA levels were low. After axotomy, mRNA levels increased sevenfold and GAP‐43 protein was significantly increased. GAP‐43 was localized in retinal axons and in a subset of RGC cell bodies and dendrites. This upregulation of GAP‐43 was sustained through the period in which retinal axons reconnect with their target in the tectum. FGF‐2 application to the injured nerve, but not to the eyeball, increased GAP‐43 mRNA in the retina but decreased GAP‐43 protein levels and decreased the number of immunopositive cell bodies. In the tectum, no treatment affected GAP‐43 mRNA but FGF‐2 application to the axotomized optic nerve increased GAP‐43 protein in regenerating retinal projections. We conclude that FGF‐2 upregulates the synthesis and alters the distribution of the axonal growth‐promoting protein GAP‐43, suggesting that it may enhance axonal regrowth. © 2003 Wiley‐Liss, Inc.
Expression and subcellular localization of Ror tyrosine kinase receptors are developmentally regulated in cultured hippocampal neurons
Authors: Paganoni Sabrina , Ferreira Adriana
Published: July 2003

Ror1 and Ror2 are two novel receptor tyrosine kinases that have been implicated in neuronal differentiation in Caenorhabditis elegans. As a first step toward elucidating their role in the mammalian brain, we analyzed their expression and localization patterns in hippocampal neurons. Our results showed that both receptors are expressed from early stages of development and that their protein levels peak during periods of active synapse formation. Immunocytochemical analysis indicated that Ror1 and Ror2 are highly concentrated in the growth cones of immature neurons and are present throughout the somatodendritic compartment of mature hippocampal cells. Further analysis indicated that they are present not only in the cell membrane but also in Triton‐ and saponin‐insoluble fractions, suggesting that they may be associated with both the cytoskeleton and membrane‐bound organelles. Taken collectively, our results suggest that Ror1 and Ror2 might play a role during early stages of development in mammalian central neurons. © 2003 Wiley‐Liss, Inc.
Dysregulation of axonal sodium channel isoforms after adult‐onset chronic demyelination
Authors: Rasband Matthew N. , Kagawa Tetsushi , Park Eunice W. , Ikenaka Kazuhiro , Trimmer James S.
Published: July 2003

Demyelination results in conduction block through changes in passive cable properties of an axon and in the expression and localization of axonal ion channels. We show here that adult‐onset chronic demyelination, such as occurs in demyelinating disorders and after nerve injury, alters the complement of axonal voltage‐dependent Na+ (Nav) channel isoforms and their localization. As a model, we used heterozygous transgenic mice with two extra copies of the proteolipid protein gene (Plp/−). Retinal ganglion cell axons in these mice myelinate normally, with young Plp/− and wild‐type mice expressing Nav1.2 at low levels, whereas Nav1.6 is clustered in high densities at nodes of Ranvier. At 7 months of age, however, Plp/− mice exhibit severe demyelination and oligodendrocyte cell death, leading to a profound reduction in Nav1.6 clusters, loss of the paranodal axoglial apparatus, and a marked increase in Nav1.2. We conclude that myelin is crucial not only for node of Ranvier formation, but also to actively maintain the proper localization and complement of distinct axonal Nav channel isoforms throughout life. The altered Nav channel isoform localization and complement induced by demyelination may contribute to the pathophysiology of demyelinating disorders and nerve injury. © 2003 Wiley‐Liss, Inc.
Hyperalgesic effects of γ‐aminobutyric acid transporter I in mice
Authors: Hu Jia‐Hua , Yang Na , Ma Ying‐Hua , Zhou Xiao‐Gang , Jiang Jie , Duan Shu‐hui , Mei Zhen‐Tong , Fei Jian , Guo Li‐He
Published: July 2003

The present study focused on the involvement of γ‐aminobutyric acid transporter I (GAT1) in pain. We found that GABA uptake was increased in mouse spinal cord at 20 min and 120 min after formalin injection and in mouse brain at 120 min, but not 20 min, after formalin injection. In addition, the antinociceptive effects of GAT1‐selective inhibitors were examined using assays of thermal (tail‐flick) and chemical (formalin and acetic acid) nociception in C57BL/6J mice. The GAT1‐selective inhibitors, ethyl nipecotate and NO‐711, exhibited significant antinociceptive effects in these nociceptive assays. To study further the effects of GAT1 on pain, we used two kinds of GAT1‐overexpressing transgenic mice (under the control of a CMV promoter or a NSE promoter) to examine the nociceptive responses in these mice. In the thermal, formalin, and acetic acid assays, both kinds of transgenic mice displayed significant hyperalgesia after nociceptive stimuli. In addition, the μ opioid receptor antagonist naloxone had no influence on nociceptive responses in wild‐type and transgenic mice. The results indicate that GAT1 is involved in the regulation of pain processes, and point to the possibility of developing analgesic drugs that target GAT1 other than opioid receptors. © 2003 Wiley‐Liss, Inc.
Expression of 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase) in the developing olfactory bulb and subventricular zone rostral extension
Authors: Gomes Silvana S. , Carvalho Sergio L. , Santiago Marcelo F. , Lopez Luciane B. , Barradas Penha C. , Cavalcante Leny A.
Published: July 2003

The olfactory bulb (OB) presents a unique pattern of permanent acquisition of primary afferents and interneurons, but not much detail is known about the differentiation of its oligodendroglial cells. We studied the expression of 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase), a protein related to axonal ensheathment by myelinating cells. Expression of CNPase in OB follows a general caudorostral gradient, with the exception of the glomerular layer (GL). At postnatal day 5–6 (P5–P6), the first CNPase+ profiles appeared in the dorsal lateral olfactory tract adjacent to the accessory OB (AOB), followed by rare cell bodies and processes in AOB internal plexiform layer at P7. At P9, the main OB (MOB) granular cell layer (GrCL) already showed intensely stained CNPase+ processes. From P5 to P12, small numbers of CNPase+ cells were found in the subventricular zone (SVZ), throughout its rostral extension (SVZ‐RE), and in the intrabulbar subependymal layer. The appearance of CNPase+ profiles delimiting glomeruli started in the GL rostralmost region at P12, extending to all GL levels, but glomeruli remained open caudally at P15. At P18, oligodendroglial glomeruli were evident throughout OB, but the adult pattern was established only after P30. There was no age‐related loss of CNPase immunoreactivity in glial cell bodies, possibly indicating de novo ensheathment of neurites. Our results show an earlier onset of oligodendroglial differentiation in OB than previously reported and a rostrocaudal gradient of formation of oligodendroglial glomeruli. They also raise the possibility that a minor fraction of OB oligodendrocytes might derive from the SVZ‐RE. © 2003 Wiley‐Liss, Inc.
Microarray analysis of gene expression in proliferating Schwann cells: Synergistic response of a specific subset of genes to the mitogenic action of heregulin plus forskolin
Authors: Schworer Charles M. , Masker Kathryn K. , Wood G. Craig , Carey David J.
Published: July 2003

Cultured Schwann cells treated with heregulin growth factor require costimulation with a cyclic adenosine monophosphate‐elevating agent to produce maximal cell proliferation. Gene chip expression analysis was used to identify genes that are induced or repressed when Schwann cells are treated with heregulin and/or forskolin. By utilizing arrays that contained 8,799 probes, the expression of over 1,000 genes was found to be significantly changed after 30 hr of treatment with heregulin, forskolin, or heregulin plus forskolin. Hierarchical clustering revealed groups of genes with distinct expression patterns. Of particular interest was a cluster of 140 genes that were up‐regulated by heregulin plus forskolin but not by heregulin or forskolin alone. Many of the genes in this group have roles in cell division, such as cyclin B, cyclin D3, E2F‐5, cdc 25B, polo‐like kinase, and protein kinase C type III. These findings identify a profile of gene expression for Schwann cell proliferation. © 2003 Wiley‐Liss, Inc.
Astrocyte‐targeted expression of interleukin‐6 protects the central nervous system during neuroglial degeneration induced by 6‐aminonicotinamide
Authors: Penkowa Milena , Camats Jordi , Hadberg Hanne , Quintana Albert , Rojas Santiago , Giralt Mercedes , Molinero Amalia , Campbell Iain L. , Hidalgo Juan
Published: July 2003

6‐Aminonicotinamide (6‐AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes mainly in the brainstem. We have examined the role of interleukin‐6 (IL‐6) in this degenerative process by using transgenic mice with astrocyte‐targeted IL‐6 expression (GFAP‐IL6 mice). This study demonstrates that transgenic IL‐6 expression significantly increases the 6‐AN‐induced inflammatory response of reactive astrocytes, microglia/macrophages, and lymphocytes in the brainstem. Also, IL‐6 induced significant increases in proinflammatory cytokines IL‐1, IL‐12, and tumor necrosis factor‐α as well as growth factors basic fibroblast growth factor (bFGF), transforming growth factor‐β, neurotrophin‐3, angiopoietin, vascular endothelial growth factor, and the receptor for bFGF. In accordance, angiogenesis was increased in GFAP‐IL6 mice relative to controls after 6‐AN. Moreover, oxidative stress and apoptotic cell death were significantly reduced by transgenic IL‐6 expression. IL‐6 is also a major inducer in the CNS of metallothionein I and II (MT‐I+II), which were significantly increased in the GFAP‐IL6 mice. MT‐I+II are antioxidants and neuroregenerative factors in the CNS, so increased MT‐I+II levels in GFAP‐IL6 mice could contribute to the reduction of oxidative stress and cell death in these mice. © 2003 Wiley‐Liss, Inc.
Increased neurogenesis after experimental Streptococcus pneumoniae meningitis
Authors: Gerber Joachim , Böttcher Tobias , Bering Judith , Bunkowski Stephanie , Brück Wolfgang , Kuhnt Ulrich , Nau Roland
Published: July 2003

Neuronal damage in the hippocampal formation is a common feature in animal models of bacterial meningitis and human disease. In mouse and rabbit models of Streptococcus pneumoniae meningitis, proliferation of neural progenitor cells quantified by bromodeoxyuridine (BrdU) incorporation was enhanced in the subgranular layer of the dentate gyrus. In mice, the density of BrdU‐labeled cells was maximal on Day 2 after infection. Approximately 60% of the cells labeled by BrdU between Days 7 and 10 after infection that remained present 28 days later had migrated into deeper layers of the dentate gyrus and differentiated into neurons, as evidenced by immunohistochemical staining for TUC‐4, MAP‐2 and beta‐tubulin. This suggests that endogenous repair mechanisms may limit consequences of neuronal destruction after meningitis. © 2003 Wiley‐Liss, Inc.
Unusual topographical pattern of proximal astrogliosis around a cortical devascularizing lesion
Authors: Wang Kai , Walz Wolfgang
Published: July 2003

Class II vessels were disrupted on the cortical surface of adult rats within a circular 5‐mm‐diameter area. This consistently resulted in the formation of a conical lesion by day 1, with a cystic cavity forming by day 21. Four markers were used to identify the glial response surrounding the lesion. The antibody used against S100β marked the largest astrocytic pool in the gray matter of the cerebral cortex; only ∼5% of astrocytes were glial fibrillary acidic protein (GFAP)+ in control animals. GFAP served as a marker for distal reactive gliosis and vimentin (VIM) for proximal gliosis. Isolectin B4 was used as an additional marker to distinguish VIM+ microglia from astrocytes inside the lesion area. Three immunohistochemically distinct areas of reactive astrocytes surrounding the lesion were found within 24 hr of injury and lasted through day 6. The first area, in contrast to focal traumatic injuries, consisted of a 196‐μm‐thick boundary layer of S100β+ cells immediately surrounding the lesion that never expressed GFAP or VIM by day 6. This boundary layer turns into a GFAP+ glial limitans encasing the cystic cavity by day 21. A second unusual extended area around the base of the lesion reaching partly into the corpus callosum consisted of S100β+/GFAP+/VIM+ cells. This region appears to be compatible with the local or proximal gliotic response usually found completely surrounding other focal‐type injuries. The proximal response at the base of the lesion developed over the first 3 days in the following sequence: S100β+/GFAP−/VIM− to S100β+/GFAP+/VIM− to S100β+/GFAP+/VIM+. Ninety percent of the astrocytes in this area express VIM. This is very high compared with findings in stab‐wound preparations, where only 10% of astrocytes (surrounding entire lesion) are found to be VIM+. A third region, consistent with a remote or distal reactive gliotic response, demonstrated staining for S100β and had increased GFAP contents throughout the neocortical hemisphere. Cells in this region were never found to be VIM+. Among S100β+ cells close to the boundary region, more than 80% expressed detectable GFAP by 2 days after lesioning. S100β+ cells 1 mm more laterally (distal to lesion) did not express GFAP to the same level until day 6. Thus, we find three immunohistochemically distinct populations of reactive astrocytes surrounding the focal ischemic lesion. In contrast to the case for stab‐wound traumatic injury, the response closest to and surrounding the lesion did not up‐regulate GFAP or VIM by day 6. The proximal response was, instead, more remote and only at the base of the lesion, extending partly into the corpus callosum. © 2003 Wiley‐Liss, Inc.
Glucose uptake in PC12 cells: GLUT3 vesicle trafficking and fusion as revealed with a novel GLUT3‐GFP fusion protein
Authors: Heather West Greenlee M. , Uemura Etsuro , Carpenter Susan L. , Doyle Robert T. , Buss Janice E.
Published: July 2003

The distribution of glucose transporters at the cell surface has a major impact on cellular glucose uptake. In muscle cells and adipocytes, this distribution is under the control of insulin; however, neuronal glucose uptake is not acutely regulated by insulin. Factors that affect the translocation of the neuronal glucose transporter isoform GLUT3 vesicles to and their fusion with the plasma membrane are not well understood. We report that GLUT3 in PC12 cells colocalizes with SNARE complex proteins SNAP‐25 and syntaxin 1, suggesting that fusion of GLUT3‐containing vesicles with the plasma membrane is mediated by these proteins. In addition, it seems that GLUT3 vesicle fusion is regulated, as depolarization increases GLUT3 insertion into the plasma membrane. To study the dynamics of GLUT3 vesicle trafficking, we have created a GLUT3‐GFP fusion protein that is easily expressed in PC12 cells. Trafficking of GLUT3‐GFP seems normal, as 1) its distribution is similar to endogenous GLUT3, 2) GLUT3‐GFP containing vesicles fuse with the plasma membrane evidenced by labeling of the fusion protein with an antibody directed against the exofacial epitope of GLUT3, and 3) glucose uptake is similar to PC12 cells not transfected with GLUT3 fusion protein. These studies are the first to examine GLUT3 trafficking and fusion in PC12 cells, and establish a model system to study regulation of the neuronal glucose transporter. © 2003 Wiley‐Liss, Inc.
Acquisition of an appetitive behavior prevents development of stress‐induced neurochemical modifications in rat nucleus accumbens
Authors: Nanni Giulio , Scheggi Simona , Leggio Benedetta , Grappi Silvia , Masi Flavio , Rauggi Riccardo , De Montis Maria Graziella
Published: July 2003

In rats, exposure to chronic unavoidable stress produces a decrease in dopamine output in the nucleus accumbens shell that is accompanied by a decreased density of the dopamine transporter and an increased activity of the dopamine‐D1 receptor complex. These modifications have been hypothesized to be adaptive to decreased dopamine output in stressed rats. We investigated whether the learning of an appetitive behavior sustained by palatable food, which is associated with increased dopamine output in the nucleus accumbens shell as measured by microdialysis experiments, would affect the modifications induced by chronic stress exposure on dopamine transporter density and dopamine‐D1 receptor complex activity in the nucleus accumbens. Rats exposed to chronic unavoidable stress after acquisition of the appetitive behavior showed a higher dopamine extraneuronal release in the nucleus accumbens shell than that of stressed animals, and similar to that of control rats. Moreover, previous acquisition of the appetitive behavior prevented development of a stress‐induced decrease in dopamine transporter density, measured by [3H]‐WIN 35428 binding, a stress‐induced increase in dopamine‐D1 receptor density, measured by binding of [3H]‐SCH 23390, and SKF 38393‐stimulated adenylyl cyclase activity in the nucleus accumbens. These results support the hypothesis that changes induced in pre‐ and postsynaptic dopaminergic transmission by chronic stress exposure are related to decreased dopamine output. © 2003 Wiley‐Liss, Inc.