bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technology options for new nutritional concepts
Authors: Korhonen Hannu 
Published: March 2003

Recent advances in the food and nutrition sciences support the concept that the diet has a significant role in the modulation of various functions in the body. The diet and/or its components may contribute to an improved state of well‐being, a reduction of risks related to certain diseases and even an improvement in the quality of life. These new concepts have led to the introduction of a new category of health‐promoting foodstuffs, i.e. functional foods.The concern about health embraces a number of driving issues, needs and opportunities which may be approached by designing specific diets from various food raw materials. These tailor‐made products provide physiological benefits that are targeted at particular consumer groups.The functionality of functional foods is based on bioactive components, which may be contained naturally in the product but usually require formulation by appropriate technologies in order to optimise the desired beneficial properties. To this end, it is often necessary to develop and apply novel technologies, e.g. membrane separation, high hydrostatic pressure and supercritical fluid extraction techniques. Also the minimal processing concept could be employed in this context.This review discusses the current technological options available and the future challenges faced in the area. Particular attention is paid to the exploitation of bovine colostrum and milk‐derived bioactive compounds for the development of functional foods.
Health information: an evaluation of the use of touch screen kiosks in two hospitals
Authors: Nicholas David , Huntington Paul , Williams Peter , Vickery Pam 
Published: March 2003

AbstractAn exit questionnaire survey of 150 hospital users of a touch screen health information kiosk was undertaken. It was compiled by Royal Cornwall Hospitals NHS to evaluate kiosk use and was reanalysed by researchers at City University to determine whether the information obtained went anyway to meeting patients’ information needs. The study established two effective outcome variables on kiosk use: whether the information found answered the users’ questions and if users intended, after using the kiosk, to find more information elsewhere. Two‐thirds of respondents said that the information found had answered their question, whilst 16% said that after using the kiosk they still had further questions and intended to talk to a health professional to obtain this information. The variables found to have an impact on the information outcome included: gender, navigational ease, object of search, and ease of reading and understanding the information.
Developing evidence‐based librarianship: practical steps for implementation*
Authors: Crumley Ellen , Koufogiannakis Denise 
Published: March 2003

AbstractEvidence‐based librarianship (EBL) is a relatively new concept for librarians. This paper lays out a practical framework for the implementation of EBL. A new way of thinking about research in librarianship is introduced using the well‐built question process and the assignment of librarian research questions to one of six domains specific to librarianship. As a profession, librarianship tends to reflect more qualitative, social sciences/humanities in its research methods and study types which tend to be less rigorous and more prone to bias. Randomised controlled trials (RCT) do not have to be placed at the top of an evidence ‘hierarchy’ for librarianship. Instead, a more encompassing model reflecting librarianship as a whole and the kind of research likely to be done by librarians is proposed. ‘Evidence’ from a number of disciplines including health sciences, business and education can be utilized by librarians and applied to their practice. However, access to and availability of librarianship literature needs to be further studied. While using other disciplines (e.g. EBHC) as a model for EBL has been explored in the literature, the authors develop models unique to librarianship. While research has always been a minor focus in the profession, moving research into practice is becoming more important and librarians need to consider the issues surrounding research in order to move EBL forward.
Evaluation of distance learning delivery of health information management and health informatics programmes: a UK perspective
Authors: Urquhart Christine , Chambers Mary , Connor Samantha , Lewis Leo , Murphy Jeannette , Roberts Ruth , Thomas Rhian 
Published: March 2003

AbstractThe aim of the article is to review evaluations of distance learning programmes in health information management, in order to identify the critical success factors for such programmes and discuss future directions. The emphasis is on the UK experience, based partly on reflections on the experience of one programme at University of Wales Aberystwyth (now over 10 years old), and partly on a policy review conducted for the NHS Information Authority and the NHS Information Policy Unit. The methods are, as far as possible, those of a systematic review of existing research, with, additionally, an overview of relevant policy developments for lifelong learning. The topics covered include the aims, objectives and educational philosophies of the programmes. The evidence, combined with the UWA experience, indicates the importance of face‐to‐face interaction, to complement distance or virtual learning. A student‐centred approach to curriculum design and delivery is essential.
A novel transverse push–pull microprobe: in vitro characterization and in vivo demonstration of the enzymatic production of adenosine in the spinal cord dorsal horn
Authors: Patterson Shawnna L. , Sluka Kathleen A. , Arnold Mark A. 
Published: March 2003

Adenosine produces analgesia in the spinal cord and can be formed extracellularly through enzymatic conversion of adenine nucleotides. A transverse push–pull microprobe was developed and characterized to sample extracellular adenosine concentrations of the dorsal horn of the rat spinal cord. Samples collected via this sampling technique reveal that AMP is converted to adenosine in the dorsal horn. This conversion is decreased by the ecto‐5′‐nucleotidase inhibitor, α,β‐methylene ADP. Related behavioral studies demonstrate that AMP administered directly to the spinal cord can reverse the secondary mechanical hyperalgesia characteristic of the intradermal capsaicin model of inflammatory pain. The specific adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dimethylxanthine (CPT) inhibits the antihyperalgesia produced by AMP. This research introduces a novel microprobe that can be used as an adjunct sampling technique to microdialysis and push–pull cannulas. Furthermore, we conclude that AMP is converted to adenosine in the dorsal horn of the spinal cord by ecto‐5′‐nucleotidase and subsequently may be one source of adenosine, acting through adenosine A1 receptors in the dorsal horn of the spinal cord, which produce antihyperalgesia.
Cyclic AMP‐dependent protein kinase (PKA) and protein kinase C phosphorylate sites in the amino acid sequence corresponding to the M3/M4 cytoplasmic domain of α4 neuronal nicotinic receptor subunits
Authors: Wecker Lynn , Guo Xiang , Rycerz Anthony M. , Edwards Samuel C. 
Published: March 2003

To determine whether α4 subunits of α4β2 neuronal nicotinic receptors are phosphorylated within the M3/M4 intracellular region by cyclic AMP‐dependent protein kinase A (PKA) or protein kinase C (PKC), immunoprecipitated receptors from Xenopus oocytes and a fusion protein corresponding to the M3/M4 cytoplasmic domain of α4 (α4336−597) were incubated with ATP and either PKA or PKC. Both α4 and α4336−597 were phosphorylated by PKA and PKC, providing the first direct biochemical evidence that the M3/M4 cytoplasmic domain of neuronal nicotinic receptor α4 subunits is phosphorylated by both kinases. When the immunoprecipitated receptors and the α4336−597 fusion protein were phosphorylated and the labeled proteins subjected to phosphoamino acid analysis, results indicated that α4 and α4336−597 were phosphorylated on the same amino acid residues by each kinase. Furthermore, PKA phosphorylated serines exclusively, whereas PKC phosphorylated both serines and threonines. To determine whether Ser368 was a substrate for both kinases, a peptide corresponding to amino acids 356–371 was synthesized (α4356−371) and incubated with ATP and the kinases. The phosphorylation of α4356−371 by both PKA and PKC was saturable with Kms of 15.3 ± 3.3 µm and 160.8 ± 26.8 µm, respectively, suggesting that Ser368 was a better substrate for PKA than PKC.
The octadecaneuropeptide ODN stimulates neurosteroid biosynthesis through activation of central‐type benzodiazepine receptors
Authors: Do‐Rego Jean‐Luc , Mensah‐Nyagan Ayikoe Guy , Beaujean Delphine , Leprince Jérôme , Tonon Marie‐Christine , Luu‐The Van , Pelletier Georges , Vaudry Hubert 
Published: March 2003

Neurosteroids may play a major role in the regulation of various neurophysiological and behavioural processes. However, while the biochemical pathways involved in the synthesis of neuroactive steroids in the central nervous system are now elucidated, the mechanisms controlling the activity of neurosteroid‐producing cells remain almost completely unknown. In the present study, we have investigated the effect of the octadecaneuropeptide (ODN), an endogenous ligand of benzodiazepine receptors, in the control of steroid biosynthesis in the frog hypothalamus. Glial cells containing ODN‐like immunoreactivity were found to send their thick processes in the close vicinity of neurones expressing the steroidogenic enzyme 3β‐hydroxysteroid dehydrogenase. Exposure of frog hypothalamic explants to graded concentrations of ODN (10−10−10−5m) produced a dose‐dependent increase in the conversion of tritiated pregnenolone into various radioactive steroids, including 17‐hydroxypregnenolone, progesterone, 17‐hydroxyprogesterone, dehydroepiandrosterone and dihydrotestosterone. The ODN‐induced stimulation of neurosteroid biosynthesis was mimicked by the central‐type benzodiazepine receptor (CBR) inverse agonists methyl β‐carboline‐3‐carboxylate (β‐CCM) and methyl 6,7‐dimethoxy‐4‐ethyl‐β‐carboline‐3‐carboxylate (DMCM). The stimulatory effects of ODN, β‐CCM and DMCM on steroid formation was markedly reduced by the CBR antagonist flumazenil. The ODN‐evoked stimulation of neurosteroid production was also significantly attenuated by GABA. Collectively, these data indicate that the endozepine ODN, released by glial cell processes in the vicinity of 3β‐hydroxysteroid dehydrogenase‐containing neurones, stimulates the biosynthesis of neurosteroids through activation of central‐type benzodiazepines receptors.
Light scattering and transmission electron microscopy studies reveal a mechanism for calcium/calmodulin‐dependent protein kinase II self‐association
Authors: Hudmon Andy , Kim Sally A. , Kolb Stephen J. , Stoops James K. , Waxham M. Neal 
Published: March 2003

Calmodulin (CaM)‐kinase II holoenzymes composed of either α or β subunits were analyzed using light scattering to determine a mechanism for self‐association. Under identical reaction conditions, only αCaM‐kinase II holoenzymes self‐associated. Self‐association was detected at a remarkably low enzyme concentration (0.14 µmor 7 µg/mL). Light scattering revealed two phases of self‐association: a rapid rise that peaked, followed by a slower decrease that stabilized after 2–3 min. Electron microscopy identified that the rapid rise in scattering was due to the formation of loosely packed clusters of holoenzymes that undergo further association into large complexes of several microns in diameter over time. Self‐association required activation by Ca2+/CaM and was strongly dependent on pH. Self‐association was not detected at pH 7.5, however, the extent of this process increased as reaction pH decreased below 7.0. A peptide substrate (autocamtide‐2) and inhibitor (AIP) designed from the autoregulatory domain of CaM‐kinase II potently prevented self‐association, whereas the peptide substrate syntide‐2 did not. Thus, CaM‐kinase II self‐association is isoform specific, regulated by the conditions of activation, and is inhibited by peptides that bind to the catalytic domain likely via their autoregulatory‐like sequence. A model for CaM‐kinase II self‐association is presented whereby catalytic domains in one holoenzyme interact with the regulatory domains in neighboring holoenzymes. These intersubunit–interholoenzyme autoinhibitory interactions could contribute to both the translocation and inactivation of CaM‐kinase II previously reported in models of ischemia.
Paracrine neuroprotective effect of nitric oxide in the developing retina
Authors: Guimarães Cinthya A. , Assreuy Jamil , Linden Rafael 
Published: March 2003

The retina of newborn rats consists of the ganglion cell layer (GCL), the inner plexiform layer (IPL), the inner nuclear layer (INL) containing amacrine cells and the neuroblastic layer (NBL). In retinal explants, the GCL enters cell death after sectioning of the optic nerve, whereas there is almost no cell death in the NBL. When protein synthesis is inhibited with anisomycin, cell death is blocked in the GCL and induced in the NBL. We tested the roles of nitric oxide (NO) on cell death in the retina in vitro. Either l‐arginine, the substrate for NO synthase or the NO donor S‐nitroso‐acetylpenicillamine (SNAP) blocked cell death induced by anisomycin in the NBL, but had no effect in the GCL. Sepiapterin, a precursor of the nitric oxide synthase (NOS)‐cofactor tetrahydrobiopterin also had a protective effect against anisomycin. The use of 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one, an inhibitor of soluble form of guanylyl cyclase, showed that anti‐apoptotic effect of SNAP is partially mediated by cGMP generated by activation of guanylyl cyclase. NADPH‐diaphorase histochemistry stained cells only in the GCL and INL. Thus, the degenerative effect of anisomycin is observed within the NBL, whereas the localization of NOS is restricted to the GCL and INL. The protective effect of both the NO substrate and cofactor upon cell death induced by anisomycin in the NBL, indicates that NO produced by amacrine and ganglion cells is a paracrine modulator of cell death within the retinal tissue.
Adjuvant‐induced joint inflammation causes very rapid transcription of β‐preprotachykinin and α‐CGRP genes in innervating sensory ganglia
Authors: Bulling Duncan G. S. , Kelly David , Bond Susan , McQueen Daniel S. , Seckl Jonathan R. 
Published: March 2003

Neuropeptides synthesized in dorsal root ganglia (DRG) have been implicated in neurogenic inflammation and nociception in experimental and clinical inflammatory arthritis. We examined the very early changes in response to adjuvant injection in a rat model of unilateral tibio‐tarsal joint inflammation and subsequent monoarthritis. Within 30 min of adjuvant injection ipsilateral swelling and hyperalgesia were apparent, and marked increases in β‐preprotachykinin‐A (β‐PPT‐A) and α‐calcitonin gene‐related peptide (CGRP)‐encoding mRNAs were observed in small‐diameter L5 DRG neurones innervating the affected joint. This response was augmented by recruitment of additional small‐diameter DRG neurones expressing β‐PPT‐A and CGRP transcripts. The increased mRNA was paralleled by initial increases in L5 DRG content of the protein products, substance P and calcitonin gene‐related peptide. Within 15 min of adjuvant injection there were increases in electrical activity in sensory nerves innervating a joint. Blockade of this activity prevented the rapid induction in β‐PPT‐A and CGRP mRNA expression in DRG neurones. Increased expression of heteronuclear (intron E) β‐PPT‐A RNA suggests that increases in β‐PPT‐A mRNA levels were, at least in part, due to transcription. Pre‐treatment with the protein synthesis inhibitor cycloheximide had no effect upon the early rise in neuropeptide mRNAs. This and the rapid time course of these changes suggest that increased sensory neural discharge and activation of a latent modulator of transcription are involved.
Activation of 5‐HT1A but not 5‐HT1B receptors attenuates an increase in extracellular dopamine derived from exogenously administered l‐DOPA in the striatum with nigrostriatal denervation
Authors: Kannari Kazuya , Yamato Hiroshi , Shen Huo , Tomiyama Masahiko , Suda Toshihiro , Matsunaga Muneo 
Published: March 2003

In order to determine whether l‐DOPA‐derived extracellular dopamine (DA) in the striatum with dopaminergic denervation is affected by activation of serotonin autoreceptors (5‐HT1A and 5‐HT1B receptors), we applied in vivo brain microdialysis technique to 6‐hydroxydopamine‐lesioned rats and examined the effects of the selective 5‐HT1A receptor agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) and the selective 5‐HT1B receptor agonist CGS‐12066 A on l‐DOPA‐derived extracellular DA levels. Single l‐DOPA injection (50 mg/kg i.p.) caused a rapid increase and a following decrease of extracellular DA, with a peak value at 100 min after l‐DOPA injection. Pretreatment with both 0.3 mg/kg and 1 mg/kg 8‐OH‐DPAT (i.p.) significantly attenuated an increase in l‐DOPA‐derived extracellular DA and the times of peak DA levels were prolonged to 150 min and 225 min after l‐DOPA injection, respectively. These 8‐OH‐DPAT‐induced changes in l‐DOPA‐derived extracellular DA were antagonized by further pretreatment with WAY‐100635, a selective 5‐HT1A antagonist. In contrast, intrastriatal perfusion with the 5‐HT1B agonist CGS‐12066 A (10 nm and 100 nm) did not induce any changes in l‐DOPA‐derived extracellular DA. Thus, stimulation of 5‐HT1A but not 5‐HT1B receptors attenuated an increase in extracellular DA derived from exogenous l‐DOPA. These results support the hypothesis that serotonergic neurons are primarily responsible for the storage and release of DA derived from exogenous l‐DOPA in the absence of dopaminergic neurons.
Tyrosine phosphorylation of insulin receptor substrate‐1 (IRS‐1) by oxidant stress in cerebellar granule neurons: modulation by N‐methyl‐d‐aspartate through calcineurin activity
Authors: Hallak Hazem , Ramadan Bassel , Rubin Raphael 
Published: March 2003

Insulin receptor‐substrate‐1 (IRS‐1) is a docking protein for several tyrosine kinase receptors. Upon tyrosine phosphorylation, IRS‐1 binds to signaling molecules that express Src homology 2 (SH‐2) binding domains, including phosphatidylinositol 3‐kinase (PI 3‐kinase), phosphotyrosine phosphatase SHP‐2 (Syp), Nck, Crk and Grb‐2. Hydrogen peroxide (H2O2) induces tyrosine phosphorylation of key signaling mediators presumably by inhibition of tyrosine phosphatases. In many cell types, the activation of extracellular signal‐related kinases (e.g. MAPK) and other protein kinases by H2O2 leads to transcriptional activation. In the current study, we examined the effect of H2O2 on IRS‐1 tyrosine phosphorylation in primary cultured rat cerebellar granule neurons. H2O2 stimulated the rapid tyrosine phosphorylation of IRS‐1 and p42/p44 MAP kinase, and induced its association with PI 3‐kinase. H2O2‐induced IRS‐1 phosphorylation was rapidly reversible (5 min) whereas MAPK phosphorylation persisted for up to 1 h. NMDA reversed H2O2‐mediated tyrosine phosphorylation of IRS‐1 and its association with PI 3‐kinase. The dephosphorylation of IRS‐1 by NMDA was calcium‐dependent and was inhibited by the calcineurin inhibitor cyclosporine. Calmodulin‐dependent tyrosine phosphatase activity of calcineurin was observed in vitro using both immunoprecipitated and recombinant tyrosine‐phosphorylated IRS‐1 as substrates. These data highlight the role of multiple phosphatases in the regulation of IRS‐1 tyrosine phosphorylation and identify a novel functional property of calcineurin.
Differential expression of 14 genes in amyotrophic lateral sclerosis spinal cord detected using gridded cDNA arrays
Authors: Malaspina Andrea , Kaushik Narendra , De Belleroche Jackie 
Published: March 2003

In order to obtain insight into the aetiology and pathogenesis of amyotrophic lateral sclerosis (ALS), high‐density gene discovery arrays (GDA human version 1.2) containing 18 400 non‐redundant EST cDNAs pooled from different tissue libraries have been used to monitor gene expression in lumbar spinal cord from ALS cases compared with controls. Quantitative filter analysis revealed differential expression of cDNAs normalized to internal standards. These candidates have been further investigated and their expression in spinal cord characterized in a panel of ALS and control subjects. Significant differential expression was obtained for 14 genes, 13 being elevated (up to six‐fold) and one decreased (by 80%) in ALS. Amongst those elevated in ALS were thioredoxin and glial fibrilary acid protein, which have already been shown to be up‐regulated in ALS, thus supporting the reliability of this approach. The other differentially regulated transcripts confirmed in the expression studies represent potential candidates in ALS pathogenesis being involved in antioxidant systems, neuroinflammation, the regulation of motor neurone function, lipid metabolism, protease inhibition and protection against apoptosis. The use of the GDA system has greatly facilitated the screening and retrieval of sequence information and has generated useful information on the cascade of molecular events occurring in ALS and potentially may highlight new candidates playing a role in the aetiology and progression of this disease.
Cannabinoids activate p38 mitogen‐activated protein kinases through CB1 receptors in hippocampus
Authors: Derkinderen Pascal , Ledent Catherine , Parmentier Marc , Girault Jean‐Antoine 
Published: March 2003

Cannabinoid receptors (CB1‐R) are the target of a novel class of neuromodulators, the endocannabinoids. Yet, their signalling mechanisms in adult brain are poorly understood. We report that, in rat and mouse hippocampal slices, anandamide and 2‐arachidonoylglycerol, synthetic cannabinoids, and Δ9‐tetrahydrocannabinol activated p38 mitogen‐activated protein kinases (MAPK), but not c‐Jun N‐terminal kinase (JNK). In contrast, lysophosphatidic acid (LPA), a lipid messenger acting on different receptors, increased both p38‐MAPK and JNK phosphorylation. The effects of cannabinoids on p38‐MAPK were mediated through activation of CB1‐R because they were blocked in the presence of SR 141716 A and absent in CB1‐R knockout mice, two conditions that did not alter the effects of LPA. The activation of p38‐MAPK by cannabinoids was insensitive to inhibitors of Src. These results provide new insights into the cellular mechanisms by which cannabinoids exert their effects in hippocampus.
Cyclic AMP modulates the response of central nervous system glia to fibroblast growth factor‐2 by redirecting signalling pathways
Authors: Bayatti Nadhim , Engele Jürgen 
Published: March 2003

Fibroblast growth factor‐2 (FGF‐2) acts as both a potent mitogen and differentiation factor for CNS glia. In the present study, we provide evidence that intracellular cAMP determines the proliferation‐differentiation decision of astroglia to FGF‐2 by either facilitating FGF‐2 signalling to extracellular signal‐related protein kinase (ERK) or cAMP response element binding protein (CREB). Pharmacologically increasing intracellular cAMP levels in cultured cortical astroglia by treatment with dbcAMP or forskolin attenuated FGF‐2‐induced ERK phosphorylation and glial cell proliferation. Similarly, FGF‐2‐induced glial proliferation was attenuated in the presence of the MEK inhibitor, PD98059, thus, confirming a direct correlation between FGF‐2‐induced ERK activation and glial cell proliferation. On the other hand, increases in intracellular cAMP levels in cortical astroglia prolonged FGF‐2‐induced CREB phosphorylation and subsequently potentiated the cAMP response element‐dependent transcription of the immediate early gene, c‐fos. Moreover, the effects of cAMP on the time‐course of FGF‐2‐dependent CREB phosphorylation were mimicked by PD98059, suggesting that the cAMP‐induced redirection of FGF‐2‐signalling is linked to the RAF‐MEK‐ERK signalling pathway.