bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does phosphorylation of eukaryotic elongation factor eEF2 regulate protein synthesis in ischemic preconditioning?
Authors: García L. , O'Loghlen A. , Martín M.E. , Burda J. , Salinas M. 
Published: May 2004

AbstractIschemia/reperfusion‐associated translation inhibition in the hippocampus is attenuated significantly at reinitiation and elongation steps by ischemic preconditioning (Burda et al. [2003] Neurochem. Res. 28:1237–1243). To address potential regulation of the elongation step by changes in eukaryotic elongation factor 2 (eEF2) phosphorylation with and without acquired ischemic tolerance (IT), Wistar rats were preconditioned by 5‐min sublethal ischemia and 2 days later, 30‐min lethal ischemia was induced. Given the important role that oxidative stress plays in the ischemic process, eEF2 phosphorylation was also studied in a model of oxidative stress in vitro. Three blocks of our results support a lack of correlation between eEF2 phosphorylation status and protein synthesis rate. First, eEF2 was dephosphorylated significantly (activated) after transient cerebral ischemia in rats with and without IT or H2O2‐treated cells; however, protein synthesis was significantly inhibited under these three conditions. Second, after 30‐min reperfusion, the protein synthesis rate was maintained below control levels in cortex and hippocampus of rats without IT. Eukaryotic EF2 phosphorylated levels were notably low only in the cortex, whereas levels in the hippocampus were close to that of sham controls. In rats with IT, protein synthesis was virtually restored in both brain regions, but phosphorylated eEF2 levels were even higher than in rats without IT. Third, after 4‐hr reperfusion, the protein synthesis rate in cortex and hippocampus was observed to be below sham control values in rats with and without IT. Conversely, phosphorylated eEF2 levels were below sham control in rats with IT and reached sham control values in rats without IT. © 2004 Wiley‐Liss, Inc.
Insulin‐like growth factor type 1 prevents hyperglycemia‐induced uncoupling protein 3 down‐regulation and oxidative stress
Authors: Gustafsson Helena , Söderdahl Therése , Jönsson Gunn , Bratteng Jan‐Ove , Forsby Anna 
Published: May 2004

AbstractUncoupling proteins (UCPs) have been reported to decrease the mitochondrial production of reactive oxygen species (ROS) by lowering the mitochondrial inner membrane potential (MMP). We have previously shown that UCP3 expression is positively regulated by insulin‐like growth factor‐1 (IGF‐1). The aim of this study was to investigate the role of UCPs in IGF‐1‐mediated protection from hyperglycemia‐induced oxidative stress and neurodegeneration. Human neuroblastoma SH‐SY5Y cells were differentiated with retinoic acid for 6 days, after which exposure to 8, 30, or 60 mM glucose with or without 10 nM IGF‐1 was started. After 48–72 hr, the number of neurites per cell, UCP3 protein expression, MMP, and intracellular levels of ROS and total glutathione were examined. These studies showed that glucose concentration‐dependently reduced the number of neurites per cell, with a 50% reduction at 60 mM. In parallel, the UCP3 protein expression was down‐regulated, and the MMP was raised 3.5‐fold, compared with those in cells incubated with 8 mM glucose. Also, the ROS levels were increased, showing a twofold maximum at 60 mM glucose. This was accompanied by a twofold elevation of total glutathione levels, confirming an altered cellular redox state. IGF‐1 treatment prevented the glucose‐induced neurite degeneration and UCP3 down‐regulation. Furthermore, the MMP and the intracellular levels of ROS and glutathione were normalized to those of control cells. These data indicate that IGF‐1 may protect from hyperglycemia‐induced oxidative stress and neuronal injuries by regulating MMP, possibly by the involvement of UCP3. © 2004 Wiley‐Liss, Inc.
Recurrent paraplegia after remyelination of the spinal cord
Authors: Jasmin Luc , Ohara Peter T. 
Published: May 2004

AbstractWe have conducted a long‐term study of spinal cord morphology and motor function recovery in rats that have undergone lumbar spinal demyelination induced by the B‐fragment of cholera toxin (CTB)‐saporin. We found that, after the initial demyelination and paraplegia, motor function recovered and was stable for up to 9 months, after which there occurred a slow deterioration of motor function accompanied by loss of motoneurons and loss of spinal white matter. A striking morphological feature was the appearance of large spheroids of calcium in the ventral and dorsal horns and occasionally in the white matter. Motor performance deterioration occurred earlier and was more severe in rats that had been exercised on a treadmill, but the same morphological changes occurred in both exercise‐ and nonexercise‐treated animals. Rats given treadmill exercise starting 3 weeks after toxin injection had a mean motor deficit score of 3.0 (i.e., paraplegia) at perfusion, whereas the nontreadmill‐treated rats had a mean score of 1.8 (SD 0.38; n = 6; P < .05). These findings suggest that, in addition to the acute effects of the toxin‐induced demyelination from which there is recovery of motor function, there are chronic irreversible effects of the toxin, or the initial demyelination, that cause a slow progressive degeneration of the spinal cord. This model might therefore be useful in studying the long‐term effects of spinal insult of the type associated with conditions such as postpolio syndrome. © 2004 Wiley‐Liss, Inc.
Caloric restriction augments brain glutamic acid decarboxylase‐65 and ‐67 expression
Authors: Cheng Clara M. , Hicks Kristin , Wang Jie , Eagles Douglas A. , Bondy Carolyn A. 
Published: May 2004

AbstractThe ketogenic diet is a very low‐carbohydrate, high‐fat diet used to treat refractory epilepsy. We hypothesized that this diet may act by increasing expression of glutamic acid decarboxylase (GAD), the rate‐limiting enzyme in γ‐aminobutyric acid (GABA) synthesis. Thus, we evaluated brain GAD levels in a well‐established, seizure‐suppressing, rodent model of the ketogenic diet. Because the diet is most effective when administered with a modest (∼10%) calorie restriction, we studied three groups of animals: rats fed ad libitum standard rat chow (Ad lib‐Std); calorie‐restricted standard chow (CR‐Std); and an isocaloric, calorie‐restricted ketogenic diet (CR‐Ket). We found that GAD67 mRNA was significantly increased in the inferior and superior colliculi and cerebellar cortex in both CR diet groups compared with control (e.g., by 45% in the superior colliculus and by 71% in the cerebellar cortex;P< .001). GAD65 mRNA was selectively increased in the superior colliculus and temporal cortex in both CR‐Std and CR‐Ket diet groups compared with ad lib controls. The only apparent CR‐Ket‐specific effect was a 30% increase in GAD67 mRNA in the striatum (P= .03). Enhanced GAD immunoreactivity was detected in parallel with the mRNA changes. These data clearly show that calorie restriction increases brain GAD65 and ‐67 expression in several brain regions, independent of ketogenic effects. These observations may explain why caloric restriction improves the efficacy of the ketogenic diet in treating epilepsy and suggest that diet modification might be useful in treatment of a number of brain disorders characterized by impaired GAD or GABA activity. © 2004 Wiley‐Liss, Inc.
Estrogen treatment induces a novel population of regulatory cells, which suppresses experimental autoimmune encephalomyelitis
Authors: Matejuk Agata , Bakke Antony C. , Hopke Corwyn , Dwyer Jami , Vandenbark Arthur A. , Offner Halina 
Published: May 2004

AbstractMultiple sclerosis (MS) is a debilitating neurological disease characterized by a progressive loss of motor and sensory function, eventually leading to paralysis and death. The primary cause of neurological impairment is demyelination of the central nervous system (CNS) caused by an inflammatory autoimmune response. Previous studies have shown that the severity of MS is reduced during pregnancy, suggesting that the increased level of sex hormones may reduce the autoimmune response. Recently, we have shown that estrogen treatment confers protection from experimental autoimmune encephalomyelitis (EAE), which is an animal model for MS. However, the cellular basis of estrogen's action remains unknown. In the current study, we demonstrate that estrogen treatment led to the induction of a novel subpopulation of regulatory cells in spleen and CNS, which also occurs naturally in pregnant mice. These previously uncharacterized cells display a low level expression of CD45 (CD45dim) and no detectable expression of many cell surface markers related to TCR signaling, including CD3 and TCR. However, these cells retained expression of VLA‐4, an extracellular protein involved in cellular migration. Several lines of evidence suggest that these novel cells, defined as CD45dimVLA‐4+ cells, may play a role in the protective effects of estrogen in EAE. Injection of purified CD45dimVLA‐4+ cells conferred protection from spontaneous EAE (Sp‐EAE). In contrast, injection of CD45highVLA‐4+ cells exacerbated the disease course. CD45dimVLA‐4+ cells also suppressed antigen‐specific proliferation of primed lymphocytes in coculture. A better understanding of how CD45dimVLA‐4+ cells suppress the harmful immune response of EAE may help in explaining the induction of immune tolerance during pregnancy and lead to novel therapeutic approaches to combat MS and other autoimmune diseases. © 2004 Wiley‐Liss, Inc.
Beta‐secretase BACE1 is differentially controlled through muscarinic acetylcholine receptor signaling
Authors: Züchner Thole , Perez‐Polo J. Regino , Schliebs Reinhard 
Published: May 2004

AbstractThe β‐amyloid peptides derived by proteolytic cleavage from the amyloid precursor protein (APP) play a major role in the pathogenesis of Alzheimer's disease (AD) by forming aggregated, fibrillary complexes that have been shown to be neurotoxic. The β‐site APP‐cleaving enzyme (BACE1) has been identified as the key enzyme leading to β‐amyloid formation, and cholinergic mechanisms have been shown to control APP processing. The present study sought to determine whether BACE1 expression is controlled by muscarinic acetylcholine receptor (mAChR) subtypes in the neuroblastoma cell line SK‐SH‐SY5Y. Stimulation of cells with the M1/M3‐selective mAChR agonist talsaclidine for 1 hr resulted in a dose‐dependent increase in BACE1 expression up to twofold over basal levels. Similar effects of BACE1 up‐regulation were observed when protein kinase C was directly activated by phorbol esters. However, when the MAP kinases MEK/ERK were inhibited, BACE1 expression was no longer up‐regulated by the activation of M1‐mAChR. In contrast, BACE1 expression was suppressed by stimulation of M2‐mediated pathways via selective M2‐agonist binding or direct activation of adenylate cyclase with forskolin, an effect that was prevented by inhibiting protein kinase A. These results may explain the observed deterioration of AD patients after initial improvements with AChE inhibitor or M1‐mAChR agonist treatment. © 2004 Wiley‐Liss, Inc.
Metallothionein prevents neurodegeneration and central nervous system cell death after treatment with gliotoxin 6‐aminonicotinamide
Authors: Penkowa Milena , Quintana Albert , Carrasco Javier , Giralt Mercedes , Molinero Amalia , Hidalgo Juan 
Published: May 2004

AbstractTransgenic expression of interleukin‐6 (IL‐6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP‐IL6 mice) induces significant inflammation and neurodegeneration but also affords neuroprotection against acute traumatic brain injury. This neuroprotection is likely mediated by the IL‐6‐induced protective factors metallothioneins‐I and ‐II (MT‐I+II). Here we evaluate the neuroprotective roles of IL‐6 vs. MT‐I+II during 6‐aminonicotinamide (6‐AN)‐induced neurotoxicity, by using GFAP‐IL6 mice and transgenic mice overexpressing MT‐I (TgMT) as well as GFAP‐IL6 mice crossed with TgMT mice (GFAP‐IL6 × TgMT). 6‐AN caused acute damage of brainstem gray matter areas identified by necrosis of astrocytes, followed by inflammatory responses. After 6‐AN‐induced toxicity, secondary damage was observed, consisting of oxidative stress, neurodegeneration, and apoptotic cell death. We hereby show that the primary injury caused by 6‐AN was comparable in wild‐type and GFAP‐IL6 mice, but MT‐I overexpression could significantly protect the brain tissue. As expected, GFAP‐IL6 mice showed increased CNS inflammation with more gliosis, macrophages, and lymphocytes, including increased cytokine expression, relative to the other mice. However, GFAP‐IL6 mice showed reduced oxidative stress (judged from nitrotyrosine, malondialdehyde, and 8‐oxoguanine stainings), neurodegeneration (accumulation of neurofibrillary tangles), and apoptosis (determined from TUNEL and caspase‐3). MT‐I+II expression was significantly higher in GFAP‐IL6 mice than in wild types, which may contribute to the IL‐6‐induced neuroprotection. In support of this, overexpression of MT‐I in GFAP‐IL6 × TgMT as well as TgMT mice protected the brainstem tissue significantly from 6‐AN‐induced toxicity and secondary brain tissue damage. Overall, the results demonstrate that brain MT‐I+II proteins are fundamental neuroprotective factors, which in the future may become therapeutic agents. © 2004 Wiley‐Liss, Inc.
Dysmyelination and reduced myelin basic protein gene expression by oligodendrocytes of SHP‐1‐deficient mice
Authors: Massa Paul T. , Wu Charlene , Fecenko‐Tacka Karen 
Published: May 2004

AbstractWe have shown previously that myelin‐forming oligodendrocytes express the protein tyrosine phosphatase SHP‐1 and that myelin formation was decreased in SHP‐1‐deficient motheaten mice compared to that in normal littermates. These studies suggested a potential importance for SHP‐1 in oligodendrocyte and myelin development. To address further this possibility, we analyzed myelin formation by microscopy and myelin basic protein (MBP) gene expression in motheaten mice at ages when myelination occurs in the developing central nervous system (CNS). Furthermore, we correlate these findings with MBP gene expression in oligodendrocytes grown in vitro. We have found that CNS myelination was significantly reduced in SHP‐1‐deficient mice relative to their normal littermates at multiple times during the active period of myelination. Under electron microscopy, greater numbers of axons in spinal cords of motheaten mice were either unmyelinated or had thinner myelin sheathes compared to those in matched areas of normal littermates. Accordingly, MBP protein and mRNA levels were reduced in SHP‐1‐deficient mice compared to that in the CNS of normal littermates. In vitro, O1+ oligodendrocytes from motheaten mice expressed much less MBP than O1+ oligodendrocytes of normal littermates indicating an alteration in oligodendrocyte differentiation. The latter correlated with reduced MBP mRNA relative to cerebroside galactosyl transferase (CGT) gene mRNA in SHP‐1‐deficient oligodendrocytes in purified cultures. We propose that SHP‐1 is a critical regulator of developmental signals leading to terminal differentiation and myelin sheath formation by oligodendrocytes. © 2004 Wiley‐Liss, Inc.
Vibrational spectra of some pharmacologically interesting pyroglutamato complexes
Authors: Wagner Claudia C. , Baran Enrique J. 
Published: May 2004

AbstractThe infrared and Raman spectra of lithium, zinc, calcium and magnesium complexes of L‐pyroglutamic acid were recorded and are briefly discussed. For the first three compounds the spectral discussion is based on their known structural characteristics. Comparing the spectroscopic behaviour of the complexes and the free acid, some comments on the structural peculiarities of the magnesium compound could be advanced. The pharmacological interest of these complexes is also briefly discussed. Copyright © 2004 John Wiley & Sons, Ltd.
A theoretical and spectroscopic study of carbamazepine polymorphs
Authors: Strachan Clare J. , Howell Sarah L. , Rades Thomas , Gordon Keith C. 
Published: May 2004

AbstractThe drug carbamazepine has been modeled, using ab initio density functional theory calculations [B3LYP/6–31G(d)], both as a single molecule and as a dimer. The predicted geometry of the single molecule calculation is compared with the crystallographic data on each of the polymorphs (carbamazepine forms I and III). From the predicted geometry it is possible to calculate the IR and Raman spectra; these predictions compare favorably with the observed spectra of both polymorphs of carbamazepine for most of the bands. The spectral differences between the polymorphs are more striking in the IR than the Raman spectra, with strong IR bands at 1688 and 1396 cm−1 in form I shifting to 1678 and 1388 cm−1 in form III. Analysis of the potential energy distributions for the calculated normal modes reveals that the vibrations are localized across different ring systems of the carbamazepine structure. Most notably, the polymorph‐sensitive modes in the IR spectra are localized to the pendant CONH2 group; it is these modes that show the greatest disparity from the calculated spectra, and it is this group that is perturbed in the polymorph crystal structures. The calculated dimer structure is similar to that of the single molecule, but the polymorph‐sensitive IR modes are significantly better predicted by the dimer calculation. Copyright © 2004 John Wiley & Sons, Ltd.
Surface‐enhanced Raman scattering of D‐penicillamine on silver colloids
Authors: López‐Ramírez M. R. , Arenas J. F. , Otero J. C. , Castro J. L. 
Published: May 2004

AbstractThe Raman spectra of D‐penicillamine in H2O and D2O were recorded under different acidity conditions, together with the respective SERS spectra on silver colloids. Vibrational assignments of the spectra obtained are proposed. The analysis of the SERS spectra shows that two of the conformers of D‐penicillamine are adsorbed at least in their dianionic forms, and a stable chemical bond is established between the sulfur atom and silver. Additionally, carboxylate and amino groups also interact with the metal. The pK and pK apparent values are decreased upon adsorption. Copyright © 2004 John Wiley & Sons, Ltd.
Polymorphism and devitrification of nifedipine under controlled humidity: a combined FT‐Raman, IR and Raman microscopic investigation
Authors: Chan K. L. A. , Fleming O. S. , Kazarian S. G. , Vassou D. , Chryssikos G. D. , Gionis V. 
Published: May 2004

AbstractFT‐Raman and FT‐IR spectroscopy and Raman microscopy were employed to identify the structural characteristics of one amorphous and three crystalline phases of nifedipine, a common antihypertension drug of the 1,4‐dihydropyridine family. A significant fraction of the nifedipine molecules in the glass are found to be frozen into metastable rotational conformations as a result of melt quenching. Moreover, the effect of relative humidity (RH = 20–80%) on the onset and rate of crystallization was studied at 40 °C by means of in situ IR and Raman microscopy employing a controlled humidity cell. The nature and the relative abundance of the various crystallization products were analysed on the basis of the corresponding spectra of the neat compounds. Glassy nifedipine is found to crystallize to the thermodynamically stable α‐polymorph via a transient metastable β‐nifedipine phase. Increasing RH in the range 20–60% is found to favour the surface crystallization of the glass to β‐nifedipine. At high RH (80%), β‐nifedipine is rapidly converted to α‐nifedipine. Copyright © 2004 John Wiley & Sons, Ltd.
Quantitative analysis of polymorphic mixtures of carbamazepine by Raman spectroscopy and principal components analysis
Authors: Strachan Clare J. , Pratiwi Destari , Gordon Keith C. , Rades Thomas 
Published: May 2004

AbstractThe polymorphic behaviour of drugs is a major concern of the pharmaceutical industry as it may have considerable formulation, therapeutic, legal and commercial implications. It is therefore crucial to be able adequately to identify and quantify different polymorphic forms of drugs as early as possible in the drug discovery and development process. The aim of the present study was to investigate the application of Raman spectroscopy and principal components analysis (PCA) to the quantitative analysis of polymorphic mixtures of carbamazepine forms III and I, based on both individual peak areas and heights in the Raman spectra and whole wavenumber ranges. Various linear regressions indicated that in general using every fourth wavenumber value of a larger region of the Raman spectrum gives better quantitative results than choosing defined peak areas and peak heights, as the spectral differences between the polymorphs were only subtle. Baseline correction of the spectral data did not appear to improve the quantitative analysis, with detection and quantification limits being the lowest (0.33 and 1.09%, respectively) and R2 being the highest (0.96) when using every fourth wavenumber value from 2950 to 3100 cm−1 as input data for the PCA analysis without baseline correction. This study demonstrated that PCA of Raman spectroscopic data provides a sensitive method for the quantitative analysis of polymorphic forms, with a quantitation limit of <2%, if the spectral input data are selected carefully. In the absence of clear and distinct spectral differences at certain wavenumbers between the polymorphic forms, selection of larger spectral regions that contain most of the detectable differences between the two forms appears to be the best data selection technique. Copyright © 2004 John Wiley & Sons, Ltd.
Structural compatibility of novel nucleotide modifications with shortened linkages designed for antigene/antisense therapy
Authors: Hanuš J. , Němeček D. , Štěpánek J. , Turpin P.‐Y. , Králíková Š. , Bok J. , Rosenberg I. 
Published: May 2004

AbstractThe impact of isopolar shortened internucleotide linkage modification on the hybridization properties of potential antisense or antigene oligonucleotides was studied by using a model molecular system consisting of polyuridylic acid (PolyU) and analogs of diadenosine monophosphate with the modified linkage. Raman spectra of mixed aqueous solutions were measured at various temperatures and compositions of the mixtures for four types of modified linkage and natural ApA (3′–5′) as a reference. Analysis of the spectral sets provided amounts of formed complexes and their Raman spectra. It has been found that as in the case of ApA (3′–5′), the studied ApA analogs form with PolyU triplex‐like complexes containing a central pseudo‐chain of closely arranged adenosine dimers. In the case of S‐ and R‐configured 2′–5′ and 3′–5′ ApCOH A analogs, respectively, the amounts of complexes formed even exceed the ApA. This hybridization effectiveness is reached, however, by a more feasible prolongation of the pseudo‐chain, while the stability constant for the initiation step is significantly lower. Raman spectra of the complexes showed that for both of the above analogs the structural compatibility with the natural nucleic acid chain is decreased, because of the distorted position of one adenine residue. This distortion influences the Watson–Crick hydrogen bonds. The two types of linkages may be suitable just for construction of longer antigene or antisense oligonucleotides with alternating lengthened and shortened linkages. There is, however, a warning of possible decreased binding specificity. Copyright © 2004 John Wiley & Sons, Ltd.