bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer's disease and link to cognitive impairment
Authors: Ahmed Naila , Ahmed Usman , Thornalley Paul J. , Hager Klaus , Fleischer Gerd , Münch Gerald
Published: January 2005

Increased damage to proteins by glycation, oxidation and nitration has been implicated in neuronal cell death leading to Alzheimer's disease (AD). Protein glycation, oxidation and nitration adducts are consequently formed. Quantitative screening of these adducts in CSF may provide a biochemical indicator for the diagnosis of AD. To assess this, we measured 11 glycation adducts, three oxidation adducts and a nitration adduct, determining both protein adduct residues and free adducts, in CSF samples of age‐matched normal healthy subjects (n = 18) and subjects with Alzheimer's disease (n = 32). In CSF protein, the concentrations of 3‐nitrotyrosine, Nɛ‐carboxymethyl‐lysine, 3‐deoxyglucosone‐derived hydroimidazolone and N‐formylkynurenine residues were increased in subjects with Alzheimer's disease. In CSF ultrafiltrate, the concentrations of 3‐nitrotyrosine, methylglyoxal‐derived hydroimidazolone and glyoxal‐derived hydroimidazolone free adducts were also increased. The Mini‐Mental State Examination (MMSE) score correlated negatively with 3‐nitrotyrosine residue concentration (p < 0.05), and the negative correlation with fructosyl‐lysine residues just failed to reach significance (p = 0.052). Multiple linear regression gave a regression model of the MMSE score on 3‐nitrotyrosine, fructosyl‐lysine and Nɛ‐carboxyethyl‐lysine residues with p‐values of 0.021, 0.031 and 0.052, respectively. These findings indicate that protein glycation, oxidation and nitration adduct residues and free adducts were increased in the CSF of subjects with Alzheimer's disease. A combination of nitration and glycation adduct estimates of CSF may provide an indicator for the diagnosis of Alzheimer's disease.
Involvement of 3′,5′‐cyclic adenosine monophosphate‐dependent protein kinase in regulation of Fos expression and tyrosine hydroxylase levels during morphine withdrawal in the hypothalamic paraventricular nucleus and medulla oblongata catecholaminergic cell groups
Authors: Benavides Marta , Laorden M. Luisa , Milanés M. Victoria
Published: January 2005

Morphine withdrawal stimulates the hypothalamic‐pituitary‐adrenocortical axis activity by activation of nucleus tractus solitarius (NTS)/ventrolateral medulla (VLM) noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN). We investigated whether cAMP‐dependent protein kinase (PKA) plays a role in this process by estimating changes in PKA immunoreactivity and the influence of inhibition of PKA on Fos protein expression and tyrosine hydroxylase (TH) immunoreactivity levels in the PVN and NTS/VLM during morphine withdrawal. Dependence on morphine was induced by a 7‐day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (5 mg/kg s.c.). When opioid withdrawal was precipitated, an increase in PKA immunoreactivity levels was observed 90 min after naloxone administration in the PVN and NTS/VLM areas. Morphine withdrawal induced expression of Fos in the PVN and NTS/VLM, indicating an activation of neurones in those nuclei. TH immunoreactivity in NTS/VLM was increased 90 min after induction of morphine withdrawal, whereas there was a decrease in TH levels in the PVN at the same time point. When the selective PKA inhibitor HA‐1004 was infused it greatly diminished the Fos expression observed in morphine‐withdrawn rats. Furthermore, the changes in TH immunoreactivity were significantly modified by infusion of HA‐1004. The present findings suggest that an up‐regulated PKA‐dependent transduction pathway might contribute to the activation of the hypothalamic‐pituitary‐adrenocortical axis in response to morphine withdrawal.
Stimulation of the locus coeruleus elicits noradrenaline and dopamine release in the medial prefrontal and parietal cortex
Authors: Devoto Paola , Flore Giovanna , Saba Pierluigi , Fà Mauro , Gessa Gian Luigi
Published: January 2005

Our previous studies have suggested that dopamine and noradrenaline may be coreleased from noradrenergic nerve terminals in the cerebral cortex. To further clarify this issue, the effect of electrical stimulation of the locus coeruleus on extracellular noradrenaline, dopamine and DOPAC in the medial prefrontal cortex, parietal cortex and caudate nucleus was analysed by microdialysis in freely moving rats. Stimulation of the locus coeruleus for 20 min with evenly spaced pulses at 1 Hz failed to modify cortical catecholamines and DOPAC levels. Stimulation with bursts of pulses at 12 and 24 Hz increased, in a frequency‐related manner, not only noradrenaline but also dopamine and DOPAC in the two cortices. In both cortices noradrenaline returned to baseline within 20 min of stimulation, irrespective of the stimulation frequency, whereas dopamine returned to normal within 20 and 60 min in the medial prefrontal cortex and within 60 and 80 min in the parietal cortex after 12 and 24 Hz stimulation, respectively. DOPAC remained elevated throughout the experimental period. Phasic stimulation of the locus coeruleus at 12 Hz increased noradrenaline in the caudate nucleus as in the cerebral cortices but was totally ineffective on dopamine and DOPAC. Tetrodotoxin perfusion into the medial prefrontal cortex dramatically reduced noradrenaline and dopamine levels and suppressed the effect of electrical stimulation. These results indicate that electrical stimulation‐induced increase of dopamine is a nerve impulse exocytotic process and suggest that cortical dopamine and noradrenaline may be coreleased from noradrenergic terminals.
Mutagenesis analysis of the serotonin 5‐HT2C receptor and a Caenorhabditis elegans 5‐HT2 homologue: conserved residues of helix 4 and helix 7 contribute to agonist‐dependent activation of 5‐HT2 receptors
Authors: Xie Jinling , Dernovici Serghei , Ribeiro Paula
Published: January 2005

An alignment of serotonin [5‐hydroxytryptamine (5‐HT)] G protein‐coupled receptors identified a lysine at position 4.45 (helix 4) and a small polar residue (serine or cysteine) at 7.45 (helix 7) that occur exclusively in the 5‐HT2 receptor family. Other serotonin receptors have a hydrophobic amino acid, typically a methionine, at 4.45 and an invariant asparagine at 7.45. The functional significance of these class‐specific substitutions was tested by site‐directed mutagenesis of two distantly related 5‐HT2 receptors, Caenorhabditis elegans 5‐HT2ce and rat 5‐HT2C. Residues 4.45 and 7.45 were each mutated to a methionine and asparagine, respectively, or an alanine and the resulting constructs were tested for activity. A K4.45M mutation decreased serotonin‐dependent activity (Emax) of the rat 5‐HT2C receptor by 60% and that of the C. elegans homologue by 40%, as determined by a fluorometric plate‐based calcium assay. The rat mutant also exhibited nearly sixfold higher agonist binding affinity and significantly lower constitutive activity compared with wildtype. Mutagenesis of S7.45 in the C. elegans receptor increased serotonin binding affinity by up to 25‐fold and decreased Emax by up to 65%. The same mutations of the cognate C7.45 in rat 5‐HT2C produced a smaller fourfold change in the affinity for serotonin and decreased agonist efficacy by up to 50%. Substitutions of S/C7.45 did not produce a significant change in the basal activity of either receptor. All mutants tested exhibited levels of receptor expression similar to the corresponding wildtype based on measurements of specific [3H]‐mesulergine binding or flow cytometry analyses. Taken together, these results suggest that K4.45 and S/C7.45 play an important role in the conformational rearrangements leading to agonist‐induced activation of 5‐HT2 receptors.
Inhibition of the α‐ketoglutarate dehydrogenase complex by the myeloperoxidase products, hypochlorous acid and mono‐N‐chloramine
Authors: Jeitner Thomas M. , Xu Hui , Gibson Gary E.
Published: January 2005

α‐Ketoglutarate dehydrogenase (KGDHC) complex activity is diminished in a number of neurodegenerative disorders and its diminution in Alzheimer Disease (AD) is thought to contribute to the major loss of cerebral energy metabolism that accompanies this disease. The loss of KGDHC activity appears to be predominantly due to post‐translation modifications. Thiamine deficiency also results in decreased KGDHC activity and a selective neuronal loss. Recently, myeloperoxidase has been identified in the activated microglia of brains from AD patients and thiamine‐deficient animals. Myeloperoxidase produces a powerful oxidant, hypochlorous acid that reacts with amines to form chloramines. The aim of this study was to investigate the ability of hypochlorous acid and chloramines to inhibit the activity of KGDHC activity as a first step towards investigating the role of myeloperoxidase in AD. Hypochlorous acid and mono‐N‐chloramine both inhibited purified and cellular KGDHC and the order of inhibition of the purified complex was hypochlorous acid (1×) > mono‐N‐chloramine (∼50x) > hydrogen peroxide (∼1 500). The inhibition of cellular KGDHC occurred with no significant loss of cellular viability at all exposure times that were examined. Thus, hypochlorous acid and chloramines have the potential to inactivate a major target in neurodegeneration.
Direct interaction of myosin regulatory light chain with the NMDA receptor
Authors: Amparan David , Avram Dorina , Thomas Christopher G. , Lindahl Michaela G. , Yang Jing , Bajaj Gaurav , Ishmael Jane E.
Published: January 2005

NMDA receptors interact with a variety of intracellular proteins at excitatory synapses. In this paper we show that myosin regulatory light chain (RLC) isolated from mouse brain is a NMDA receptor‐interacting protein. Myosin RLC bound directly to the C‐termini of both NMDA receptor 1 (NR1) and NMDA receptor 2 (NR2) subunits, rendering the interaction of myosin RLC with NMDA receptors distinct from that of calmodulin which is considered a NR1‐interacting protein. Myosin RLC co‐localized with NR1 in the dendritic spines of isolated hippocampal neurons, and was co‐immunoprecipitated from brain extracts in a complex with NR1, NR2A, NR2B, PSD‐95, Adaptor protein‐2 and myosin II heavy chain. The C0 region of NR1 was necessary and sufficient for binding myosin RLC. Ca2+/calmodulin, but not calmodulin alone, displaced recombinant myosin RLC from the carboxy tail of NR1 indicating that myosin RLC and Ca2+/calmodulin can compete for a common binding site on NR1 in vitro. Myosin RLC is the only known substrate for myosin regulatory light chain kinase, which has recently been shown to modulate NMDA receptor function in isolated hippocampal neurons. Our results suggest that an additional level of NMDA receptor regulation may be mediated via a direct interaction with a light chain of myosin II. Thus, myosin RLC–NMDA receptor interactions may contribute to the contractile and motile forces that are placed upon NMDA receptor subunits during changes associated with synaptic plasticity and neural morphogenesis.
Calcium‐dependent dephosphorylation of brain mitochondrial calcium/cAMP response element binding protein (CREB)
Authors: Schuh Rosemary A. , Kristián Tibor , Fiskum Gary
Published: January 2005

Calcium‐mediated signaling regulates nuclear gene transcription by calcium/cAMP response element binding protein (CREB) via calcium‐dependent kinases and phosphatases. This study tested the hypothesis that CREB is also present in mitochondria and subject to dynamic calcium‐dependent modulation of its phosphorylation state. Antibodies to CREB and phosphorylated CREB (pCREB) were used to demonstrate the presence of both forms in isolated mitochondria and mitoplasts from rat brain. When energized mitochondria were exposed to increasing concentrations of Ca2+ in the physiological range, pCREB was lost while total CREB remained constant. In the presence of Ru360, an inhibitor of the mitochondrial Ca2+ uptake uniporter, calcium‐dependent loss of pCREB levels was attenuated, suggesting that intramitochondrial calcium plays an important role in pCREB dephosphorylation. pCREB dephosphorylation was not, however, inhibited by the phosphatase inhibitors okadaic acid and Tacrolimus. In the absence of Ca2+, CREB phosphorylation was elevated by the addition of ATP to the mitochondrial suspension. Exposure of mitochondria to the pore‐forming molecule alamethicin that causes osmotic swelling and release of intermembrane proteins enriched mitochondrial pCREB immunoreactivity. These results further suggest that mitochondrial CREB is located in the matrix or inner membrane and that a kinase and a calcium‐dependent phosphatase regulate its phosphorylation state.
Group I and II metabotropic glutamate receptors alter brain cortical metabolic and glutamate/glutamine cycle activity: a 13C NMR spectroscopy and metabolomic study
Authors: Rae Caroline , El‐Hajj Moussa Charbel , Griffin Julian L. , Bubb William A. , Wallis Trent , Balcar Vladimir J.
Published: January 2005

Metabotropic glutamate receptors (mGluR) modulate neuronal function. Here, we tested the effect on metabolism of a range of Group I and II mGluR ligands in Guinea pig brain cortical tissue slices, applying 13C NMR spectroscopy and metabolomic analysis using multivariate statistics. The effects of Group I agonists (S)‐3,5‐dihydroxyphenylglycine (DHPG) and (RS)‐2‐chloro‐5‐hydroxyphenylglycine (CHPG) depended upon concentration and were mostly stimulatory, increasing both net metabolic flux through the Krebs cycle and glutamate/glutamine cycle activity. Only the higher (50 µm) concentrations of CHPG had the opposite effect. The Group I antagonist (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA), consistent with its neuroprotective role, caused significant decreases in metabolism. With principal components analysis of the metabolic profiles generated by these ligands, the effects could be separated by two principal components. Agonists at Group II mGluR [(2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG IV) and 2R,4R‐4‐aminopyrrolidine‐2,4‐dicarboxylate (APDC)] generally stimulated metabolism, including glutamate/glutamine cycling, although this varied with concentration. The antagonist (2S)‐α‐ethylglutamic acid (EGLU) stimulated astrocyte metabolism with minimal impact on glutamate/glutamine cycling. (RS)‐1‐Aminophosphoindan‐1‐carboxylic acid (APICA) decreased metabolism at 5 µm but had a stimulatory effect at 50 µm. All ligand effects were separated from control and from each other using two principal components. The ramifications of these findings are discussed.
Role of basic region leucine zipper transcription factors cyclic AMP response element binding protein (CREB), CREB2, activating transcription factor 2 and CAAT/enhancer binding protein α in cyclic AMP response element‐mediated transcription
Authors: Thiel Gerald , Al Sarraj Jude , Vinson Charles , Stefano Luisa , Bach Karl
Published: January 2005

The transcription factor cAMP response element binding protein (CREB), a member of the basic region leucine zipper (bZIP) family of proteins, is the major cAMP response element (CRE) binding. Other bZIP proteins, including CREB2, activating transcription factor 2 (ATF2), or CAAT/enhancer binding protein (C/EBP) have been reported to transactivate CRE‐containing genes or to interfere with transactivation by CREB. We have designed a simple transactivation assay using expression of either a constitutively active CREB mutant or a nuclear targeted mutant of the catalytic subunit of cAMP‐dependent protein kinase. In both cases, a striking stimulation of transcription of CRE‐containing reporter genes was observed in noradrenergic locus coeruleus‐like CATH.a cells. In addition, a constitutively active mutant of ATF2 specifically transactivated a secretogranin II promoter/luciferase reporter gene, but had no effect on the tyrosine hydroxylase promoter. In contrast, CREB2 and C/EBPα did not transactivate CRE‐containing reporter genes, indicating that these bZIP proteins target distinct genetic elements. Experiments involving dominant‐negative bZIP mutants revealed that CREB does not heterodimerize with CREB2, ATF2, c‐Jun or C/EBP. Rather, CREB and ATF2 compete for binding to the CRE, and are independently able to up‐regulate transcription of genes containing CRE motifs in their regulatory regions.
Charge selectivity of the Cys‐loop family of ligand‐gated ion channels
Authors: Jensen Marianne L. , Schousboe Arne , Ahring Philip K.
Published: January 2005

The determinants of charge selectivity of the Cys‐loop family of ligand‐gated ion channels have been studied for more than a decade. The investigations have mainly covered homomeric receptors e.g. the nicotinic acetylcholine receptor α7, the glycine receptor α1 and the serotonin receptor 5‐HT3A. Only recently, the determinants of charge selectivity of heteromeric receptors have been addressed for the GABAA receptor α2β3γ2. For all receptor subtypes, the selectivity determinants have been located to an intracellular linker between transmembrane domains M1 and M2. Two features of the M1–M2 linker appear to control ion selectivity. A central role for charged amino acid residues in selectivity has been almost universally observed. Furthermore, recent studies point to an important role of the size of the narrowest constriction in the pore. In the present review, these determinants of charge selectivity of the Cys‐loop family of ligand‐gated ion channels will be discussed in detail.
Multifocal electroretinography in isolated arterially perfused bovine eye
Authors: Shahidullah Mohammad , Chan Henry H. L. , Yap Maurice K. , Liu Quan , To Chi‐Ho
Published: January 2005

Aim:  To develop an isolated arterially perfused bovine eye as an in vitro model for studying retinal electrophysiology using multifocal electroretinography (mfERG).

Methods:  Fresh bovine eyes were cannulated through the ophthalmic artery and perfused with oxygenated Krebs’ solution at 37°C within 15 min postmortem. Multifocal ERG was recorded using the veris 1.0 (Visual Evoked Response Imaging System).

Results:  The mfERG waveform of in vitro bovine eyes had a typical trough (negative wave, N1) and peak (positive wave, P1) similar to those of human mfERG. The implicit times (peak latencies) for N1 and P1 were 20 and 42 ms respectively, and the average response amplitude (N1P1) was 55 nV. The implicit times of N1 and P1 were maintained for more than 4 h. The mfERG responses were affected proportionately by the stimulus intensity. Without a neutral density filter, the mean response amplitude was about 55 nV, which was diminished to 26, 18 and 10 nV under neutral density filters of 0.4, 1.0 and 1.4, respectively. Partial occlusion of the pupil completely abolished mfERG responses from the corresponding part of the retina.

Conclusions:  Isolated arterially perfused bovine eye may be used as an experimental model to study retinal electrophysiology using mfERG. The in vitro eye may offer a convenient and easily obtainable alternative to live animals, particularly for drug screening and invasive studies.
When Practice Oversteps the Limits of Theory: An Assessment of Fair Media Coverage for Political Parties in Great Britain and Mexico
Authors: Mena David
Published: January 2005

Over stressing the rights‐safeguarding role of democracy has led to a widespread neglect of democracy's essential function: to ensure the legitimacy of elected rulers and by doing so, to ensure political stability. The effects of this neglect are apparent in the disputes that arise concerning media coverage of elections. This article examines the difficulties democratic statesmen face to justify and consistently implement arrangements that limit the freedom of expression of the media in order to minimize the challenges to the legitimacy of electoral outcomes that a biased coverage of elections could incite. Current democratic theory does not address this problem. Indeed its emphasis on safeguarding the rights of citizens can suggest that the freedom of expression of the media should prevail over considerations of legitimacy and stability. This study examines the justifications adduced, and the implementation of, arrangements that curtail the right to advocacy of broadcasters and limit their right to editorial discretion in order to provide political parties with what I refer to here as “fair media coverage.” In particular, the article highlights and assesses the experiences in fair media coverage of election campaigns in the British General Election of 1997 and the Mexican Federal Election of 2000. In full view of these case studies, and on the basis of the theoretical guidelines I develop at the beginning of this article, I argue for limiting freedom of expression and stress the urgent need for democratic theories to address the practical problems that trouble democratic authorities.
“Like Butter Scraped over Too Much Bread”: Animal Protection Policy in Mexico1
Authors: Norman Emma R. , Hernández Norma Contreras
Published: January 2005

Over the past fifteen years Mexico has developed a string of comprehensive animal protection regulations designed to address the serious problems that affect both wild and domestic animals in the territory. Yet for all their detailed coherence and despite serious government efforts, the regulations continue to lack effective enforcement and authorities are increasingly overstretched. This study discusses three key areas that obstruct the effective implementation of Mexican animal protection policy, but where advances could be feasibly initiated. The first concerns deficiencies at the political level. The second addresses the awkward relation between government and civil society on the issue. The third examines the scope of the problem in Mexico and some implications this has for international involvement. Finally the study suggests a more collaborative approach for implementing the policy that attempts to address central concerns in each of the three areas considered.
Acute polymyositis after donor lymphocyte infusion
Authors: Lin Peng‐Chan , Hsiao Liang‐Tsai , Chen Po‐Min
Published: January 2005

Abstract:  Polymyositis usually occurred along with other manifestations of chronic graft‐versus‐host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) had been reported. However, polymyositis with a sole manifestation of acute GVHD following donor lymphocyte infusion (DLI) is rare. We reported a 45‐yr‐old man of acute lymphoid leukemia post‐allogeneic HSCT 6 months developed acute polymyositis after DLI. He did not develop any symptoms, signs of acute or chronic GVHD following allogeneic HSCT, despite withdraw of immuosuppresive agents, cyclosporin A (CsA). As the DNA‐STR of bone marrow analysis showed mixed chimerism, he received the DLI for remission on May 16, 2002. Acute polymyositis developed following DLI 22 d later. The clinical presentation of polymyositis is compatible with a manifestation of acute GVHD following DLI. It also responds to the treatment of steroid and CsA.
Various immunostaining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell carcinomas
Authors: Nagatsuka Hitoshi , Hibi Kazuteru , Gunduz Mehmet , Tsujigiwa Hidetsugu , Tamamura Ryou , Sugahara Toshio , Sasaki Akira , Nagai Noriyuki
Published: January 2005

Background:  Intratumoral blood vessels are known to play an important role in cancer growth and metastasis. The discrepancy in previous reports using various endothelial markers individually suggested us to investigate both normal and various tumor areas with a wide panel of vascular markers.

Methods:  Here, we used a panel of three antibodies (CD31, CD34, and endoglin) as blood vessel markers to investigate the distribution and properties of blood vessels in normal oral tissues and squamous cell carcinomas.

Results:  Many microvessels with strong remodeling activity as well as undifferentiated tumoral vascular endothelial cells and immature endothelial cells were present in the cancer cell nest and marginal area of cancer infiltration. Our results showed different vascular distribution patterns using various immunostaining markers in normal and tumoral tissues.

Conclusion:  Vascular distribution and properties of endothelial cells appear to be closely associated with metastasis.
Bilateral synchronous submandibular lumps in a patient with gastric carcinoma
Authors: Böckmann Roland A. , Schulz Tim , Stein Henning , Mielke Eckhart , Dengler Kathrin , Wolff Klaus‐Dietrich , Nolte Dirk
Published: January 2005

This case report deals with a patient who was readmitted with a bilateral submandibular swelling after having received primary surgery due to gastric adenocarcinoma 6 months before. After bilateral submandibulectomy both glands were diagnosed histopathologically as metastasis of adenocarcinoma. This is the rare case of a submandibular gland metastasis and the first case of a bilateral synchronous submandibular gland metastasis from gastric carcinoma.
Quantitative histological features and ultrastructure of opercula of human teeth showing normal and delayed eruption
Authors: Verma D. K. , Nair P. N. R. , Luder H. U.
Published: January 2005

Background:  Failure of eruption of human permanent molars has been attributed to opercular lesions, although comparisons with specimens from normally erupting teeth are scarce. The aim of this study was to quantitatively analyse opercula associated with normal and delayed tooth eruption.

Method:  Twenty opercula covering permanent molars delayed in eruption were obtained from 13 patients aged 7.3–18.1 years. Six opercula from normally erupting molars of five 7.3–17.5‐year‐old subjects served as controls. Specimens were analysed light and electron microscopically and morphometrically.

Results:  In addition to features recognized previously, prominent numbers of nerves, high endothelial‐like venules and mast cells were observed. Ultrastructurally, large multinucleated cells did not reveal cell boundaries running between the nuclei, and mast cells seemed belonging to the MCTC‐type. None of the features differed significantly between opercula from cases of delayed and normal tooth eruption.

Conclusions:  Disturbances of tooth eruption that are attributed to opercular lesions may represent retentions resulting from the failure of the eruption mechanism, rather than impactions because of a physical barrier.
Enhanced Bax in oral SCC in relation to antitumor effects of chemotherapy
Authors: Takemura Kanako , Noguchi Makoto , Ogi Kazuhiro , Tokino Takashi , Kubota Hiromi , Miyazaki Akihiro , Kohama Geniku , Hiratsuka Hiroyoshi
Published: January 2005

Background:  Antitumor effects of chemotherapeutic agents are commonly associated with the induction of apoptosis. Bax belongs to the Bcl‐2 family and induces apoptosis. The present study was conducted to investigate the relationship between enhanced Bax expression in oral squamous cell carcinoma (SCC; cell lines and clinical cases) and the antitumor effects of chemotherapy.

Methods:  In three oral SCC cell lines, Bax expression before and after treatment with chemotherapeutic agents [docetaxel (TXT), cisplatin and 5‐fluorouracil] was examined by reverse transcriptase‐polymerase chain reaction and immunoblotting. The effects of treatment were assessed by counting the number of viable cells and determining sub‐G1 cells. Tissue samples (both biopsy specimens before chemotherapy and surgically excised specimens after chemotherapy) from nine patients with oral SCC who underwent neoadjuvant chemotherapy were immunostained for Bax. The relationship between enhancement of Bax expression and chemotherapeutic effects was established.

Results:  Two of three cell lines did not express Bax mRNA or protein before treatment. After treatment, Bax expression was enhanced only by TXT in one cell line, but by all chemotherapeutic agents in the other two cell lines. In three of nine patients, Bax expression was not found before chemotherapy. Two of these three patients showed enhanced Bax expression after chemotherapy including TXT, but one still failed to express Bax. Both in cell lines and clinical cases, enhancement of Bax after chemotherapy was associated with antitumor effects.

Conclusion:  Certain chemotherapeutic agents enhance Bax expression in oral SCC, and it is suggested that this contributes to the antitumor effects of chemotherapy.
Avascular jaw osteonecrosis in association with cancer chemotherapy: series of 10 cases
Authors: Bagan J. V. , Murillo J. , Jimenez Y. , Poveda R. , Milian M. A. , Sanchis J. M. , Silvestre F. J. , Scully C.
Published: January 2005

Background:  We present a series of 10 patients with osteonecrosis of the jaws (ONJ) that appeared following cancer chemotherapy.

Material and methods:  Of the 10 cases with ONJ, six had bone metastases from breast cancers and the other four had multiple myeloma. We analysed the location of bone metastases, as well as the characteristics of the ONJ, and the drugs with which they had been treated for their bone metastases.

Results:  Of the 10 patients, all had ONJ in the mandible; 50% also had maxillary involvement. The average number of areas of painful exposed was 2.1 per patient (range 1–5). In seven patients a tooth extraction preceded the onset of ONJ. Two patients developed oroantral communications and another a cutaneous fistula to the neck with suppuration. In all the 10 patients the histopatholological diagnosis was of chronic osteomyelitis without evidence of metastatic disease to the jaws. All the patients had received treatment for their malignant bone disease with bisphosphonates. These were the only drugs that all patients had received.

Conclusion:  ONJ appears to have a relationship with the use of bisphosphonates.
Oral lichenoid drug reaction by lithium in a patient with bipolar disorder
Authors: Campisi G. , Florena A. M. , Franco V. , Coccia E. , Muzio L. Lo
Published: January 2005

Bipolar disorder (BD) is a psychiatric disease characterized by recurrent and alternated episodes of depression and mania. For the treatment of BD, anticonvulsants drugs as lithium, carbamazepine and oxcarbazepine can be used. These drugs can be associated with potential adverse effects: weight gain, tremors, thyroid abnormalities, and cognitive, gastrointestinal, cardiac or dermatological problems. We describe a case of BD with oral lichenoid drug reaction probably because of the mood stabilizers.
Oxpentifylline is not effective for symptomatic oral lichen planus
Authors: Wongwatana Sasiwong , Leao Jair C. , Scully Crispian , Porter Stephen
Published: January 2005

Background:  There are no reliably effective therapies for oral lichen planus (OLP). The aim of the present work was to determine the potential efficacy of oxpentifylline in the management of OLP.

Methods:  Fifteen patients (six males, median age for the group 52 years, ranging from 33 to 72) with clinically and histopathologically confirmed OLP were treated with oxpentifylline at a dose of 400 mg three times daily.

Results:  Only 10 patients completed an 8 week course, the other five having to stop therapy because of adverse effects. Only three patients had any relief of their signs and symptoms of OLP.

Conclusion:  The results indicate that oxpentifylline is unlikely to be of benefit for the treatment of OLP.
Prevalence of oral trauma in children with bilateral clefts
Authors: Da Silva Juliana Yassue Barbosa , Aranha Andreza Maria Fabio , Peixoto Virginia , Costa Beatriz , Gomide Marcia Ribeiro
Published: January 2005

Abstract –  The main object of this study is to analyze the prevalence of oral trauma in subjects with complete bilateral clefts, with anterior projection of the premaxilla. A total of 106 children aging 6 months to 9 years were analyzed. The caretakers answered a specific questionnaire, in order to report the presence or absence of trauma to the soft and/or hard tissues of the child's mouth. Whenever there was a history of trauma, the patients were submitted to clinical examination. The prevalence of oral trauma was 53%, being 91% of soft tissue lesions, 8.9% of avulsion, 7% of luxation and 1.8% of intrusion. For the males, the prevalence was 56% and for the females it was 47%, with no statistical significance. Regarding the following aspects:period of time spent with the parents and at school, and presence or absence of siblings, no statistical difference could be found. Among the traumatized individuals, 80% aged less than 3 years by the moment of the trauma, 89% suffered the trauma at home, 75% presented lesions in the soft tissue at the premaxilla, 16% in the maxillary incisors, and 8.9% presented lesions in both structures. It was noticed that 45% of the permanent incisors that succeeded the traumatized deciduous teeth presented alterations, being 48% of structure and 52% of structure and position. The prevalence of trauma in this sample was superior to that observed in the literature, without any positive associations between the evaluated aspects. These results suggest that the projection of the premaxilla brings about a higher risk of oral trauma around this area.
Treatment of avulsed teeth with Emdogain®– a case report
Authors: Çaglar Esber , Tanboga Ilknur , Süsal Seckin
Published: January 2005

Abstract –  The present case report describes the reimplantation of avulsed teeth with the treatment of Emdogain®. Case was avulsed right maxillary permanent central and lateral incisor in a 9‐year‐old girl suffering from a traumatic injury. After pretreatment of avulsed teeth, Emdogain® was applied to the root surface and into the extraction socket with subsequent replantation of the tooth. Evaluation parameters included horizontal and vertical percussion sound and periapical radiographs. At 1–2–6–12‐month follow‐up period, the clinical and radiographic appearance of the teeth showed resolution of mobility and no signs of replacement resorbption.
Treatment of a severe dental lateral luxation associated with extrusion in an 8‐month‐old baby: a conservative approach
Authors: Cunha Robson Frederico , Delbem Alberto Carlos Botazzo , De Mello Vieira Ana Elisa , Pugliesi Daniela Maria Carvalho
Published: January 2005

Abstract –  This case report documents the trauma and follow‐up care of lateral luxation associated with extrusion of the lower central incisors in an 8‐month‐old patient. The teeth were repositioned by digital pressure and stabilized using proximal sutures. Clinical and radiographic follow‐up 40 months after the injury showed alterations in both incisors, but both remained functional and free of pathology.
Traumatic injuries of the permanent incisors in children in southern Turkey: a retrospective study
Authors: Zuhal Kırzıoğlu , Semra Özay Ertürk M. , Hüseyin Karayılmaz
Published: January 2005

Abstract –  The aim of this study is to investigate the incidence, etiologic factors and results of dental trauma and the effects of age and gender on the trauma in permanent incisors. Over a 3‐year period, 514 permanent incisor teeth in 317 patients with trauma history, who applied to Süleyman Demirel University School of Dentistry, Department of Pedodontics from the southern cities of Turkey, were evaluated. Standardized trauma forms were filled for each patient. In all age groups, the most frequent cause of trauma was found to be unspecified falls (47.6%). Maxillary teeth (88.5%) and central incisors (87.5%) were the most affected teeth from dental trauma. Ellis class II crown fracture was the most frequently seen type of injury (43.8%). The percent of the patients who applied to a dental clinic in the first 3 days after the trauma occurred (22.8%) was less than the percent of the patients who applied after 3 months and more time period (45.1%). It reveals that it is important to inform the public about dental trauma and the importance of time in these cases.
Factors affecting coronal fracture of anterior teeth in North Jordanian children
Authors: Al‐Khateeb Susan , Al‐Nimri Kazem , Alhaija Elham Abu
Published: January 2005

Abstract –  The aims of this study were to investigate the incidence of coronal fracture of the anterior teeth in North Jordanian schoolchildren and to study the main predisposing factors and the factors that may affect the severity of this fracture. A study group (958) comprising schoolchildren aged 13–15 years was chosen by a simple random method from five geographical areas in Irbid Governate, Jordan. All children completed a questionnaire related to history of trauma to their anterior teeth before they had a clinical examination for lip competence, lip line and amount of fracture. Overjet was recorded from a study cast made for each student. Statistical analysis was performed using chi‐square test. The results showed a prevalence of 11% of coronal fracture with female‐male ratio of 1:1. An increase in the overjet more than 3 mm doubled the incidence of coronal fracture while overjet more than 6 mm increased the incidence fourfold. There was higher incidence of coronal fracture associated with lip incompetence and low lip line (P < 0.01). The severity of fracture increased in children with a larger overjet (P < 0.001). It was concluded that overjet, lip competence and lip line were important predisposing factors to coronal fracture of the anterior teeth while the severity of the fracture was mainly determined by overjet.
Adhesive fragment reattachment after orthodontic extrusion: a case report
Authors: Cengiz Sevi Burcak , Kocadereli Ilken , Cem Gungor H. , Altay Nil
Published: January 2005

Abstract –  In the treatment of crown fractures, adhesive fragment reattachment provides a good alternative to other restorative techniques, offering several advantages. The present paper reports a case in which the treatment of a cervical crown fracture was accomplished by reattaching the tooth fragment with a flowable resin composite. Orthodontic root extrusion was performed with a modified Hawley appliance prior to fragment reattachment. The clinical and radiographic results after 2.5 years were successful.
Apexification: a review
Authors: Rafter Mary
Published: January 2005

Abstract –  This paper reviews the rationale and techniques for treatment of the non‐vital immature tooth. The importance of careful case assessment and accurate pulpal diagnosis in the treatment of immature teeth with pulpal injury cannot be overemphasized. The treatment of choice for necrotic teeth is apexification, which is induction of apical closure to produce more favorable conditions for conventional root canal filling. The most commonly advocated medicament is calcium hydroxide, although recently considerable interest has been expressed in the use of mineral trioxide aggregate. Introduction of techniques for one‐visit apexification provide an alternative treatment option in these cases. Success rates for calcium hydroxide apexification are high although risks such as reinfection and tooth fracture exist. Prospective clinical trials comparing this and one‐visit apexification techniques are required.
Effect of electrophoretically activated calcium hydroxide on bacterial viability in dentinal tubules –in vitro
Authors: Lin Shaul , Tsesis Igor , Zukerman Offer , Weiss Ervin I. , Fuss Zvi
Published: January 2005

Abstract –  To evaluate the ability of electrophoretically activated calcium hydroxide (CH) to eliminate bacteria in dentinal tubules. In an in vitro model of dentinal tubule infection, 18 cylindrical root specimens prepared from freshly extracted bovine teeth were used. After removal of the smear layer, intracanal dentinal tubules were infected with Enterococcus faecalis for 21 days. In 12 specimens, CH paste was placed in the root canals for 7 days. In six of these, an electrophoretic current (10 mA per 10 min), using two electrodes, was applied after placing the medicament in the canal. Powder dentin samples obtained from within the canal lumina using ISO 025, 027, 029, 031 and 033 burs were examined for the presence of vital bacteria by inoculating agar plates and counting colony forming units. anova with repeated measures was used to analyze results. A significant difference was found between experimental groups and the positive control group. CH and electrophoretically activated CH significantly (P < 0.001) reduced bacterial viabilities in dentinal tubules to a depth of 200 μm. Treatment with electrophoresis was significantly (P < 0.001) more effective than pure CH in depths of 200–500 μm. Specimens treated with electrophoretically activated CH showed no viable bacteria in dentinal tubules to a depth of 500 μm from the root canal space within 7 days. The time required for treatment of pulpal infection root resorption may be decreased, thus minimizing the risk of coronal fractures in young patients with traumatized teeth.
Emdogain® does not prevent progressive root resorption after replantation of avulsed teeth: a clinical study
Authors: Schjøtt M. , Andreasen J. O.
Published: January 2005

Abstract –  Emdogain® has been shown in clinical and experimental studies to promote regeneration of all periodontal tissues: cementum with anchoring fibres, a functional, periodontal ligament and alveolar bone in connection with treatment of marginal periodontitis.

The intention of this study was to analyse whether this regenerative capacity upon the periodontal ligament also worked in a trauma situation where a significant number of PDL cells have been eliminated because of unphysiologic storage or actual damage during avulsion or replantation. Furthermore if ankylosis sites already established because of earlier replantation after avulsion could be surgical removed and application of Emdogain® could revert the ankylosis stage to a normal PDL situation. The first treatment situation was tested in seven patients with a total of 16 avulsed teeth with varying time of extra oral storage. The teeth were extra‐orally endodontically treated and the root and socket covered with Emdogain® before replantation. All teeth demonstrated subsequent ankylosis, primarily diagnosed by a percussion test. The second treatment situation where an ankylosis was already established constituted of seven patients with a total of 11 teeth because of previous replantation after avulsion. These teeth were all extracted, the ankylosis sites removed and the root and socket treated with Emdogain®. After 6 months all teeth showed recurrence of ankylosis. It is concluded that Emdogain® was not able to prevent or cure ankylosis.
A gain‐of‐function mutation in the GABAA receptor produces synaptic and behavioral abnormalities in the mouse
Authors: Homanics G. E. , Elsen F. P. , Ying S.‐W. , Jenkins A. , Ferguson C. , Sloat B. , Yuditskaya S. , Goldstein P. A. , Kralic J. E. , Morrow A. L. , Harrison N. L.
Published: January 2005

In mammalian species, inhibition in the brain is mediated predominantly by the activation of GABAA receptors. We report here changes in inhibitory synaptic function and behavior in a mouse line harboring a gain‐of‐function mutation at Serine 270 (S270) in the GABAA receptor α1 subunit. In recombinant α1β2γ2 receptors, replacement of S270 by Histidine (H) results in an increase in sensitivity to γ‐aminobutyric acid (GABA), and slowing of deactivation following transient activation by saturating concentrations of GABA. Heterozygous mice expressing the S270H mutation are hyper‐responsive to human contact, exhibit intention tremor, smaller body size and reduced viability. These mice also displayed reduced motor coordination, were hypoactive in the home cage, but paradoxically were hyperactive in a novel open field environment. Heterozygous knockin mice of both sexes were fertile but females failed to care for offspring. This deficit in maternal behavior prevented production of homozygous animals. Recordings from brain slices prepared from these animals revealed a substantial prolongation of miniature inhibitory postsynaptic currents (IPSCs) and a loss of sensitivity to the anesthetic isoflurane, in neurons that express a substantial amount of the α1 subunit. The results suggest that the biophysical properties of GABAA receptors are important in determining the time‐course of inhibition in vivo, and suggest that the duration of synaptic inhibition is a critical determinant that influences a variety of behaviors in the mouse.
Clinical studies to determine the effectiveness of a whitening toothpaste at reducing stain (using a forced stain model)
Authors: Moran J , Claydon NCA , Addy M , Newcombe R
Published: January 2005

Aims:  Two single centre, randomized single‐blind, crossover studies were performed, to compare the effect of a test toothpaste with a conventional fluoride paste in the inhibition and removal of extrinsic dental stain promoted by repeated chlorhexidine/tea rinses.

Methods:  These studies used 24 subjects in each of two separate clinical trials. On the Friday before each trial period, the subjects received a prophylaxis to remove all staining, plaque and calculus deposits. On the following Monday, subjects were checked whether they were stain free and then under direct supervision they rinsed with a 0.2% chlorhexidine mouthrinse, immediately followed by a rinse with a warm black tea solution. This cycle was repeated hourly eight times throughout the day and on the following days until the Friday. In addition subjects also received daily a single toothpaste slurry rinse or control water rinse in the morning and lunchtime. No other form of oral hygiene was permitted during this period. On the Friday, both stain area and intensity was assessed using the Lobene Stain Index. For the stain removal study, stain was promoted again using chlorhexidine and tea rinses. After 4 days, stain was measured both prior to and immediately after brushing with the allocated toothpaste for 2 min. Subjects were then instructed to use the toothbrush at home according to their normal oral hygiene practices. On the following Wednesday, the amount of stain present was re‐assessed. Each subject subsequently received a thorough prophylaxis to remove all plaque calculus and staining before starting the following periods of the study.

Results:  The study showed no difference in the ability of the test whitening toothpaste, control toothpaste and water control at inhibiting stain. There was also only a small difference (3.5% for product of area and intensity) between the ability of the two toothpastes to help remove stain after a single brushing. The difference was however in favour of the test product which approached a conventional level of significance (P = 0.089). There was no evidence of superiority for either of the pastes after normal home usage.

Conclusions:  This study has suggested that the test product may have some advantage over the conventional paste at removing stain but the magnitude of difference would appear to be small and of little clinical relevance.
A study in vitro of the combined effects of soft drinks and tooth brushing with fluoride toothpaste on the wear of dentine
Authors: Ponduri S , Macdonald E , Addy M
Published: January 2005

The aim of this study was to measure loss of dentine produced by soft drinks alone and combined with tooth brushing with and without toothpastes. Groups of flat human dentine specimens were exposed for 10 min and then 30 min to orange juice (OJ), carbonated cola (CC) or modified blackcurrant (MB) drinks alone or after the exposures brushed with a fluoride toothpaste for 10 s. Further groups were exposed to OJ as before but brushed with water or non‐fluoride toothpaste or placed in slurries of fluoride paste. Five cycles of each regimen were carried out. Tissue loss was determined by profilometry. Water immersion/brushing and brushing controls were included. OJ and CC produced similar erosion and significantly more than MB. Compared with drinks alone, dentine loss was reduced by fluoride toothpaste brushing but increased by water and non‐fluoride toothpaste brushing. Fluoride toothpaste slurry had no significant effect on soft drink erosion. Very little abrasion with brushing alone was recorded over the time frame of these experiments. It is concluded that fluoride toothpaste could provide protection, albeit small, against erosion. The data again support the concept of brushing before meals.