bluuebunny/crossref_metadata_2025 huggingface dataset:
HaRas activates the NADPH oxidase complex in human neuroblastoma cells via extracellular signal‐regulated kinase 1/2 pathway
Authors: Serù Rosalba , Mondola Paolo , Damiano Simona , Svegliati Silvia , Agnese Savina , Avvedimento Enrico V. , Santillo Mariarosaria
Published: October 2004

In this study we have investigated the effects of the small GTP‐binding‐protein Ras on the redox signalling of the human neuroblastoma cell line, SK‐N‐BE stably transfected with HaRas(Val12). The levels of reactive oxygen species (ROS) and superoxide anions were significantly higher in HaRas(Val12) expressing (SK‐HaRas) cells than in control cells. The treatment of cells with 4‐(2‐aminoethyl) benzenesulfonylfluoride, a specific inhibitor of the membrane superoxide generating system NADPH oxidase, suppressed the rise in ROS and significantly reduced superoxide levels produced by SK‐HaRas cells. Moreover, HaRas(Val12) induced the translocation of the cytosolic components of the NADPH oxidase complex p67phox and Rac to the plasma membrane. These effects depended on the mitogen‐activated protein kinase kinase/extracellular signal‐regulated kinase (MEK/ERK1/2) pathway, as the specific MEK inhibitor, PD98059, prevented HaRas‐mediated increase in ROS and superoxide anions. In contrast, the specific phosphoinositide 3‐kinase (PI3K) inhibitors LY294002 and wortmannin were unable to reverse the effects of HaRas(Val12). Moreover, cholinergic stimulation of neuroblastoma cells by carbachol, which activated endogenous Ras/ERK1/2, induced a significant increase in ROS levels and elicited membrane translocation of p67phox and Rac. ROS generation induced by carbachol required the activation of ERK1/2 and PI3K. Hence, these data indicate that HaRas‐induced ERK1/2 signalling selectively activates NADPH oxidase system in neuroblastoma cells.
Evaluation of 5‐(2‐(4‐pyridinyl)vinyl)‐6‐chloro‐3‐(1‐methyl‐2‐(S)‐pyrrolidinylmethoxy)pyridine and its analogues as PET radioligands for imaging nicotinic acetylcholine receptors
Authors: Brown LaVerne , Chefer Svetlana , Pavlova Olga , Vaupel D. Bruce , Koren Andrei O. , Kimes Alane S. , Horti Andrew G. , Mukhin Alexey G.
Published: October 2004

A novel series of compounds derived from the high‐affinity nicotinic acetylcholine receptor (nAChR) ligand, 5‐(2‐(4‐pyridinyl)vinyl)‐6‐chloro‐3‐((1‐methyl‐2‐(S)‐pyrrolidinyl)methoxy)pyridine (Me‐p‐PVC), originally developed by Abbott Laboratories, was characterized in vitro in nAChR binding assays at 37°C to show Ki values in the range of 9–611 pm. Several compounds of this series were radiolabeled with 11C and evaluated in vivo in mice and monkeys as potential candidates for PET imaging of nAChRs. [11C]Me‐p‐PVC (Ki =56 pm at 37°C; logD = 1.6) was identified as a radioligand suitable for the in vivo imaging of the α4β2* nAChR subtype. Compared with 2‐[18F]FA, a PET radioligand that has been successfully used in humans and is characterized by a slow kinetic of brain distribution, [11C]Me‐p‐PVC is more lipophilic. As a result, [11C]Me‐p‐PVC accumulated in the brain more rapidly than 2‐[18F]FA. Pharmacological evaluation of Me‐p‐PVC in mice demonstrated that the toxicity of this compound was comparable with or lower than that of 2‐FA. Taken together, these results suggest that [11C]Me‐p‐PVC is a promising PET radioligand for studying nAChR occupancy by endogenous and exogenous ligands in the brain in vivo.
Macrophage colony stimulatory factor and interferon‐γ trigger distinct mechanisms for augmentation of β‐amyloid‐induced microglia‐mediated neurotoxicity
Authors: Li M. , Pisalyaput K. , Galvan M. , Tenner A. J.
Published: October 2004

Dysregulated stimulation of microglia, the resident macrophages in the brain, can lead to excessive induction of inflammatory agents and subsequently damage to neurons. Fibrillar β‐amyloid peptide (fAβ), a major component of senile plaques in Alzheimer's disease (AD) brain, is known to induce microglial‐mediated neurotoxicity under certain conditions. Microglial ‘priming’ by macrophage colony stimulatory factor (MCSF) or interferon‐gamma (IFNγ) appears to be required for this fAβ‐induced microglia mediated neurotoxicity in vitro. We report here that while both MCSF and IFNγ induce microglial‐mediated fAβ neurotoxicity, their mechanisms of toxicity differ. The enhancement of neurotoxicity by IFNγ or MCSF is not due to enhanced Aβ ingestion by microglia or to the direct effect of proinflammatory cytokine production. The neurotoxicity resulting from IFNγ/fAβ treatment was blocked by pretreatment with nitric oxide synthase inhibitor l‐N‐5‐(1‐iminoethyl) ornithine hydrochloride (l‐NIO), consistent with a role for nitric oxide in the IFNγ‐mediated toxicity mechanism. In contrast, no induction of nitric oxide production was detected for microglia treated with MCSF/fAβ. Furthermore, inhibiting the generation of reactive oxygen species (ROS) using the specific NADPH oxidase inhibitor apocynin reversed fAβ/MCSF‐induced neurotoxicity while l‐NIO had little effect. As MCSF is endogenously expressed within the brain, and both its level and that of the MCSF receptor are dramatically increased in the AD brain, the neurotoxicity resulting from ROS release by fAβ/MCSF coactivated microglia may be a more appropriate model for assessing fAβ‐induced microglial‐mediated neuropathology in AD.
Induction of cyclin‐dependent kinase 5 and its activator p35 through the extracellular‐signal‐regulated kinase and protein kinase A pathways during retinoic‐acid mediated neuronal differentiation in human neuroblastoma SK‐N‐BE(2)C cells
Authors: Lee Jong‐Hee , Kim Kyong‐Tai
Published: October 2004

Cyclin‐dependent kinase 5 (Cdk5), a neuronal Cdc2‐like kinase, exhibits a variety of functions in neuronal differentiation and neurocytoskeleton dynamics, as well as neuronal degeneration. However, its role and induction mechanisms in retinoic acid (RA)‐induced neuronal differentiation have not been well understood. In this study we newly found that RA treatment of SK‐N‐BE(2)C, human neuroblastoma cells, increased the expression of Cdk5 and its neuron specific activator p35 through the extracellular‐signal‐regulated kinase1/2 (ERK1/2) and cAMP‐dependent protein kinase A (PKA) pathway. Inhibition of Cdk5 activity either by an inhibitor, roscovitine, or by transfection with a dominant negative form of Cdk5 caused a dramatic decrease in RA‐induced differentiation, suggesting the requirement of Cdk5 kinase activity for the RA‐induced neurite outgrowth. Furthermore, Cdk5 and p35 expression was decreased by ERK1/2 inhibition with PD98059 and increased by overexpression of a constitutive active mitogen‐activated protein kinase kinase 1 (MEK1) mutant, suggesting the critical role of ERK1/2 in the induction of Cdk5 and p35. In addition, a transcription factor early growth response 1 (Egr‐1) was induced by RA through the ERK1/2 pathway, suggesting its possible involvement in the p35 induction. RA treatment also induced c‐fos mediated AP‐1 binding, and cAMP‐responsive element binding protein (CREB) mediated CRE binding via ERK1/2 and PKA pathway, respectively, in the Cdk5 promoter region, resulting in the induction of Cdk5. Our results suggest that ERK1/2 and PKA‐induced regulation of Cdk5 activity possibly through Egr‐1, c‐fos, and CREB plays a critical role in the RA‐induced neuronal differentiation.
ShcA regulates neurite outgrowth stimulated by neural cell adhesion molecule but not by fibroblast growth factor 2: evidence for a distinct fibroblast growth factor receptor response to neural cell adhesion molecule activation
Authors: Hinsby Anders M. , Lundfald Line , Ditlevsen Dorte K. , Korshunova Irina , Juhl Lone , Meakin Susan O. , Berezin Vladimir , Bock Elisabeth
Published: October 2004

Homophilic binding in trans of the neural cell adhesion molecule (NCAM) mediates adhesion between cells and leads, via activation of intracellular signaling cascades, to neurite outgrowth in primary neurons as well as in the neuronal cell line PC12. NCAM mediates neurite extension in PC12 cells by two principal routes of signaling: NCAM/Fyn and NCAM/fibroblast growth factor receptor (FGFR), respectively. Previous studies have shown that activation of mitogen‐activated protein kinases is a pivotal point of convergence in NCAM signaling, but the mechanisms behind this activation are not clear. Here, we investigated the involvement of adaptor proteins in NCAM and fibroblast growth factor 2 (FGF2)‐mediated neurite outgrowth in the PC12‐E2 cell line. We found that both FGFR substrate‐2 and Grb2 play important roles in NCAM as well as in FGF2‐stimulated events. In contrast, the docking protein ShcA was pivotal to neurite outgrowth induced by NCAM, but not by FGF2, in PC12 cells. Moreover, in rat cerebellar granule neurons, phosphorylation of ShcA was stimulated by an NCAM mimicking peptide, but not by FGF2. This activation was blocked by inhibitors of both FGFR and Fyn, indicating that NCAM activates FGFR signaling in a manner distinct from FGF2 stimulation, and regulates ShcA phosphorylation by the concerted efforts of the NCAM/FGFR as well as the NCAM/Fyn signaling pathway.
Distribution and localization of pro‐brain‐derived neurotrophic factor‐like immunoreactivity in the peripheral and central nervous system of the adult rat
Authors: Zhou Xin‐Fu , Song Xing‐Yun , Zhong Jin‐Hua , Barati Shahram , Zhou Fiona H.‐H. , Johnson Stephen M.
Published: October 2004

The precursors for neurotrophins are proteolytically cleaved to form biologically active mature molecules which activate their receptors p75NTR and trks. A recent study showed that the precursor for nerve growth factor (NGF) can bind to p75NTR with a high affinity and induces apoptosis of neurons in vitro. Mutation in Val66Met of brain‐derived neurotrophic factor (BDNF) results in reduction in hippocampal function in learning and in the dysfunction of intracellular BDNF sorting and secretion. To examine the functions of pro‐neurotrophins in vivo, it is essential to know where they are expressed in the nervous system. In the present study, we have raised and characterized rabbit polyclonal antibodies against a peptide coding for the precursor region of the BDNF gene. The antibody specifically recognizes the precursor for BDNF by western blot. With the affinity purified precursor antibody, we have mapped the distribution and localization of the precursor for BDNF. The results showed that, like mature BDNF, pro‐BDNF is localized to nerve terminals in the superficial layers of dorsal horn, trigeminal nuclei, nuclei tractus solitarius, amygdaloid complex, hippocampus, hypothalamus and some peripheral tissues. These results suggest that pro‐BDNF, like mature BDNF, is anterogradely transported to nerve terminals and may have important functions in synaptic transmission in the spinal cord and brain.
Preparing for Portfolio Assessment in Art and Design: A Study of the Opinions and Experiences of Exiting Secondary School Students in Canada, England and The Netherlands
Authors: Blaikie Fiona , Schönau Diederik , Steers John
Published: October 2004

This study utilises survey questionnaires to compare 107 Canadian, English and Dutch students' opinions and experiences of portfolio preparation for final assessment in the terminal year of secondary school. The aim is to reveal what students value about portfolio assessment and if they see portfolio assessment as a valid preparation for their futures, particularly for those who plan to continue on studying art and design at college or university. Common approaches to assessment are examined, followed by a more focused discussion of curriculum and assessment practices in all three countries at the time of writing (March 2004). This is followed by a description of methodology; tentative findings are presented and the article concludes with a short discussion of some implications for art and design education.
Examining the Impact of Charter Schools on Performance in Traditional Public Schools
Authors: Bohte John
Published: October 2004

Charter schools have grown in popularity, as both citizens and government officials search for ways to improve public education in America. Much of the research on charter schools focuses on academic performance comparisons between charter schools and traditional public schools. Far less attention has been devoted to whether the presence of charter schools creates marketlike environments that bring about systemic improvements in public education. This study examines the extent to which charter schools stimulate performance gains in traditional public schools. The results show that charter schools contribute to modest overall performance improvements for students enrolled in traditional public schools. Charter schools help bring about stronger performance gains for low‐income students enrolled in traditional public schools. The presence of charter schools also affects how financial and programmatic resources are allocated in traditional public schools.
Rethinking Bureaucrats in the Policy Process: Criminal Justice Agents and the National Crime Agenda
Authors: Miller Lisa L.
Published: October 2004

Policy scholars have noted that bureaucrats can play an important role in defining policy alternatives. Few studies, however, examine the extent of their involvement in this process. This study contributes to public policy scholarship by offering a framework for understanding the strength of bureaucratic involvement in the process of defining problems and policy alternatives. Using witness data from congressional hearings on crime between 1947 and 1998, I find that federal, state, and local criminal justice bureaucrats have come to occupy a central role in the process of defining policy alternatives. In addition, I find that the centrality of criminal justice actors comes at the expense of interest groups, community organizations, and citizens/victims. Implications for criminal justice policy and understanding bureaucratic involvement in the policy process are discussed.
The Influence of Local Contextual Characteristics on the Implementation of a Statewide Voter Initiative: The Case of California's Substance Abuse and Crime Prevention Act (Proposition 36)
Authors: Percival Garrick L.
Published: October 2004

Much of the scholarship on initiatives emphasizes the link between voting behavior and initiative election outcomes or the strategies employed during the policy enactment phase. Little research has considered implementation or whether initiatives ultimately achieve their intended goals. Although the initiative process provides a direct link between the people and policy, it cannot be assumed that upon voter approval, an initiative will simply be implemented in a meaningful and uniform manner within the scope of the initiative's original intent. Using a case study of California's Substance Abuse and Crime Prevention Act (SACPA/Proposition 36) I ask how local politics and other contextual factors influence the implementation of a statewide voter initiative. Using aggregate data drawn from each of California's 58 counties, results indicate that politics at the county‐level, measured via counties’ general ideological dispositions and more specific policy preferences toward drug abuse and drug offenders affect how they implement the initiative. Contrary to popular conceptions, results here confirm that initiatives are not uniformly implemented, but in fact, will be manifested in quite different ways due to local contextual differences.
Beat‐to‐Beat Heart Rate and QT Variability in Patients with Congestive Cardiac Failure: Blunted Response to Orthostatic Challenge
Authors: Desai Nagaraj , D.S. Raghunandan , Mallavarapu Mallika , Berger Ronald D. , Yeragani Vikram K.
Published: October 2004

Background: Congestive cardiac failure is associated with increased sympathetic activity and impaired baroreflex function. We sought to test the hypothesis that these patients also have blunted response of beat‐to‐beat QT interval variability during orthostatic challenge.

Methods: We compared beat‐to‐beat heart rate and QT interval data in 17 patients with congestive cardiac failure and 17 age‐matched normal controls in supine normal breathing, supine controlled breathing, and standing controlled breathing conditions. The ECG data were acquired in lead II configuration at a sampling rate of 1000 Hz.

Results: Supine controlled breathing was associated with an increase in spectral HF power (0.15–0.5 Hz) of HR and QT interval time series compared to spontaneous breathing condition only in controls. While there were significant changes in HR, HR LF power, HR LF/HF ratios, and QT variability measures in standing posture in controls, there were no such changes in patients.

Conclusions: This impairment of postural changes of HR variability is most likely due to an impaired baroreceptor function in patients with congestive heart failure. The etiology of this is likely due to an increased cardiac sympathetic and a decreased vagal function. However, the relationship of postural changes in beat‐to‐beat QT interval variability and baroreflex need further investigation.
Wavelet‐Based Analysis of Heart‐Rate‐Dependent ECG Features
Authors: Stiles Martin K. , Clifton David , Grubb Neil R. , Watson James N. , Addison Paul S.
Published: October 2004

Background: Wavelet‐based methods of analyzing ECG signals have been used to identify specific features in cardiac arrhythmias. Since some of these features are rate dependent, it is a requirement that they are examined across a range of physiological heart rates. The wavelet transform is a signal analysis tool that can elucidate spectral and temporal information simultaneously from complex signals, including the ECG. The aim of this study was to identify the local frequency characteristics of the ECG using a real‐time wavelet scalogram and to study the rate dependence of these features.

Methods: We examined the spectral temporal behavior of the local characteristics of the electrocardiogram (ECG) of 10 patients, in whom precise control of heart rate was achieved using right atrial pacing. Temporary reprogramming was used to adjust the paced atrial rate to predetermined values so that a rate‐controlled rhythm was produced that closely resembled sinus rhythm.

Results: Rate‐dependent features are seen on time–frequency scalograms. As the rate increases, the temporal spacing of features decrease and the frequency bands shift upward on the plot. Two patients with abnormal atrioventricular conduction demonstrate features of Wenckebach conduction and fusion.

Conclusions: Characterization of the rate‐dependent features of the ECG in a paced atrial rhythm by wavelet transform techniques has revealed some additional information not readily seen on single lead ECG analysis. This model provides a surrogate for changes that might be expected during rate changes in physiological sinus rhythm. It is envisaged that this method will offer advantages in detecting features of clinical significance that may not be readily seen by existing methods.
Association of Stage of Left Ventricular Diastolic Dysfunction with P Wave Dispersion and Occurrence of Atrial Fibrillation after First Acute Anterior Myocardial Infarction
Authors: Yilmaz Remzi , Demirbag Recep , Durmus Ismet , Kasap Hasan , Baykan Merih , Kucukosmanoglu Mehmet , Celik Sukru , Erdol Cevdet
Published: October 2004

Objectives: The aim of this study was to investigate the association of stage of left ventricular diastolic dysfunction after acute myocardial infarction (AMI) with P maximum, P dispersion, and atrial fibrillation (AF) occurrence rate.

Background: The occurrence of AF following AMI is frequently associated with a left ventricle restrictive filling pattern. Increased P dispersion is also associated with the occurrence of AF after AMI. But, the relation between the stage of left ventricular diastolic dysfunction and the P wave measurements after AMI has not yet been investigated.

Methods: Electrocardiograms of 90 patients with first anterior AMI were recorded on admission, and P wave measurements were performed. The left ventricular diastolic functions were evaluated by transthoracic echocardiography. On the basis of mitral inflow, subjects were stratified into three left ventricular diastolic filling patterns. All patients were monitored continuously for the detection of AF in the Coronary Care Unit.

Results: Thirty patients had a normal filling pattern (33.3%) (NF group), 37 had impaired relaxation (41.1%) (IR group), and 23 had pseudonormal/restrictive filling pattern (25.6%) (PN/R group). P maximum was longer in the PN/R group (103 ± 12 ms) compared with the NF group (94 ± 9 ms, P = 0.019), but no significant difference was found between PN/R and IR (96 ± 13 ms, P > 0.05) groups, and between NF and IR groups (P > 0.05). There was no significant difference for P minimum among the groups (P > 0.05). P dispersion was longer in the PN/R group (35 ± 6 ms) than in the NF (26 ± 7 ms, P < 0.001) and IR groups (26 ± 6 ms, P < 0.001), but not different between the NF and IR groups (P > 0.05). Occurrence of AF was significantly more frequent in the PN/R group (52.2%) than in the NF (16.7%, P = 0.007) and IR groups (10.8%, P = 0.001). Frequency of AF was not different between the NF and IR groups (P > 0.05). In multivariate analyses, the stage of diastolic dysfunction was independently associated with P maximum, P minimum, P dispersion, and the occurrence of AF (P < 0.001, P = 0.035, P < 0.001, and P = 0.002, respectively).

Conclusions: P maximum and P dispersion are increased, and AF occurrence risk is higher in patients with pseudonormal/restrictive filling pattern after first anterior AMI. The stage of diastolic dysfunction is an independent predictor of P wave measurements and AF occurrence.
The Significance of P Wave Duration and P Wave Dispersion for Risk Assessment of Atrial Tachyarrhythmias in Patients with Corrected Tetralogy of Fallot
Authors: Hallioglu Olgu , Aytemir Kudret , Celiker Alpay
Published: October 2004

Background: The aim of the present study was to determine the potential role of P wave duration and P wave dispersion for risk assessment of atrial tachyarrhythmias in patients with corrected tetralogy of Fallot (ToF).

Methods: The maximum P wave duration, minimum P wave duration, and the P wave dispersion from the 12‐lead surface electrocardiogram of the patients and controls were measured. Electrophysiological study was performed only in the patient group.

Results: The study group consisted of 25 patients with corrected ToF with a mean age of 16.4 ± 4.25 years and 25 age‐matched healthy control subjects. Patients underwent repair at a mean age of 4.6 ± 3.41 years (range: 1–19), and the mean duration of follow‐up of 11.8 ± 1.7 years (range: 9–15) after surgery. On electrophysiological study sinus node dysfunction was detected in 3 patients (12%), atrial tachyarrythmias—atrial flutter or fibrillation—in 5 patients (20%), both sinus node dysfunction and atrial flutter in 1 patient (4%), and AV conduction delay in 1 patient (4%). P wave dispersion is significantly higher in patients with atrial tachyarrhythmia inducible by electrophysiological study than in other patients (P < 0.05). A P wave dispersion value of >35 ms has a high predictive accuracy (sensitivity = 83% and specificity = 89%) for inducible atrial tachyarrhythmia in patients with corrected tetralogy of Fallot.

Conclusion: P wave dispersion is an easily measured electrocardiographic marker with a good sensitivity and specificity for predicting atrial arrhythmias in patients after correction of ToF.
Sympathetic Overactivity in Patients with Rheumatic Mitral Stenosis
Authors: Ozdemir Ozcan , Alyan Omer , Soylu Mustafa , Metin Fatma , Demir Ahmet Duran , Geyik Bilal , Aras Dursun , Özbakir Cemal , Cihan Gökhan , Sasmaz Hatice , Korkmaz Sule
Published: October 2004

Background: Mitral stenosis may increase sympathetic nervous activity by increasing left atrial pressure and reducing cardiac output. And elevated sympathetic nerve activity may be a risk factor for the development of clinical manifestations of mitral stenosis. In this study, we assessed the autonomic nervous system activity in patients with mitral stenosis by heart rate variability analysis and defined factors affecting autonomic functions.

Methods and Results: Fifty‐four patients with rheumatic mitral stenosis were compared with an age‐ and gender‐matched control group composed of 42 healthy individuals. SDNN, RMSSD, PNN50, and HF were lower; mean heart rate (HR), LF and LF/HF ratio were higher in the patients with mitral stenosis compared to the control group. SDNN was correlated positively with left ventricle ejection fraction (LVEF), negatively with mitral valve area, left atrial (LA) diameter, and duration of symptoms. RMSSD was correlated positively with mean transmitral gradient, negatively correlated with age; PNN50 was correlated negatively with mitral valve area and positively correlated with transmitral gradient. LF was positively and HF was negatively correlated with LA diameter; LF was correlated positively, and HF was negatively correlated with duration of symptoms. LF/HF ratio was positively correlated with LA diameter and duration of symptoms, negatively with LVEF and mean valve area.

Conclusion: As a result, sympathetic nervous system activity is increased in patients with mitral stenosis and sympathetic overactivity worsens their symptoms. Most significant factors that affect autonomic functions in these patients are left atrial dilatation and mitral valve area.
QT Interval Dispersion Analysis in Patients Undergoing Left Partial Ventriculectomy (Batista Operation)
Authors: Pastore Carlos Alberto , Arcêncio Sandra Regina , Tobias Nancy M.M.O. , Kaiser Elisabeth , Filho Martino Martinelli , Moreira Luis Felipe P. , Stolf Noedir A. , Bocchi Edimar , Ramires José Antonio Franchini
Published: October 2004

Background: QT interval dispersion (QTd) has been valued as a marker of increased vulnerability for cardiac arrhythmias. QTd was analyzed in patients undergoing the left partial ventriculectomy (LPV) or Batista operation, a palliative surgery for patients in the line for heart transplantation, which is associated with complex arrhythmia and death from sustained ventricular tachyarrhythmia (SVT).

Methods: Pre‐ and postoperative R‐R, QT, QTc, JT (QT – QRS), and aT (apex to end of T wave) intervals were obtained by 87‐lead body surface mapping from 24 patients (18 male), mean age 46.4 ± 9.15 years. Dispersions of QT, QTc, JT, and aT intervals were calculated, and the total number of arrhythmic events were assessed, aiming to verify a possible risk predictor for the occurrence of SVTs. Subgroups of patients who survived and who died after LPV were also compared, aiming to obtain a QTd cutoff value that could be used prognostically.

Results: No difference between pre‐ and postoperative mean values were found, but a very significant difference was seen when comparing QTd and QTcD values for surviving and dead patients: QTd, cutoff value was 95 ms, while QTcD value was 114 ms.

Conclusion: There were no significant differences between pre‐ and postoperative variables or the number of arrhythmic events, but there were significant differences between both pre‐ and postoperative QTd and QTcD data from surviving and dead patients; this enabled the determination of cutoff values that we believe may be useful for the prognosis of the LPV outcome.
Polymorphisms in genes coding for enzymes metabolizing smoking‐derived substances and the risk of periodontitis
Authors: Kim Jeong‐Sook , Park Jong Y. , Chung Won‐Yoon , Choi Min‐Ah , Cho Kyoo‐Sung , Park Kwang‐Kyun
Published: October 2004

Objectives: Although the direct cause for periodontitis is oral bacterial infection, its progression depends upon genetic and environmental factors. Smoking, one of the environmental factors, is a risk factor for the development and severity of periodontitis. Therefore, individual susceptibility to periodontitis may be influenced by the polymorphisms of genes coding for enzymes metabolizing tobacco‐derived substances. The object of this study is to investigate roles of genetic polymorphisms of these metabolizing enzymes in the risk for periodontitis.

Material and Methods: We investigated three important enzymes: cytochrome P450 (CYP) 1A1, CYP2E1 and glutathione S‐transferase (GST) M1, involved in the metabolic activation and detoxification of tobacco‐derived substances. The prevalence of the polymorphisms of these genes was examined in 115 patients with periodontitis as well as in 126 control subjects.

Results: Significantly increased risk for periodontitis was observed for subjects with the polymorphic CYP1A1 m2 allele (odds ratio (OR)=2.3, 95% confidence interval (CI)=1.2–4.4). A significant risk increase for periodontitis associated with the GSTM1 allele was observed (OR=2.1, 95% CI=1.3–3.6). However, no association was observed between the CYP2E1 Pst1 polymorphism and risk for periodontitis (OR=1.3, 95% CI=0.6–2.5).

Conclusion: These results suggest that the GSTM1 and CYP1A1 polymorphisms may play an important role in risk for periodontitis.
Smoking affects the outcome of guided tissue regeneration with bioresorbable membranes: a retrospective analysis of intrabony defects
Authors: Stavropoulos Andreas , Mardas Nikolaos , Herrero Federiko , Karring Thorkild
Published: October 2004

Objectives: To disclose factors that may influence the results of guided tissue regeneration (GTR) treatment in intrabony defects with bioresorbable membranes.

Methods: Forty‐seven intrabony defects in 32 patients were treated by means of polylactic acid/citric acid ester copolymer bioresorbable membranes. At baseline and after 1 year, the following parameters were recorded: (1) probing pocket depth (PPD), (2) gingival recession (REC), (3) probing attachment level (PAL)=PPD+REC, (4) presence/absence of plaque (PI), (5) presence/absence of bleeding on probing (BOP) and (6) intrabony component (IC) configuration (i.e. primarily presence of one, two, or three bone walls). Occurrence of membrane exposure and smoking habits were also recorded. Significance of differences between categorical variables was evaluated with McNemar's test, and between numerical variables with the t‐test for paired observations. Generalized linear models were constructed to evaluate the influence of various factors on PAL gain and PPD after 1 year, including in the analysis only one defect per patient (i.e. 32 defects) chosen at random. Odds ratios were calculated using the Mantel–Haenszel method. Differences between smokers and non‐smokers were evaluated by means of Pearson's χ2 and Student's t‐test for non‐paired observations.

Results: At baseline, a mean PPD of 8.6±1.1 mm and a mean PAL of 9.8±1.6 mm was recorded. Statistically significant clinical improvements were observed 1 year after GTR treatment. An average residual PPD of 3.7±1.1 mm and a mean PAL gain of 3.8±1.5 mm were recorded. IC configuration and exposure of the membrane did not seem to influence the results, while a negative effect of smoking on the clinical parameters was observed. Smokers gained approximately 1 mm less in PAL than non‐smokers (3.2±1.4 versus 4.3±1.3, respectively; p=0.03) and had approximately seven times less chances to gain 4 mm in PAL as compared with patients who did not smoke (odds ratio: 0.15). PPD reduction was less pronounced in smokers than in non‐smokers (4.5±0.7 versus 5.5±0.7, respectively; p<0.01), resulting in somewhat deeper residual PPD in smokers than in non‐smokers (3.6±1.0 versus 3.4±1.1; p>0.05).

Conclusion: Smoking impairs the healing outcome of GTR treatment of intrabony defects with bioresorbable membranes.
Periodontal treatment of patients with Papillon–Lefèvre syndrome: a 3‐year follow‐up
Authors: Lundgren T. , Renvert S.
Published: October 2004

Background/aim: Conventional mechanical periodontal treatment of Papillon–Lefèvre syndrome (PLS) has often been reported to fail. This study describes the outcome of a non‐surgical periodontal therapy including antimicrobial treatment of nine patients diagnosed with PLS. The patients originate from a total of 15 children and adolescents with PLS for which clinical characteristics are presented.

Methods: Clinical examination including conventional periodontal measurements. Initial treatment including oral hygiene instruction, scaling and root planing and systemic amoxicillin–metronidazole therapy for 6 weeks. After that the patients were enrolled in a 3‐month recall maintenance program. In addition to this mechanical supportive maintenance treatment, tetracycline was prescribed and used continuously for 1.5 years.

Results/Conclusion: On five patients who were showing acceptable standard of oral hygiene and also compliance with the antibiotic medication, development of periodontitis on erupting teeth was prevented and disease activity on the previously periodontally involved teeth controlled during a 3‐year period. Poor results of treatment were observed for three patients, all siblings. These patients failed to comply with the medication and also failed to improve their oral hygiene.
Efficacy of plaque removal of the Sonicare Elite versus the Sonicare Advance from hard‐to‐reach sites
Authors: McCracken G. I. , Preshaw P. M. , Heasman L. , Stacey F. , Steen N. , Heasman P. A.
Published: October 2004

Objective: To compare the Sonicare Elite with the Sonicare Advance in terms of the reduction in supragingival plaque in the posterior, hard‐to‐reach areas of the mouth.

Method: This was a single‐cohort, 6‐week, two‐treatment, single‐blind, cross‐over clinical trial that recruited 45 subjects. Plaque scores were recorded throughout the study using a modification of the Quigley and Hein plaque index (PI). All subjects had a minimum pre‐brushing PI of 1.8 at screening following 24 h abstention from tooth cleaning. Subjects then used a Sonicare Advance powered toothbrush at home for 4 weeks for familiarisation purposes. At the next visit (2), subjects were given either the Sonicare Elite or the Sonicare Advance powered toothbrush for a further 2 weeks of home use. Twenty‐four hours prior to visit 3, subjects abstained again from tooth cleaning. At visit 3, the PI was recorded pre‐ and post‐tooth brushing and then all remaining “mature” plaque was removed professionally with a dental prophylaxis. After a further period of 24 h (to accumulate new plaque) without tooth brushing the subjects returned for visit 4 at which PIs were again recorded pre‐ and post‐tooth brushing. The subjects were then given the second toothbrush in the cross‐over sequence and attended for visits 5 and 6 at which the protocol for visits 3 and 4 was repeated.

Results: The Sonicare Elite powered toothbrush was more effective than the Sonicare Advance model in removing both mature and newly formed plaque. The magnitude of the differences between the toothbrushes for all posterior sites, interproximal and smooth surfaces, respectively, was 0.35 U (p<0.001), 0.39 U (p<0.001) and 0.32 U (p<0.001) of the modified Quigley and Hein PI. There was no evidence of a significant period effect comparing data from visits 5 and 6 against those from visits 3 and 4. There was, however, a significant visit effect with full‐mouth (p<0.01), interproximal (p<0.001) and smooth surface (p<0.01) post‐brushing plaque scores being significantly lower at visits 4 and 6 than at visits 3 and 5.

Conclusion:  The data support the observation that the Sonicare Elite toothbrush is more effective than the Sonicare Advance model in removing both newly formed and mature plaque from all posterior, interproximal and smooth tooth surfaces.
Life‐threatening thrombotic thrombocytopenic purpura associated with dental foci
Authors: Fenner Matthias , Frankenberger Roland , Pressmar Katharina , John Stefan , Neukam Friedrich Wilhelm , Nkenke Emeka
Published: October 2004

Objectives: Thrombotic thrombocytopenic purpura (TTP) is a rare haematological disease of unknown aetiology. This thrombotic microangiopathy is characterized by microvascular lesions with platelet aggregation. It is found in adults and can be associated with pregnancy, cancer, autoimmune diseases, bone marrow transplantation, drugs and bacterial as well as viral infections. The therapy requires a multi‐disciplinary team approach involving dentistry. Even if TTP is immediately treated in an adequate manner, it still shows a mortality of up to 20%.

Aim: To define a specific treatment concept for periodontal disease and decayed teeth in patients suffering from TTP based on the experiences gained from two cases.

Conclusion: The two patient cases revealed a possible association of TTP with dental foci. Because of the severity and mortality of this disease, both prognosis evaluation and treatment standards of periodontologically compromised or decayed teeth have to be strictly followed in patients suffering from TTP. In order to avoid recurrence of TTP, it seems important to remove radically teeth of questionable prognosis.
Behavior of human periodontal ligament cells on CO2 laser irradiated dentinal root surfaces: an in vitro study
Authors: Pant V. , Dixit J. , Agrawal A. K. , Seth P. K. , Pant A. B.
Published: October 2004

Objective: 
The aim of this study was to investigate the in vitro attachment behavior of human periodontal ligament fibroblasts on periodontally involved root surface after conditioning with CO2 laser and to compare its efficacy with chemical conditioning agents, namely tetracycline hydrochloride, citric acid, hydrogen peroxide (H2O2) and EDTA, using scanning electron microscopy.

Methods:  A total of 84 scaled and root‐planed specimens from periodontally involved single‐rooted human teeth showing hopeless prognosis were selected and assigned to two groups. One group was lased with a CO2 laser (from 5 cm at 3 W for 0.8, 1.0 and 1.2 s), and the other group was treated with either tetracycline hydrochloride (2.5%), citric acid (saturated solution, pH 1), H2O2 (6%) or EDTA (5%; pH 7.4) for 3 min. The specimens were then seeded with human periodontal ligament fibroblasts, incubated for either 12 h or 24 h, and then the cell attachment behavior was observed.

Results:  CO2 laser irradiation for 1.0 s was found to be the most efficient, showing consistently good cell attachment with the highest mean value (15.00 ± 3.41 cells/10,000 µm2 after incubation for 12 h and 29.17 ± 2.04 cells/10,000 µm2 after 24 h), followed by irradiation for 0.8 s (13.11 ± 3.04 cells/10,000 µm2 after incubation for 12 h and 22.91 ± 7.10 cells/10,000 µm2 after 24 h). Charring was observed following irradiation for 1.2 s. Amongst chemical conditioning agents, citric acid was found to be the most efficient, with a mean cell attachment of 17.82 ± 2.16 cells/10,000 µm2 after incubation for 12 h and 23.62 ± 1.94 cells/10,000 µm2 after 24 h. EDTA and H2O2 did not do well in the study.

Conclusion:  The results suggest that CO2 laser irradiation for 1.0 s may promote comparatively better attachment of periodontal ligament fibroblast on dentinal root surfaces than the conventional chemical conditioning agents used in the study.
The distribution of periodontopathic bacteria among Japanese children and their parents
Authors: Umeda Makoto , Miwa Zenzo , Takeuchi Yasuo , Ishizuka Motoko , Huang Yi , Noguchi Kazuyuki , Tanaka Mitsuro , Takagi Yuzo , Ishikawa Isao
Published: October 2004

Objective and background:  It is not well known how periodontopathic bacteria colonize in the oral cavity during childhood. The purpose of this study was to investigate the distribution of periodontopathic bacteria in oral cavities of children and their parents and the relationship between the bacterial findings and clinical parameters.

Methods:  Fifty‐six children (mean age: 8.3 ± 3.5, range: 1–15 years), including 15 with deciduous dentition, 26 with mixed dentition and 15 with permanent dentition, and their parents participated in this study. Whole saliva and dental plaque of the children and whole saliva of their parents were collected for detection of seven species of periodontopathic bacteria (Actinobacillus actinomycetemcomitans, Tannerella forsythensis (Bacteroides forsythus), Campylobacter rectus, Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Treponema denticola) using the polymerase chain reaction method. Clinical parameters including simplified Oral Hygiene Index and Papillary‐Marginal‐Attachment Index were recorded for the children and their accompanied parents.

Results:  The detection frequencies of T. forsythensis, C. rectus, P. nigrescens, T. denticola, A. actinomycetemcomitans and P. gingivalis in the oral cavities of children were 42.9%, 94.6%, 42.9%, 48.2%, 1.8% and 8.9%, respectively. T. forsythensis, P. gingivalis and T. denticola were detected more frequently in the saliva of parents (54.8%, 54.8%, 88.1%, respectively) than in the saliva of children (25.5%, 7.3%, 41.8%, respectively). Different detection frequencies of P. nigrescens were found among the oral cavities of children with deciduous, mixed and permanent dentitions. In mixed dentition, females harbored T. forsythensis more frequently than males did. Children who harbored T. forsythensis, P. intermedia, P. nigrescens and T. denticola showed high scores for oral debris measurement by simplified Oral Hygiene Index. T.  forsythensis, P. intermedia and P. nigrescens were detected more frequently in children whose parents were positive for these pathogens than in children whose parents were negative.

Conclusions:  High plaque retention seems to promote the colonization of periodontal pathogens in the oral cavities of children. T. forsythensis, P. intermedia and P. nigrescens were detected more frequently in the oral cavities of children whose parents already harbored these bacteria. Familial transmission of these bacteria is suggested.
Pre‐exposure to high glucose augments lipopolysaccharide‐stimulated matrix metalloproteinase‐1 expression by human U937 histiocytes
Authors: Maldonado Alejandro , He Lin , Game Bryan A. , Nareika Alena , Sanders John J. , London Steve D , Lopes‐Virella Maria F. , Huang Yan
Published: October 2004

Background and objectives:  It has been well established that patients with diabetes have increased prevalence and severity of periodontal diseases. However, the underlying mechanisms are not well understood. Given that bacterial infection is the primary cause of periodontal disease, we postulated that hyperglycemia may interplay with bacterial virulence factors such as lipopolysaccharide to up‐regulate matrix metalloproteinase (MMP), leading to increased periodontal tissue destruction.

Methods and results:  We showed that prolonged pre‐exposure of U937 histiocytes to high glucose markedly increased lipopolysaccharide‐stimulated MMP‐1 secretion and mRNA expression. Our results also showed that the effect of high glucose on lipopolysaccharide‐induced MMP‐1 expression is cell type‐specific because no similar response was observed in human gingival fibroblasts. In addition to MMP‐1, high glucose also augments lipopolysaccharide‐stimulated MMP‐7, ‐8, and ‐9 mRNA expression. In the investigation of the signaling pathways involved in the enhancement of lipopolysaccharide‐induced MMP‐1 expression by high glucose, we found that both high glucose and lipopolysaccharide regulate MMP‐1 expression through the nuclear factor κB (NFκB) and mitogen‐activated protein kinase (MAPK) cascades.

Conclusions:  The present study has shown that pre‐exposure to high glucose and subsequent lipopolysaccharide treatment synergistically stimulates MMP‐1 expression by mononuclear phagocytes through the NFκB and MAPK signaling pathways. This study has thus delineated a pathogenic mechanism that may be involved in the exacerbated periodontal disease in diabetic patients.
Factor XIIIa+ dendritic cells and S‐100 protein+ Langerhans' cells in adult periodontitis
Authors: Dereka X. E. , Tosios K. I. , Chrysomali E. , Angelopoulou E.
Published: October 2004

Objective:  The purpose of this study was to evaluate the presence of factor XIIIa+ dendritic cells and S‐100 protein+ Langerhans' cells in the gingival epithelium and connective tissue of periodontal pockets, before and after non‐surgical periodontal therapy.

Background:  The microbial flora in periodontal pockets provokes complex immune reactions. Dendritic cells play a critical role in primary and secondary immune responses and are considered as antigen‐presenting cells. Factor XIIIa positive dendritic cells and S‐100 protein positive Langerhans' cells identified by immunoreactivity against factor XIIIa antigen and S‐100 protein, respectively, are two distinct subpopulations of dendritic cells.

Methods:  Fifty‐four gingival tissue samples were obtained from periodontal pockets of initial depth 4–5 mm and ≥ 6 mm. Each group was subdivided in to three subgroups. The first subgroup consisted of samples taken on baseline day and used as control. The second and third subgroups included those obtained 1 month after plaque and calculus removal, and 1 month after scaling and root planing, respectively, additionally to oral hygiene instructions. The tissues were removed from the palatal gingiva under local anaesthesia during routine periodontal surgery. Immunohistochemical staining with antibodies against factor XIIIa and S‐100 protein was performed to identify dendritic cells positive and Langerhans' cells positive, respectively.

Results:  Factor XIIIa+ dendritic cell numbers decreased compared to controls after plaque and calculus removal, oral hygiene instructions and scaling and root planing in periodontal pockets of 4–5 mm, but not in those of ≥ 6 mm depth. S‐100+ Langerhans' cell numbers decreased after periodontal treatment in the periodontal pockets ≥ 6 mm.

Conclusion:  These results may reflect a tendency for reduction of these two distinctive subpopulations of dendritic cells after non‐surgical periodontal therapy.
Use of water ‘softening and conditioning systems’ significantly increases the risk of periodontitis: smoking considerations
Authors: Wood Nelson , Johnson Roger B.
Published: October 2004

Background:  The role of water in the etiology of periodontal disease is poorly understood.

Objectives:  The objective of this study was to examine the association amongst water softness, risk for periodontitis, and smoking status.

Methods:  We examined the association between use of water ‘softening and conditioning systems’ and the risk for periodontal disease in smokers and non‐smokers, using adult participants (18+ years), from the third National Health and Nutrition Examination Survey (NHANES III) data. Zero to 33 per cent (0–33%) of sites with periodontal attachment loss ≥ 3 mm was considered a healthy periodontium, and > 33% of sites with periodontal attachment loss ≥ 3 mm was defined as periodontitis. Soft water users were divided into ‘yes’ or ‘no’ using the question, ‘Does your home have a “softening or conditioning system?”.’ Smoking subjects were divided into groups as follows: current smokers (had smoked ≥ 100 cigarettes in their lifetime and currently smoked), former smokers (had smoked ≥ 100 cigarettes in their lifetime, not currently smoking), or never smokers (had not smoked ≥ 100 cigarettes in their lifetime). Data was analyzed by univariate analyses using SPSS®. The 5% level of statistical significance was adopted throughout.

Results:  Subjects that answered the question ‘yes’ to soft water use had a significantly higher risk of periodontitis (p < 0.05), adjusting for confounders. When mineral intake from foods was added to the model, the significance of periodontitis risk remained the same for the non‐smoking, soft water‐using subjects, whereas for the smoking, soft water‐using subjects the risk for periodontitis increased significantly (p < 0.05) in most cases.

Conclusions:  Thus, use of water ‘softening and conditioning systems’ significantly increased the risk for periodontitis, and smoking increased this risk.