bluuebunny/crossref_metadata_2025_split huggingface dataset:
GLT‐1 down‐regulation induced by clozapine in rat frontal cortex is associated with synaptophysin up‐regulation
Authors: Bragina Luca , Melone Marcello , Fattorini Giorgia , Torres‐Ramos Monica , Vallejo‐Illarramendi Ainara , Matute Carlos , Conti Fiorenzo 
Published: July 2006

AbstractIn rat frontal cortex, extracellular levels of glutamate are raised by the anti‐psychotic drug clozapine. We have recently shown that a significant reduction in the levels of the glutamate transporter GLT‐1 may be one of the mechanisms responsible for this elevation. Here we studied whether GLT‐1 down‐regulation induced by chronic clozapine treatment is associated with changes in the expression of synaptophysin, synaptosome‐associated protein of 25 kDa (SNAP‐25) and vesicular glutamate transporter 1 (VGLUT1), three major presynaptic proteins involved in neurotransmitter release. Quantitative high‐resolution confocal microscopy studies in vivo showed that GLT‐1 down‐regulation is closely associated with a significant increase in synaptophysin, but not SNAP‐25 and VGLUT1, expression. This was confirmed in vitro studies, and in western blotting studies of synaptophysin, SNAP‐25 and VGLUT1. In addition, our results show that, following clozapine treatment, synaptophysin expression increases in the very cortical regions in which GLT‐1 expression is down‐regulated. These findings suggest that part of the effects of clozapine may be exerted via an action on the presynaptic machinery involved in neurotransmitter release.
Cyclic ADP‐ribose is a second messenger in the lipopolysaccharide‐stimulated activation of murine N9 microglial cell line
Authors: Franco Luisa , Bodrato Nicoletta , Moreschi Iliana , Usai Cesare , Bruzzone Santina , Scarf ì Sonia , Zocchi Elena , De Flora Antonio 
Published: July 2006

AbstractLipopolysaccharide, the main component of the cell wall of Gram‐negative bacteria, is known to activate microglial cells following its interaction with the CD14/Toll‐like receptor complex (TLR‐4). The activation pathway triggered by lipopolysaccharide in microglia involves enhanced basal levels of intracellular calcium ([Ca2+]i) and terminates with increased generation of cytokines/chemokines and nitric oxide. Here we demonstrate that in lipopolysaccharide‐stimulated murine N9 microglial cells, cyclic ADP‐ribose, a universal and potent Ca2+ mobiliser generated from NAD+ by ADP‐ribosyl cyclases (ADPRC), behaves as a second messenger in the cell activation pathway. Lipopolysaccharide induced phosphorylation, mediated by multiple protein kinases, of the mammalian ADPRC CD38, which resulted in significantly enhanced ADPRC activity and in a 1.7‐fold increase in the concentration of intracellular cyclic ADP‐ribose. This event was paralleled by doubling of the basal [Ca2+]i levels, which was largely prevented by the cyclic ADP‐ribose antagonists 8‐Br‐cyclic ADP‐ribose and ryanodine (by 75% and 88%, respectively). Both antagonists inhibited, although incompletely, functional events downstream of the lipopolysaccharide‐induced microglia‐activating pathway, i.e. expression of inducible nitric oxide synthase, overproduction and release of nitric oxide and of tumor necrosis factor α. The identification of cyclic ADP‐ribose as a key signal metabolite in the complex cascade of events triggered by lipopolysaccharide and eventually leading to enhanced generation of pro‐inflammatory molecules may suggest a new therapeutic target for treatment of neurodegenerative diseases related to microglia activation.
Glial fibrillary acidic protein is a major target of glycoxidative and lipoxidative damage in Pick's disease
Authors: Muntané G. , Dalfó E. , Martínez A. , Rey M. J. , Avila J. , Pérez M. , Portero M. , Pamplona R. , Ayala V. , Ferrer I. 
Published: July 2006

AbstractPick's disease is a subset of fronto‐temporal dementia characterised by severe atrophy of the temporal and frontal lobes due to marked neuronal loss accompanied by astrocytic gliosis enriched in glial acidic protein. The remaining neurones have intracytoplasmic inclusions composed of hyperphosphorylated tau, called Pick bodies, in addition to hyperphosphorylated tau in astrocytes and oligodendrocytes. Gel electrophoresis and western blotting using markers of glycoxidation (advanced glycation end products, N‐carboxyethyl‐lysine and N‐carboxymethyl‐lysine: AGE, CEL, CML, respectively) and lipoxidation (4‐hydroxy‐2‐nonenal: HNE, and malondialdehyde‐lysine: MDAL) were used in the frontal and occipital cortex in three Pick's disease cases and three age‐matched controls. In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands. Bi‐dimensional gel electrophoresis and western blotting also disclosed increased amounts and numbers of glial acidic protein isoforms in the frontal cortex in Pick's disease. Moreover, redox proteomics showed glycoxidation, as revealed with anti‐CEL antibodies and lipoxidation using anti‐HNE antibodies, of at least three glial acidic protein isoforms. The present results demonstrate that glial acidic protein is a target of oxidative damage in the frontal cortex in Pick's disease.
Astrocyte swelling leads to membrane unfolding, not membrane insertion
Authors: Pangršič Tina , Potokar Maja , Haydon Philip G. , Zorec Robert , Kreft Marko 
Published: July 2006

AbstractThe mechanisms mediating the release of chemical transmitters from astrocytes are the subject of intense research. Recent experiments have shown that hypotonic conditions stimulate the release of glutamate and ATP from astrocytes, but a mechanistic understanding of this process is not available. To determine whether hypotonicity activates the process of regulated exocytosis, we monitored membrane capacitance by the whole‐cell patch‐clamp technique whilst a hypotonic medium was applied to cultured astrocytes. If exocytosis is triggered under hypotonic conditions, as it is following increases in cytosolic calcium, a net increase in membrane surface area, monitored by measuring the whole‐cell membrane capacitance, is expected. Simultaneous measurements of cell size and whole‐cell membrane conductance and surface area demonstrated that hypotonic medium (210 mOsm for 200 s) resulted in an increase in membrane conductance and in the swelling of cultured astrocytes by an average of 40%, as monitored by cell cross‐sectional area, but without any corresponding change in membrane surface area. As we have demonstrated that capacitance measurements have the sensitivity to detect increases in cell surface area as small as 0.5%, we conclude that cell swelling occurs via an exocytosis‐independent mechanism, probably involving the unfolding of the plasma membrane.
Effects of Parecoxib on Plasma Protein Extravasation and c‐Fos Expression in the Rat
Authors: Schuh‐Hofer Sigrid , Tayefeh Mandana , Reuter Uwe , Dirnagl Ulrich , Arnold Guy 
Published: July 2006

Objective.—We aimed to investigate the effects of the cyclooxygenases‐2 (COX‐2) inhibitor parecoxib on meningeal plasma protein extravasation (PPE) and on c‐fos expression in the nucleus trigeminalis caudalis in an animal model of trigeminovascular activation.Background.—Recent reports about the efficacy of COX‐2 inhibitors in migraine treatment suggest the involvement of COX‐2 in migraine pathophysiology. So far, studies on the role of COX‐2 in animal models of migraine are lacking.Methods.—Unilateral electrical stimulation of the trigeminal ganglion was performed in anesthetized male Sprague Dawley rats. We assessed PPE in the ipsilateral dura mater and expression of c‐fos within the ipsilateral trigeminal nucleus caudalis (TNC) under control conditions and after pretreatment with parecoxib.Results.—Parecoxib significantly attenuated PPE in the rat dura mater. The PPE ratio under control conditions (1.73 ± 0.19 (mean ± SD)) was reduced by 58.9 ± 30% after pretreatment with 10 mg/kg parecoxib and by 78.1 ± 23% after pretreatment with 50 mg/kg. c‐fos experiments: Compared with vehicle, all doses of parecoxib (1 mg/kg, 10 mg/kg, 50 mg/kg) significantly reduced the number of c‐fos positive cells in the ipsilateral TNC (P < .05). The number of c‐fos positive cells in the ipsilateral TNC was 50 ± 2.7 (mean ± SEM) under control conditions and 9.1 ± 0.6 after pretreatment with 50 mg/kg parecoxib.Conclusion.—Our study results suggest that COX‐2 is involved in neurogenic inflammation of the rat dura mater. Moreover, the study points to a role of COX‐2 inhibitors in trigeminal nociception at the second‐order level.
Ultrasonographic Predictors of Unsuccessful Cephalic Vein Approach During Pacemaker or Defibrillator Lead Implantation
Authors: CHEN JAN‐YOW , CHANG KUAN‐CHENG , LIN KUO‐HUNG , LIN YU‐CHIN , LEE JENG‐DI , HUANG SHOEI K. S. 
Published: July 2006

Background: The cephalic vein approach is a preferred route for endocardial lead implantation; however, it is associated with a significant failure rate. Anatomic abnormalities likely play an important role, but specific features have not been well characterized.
Methods: Color Doppler ultrasonography was performed in 82 consecutive patients prior to endocardial lead implantation. Venous diameter, depth, flow velocity, and morphology were evaluated and comparisons made between the successful and failed implantations at various stages of the procedure.
Results: Endocardial lead implantation was unsuccessful in 14 patients (17%), with eight patients of venous isolation failure, 4 patients of cannulation failure, and 2 patients of guidewire crossing failure. Venous diameter was found to be the only independent predictor for isolation and implantation failure. The best cutoff value of cephalic venous diameter to predict unsuccessful cephalic venous approach was ≤2.2 mm. In total, there were 10 patients with extensive cephalic vein tortuosity. In seven of these 10 patients, the incidence of standard guidewire crossing failure was significantly higher than that without a tortuous cephalic vein (7/10 vs 6/60, P < 0.001). After switching to a hydrophilic guidewire, crossing and navigation were successful in five of the seven patients.
Conclusions: Color Doppler imaging is useful to identify cephalic vein characteristics. A small venous diameter is the ultrasonographic predictor for failure of cephalic vein approach. A tortuous venous morphology is associated with a high incidence of guidewire crossing failure, which can be mostly overcome by using a hydrophilic guidewire.
Clinical Study of Amiodarone‐Associated Torsade De Pointes in Chinese People
Authors: GENG DENG‐FENG , JIN DONG‐MEI , WANG JING‐FENG , LUO YING‐JIA , WU WEI 
Published: July 2006

Objects: Amiodarone‐associated torsade de pointes (Tdp) has been reported increasingly in China in recent years. In this study, we made clinical analysis of amiodarone‐associated Tdp in Chinese people.
Methods: Two major Chinese medical databases were searched to identify articles published during the last 26 years that presented data on amiodarone‐associated proarrhythmic events. The articles were divided into two categories: case reports and observational studies.
Results: Fifty‐two Chinese‐language case reports with 98 patients and 2 patients registered in our hospital, total 100 patients about amiodarone‐associated Tdp, were enrolled in the study. Amiodarone‐associated Tdp occurred more frequently in females (68.0%, 68/100). The major primary disease of females was rheumatic heart disease (40.7%, 24/59), while that of males was coronary heart disease (45.8%, 11/24). In most patients, Tdp occurred repeatedly and terminated in 24–48 hours. Some Tdp worsen to ventricular fibrillation and caused 19 patients' death (mortality rate 21.8%, 19/87). Known predisposing factors to the development of Tdp, such as heart failure, hypokalemia, drugs combination, and bradyarrhythmia, existed in many cases. Tdp also occurred in six patients (4 females, 2 males) without any known predisposing factors except QTc interval prolongation. Fourteen observational studies each reported data from at least 100 patients who were treated with amiodarone for at least 1 month. Of 2,354 patients included in these studies, 455 patients exposed to amiodarone were reported to have proarrhythmic events (an overall incidence of 19.3%), while only 4 patients were reported to have Tdp or ventricular fibrillation (an incidence of 0.17%).
Conclusions: In conclusion, approximately one‐fifth of the patients have amiodarone‐induced proarrhythmic events, while the incidence of Tdp or ventricular fibrillation is remarkably low. Amiodarone‐associated Tdp occurred more frequently in Chinese females. Known predisposing factors for occurrence of Tdp prevailed in Chinese patients. QTc interval prolongation may be an independent risk factor of amiodarone‐associated Tdp.
The Superior Transseptal Surgical Approach to Mitral Valve Creates Slow Conduction
Authors: LUKAC PETER , HJORTDAL VIBEKE , PEDERSEN ANDERS K. , JENSEN HENRIK K. , MORTENSEN PETER T. , HANSEN PETER S. 
Published: July 2006

Background: Atrial tachycardia is very frequent after mitral valve surgery using the superior transseptal approach.
Methods: Sixteen patients operated on for mitral valve disease (superior transseptal approach = Group A, n = 9, and left atrial approach = Group B, n = 7) underwent radiofrequency catheter ablation of atrial tachycardia guided by electroanatomic mapping. Twenty‐six consecutive patients without previous cardiac surgery with typical atrial flutter served as controls (Group C).
Results: Atrial tachycardia occurred earlier after the operation in Group A than in Group B (median 97 vs 2,159 days, P = 0.003). Typical atrial flutter was the most frequent circuit in all groups (Group A—7 patients, Group B—5 patients, Group C—26 patients). Three patients in Group A developed right atrial incisional tachycardia. Ten of 14 tachycardia circuits (typical atrial flutter, n = 7, incisional tachycardia, n = 3) in Group A depended on the corridor between the right atrial part of the atriotomy and the tricuspid annulus. Slow conduction during typical atrial flutter was detected in this corridor in Group A, but not in the corresponding region in Groups B and C (P < 0.001). The cycle length of typical atrial flutter was longer in Groups A and B than in Group C (mean 283 ms and 282 ms vs 233 ms, P = 0.003). Patients in Group B with typical atrial flutter had larger right atria than patients in Group A or Group C (mean 156 mL vs 96 mL and 113 mL, P = 0.033).
Conclusions: The superior transseptal incision may predispose to atrial tachycardia by creating slow conduction between the atriotomy and the tricuspid annulus.
Microvolt T‐Wave Alternans with Exercise in Pediatrics and Congenital Heart Disease: Limitations and Predictive Value
Authors: ALEXANDER MARK E. , CECCHIN FRANK , HUANG KATHIE P. , BERUL CHARLES I. 
Published: July 2006

Background: Microvolt t‐wave alternans (TWA) in early exercise is a noninvasive marker of life‐threatening ventricular arrhythmia in some adult cardiac populations. The incidence and potential significance of sustained TWA in pediatric and congenital heart disease (CHD) populations has not been well defined.
Methods: TWA treadmill exercise studies in pediatric patients with CHD, myopathy, potential myocardial ischemia, syncope, or history of cardiac arrest were analyzed. Tests were categorized as abnormal for sustained TWA with onset heart rate <130 beats/min with specific analyses for lower onset heart rates. Patient characteristics were analyzed as possible correlates of TWA.
Results: Over 2 years, 318 consecutive TWA exercise studies were performed in 304 patients (60% male, median 14 years, 6–41) for indications of syncope, cardiac arrest, possible ventricular arrhythmia, or evaluation of functional myocardial perfusion. Underlying conditions included apparently normal hearts (45%), CHD (16%), cardiomyopathy (11%), coronary anomalies (11%), electrical myopathy (9%), and transplant (8%). Abnormal TWA was seen in 24 (7%, onset HR 106 ± 18) and included 19 at high clinical risk for serious events including 3 with cardiac arrest. By multivariate analysis sustained TWA was associated with cardiac arrest, ventricular arrhythmias, and a clinical classification of high risk.
Conclusions: TWA is associated with pediatric and CHD diagnoses at high risk of serious events and may contribute, with other diagnostic tools, to management choices. While the absence of TWA has relatively high negative predictive value, it does not completely exclude the potential for serious sustained ventricular arrhythmias. A more robust noninvasive marker for risk stratification in these populations is required.
Anti‐Inflammatory Effect of Cardiac Resynchronization Therapy
Authors: LAPPEGÅRD KNUT T. , BJØRNSTAD HANNE 
Published: July 2006

Background: Congestive heart failure (CHF) is associated with persistent immune activation. Medical therapy has been shown to exert only limited anti‐inflammatory effects. Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in a subset of patients with heart failure, but it is not known whether this treatment affects the immune system as well. To test this hypothesis, eight patients with heart failure scheduled for CRT were investigated for immune activation before and 6 months after CRT treatment.
Methods and Results: After 6 months, all patients had improved in NYHA‐class and LVEF, and there was a statistically significant reduction in serum N‐terminal pro brain natriuretic peptide (BNP). Furthermore, there was a statistically significant reduction in plasma levels of the chemokines monocyte chemoattractant protein 1 (MCP‐1) and interleukin 8 (IL‐8) and the cytokine interleukin 6 (IL‐6). We observed no changes in the levels of interleukin 1β (IL‐1β), tumor necrosis factor α (TNF‐α), interleukin 10 (IL‐10), or complement activation products. There was a significant correlation between changes in BNP and IL‐6 (r = 0.74, P = 0.037).
Conclusion: Although based upon a limited number of patients, this report indicates that CRT reduces peripheral markers of immune activation in patients with CHF. Further large scale studies are warranted to verify these findings.
Antitachycardia Pacing for Spontaneous Rapid Ventricular Tachycardia in Patients with Prophylactic Cardioverter‐Defibrillator Therapy
Authors: GRIMM WOLFRAM , PLACHTA EVELINE , MAISCH BERNHARD 
Published: July 2006

Aims: Antitachycardia pacing (ATP) has not routinely been used in patients who received implantable cardioverter defibrillators (ICDs) for primary prevention of sudden death. This study investigated the efficacy of empirical ATP to terminate rapid ventricular tachycardia (VT) in heart failure patients with prophylactic ICD therapy.
Methods and Results: Ninety‐three patients with a mean left ventricular ejection fraction of 22 ± 7% (range: 9–35%) due to nonischemic or ischemic cardiomyopathy received prophylactic ICDs with empiric ATP. At least 2 ATP sequences with 6‐pulse burst pacing trains at 81% of VT cycle length (CL) were programmed in one or two VT zones for CL below 335 ± 23 ms and above 253 ± 18 ms. Ventricular flutter and fibrillation (VF) with CL below 253 ± 18 ms were treated in a separate VF zone with ICD shocks without preceding ATP attempts. During 38 ± 27 months follow‐up, 339 spontaneous ventricular tachyarrhythmias occurred in 36 of 93 study patients (39%). A total of 232 VT episodes, mean CL 293 ± 22 ms, triggered ATP in 25 of 36 patients with ICD interventions (69%). ATP terminated 199 of 232 VT episodes (86%) with a mean CL of 294 ± 23 ms in 23 of 25 patients (88%) who received ATP therapy. ATP failed to terminate or accelerated 33 of 232 VT episodes (14%) with a mean CL of 287 ± 19 ms in 12 of 25 patients (48%) who received ATP therapy.
Conclusions: Painfree termination of rapid VT with empirical ATP is common in heart failure patients with prophylactic ICD therapy. The occasional inability of empiric ATP to terminate rapid VT in almost 50% of patients who receive ATP for rapid VT warrants restrictive ICD programming with regard to the number of ATP attempts in order to avoid syncope before VT termination occurs.
Upgrading of VVIR Pacemakers with Nonfunctional Endocardial Ventricular Leads to VDD Pacemakers in Adolescents
Authors: SILVETTI MASSIMO S. , DRAGO FABRIZIO 
Published: July 2006

Background: In some children with ventricular rate responsive demand (VVIR) pacemakers (PM), transvenous leads fail for technical reasons or patient's growth.
Aim: The aim of this study is to describe our experience in adolescents with a nonfunctional ventricular lead in whom the lead was abandoned and an additional VDD lead was implanted. Of the 136 children who received a VVIR PM with an endocardial lead in our center, seven patients aged 7 (0.3–12) years [median (range)] at initial implantation, after 10 (5–15) years showed lead malfunction and underwent atrial synchronous ventricular inhibited pacing (VDD) PM upgrading at 16 (10–20) years.
Results: The VDD lead was inserted through the ipsilateral subclavian vein in five patients, the contralateral in two (venous occlusion in one and for operator choice in the first patient). The tip was positioned into the right ventricular apex, the atrial dipole along the lateral atrial wall. Fluoroscopy times were not significantly different from those measured in SSI PM implantation and in VVIR dual‐chamber demand pacing (VVIR‐DDD) upgrading. There were no intraprocedural complications. Follow‐up duration is 12 (6–62) months. The VDD PM showed good function, no undersensing or oversensing. Tricuspid damage, new venous occlusion, and “twisting” of the two leads at x‐ray were not documented. The first patient showed an infection of the old PM pocket after 1 year, local pain after 3 years, and endocarditis of the leads after 5 years.
Conclusion:The upgrading of VVIR PM to VDD PM with the abandonment of the nonfunctional lead is feasible, with no intraprocedural complications and good PM function. Lead endocarditis occurred in one patient.
Smokeless tobacco (snuff) use and periodontal bone loss
Authors: Bergström Jan , Keilani Hamed , Lundholm Christian , Rådestad Urban 
Published: July 2006

AbstractObjective: The aim of the present cross‐sectional study was to investigate a possible association between the use of Swedish moist snuff and periodontal bone loss.Material and Methods: The study was carried out on 84 apparently healthy men in the age range 26–54 years, 25 current snuff users, 21 former snuff users, and 38 never‐users. The periodontal bone height was evaluated from bitewing radiographs measuring the distance from the cement–enamel junction (CEJ) to the periodontal bone crest (PBC) at pre‐molars and molars in each quadrant of the dentition.Results: The mean (95% confidence interval (95% CI)) CEJ−PBC distance was 1.00 (0.87–1.13), 1.12 (0.97–1.26), and 1.06 (0.95–1.16) mm for current users, former users, and never‐users, respectively. The association between snuff use and bone height level controlling for age was not statistically significant (anovaF=0.3, p>0.05). There was, further, no statistically significant difference between light and heavy exposure users controlling for age (anovaF=1.0, p>0.05).Conclusion: Our observations suggest that the use of Swedish moist snuff is not associated with periodontal bone loss.