36 resultados para Moving block signalling


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We report a 30-year-old man with moving ear syndrome caused by focal myoclonic jerks of the right temporal muscle. This focal myoclonus would disappear while the patient was sleeping, swallowing, or speaking. He was treated with botulinum toxin type A with a favorable outcome. Previous reports of this condition and possible therapeutic approaches are discussed. (c) 2007 Movement Disorder Society.

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Early Alzheimer`s disease (AD) pathophysiology is characterized by synaptic changes induced by degradation products of amyloid precursor protein (APP). The exact mechanisms of such modulation are unknown. Here, we report that nanomolar concentrations of intraaxonal oligomeric (o)A beta 42, but not oA beta 40 or extracellular oA beta 42, acutely inhibited synaptic transmission at the squid giant synapse. Further characterization of this phenotype demonstrated that presynaptic calcium currents were unaffected. However, electron microscopy experiments revealed diminished docked synaptic vesicles in oA beta 42-microinjected terminals, without affecting clathrin-coated vesicles. The molecular events of this modulation involved casein kinase 2 and the synaptic vesicle rapid endocytosis pathway. These findings open the possibility of a new therapeutic target aimed at ameliorating synaptic dysfunction in AD.

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Aims: Many fundamental pharmacological studies in pain and inflammation have been performed on rats. However, the pharmacological findings were generally not extended to other species in order to increase their predictive therapeutic value. We studied acute and chronic inflammatory nociceptive sensitisation of mouse hind paws by prostaglandin E(2) (PGE(2)) or dopamine (DA), as previously described in rats. We also investigated the participation of the signalling pathways in acute and persistent sensitisation. Main methods: Mechanical sensitisation (hypernociception) induced by intraplantar administrations of PGE(2) or DA was evaluated with an electronic pressure meter. The signalling pathways were pharmacologically investigated with the pre-administration of adenylyl cyclase (AC), cAMP-dependent protein kinase (PKA), protein kinase C epsilon (PKC epsilon), and the extracellular signal-related kinase (ERK) inhibitors. Key findings: Single or 14 days of successive intraplantar injections of PGE(2) or DA-induced acute and persistent hypernociception (lasting for more than 30 days), respectively. The involvement of AC, PKA or PKC epsilon was observed in the acute hypernociception induced by PGE(2), while PKA or PKC epsilon were continuously activated during the period of persistent hypernociception. The acute hypernociception induced by DA involves activation of ERK, PKC epsilon, AC or PKA, while persistent hypernociception implicated ERK activation, but not PKA, PKC epsilon or AC. Significance: In mice, acute and persistent paw sensitisation involves the different activation of kinases, as previously described for rats. This study opens the possibility of comparing pharmacological approaches in both species to further understand acute and chronic inflammatory sensitisation, and possibly associated genetic manipulations. (C) 2009 Elsevier Inc. All rights reserved.

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Background-Fetal atrioventricular (AV) block is an uncommon lesion with significant mortality. Because of the rarity of this disorder, the natural course, extensive evaluation of untreated fetuses, and late follow-up remain unclear. Methods and Results-Of the 116 consecutive cases of fetal AV block studied from 1988 to 2006, only 1 was terminated, and 75% were live births. Fifty-nine cases of AV block were associated with major structural heart disease, mainly left atrial isomerism (n = 40), with only 26% of neonatal survivors. Of the 57 fetuses with normal cardiac anatomy, 41 (72%) were positive for maternal antinuclear antibodies, and 32 of these seropositive mothers did not receive any treatment. This untreated group had live-birth and 1-year infant survival rates of 93% and 90%, respectively. Five fetuses from seronegative mothers showed regression to sinus rhythm during pregnancy. The presence of major structural heart disease, hydrops, an atrial rate <= 120 bpm, and a ventricular rate <= 55 bpm were identified as risk factors for mortality. Logistic regression analysis of the whole group showed that the presence of structural heart disease was the only independent predictor of death (P < 0.001). Conclusions-This long-term study confirms that fetal AV block has a poor outcome when associated with structural heart disease and that spontaneous regression of AV block is possible in seronegative forms. The survival rate of >90% of our untreated patients with isolated forms of AV block raises concerns about any decision to intervene with immunosuppressive agents.

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Purpose: The Gow-Gates technique is said to have several advantages over traditional techniques to achieve mandibular nerve anesthesia; however, its routine use is quite limited, mainly due to complications during visual alignment of reference landmarks. The purpose of this study was to verify the validity and accuracy of a new method to reach the injection site. Material and Methods: Fifteen magnetic resonance images were captured. Distances from the ideal injection point in the condylar neck (puncture ideal) to the injection points located in the a and 0 plane intersection (Puncture Gow-Gates and puncture modified) were measured and compared. Results: Positive and significant (P <= .003) Pearson correlations between landmarks and injection points confirmed the validity of the modified technique. Paired t test showed that the segment line puncture ideal-puncture modified, 5.17 mm, was 3 times shorter (P < .001) than the segment line puncture ideal-puncture Gow-Gates, 17.91 mm. As calculated by linear regression, establishing the injection point of the modified technique depended only on the anteroposterior and lateromedial condyle positions. Conclusions: The modified technique proved to be valid and precise and has a determined and an effective injection site. (C) 2009 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 67:2609-2616, 2009

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To histomorphometrically investigate the repair of critical size defects (CSDs) and bone augmentation in cranial walls using block of sintered bovine-derived anorganic bone (sBDAB) graft. Forty guinea-pigs were divided into test (n=20) and CSD control (n=20) groups. In each animal, a full-thickness bone defect with 9.5 mm diameter was made in the frontal bone. The defects were filled with an sBDAB block soaked in blood in the test group and with blood clot in the CSD control group. The skulls were collected at 0 h (n=2) and 30, 90 and 180 days (n=6/group and period) postoperatively. The volume density and total volume of newly formed bone, sBDAB, blood vessels and connective tissue, vertical thickness of removed bone plug, sBDAB block and graft area were evaluated. The vertical thickness of the adapted sBDAB block was 3.8 times higher than that of the removed bone plug and did not show significant difference between periods, filling in average 29.8% of the total graft region. The sBDAB block exhibited complete osseointegration with the borders of the defect at 90 days. At 90 and 180 days, the vertical thickness of the graft was 279% in the average, and the total volume of bone augmentation was, respectively, 78.8% and 148.5% higher compared with the removed bone plug. The defects of the CDS control group showed limited osteogenesis and filling by connective tissue plus tegument. The sBDAB block can be used to promote repair of CSDs and bone augmentation in the craniomaxillofacial region, due to its good osteoconductive and slow resorptive properties. To cite this article:Cestari TM, Granjeiro JM, de Assis GF, Garlet GP, Taga R. Bone repair and augmentation using block of sintered bovine-derived anorganic bone graft in cranial bone defect model.Clin. Oral Impl. Res. 20, 2009; 340-350.doi: 10.1111/j.1600-0501.2008.01659.x.

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Purpose: The aim of this study was to perform qualitative and quantitative analyses of the effect of nicotine on autogenous bone block grafts and to describe events in the initial healing phase and the differences in the repair processes between animals exposed to nicotine and controls. Materials and Methods: Forty-eight female Wistar rats were randomly divided into 2 groups, the nicotine group and the saline group. All animals received either nicotine (3 mg/kg) or saline 4 weeks before the surgical procedure and continued to receive nicotine from surgery to sacrifice at 7, 14, or 28 days. The autogenous bone block graft was harvested from the calvaria and stabilized on the external cortical area near the angle of the mandible. Results: The histologic analyses of the nicotine group depicted a delay in osteogenic activity at the bed-graft interface, as well as impairment of the organization of the granulation tissue that developed instead of blood clot. Nicotine-group specimens exhibited less bone neoformation, and the newly formed bone was poorly cellularized and vascularized. The histometric analysis revealed significantly less bone formation in the nicotine group at both 14 days (23.75% +/- 6.18% versus 51.31% +/- 8.31%) and 28 days (42.44% +/- 8.70% versus 73.00% +/- 4.99%). Conclusion: Nicotine did jeopardize the early healing process of autogenous bone block grafts in rats but did not prevent it.

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Objective. We compared the anesthetic efficacy of inferior alveolar nerve block (IANB) plus buccal infiltration (BI) and IANB plus periodontal ligament (PDL) articaine injections in patients with irreversible pulpitis in the mandibular first molar. Study design. Fifty-seven volunteers, patients with irreversible pulpitis in the mandibular first molar admitted to the Department of Stomatology, Second Affiliated Hospital, Sun Yat-Sen University, randomly received conventional IANB, containing 1.7 mL 4% articaine/HCl with 1:100,000 epinephrine, plus either BI or PDL injections containing 0.4 mL articaine/HCl with 1: 100,000 epinephrine. The patients recorded the pain of the injections and endodontic access on a Heft-Parker visual analog scale (VAS). Results. According to the VAS scores, all patients experienced no or mild pain with BI and PDL injections after the application of IANB. Anesthetic success occurred in 81.48% for IANB plus BI (IANB/BI) compared with 83.33% for IANB plus PDL injection (IANB/PDL injection). None of the observed differences between the 2 groups was significant (P > .05). Conclusion. Both injection combinations resulted in high anesthetic success in patients with irreversible pulpitis in the mandibular first molar. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:e89-e93)

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Plasmodium falciparum, the most important etiological agent of human malaria, is endowed with a highly complex cell cycle that is essential for its successful replication within the host. A number of evidence suggest that changes in parasite Ca(2+) levels occur during the intracellular cycle of the parasites and play a role in modulating its functions within the RBC. However, the molecular identification of Plasmodium receptors linked with calcium signalling and the causal relationship between Ca(2+) increases and parasite functions are still largely mysterious. We here describe that increases in P. falciparum Ca(2+) levels, induced by extracellular ATP, modulate parasite invasion. In particular, we show that addition of ATP leads to an increase of cytosolic Ca(2+) in trophozoites and segmented schizonts. Addition of the compounds KN62 and Ip5I on parasites blocked the ATP-induced rise in [Ca(2+)](c). Besides, the compounds or hydrolysis of ATP with apyrase added in culture drastically reduce RBC infection by parasites, suggesting strongly a role of extracellular ATP during RBC invasion. The use of purinoceptor antagonists Ip5I and KN62 in this study suggests the presence of putative purinoceptor in P. falciparum. In conclusion, we have demonstrated that increases in [Ca(2+)](c) in the malarial parasite P. falciparum by ATP leads to the modulation of its invasion of red blood cells.

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Objectives: Early weaning (EW) increases proliferation of the gastric epithelium in parallel with higher expression of transforming growth factor alpha and its receptor epidermal growth factor receptor (EGFR). The primary objective of the present study was to examine involvement of EGFR signalling in regulating mucosal cell proliferation during the early weaning period. Materials and methods: Fifteen-day-old rats were split into two groups: suckling (control) and EW, in which pups were separated from the dam. Animals were killed daily until the 18th day, 3 days after onset of treatment. To investigate the role of EGFR in proliferation control, EW pups were injected with AG1478, an EGFR inhibitor; signalling molecules, proliferative indices and cell cycle-related proteins were evaluated. Results: EW increased ERK1/2 and Src phosphorylation at 17 days, but p-Akt levels were unchanged. Moreover, at 17 days, AG1478 administration impaired ERK phosphorylation, whereas p-Src and p-Akt were not altered. AG1478 treatment reduced mitotic and DNA synthesis indices, which were determined on HE-stained and BrdU-labelled sections. Finally, AG1478 injection decreased p21 levels in the gastric mucosa at 17 days, while no changes were detected in p27, cyclin E, CDK2, cyclin D1 and CDK4 concentrations. Conclusions: EGFR is part of the mechanism that regulates cell proliferation in rat gastric mucosa during early weaning. We suggest that such responses might depend on activation of MAPK and/or Src signalling pathways and regulation of p21 levels.

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The representation of interfaces by means of the algebraic moving-least-squares (AMLS) technique is addressed. This technique, in which the interface is represented by an unconnected set of points, is interesting for evolving fluid interfaces since there is]to surface connectivity. The position of the surface points can thus be updated without concerns about the quality of any surface triangulation. We introduce a novel AMLS technique especially designed for evolving-interfaces applications that we denote RAMLS (for Robust AMLS). The main advantages with respect to previous AMLS techniques are: increased robustness, computational efficiency, and being free of user-tuned parameters. Further, we propose a new front-tracking method based on the Lagrangian advection of the unconnected point set that defines the RAMLS surface. We assume that a background Eulerian grid is defined with some grid spacing h. The advection of the point set makes the surface evolve in time. The point cloud can be regenerated at any time (in particular, we regenerate it each time step) by intersecting the gridlines with the evolved surface, which guarantees that the density of points on the surface is always well balanced. The intersection algorithm is essentially a ray-tracing algorithm, well-studied in computer graphics, in which a line (ray) is traced so as to detect all intersections with a surface. Also, the tracing of each gridline is independent and can thus be performed in parallel. Several tests are reported assessing first the accuracy of the proposed RAMLS technique, and then of the front-tracking method based on it. Comparison with previous Eulerian, Lagrangian and hybrid techniques encourage further development of the proposed method for fluid mechanics applications. (C) 2008 Elsevier Inc. All rights reserved.

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This paper describes the development of an implicit finite difference method for solving transient three-dimensional incompressible free surface flows. To reduce the CPU time of explicit low-Reynolds number calculations, we have combined a projection method with an implicit technique for treating the pressure on the free surface. The projection method is employed to uncouple the velocity and the pressure fields, allowing each variable to be solved separately. We employ the normal stress condition on the free surface to derive an implicit technique for calculating the pressure at the free surface. Numerical results demonstrate that this modification is essential for the construction of methods that are more stable than those provided by discretizing the free surface explicitly. In addition, we show that the proposed method can be applied to viscoelastic fluids. Numerical results include the simulation of jet buckling and extrudate swell for Reynolds numbers in the range [0.01, 0.5]. (C) 2008 Elsevier Inc. All rights reserved.

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Purpose - The purpose of this paper is to develop a novel unstructured simulation approach for injection molding processes described by the Hele-Shaw model. Design/methodology/approach - The scheme involves dual dynamic meshes with active and inactive cells determined from an initial background pointset. The quasi-static pressure solution in each timestep for this evolving unstructured mesh system is approximated using a control volume finite element method formulation coupled to a corresponding modified volume of fluid method. The flow is considered to be isothermal and non-Newtonian. Findings - Supporting numerical tests and performance studies for polystyrene described by Carreau, Cross, Ellis and Power-law fluid models are conducted. Results for the present method are shown to be comparable to those from other methods for both Newtonian fluid and polystyrene fluid injected in different mold geometries. Research limitations/implications - With respect to the methodology, the background pointset infers a mesh that is dynamically reconstructed here, and there are a number of efficiency issues and improvements that would be relevant to industrial applications. For instance, one can use the pointset to construct special bases and invoke a so-called ""meshless"" scheme using the basis. This would require some interesting strategies to deal with the dynamic point enrichment of the moving front that could benefit from the present front treatment strategy. There are also issues related to mass conservation and fill-time errors that might be addressed by introducing suitable projections. The general question of ""rate of convergence"" of these schemes requires analysis. Numerical results here suggest first-order accuracy and are consistent with the approximations made, but theoretical results are not available yet for these methods. Originality/value - This novel unstructured simulation approach involves dual meshes with active and inactive cells determined from an initial background pointset: local active dual patches are constructed ""on-the-fly"" for each ""active point"" to form a dynamic virtual mesh of active elements that evolves with the moving interface.

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We show that the Hausdorff dimension of the spectral measure of a class of deterministic, i.e. nonrandom, block-Jacobi matrices may be determined with any degree of precision, improving a result of Zlatos [Andrej Zlatos,. Sparse potentials with fractional Hausdorff dimension, J. Funct. Anal. 207 (2004) 216-252]. (C) 2010 Elsevier Inc. All rights reserved.

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We focus this work on the theoretical investigation of the block-copolymer poly [oxyoctyleneoxy-(2,6-dimethoxy-1,4phenylene-1,2-ethinylene-phenanthrene-2,4diyl) named as LaPPS19, recently proposed for optoelectronic applications. We used for that a variety of methods, from molecular mechanics to quantum semiempirical techniques (AMI, ZINDO/S-CIS). Our results show that as expected isolated LaPPS19 chains present relevant electron localization over the phenanthrene group. We found, however, that LaPPS19 could assemble in a pi-stacked form, leading to impressive interchain interaction; the stacking induces electronic delocalization between neighbor chains and introduces new states below the phenanthrene-related absorption; these results allowed us to associate the red-shift of the absorption edge, seen in the experimental results, to spontaneous pi-stack aggregation of the chains. (C) 2009 Wiley Periodicals, Inc. Int J Quantum Chem 110: 885-892, 2010