bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytoplasmic accumulation of long‐chain coenzyme A esters activates KATP and inhibits Kir2.1 channels
Authors: Shumilina Ekaterina , Klöcker Nikolaj , Korniychuk Ganna , Rapedius Markus , Lang Florian , Baukrowitz Thomas
Published: June 2006

Long‐chain fatty acids acyl coenzyme A esters (LC‐CoA) are obligate intermediates of fatty acid metabolism and have been shown to activate KATP channels but to inhibit most other Kir channels (e.g. Kir2.1) by direct channel binding. The activation of KATP channels by elevated levels of LC‐CoA may be involved in the pathophysiology of type 2 diabetes, the hypothalamic sensing of circulating fatty acids and the regulation of cardiac KATP channels. However, LC‐CoA are effectively buffered in the cytoplasm and it is currently not clear whether their free concentration can reach levels sufficient to affect Kir channels in vivo. Here, we report that extracellular oleic acid complexed with albumin at an unbound concentration of 81 ± 1 nm strongly activated KATP channels and inhibited Kir2.1 channels in Chinese hamster ovary (CHO) cells as well as endogenous Kir currents in human embryonic kidney (HEK293) cells. These effects were only seen in the presence of a high concentration of glucose (25 mm), a condition known to promote the accumulation of LC‐CoA by inhibiting their mitochondrial uptake via carnitine‐palmitoyl‐transferase‐1 (CPT1). Accordingly, pharmacological inhibition of CPT1 by etomoxir restored the effects of oleic acid under low glucose conditions. Finally, triacsin C, an inhibitor of the acyl‐CoA synthetase, which is necessary for LC‐CoA formation, abolished the effects of extracellular oleic acid on the various Kir channels. These results establish the direct regulation of Kir channels by the cytoplasmic accumulation of LC‐CoA, which might be of physiological and pathophysiological relevance in a variety of tissues.
Sarcoplasmic reticulum Ca2+ release and depletion fail to affect sarcolemmal ion channel activity in mouse skeletal muscle
Authors: Allard Bruno , Couchoux Harold , Pouvreau Sandrine , Jacquemond Vincent
Published: June 2006

In skeletal muscle, sarcoplasmic reticulum (SR) Ca2+ depletion is suspected to trigger a calcium entry across the plasma membrane and recent studies also suggest that the opening of channels spontaneously active at rest and possibly involved in Duchenne dystrophy may be regulated by SR Ca2+ depletion. Here we simultaneously used the cell‐attached and whole‐cell voltage‐clamp techniques as well as intracellular Ca2+ measurements on single isolated mouse skeletal muscle fibres to unravel any possible change in membrane conductance that would depend upon SR Ca2+ release and/or SR Ca2+ depletion. Delayed rectifier K+ single channel activity was routinely detected during whole‐cell depolarizing pulses. In addition the activity of channels carrying unitary inward currents of ∼1.5 pA at −80 mV was detected in 17 out of 127 and in 21 out of 59 patches in control and mdx dystrophic fibres, respectively. In both populations of fibres, large whole‐cell depolarizing pulses did not reproducibly increase this channel activity. This was also true when, repeated application of the whole‐cell pulses led to exhaustion of the Ca2+ transient. SR Ca2+ depletion produced by the SR Ca2+ pump inhibitor cyclopiazonic acid (CPA) also failed to induce any increase in the resting whole‐cell conductance and in the inward single channel activity. Overall results indicate that voltage‐activated SR Ca2+ release and/or SR Ca2+ depletion are not sufficient to activate the opening of channels carrying inward currents at negative voltages and challenge the physiological relevance of a store‐operated membrane conductance in adult skeletal muscle.
Chronic intermittent hypoxia induces hypoxia‐evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress
Authors: Kumar Ganesh K. , Rai Vandana , Sharma Suresh D. , Ramakrishnan Devi Prasadh , Peng Ying‐Jie , Souvannakitti Dangjai , Prabhakar Nanduri R.
Published: June 2006

Chronic intermittent hypoxia (CIH) augments physiological responses to low partial pressures of O2 in the arterial blood. Adrenal medullae from adult rats, however, are insensitive to direct effects of acute hypoxia. In the present study, we examined whether CIH induces hypoxic sensitivity in the adult rat adrenal medulla and, if so, by what mechanism(s). Experiments were performed on adult male rats exposed to CIH (15 s of 5% O2 followed by 5 min of 21% O2; 9 episodes h−1; 8 h d−1; for 3 or 10 days) or to comparable, cumulative durations of continuous hypoxia (CH; 4 h of 7% O2 followed by 20 h of 21% O2 for 1 or 10 days). Noradrenaline (NA) and adrenaline (ADR) effluxes were monitored from ex vivo adrenal medullae. In adrenal medullae of rats exposed to CIH, acute hypoxia evoked robust NA and ADR effluxes, whereas these responses were absent in control rats or in those exposed to CH for 1 or 10 days. Hypercapnia (10% CO2; either acidic, pH 6.8, or isohydric, pH 7.4) was ineffective in eliciting catecholamine (CA) efflux from control, CIH or CH rats. Nicotine (100 μm) evoked NA and ADR effluxes in control rats, and this response was abolished in CIH but not in CH rats. Systemic administration of 2‐deoxyglucose depleted ADR content in control rats, and CIH attenuated this response, indicating downregulation of neurally regulated CA secretion. Cytosolic and mitochondrial aconitase enzyme activities decreased in CIH adrenal medullae, suggesting increased generation of superoxide anions. Systemic administration of antioxidants reversed the effect of CIH on the adrenal medulla. Rats exposed to CIH exhibited increased blood pressures and elevated plasma CA, and antioxidants abolished these responses. These observations demonstrate that CIH induces hypoxic sensing in the adult rat adrenal medulla via mechanisms involving increased generation of superoxide anions and suggest that hypoxia‐evoked CA efflux from the adrenal medulla contributes, in part, to elevated blood pressure and plasma CA.
KCNQ/M‐currents contribute to the resting membrane potential in rat visceral sensory neurons
Authors: Wladyka Cynthia L. , Kunze Diana L.
Published: June 2006

The M‐current is a slowly activating, non‐inactivating potassium current that has been shown to be present in numerous cell types. In this study, KCNQ2, Q3 and Q5, the molecular correlates of M‐current in neurons, were identified in the visceral sensory neurons of the nodose ganglia from rats through immunocytochemical studies. All neurons showed expression of each of the three proteins. In voltage clamp studies, the cognition‐enhancing drug linopirdine (1–50 μm) and its analogue, XE991 (10 μm), quickly and irreversibly blocked a small, slowly activating current that had kinetic properties similar to KCNQ/M‐currents. This current activated between −60 and −55 mV, had a voltage‐dependent activation time constant of 208 ± 12 ms at −20 mV, a deactivation time constant of 165 ± 24 ms at −50 mV andV1/2of −24 ± 2 mV, values which are consistent with previous reports for endogenous M‐currents. In current clamp studies, these drugs also led to a depolarization of the resting membrane potential at values as negative as −60 mV. Flupirtine (10–20 μm), an M‐current activator, caused a 3–14 mV leftward shift in the current–voltage relationship and also led to a hyperpolarization of resting membrane potential. These data indicate that the M‐current is present in nodose neurons, is activated at resting membrane potential and that it is physiologically important in regulating excitability by maintaining cells at negative voltages.
Different composition of glutamate receptors in corticothalamic and lemniscal synaptic responses and their roles in the firing responses of ventrobasal thalamic neurons in juvenile mice
Authors: Miyata Mariko , Imoto Keiji
Published: June 2006

Thalamic ventrobasal (VB) relay neurons receive information via two major types of glutamatergic synapses, that is, from the medial lemniscus (lemniscal synapses) and primary somatosensory cortex (corticothalamic synapses). These two synapses influence and coordinate firing responses of VB neurons, but their precise operational mechanisms are not yet well understood. In this study, we compared the composition of glutamate receptors and synaptic properties of corticothalamic and lemniscal synapses. We found that the relative contribution of NMDA receptor‐mediated excitatory postsynaptic currents (EPSCs) to non‐NMDA receptor‐mediated EPSCs was significantly greater in corticothalamic synapses than in lemniscal synapses. Furthermore, NMDA receptor 2B‐containing NMDA receptor‐ and kainate receptor‐mediated currents were observed only in corticothalamic synapses, but not in lemniscal synapses. EPSCs in corticothalamic synapses displayed the postsynaptic summation in a frequency‐dependent manner, in which the summation of the NMDA receptor‐mediated component was largely involved. The summation of kainate receptor‐mediated currents also partially contributed to the postsynaptic summation in corticothalamic synapses. In contrast, the contribution of NMDA receptor‐mediated currents to the postsynaptic summation of lemniscal EPSCs was relatively minor. Furthermore, our results indicated that the prominent NMDA receptor‐mediated component in corticothalamic synapses was the key determinant for the late‐persistent firing of VB neurons in response to corticothalamic stimuli. In lemniscal synapses, in contrast, the onset‐transient firing in response to lemniscal stimuli was regulated mainly by AMPA receptors.
A Relaxation Method for Simulating the Kinematics of Compound Nonlinear Mechanisms
Authors: Lipson Hod
Published: June 2006

This paper describes a relaxation-based method for simulating 2D and 3D compound kinematic mechanisms. The relaxational process iteratively propagates node motions and degrees of freedom throughout a given kinematic mechanism. While relaxation methods were classically used to solve static problems, we show that the propagation of displacements during the calculation process itself reveals the kinematics of the structure. The method is slower than approaches based on solving simultaneous differential equations of motion, but provides several advantages: It achieves a higher level of accuracy, is more robust in handling transient singularities and degeneracies of the mechanism, and can handle more complex compound mechanisms with many links in multiple entangled kinematic chains. It also allows straightforward introduction of linkages with nonlinear behaviors such as wrapping strings, hydraulics, actuators, contacts, and other arbitrary responses. The basic simulation algorithm is presented, and a number of applications are provided including robotics, design, and biomechanics.
Generalized Shooting Method for Analyzing Compliant Mechanisms With Curved Members
Authors: Lan Chao-Chieh , Lee Kok-Meng
Published: June 2006

We consider here a class of compliant mechanisms consisting of one or more flexible beams, the manipulation of which relies on the deflection of the flexible beams. As compared with traditional rigid-body mechanisms, compliant mechanisms have the advantages of no relative moving parts and thus involve no wear, backlash, noises, and lubrication. This paper presents a formulation based on shooting method (SM) and two numerical solvers for analyzing compliant mechanisms consisting of multiple flexible members that may be initially straight or curved. Five compliant mechanisms, which are chosen to illustrate both initially straight and curved members and different types of joint/contact conditions, are formulated to exemplify analyses using the generalized shooting method for a wide spectrum of applications. The advantages of the generalized SM over the finite difference FD and finite element FE methods are demonstrated numerically. Unlike FD or FE methods that rely on fine discretization of beam members to improve its accuracy, the generalized SM that treats the boundary value problem (BVP) as an initial value problem can achieve higher-order accuracy relatively easily, and hence is more efficient computationally. In addition, the computed results were validated experimentally. It is expected that the generalized SM presented here will offer designers a useful analysis tool, and will effectively facilitate the process of design and optimization of compliant mechanisms.
Assembly Configurations of Planar Multi-Loop Mechanisms With Kinematic Limitations
Authors: Foster David E. , Cipra Raymond J.
Published: June 2006

This paper examines the problem of identifying the assembly configurations (ACs), also called circuits, of planar multi-loop mechanisms with kinematic limitations, such as joint limits, link interference, collision with stationary obstacles, and constraint regions. First, a technique is given to describe numerically the satisfaction or violation of these kinematic limitations, and then it is applied to find the ACs of mechanisms with kinematic limitations. The method is valid for planar mechanisms with one or two degrees of freedom, and is illustrated with two examples.
A New Deterministic Approach Using Sensitivity Region Measures for Multi-Objective Robust and Feasibility Robust Design Optimization
Authors: Li Mian , Azarm Shapour , Boyars Art
Published: June 2006

We present a deterministic non-gradient based approach that uses robustness measures in multi-objective optimization problems where uncontrollable parameter variations cause variation in the objective and constraint values. The approach is applicable for cases that have discontinuous objective and constraint functions with respect to uncontrollable parameters, and can be used for objective or feasibility robust optimization, or both together. In our approach, the known parameter tolerance region maps into sensitivity regions in the objective and constraint spaces. The robustness measures are indices calculated, using an optimizer, from the sizes of the acceptable objective and constraint variation regions and from worst-case estimates of the sensitivity regions’ sizes, resulting in an outer-inner structure. Two examples provide comparisons of the new approach with a similar published approach that is applicable only with continuous functions. Both approaches work well with continuous functions. For discontinuous functions the new approach gives solutions near the nominal Pareto front; the earlier approach does not.
Possibility-Based Design Optimization Method for Design Problems With Both Statistical and Fuzzy Input Data
Authors: Du Liu , Choi K. K. , Youn Byeng D. , Gorsich David
Published: June 2006

The reliability based design optimization (RBDO) method is prevailing in stochastic structural design optimization by assuming the amount of input data is sufficient enough to create accurate input statistical distribution. If the sufficient input data cannot be generated due to limitations in technical and/or facility resources, the possibility-based design optimization (PBDO) method can be used to obtain reliable designs by utilizing membership functions for epistemic uncertainties. For RBDO, the performance measure approach (PMA) is well established and accepted by many investigators. It is found that the same PMA is a very much desirable approach also for the PBDO problems. In many industry design problems, we have to deal with uncertainties with sufficient data and uncertainties with insufficient data simultaneously. For these design problems, it is not desirable to use RBDO since it could lead to an unreliable optimum design. This paper proposes to use PBDO for design optimization for such problems. In order to treat uncertainties as fuzzy variables, several methods for membership function generation are proposed. As less detailed information is available for the input data, the membership function that provides more conservative optimum design should be selected. For uncertainties with sufficient data, the membership function that yields the least conservative optimum design is proposed by using the possibility-probability consistency theory and the least conservative condition. The proposed approach for design problems with mixed type input uncertainties is applied to some example problems to demonstrate feasibility of the approach. It is shown that the proposed approach provides conservative optimum design.
A Methodology to Manage System-level Uncertainty During Conceptual Design
Authors: Martin Jay D. , Simpson Timothy W.
Published: June 2006

Current design decisions must be made while considering uncertainty in both models of the design and inputs to the design. In most cases, high fidelity models are used with the assumption that the resulting model uncertainties are insignificant to the decision making process. This paper presents a methodology for managing uncertainty during system-level conceptual design of complex multidisciplinary systems. This methodology is based upon quantifying the information available in a set of observations of computationally expensive subsystem models with more computationally efficient kriging models. By using kriging models, the computational expense of a Monte Carlo simulation to assess the impact of the sources of uncertainty on system-level performance parameters becomes tractable. The use of a kriging model as an approximation to an original computer model introduces model uncertainty, which is included as part of the methodology. The methodology is demonstrated as a decision-making tool for the design of a satellite system.
Risk-Based Decision-Making for Managing Resources During the Design of Complex Space Exploration Systems
Authors: Farhang Mehr Ali , Tumer Irem Y.
Published: June 2006

Complex space exploration systems are often designed in collaborative engineering environments where requirements and design decisions by various subsystem engineers have a great impact on the overall risk of the mission. As a result, the system-level management should allocate risk mitigation resources (e.g., capital to place additional sensors or to improve the current technology) among various risk elements such that the main objectives of the system are achieved as closely as possible. Minimizing risk has been long accepted as one of the major drivers for system-level decisions and particularly resource management. In this context, Risk-Based Decision Making refers to a process that allocates resources in such a way that the expected risk of the overall system is minimized. This paper presents a new risk-based design decision-making method, referred to as Risk and Uncertainty Based Concurrent Integrated Design Methodology or RUBIC Design Methodology for short. The new approach is based on concepts from portfolio optimization theory and continuous resource management, extended to provide a mathematical rigor for risk-based decision-making during the design of complex space exploration systems. The RUBIC design method is based on the idea that a unit of resource, allocated to mitigate a certain risk in the system, contributes to the overall system risk reduction in the following two ways: (1) by mitigating that particular risk; and (2) by impacting other risk elements in the system (i.e., the correlation among various risk elements). RUBIC then provides a probabilistic framework for reducing the expected risk of the final system via optimal allocation of available risk-mitigation resources. The application of the proposed approach is demonstrated using a satellite reaction wheel example.
Characterization of the piRNA Complex from Rat Testes
Authors: Lau Nelson C. , Seto Anita G. , Kim Jinkuk , Kuramochi-Miyagawa Satomi , Nakano Toru , Bartel David P. , Kingston Robert E.
Published: June 2006

Small noncoding RNAs regulate processes essential for cell growth and development, including mRNA degradation, translational repression, and transcriptional gene silencing (TGS). During a search for candidate mammalian factors for TGS, we purified a complex that contains small RNAs and Riwi, the rat homolog to human Piwi. The RNAs, frequently 29 to 30 nucleotides in length, are called Piwi-interacting RNAs (piRNAs), 94% of which map to 100 defined (≤101 kb) genomic regions. Within these regions, the piRNAs generally distribute across only one genomic strand or distribute on two strands but in a divergent, nonoverlapping manner. Preparations of piRNA complex (piRC) contain rRecQ1, which is homologous to
qde-3
from
Neurospora
, a gene implicated in silencing pathways. Piwi has been genetically linked to TGS in flies, and slicer activity cofractionates with the purified complex. These results are consistent with a gene-silencing role for piRC in mammals.
FOUR-WING ATTRACTORS: FROM PSEUDO TO REAL
Authors: QI GUOYUAN , CHEN GUANRONG , LI SHAOWEN , ZHANG YUHUI
Published: June 2006

Some basic dynamical behaviors and the compound structure of a new four-dimensional autonomous chaotic system with cubic nonlinearities are investigated. A four-wing chaotic attractor is observed numerically. This attractor, however, is shown to be an numerical artifact by further theoretical analysis and analog circuit experiment. The observed four-wing attractor actually has two coexisting (upper and lower) attractors, which appear simultaneously and are located arbitrarily closely in the phase space. By introducing a simple linear state-feedback control term, some symmetries of the system and similarities of the linearized characteristics can be destroyed, thereby leading to the appearance of some diagonal and anti-diagonal periodic orbits, through which the upper and lower attractors can indeed be merged together to form a truly single four-wing chaotic attractor. This four-wing attractor is real; it is further confirmed analytically, numerically, as well as electronically in the paper. Moreover, by introducing a sign-switching control function, the system orbit can be manipulated so as to switch between two equilibria or among four equilibria, generating two one-side double-wing attractors, which can also be merged to yield a real four-wing attractor.
ELLIPTIC AND AUTOMORPHIC DYNAMICAL SYSTEMS ON SURFACES
Authors: BANKS S. P. , YI SONG
Published: June 2006

We derive explicit differential equations for dynamical systems defined on generic surfaces applying elliptic and automorphic function theory to make uniform the surfaces in the upper half of the complex plane with the hyperbolic metric. By modifying the definition of the standard theta series we will determine general meromorphic systems on a fundamental domain in the upper half plane the solution trajectories of which "roll up" onto an appropriate surface of any given genus.
ANTI-SYNCHRONIZATION OF A CLASS OF COUPLED CHAOTIC SYSTEMS VIA LINEAR FEEDBACK CONTROL
Authors: LI CHUANDONG , LIAO XIAOFENG
Published: June 2006

As a special case of generalized synchronization, chaos anti-synchronization can be characterized by the vanishing of the sum of relevant variables. In this paper, based on Lyapunov stability theorem for ordinary differential equations, several sufficient conditions for guaranteeing the existence of anti-synchronization in a class of coupled identical chaotic systems via linear feedback or adaptive linear feedback methods are derived. Chua's circuit is presented as an example to demonstrate the effectiveness of the proposed approach by computer simulations.
BISTABILITY AND SELF-OSCILLATIONS IN CELL CYCLE CONTROL
Authors: PETROV VALKO , PEIFER MARTIN , TIMMER JENS
Published: June 2006

A qualitative model of cell cycle control is presented and its transition from bistability to limit cycle oscillations and vice versa is discussed. The origin of this model is the two-dimensional system of kinetic equations introduced by Novak–Tyson which is illustrated computationally and analytically. For this purpose a qualitative model is numerically reconstructed from the steady state behavior of the dynamical variables including the bifurcation parameter. Then, the reconstructed cubic polynomial model is generalized to an appropriate canonical form and is analyzed in terms of Lyapunov values. On this basis, the relationship between bistability and self-oscillatory behavior of mitotic cell cycle is approached qualitatively.
PARAMETER ESTIMATION USING KALMAN FILTERS WITH CONSTRAINTS
Authors: WALKER DAVID M.
Published: June 2006

We suggest incorporating dynamical information such as locations of unstable fixed points into parameter estimation algorithms in order to improve the method of reconstructing dynamics from time series data. We show how the process of reconstruction using nonlinear filters such as the extended Kalman filter can be easily modified to take advantage of the additional information. We demonstrate the methods using data from two systems exhibiting chaotic dynamics — the Chua circuit and Chen's equations. In both cases we find the models reconstructed using constraints that better approximate the unstable fixed point structure of the underlying systems.
Errata: “Pitting Corrosion of Metals. A Review of the Critical Factors” [J. Electrochem. Soc., 145, 2186 (1998)]
Authors: Frankel G. S.
Published: June 2006

Abstract not Available.
Modulation of cardiac contractility by muscle metaboreflex following efforts of different intensities in humans
Authors: Crisafulli Antonio , Salis Enrico , Pittau Gianluigi , Lorrai Luigi , Tocco Filippo , Melis Franco , Pagliaro Pasquale , Concu Alberto
Published: June 2006

Accumulation of metabolic end products within skeletal muscle stimulates sensory nerves, thus evoking a pressor response termed “metaboreflex.” The aim of this study was to evaluate changes in hemodynamics occurring during metaboreflex activation obtained by postexercise muscle ischemia (PEMI) after two different exercise intensities. In twelve healthy subjects, the metaboreflex was studied with the PEMI method at the start of recovery from one leg-dynamic knee extension performed at intensities of 30% (PEMI 30%) and 70% (PEMI 70%) of the maximum workload achieved in a preliminary test. Control exercise recovery tests at the same intensities were also conducted. Central hemodynamics were evaluated by means of impedance cardiography. The main findings were that 1) during metaboreflex, exercise conducted against the higher workload caused a more pronounced blood pressure increase than the strain conducted against the lower workload; and 2) during PEMI 70%, this blood pressure response was mainly achieved through enhancement of myocardial contractility that increased stroke volume and, in turn, cardiac output, whereas during PEMI 30%, the blood pressure response was reached predominantly by means of vasoconstriction. Thus a substantial enhancement of myocardial contractility was reached only in the PEMI 70% test. These results suggest that hemodynamic regulation during metaboreflex engagement caused by PEMI in humans is dependent on the intensity of the previous effort. Moreover, the cardiovascular response during metaboreflex is not merely achieved by vasoconstriction alone, but it appears that there is a complex interplay between peripheral vasoconstriction and heart contractility recruitment.
Chronic antidiabetic and cardiovascular actions of leptin: role of CNS and increased adrenergic activity
Authors: da Silva Alexandre A. , Tallam Lakshmi S. , Liu Jiankang , Hall John E.
Published: June 2006

This study examined the importance of direct central nervous system (CNS) actions and increased adrenergic activity in mediating the chronic antidiabetic and cardiovascular actions of leptin. Insulin-deficient rats (streptozotocin, 50 mg/kg) were used to examine the effects of leptin on glucose homeostasis independent of changes in insulin. Male Sprague-Dawley rats were instrumented with arterial and venous catheters and intracerebroventricular cannula for 24-h/day blood pressure (BP) and heart rate (HR) monitoring and intravenous and intracerebroventricular infusions. Insulin-deficient diabetes was associated with marked hyperglycemia, hyperphagia, decreased BP, and pronounced fall in HR. Leptin treatment, intravenous or intracerebroventricular, completely restored to control values plasma glucose levels (384 ± 58 to 102 ± 28 and 307 ± 38 to 65 ± 7 mg/dl, respectively), food intake, BP, and HR (304 ± 8 to 364 ± 7 and 317 ± 13 to 423 ± 9 bpm, respectively). Combined blockade of α1-, β1-, and β2-adrenergic receptors attenuated the rise in HR by 30 to 50% but had no effect on the antidiabetic and dietary actions of leptin. Blockade of β3-adrenergic receptors did not attenuate the chronic cardiovascular or metabolic effects of leptin. These data demonstrate that leptin, via its direct actions in the CNS, has powerful antidiabetic actions in insulin-deficient rats independent of increased peripheral α1, β1, β2, and β3-adrenergic activity. Leptin also exerts important long-term cardiovascular actions that are partially mediated via α1- and β1/β2-adrenergic activation. These findings provide new insights into novel pathways for long-term control of glucose homeostasis and cardiovascular regulation.
Inhibited skeletal muscle healing in cyclooxygenase-2 gene-deficient mice: the role of PGE2and PGF2α
Authors: Shen Wei , Prisk Victor , Li Yong , Foster William , Huard Johnny
Published: June 2006

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat skeletal muscle injury. However, studies have shown that NSAIDs may be detrimental to the healing process. Mediated by prostaglandin F2α(PGF2α) and prostaglandin E2(PGE2), the cycloxygenase-2 (COX-2) pathway plays an important role in muscle healing. We hypothesize that the COX-2 pathway is important for the fusion of muscle cells and the regeneration of injured muscle. For the in vitro experiments, we isolated myogenic precursor cells from wild-type (Wt) and COX-2 gene-deficient (COX-2−/−) mice and examined the effect of PGE2and PGF2αon cell fusion. For the in vivo experiments, we created laceration injury on the tibialis anterior (TA) muscles of Wt and COX-2−/−mice. Five and 14 days after injury, we examined the TA muscles histologically and functionally. We found that the secondary fusion between nascent myotubes and myogenic precursor cells isolated from COX-2−/−mice was severely compromised compared with that of Wt controls but was restored by the addition of PGF2αor, to a lesser extent, PGE2to the culture. Histological and functional assessments of the TA muscles in COX-2−/−mice revealed decreased regeneration relative to that observed in the Wt mice. The findings reported here demonstrate that the COX-2 pathway plays an important role in muscle healing and that prostaglandins are key mediators of the COX-2 pathway. It suggests that the decision to use NSAIDs to treat muscle injuries warrants critical evaluation because NSAIDs might impair muscle healing by inhibiting the fusion of myogenic precursor cells.
Relative Contribution of Smoker Prototypes in Predicting Smoking among Adolescents: A Comparison with Factors from the Theory of Planned Behavior
Authors: van den Eijnden Regina J.J.M. , Spijkerman Renske , Engels Rutger C.M.E.
Published: June 2006

Background:It has frequently been suggested that adolescents are more likely to start smoking when they hold favorable social images or prototypes of smoking peers. Although empirical evidence supports the role of smoker prototypes in predicting smoking, little is known about the relative contribution of smoker prototypes, in comparison to more well-established social cognitive factors. Therefore, the present study investigated the relative impact of smoker prototypes, in comparison to factors of the theory of planned behavior, in predicting smoking among adolescents. Methods: A three-wave prospective study was conducted among 612 Dutch 8th grade students (aged 12–13 years). Questionnaires were administered and adolescents were followed during one year. Results: The results indicate that smoker prototypes are predictive of adolescent smoking behavior. Adolescents who believe that smoking peers are sociable more frequently engage in smoking behavior. Moreover, adolescents who hold the image that smoking peers are rebellious are less inclined to engage in smoking. These prototype factors predict a significant proportion of variance in smoking status, over and above the components of the theory of planned behavior. Conclusion: The findings of the present study are interesting because they suggest that intervening on the level of smoker prototypes may contribute to the effectiveness of current programs aiming at the prevention of adolescents’ smoking behavior.
Methadone Treatment in Clinical Practice in Italy: Need for Improvement
Authors: Schifano Patrizia , Bargagli Anna Maria , Belleudi Valeria , Amato Laura , Davoli Marina , Diecidue Roberto , Versino Elisabetta , Vigna-Taglianti Federica , Faggiano Fabrizio , Perucci Carlo A.
Published: June 2006

Background: Methadone at appropriate doses has been demonstrated to be the most effective means for retaining patients in treatment and suppressing heroin use. Aim: To describe the modalities of day-to-day provision of methadone maintenance treatments (MMT) in Italian public health centres and to analyze the duration of MMTs by dose and by association with psychosocial treatments. Patients and Methods: We analyzed 8,378 subjects, 18 years of age or over, enrolled between September 1998 and March 2001 in one of 115 public treatment centres for heroin dependence in Italy. Treatment data were collected for each subject from enrolment to the end of the study period (maximum of 18 months). Results: Of the total of 29,495 treatments delivered, 21.0% were methadone maintenance, and 34.4% were methadone detoxification. Fifty percent of MMTs offered had a mean dose less than or equal to 40 mg/day, and only 19% had doses higher than or equal to 60 mg/day; treatments with doses higher than 60 mg/day lasted longer than treatments with lower doses. Differences in treatment length were observed between MMTs associated with a psychosocial treatment and those offered alone, only for doses <60 mg/day. Conclusions: In Italy, MMTs are delivered at inappropriate doses in more than 80% of the cases. The increase of methadone doses to adequate levels as indicated by the literature is necessary to ensure proper and effective use of MMTs in public treatment centres for heroin users.
Socioeconomic Influences on Benzodiazepine Consumption in an Irish Region
Authors: Quigley P. , Usher C. , Bennett K. , Feely J.
Published: June 2006

Misuse of prescription sedatives is a significant problem for addiction treatment services. The aim of this study was to examine the prescribing of diazepam in disadvantaged Irish communities, and to identify factors which may predict diazepam consumption in that population. We examined prescribing trends for those aged 16–69 years in 2002 in a region of the state-funded General Medical Services Scheme. Material deprivation was based on the 2002 Small Area Health Research Unit (SAHRU) deprivation index. The average defined daily dose (DDD) was calculated and logistic regression analysis was used to predict diazepam use by age, gender and deprivation index. Results showed that patients living in the most-deprived areas were more likely to receive diazepam than patients living in the least-deprived areas (OR = 1.21, 95% CI 1.15–1.27). Female patients living in the most-deprived areas were also more likely to receive diazepam than those living in the least-deprived areas (OR = 1.36, 95% CI 1.18–1.57). It is concluded that there is a pattern of higher diazepam prescribing in areas of greatest deprivation, where prescription sedatives play a complex role within troubled families.
Transobturatorische Bänder: Besser als TVT?
Authors: Tamussino K. , Bjelic-Radisic V.
Published: June 2006

Transobturatorische suburethrale Schlingen scheinen eine Alternative zu etablierten retropubischen Verfahren darzustellen. Vergleiche sind durch die Vielzahl an Systemen erschwert. Verletzungen von Blase, Darm und grossen Gefässen scheinen mit transobturatorischen Systemen seltener als mit TVT, Banderosionen und infektiöse Komplikationen dagegen häufiger. Die Ergebnisse ausreichend grosser randomisierter Studien stehen aus.
Could Jessner’s Lymphocytic Infiltrate of the Skin Be a Dermal Variant of Lupus Erythematosus? An Analysis of 210 Cases
Authors: Lipsker Dan , Mitschler Audrey , Grosshans Edouard , Cribier Bernard
Published: June 2006

Background and Objective: The objective of this study was to evaluate the relationship between Jessner’s lymphocytic infiltration of the skin (JLI) and lupus erythematosus (LE), which has been the subject of debate since its initial description in 1953. Material and Methods: This is a retrospective study including all patients with a histopathologically ascertained diagnosis of JLI performed at the Laboratoire d’Histopathologie Cutanée of the Strasbourg University Hospital between 1993 and 2003. Information about patient characteristics and follow-up data were retrieved between 2004 and 2005. Special attention was paid to features indicative of LE. Results: 210 consecutive patients (102 women and 108 men) with a mean age 42 years were diagnosed with JLI in the reference period. 175 patients (83%) had multiple lesions and 32 patients (15%) had only a single lesion at the time of diagnosis (data not available in 3 patients). The head, neck and upper part of the thorax were involved in 171 patients (81%). An annular or arciform configuration and/or arrangement were present in 111 patients (53%). Lesions consisted of red (100%) papules or plaques (98%). Mean follow-up was 4 years. Sixteen patients (7.6%) had proven LE. Only 2 patients (1%) developed >4 ACR criteria of systemic LE. Furthermore, 1 patient had antiphospholipid antibody syndrome and 2 patients had rheumatoid arthritis. Conclusions: This high frequency of patients with typical features of LE strongly argues that JLI could be a dermal variant of LE and not an autonomous entity. It might be the cutaneous marker of a subset of LE patients with excellent prognosis.
Clinicopathological and Ultrastructural Study of Multiple Lobular Capillary Hemangioma after Scalding
Authors: Liao Wen-Jun , Fan Ping-Shen , Fu Meng , Gao Tian-Wen , Liu Yu-Feng , Ikeda Shigaku
Published: June 2006

We herein report 2 cases of multiple lobular capillary hemangiomas after scalding. The patients exhibited papules and nodules on the scalded areas after healing. Histopathological examination of the lesions showed capillary proliferation in the upper dermis with edematous stroma containing inflammatory infiltrates predominantly composed of neutrophils. Biopsy tissue and secretion specimens from lesions of case 1 were cultured for bacteria, and both grew Enterobacter cloacae. Ultrastructural examination revealed features typical of a lobular capillary hemangioma and viral inclusion bodies in the epidermis of case 1. Multiple lobular capillary hemangiomas after scalding are rarely reported. Trauma may play an important role in the development of this rare condition. Accumulation of similar cases and its precise observation is needed to confirm the associations and to establish an etiological link between the disease and the pathogens.
Oral Prednisolone Induced Acute Generalized Exanthematous Pustulosis due to Corticosteroids of Group A Confirmed by Epicutaneous Testing and Lymphocyte Transformation Tests
Authors: Buettiker U. , Keller M. , Pichler W.J. , Braathen L.R. , Yawalkar N.
Published: June 2006

Background:Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. Case Report:We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. Conclusion: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.
Associations between Delusion Proneness and Personality Structure in Non-Clinical Participants: Comparison between Young and Elderly Samples
Authors: Larøi Frank , van der Linden Martial , DeFruyt Filip , van Os Jim , Aleman André
Published: June 2006

Background: Few studies have explored the prevalence of delusions in the non-clinical, elderly population. In addition, the association between personality structure and delusions remains poorly investigated. The aims of the present study were, first, to explore the relation between age and the prevalence of delusion proneness and, second, to examine the association between personality and delusion proneness in young and elderly participants. Sampling and Methods: A sample of young (n = 343; aged 18–30 years) and elderly (n = 183; aged 60–75 years) non-clinical participants completed the 21-item version of the Peters et al. Delusions Inventory (PDI-21), an elaborated and validated version of the Launay-Slade Hallucinations Scale, and the revised version of the NEO Personality Inventory (NEO-PI-R). Results: Mean scores on the PDI-21 for the young and elderly participants were compared. An independent t test revealed that the total mean scores were significantly higher for young participants compared to elderly participants. PDI-21 items were then re-grouped into previously validated factors. Independent t tests revealed that young participants had significantly higher scores for items related to suspiciousness and persecutory ideas, thought disturbances and jealousy, grandiose ideas, paranormal beliefs and apocalyptic ideas. In contrast, elderly participants scored significantly higher than young participants on the religious ideation factor. Associations between scores on the NEO-PI-R and the PDI-21 were then examined for the two groups. For the young sample, correlational analyses revealed a significant relationship between the total score on the PDI-21 and scores on the openness, neuroticism and agreeability facets of the NEO-PI-R. For the elderly sample, correlational analyses revealed a significant relationship between the total score on the PDI-21 and the openness facet of the NEO-PI-R. Discussion: Results from the study reveal that delusional ideation is a relatively common experience for both young and elderly non-clinical participants. In addition, findings are in line with studies suggesting that neuroticism and aspects related to neuroticism increase the risk for the development of psychotic symptoms such as delusions. However, it is important to mention that, because the present study includes non-clinical subjects and is a cross-sectional study, more research is needed.
The Role of Trauma and PTSD-Related Symptoms for Dissociation and Psychopathological Distress in Inpatients with Schizophrenia
Authors: Vogel Matthias , Spitzer Carsten , Barnow Sven , Freyberger Harald J. , Grabe Hans Jörgen
Published: June 2006

Background: To investigate the relationship between dissociative experiences, psychopathological distress, a history of trauma and posttraumatic symptoms in adult schizophrenia. Methods: Eighty-seven schizophrenic inpatients returned self-questionnaires [Dissociative Experience Scale (DES); Symptom Checklist (SCL-90-R); PTSD Symptom Scale (PDS)]. Based upon this self-rating, 14 of the participants fulfilled the cut-off definition of PTSD according to DSM-IV criteria, 43 had a history of trauma without a self-rated diagnosis of PTSD. DES scores were also compared to a convenience sample of 297 non-clinical controls. Results: We found no significant impact of trauma alone but a significant influence of posttraumatic symptomatology on the level of current psychopathological distress (GSI) and the DES subscale absorption. However, in logistic regression, posttraumatic symptomatology was associated with GSI but not with DES. Schizophrenic patients even without trauma or posttraumatic symptoms had significantly higher scores in all three DES subscales than non-clinical controls. Conclusion: Pronounced posttraumatic symptoms in schizophrenia are associated with severe additional psychopathological distress whereas the increase in dissociation (absorption) in this group of patients may be secondary to the increase in symptom load. However, schizophrenia itself seems to be associated independently from trauma and pathological posttraumatic conditions with a broad range of dissociative symptoms.
Impact of Methionine Synthase Gene and Methylenetetrahydrofolate Reductase Gene Polymorphisms on the Risk of Sudden Sensorineural Hearing Loss
Authors: Gross Menachem , Friedman Gideon , Eliashar Ron , Koren-Morag Nira , Goldschmidt Neta , Atta Iman Abou , Ben-Yehuda Arie
Published: June 2006

Idiopathic sudden sensorineural hearing loss (SSNHL) represents a frequently encountered otological disease of unknown etiology. In recent years, several inherited risk factors have been found in the pathogenesis of vascular diseases. In the present study, we determined whether specific polymorphism or the combination of polymorphisms in folate-dependent homocysteine metabolism genes can act as predisposing inherited vascular risk factors in the development of SSNHL. We conducted a prospective case-control study using DNA samples extracted from 81 patients diagnosed as suffering from SSNHL and 264 healthy control subjects. Three functional polymorphisms were analyzed by polymerase chain reaction amplification, restriction enzyme digestion, and DNA fragment separation by electrophoresis: methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and methionine synthase (MTR) A2756G polymorphisms. The prevalence of the homozygous genotype of MTR 2756GG in the SSNHL patients (9%) was significantly higher than in the control group (4%) (p = 0.011). The allelic frequency of the G allele of the MTR A2756G polymorphism among SSNHL patients (12.5%) was also significantly higher than in the control group (5%) (p = 0.033). The prevalence of patients possessing two polymorphisms (31%) and three polymorphisms (17%) in the SSNHL group was significantly higher than in the control group (23 and 9%, respectively; p = 0.019). The frequency of patients with a very high rank risk (double homozygous) was significantly higher in the SSNHL group, MTHFR 677TT/MTR 2675GG – 7%, than the frequency of patients in the control group, MTHFR 677TT/MTR 2675GG – 3% (p = 0.030). Certain polymorphisms in genes encoding enzymes in the folate-dependent homocysteine metabolism are associated with SSNHL. In our case-control study, a significant association between MTR 2756GG genotype and SSNHL was found which may represent an inherited vascular risk factor in the pathogenesis of SSNHL.