bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocardial Pacing After Fontan‐Type Procedures
Authors: HANSKY BERT , BLANZ UTE , PEUSTER MATTHIAS , GUELDNER HOLGER , SANDICA EUGEN , CRESPO‐MARTINEZ EUGENIA , MATHIES WOLFGANG , MEYER HANS , KOERFER REINER
Published: January 2005

Background: Sinus node dysfunction is a frequent complication of Fontan‐type procedure. Epicardial pacing is considered as the standard treatment for these patients.

Methods and Results: We evaluated an endocardial approach in seven patients using a 4.1 French bipolar lumenless lead (SelectSecure) that is positioned through a steerable guiding catheter. Either a purely transvenous or an open transatrial approach can be used for lead placement. The smallest child weighed 12 kg. Individual anatomy was assessed preimplantation using magnetic resonance imaging and injection of radiographic contrast agent through the guiding catheter. A pullback pressure recording was used to confirm unimpaired blood flow into the pulmonary artery. Five of our seven patients underwent de novo transvenous atrial lead implantation for AAIR pacing. In the remaining two patients, both atrial and ventricular leads were inserted. One patient with an intraatrial tunnel underwent transvenous‐lead placement. The remaining patient with an extracardiac conduit received atrial and ventricular leads implanted through a guiding catheter inserted through an atriotomy. The postoperative management included short‐ or long‐term oral anticoagulation.

Conclusions: Transvenous endocardial lead implantation avoids the problem of increasing capture thresholds typically observed with epicardial leads. Due to its high tensile strength and lumenless design, the isodiametric lead is expected to remain extractable for an extended period of time.
Double Wire Technique to Catheterize Sharply Angulated Coronary Sinus Branches in Cardiac Resynchronization Therapy
Authors: CHIERCHIA GIAN‐BATTISTA , GEELEN PETER , RIVERO‐AYERZA MAXIMO , BRUGADA PEDRO
Published: January 2005

Placing a pacing lead for left ventricular pacing through the coronary sinus can be hampered by anatomic obstacles. In this case report we describe a technique that can overcome the problem of sharply angulated coronary sinus branches by using simultaneously two guidewires in the target vessel.
Acute and Long‐Term Results of Slow Pathway Ablation in Patients with Atrioventricular Nodal Reentrant Tachycardia—An Analysis of the Predictive Factors for Arrhythmia Recurrence
Authors: ESTNER HEIDI LUISE , NDREPEPA GJIN , DONG JUN , DEISENHOFER ISABEL , SCHREIECK JUERGEN , SCHNEIDER MICHAEL , PLEWAN ANDREAS , KARCH MARTIN , WEYERBROCK SONJA , WADE DIANA , ZRENNER BERNHARD , SCHMITT CLAUS
Published: January 2005

Backqround: Predictors of atrioventricular nodal reentrant tachycardia (AVNRT) recurrence after radiofrequency ablation including the importance of residual slow pathway conduction are not known. The aim of this study was to report the acute and long‐term results of slow pathway ablation in a large series of consecutive patients with AVNRT and to analyze the potential predictors of arrhythmia recurrence with a particular emphasis on the residual slow pathway conduction after ablation.

Methods: The study included 506 consecutive patients with AVNRT (mean age 52.6 ± 16 years, 315 women) who underwent slow pathway ablation using a combined electrophysiological and anatomical approach. The end point of ablation procedure was noninducibility of the arrhythmia. The primary end point of the study was the recurrence of AVNRT.

Results: Acute success was achieved in 500 patients (98.8%). After ablation, 471 patients (93%) were followed up for a mean of 903 ± 692 days. Of the 465 patients with successful ablation, 24 patients (5.2%) developed AVNRT recurrences during the follow‐up. No significant differences in the cumulative rates of AVNRT recurrence were observed in groups with or without electrophysiological evidence of residual slow pathway conduction (P = 0.25, log‐rank test). Multivariate analysis identified only age as an independent predictor of AVNRT recurrence (hazard ratio 0.96, 95% confidence interval 0.94–0.99, P = 0.004) with younger patients being at an increased risk for arrhythmia recurrence.

Conclusions: Our study demonstrated that only younger age, but not other clinical or electrophysiological parameters including residual slow pathway conduction predicted an increased risk for AVNRT recurrence after slow pathway radiofrequency ablation.
Radiofrequency Catheter Ablation of a Coronary Sinus‐Ventricular Accessory Connection in Dextrocardia with Complete Situs Inversus and an Anomalous Inferior Vena Cava
Authors: TANIGUCHI HIROSHI , MIYAUCHI YASUSHI , KOBAYASHI YOSHINORI , HIRASAWA YASUHIRO , HOSAKA HIROKI , IWASAKI YU‐KI , KATOH TAKAO , TAKANO TERUO
Published: January 2005

An anomalous inferior vena cava (IVC) is often associated with patients with dextrocardia. However, radiofrequency catheter ablation in such a case with that combination has not been reported. We encountered a case of Wolff‐Parkinson‐White syndrome with dextrocardia associated with complete situs inversus and an azygos continuation of the IVC. A steep angulation at the junction of the azygos vein and superior vena cava precluded the precise mapping of the anatomical right cavity with a femoral vein approach. Successful catheter ablation of an accessory connection between the coronary sinus and left ventricle could be achieved with a right cubital vein approach.
Muscular mechanical hyperalgesia revealed by behavioural pain test and c‐Fos expression in the spinal dorsal horn after eccentric contraction in rats
Authors: Taguchi Toru , Matsuda Teru , Tamura Ryoko , Sato Jun , Mizumura Kazue
Published: January 2005

Delayed onset muscle soreness (DOMS) is quite common, but the mechanism for this phenomenon is still not understood; even the existence of muscle tenderness (mechanical hyperalgesia) has not been demonstrated in experimental models. We developed an animal model of DOMS by inducing eccentric contraction (lengthening contraction, ECC) to the extensor digitorum longus muscle (EDL), and investigated the existence of mechanical hyperalgesia in the EDL by means of behavioural pain tests (Randall‐Selitto test and von Frey hair test, applied to/through the skin on the EDL muscle) and c‐Fos expression in the spinal dorsal horn. We found that the mechanical withdrawal threshold measured with the Randall‐Selitto apparatus decreased significantly between 1 and 3 days after ECC, while that measured by von Frey hairs did not. The group that underwent stretching of the muscle only (SHAM group) showed no change in mechanical pain threshold in either test. These results demonstrated that the pain threshold of deep tissues (possibly of the muscle) decreased after ECC. c‐Fos immunoreactivity in the dorsal horn (examined 2 days after ECC/SHAM exercise) was not changed by either ECC or compression (1568 mN) to the EDL muscle by itself, but it was significantly increased by applying compression to the EDL muscle 2 days after ECC. This increase was observed in the superficial dorsal horn of the L4 segment of the ipsilateral side, and was clearly suppressed by morphine treatment (10 mg kg−1, i.p.). These results demonstrated the existence of mechanical hyperalgesia in the muscle subjected to ECC. This model could be used for future study of the neural mechanism of muscle soreness.
Short openings in high resolution single channel recordings of mouse nicotinic receptors
Authors: Hallermann Stefan , Heckmann Sabine , Dudel Josef , Heckmann Manfred
Published: January 2005

The temporal fine structure of single channel currents was studied to obtain information on how agonists open nicotinic acetylcholine receptor channels. Currents were recorded from mouse myoballs with quartz pipettes in the on‐cell mode of the patch‐clamp technique. With 62 kHz filter cut‐off and root mean square (r.m.s.) noise levels as low as 1.45 pA at 200 mV hyperpolarization, events down to 6 μs duration could be resolved with negligible error rate. Three types of openings with mean durations of 750 μs, 89 μs and 4 μs were identified with 0.1–10 μm suberyldicholine (SubCh). The relative frequencies of the three types of openings were 84% for long, 5% for medium and 11% for short openings with 1 μm SubCh. Stability plots and single channel current amplitude comparisons suggest that the three types of openings arise from a homogenous channel population. Above 10 μm SubCh, the three types of openings could not be discerned because channel openings occurred too closely spaced and open channels were increasingly blocked. Three types of openings can be generated with a mechanistic receptor model with two unequal binding sites, short and medium openings arising from one or the other monoliganded state, and long openings from the fully liganded state of the receptor. Maximum likelihood fitting of the rate constants of this model directly to the sequence of observed open and shut times accurately predicted the main physiological properties of the receptors with 0.1 μm SubCh. However, fitting recordings with 0.1–10 μm SubCh simultaneously revealed that this model cannot reproduce the weak influence of SubCh concentration on the proportions of the three types of openings. Therefore we conclude that short and medium openings are unlikely to arise preferentially from one or the other monoliganded state of nicotinic acetylcholine receptor channels.
Fast erg K+ currents in rat embryonic serotonergic neurones
Authors: Hirdes Wiebke , Schweizer Michaela , Schuricht Kristina S. , Guddat Saskia S. , Wulfsen Iris , Bauer Christiane K. , Schwarz Jürgen R.
Published: January 2005

Ether‐à‐go‐go‐related gene (erg) channels form one subfamily of the ether‐à‐go‐go (EAG) K+ channels and all three erg channels (erg1–3) are expressed in the brain. In the present study we characterize a fast erg current in neurones in primary culture derived from the median part of rat embryonic rhombencephala (E15–16). The relatively uniform erg current was regularly found in large multipolar serotonergic neurones, and occurred also in other less well characterized neurones. The erg current was blocked by the antiarrhythmic substance E‐4031. Single‐cell RT‐PCR revealed the expression of erg1a, erg1b, erg2 and erg3 mRNA in different combinations in large multipolar neurones. These cells also contained neuronal tryptophan hydroxylase, a key enzyme for serotonin production. To characterize the molecular properties of the channels mediating the native erg current, we compared the voltage and time dependence of activation and deactivation of the neuronal erg current to erg1a, erg1b, erg2 and erg3 currents heterologously expressed in CHO cells. The biophysical properties of the neuronal erg current were well within the range displayed by the different heterologously expressed erg currents. Activation and deactivation kinetics of the neuronal erg current were fast and resembled those of erg3 currents. Our data suggest that the erg channels in rat embryonic rhombencephalon neurones are heteromultimers formed by different erg channel subunits.
Control of Excitatory and Inhibitory Synapse Formation by Neuroligins
Authors: Chih Ben , Engelman Holly , Scheiffele Peter
Published: January 2005

The normal function of neural networks depends on a delicate balance between excitatory and inhibitory synaptic inputs. Synapse formation is thought to be regulated by bidirectional signaling between pre- and postsynaptic cells. We demonstrate that members of the Neuroligin family promote postsynaptic differentiation in cultured rat hippocampal neurons. Down-regulation of neuroligin isoform expression by RNA interference results in a loss of excitatory and inhibitory synapses. Electrophysiological analysis revealed a predominant reduction of inhibitory synaptic function. Thus, neuroligins control the formation and functional balance of excitatory and inhibitory synapses in hippocampal neurons.
Demanding pure motives for donation: the moral acceptability of blood donations by haemochromatosis patients
Authors: Pennings G
Published: January 2005

Blood banks all over the world attempt to cover the demand for blood by donations from voluntary non-remunerated donors. The discussion regarding the acceptability of blood donations by haemochromatosis patients focuses on the question of whether health benefits violate the rule of the altruistic donor. Utilitarian and deontological arguments for and against the policy of accepting blood donors who need to let blood regularly in order to stay healthy are considered by this article. A closer look at the procedure reveals that the confusion is due to the conflation of, on the one hand the phlebotomy, and on the other hand, the decision about the destination of the blood afterwards. The health benefits are connected to the phlebotomy and not to the donation. The morally relevant point in the decision as to whether the candidate is a truly altruistic donor is whether he donates without asking for a benefit in return. It is concluded that haemochromatosis patients can be free, voluntary, and altruistic blood donors.
What makes a good GP? An empirical perspective on virtue in general practice
Authors: Braunack-Mayer A
Published: January 2005

This paper takes a virtuist approach to medical ethics to explore, from an empirical angle, ideas about settled ways of living a good life. Qualitative research methods were used to analyse the ways in which a group of 15 general practitioners (GPs) articulated notions of good doctoring and the virtues in their work. I argue that the GPs, whose talk is analysed here, defined good general practice in terms of the ideals of accessibility, comprehensiveness, and continuity. They regarded these ideals significant both for the way they dealt with morally problematic situations and for how they conducted their professional lives more generally. In addition, I argue that the GPs who articulated these ideals most clearly were able to, in part, because they shared the experience of working in rural areas. This experience helped them to develop an understanding of the nature of general practice that their urban colleagues were less able to draw on. In that sense, the structural and organisational framework of general practice in rural areas provided the context for their understanding of ideals in general practice.
Subtracting insult from injury: addressing cultural expectations in the disclosure of medical error
Authors: Berlinger N , Wu A W
Published: January 2005

This article proposes that knowledge of cultural expectations concerning ethical responses to unintentional harm can help students and physicians better to understand patients’ distress when physicians fail to disclose, apologise for, and make amends for harmful medical errors. While not universal, the Judeo-Christian traditions of confession, repentance, and forgiveness inform the cultural expectations of many individuals within secular western societies. Physicians’ professional obligations concerning truth telling reflect these expectations and are inclusive of the disclosure of medical error, while physicians may express a need for self-forgiveness after making errors and should be aware that patients may also rely upon forgiveness as a means of dealing with harm. The article recommends that learning how to disclose errors, apologise to injured patients, ensure that these patients’ needs are met, and confront the emotional dimensions of one’s own mistakes should be part of medical education and reinforced by the conduct of senior physicians.
Passive euthanasia
Authors: Garrard E , Wilkinson S
Published: January 2005

The idea of passive euthanasia has recently been attacked in a particularly clear and explicit way by an “Ethics Task Force” established by the European Association of Palliative Care (EAPC) in February 2001. It claims that the expression “passive euthanasia” is a contradiction in terms and hence that there can be no such thing. This paper critically assesses the main arguments for the Task Force’s view. Three arguments are considered. Firstly, an argument based on the (supposed) wrongness of euthanasia and the (supposed) permissibility of what is often called passive euthanasia. Secondly, the claim that passive euthanasia (so-called) cannot really be euthanasia because it does not cause death. And finally, a consequence based argument which appeals to the (alleged) bad consequences of accepting the category of passive euthanasia.

We conclude that although healthcare professionals’ nervousness about the concept of passive euthanasia is understandable, there is really no reason to abandon the category provided that it is properly and narrowly understand and provided that “euthanasia reasons” for withdrawing or withholding life-prolonging treatment are carefully distinguished from other reasons.
“Idiots, infants, and the insane”: mental illness and legal incompetence
Authors: Szasz T
Published: January 2005

Prior to the second world war, most persons confined in insane asylums were regarded as legally incompetent and had guardians appointed for them. Today, most persons confined in mental hospitals (or treated involuntarily, committed to outpatient treatment) are, in law, competent; nevertheless, in fact, they are treated as if they were incompetent. Should the goal of mental health policy be providing better psychiatric services to more and more people, or the reduction and ultimate elimination of the number of persons in the population treated as mentally ill?
TEXT-INDEPENDENT SPEAKER VERIFICATION USING MINIMAL RESOURCE ALLOCATION NETWORKS
Authors: GUOJIE LI , SARATCHANDRAN P. , SUNDARARAJAN N.
Published: January 2005

This paper presents a text-independent speaker verification system based on an online Radial Basis Function (RBF) network referred to as Minimal Resource Allocation Network (MRAN). MRAN is a sequential learning RBF, in which hidden neurons are added or removed as training progresses. LP-derived cepstral coefficients are used as feature vectors during training and verification phases. The performance of MRAN is compared with other well-known RBF and Elliptical Basis Function (EBF) based speaker verification methods in terms of error rates and computational complexity on a series of speaker verification experiments. The experiments use data from 258 speakers from the phonetically balancedcontinuous speech corpus TIMIT. The results show that MRAN produces comparable error rates to other methods with much less computational complexity.
ON THE STRUCTURE AND INITIAL PARAMETER IDENTIFICATION OF GAUSSIAN RBF NETWORKS
Authors: BHATT RAJEN B. , GOPAL M.
Published: January 2005

We consider the efficient initialization of structure and parameters of generalized Gaussian radial basis function (RBF) networks using fuzzy decision trees generated by fuzzy ID3 like induction algorithms. The initialization scheme is based on the proposed functional equivalence property of fuzzy decision trees and generalized Gaussian RBF networks. The resulting RBF network is compact, easy to induce, comprehensible, and has acceptable classification accuracy with stochastic gradient descent learning algorithm.
UNSUPERVISED FUZZY CLUSTERING USING WEIGHTED INCREMENTAL NEURAL NETWORKS
Authors: MUHAMMED HAMED HAMID
Published: January 2005

A new more efficient variant of a recently developed algorithm for unsupervised fuzzy clustering is introduced. A Weighted Incremental Neural Network (WINN) is introduced and used for this purpose. The new approach is called FC-WINN (Fuzzy Clustering using WINN). The WINN algorithm produces a net of nodes connected by edges, which reflects and preserves the topology of the input data set. Additional weights, which are proportional to the local densities in input space, are associated with the resulting nodes and edges to store useful information about the topological relations in the given input data set. A fuzziness factor, proportional to the connectedness of the net, is introduced in the system. A watershed-like procedure is used to cluster the resulting net. The number of the resulting clusters is determined by this procedure. Only two parameters must be chosen by the user for the FC-WINN algorithm to determine the resolution and the connectedness of the net. Other parameters that must be specified are those which are necessary for the used incremental neural network, which is a modified version of the Growing Neural Gas algorithm (GNG). The FC-WINN algorithm is computationally efficient when compared to other approaches for clustering large high-dimensional data sets.
AN IMPROVED TRANSIENTLY CHAOTIC NEURAL NETWORK FOR THE MAXIMUM INDEPENDENT SET PROBLEM
Authors: XU XINSHUN , TANG ZHENG , WANG JIAHAI
Published: January 2005

By analyzing the dynamic behaviors of the transiently chaotic neural network and greedy heuristic for the maximum independent set (MIS) problem, we present an improved transiently chaotic neural network for the MIS problem in this paper. Extensive simulations are performed and the results show that this proposed transiently chaotic neural network can yield better solutions to p-random graphs than other existing algorithms. The efficiency of the new model is also confirmed by the results on the complement graphs of some DIMACS clique instances in the second DIMACS challenge. Moreover, the improved model uses fewer steps to converge to stable state in comparison with the original transiently chaotic neural network.
STEP TO IMPROVE NEURAL CRYPTOGRAPHY AGAINST FLIPPING ATTACKS
Authors: ZHOU JIANTAO , XU QINZHEN , PEI WENJIANG , HE ZHENYA , SZU HAROLD
Published: January 2005

Synchronization of neural networks by mutual learning has been demonstrated to be possible for constructing key exchange protocol over public channel. However, the neural cryptography schemes presented so far are not the securest under regular flipping attack (RFA) and are completely insecure under majority flipping attack (MFA). We propose a scheme by splitting the mutual information and the training process to improve the security of neural cryptosystem against flipping attacks. Both analytical and simulation results show that the success probability of RFA on the proposed scheme can be decreased to the level of brute force attack (BFA) and the success probability of MFA still decays exponentially with the weights' level L. The synchronization time of the parties also remains polynomial with L. Moreover, we analyze the security under an advanced flipping attack.
THE CARDIAC FIBROBLAST: Therapeutic Target in Myocardial Remodeling and Failure
Authors: Brown R. Dale , Ambler S. Kelly , Mitchell M. Darren , Long Carlin S.
Published: January 2005

▪ Abstract  Cardiac fibroblasts play a central role in the maintenance of extracellular matrix in the normal heart and as mediators of inflammatory and fibrotic myocardial remodeling in the injured and failing heart. In this review, we evaluate the cardiac fibroblast as a therapeutic target in heart disease. Unique features of cardiac fibroblast cell biology are discussed in relation to normal and pathophysiological cardiac function. The contribution of cardiac fibrosis as an independent risk factor in the outcome of heart failure is considered. Candidate drug therapies that derive benefit from actions on cardiac fibroblasts are summarized, including inhibitors of angiotensin-aldosterone systems, endothelin receptor antagonists, statins, anticytokine therapies, matrix metalloproteinase inhibitors, and novel antifibrotic/anti-inflammatory agents. These findings point the way to future challenges in cardiac fibroblast biology and pharmacotherapy.
CLINICAL AND TOXICOLOGICAL RELEVANCE OF CYP2C9: Drug-Drug Interactions and Pharmacogenetics
Authors: Rettie Allan E. , Jones Jeffrey P.
Published: January 2005

▪ Abstract  CYP2C9 is a major cytochrome P450 enzyme that is involved in the metabolic clearance of a wide variety of therapeutic agents, including nonsteroidal antiinflammatories, oral anticoagulants, and oral hypoglycemics. Disruption of CYP2C9 activity by metabolic inhibition or pharmacogenetic variability underlies many of the adverse drug reactions that are associated with the enzyme. CYP2C9 is also the first human P450 to be crystallized, and the structural basis for its substrate and inhibitor selectivity is becoming increasingly clear. New, ultrapotent inhibitors of CYP2C9 have been synthesised that aid in the development of quantitative structure-activity relationship (QSAR) models to facilitate drug redesign, and extensive resequencing of the gene and studies of its regulation will undoubtedly help us understand interindividual variability in drug response and toxicity controlled by this enzyme.
GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats
Authors: Qin Xiaofa , Shen Hui , Liu Min , Yang Qing , Zheng Shuqin , Sabo Mary , D'Alessio David A. , Tso Patrick
Published: January 2005

Glucagon-like peptide 1 (GLP-1) is a gastrointestinal hormone secreted in response to meal ingestion by enteroendocrine L cells located predominantly in the lower small intestine and large intestine. GLP-1 inhibits the secretion and motility of the upper gut and has been suggested to play a role in the “ileal brake.” In this study, we investigated the effect of recombinant GLP-1-(7–36) amide (rGLP-1) on lipid absorption in the small intestine in intestinal lymph duct-cannulated rats. In addition, the effects of rGLP-1 on intestinal production of apolipoprotein (apo) B and apo A-IV, two apolipoproteins closely related to lipid absorption, were evaluated. rGLP-1 was infused through the jugular vein, and lipids were infused simultaneously through a duodenal cannula. Our results showed that infusion of rGLP-1 at 20 pmol·kg−1·min−1caused a dramatic and prompt decrease in lymph flow from 2.22 ± 0.15 (SE) ml/h at baseline ( n = 6) to 1.24 ± 0.06 ml/h at 2 h ( P < 0.001). In contrast, a significant increase in lymph flow was observed in the saline (control) group: 2.19 ± 0.20 and 3.48 ± 0.09 ml/h at baseline and at 6 h of lipid infusion, respectively ( P < 0.001). rGLP-1 also inhibited intestinal triolein absorption ( P < 0.05) and lymphatic apo B and apo A-IV output ( P < 0.05) but did not affect cholesterol absorption. In conclusion, rGLP-1 dramatically decreases intestinal lymph flow and reduces triglyceride absorption and apo B and apo A-IV production. These findings suggest a novel role for GLP-1 in lipid absorption.
Role of short-chain fatty acids in colonic HCO3secretion
Authors: Vidyasagar Sadasivan , Barmeyer Christian , Geibel John , Binder Henry J. , Rajendran Vazhaikkurichi M.
Published: January 2005

Luminal isobutyrate, a relatively poor metabolized short-chain fatty acid (SCFA), induces HCO3secretion via a Cl-independent, DIDS-insensitive, carrier-mediated process as well as inhibiting both Cl-dependent and cAMP-induced HCO3secretion. The mechanism(s) responsible for these processes have not been well characterized. HCO3secretion was measured in isolated colonic mucosa mounted in Lucite chambers using pH stat technique and during microperfusion of isolated colonic crypts.14C-labeled butyrate,14C-labeled isobutyrate, and36Cl uptake were also determined by apical membrane vesicles (AMV) isolated from surface and/or crypt cells. Butyrate stimulation of Cl-independent, DIDS-insensitive 5-nitro-3-(3-phenylpropyl-amino)benzoic acid-insensitive HCO3secretion is greater than that by isobutyrate, suggesting that both SCFA transport and metabolism are critical for HCO3secretion. Both lumen and serosal 25 mM butyrate inhibit cAMP-induced HCO3secretion to a comparable degree (98 vs. 90%). In contrast, Cl-dependent HCO3secretion is downregulated by lumen 25 mM butyrate considerably more than by serosal butyrate (98 vs. 37%). Butyrate did not induce HCO3secretion in isolated microperfused crypts, whereas an outward-directed HCO3gradient-driven induced14C-butyrate uptake by surface but not crypt cell AMV. Both36Cl/HCO3exchange and potential-dependent36Cl movement in AMV were inhibited by 96–98% by 20 mM butyrate. We conclude that 1) SCFA-dependent HCO3secretion is the result of SCFA transport across the apical membrane via a SCFA/HCO3exchange more than intracellular SCFA metabolism; 2) SCFA-dependent HCO3secretion is most likely a result of an apical membrane SCFA/HCO3exchange in surface epithelial cells; 3) SCFA downregulates Cl-dependent and cAMP-induced HCO3secretion secondary to SCFA inhibition of apical membrane Cl/HCO3exchange and anion channel activity, respectively.
Cutaneous warming promotes sleep onset
Authors: Raymann Roy J. E. M. , Swaab Dick F. , Van Someren Eus J. W.
Published: January 2005

Sleep occurs in close relation to changes in body temperature. Both the monophasic sleep period in humans and the polyphasic sleep periods in rodents tend to be initiated when core body temperature is declining. This decline is mainly due to an increase in skin blood flow and consequently skin warming and heat loss. We have proposed that these intrinsically occurring changes in core and skin temperatures could modulate neuronal activity in sleep-regulating brain areas (Van Someren EJW, Chronobiol Int 17: 313–54, 2000). We here provide results compatible with this hypothesis. We obtained 144 sleep-onset latencies while directly manipulating core and skin temperatures within the comfortable range in eight healthy subjects under controlled conditions. The induction of a proximal skin temperature difference of only 0.78 ± 0.03°C (mean ± SE) around a mean of 35.13 ± 0.11°C changed sleep-onset latency by 26%, i.e., by 3.09 minutes [95% confidence interval (CI), 1.91 to 4.28] around a mean of 11.85 min (CI, 9.74 to 14.41), with faster sleep onsets when the proximal skin was warmed. The reduction in sleep-onset latency occurred despite a small but significant decrease in subjective comfort during proximal skin warming. The induction of changes in core temperature (δ = 0.20 ± 0.02°C) and distal skin temperature (δ = 0.74 ± 0.05°C) were ineffective. Previous studies have demonstrated correlations between skin temperature and sleep-onset latency. Also, sleep disruption by ambient temperatures that activate thermoregulatory defense mechanisms has been shown. The present study is the first to experimentally demonstrate a causal contribution to sleep-onset latency of skin temperature manipulations within the normal nocturnal fluctuation range. Circadian and sleep-appetitive behavior-induced variations in skin temperature might act as an input signal to sleep-regulating systems.
Time-dependent modulation of carotid body afferent activity during and after intermittent hypoxia
Authors: Cummings Kevin J. , Wilson Richard J. A.
Published: January 2005

The ventilatory response to several minutes of hypoxia consists of various time-dependent phenomena, some of which occur during hypoxia (e.g., short-term depression), whereas others appear on return to normoxia (e.g., posthypoxic frequency decline). Additional phenomena can be elicited by acute, intermittent hypoxia (e.g., progressive augmentation, long-term facilitation). Current data suggest that these phenomena originate centrally. We tested the hypothesis that carotid body afferent activity undergoes time-dependent modulation, consistent with a direct role in these ventilatory phenomena. Using an in vitro rat carotid body preparation, we found that 1) afferent activity declined during the first 5 min of severe (40 Torr Po2), moderate (60 Torr Po2), or mild (80 Torr Po2) hypoxia; 2) after return to normoxia (100 Torr Po2) and after several minutes of moderate or severe hypoxia, afferent activity was transiently reduced compared with prehypoxic levels; and 3) with successive 5-min bouts of mild, moderate, or severe hypoxia, afferent activity during bouts increased progressively. We call these phenomena sensory hypoxic decline, sensory posthypoxic decline, and sensory progressive augmentation, respectively. These phenomena were stimulus specific: similar phenomena were not seen with 5-min bouts of normoxic hypercapnia (100 Torr Po2 and 50–60 Torr Pco2) or hypoxic hypocapnia (60 Torr Po2 and 30 Torr Pco2). However, bouts of either normoxic hypercapnia or hypocapnic hypoxia resulted in sensory long-term facilitation. We suggest time-dependent carotid body activity acts in parallel with central mechanisms to shape the dynamics of ventilatory responses to respiratory chemostimuli.
Dorsomedial hypothalamic corticotropin-releasing factor mediation of exercise-induced anorexia
Authors: Kawaguchi Maiko , Scott Karen A. , Moran Timothy H. , Bi Sheng
Published: January 2005

Running wheel access and resulting voluntary exercise alter food intake and reduce body weight. The neural mechanisms underlying these effects are unclear. In this study, we first assessed the effects of 7 days of running wheel access on food intake, body weight, and hypothalamic gene expression. We demonstrate that running wheel access significantly decreases food intake and body weight and results in a significant elevation of CRF mRNA expression in the dorsomedial hypothalamus (DMH) but not the paraventricular nucleus. Seven-day running wheel access also results in elevated arcuate nucleus and DMH neuropeptide Y gene expression. To assess a potential role for elevated DMH CRF activity in the activity-induced changes in food intake and body weight, we compared changes in food intake, body weight, and hypothalamic gene expression in rats receiving intracerebroventricular (ICV) CRF antagonist α-helical CRF or vehicle with or without access to running wheels. During a 4-day period of running wheel access, we found that exercise-induced reductions of food intake and body weight were significantly attenuated by ICV injection of the CRF antagonist. The effect on food intake was specific to a blockade of activity-induced changes in meal size. Central CRF antagonist injection further increased DMH CRF mRNA expression in exercised rats. Together, these data suggest that DMH CRF play a critical role in the anorexia resulting from increased voluntary exercise.
Cerebral and systemic hemodynamic changes during cognitive and motor activation paradigms
Authors: Moody Michelle , Panerai Ronney B. , Eames Penelope J. , Potter John F.
Published: January 2005

Cognitive and/or sensorimotor stimulations of the brain induce increases in cerebral blood flow that are usually associated with increased metabolic demand. We tested the hypothesis that changes in arterial blood pressure (ABP) and arterial Pco2 also take place during brain activation protocols designed to induce hemispheric lateralization, leading to a pressure-autoregulatory response in addition to the metabolic-driven changes usually assumed by brain stimulation paradigms. Continuous recordings of cerebral blood flow velocity [CBFV; bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal Pco2 (PetCO2) were performed in 15 right-handed healthy subjects (aged 21–43 yr), in the seated position, at rest and during 10 repeated presentations of a word generation and a constructional puzzle paradigm that are known to induce differential cortical activation. Derived variables included heart rate, cerebrovascular resistance, critical closing pressure, resistance area product, and the difference between the right and left MCA recordings (CBFVR-L). No adaptation of the CBFVR-L difference was detected for the repeated presentation of 10 activation tasks, for either paradigm. During activation with the word generation tasks, CBFV changed by (mean ± SD) 9.0 ± 3.7% (right MCA, P = 0.0007) and by 12.3 ± 7.6% (left MCA, P = 0.0007), ABP by 7.7 ± 6.0 mmHg ( P = 0.0007), heart rate by 7.1 ± 5.3 beats/min ( P = 0.0008), and PetCO2 by −2.32 ± 2.23 Torr ( P = 0.002). For the puzzle paradigm, CBFV changed by 13.9 ± 6.6% (right MCA, P = 0.0007) and by 11.5 ± 6.2% (left MCA, P = 0.0007), ABP by 7.1 ± 8.4 mmHg ( P = 0.0054), heart rate by 7.9 ± 4.6 beats/min ( P = 0.0008), and PetCO2 by −2.42 ± 2.59 Torr ( P = 0.001). The word paradigm led to greater left hemispheric dominance than the right hemispheric dominance observed with the puzzle paradigm ( P = 0.004). We concluded that significant changes in ABP and PetCO2 levels occur during brain activation protocols, and these contribute to the evoked change in CBFV. A pressure-autoregulatory response can be observed in addition to the hemodynamic changes induced by increases in metabolic demand. Simultaneous changes in Pco2 and heart rate add to the complexity of the response, indicating the need for more detailed modeling and better understanding of brain activation paradigms.
TNF-α, but not IL-6, stimulates plasminogen activator inhibitor-1 expression in human subcutaneous adipose tissue
Authors: Plomgaard Peter , Keller Pernille , Keller Charlotte , Pedersen Bente Klarlund
Published: January 2005

Plasminogen activator inhibitor-1 (PAI-1) is produced by adipose tissue, and elevated PAI-1 levels in plasma are a risk factor in the metabolic syndrome. We investigated the regulatory effects of TNF-α and IL-6 on PAI-1 gene induction in human adipose tissue. Twenty healthy men underwent a 3-h infusion of either recombinant human TNF-α ( n = 8), recombinant human IL-6 ( n = 6), or vehicle ( n = 6). Biopsies were obtained from the subcutaneous abdominal adipose tissue at preinfusion, at 1, 2, and 3 h during the infusion, and at 2 h after the infusion. The mRNA expression of PAI-1 in the adipose tissue was measured using real-time PCR. The plasma levels of TNF-α and IL-6 reached 18 and 99 pg/ml, respectively, during the infusions. During the TNF-α infusion, adipose PAI-1 mRNA expression increased 2.5-fold at 1 h, 6-fold at 2 h, 9-fold at 3 h, and declined to 2-fold 2 h after the infusion stopped but did not change during IL-6 infusion and vehicle. These data demonstrate that TNF-α rather than IL-6 stimulates an increase in PAI-1 mRNA in the subcutaneous adipose tissue, suggesting that TNF-α may be involved in the pathogenesis of related metabolic disorders.
Endothelial function of young healthy males following whole body resistance training
Authors: Rakobowchuk M. , McGowan C. L. , de Groot P. C. , Hartman J. W. , Phillips S. M. , MacDonald M. J.
Published: January 2005

Given the increasing emphasis on performance of resistance exercise as an essential component of health, we evaluated, using a prospective longitudinal design, the potential for resistance training to affect arterial endothelial function. Twenty-eight men (23 ± 3.9 yr old; mean ± SE) engaged in 12 wk of whole body resistance training five times per week using a repeating split-body 3-day cycle. Brachial endothelial function was measured using occlusion cuff-induced flow-mediated dilation. After occlusion of the forearm for 4.5 min, brachial artery dilation and postocclusion blood flow was measured continuously for 15 and 70 s, respectively. Peak and 10-s postocclusion blood flow, shear rate, and brachial artery flow-mediated dilation (relative and normalized to shear rate) were measured pretraining (Pre), at 6 wk of training (Mid), and at 13 wk of training (Post). Results indicated an increase of mean brachial artery diameter by Mid and Post vs. Pre. Peak and 10-s postocclusion blood flow increased by Mid and remained elevated at Post; however, shear rates were not different at any time point. Relative and normalized flow-mediated dilation was also not different at any time point. This study is the first to show that peripheral arterial remodeling does occur with resistance training in healthy young men. In addition, the increase in postocclusion blood flow may indicate improved resistance vessel function. However, unlike studies involving endurance training, flow-mediated dilation did not increase with resistance training. Thus arterial adaptations with high-pressure loads, such as those experienced during resistance exercise, may be quite different compared with endurance training.
Rosuvastatin, but not Simvastatin, Provides End-Organ Protection in Stroke-Prone Rats by Antiinflammatory Effects
Authors: Sironi Luigi , Gianazza Elisabetta , Gelosa Paolo , Guerrini Uliano , Nobili Elena , Gianella Anita , Cremonesi Benedetta , Paoletti Rodolfo , Tremoli Elena
Published: January 2005

Objective—Brain abnormalities, preceded by a systemic inflammation, develop in spontaneously hypertensive stroke-prone rats (SHRSP). In this model, we investigated whether the hydrophilic statin, rosuvastatin, influences the development of inflammation associated with brain abnormalities. Because differences in hydrophilicity/hydrophobicity contribute to the differences in statin pharmacology, we also evaluated the effects of simvastatin, a lipophilic molecule

Methods and Results—SHRSP, fed a high-salt diet, were treated long-term with vehicle or rosuvastatin (1 and 10 mg/kg per day). Brain abnormalities developed after 40±5 days and after 60±5 days of salt loading, in vehicle-treated and in rosuvastatin-treated (1 mg/kg per day) SHRSP, respectively. After 100 days of treatment, no damage was detectable in 30% of the rats treated with the highest dose of the drug. In comparison with vehicle-treated SHRSP, rosuvastatin treatment attenuated the transcription of monocyte chemoattractant protein-1, transforming growth factor-β1, IL-1β, and tumor necrosis factor-α in the kidney, and of P-selectin in brain vessels and increased the transcription of endothelial nitric oxide synthase mRNA in the aorta. Urinary excretion of acute-phase proteins increased with time in vehicle-treated animals but remained negligible in drug-treated animals. These effects are independent of changes in physiological parameters. Treatment of SHRSP with simvastatin (2 to 20 mg/kg per day) did not exert any protective effect.

Conclusions—Rosuvastatin attenuates inflammatory processes associated with cerebrovascular disease.
Adverse Associations Between CX3CR1 Polymorphisms and Risk of Cardiovascular or Cerebrovascular Disease
Authors: Lavergne Elise , Labreuche Julien , Daoudi Mehdi , Debré Patrice , Cambien François , Deterre Philippe , Amarenco Pierre , Combadière Christophe
Published: January 2005

Objective—

We investigated the role of monocyte-recruiting chemokines in cerebrovascular diseases among the subjects of the GENIC case-control study of brain infarction (BI).

Methods and Results—

Of the genotypes tested, only homozygosity for the rare CX3CR1 alleles was more frequent in cases than in controls: the I249 and M280 alleles were associated with an increased risk of BI (OR, 1.66 and OR, 2.62 with
P
<0.05, respectively). This effect was independent of other established risk factors and uncorrelated with disease severity. The study confirmed previous reports of a dominant protective association between CX3CR1-I249 allele and the risk of cardiovascular history. The risk of BI associated with homozygosity for the rare CX3CR1 alleles was enhanced in patients with no previous cardiovascular events. Ex vivo studies showed that the number of monocytes adhering to immobilized CX3CL1, the CX3CR1 ligand, increased proportionally to the number of CX3CR1 mutated alleles carried by the individual.

Conclusions—

The rare CX3CR1 alleles were associated with an increased risk of BI and with reduced frequency of cardiovascular history. We propose that the extra adhesion of monocytes observed in individuals carrying rare alleles of CX3CR1 may favor mechanisms leading to stroke.
B1 Kinin Receptor Does Not Contribute to Vascular Tone or Tissue Plasminogen Activator Release in the Peripheral Circulation of Patients With Heart Failure
Authors: Cruden Nicholas L.M. , Tse George H. , Fox Keith A.A. , Ludlam Christopher A. , Megson Ian , Newby David E.
Published: January 2005

Objective—

Vascular expression of the B
1
kinin receptor is markedly upregulated with left ventricular dysfunction and angiotensin-converting enzyme (ACE) inhibition, but its function remains unclear. Inhibitors of ACE potentiate bradykinin-mediated B
2
receptor-dependent vasodilatation and tissue plasminogen activator (tissue-type plasminogen activator [t-PA]) release. We investigated the contribution of the B
1
receptor to the maintenance of vascular tone and t-PA release in patients with heart failure.

Methods and Results—

Eleven patients were treated with enalapril (10 mg twice daily) or losartan (50 mg twice daily) in a randomized double-blind crossover trial. During week 6 of each treatment, patients received an intrabrachial infusion of Lys-des-Arg
9
-bradykinin (B
1
agonist; 1 to 10 nmol/min), bradykinin (30 to 300 pmol/min), Lys-[Leu
8
]-des-Arg
9
-bradykinin (B
1
antagonist; 1 to 10 nmol/min), and norepinephrine (60 to 540 pmol/min). Blood flow and t-PA release were measured using venous occlusion plethysmography and blood sampling. Bradykinin (
P
<0.001 for all), but not Lys-des-Arg
9
-bradykinin, caused vasodilatation and t-PA antigen and activity release. Norepinephrine (
P
<0.001), but not Lys-[Leu
8
]-des-Arg
9
-bradykinin, caused vasoconstriction. Compared with losartan, enalapril augmented bradykinin-mediated vasodilatation (
P
<0.05) and t-PA release (
P
<0.01 for all) but had no effect on B
1
receptor-mediated responses.

Conclusions—

The B
1
kinin receptor does not have a major vasomotor or fibrinolytic role in patients with heart failure. Augmentation of kinin-mediated vasodilatation and t-PA release by ACE inhibition is restricted to the B
2
receptor.
Allelic Variants of the Human Scavenger Receptor Class B Type 1 and Paraoxonase 1 on Coronary Heart Disease
Authors: Rodríguez-Esparragón Francisco , Rodríguez-Pérez José C. , Hernández-Trujillo Yaridé , Macías-Reyes Antonio , Medina Alfonso , Caballero Araceli , Ferrario Carlos M.
Published: January 2005

Objective—

The antioxidant properties of high-density lipoprotein (HDL) have been attributed to paraoxonase (PON) enzyme activity. Human scavenger receptor class B type 1 (SR-BI; CD36 and lysosomal integral membrane protein-II analogous-1 [CLA-1]) plays a central role in HDL-mediated native and oxidized cholesteryl ester uptake. We tested for a significant contribution of common variant of these genes to coronary heart disease (CHD) risk and hypothesized that genetic-mediated PON activity and CLA-1/SR-BI receptor functional properties jointly reduce plasma oxidation status.

Methods and Results—

We studied 304 cases and 315 controls. Polymorphisms were analyzed by polymerase chain reaction-restriction fragment analysis. CLA-1/SR-BI-relative expression levels and mRNA stability were analyzed by the comparative threshold cycle method. There was a significant difference in the male genotype distribution of the CLA-1/SR-BI exon 8 (C
8
/T
8
) variant between groups with an odds ratio of 1.7 (95% CI, 1.16 to 2.51). This significant risk was restricted to those subject carriers of Arg (R) and Leu (L) allele of the PON1 192 and 55 variants and was confirmed in multiple logistic regression analysis. CLA-1/SR-BI mRNA expression levels differed according to CLA-1/SR-BI genotypes.

Conclusions—

These data suggest a plausible genetic interaction between the CLA-1 exon 8 gene polymorphism and the risk of CHD in males.
Soluble CD40L and Cardiovascular Risk in Asymptomatic Low-Grade Carotid Stenosis
Authors: Novo Salvatore , Basili Stefania , Tantillo Rosalba , Falco Angela , Davì Valentina , Novo Giuseppina , Corrado Egle , Davì Giovanni
Published: January 2005

Background and Purpose—

We investigated whether soluble CD40L (sCD40L) may predict the risk of cardiovascular (CV) events in patients with asymptomatic carotid plaques.

Methods—

Forty-two patients with asymptomatic low-grade carotid stenosis (ALCS) and 21 controls without any carotid stenosis were enrolled. All subjects had at least a major cardiovascular risk factor (CRF). Plasma levels of C-reactive protein (CRP), IL-6, and sCD40L were measured. Subjects were reviewed every 12 months (median follow-up, 8 years).

Results—

ALCS patients had higher (
P
<0.0001) CRP, IL-6, and sCD40L than controls. Fourteen patients experienced a CV event. Cox regression analysis showed that only high sCD40L levels (
P
=0.003) independently predicted cardiovascular risk.

Conclusions—

High levels of sCD40L may predict the risk of CV events in ALCS.