bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic inhibition of nitric oxide synthesis enhances both subventricular zone neurogenesis and olfactory learning in adult mice
Authors: Romero‐Grimaldi Carmen , Gheusi Gilles , Lledo Pierre‐Marie , Estrada Carmen 
Published: November 2006

AbstractThe ability to generate new neurons during the course of adult life is preserved in the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus in the mammalian brain. These two regions constitute specifically regulated neurogenic niches, and provide newborn neurons involved in olfactory and spatial learning, respectively. Nitric oxide (NO) is a negative regulator of neurogenesis in the subventricular zone, whereas its role in the dentate gyrus remains controversial. Using systemic administration of NO synthase (NOS) inhibitors to chronically inhibit NO production, we increased neural precursor proliferation in the subventricular zone as well as neurogenesis in the olfactory bulb, without modifying the number of mitotic cells or the granular cell layer thickness in the dentate gyrus. The same treatment specifically improved olfactory learning performance, whereas spatial learning and memory was unchanged, thus demonstrating that olfactory memory is closely associated with the level of ongoing neurogenesis in the subventricular zone–olfactory bulb. The anatomical specificity of the NOS inhibitor actions was not due to differences in the availability of NO, as demonstrated by immunohistochemical detection of neuronal NOS and S‐nitrosylated proteins in both regions. Remarkably, the distinct NO sensitivity might result from a differential expression of epidermal growth factor receptor in precursor cells in both regions, as the proliferative effect of NOS inhibitors in the subventricular zone was restricted to the cells that expressed this receptor.
Corticotropin‐releasing factor promotes growth of brain norepinephrine neuronal processes through Rho GTPase regulators of the actin cytoskeleton in rat
Authors: Swinny Jerome D. , Valentino Rita J. 
Published: November 2006

AbstractCognitive aspects of the acute stress response are partly mediated through activation of the locus coeruleus (LC)–norepinephrine (NE) system via corticotropin‐releasing factor (CRF). Apart from mediating the acute responses to stress, CRF can mediate the long‐term impact of stress on the brain through its potent modulation of neuronal morphology. Importantly, the cellular pathways engaged by stress in general, and CRF in particular, in remodeling neuronal structure are poorly understood. Here, we demonstrate that apart from its well‐established acute effects on LC neuronal activity, CRF also stimulates growth and arborization of LC neuronal processes. By contrast, urocortin 2 (UCN 2), a related peptide, inhibits outgrowth of such processes. These opposing effects are transduced by a common receptor (CRF1) but distinct intracellular signaling pathways. The structural effects of CRF required protein kinase A and mitogen‐activated protein kinase, as well as Rac1, a member of the Rho family of GTPases that regulates the actin and microtubule cytoskeleton. By contrast, the effects of UCN II were mediated by the protein kinase C and RhoA pathways. This is the first study to link stress‐related substrates to molecular mediators of actin cytoskeletal remodeling in the LC. We propose a model of dynamic LC neuronal plasticity that is reciprocally controlled by CRF and UCN II, eventually determining actin rearrangement by Rho‐specific pathways. By regulating the extension of processes into pericoerulear regions where limbic afferents terminate, these peptides may determine the degree to which the LC–NE system is influenced by limbic structures that mediate emotional expression.
Repetition suppression of induced gamma band responses is eliminated by task switching
Authors: Gruber Thomas , Giabbiconi Claire‐Marie , Trujillo‐Barreto Nelson J. , Müller Matthias M. 
Published: November 2006

AbstractThe formation of cortical object representations requires the activation of cell assemblies, correlated by induced oscillatory bursts of activity > 20 Hz (induced gamma band responses; iGBRs). One marker of the functional dynamics within such cell assemblies is the suppression of iGBRs elicited by repeated stimuli. This effect is commonly interpreted as a signature of ‘sharpening’ processes within cell‐assemblies, which are behaviourally mirrored in repetition priming effects. The present study investigates whether the sharpening of primed objects is an automatic consequence of repeated stimulus processing, or whether it depends on task demands. Participants performed either a ‘living/non‐living’ or a ‘bigger/smaller than a shoebox’ classification on repeated pictures of everyday objects. We contrasted repetition‐related iGBR effects after the same task was used for initial and repeated presentations (no‐switch condition) with repetitions after a task‐switch occurred (switch condition). Furthermore, we complemented iGBR analysis by examining other brain responses known to be modulated by repetition‐related memory processes (evoked gamma oscillations and event‐related potentials; ERPs). The results obtained for the ‘no‐switch’ condition replicated previous findings of repetition suppression of iGBRs at 200–300 ms after stimulus onset. Source modelling showed that this effect was distributed over widespread cortical areas. By contrast, after a task‐switch no iGBR suppression was found. We concluded that iGBRs reflect the sharpening of a cell assembly only within the same task. After a task switch the complete object representation is reactivated. The ERP (220–380 ms) revealed suppression effects independent of task demands in bilateral posterior areas and might indicate correlates of repetition priming in perceptual structures.
Passive avoidance training is correlated with decreased cell proliferation in the chick hippocampus
Authors: Nikolakopoulou A. M. , Dermon C. R. , Panagis L. , Pavlidis M. , Stewart M. G. 
Published: November 2006

AbstractOne‐trial passive avoidance learning (PAL), where the aversive stimulus is the bitter‐tasting substance methylanthranilate (MeA), affects neuronal and synaptic plasticity in learning‐related areas of day‐old domestic chicks (Gallus domesticus). Here, cell proliferation was examined in the chick forebrain by using 5‐bromo‐2‐deoxyuridine (BrdU) at 24 h and 9 days after PAL. At 24 h post‐BrdU injection, there was a significant reduction in labelling in MeA‐trained chicks in both the dorsal hippocampus and area parahippocampalis, in comparison to controls. Moreover, double‐immunofluorescence labelling for BrdU and the nuclear neuronal marker (NeuN) showed a reduction of neuronal cells in the dorsal hippocampus of the MeA‐trained group compared with controls (35 and 49%, respectively). There was no difference in BrdU labelling in hippocampal regions between trained and control groups of chicks at 9 days post‐BrdU injection; however, the number of BrdU‐labelled cells was considerably lower than at 24 h post‐BrdU injection, possibly due to migration of cells within the telencephalon rather than cell loss as apoptotic analyses at 24 h and 9 days post‐BrdU injection did not demonstrate differences in cell death between treatment groups. Cortisol levels increased in the chick hippocampus of MeA‐trained birds 20 min after PAL, suggesting the possibility of a stress‐related mechanism of cell proliferation reduction in the hippocampus. In contrast to hippocampal areas, the olfactory bulb, an area strongly stimulated by the strong‐smelling MeA, showed increased cell genesis in comparison to controls at both 24 h and 9 days post‐training.
Haemodynamic and neural responses to hypercapnia in the awake rat
Authors: Martin Chris , Jones Myles , Martindale John , Mayhew John 
Published: November 2006

AbstractThe relationship between localized changes in brain activity and metabolism, and the blood oxygenation level‐dependent (BOLD) signal used in functional magnetic resonance imaging studies is not fully understood. One source of complexity is that stimulus‐elicited changes in the BOLD signal arise both from changes in oxygen consumption due to increases in activity and purely ‘haemodynamic’ changes such as increases in cerebral blood flow. It is well established that robust cortical haemodynamic changes can be elicited by increasing the concentration of inspired CO2 (inducing hypercapnia) and it is widely believed that these haemodynamic changes occur without significant effects upon neural activity or cortical metabolism. Hypercapnia is therefore commonly used as a calibration condition in functional magnetic resonance imaging studies to enable estimation of oxidative metabolism from subsequent stimulus‐evoked functional magnetic resonance imaging BOLD signal changes. However, there is little research that has investigated in detail the effects of hypercapnia upon all components of the haemodynamic response (changes in cerebral blood flow, volume and oxygenation) in addition to recording neural activity. In awake animals, we used optical and electrophysiological techniques to measure cortical haemodynamic and field potential responses to hypercapnia (60 s, 5% CO2). The main findings are that firstly, in the awake rat, the temporal structure of the haemodynamic response to hypercapnia differs from that reported previously in anaesthetized preparations in that the response is more rapid. Secondly, there is evidence that hypercapnia alters ongoing neural activity in awake rats by inducing periods of cortical desynchronization and this may be associated with changes in oxidative metabolism.
Axonal transport of BDNF precursor in primary sensory neurons
Authors: Wang Hui , Wu Linda Lin‐yan , Song Xing‐Yun , Luo Xue‐Gang , Zhong Jin‐Hua , Rush Robert A. , Zhou Xin‐Fu 
Published: November 2006

AbstractRecent studies have shown that the precursor of brain‐derived neurotrophic factor (pro‐BDNF) activates p75NTR with high affinity to induce apoptosis. Here we show that pro‐BDNF is transported anterogradely and retrogradely in sensory neurons of adult rats. After a crush injury of sciatic nerves, dorsal roots or dorsal column in adult Sprague–Dawley rats, the immunoreactivity for pro‐BDNF accumulated at both the proximal and distal segments. The accumulation reached a maximum at 24 h after injury. Western blot analysis also revealed pro‐BDNF in sciatic nerve segments proximal and distal to the ligature and in the spinal cord. Biotinylated or Alexa‐488‐labelled pro‐BDNF injected into sciatic nerve was internalized and transported both retrogradely and anterogradely within sensory neurons. These results demonstrate that pro‐BDNF is anterogradely and retrogradely transported in sensory neurons, suggesting that endogenous pro‐BDNF may be released and play important functions.
Developmental expression of Na+ currents in mouse Purkinje neurons
Authors: Fry Mark 
Published: November 2006

AbstractAs Purkinje neurons mature during postnatal development, they change from electrically quiescent to active and exhibit high frequency spontaneous action potentials. This change in electrical activity is determined by both alteration in ion channel expression and the acquisition of synaptic input. To gain a better understanding of the development the intrinsic electrical properties of these neurons, acutely isolated Purkinje neurons from mice aged postnatal day 4 (P4) to P18 were examined. This included recording action potential frequency, threshold, height and slope, and input resistance and capacitance. Changes in a number of these properties were observed, suggesting significant changes in voltage‐gated Na+ currents. Because voltage‐gated Na+ currents, including the transient, resurgent and persistent currents, are known to play important roles in generating spontaneous action potentials, the developmental changes in these currents were examined. A large increase in the density of transient current, resurgent current and persistent current was observed at times corresponding with changes in action potential properties. Interestingly, the developmental up‐regulation of the persistent current and resurgent current occurred at rate which was faster than the up‐regulation of the transient current. Moreover, the relative amplitudes of the persistent and resurgent currents increased in parallel, suggesting that they share a common basis. The data indicate that developmental up‐regulation of Na+ currents plays a key role in the acquisition of Purkinje neuron excitability.
CaMK‐II modulation of GABAAreceptors expressed in HEK293, NG108‐15 and rat cerebellar granule neurons
Authors: Houston C. M. , Smart T. G. 
Published: November 2006

AbstractThe γ‐aminobutyric acid type A (GABAA) receptor is a pentameric ligand‐gated ion channel responsible for fast synaptic inhibition in the brain. Phosphorylation of the GABAAreceptor by serine/threonine protein kinases, at residues located in the intracellular loop between the third and fourth transmembrane domains of each subunit, can dynamically modulate receptor trafficking and function. In this study, we have assessed the effect that Ca2+‐calmodulin‐dependent protein kinase‐II (CaMK‐II) has on GABAAreceptors. The intracellular application of preactivated CaMK‐II failed to modulate the function of αβ and αβγ subunit GABAAreceptors heterologously expressed in human embryonic kidney (HEK)293 cells. However, application of similarly preactivated α‐CaMK‐II significantly potentiated the amplitudes of whole‐cell GABA currents recorded from rat cultured cerebellar granule neurons and from recombinant GABAAreceptors expressed in neuroblastoma, NG108‐15, cells. The modulation by α‐CaMK‐II of current amplitude depended upon the subunit composition of GABAAreceptors. α‐CaMK‐II potentiated GABA currents recorded from α1β3 and α1β3γ2 GABAAreceptors, but was unable to functionally modulate β2 subunit‐containing receptors. Similar results were obtained from β2 –/– mouse cerebellar granule cell cultures and from rat granule cell cultures overexpressing recombinant α1β2 or α1β3 GABAAreceptors. α‐CaMK‐II had a greater effect on the modulation of GABA responses mediated by α1β3γ2 compared with α1β3 receptors, indicating a possible role for the γ2 subunit in CaMK‐II‐mediated phosphorylation. In conclusion, CaMK‐II can upregulate the function of GABAAreceptors expressed in neurons or a neuronal cell line that is dependent on the β subunit co‐assembled into the receptor complex.
Sacral nerve stimulation induces pan‐colonic propagating pressure waves and increases defecation frequency in patients with slow‐transit constipation
Authors: Dinning P. G. , Fuentealba S. E. , Kennedy M. L. , Lubowski D. Z. , Cook I. J. 
Published: November 2006

AbstractObjective  Colonic propagating sequences are important for normal colonic transit and defecation. The frequency of these motor patterns is reduced in slow‐transit constipation. Sacral nerve stimulation (SNS) is a useful treatment for faedcal and urinary incontinence. A high proportion of these patients have also reported altered bowel function. The effects of SNS on colonic propagating sequences in constipation are unknown. Our aims were to evaluate the effect of SNS on colonic pressure patterns and evaluate its therapeutic potential in severe constipation.Method  In eight patients with scintigraphically confirmed slow‐transit constipation, a manometry catheter (16 recording sites at 7.5 cm intervals) was positioned colonoscopically and the tip fixed in the caecum. Temporary electrodes (Medtronic) were implanted in the S2 and S3 sacral nerve foramina under general anaesthesia. In the fasted state, 14 Hz stimulation was administered and four sets of parameters (pulse width 300 or 400 μs; S2 and S3) were tested in four 2‐h epochs, in random order, over 2 days. Patients were then discharged home with the sacral wires in situ and a 3‐week trial stimulation commenced during which patients completed a daily stool diary.Results  When compared with basal activity, electrical stimulation to S3 significantly increased pan‐colonic antegrade propagating sequence (PS) frequency (5.4 ± 4.2 vs 11.3 ± 6.6 PS/h; P = 0.01). Stimulation at S2 significantly increased retrograde PSs (basal 2.6 ± 1.8 vs SNS 5.6 ± 4.8 PS/h; P = 0.03). During the subsequent three‐week trial (continuous stimulation), six of eight reported increased bowel frequency with a reduction in laxative usage.Conclusion  These data demonstrate that SNS induces pan‐colonic propagating pressure waves and therefore shows promise as a potential therapy for severe refractory constipation.
Endoscopic trans‐anal resection of rectal tumours: critical appraisal of an interdisciplinary approach
Authors: Shaikh S. , Nabi G. , O'Kelly T. , Swami S. K. 
Published: November 2006

AbstractObjective  Endoscopic trans‐anal resection (ETAR) is an accepted technique for treating benign rectal adenomas that relies on technical expertise with the urological resectoscope. We present our experience with ETAR in an interdisciplinary setting combining the decision‐making of the colorectal surgeon with the technical skill of the urologist.Method  Assessment of all patients with adenomas and their subsequent care was organized by the colorectal team. Those with carpet‐like rectal adenomas were referred to the urologist for ETAR performed using a Storz‐Olympus 27/28Ch resectoscope, with roller‐ball for haemostasis and glycine for irrigation.Results  Twenty‐four patients (43–93 years, median 71 years; 14 men and 10 women) underwent 51 ETAR procedures from 1999 to 2005, with a median of two (range 1–6) procedures per patient. Complete clearance was achieved on 25 occasions. Two intra‐operative extra‐peritoneal perforations occurred which were managed conservatively. There were four cases of postoperative haemorrhage, two of which required a repeat procedure to secure haemostasis. Four patients had postoperative pyrexia that settled with oral antibiotics.Mean tumour distance from the anal verge was 7 cm (range 2–12 cm); the mean tumour area was 8 cm2 (range 3–20 cm2); the mean operating time was 34 min (range 15–60 min) and the mean hospital stay was 32 h (range 24–120 h).Conclusion  An interdisciplinary approach to ETAR uses available clinical resources efficiently as the colorectal surgeon does need to acquire the technical skills of endoscopic resection. Our results compare favourably with other published series and this approach can be adopted by any centre where colorectal and urological surgeons work together.
Endoscopically placed caecostomy buttons: a trial ACE procedure
Authors: Biyani D. , Barrow E. , Hodson P. , Watson A. J. M. , Maclennan I. 
Published: November 2006

AbstractThe use of the antegrade continence enema (ACE) is becoming more widespread. Preliminary studies have been promising, but the procedure is not universally successful. A colonoscopic insertion of a caecostomy button is a relatively minor procedure. This allows the ACE to be used for a trial period to assess whether a permanent procedure would be beneficial. If successful, enemas can be continued by the caecostomy, or a formal ACE can be performed. We report a series of five patients who underwent staged endoscopic insertion of a MIC‐KEY caecostomy button, and we discuss the technical aspects of the procedure.
Normalization of metabolic syndrome using fenofibrate, metformin or their combination
Authors: Nieuwdorp M. , Stroes E. S. G. , Kastelein J. J. P. ,   Fenofibrate/Metformin study group
Published: November 2006

Aim:  The aim of this study was to evaluate whether and to what extent fenofibrate (F), metformin (M) or a combination of these drugs improve characteristics of the metabolic syndrome (MetS).Methods:  MetS was defined as the presence of ≥3 National Cholesterol Education Programme criteria, including ≥2 biochemical abnormalities. Patients with MetS were randomized to receive one of seven treatments twice daily for three months: F 80 mg + M 850 mg, F 80 mg + M 500 mg, F 40 mg + M 850 mg, F 40 mg + M 500 mg, F 80 mg + placebo, M 850 mg + placebo or placebo. ‘Normalized’ was defined as not having MetS biochemical abnormalities at the 3‐month treatment period. A total of 681 patients were analysed (mean age 56 years, 59% men, mean body mass index 31.6 and 33.3 in male and female patients respectively).Results:  High dose combination therapy led to normalization of biochemical parameters in 17.4% of patients, whereas only 5.8% of patients during F (p = 0.009) and 5.0% during M monotherapy (p = 0.005) exhibited normal biochemical values. Accordingly, F 80 mg + M 850 mg twice daily was most effective for normalizing triglycerides (55.0%), high‐density lipoprotein cholesterol (35.0%) and fasting glucose (39.4%). All the treatments were well tolerated, with comparable adverse‐event rates between groups.Conclusions:  Treatment with fenofibrate and metformin in combination led to normalization of biochemical abnormalities associated with the MetS more effectively compared with either therapy alone, without additional adverse effects. These data imply that high‐dose combination therapy may offer additional therapeutic benefit particularly in patients with MetS.
PUBLIC DEBT AS PRIVATE WEALTH: SOME EQUILIBRIUM CONSIDERATIONS
Authors: Schlicht Ekkehart 
Published: November 2006

ABSTRACTGovernment bonds are interest‐bearing assets. Increasing public debt increases wealth, income and consumption demand. The smaller government expenditure is, the larger consumption demand must be in equilibrium, and the larger must be public debt. Conversely, lower public debt implies higher government spending and taxation. Public debt plays, thus, an important role in establishing equilibrium. It distributes output between consumers and government. In case of insufficient demand, a larger public debt entails higher private consumption and less public spending. If upper bounds on public debt are introduced (as in the Maastricht treaty), such constraints place lower bounds on taxation and public spending and may rule out macroeconomic equilibrium. As an aside, a minor flaw in Domar's (American Economic Review, 34 (4), pp. 798–827) classical analysis is corrected.
Lipid abnormalities in HIV/hepatitis C virus‐coinfected patients
Authors: Bedimo R , Ghurani R , Nsuami M , Turner D , Kvanli M‐B , Brown G , Margolis D 
Published: November 2006

BackgroundAmong HIV‐infected patients, hepatitis C virus (HCV) coinfection is associated with increased rates of lipodystrophy and insulin resistance. Its impact on HIV‐associated dyslipidaemia is less clear.MethodsThe lipid profiles of all HIV‐infected patients and a subset of HCV‐infected patients seen at the VA Medical Center in Dallas from January 2003 to March 2004 were analysed. Demographic data, HCV serostatus, and HIV treatment history were recorded. Lipid profiles of HIV/HCV‐coinfected patients were compared with those of HIV‐monoinfected and HCV‐monoinfected patients.ResultsA total of 359 HIV‐infected patients, 91 (25.3%) of whom were HCV coinfected, and 112 HCV‐infected patients were included in the analysis. Among the HIV‐infected patients, HCV coinfection was associated with a reduced risk of hypercholesterolaemia [9.9% vs 24.8%; relative risk (RR)=0.333; 95% confidence interval (CI)=0.158–0.699; P<0.001] and hypertriglyceridaemia (48.4% vs 60.3%; RR=0.616; 95% CI=0.382–0.994; P=0.031). After controlling for duration of protease inhibitor (PI) therapy, race, alanine aminotransferase (ALT) concentration and platelet count, HCV remained an independent predictor of hypercholesterolaemia (RR=0.369; P=0.01) and any dyslipidaemia (RR=0.531; P=0.019). In addition, the rate of dyslipidaemias was lower among HCV‐monoinfected than HIV/HCV‐coinfected patients (29.5% vs 50.5; P=0.002). White race was also an independent predictor of dyslipidaemia (73.8% vs 50.7%; RR=2.32; 95% CI=1.44–3.76; P=0.001).ConclusionsHCV coinfection independently predicted lower rates of dyslipidaemia among HIV‐infected patients. An analysis of lipid kinetics among mono‐ and coinfected patients may elucidate the mechanisms of the apparent protective effect of HCV infection.