bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory bio‐markers and cardiovascular risk prediction
Authors: Blake G. J. , Ridker P. M. 
Published: March 2003

Abstract. Blake GJ, Ridker PM (Harvard Medical School, Boston, MA, USA). Inflammatory bio‐markers and cardiovascular risk prediction (Review). J Intern Med 2002; 252: 283–294.Inflammatory processes are now recognized to play a central role in the pathogenesis of atherosclerosis and its complications. Plasma levels of several markers of inflammation have been found to be associated with future cardiovascular risk in a variety of clinical settings. These markers include cell adhesion molecules, cytokines, pro‐atherogenic enzymes and C‐reactive protein (CRP). Initially thought of as an inactive downstream marker of the inflammatory cascade, emerging evidence suggests that CRP may be directly involved in atherogenesis, and that arterial plaque can produce CRP, independent of traditional hepatic pathways. In addition to being a strong predictor of future cardiovascular risk amongst patients presenting with acute coronary syndromes, numerous studies have found that baseline levels of CRP are associated with risk of future myocardial infarction, stroke, peripheral vascular disease and cardiovascular death amongst apparently healthy populations. The combination of measurement of a marker of inflammation with lipid testing may improve upon risk stratification based on lipid testing alone, and intensification of programmes for exercise, weight loss, and smoking cessation is recommended for those with elevated CRP levels. Further trials are needed to confirm the potential benefits of statins amongst individuals with elevated CRP levels.
The effect of streptokinase neutralizing antibodies on fibrinolytic activity and reperfusion following streptokinase treatment in acute myocardial infarction
Authors: Nilsson J. B. , Nilsson T. K. , Jansson J.‐H. , Boman K. , Söderberg S. , Näslund U. 
Published: March 2003

Abstract. Nilsson JB, Nilsson TK, Jansson J‐H, Boman K, Söderberg S, Näslund U (Heart Centre, University Hospital, Umeå; Örebro Medical Centre, Örebro; Skellefteå Hospital, Skellefteå; Sweden). The effect of streptokinase neutralizing antibodies on fibrinolytic activity and reperfusion following streptokinase treatment in acute myocardial infarction. J Intern Med 2002; 252: 405–411.Objectives. To evaluate tissue plasminogen activator (tPA) activity as a measure of fibrinolytic response to treatment with streptokinase (SK) and to relate this to the effect of pretreatment SK antibodies and to successful reperfusion assessed by continuous computerized vectorcardiography (VCG).Setting. Umeå University Hospital.Subjects. A total of 104 patients with acute myocardial infarction (AMI) treated with SK and no history of previous SK treatment were studied. The tPA activity was measured 4 h after the start of treatment. The effect of pre‐existing neutralizing antibodies to SK was analysed with a functional assay in pretreatment samples. Reperfusion was evaluated with VCG.Main outcome measures. Successful reperfusion.Results. Fifty‐five patients (53%) were classified as successfully reperfused. The risk for failed reperfusion was calculated in logistic regression models. In a univariate model, a borderline significant increase in the risk of failed reperfusion was observed in intermediate levels of SK neutralizing antibodies, but not in the highest levels. In a multivariate model, only high tPA activity, >25 U mL−1, at 4 h (OR 0.17; 95% CI: 0.06–0.51) was associated with a higher rate of reperfusion whilst longer time to treatment (OR 1.17; 95% CI: 1.02–1.35) was associated with a higher risk of failed reperfusion. There was no significant correlation between neutralizing antibodies to SK and tPA activity at 4 h.Conclusion. The SK treatment of AMI induced high levels of tPA activity which were associated with successful reperfusion. The effect of pre‐existing SK antibodies had no significant influence on reperfusion and were not correlated to the fibrinolytic activity obtained.
Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial
Authors: Mangoni A. A. , Sherwood R. A. , Swift C. G. , Jackson S. H. D. 
Published: March 2003

Abstract.  Mangoni AA, Sherwood RA, Swift CG, Jackson SHD (Guy's, King's, and St Thomas' School of Medicine, King's College London, UK). Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial. J Intern Med 2002; 252: 497–503.Objective.  Cigarette smoking is associated with increased plasma homocysteine concentrations, endothelial dysfunction and arterial stiffening. Homocysteine per se induces endothelial dysfunction and arterial stiffening and might account, at least partly, for the vascular abnormalities observed in smokers. We sought to determine whether folic acid supplementation, by reducing plasma homocysteine concentrations, enhanced endothelial function and reduced arterial stiffness in smokers.Design.  Double‐blind, randomized controlled, parallel‐group, trial.Setting. Academic medical centre.Subjects.  A consecutive sample of 24 healthy cigarette smokers (age 37.8 ± 2.5 years, mean ± SEM).Intervention.  Subjects were randomly assigned to 4‐week folic acid 5 mg day−1 or placebo.Main outcome measures.  The following were measured before and after treatment: (i) peripheral vasoreactivity (forearm arterial blood flow, FABF) during intra‐arterial administration of endothelium‐dependent (acetylcholine 1.5, 4.5 and 15 μg min−1) and endothelium‐independent (sodium nitroprusside 1, 2 and 4 μg min−1) vasodilators; (ii) carotid‐femoral pulse‐wave velocity (PWV); (iii) blood pressure (BP).Results.  Folic acid reduced homocysteine concentrations (10.8 ± 0.6 vs. 8.2 ± 0.5 μmol L−1, P < 0.001) and enhanced endothelium‐dependent vasodilatation during each acetylcholine infusion rate (ratio between the FABF in the infused and control arm during increasing infusion rates at baseline 1.09 ± 0.03 vs. 1.41 ± 0.09 after treatment, P < 0.01; 1.39 ± 0.07 vs. 1.83 ± 0.12, P < 0.01; 1.65 ± 0.16 vs. 2.72 ± 0.36, P < 0.05) whilst endothelium‐independent vasodilatation was unaffected. A significant fall in BP was also observed (mean BP 88 ± 2 vs. 83 ± 1 mmHg, P < 0.01). By contrast, PWV did not significantly change (8.4 ± 0.3 vs. 7.8 ± 0.4 m s−1). No significant changes in plasma homocysteine concentrations, FABF, BP, and PWV were observed in the placebo group. A multiple regression analysis showed that changes in folic acid plasma concentrations independently predicted both FABF changes during maximal acetylcholine‐mediated vasodilatation (P < 0.01) and BP changes (P = 0.01).Conclusions.  Short‐term folic acid supplementation significantly enhanced endothelial function and reduced BP in young chronic smokers. These effects were largely independent from the homocysteine lowering effects. Thus, a simple, nontoxic, and relatively inexpensive vitamin intervention might be useful in primary cardiovascular prevention in this high‐risk group.
Voronoi cells, fractal dimensions and fibre composites
Authors: Summerscales J. , Guild F. J. , Pearce N. R. L. , Russell P. M. 
Published: March 2003

The use of fibre‐reinforced polymer matrix composite materials is growing at a faster rate than the gross domestic product (GDP) in many countries. An improved understanding of their processing and mechanical behaviour would extend the potential applications of these materials. For unidirectional composites, it is predicted that localized absence of fibres is related to longitudinal compression failure. The use of woven reinforcements permits more effective manufacture than for unidirectional fibres. It has been demonstrated experimentally that compression strengths of woven composites are reduced when fibres are clustered. Summerscales predicted that clustering of fibres would increase the permeability of the reinforcement and hence expedite the processing of these materials. Commercial fabrics are available which employ this concept using flow‐enhancing bound tows. The net effect of clustering fibres is to enhance processability whilst reducing the mechanical properties.The effects reported above were qualitative correlations. To improve the design tools for reinforcement fabrics we have sought to quantify the changes in the micro/meso‐structure of woven reinforcement fabrics. Gross differences in the appearance of laminate sections are apparent for different weave styles. The use of automated image analysis is essential for the quantification of subtle changes in fabric architecture. This paper considers Voronoi tessellation and fractal dimensions for the quantification of the microstructures of woven fibre‐reinforced composites. It reviews our studies in the last decade of the process‐property‐structure relationships for commercial and experimental fabric reinforcements in an attempt to resolve the processing vs. properties dilemma. A new flow‐enhancement concept has been developed which has a reduced impact on laminate mechanical properties.
Stereological length estimation using spherical probes
Authors: Mouton P. R. , Gokhale A. M. , Ward N. L. , West M. J. 
Published: March 2003

SummaryLineal structures in biological tissue support a wide variety of physiological functions, including membrane stabilization, vascular perfusion, and cell‐to‐cell communication. In 1953, Smith and Guttman demonstrated a stereological method to estimate the total length density (Lv) of linear objects based on random intersections with a two‐dimensional sampling probe. Several methods have been developed to ensure the required isotropy of object–probe intersections, including isotropic‐uniform‐random (IUR) sections, vertical‐uniform‐random (VUR) slices, and isotropic virtual planes. The disadvantages of these methods are the requirements for inconvenient section orientations (IUR, VUR) or complex counting rules at multiple focal planes (isotropic virtual planes). To overcome these limitations we report a convenient and straightforward approach to estimate Lv and total length, L, for linear objects on tissue sections cut at any arbitrary orientation. The approach presented here uses spherical probes that are inherently isotropic, combined with unbiased fractionator sampling, to demonstrate total L estimation for thin nerve fibres in dorsal hippocampus of the mouse brain.
Surface plasmon fluorescence microscopy: an analysis
Authors: Somekh M. G. 
Published: March 2003

SummaryThis paper examines the imaging performance of surface plasmon microscopes operating in the far field. Until recently the accepted view has been that the achievable lateral resolution with a surface plasmon imaging system is limited by propagation decay length of the surface plasmons rather than by diffraction. We show by simulation that the lateral resolution of a surface plasmon imaging system can be comparable to that of the best optical microscopes. We also show that new imaging modes such as two‐photon and also second harmonic surface plasmon microscopy are extremely promising imaging modes that may be expected to be powerful techniques for the analysis of surface structures.
Permissive Effect of Centrally Administered Oxytocin on the Excitatory Response of Oxytocin Neurones to Ventral Tegmental Stimulation in the Suckled Lactating Rat
Authors: Cosgrave A. S. , Richardson C. M. , Wakerley J. B. 
Published: March 2003

AbstractThe mesencephalic ventral tegmentum has been implicated in the milk‐ejection reflex and modulation of inputs from this region could provide a mechanism whereby central oxytocin facilitates synchronous bursting of oxytocin neurones during suckling. Experiments were therefore undertaken to investigate the effect of intracerebroventricular (i.c.v.) oxytocin on the response of oxytocin neurones to ventral tegmental stimulation. Oxytocin neurones were recorded in the supraoptic nucleus of urethane‐anaesthetized lactating rats during suckling, and their response to single shock stimulation of the ventral tegmentum was monitored using peri‐stimulus time‐interval histograms. Before i.c.v. oxytocin, oxytocin neurones were either unresponsive to ventral tegmental stimulation, or displayed a small inhibition. However, after administration of oxytocin (2.2 ng i.c.v.), seven out of eight neurones tested displayed a pronounced excitatory response (onset latency 78.4 ± 4.8 ms, duration 73.4 ± 8.3 ms). This permissive effect on the excitatory response was only observed in the presence of suckling, and followed the same time course as facilitation of the milk‐ejection reflex, being maximal immediately before each facilitated bursting response in the oxytocin neurones. The response to ventral tegmental stimulation remained unaltered after intraperitoneal administration of hypertonic saline to cause a generalized increase in the excitability of the oxytocin neurones. Moreover, i.c.v. oxytocin had no effect on the response of oxytocin neurones to stimulation of a descending input from the medial septum. In conclusion, administration of i.c.v. oxytocin has a selective permissive effect on the excitation of oxytocin neurones from the ventral tegmentum, and this supports previous in vitro studies suggesting that centrally released oxytocin may act as a modulator of afferent transmission to the magnocellular nuclei. This effect on the afferent excitation of oxytocin neurones may provide a mechanism whereby i.c.v. oxytocin facilitates suckling‐evoked bursting activity.
Rat Adrenal Transplants are Reinnervated: An Invalid Model of Denervated Adrenal Cortical Tissue
Authors: Ulrich‐Lai Y. M. , Engeland W. C. 
Published: March 2003

AbstractAdrenal autotransplantation is a widely used approach to investigate the potential for neural modulation of adrenal cortical function. It is believed that regenerating adrenal transplants are not reinnervated, thereby providing a model to investigate adrenal function in the absence of neural modulation. However, the hypothesis that adrenal transplants become reinnervated has not been directly tested. The purpose of the present study was to characterize the time course, extent, and nature of the reinnervation of the regenerating adrenal transplant and to assess whether the recovery of steroidogenic function and enzyme expression correlates temporally with the presence of innervation. Using immunohistofluorescent detection of tyrosine hydroxylase (TH), neuropeptide Y (NPY), calcitonin gene‐related peptide (CGRP), and vasoactive intestinal peptide (VIP), the innervation of regenerating adrenals was assessed 14–30 days after transplantation of adrenal capsules beneath the kidney capsule in rats. Extensive reinnervation by TH‐, NPY‐, and VIP‐positive fibres was present by 14 days after transplantation including regions of the adrenal capsule and cortex, with only minimal reinnervation by CGRP‐positive fibres up to 30 days. TH‐ and NPY‐positive chromaffin cells were also observed in the regenerating transplants. In addition, there was marked recovery of steroidogenic function and steroidogenic enzyme expression up to 30 days. The finding that nerve fibres are present in the transplants during the re‐establishment of steroidogenic function and enzyme expression suggests that innervation may modulate the regeneration and functional recovery of adrenal transplants. In an attempt to prevent reinnervation of transplants, adrenal capsules were autotransplanted to denervated kidneys. Immunohistochemical analysis showed that, despite extensive denervation of the kidney tissue, the reinnervation and regeneration of the adrenal transplants still occurred. These data demonstrate the marked capacity of the regenerating adrenal to become reinnervated and reinforces the conclusion that adrenal transplants are an invalid model of denervated adrenal cortical tissue.
Glutamatergic Regulation of Gonadotropin Releasing Hormone mRNA Levels During Development in the Mouse
Authors: Ford H. , Ebling F. J. P. 
Published: March 2003

AbstractThe aims of these studies were to investigate the time course of the increase in gonadotropin releasing hormone (GnRH) mRNA levels during sexual development in the mouse, and to test the hypothesis that the neurotransmitter glutamate regulates the GnRH secretory system via actions at the level of GnRH gene expression. GnRH mRNA abundance was estimated by measuring silver grains generated by in situ hybridization of an 35S‐labelled oligonucleotide probe. There was a significant increase in GnRH mRNA abundance between the day of birth (P0) and postnatal day 2 (P2) in male mice, but no further increases at later ages when overt pubertal changes are manifest. GnRH mRNA levels also increased significantly between P0 and P2 in female mice. Treatment with the glutamate agonist NMDA caused a significant increase in GnRH mRNA levels in neonatal (P0) mice and adult male mice within 30 min of treatment, which is consistent with previous studies in the rat implicating glutamate in the regulation of GnRH mRNA stability. Treatment with the glutamate antagonist CGP40116 caused an equally rapid decrease in GnRH mRNA levels in adult mice and in mice on P5 after the neonatal increase in GnRH gene expression, but was without effect in mice on P0, prior to the developmental increase. These observations that the effect on GnRH mRNA levels of blocking endogenous glutamatergic signalling depends upon the developmental stage suggest that endogenous glutamate maintains GnRH mRNA levels in adult mouse, and is a potential regulator of the developmental increase seen in the neonatal period.
Chronic Iodine Deprivation Attenuates Stress‐Induced and Diurnal Variation in Corticosterone Secretion in Female Wistar Rats
Authors: Nolan L. A. , Windle R. J. , Wood S. A. , Kershaw Y. M. , Lunness H. R. , Lightman S. L. , Ingram C. D. , Levy A. 
Published: March 2003

AbstractMany millions of people throughout the world are at risk of developing iodine deficiency‐associated disorders. The underlying effects of iodine deficiency on neuroendocrine function are poorly defined. We have studied stress‐induced and diurnal variation in corticosterone secretion in female rats rendered chronically hypothyroid by feeding them an iodine‐free diet for 6 months. Corticosterone secretory responses in iodine deficient animals were compared to those seen in animals rendered hypothyroid with propylthiouracil and untreated controls. By using a well‐validated, automated blood sampling system to collect small samples of blood over the complete daily cycle in unrestrained animals, we have demonstrated for the first time that the normal diurnal rhythm of corticosterone secretion is lost in chronic iodine deficiency and that the corticosterone secretory response to the psychological stress of 10 min exposure to white noise is attenuated. Despite restoration of circulating triiodothyronine and thyrotropin releasing hormone‐ and thyroid stimulating hormoneβ‐transcript prevalence in the hypothalamus and pituitary, respectively, 1 month after restoration of normal iodine‐containing diet both the diurnal variation in corticosterone levels and the corticosterone secretory response to the noise stress remained reduced in amplitude compared to control animals. Thus, chronic hypothyroidism induced by iodine deficiency significantly attenuates hypothalamo‐pituitary‐adrenal axis activity, an effect that persists after functional recovery of the thyroid axis.
Effects of Serotonin, GABA and Neuropeptide Y on Seabream Gonadotropin Releasing Hormone Release In Vitro from Preoptic‐Anterior Hypothalamus and Pituitary of Red Seabream, Pagrus major
Authors: Senthilkumaran B. , Okuzawa K. , Gen K. , Kagawa H. 
Published: March 2003

AbstractThe effects of serotonin (5‐HT), GABA and neuropeptide Y (NPY) on in vitro release of seabream (sb) gonadotropin releasing hormone (GnRH) from slices of the preoptic‐anterior hypothalamus (P‐AH) and pituitary of red seabream were studied. 5‐HT, GABA and NPY all stimulated the release of sbGnRH from the P‐AH but not from the pituitary of immature red seabream. They also stimulated sbGnRH release from the P‐AH with a similar potency during the course of gonadal development. Specific agonists and/or antagonists of 5‐HT, GABA and NPY showed that 5‐HT and GABA utilize 5‐HT2 and GABAA receptor subtypes, respectively, to mediate their action, and that NPY employs at least NPYY1 and NPYY2 receptor subtypes to stimulate sbGnRH release. Combinations of different antagonists for 5‐HT, GABA and noradrenaline/adrenaline did not block the stimulatory influence of NPY on release of sbGnRH, indicating that the action of NPY on the sbGnRH neuronal system is probably direct.
GABAergic Nature of Hypothalamic Leptin Target Neurones in the Ventromedial Arcuate Nucleus
Authors: Ovesjö M.‐L. , Gamstedt M. , Collin M. , Meister B. 
Published: March 2003

AbstractLeptin is an adipose tissue‐derived cytokine hormone, which reduces body weight via interactions with hypothalamic neurones. Leptin receptors capable of activating the JAK‐STAT signal transduction pathway are expressed at high levels in the hypothalamus, particularly in the arcuate nucleus. In order to identify the chemical mediators of leptin's action in the hypothalamus, we have examined whether GABA neurones of the hypothalamic arcuate nucleus contain leptin receptors and the leptin‐activated transcription factor STAT3. GABAergic neurones, as visualized by antisera to the GABA‐synthesizing enzyme glutamic acid decarboxylase (GAD) and GABA, were demonstrated in the ventromedial and ventrolateral parts of the arcuate nucleus. GABA neurones in the ventromedial arcuate nucleus were shown to contain leptin receptor immunoreactivity, as revealed using an antiserum generated to a sequence common to all isoforms of the leptin receptor (Ob‐R), as well as an antiserum generated to the carboxy‐terminal end of the long leptin receptor (Ob‐Rb), and immunoreactivity for the leptin‐induced signal transduction molecule STAT3. Ventromedial GABA neurones were also shown to contain neuropeptide Y, whereas ventrolateral proopiomelanocortin‐containing neurones lacked GAD and GABA immunoreactivity. Levels of mRNA for GAD65, GAD67 and the vesicular GABA transporter (VGAT) were analysed in the arcuate nucleus of leptin‐deficient ob/ob mice and lean control mice by in situ hybridization. No significant differences in GAD65, GAD67 or VGAT mRNA were detected in the arcuate nucleus of ob/ob mice as compared to lean control mice. The presence of leptin receptor and STAT3 in GABAergic arcuate neurones, but absence of changes in gene transcription for GAD and VGAT mRNA suggests, that leptin does not transcriptionally regulate the expression of proteins involved in GABAergic transmission in arcuate neurones. However, mechanisms other than transcriptional regulation for leptin to influence arcuate GABA neurones may exist.