bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drugs for asthma
Authors: Barnes Peter J 
Published: January 2006

Current drug therapy for asthma is highly effective and has evolved from naturally occurring substances through logical pharmaceutical developments. Pharmacology has played a critical role in asthma drug development and several key experimental observations have been published in this journal. Understanding the pharmacology of effective drug therapies has also taught us much about the underlying mechanisms of asthma.β2‐Adrenoceptor agonists are the most effective bronchodilators and evolved from catecholamines from the adrenal medulla, whereas corticosteroids, from the adrenal cortex, are by far the most effective controllers of the underlying inflammatory process in the airways. The current ‘gold standard’ of asthma therapy is a combination inhaler containing a long‐actingβ2‐agonist with a corticosteroid – an improved form of adrenal gland extract. Cromoglycate, derived from a plant product and theophylline, a dietary methyl xanthine, have also been extensively used in the therapy of asthma, but we still do not understand their molecular mechanisms. Pharmacology has played an important role in improving natural products to make effective long lasting and safe asthma therapies, but has so far been challenged to produce new classes of antiasthma therapy. The only novel class of antiasthma therapy introduced in the last 30 years are leukotriene antagonists, which are less effective than existing treatments. New, more specific, therapies targeted at specific cytokines are less effective than corticosteroids, whereas more effective therapies carry a risk of side effects that may not be acceptable. It seems likely that pharmacology, rather than molecular genetics, will remain the main approach to the further improvement of treatment for asthma.British Journal of Pharmacology(2006)147, S297–S303. doi:10.1038/sj.bjp.0706437
The glutamate story
Authors: Watkins Jeffrey C , Jane David E 
Published: January 2006

Glutamatergic synaptic transmission in the mammalian central nervous system was slowly established over a period of some 20 years, dating from the 1950s. Realisation that glutamate and like amino acids (collectively known as excitatory amino acids (EAA)) mediated their excitatory actionsviamultiple receptors preceded establishment of these receptors as synaptic transmitter receptors. EAA receptors were initially classified asN‐methyl‐D‐aspartate (NMDA) and non‐NMDA receptors, the latter subdivided into quisqualate (later AMPA) and kainate receptors after agonists that appeared to activate these receptors preferentially, and by their sensitivity to a range of differentially acting antagonists developed progressively during the 1970s. NMDA receptors were definitively shown to be synaptic receptors on spinal neurones by the sensitivity of certain excitatory pathways in the spinal cord to a range of specific NMDA receptor antagonists. Importantly, specific NMDA receptor antagonists appeared to be less effective at synapses in higher centres. In contrast, antagonists that also blocked non‐NMDA as well as NMDA receptors were almost universally effective at blocking synaptic excitation within the brain and spinal cord, establishing both the existence and ubiquity of non‐NMDA synaptic receptor systems throughout the CNS. In the early 1980s, NMDA receptors were shown to be involved in several central synaptic pathways, acting in concert with non‐NMDA receptors under conditions where a protracted excitatory postsynaptic potential was effected in response to intense stimulation of presynaptic fibres. Such activation of NMDA receptors together with non‐NMDA receptors led to the phenomenon of long‐term potentiation (LTP), associated with lasting changes in synaptic efficacy (synaptic plasticity) and considered to be an important process in memory and learning. During the 1980s, it was shown that certain glutamate receptors in the brain mediated biochemical changes that were not susceptible to NMDA or non‐NMDA receptor antagonists. This dichotomy was resolved in the early 1990s by the techniques of molecular biology, which identified two families of glutamate‐binding receptor proteins (ionotropic (iGlu) and metabotropic (mGlu) receptors). Development of antagonists binding to specific protein subunits is currently enabling precise identification of discrete iGlu or mGlu receptor subtypes that participate in a range of central synaptic processes, including synaptic plasticity.British Journal of Pharmacology(2006)147, S100–S108. doi:10.1038/sj.bjp.0706444
Glucocorticoids: exemplars of multi‐tasking
Authors: Buckingham Julia C 
Published: January 2006

Well over 80 years ago Philip Smith described the beneficial clinical effects of adrenocortical extracts in animal models of adrenal insufficiency. In the ensuing years, scientists across the globe have sought to understand the mechanisms by which adrenal hormones and their synthetic analogues produce their complex and varied actions. Particular attention has focused on the glucocorticoids, partly because they have a vital place in the treatment of inflammatory and autoimmune disorders but also because dysregulation of the secretion and/or activity of endogenous glucocorticoids is increasingly implicated in a number of common disorders that pose a growing clinical burden, such as obesity, type II diabetes, the metabolic syndrome, hypertension and depression. This review considers some of the key advances that have been made in our understanding of the physiology, pathology and pharmacology of the glucocorticoids. Emphasis is placed on the molecular mechanisms of glucocorticoid signalling and the complex mechanisms that regulate the access of steroids in the systemic circulation to their receptors in their various target cells and tissues. In addition, consideration is given to the irreversible ‘organisational’ actions of glucocorticoids in perinatal life and to the potential role of the steroids in the aetiology of disease.British Journal of Pharmacology (2006) 147, S258–S268. doi:10.1038/sj.bjp.0706456
Neuropeptides and their receptors: innovative science providing novel therapeutic targets
Authors: Brain Susan D , Cox Helen M 
Published: January 2006

This review examines our current understanding of the roles of some of the best known neuropeptides that have played major roles in our combined research programmes. Evidence obtained from over 75 years of research shows involvement of these transmitters in a wide range of organs relevant to cardiovascular, respiratory, cutaneous, neuronal and intestinal systems. There is an increasing understanding of the mechanisms involved in the release of the peptides (substance P and calcitonin gene‐related peptide (CGRP)) from sensory nerves or, neuropeptide Y (NPY) from sympathetic, parasympathetic and nonadrenergic, noncholinergic (NANC) neurons. Responses in target tissues result from interactions of the neuropeptides, or related forms, with specific G‐protein coupled receptors (GPCRs or 7 transmembrane‐spanning, 7TM proteins) that belong to either rhodopsin‐like, class 1 (neurokinin (NK) and NPY Y receptors) or secretin‐like, class 2 GPCRs (CGRP receptors). The majority of receptors activated by our chosen neuropeptides are now cloned, with knowledge of preferred agonists and selective antagonists for many receptor subtypes within these families. The study of neuropeptides in animal models has additionally revealed physiological and pathophysiological roles that in turn have led to the ongoing development of new drugs, through utilization predominantly of antagonist activities.British Journal of Pharmacology(2006)147, S202–S211. doi:10.1038/sj.bjp.0706461
Drug metabolism and pharmacogenetics: the British contribution to fields of international significance
Authors: Caldwell John 
Published: January 2006

The branch of pharmacology we now call ‘drug metabolism’, the consideration of the enzymes and procesess determining the disposition of drugs in the body, emerged in the 1840s on the continent of Europe, but British science made little or no contribution until the 1920s. From this point on, the development of the field through the 20th century was shaped to a very significant extent by a series of influential British workers, whose contributions were of global significance and who can now be seen as fathers of the subject. Since the 1950s, and gaining pace inexorably from the 1970s, the significance of drug metabolism to human therapeutics has been greatly added to by the emergence of pharmacogenetics, clinically important hereditary variation in response to drugs, which underpins the current emphasis on personalised medicine. This review examines the British contributions to both these fields through the lives of seven key contributors and attempts to place their work both in the context of its time and its lasting influence.British Journal of Pharmacology (2006) 147, S89–S99. doi:10.1038/sj.bjp.0706466
Acetylcholine
Authors: Brown David A 
Published: January 2006

This article traces the development of knowledge about the physiology and pharmacology of acetylcholine and its receptors between 1930 and 2005, with emphasis on contributions by members of the British Pharmacological Society, and by other British pharmacologists and physiologists.British Journal of Pharmacology(2006)147, S120–S126. doi:10.1038/sj.bjp.0706474
The attraction of chemokines as a target for specific anti‐inflammatory therapy
Authors: Pease James E , Williams Timothy J 
Published: January 2006

Since the identification of the first chemotactic cytokines 20 years ago, the field has mushroomed, with the discovery of approximately 40 ligands, which interact with 20 different cell surface receptors. At the time of writing this review, a PubMed trawl using the word ‘chemokine’ will recover over 28,000 manuscripts. In this article, we will give a short history of the discovery of chemokines and provide examples of the potential for therapeutic targeting of the chemokine network in inflammatory disease.British Journal of Pharmacology (2006) 147, S212–S221. doi:10.1038/sj.bjp.0706475
Antiarrhythmic drug research
Authors: Walker M J A 
Published: January 2006

This article was written as part of the 75th anniversary celebration of the British Pharmacological Society (BPS). It discusses antiarrhythmic drug research conducted by members of BPS, and as published in the British Journal of Pharmacology (BJP). BPS members, past and present, as well as antiarrhythmic manuscripts published in the BJP have been identified. From these data, the article attempts to semiquantitatively summarize results published in the journal, but only quotes selected manuscripts and individuals. Apologies are offered for omissions and errors, but as in any history, a writer's biases and opinions are unavoidable.British Journal of Pharmacology (2006) 147, S222–S231. doi:10.1038/sj.bjp.0706500
Agonist‐activated ion channels
Authors: Colquhoun David 
Published: January 2006

This paper looks at ion channels as an example of the pharmacologist's stock in trade, the action of an agonist on a receptor to produce a response. Looked at in this way, ion channels have been helpful because they are still the only system which is simple enough for quantitative investigation of transduction mechanisms. A short history is given of attempts to elucidate what happens between the time when agonist first binds, and the time when the channel opens.British Journal of Pharmacology (2006) 147, S17–S26. doi:10.1038/sj.bjp.0706502
Prostaglandins, bioassay and inflammation
Authors: Flower R J 
Published: January 2006

The formation of the British Pharmacological Society coincided almost exactly with a series of ground‐breaking studies that ushered in an entirely new field of research – that of lipid mediator pharmacology. For many years following their chemical characterisation, lipids were considered only to be of dietary or structural importance. From the 1930s, all this changed – slowly at first and then more dramatically in the 1970s and 1980s with the emergence of the prostaglandins (PGs), the first intercellular mediators to be clearly derived from lipids, in a dynamic on‐demand system. The PGs exhibit a wide range of biological activities that are still being evaluated and their properties underlie the action of one of the world's all‐time favourite medicines, aspirin, as well as its more modern congeners. This paper traces the development of the PG field, with particular emphasis on the skilful utilisation of the twin techniques of bioassay and analytical chemistry by U.K. and Swedish scientists, and the intellectual interplay between them that led to the award of a joint Nobel Prize to the principal researchers in the PG field, half a century after the first discovery of these astonishingly versatile mediators.British Journal of Pharmacology (2006) 147, S182–S192. doi:10.1038/sj.bjp.0706506
Ultrasonography of the rotator cuff: a comparison with arthroscopy in one-hundred-and-ninety consecutive cases
Authors: Milosavljevic J. , Elvin A. , Rahme H. 
Published: January 2006

Purpose: To evaluate the accuracy of high-resolution ultrasonography compared to arthroscopy in the detection of rotator cuff tears. Material and Methods: Preoperative ultrasonography (US) with a 10-MHz commercially available linear-array transducer and a standardized study protocol was performed in 190 consecutive shoulders in 185 patients with a history of shoulder pain for more than 3 months. The findings at US were classified into intact cuff, partial-thickness, and full-thickness rotator cuff tears, and correlated with findings at shoulder arthroscopy. Results: US correctly depicted 118 of 124 rotator cuff tears with sensitivity 95%, specificity 94%, PPV 97%, NPV 91% and accuracy 95%, all 94 full-thickness tears (sensitivity 100%, specificity 91%, PPV 91%, NPV 100%, and accuracy 95%), 24 of 30 partial-thickness tears (sensitivity 80%, specificity 98%, PPV 86%, NPV 96%, and accuracy 95%). Conclusion: US is a highly accurate diagnostic method for detecting full-thickness rotator cuff tears, but is less sensitive in detecting partial-thickness rotator cuff tears.
Reliability of radiological and cosmetic measurements in hallux valgus
Authors: Saro C. , Johnson D. N. , Martinez de Aragón J. , Lindgren U. , Felländer-Tsai L. 
Published: January 2006

Purpose: To evaluate the reliability of angular, linear, and sesamoid position measurements on preoperative and postoperative radiographs in hallux valgus (HV), as well as cosmetic foot appearance. Material and Methods: Radiographs and photographs from 100 patients undergoing HV surgery were evaluated by two independent observers. Results: Interobserver and intraobserver agreements for HV angle using coefficient of repeatability measures were 4.4° and 3.7°, respectively. Intraclass correlation coefficient measures within and between agreements were 0.97 for HV angle. For intermetatarsal distance, interobserver and intraobserver values were 0.90 and 0.94 when measuring from the midline of each metatarsal and 0.75 and 0.92 when measuring between cortices. Using the visual analog scale to evaluate esthetic appearance, interobserver and intraobserver agreements were 0.59 and 0.79, respectively. Sesamoid position values were also measured. Interobserver and intraobserver kappa values for preoperative and postoperative evaluations with two established methods (Mann or Smith) were 0.47 and 0.70 or 0.65 and 0.75, respectively. Conclusion: Intraobserver reliability was higher than interobserver for intermetatarsal distance, cosmetics, and sesamoid position. Angular measurements were more accurate than linear. Esthetic evaluation was less reliable than radiographic, except in the case of sesamoid position measurements.
Assessing wear of the acetabular cup using computed tomography: an ex vivo study
Authors: Olivecrona L. , Jedenmalm A. , Aspelin P. , Weidenhielm L. , Noz M. E. , Maguire G. Q. , Zeleznik M. P. , Olivecrona H. 
Published: January 2006

Purpose: To validate a clinically useful method for measuring acetabular cup wear using computed tomography (CT). Material and Methods: Eight uncemented acetabular cups were scanned twice ex vivo using CT. The linear penetration depth of the femoral component head into the cup and the thickness of the remaining polyethylene liner were measured in the CT volumes using dedicated software. Two independent examiners twice assessed each volume. The CT measurements were compared to direct measurements using a coordinate measuring device and micrometer measurements. Results: Accuracy of wear measurements expressed as penetration depth was ±0.6 and ±1.0 mm for the two examiners, respectively, with no significant differences between examiners, trials, and CT scans. Accuracy of measurements of remaining polyethylene was ±1.3 and ±1.0 mm, respectively, for the two examiners. Systematic differences between examiners were found, but no significant differences between trials and CT scans. These differences were due to different interpretations of metal artifacts in the volumes. Conclusion: The proposed CT method for evaluating wear as head penetration depth allows for reliable wear detection at a clinically relevant level. Measurements of remaining polyethylene on CT volumes are not as reliable as wear measurements owing to metal artifacts.
F-18 FDG pet in detecting renal cell carcinoma
Authors: Ak İ. , Can C. 
Published: January 2006

Purpose: To assess the role of F-18 FDG imaging with a dual head coincidence mode gamma camera (Co-PET) in the detection of renal cell carcinoma (RCC) in patients with renal masses. Material and Methods: An F-18 FDG Co-PET study was performed in 19 patients (7 F, 12 M; mean age 58.15±2.5 years, age range 45–79 years) with suspected primary renal tumors based on conventional imaging techniques, including computed tomography (CT) and ultrasonography (US) before nephrectomy or surgical resection of the mass. Results: Histologically documented RCC was present in 15 patients. Of the 19 patients with suspected primary renal tumors, F-18 FDG Co-PET was true-positive in 13, false-negative in 2, true-negative in 3, and false-positive in 1 patient. Two angiomyolipomas and one renal mass due to infarction and hemorrhage showed a true-negative Co-PET result. The patient with false-positive FDG Co-PET study was diagnosed as xantogranulomatous pyelonephritis. Overall sensitivity, specificity, and accuracy of FDG Co-PET for RCC were 86% (13/15), 75% (3/4), and 84% (16/19), respectively. Positive predictive value for RCC was 92% and negative predictive value 60%. Conclusion: These findings suggest that F-18 FDG Co-PET may have a role in the diagnostic evaluation of patients with RCC and primary staging of disease. Positive F-18 FDG study may be predictive of the presence of RCC. However, a negative study does not exclude the RCC.
Adjunctive diagnostic value of targeted electrical impedance imaging to conventional methods in the evaluation of breast lesions
Authors: Szabó B. K. , Saracco A. , Wilczek B. , Boné B. , Aspelin P. 
Published: January 2006

Purpose: To determine the diagnostic accuracy of targeted electrical impedance imaging in characterizing breast lesions, and to evaluate whether lesion size, depth and histopathology affect the diagnosis. Material and Methods: A total of 137 women with 145 lesions (79 malignant and 66 benign) found by palpation or mammography were prospectively enrolled in this study. The patients were examined by means of clinical breast examination, mammography, ultrasonography, and electrical impedance imaging with TransScan TS2000. A level of suspicion (LOS) post-processing algorithm (v2.67) was used for TS2000 lesion assessment. Imaging findings were correlated with cytologic ( n = 54) and histologic diagnoses ( n = 91). Patients with benign lesions were followed up for a mean of 36 months. Results: TS2000 showed a high sensitivity (86%) which did not differ significantly from that of mammography (87%) and ultrasonography (US) (75%). The specificity of TS2000 (49%) was significantly lower compared to mammography (97%, P<0.0001) and US (100%, P<0.0001). The additive use of TS2000 to mammography and US yielded no significant increase in sensitivity (97%), but the decrease in specificity was significant (46%, P<0.0001). Diagnostic effectiveness of TS2000 (Az = 0.68), as measured by the area under the ROC curve, was significantly lower than for mammography (Az = 0.93, P<0.0001) and for US (Az = 0.91, P<0.0001). When using TS2000 in addition to mammography and US (Az = 0.86), a significant impairment was found ( P = 0.0003). Conclusion: The role of targeted electrical impedance imaging as an adjunct to mammography and ultrasonography in the diagnosis of breast lesions is not justified by the result of this study.
FFT analysis of the X-ray tube voltage waveforms of high-frequency generators for radiographic systems
Authors: Chida K. , Saito H. , Ito D. , Shimura H. , Zuguchi M. , Takai Y. 
Published: January 2006

Purpose: To present a novel method for analyzing the voltage waveform from high-frequency X-ray generators for radiographic systems. Material and Methods: The output signal of the actual voltage across the tube of a high-frequency generator was measured using the built-in voltage sense taps that are used for voltage regulation feedback in X-ray generators. The output signal was stored in an analyzing recorder, and the waveforms were analyzed using FFT analysis. The FFT analysis of high-frequency generators consisted of obtaining the power spectrum, comparing the major frequency components in the tube voltage waveforms, and examining the intensity of each frequency component. Results: FFT analysis enables an objective comparison of the complex tube voltage waveforms in high-frequency X-ray generators. FFT analysis detected the change in the X-ray tube voltage waveform that occurred when there were problems with the high-frequency generator. Conclusion: High-frequency X-ray generators are becoming the universal choice for radiographic systems. The X-ray tube voltage and its waveform are important features of an X-ray generator, and quality assurance (QA) is important, too. As a tool for engineers involved in the design and development of X-ray generators, we can see that our methods (FFT analysis) might have some value as a means of describing generator performance under varying conditions. Furthermore, since the X-ray tube voltage waveform of a high-frequency generator is complex, FFT analysis may be useful for QA of the waveform.