Since the introduction by Grüntzig et al. (1) of nonoperative treatment of coronary artery stenosis (PTCA) significant progress has been made in methods for the treatment of arterial atherosclerotic disease. Currently many recanalization methods are being developed to reopen obstructed arteries during catheterization. New methods currently being studied include a rotating abrasive tip as suggested by Ritchie et al. (2), an atherectomy catheter tip method by Simpson et al. (3) and, for instance, a hot tip method as described by Sanborn et al. (4). In addition, direct laser application is also being considered for treating arterial obstruction (5, 6).
Tubular construction is widely used in a range of civil and structural engineering applications. To date, the principal product range has comprised square, rectangular and circular hollow sections. However, hot-rolled structural steel elliptical hollow sections have been recently introduced and offer further choice to engineers and architects. Currently though, a lack of fundamental structural performance data and verified structural design guidance is inhibiting uptake. Of fundamental importance to structural metallic design is the concept of cross-section classification. This paper proposes slenderness parameters and a system of cross-section classification limits for elliptical hollow sections, developed on the basis of laboratory tests and numerical simulations. Four classes of cross-sections, namely Class 1 to 4 have been defined with limiting slenderness values. For the special case of elliptical hollow sections with an aspect ratio of unity, consistency with the slenderness limits for circular hollow sections in Eurocode 3 has been achieved. The proposed system of cross-section classification underpins the development of further design guidance for elliptical hollow sections.
COPD is one of the commonest causes of morbidity and mortality in the world and is increasing in prevalence. Current therapies are not very effective and no current treatment prevents the relentless progression of airflow limitation that characterizes this disease. Smoking cessation is the only strategy that reduces this decline in lung function and, although bupropion is the most effective aid to quitting, more effective treatments of nicotine addition are needed. The mainstay of treatment is bronchodilators for symptom relief and inhaled anticholinergics and beta2-agonists are useful by reducing hyperinflation of the lungs. A new once daily inhaled anticholinergic is the most effective bronchodilator, but long-acting inhaled beta2-agonsts are also useful. Theophylline is used as an additional bronchodilator in more severe patients and may have some anti-inflammatory action. By contrast, inhaled corticosteroids are poorly effective and do not reduce disease profession, although recent studies with combination inhalers (corticosteroid + long-acting beta2-agonist) have shown better effects. Long-term oxygen therapy is needed by patients with pulmonary hypertension and right heart failure. There is a pressing need to develop new classes of therapy, and several new drugs are currently in development, including inteleukin-8 antagonists, phosphodiesterase-4 inhibitors, protease inhibitors and antioxidants.
Abstract: This review will highlight recent advances in understanding the physiological role of calcium and effects of calcium channel blockers on pathogenetic factors in asthma, including airway smooth muscle contraction, mast cell degranulation and mucus secretion. A review of clinical studies with calcium channel blockers in asthma will also be presented.
The hypothesis that endothelium-derived relaxing factor (EDRF) modulates hypoxic pulmonary vasoconstriction (HPV) was tested in isolated, blood-perfused rat lungs ventilated with gas mixtures of 21% O2-5% CO2-74% N2 (normoxia) or of 3% O2-5% CO2-92% N2 (hypoxia); 30 µM NG-monomethyl-l-arginine (l-NMMA), an inhibitor of EDRF production, caused a reduction in the endothelium-dependent relaxant response to acetylcholine (ACh) from 62 ± 7, 88 ± 4, and 100 ± 4% to 26 ± 8, 49 ± 12, and 75 ± 7% at ACh concentrations of 1, 10, and 100 µM, respectively (p < 0.05 at all concentrations), indicating that l-NMMA acts via the inhibition of EDRF production. l-NMMA induced a concentration-related augmentation in HPV of 20 ± 5, 32 ± 8, and 34 ± 8% at concentrations of 30, 300, and 1,000 µM (p < 0.05, compared with a vehicle control group at all concentrations). The pressor response to a dose of anglotensin II (A-II), which produced the same increase in pulmonary artery pressure as that induced by hypoxia, was also significantly augmented (2 ± 0.6%), but to a lesser extent. The augmentation of HPV by 30 µM l-NMMA was completely reversed by 1 mM l-arginine (a precursor of EDRF), but not by d-arginine (an isomer of l-arginine). One and 6 mM l-arginine, but not 6 mM d-arginine caused a significant inhibition of HPV by 20 ± 2 and 47 ± 12% (p< 0.05, compared with the vehicle control group) and a small but not significant reduction in A-II-mediated contraction. We conclude that endothelium-derived relaxing factor modulates HPV and that the modulating action of EDRF on pulmonary blood pressure may be more relevant to HPV than to A-II-induced contraction. The ability of l-arginine to reduce HPV suggests that the formation of EDRF during hypoxemia may be limited by the availability of its precursor.
There is a close association between the allergic inflammatory response and neural control mechanisms. Inflammatory products may activate sensory nerves to cause symptoms, such as cough and chest tightness, sneezing, and itching, which are among the most troublesome aspects of allergic diseases. Sensory nerves themselves may also release neurotransmitters that increase inflammation, and this is termed neurogenic inflammation. The phenomenon of neurogenic inflammation is well established in the skin and in the respiratory tract of rodents, although there is less certainty about its role in human airway diseases. The peptides substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) are localized to a population of sensory neurons in the respiratory tract and the skin (1–4). These peptides have potent effects on the circulation, secretions, airway smooth muscle tone, and inflammatory and immune cells. Although some clues to the physiological and pathophysiological role of sensory neuropeptides are provided by their localization and functional effects, their role in allergic diseases will only become apparent when specific inhibitors are used in clinical studies. Depletion studies using capsaicin have proved to be very helpful in elucidating the role of sensory neuropeptides in animal models, but the recent development of specific receptor antagonists and other inhibitors is proving to be critical in understanding the role of neurogenic inflammation in the respiratory tract and skin. Most studies have concentrated on the lower airways and asthma (5),but there is increasing information about the nose and skin (4,6).
Eicosanoids such as leukotrienes, prostaglandins, lipoxins, and 15-hydroperoxyeicosatetraenoic acid (15-HETE) cause bronchoconstriction, increased microvascular permeability, mucus secretion, and polymorph chemotaxis. These pro-inflammatory effects are important in diseases such as asthma and cystic fibrosis where the levels of mediators are increased both in the stable and acute state. A study was conducted to examine the expression of the mRNA for the enzymes of the eicosanoid pathways (5-lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP), cyclo-oxygenases 1 and 2 (COX-1, COX-2), and 15-lipoxygenase (15-LO)) in normal subjects and in patients with stable atopic asthma and stable cystic fibrosis.Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of total RNA for 5-LO, FLAP, COX-1, COX-2, and 15-LO in peripheral blood polymorphonuclear cells and mononuclear cells from the three subjects groups.The expression of mRNA for 5-LO and FLAP was similar in normal subjects and in patients with asthma and cystic fibrosis. COX-1 was increased in both cell types in asthmatic patients. COX-2 and 15-LO were increased in polymorphs of patients with atopic asthma but not in mononuclear cells. COX-2 and 15-LO were undetectable in either cell type in patients with cystic fibrosis whereas COX-1 levels in polymorphs were similar to those in patients with asthma.The increased leukotriene production in asthma and cystic fibrosis is not explained by an increase in transcription of 5-LO and FLAP. Transcription of 15-LO and COX-2 is increased in atopic asthma. Transcription of COX-1 is increased in both atopic asthma and cystic fibrosis.
