Current drug targets
-
Current drug targets · Jun 2006
ReviewAntimicrobial peptides in COPD--basic biology and therapeutic applications.
A large number of studies have implicated activation of innate immune mechanisms in the pathogenesis of chronic obstructive pulmonary disease (COPD). Accumulation of inflammatory cells, chemokines and pro-inflammatory cytokines is a hallmark of activation of these mechanisms, but only a few studies have focussed on antimicrobial peptides in COPD. These peptides are a central component of innate immunity, and airway epithelial cells and neutrophils in the lung are the main cellular sources. ⋯ This is based on the observation that they not only contribute to defense against respiratory pathogens that have been associated with COPD, but may also contribute to the influx of inflammatory cells, activation of adaptive immunity and epithelial remodeling. The aim of this review is to provide an update on the basic biology of antimicrobial peptides in the lung, with a focus on their putative role in COPD. In addition, the implication of this knowledge for future treatment of COPD is discussed.
-
Current drug targets · May 2006
Airway smooth muscle phenotype and function: interactions with current asthma therapies.
Asthma incidence has climbed markedly in the past two decades despite an increased use of medications that suppress airway inflammation and repress contraction of smooth muscle that encircles the airways. Asthmatics exhibit episodes of airway inflammation that potentiates reversible airway smooth muscle spasm. A hallmark diagnostic symptom of asthma is airway hyperresponsiveness to inhaled non-allergic stimuli, such as methacholine, that directly induce airway smooth muscle contraction. ⋯ Mature airway smooth muscle cells are phenotypically plastic, enabling them to subserve contractile, proliferative, migratory and secretory functional responses that contribute to airway remodeling and persistent hyperresponsiveness. This review assesses current understanding of acute and chronic effects of common anti-asthma medications on the diverse phenotype and functional characteristics of airway smooth muscle cells. Furthermore, we describe the significance of these effects in the treatment of asthma symptoms and pathogenesis.
-
Natural products represent a rich resource for drug delivery and are currently being exploited to target tumour angiogenesis. A vast array of products of natural origin have been shown to have anti-angiogenic potential in preclinical models, including purified endogenous inhibitors, and exogenous compounds derived from varied species of plant, animal and micro-organism. Over a dozen of these agents have now entered clinical trial. This review discusses evidence for the efficacy of this drug class and key issues in the translation of pre-clinical results into the development of efficacious drugs for clinical use.
-
Delirium is a global impairment of upper brain functions caused by an organic substrate. It is frequently observed in the postoperative period, particularly in elderly people. Vascular and orthopedic surgery and long-duration surgery are associated with a higher incidence of postoperative delirium. ⋯ Atypical neuroleptics, like risperidone, have not yet been studied in postoperative delirium, although some case reports in which they were successfully used have been published. Physiostigmine is effective in delirium caused by anticholinergic syndrome; vitamins may be useful in alcoholics; melatonin use has been suggested in order to prevent and treat delirium by normalizing sleep-wake cycle alterations. Environmental interventions are often costless and may be very useful to prevent and treat postoperative delirium in patients at risk.
-
Critically ill patients, particularly those under mechanical ventilation, require analgo-sedation to control noxious stimuli and enhance comfort. Despite their harmful side effects, such as respiratory depression, physical dependence and difficult arousal, opioids are effective in providing a good level of analgesia and comfort. Traditional opioids (morphine and fentanyl) have been shown effective in providing analgesia; however, the respiratory adverse effects and their pharmacokinetics, with an high risk of accumulation, limits their use, especially for a long-term sedation. In the last decade, new synthetic opioids with limited side effects and favourable pharmacokinetics profile, such as Sufentanil and Remifentanil, have been investigated to evaluate their efficacy in mitigating pain and enhancing comfort in critically ill patients.