Library

Notes: Azithromycin is an acid-stable macrolide that achieves remarkably high concentrations in gastric tissue, persisting above the MIC90 for Helicobacter pylori over a period of 5-days, after a single 500 mg oral dose.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To evaluate and compare the efficacy, safety, and tolerability of two eradicating regimens of pantoprazole, azithromycin and tinidazole.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:A total of 100 consecutive symptomatic H. pylori-positive patients received pantoprazole 40 mg b.d. for 1 week, and were randomly assigned to either azithromycin 500 mg o.m. and tinidazole 500 mg b.d. during the first 3 days (early group, n=50) or during the last 3 days of therapy with pantoprazole (late group, n=50). H. pylori status was assessed by histology and rapid urease test at entry and by histology and 13C-urea breath test 1 month after the end of the therapy.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Ninety-nine patients completed the study. H. pylori was eradicated in 86% of patients in the early group (intention-to-treat 86%) and in 88% of patients in the late group (intention-to-treat 88%).〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:This short triple therapy is effective for H. pylori eradication. The compliance was excellent and side-effects negligible. Moreover, the pantoprazole pre-treatment did not modify the efficacy of the therapy.

Notes: Background : The dilation of oesophageal intercellular spaces, clearly apparent in transmission electron microscopy images, is a marker of cellular damage induced by acid.Aim : To analyse the presence of dilated intercellular spaces and to quantify the scores in controls and in patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux accompanied by erosive or non-erosive reflux disease.Methods : Thirty-eight symptomatic patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux and 12 asymptomatic controls, classified on the basis of pH-metry and bilimetry, underwent endoscopy. Six tissue biopsies were taken from the normal mucosa for light microscopy and transmission electron microscopy evaluation. Dilated intercellular spaces were measured on photomicrographs of the specimens (at least 100 transects were measured for each patient).Results : Twenty-two patients with gastro-oesophageal reflux disease had normal macroscopic mucosa but, at histology, five patients with erosive gastro-oesophageal reflux disease had mild oesophagitis and one had moderate oesophagitis. Seven patients with duodenal gastro-oesophageal reflux had normal mucosa, whilst three with erosive duodenal gastro-oesophageal reflux had mild oesophagitis at histology. At transmission electron microscopy, all controls had dilated intercellular spaces of less than 1.69 µm. Each symptomatic patient had a mean dilated intercellular space value and a mean value of the maximum dilated intercellular space at least three or more times greater than that in controls (P 〈 0.001). No statistical differences were observed between erosive and non-erosive oesophagitis.Conclusions : The dilated intercellular space is an extremely sensitive marker of damage in gastro-oesophageal reflux disease, duodenal gastro-oesophageal reflux and non-erosive reflux disease, and serves as the most appropriate marker of damage evaluation in non-erosive reflux disease reported to date. A mean dilated intercellular space of 0.74 µm provides a cut-off score for damage. No quantitative or qualitative differences in dilated intercellular space scores were found between pure and mixed acid reflux.

Notes: Over the last few years, the demonstration of beneficial effects of leukotriene receptor antagonists in various forms of asthma has renewed clinical and pharmacologic interest in this class of lipid mediators. Several studies demonstrated an increased biosynthesis of cysteinyl leukotrienes (CysLT) in asthmatic patients. However, the reasons for the dysregulated production of CysLTs in asthmatic patients are not completely defined. An improved method of lipid mediator detection and the availability of cells isolated from human airways (by bronchoalveolar lavage [BAL] and bronchial biopsies) have allowed initial studies to address this issue. Eosinophils retrieved from inflamed airways of asthmatics have a larger arachidonic acid (AA) content than their blood counterpart. The high level of AA in these cells is primarily due to a remodeling of endogenous arachidonate pools with the accumulation of this fatty acid in a triglyceride-associated pool. In addition, elevated levels of a secretory form of phospholipase A2, the key enzyme initiating the cascade of CysLTs, are found in the BAL of asthmatics. Finally, eosinophils isolated from the BAL of asthmatics have an increased expression of LTC4 synthase. The level of expression of this enzyme correlates with the increased amount of CysLTs produced in the airways of these patients. Taken together, these data identify at least two possible mechanisms to explain the excessive CysLT production in asthmatics:〈list xml:id="l1" style="custom"〉an increased content of AA in the glycerolipid pools of inflammatory cellsan enhanced activity of key biosynthetic enzymes involved in CysLT synthesis.

Notes: The recent advances in the knowledge of the basic mechanisms underlying asthmatic inflammation have significantly contributed to the delineation of new therapeutic perspectives for asthma. There are currently three main approaches to the development of novel antiasthma treatments:〈list xml:id="l1" style="custom"〉improvement in existing classes of drugsidentification of new compounds able to interfere with the complex network of proinflammatory mediators, cytokines, chemokines, and adhesion molecules involved in the pathogenesis of asthmautilization of new forms of immunotherapy aimed at blocking the unbalanced Th2 response which characterizes the pathophysiology of asthma.Such a remarkable expansion in available therapeutic options will probably allow us, over the next decade, to treat asthma by more selectively targeting the pathogenetic events responsible for this widespread airway disease.