Emphysema Predicts Hospitalisation and Incident Airflow Obstruction among Older Smokers: A Prospective Cohort Study

Emphysema on CT is common in older smokers. We hypothesised that emphysema on CT predicts acute episodes of care for chronic lower respiratory disease among older smokers.Participants in a lung cancer screening study age ≥ 60 years were recruited into a prospective cohort study in 2001-02. Two radiologists independently visually assessed the severity of emphysema as absent, mild, moderate or severe. Percent emphysema was defined as the proportion of voxels ≤ -910 Hounsfield Units. Participants completed a median of 5 visits over a median of 6 years of follow-up. The primary outcome was hospitalization, emergency room or urgent office visit for chronic lower respiratory disease. Spirometry was performed following ATS/ERS guidelines. Airflow obstruction was defined as FEV1/FVC ratio <0.70 and FEV1<80% predicted.Of 521 participants, 4% had moderate or severe emphysema, which was associated with acute episodes of care (rate ratio 1.89; 95% CI: 1.01-3.52) adjusting for age, sex and race/ethnicity, as was percent emphysema, with similar associations for hospitalisation. Emphysema on visual assessment also predicted incident airflow obstruction (HR 5.14; 95% CI 2.19-21.1).Visually assessed emphysema and percent emphysema on CT predicted acute episodes of care for chronic lower respiratory disease, with the former predicting incident airflow obstruction among older smokers

Inhibition of gastric acid secretion by the aqueous extract and purified extracts of Stachytarpheta cayennensis

Stachytarpheta cayennensis Schauer (Verbenaceae) is used in folk medicine to treat gastric and intestinal disturbances. the freeze-dried aqueous extract of the whole plant tested to rodents up to the dose of 2 g kg(-1), p.o., did not produce signs of toxicity. the extract (0.5-2 g kg(-1), p.o.) increased the intestinal motility and protected mice against ulcers induced by restraint-in-cold, ethanol or indomethacin. Injected into the duodenal lumen the extract inhibited the basal acid secretion as well as that induced by histamine and bethanecol in pylorus-ligated mice. Partition of the aqueous extract in organic solvents yielded semipurified fractions whose antiacid activity guided further chemical purification. All the fractions were chromatographically characterized, the main substances in the active extract being flavonoids and amines; some substances were revealed only under UV light. the most purified active fraction obtained presented a specific activity 5-10 times higher than that detected in the original extract. Data from pharmacological studies indicate that the antiulcer activity of S. cayennensis is related to a specific inhibition of gastric acid secretion. Cholinergic and histaminergic stimulation of acid secretion were similarly reduced by the extracts suggesting inhibition of common steps in both pathways, possibly at the level of histamine release/H-2 receptor interaction, or at the proton pump. Whatever the mechanisms involved, the present data confirm the plant effectiveness as antiacid/antiulcer and laxative.Universidade Federal de São Paulo,ESCOLA PAULISTA MED,DEPT PHARMACOL,NAT PROD SECT,BR-04044020 São Paulo,BRAZILUniversidade Federal de São Paulo,ESCOLA PAULISTA MED,DEPT PHARMACOL,NAT PROD SECT,BR-04044020 São Paulo,BRAZILWeb of Scienc

Sulfatase activity in the oyster Crassostrea virginica: its potential interference with sulfotransferase determination

4 pages, 2 figures.-- PMID: 15963577 [PubMed].-- Printed version published Aug 15, 2005.Two sulfatase isoforms, a soluble one with an optimum pH of 5.0, and a microsomal one with an optimum pH of 7.6, were observed in digestive gland, gonads, mantle and gills of the oyster C. virginica. The highest sulfatase activity was recorded in the digestive gland cytosol and is likely to interfere with the in vitro determination of sulfotransferase activity. Indeed, the sulfatase inhibitor Na2SO3 led to an increase of measured sulfotransferase activity (31 ± 9%), suggesting that those sulfatases might be partially responsible for the low sulfotransferase activities found in C. virginica.Peer reviewe

Esterification of vertebrate-type steroids in the Eastern oyster (Crassostrea virginica)

8 pages, 5 figures, 2 tables.-- PMID: 15013691 [PubMed].Characteristics of acyl-coenzyme A (acyl-CoA):steroid acyltransferase from the digestive gland of the oyster Crassostrea virginica were determined by using estradiol (E2) and dehydroepiandrosterone (DHEA) as substrates. The apparent Km and Vmax values for esterification of E2 with the six fatty acid acyl-CoAs tested (C20:4, C18:2, C18:1, C16:1, C18:0, and C16:0) were in the range of 9–17 μM E2 and 35–74 pmol/min/mg protein, respectively. Kinetic parameters for esterification of DHEA (Km: 45–120 μM; Vmax: 30–182 pmol/min/mg protein) showed a lower affinity of the enzyme for this steroid. Formation of endogenous fatty acid esters of steroids by microsomes of digestive gland and gonads incubated in the presence of ATP and CoA was assessed, and at least seven E2 fatty acid esters and five DHEA fatty acid esters were observed. Some peaks eluted at the same retention times as palmitoleoyl-, linoleoyl-, oleoyl/palmitoyl-, and stearoyl-E2; and palmitoleoyl-, oleoyl/palmitoyl-, and stearoyl-DHEA. The same endogenous esters, although in different proportions, were produced by gonadal microsomes. The kinetic parameters for both E2 (Km: 10 μM; Vmax: 38 pmol/min/mg protein) and DHEA (Km: 61 μM; Vmax: 60 pmol/min/mg protein) were similar to those obtained in the digestive gland. Kinetic parameters obtained are similar to those observed in mammals; thus, fatty acid esterification of sex steroids appears to be a well-conserved conjugation pathway during evolution.Partial support from NIEHS Center Grant No. ES05022, and EU Project BEEP (ENVK3-CT-2000-00025).Peer reviewe

Esterification of vertebrate-like steroids in the eastern oyster (Crassostrea virginica)

4 pages, 1 table.-- PMID: 15178069 [PubMed].-- Printed version published in issue Aug-Dec 2004.-- Issue title: "Twelfth International Symposium on Pollutant Responses in Marine Organisms" (Tampa Bay, FL, United States, May 9-13, 2003).The esterification of two model vertebrate steroid hormones –estradiol (E2) and dehidroepiandrosterone (DHEA)– was studied in the oyster Crassostrea virginica. The activity of acyl-CoA:steroid acyltransferase was characterized in microsomal fractions isolated from oyster digestive glands. The apparent Km and Vmax values changed with the fatty acid acyl-CoA used (C20:4, C18:2, C18:1, C16:1, C18:0 or C16:0), and were in the range of 9–17 μM, and 35–74 pmol/min/mg protein for E2, and in the range of 45–120 μM, and 30–182 pmol/min/mg protein for DHEA. Kinetic parameters were also assessed in gonadal tissue. The enzyme saturated at similar concentrations, although conjugation rates were lower than in digestive gland. Preliminary data shows that tributyltin (TBT) in the low μM range (1–50) strongly inhibits E2 and DHEA esterification, the esterification of E2 being more sensitive to inhibition than that of DHEA. Overall, results indicate that apolar conjugation occurs in oysters, in both digestive gland and gonads, at a very similar rate to mammals, suggesting that this is a well conserved conjugation pathway during evolution. Esterification, together with other mechanisms, can modulate endogenous steroid levels in C. virginica, and might be a target for endocrine disrupters, such as TBT.Predoctoral fellowship from the Spanish Government, and partial support from NIEHS Center Grant No. ES05022, and EU Project BEEP (ENVK3-CT-2000-00025).Peer reviewe

Impaired Flow-mediated Dilation Is Associated with Low Pulmonary Function and Emphysema in Ex-smokers: The Emphysema and Cancer Action Project (EMCAP) Study

Rationale: Basic science research suggests a causal role for endothelial dysfunction in chronic obstructive pulmonary disease (COPD). Clinical studies examining endothelial function are lacking, particularly early in the disease. Flow-mediated dilation (FMD) is a physiologic measure of endothelial reactivity to endogenous nitric oxide

Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study

INTRODUCTION: The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) remains incompletely understood and strategies for treatment and prevention have not altered significantly for many years. Improved understanding of the role of respiratory pathogens in acute exacerbations of COPD (AECOPD) is required and the use of molecular microbiological techniques may lead to insights into host–pathogen interactions and the development of more targeted therapeutic approaches. METHODS AND ANALYSES: Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) is a longitudinal epidemiological study to assess how changes in the COPD airway microbiome contribute to the incidence and severity of AECOPD. Patients with COPD aged 40–85 are followed monthly for 2 years, and reviewed within 72 h of onset of symptoms of AECOPD. Exacerbations are detected using daily electronic diary cards. Blood, sputum, nasopharyngeal and urine samples are collected at prespecified timepoints. Molecular diagnostic and typing techniques are used to describe the dynamics of airway infection during AECOPD and stable disease, and associations with clinical outcome. This study aims to refine the case definition of AECOPD to reflect the possible microbiological aetiology. AERIS will assess the impact of AECOPD on health-related quality of life and healthcare resource utilisation, and the possible interactions between nutritional status, infection and immune responses. ETHICS AND DISSEMINATION: AERIS is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, and has been approved by the institutional ethics and review board. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. DISCUSSION: Few other studies have addressed the complexity of the microbiological and systemic components of COPD or employed real-time electronic tracking of symptoms to identify AECOPD and potential aetiological triggers. RESULTS: Results of AERIS will increase our understanding of the contribution of pathogens to AECOPD, potentially leading to new targeted therapeutic and preventative interventions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01360398

Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study

INTRODUCTION: The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) remains incompletely understood and strategies for treatment and prevention have not altered significantly for many years. Improved understanding of the role of respiratory pathogens in acute exacerbations of COPD (AECOPD) is required and the use of molecular microbiological techniques may lead to insights into host-pathogen interactions and the development of more targeted therapeutic approaches.METHODS AND ANALYSES: Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) is a longitudinal epidemiological study to assess how changes in the COPD airway microbiome contribute to the incidence and severity of AECOPD. Patients with COPD aged 40-85 are followed monthly for 2 years, and reviewed within 72 h of onset of symptoms of AECOPD. Exacerbations are detected using daily electronic diary cards. Blood, sputum, nasopharyngeal and urine samples are collected at prespecified timepoints. Molecular diagnostic and typing techniques are used to describe the dynamics of airway infection during AECOPD and stable disease, and associations with clinical outcome. This study aims to refine the case definition of AECOPD to reflect the possible microbiological aetiology. AERIS will assess the impact of AECOPD on health-related quality of life and healthcare resource utilisation, and the possible interactions between nutritional status, infection and immune responses.ETHICS AND DISSEMINATION: AERIS is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, and has been approved by the institutional ethics and review board. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications.DISCUSSION: Few other studies have addressed the complexity of the microbiological and systemic components of COPD or employed real-time electronic tracking of symptoms to identify AECOPD and potential aetiological triggers.RESULTS: Results of AERIS will increase our understanding of the contribution of pathogens to AECOPD, potentially leading to new targeted therapeutic and preventative interventions.TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01360398.</p