Systemic inflammation caused by excessive production of TNF and other pro-inflammatory cytokines is a hallmark of sepsis. Recent studies demonstrate that electrical stimulation of the efferent vagus nerve inhibits TNF production and attenuates systemic inflammation (Nature, 2000, 420:853; Nature, 2003, 421:384). The α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages plays a key role in mediating the vagal anti-inflammatory effect (Nature, 2003, 421:384). These findings suggest the therapeutic potential of specifically targeting the α7nAChR to activate endogenous immunoregulatory mechanisms to temper excessive inflammatory responses. Here we examined the ability of the endogenous and selective α7nAChR agonist choline to attenuate TNF production in vitro and in vivo. Choline (0.01 - 50 mM) dose-dependently inhibited TNF release from endotoxin-stimulated RAW 264.7 mouse macrophages and primary human macrophages, which express α7nAchR (Nat. Med., 2004, 10(11): 1216; Nature, 2003, 421:384). Inhibition of TNF production from RAW 264.7 macrophages correlated with attenuation of NF-κB activity, suggesting that NF-κB represents a downstream target of cholinergic anti-inflammatory signaling. Choline treatment (5 and 50 mg/kg, i.p.), 30 min prior to endotoxin administration (6 mg/kg, i.p.) in mice, dose-dependently reduced serum TNF levels. These data demonstrate the anti-inflammatory activity of choline, an endogenous α7nAChR agonist, and indicate its therapeutic potential in restraining excessive inflammation. This study was funded in part by a FIMR research award to VAP.

Highly purified species-specific grass pollen antigens were used for inhalation bronchial challenge in 12 patients with atopic asthma. This was found to result in reproducible experimental asthma. Lodoxamide tromethamine was administered by inhalation in two different doses, 0.01 mg and 0.1 mg, to each patient, in double-blind, random, placebo-controlled manner, 15 minutes before pollen inhalation. It was found to have a significant protective action at both doses (p less than 0.05), but it produced troublesome side effects at the higher dose of 0.1 mg.

Studies were performed to investigate whether hyperresponsiveness of the airways could be induced in normal subjects by inhalation of prostaglandin E2 (PGE2). During the initial bronchodilator phase of PGE2 action the bronchoconstrictor effect of inhaled histamine was significantly antagonised. When bronchoconstrictor challenges were started shortly after the end of the bronchodilator response to PGE2, however, significant enhancement of the effects of both inhaled histamine and methacholine occurred. It was predominantly sensitivity to these agents that was increased, with a parallel shift of the dose-response curves towards increased bronchoconstriction. Thus PGE2 may be protective in the acute phase of a bronchoconstrictor challenge, but in a chronic inflammatory condition its net effect may be a balance between this beneficial action and a non-specific potentiation of the activity of bronchoconstrictor agents.

Angiotensin-converting enzyme activity in sarcoidosis is regarded both as a diagnostic feature and as an index of disease activity. Increased activity of this enzyme is thought to parallel macrophage and epithelioid cell activity. Beta-2-microglobulin, a low-molecular-weight protein associated with the histocompatibility antigens, is thought to reflect activation of immunocompetent cells, particularly lymphocytes. In 132 patients with known sarcoidosis no close association was found to exist between the results of the two assays (r = 0.53). Angiotensin-converting enzyme activity was raised in 33% and beta 2-microglobulin concentrations in 63% of patients with sarcoidosis. When analysed prospectively, the results of the two assays showed no correlation in 29 patients over periods of up to 19 months. Stage, duration of disease, and corticosteroid treatment showed no significant effect on levels of either angiotensin-converting enzyme or beta 2-microglobulin. The disparity between indices of macrophage and lymphocyte activation requires further study in sarcoidosis.

Bronchial hyper-responsiveness is a particular feature of asthma, but also occurs in normal subjects after a viral upper respiratory tract infection or ozone inhalation. Such stimuli would be expected to result in the release of chemical mediators of inflammation. In this study, the effects of one of these, prostaglandin F2 alpha (PGF2 alpha), on the response of normal subjects to inhaled histamine has been investigated. Nine normal volunteers took 10 inhalations of increasing concentrations of PGF2 alpha at 15-minute intervals from a Wright's nebuliser under standard conditions until a change in sGaw could be detected. The next lowest serial dilution of PGF2 alpha was subsequently inhaled by each subject every 15 min for 90 min to ensure the absence of a cumulative effect. Inhalation dose-response curves to histamine diphosphate were constructed on two separate occasions using the same standardised technique. Doses were administered every 15 min and sGaw determined five minutes after each. On one occasion each dose of histamine was immediately preceded by the non-active test dose of PGF2 alpha and on the second by saline as placebo. The study was performed double-blind and in random order. After pretreatment with PGF2 alpha the histamine dose-response curve was significantly shifted to the left in a parallel fashion (p less than 0.001). There was a significant decrease in the doses of histamine required to cause a 20% fall in sGaw (p less than 0.0015) but no significant change in the slopes of the dose-response regression lines, indicating that bronchial muscle sensitivity rather than reactivity had been predominantly affected.

Bronchial hyper-responsiveness isa particular feature ofasthma, butalso occursin normalsubjects after a viral upper respiratory tractinfection or ozone inhalation. Suchstimuli wouldbeexpected toresult intherelease ofchemical mediators ofinflammation. Inthis study, the effects ofone ofthese, prostaglandin F2a. (PGF2A), on theresponseofnormalsubjects toinhaled histamine hasbeeninvestigated. Ninenormal volunteers took10inhalations ofincreasing concen- trations ofPGF2oa at15-minute intervals fromaWright's nebuliser understandard conditions until a change insGawcould bedetected. Thenextlowest serial dilution ofPGF2oA was subsequently inhaled byeachsubject every 15minfor90mintoensuretheabsence ofa cumulative effect. Inhalation dose-response curves tohistamine diphosphate were constructed on two separate occasions using thesame standardised technique. Doses wereadministered every15minandsGaw determined five minutes after each. On one occasion eachdoseofhistamine was immediately preceded bythenon-active testdoseofPGF2ot andon thesecond bysaline asplacebo. Thestudy was performed double-blind andinrandomorder. After pretreatment withPGF2ot thehistamine dose-response curvewas significantly shifted totheleft inaparallel fashion (p<0-001). There was a significant decrease inthedoses ofhistamine required tocausea 20 fall insGaw(p<00015)but no significant change intheslopes ofthedose-response regression lines, indicating thatbronchial muscle sensitivity rather thanreactivity hadbeenpredominantly affected.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExperimental Thermodynamic Parameters for the Prediction of Natural Gas Hydrate Dissociation ConditionsP. B. Dharmawardhana, W. R. Parrish, and E. D. SloanCite this: Ind. Eng. Chem. Fundamen. 1980, 19, 4, 410–414Publication Date (Print):November 1, 1980Publication History Published online1 May 2002Published inissue 1 November 1980https://doi.org/10.1021/i160076a015RIGHTS & PERMISSIONSArticle Views798Altmetric-Citations130LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (558 KB) Get e-Alerts

ADVERTISEMENT RETURN TO ISSUEPREVArticleCorrection- Dissociation Pressures of Gas Hydrates Formed by Gas MixturesWilliam Parrish and John PrausnitzCite this: Ind. Eng. Chem. Process Des. Dev. 1972, 11, 3, 462Publication Date (Print):July 1, 1972Publication History Published online1 May 2002Published inissue 1 July 1972https://pubs.acs.org/doi/10.1021/i260043a025https://doi.org/10.1021/i260043a025research-articleACS PublicationsRequest reuse permissionsArticle Views133Altmetric-Citations12LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts

Current distributions on two plane, parallel electrodes embedded in the walls of a flow channel have been calculated for separation distance between electrodes to electrode length ratios of 0.5, 1, and 10. Secondary current distributions were calculated using the linear and Tafel polarization laws. Using the Tafel polarization law, current distributions were calculated at various fractions of the limiting current. In all cases considered, the electrodes are nearly independent of one another if the height to length ratio is ten or more.

The current distribution on a short, plane electrode in the wall of a flow channel is calculated at various fractions of the limiting current. Near the limiting current, the current density exceeds the local limiting value near the downstream end of the electrode.