Reactive inflammation

The likelihood that materials will produce local effects in the respiratory tract depends on their physical and chemical properties, solubiHty, reactivity with fluid-lining layers of the respiratory tract, reactivity with local tissue components, and (in the case of particulates) the site of deposition. Depending on the nature of the material, and the conditions of the exposure, the types of local response produced include acute inflammation and damage, chronic... 

Pollutant (if gaseous) Corrosiveness Inflammability Toxicity Reactivity... 

Several chemical compounds may cause inflammation or constriction of the blood vessel wall (vasoconstriction). Ergot alkaloids at high doses cause constriction and thickening of the vessel wall. Allylamine may also induce constriction of coronary arteries, thickening of their smooth muscle walls, and a disease state that corresponds to coronary heart disease. The culprit is a toxic reactive metabolite of allylamine, acrolein, that binds covalently to nucleophilic groups of proteins and nucleic acids in the cardiac myocytes. 

Acute phase reactants (e.g., C-reactive protein) are proteins that increase during inflammation and are deposited in damaged tissues. They were first discovered in the serum, but are now known to be involved in inflammatory processes in the brain (e.g., found in the brain of Alzheimer patients and associated with amyloid plaques). 

The wide range of inflammation-related factors that adipocytes secrete is linked to the inflammatory response that the tissue exhibits in obesity [1]. Obesity in general, like an increasing number of other diseases, is characterised by a state of mild chronic inflammation, and adipose tissue plays a central role in this. The production of most inflammation-related adipokines increases markedly in obesity and there is an elevated circulating level of a number of these factors as well as of other inflammatory markers such as C-reactive protein (CRP). The increased production of inflammatory adipokines (and decreased production of adiponectin with its anti-inflammatory action) in the obese is considered to play a critical role in the development of the obesity-associated pathologies, particularly type 2 diabetes and the metabolic syndrome [1]. 

Airway inflammation is a characteristic clinical feature of asthma. The distinction between the LAR and chronic inflammation becomes more difficult as the disease progresses. Infiltrated leukocytes release ototoxic mediators such as reactive oxygen species (ROS) and cationic (basic) proteins causing epithelial damage and cyfo/cmas that perpetuate the inflammation. Sustained inflammation leads to airway hyperrespon-siveness and airway remodeling. 

Inflammation. Figure 1 Sequence of events in the recruitment of leukocytes in postcapillary venules adjacent to injured tissue. At the site of lesion, diverse reactive substances stimulate the endothelium to produce inflammatory cytokines, chemoattractants and other inflammatory mediators. The cytokine-activated endothelium expresses adhesion molecules that lead to the low affinity interactions between leukocytes and endothelium, which is mediated by selectins and described as rolling. Subsequently integrins mediate the firm adhesion of leukocytes, which allows emigration of the cells from venules into the interstitial compartment. Activated mast cells, PMNs and macrophages secrete cytokines (TNFa), lipid mediators (LTB4) and other inflammatory players (histamine, NO). 

In the interstitium, angiotensin II induces proliferation of mesangial cells and fibroblasts and the synthesis of collagen and other matrix molecules by these cells via the ATI receptor. Moreover, by the concomitant stimulation of chemoattractant cytokines, inflammation is induced. These processes are mediated by endothelin, transforming growth factor(3, and reactive oxygen species, and finally lead to interstitial fibrosis and glomerulosclerosis observed in hypertension and diabetes. 

A non-allergic mechanism imderlying precipitation of asthmatic attacks by aspirin in hypersensitive patients was proposed over 30 years ago [4]. It was founded on pharmacological inhibition of COX of arachidonic acid and explained a cross-reactivity between different NSAIDs varying in chemical structure. This COX theory was confirmed by several studies [11] and was further refined following discovery of the second COX isoenzyme - COX-2. At least two COX isoenzymes, COX-1 and COX-2, are coded by separate genes. Their role in inflammation, asthma and anaphylaxis has been reviewed previously [12]. 

These proteins are called acute phase proteins (or reactants) and include C-reactive protein (CRP, so-named because it reacts with the C polysaccharide of pneumococci), ai-antitrypsin, haptoglobin, aj-acid glycoprotein, and fibrinogen. The elevations of the levels of these proteins vary from as little as 50% to as much as 1000-fold in the case of CRP. Their levels are also usually elevated during chronic inflammatory states and in patients with cancer. These proteins are believed to play a role in the body s response to inflammation. For example, C-reactive protein can stimulate the classic complement pathway, and ai-antitrypsin can neutralize certain proteases released during the acute inflammatory state. CRP is used as a marker of tissue injury, infection, and inflammation, and there is considerable interest in its use as a predictor of certain types of cardiovascular conditions secondary to atherosclerosis. Interleukin-1 (IL-1), a polypeptide released from mononuclear phagocytic cells, is the principal—but not the sole—stimulator of the synthesis of the majority of acute phase reactants by hepatocytes. Additional molecules such as IL-6 are involved, and they as well as IL-1 appear to work at the level of gene transcription. 

Han HS, Qiao Y, Karabiyikoglu M, Giffard RG, Yenari MA. Influence of mild hypothermia on inducible nitric oxide synthase expression and reactive nitrogen production in experimental stroke and inflammation. J Neurosci 2002 22 3921-3928. 

Two preparations of diesters of phosphonous acid have been reported, - One of these, which claims to be the first preparation of these derivatives, involves the reaction of ammonium hypophosphite with triaikylsilylamines to give bis(trialkylsilyl) esters (127) in excellent yield. These compounds are extremely reactive, e.g. they are spontaneously inflammable in air. Dialkyl phosphonites (128) have also been prepared by the reduction of... 

This concept meshes with another important environmental issue solvents for organic reactions. The use of chlorinated hydrocarbon solvents, traditionally the solvent of choice for a wide variety of organic reactions, has been severely curtailed. In fact, so many of the solvents favoured by organic chemists have been blacklisted that the whole question of solvents requires rethinking. The best solvent is no solvent and if a solvent (diluent) is needed then water is preferred. Water is non-toxic, non-inflammable, abundantly available, and inexpensive. Moreover, owing to its highly polar character, one can expect novel reactivities and selectivities for organometallic catalysis in water. 

The NFPA code is represented in a diamond containing 4 sectors, respectively toxicity, inflammability, reactivity and special risks . A coloured code that will appear on glass labels, at the back of transport vehicles, room doors etc enables the danger to be better noted. It is used by American companies although some French companies have also adopted it and it appears to be an efficient device. 

With regard to inflammability, NFPA coding classifies reactivity hazard into five degrees from 0 (no danger) to 4 (maximum danger), defined as follows ... 

In France these correspond to what is decided by the European UnionT The codes used for inflammable, unstable substances and for some risks linked to reactivity have already been described. There are numerous codes for toxicity and comosive-ness and these have the skull as a symbol for toxic substances, an X for harmful substances pabout risk and some cautionary advice that bear numbers preceded with the letter R, and sentences about risk and S for cautionary advice. Everything has to appear on the container labels. Cautionary advice has never seemed coherent or sufficiently exhaustive and only risk codes are mentioned in Part Three. Notes on risk appear in the following tabie. 

Penalties are attributed to this factor, which is above all a function of inflammability. These penalties consist of adding a given percentage if the substances have any specific unstable or reactive properties. The table below indicates the aggravating percentages to be applied. 

The Code du travail and NFPA hazard codes are explained in Part I in the references that are concerned with each risk. For inorganic products the inflammability, reactivity and toxicity codes are mentioned. For organic products the toxicity code is the only one that is given. Indeed, the inflammability code can be found easily (see para 1.5.1) and the reactivity code is included in chapter 6 under dangerous reactions of inorganic products. 

Physical data AWf (UAnol) (physical stale) Eb (°OmniHg) (if substance volatile) (nlBar) (T) (if substance volatile). Inflammability data LEUUH. (%) Pa,(°C) Arn°0 NFPA (flame) NFPA (reactivity) Latxxir Code (Tr). 

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