Mediators of inflammation

Inflammatory molecules include adhesion molecules, che-mokines and cytokines, many of which are up-regulated in acute cerebral ischemia and conh ibute to the inflammatory process. The release of pro-inflammatory cytokines is a direct consequence of the ionic imbalances and free calcium accu-muladon that lead to the release of free fatty acids and other 

Migration of Immune Cells Across the Blood Brain Bander 

Blockade of neudophil infildadon in experimental sdoke models, through inhibidon of adhesion molecules (ICAM-1, 

The concept of the neurovascular unit —a funcdonal endty comprising neurons, asdocytes, smooth muscle cells and endothelial cells— has now emerged and it is appreciated that this coordinated unit plays a key role in the hemodynamic response to alteradons in brain funcdon and acdvity. Disrup-don of this regulatory network occurs after sdoke and it is now believed that efforts at neuroprotecdon should target the endre unit, not just neurons (del Zoppo, 2006). 

Effects of Ischemic S troke on the Systemic Immune System 

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Histamine is a biogenic amine that is widely distributed in the body and functions as a major mediator of inflammation and allergic reactions, as a physiological regulator of gastric acid secretion in the stomach, as a neurotransmitter in the central nervous system (CNS) and may also have a role in tissue growth and repair. 

Inflammation. Table 1 Endogenously produced mediators of inflammation... 

These cells respond to a number of different chemoattractants which have specific and distinct receptors on the membrane surface (for recent reviews see Refs. 3 and 4). Such chemoattractants include N-formylpeptides, which are bacterial peptides, and mediators of inflammation such as leukotriene B4, C5a, and platelet activating factor. 

With regard to epinephrines potential adverse cardiac effects, it is important to remember that in anaphylaxis, the heart is a target organ. Mast cells located between myocardial fibers, in perivascular tissue, and in the arterial intima are activated through IgE and other mechanisms to release chemical mediators of inflammation, including histamine, leukotriene C4, and prostaglandin D2. Coronary artery spasm, myocardial injury, and cardiac dysrhythmias have been documented in some patients before epinephrine has been injected for treatment of anaphylaxis, as well as in patients with anaphylaxis who have not been treated with epinephrine [11, 12]. 

The biological membranes that surround cells and form the boundaries of intracellular organelles contain polyunsaturated fiitty acids, which are susceptible to oxidation. This reaction is used under controlled conditions by enzymes, such as the lipoxygenases or cyclooxygenases, within cells to produce oxygenated lipids, which can act as mediators of inflammation (Smith and Marnett, 1991 Yamamoto, 1992). Such compounds are characterized by their high potency and specificity in their interaction with cells (Salmon, 1986). While these enzymatic reactions... 

Increased capillary permeability may allow plasma proteins to leak into the interstitial spaces of a tissue. The presence of excess protein in these spaces causes an increase in interstitial fluid colloid osmotic pressure and pulls more fluid out of the capillaries. Mediators of inflammation such as histamine and bradykinin, which are active following tissue injury and during allergic reactions, increase capillary permeability and cause swelling. 

It is possible that nematode-secreted AChEs act on alternative substrates to ACh. We had previously suggested, on the basis of structural similarity, that platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, might represent such an alternative substrate (Blackburn and Selkirk, 1992b) but subsequent studies demonstrated that purified AChEs did not cleave PAF, and the enzyme responsible for this activity in secreted products of N. brasiliensis, PAF acetylhydrolase, was purified and defined as a distinct heterodimeric protein (Grigg et al., 1996). Although an open mind on the subject sould be kept, the strict substrate specificity of the nematode-secreted AChEs suggests that they most likely act on ACh alone. 

In method A the reaction is performed under reflux in CH2CI2. Method B is without solvent under irradiation. It has been shown that yields are higher and reaction times much lower for method B. This methodology was applied to the synthesis of the precursor of leucettamine B (mediator of inflammation). 

Tumour necrosis factor (human TNF-oc) 3 471 52 000 Mediator of inflammation and immunity... 

LPS, the immunoactive component of endotoxin, is a constituent of the outer membrane of Gram-negative bacterial cell walls. LPS is found in the environment and has been extensively studied, both as a mediator of inflammation and as a major contributing factor to bacterial pathogenesis.60 LPS exerts many of its effects through induction of pro-inflammatory cytokines, including IL-ip, TNF-a and IL-6.61 An important feature... 

Tumor necrosis factor-a (TNF-a) is a critical mediator of inflammation in autoimmune diseases like Crohn s disease and rheumatoid arthritis. Infliximab binds TNF-a and prevents its binding to the TNF receptor for treatment of these diseases. 

Sulfasalazine is composed of sulfapyridine and 5-ASA molecules linked by an azo bond. Sulfapyridine has no effect on the inflammatory bowel disease, and instillation of this agent into the colon does not heal colonic mucosa. It is, however, responsible for most of sulfasalazine s side effects, including sulfa allergic reactions. 5-ASA, the active metabolite, may inhibit the synthesis of mediators of inflammation. 

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