Inflammation, phases

During the initial acute inflammation phase, which is protective in nature, PUFA provide a steady supply of pro-inflammatory chemotactic lipid mediators such as prostaglandins and leukotrienes that help to recruit polymorphonuclear neutrophils... 

The second phase, the proliferation phase, starts when the wound is clean and the inflammation phase is almost completed. The purpose of this phase is to rebuild the... 

The inflammation phase ( 0-6 days postwounding) involves increased vascular permeability and chemotaxis of cells from the surrounding tissues into the wound. Release of cytokines and growth factors takes place and cell migration is activated... 

Theophylline s predominant mode of action appears to be bronchocHlation. However, it has also been shown that prophylactic acHriinistration of theophylline provides some protection from asthma attacks and suppresses the late-phase response (67,68). Some researchers beHeve that at therapeutic semm concentrations theophylline may inhibit the development of airway inflammation (69). There are conflicting reports on the effect of theophylline on allergen-induced bronchial hyperresponsiveness some clinical stucHes report a reduction in hyper-responsiveness, others do not (69,70). Theophylline clearly does not reverse the general bronchial hyperresponsiveness over the course of long-term therapy (71). Because of the relationship between... 

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). 

A number of adipokines are linked to inflammation and immunity (Fig. 1). This includes both leptin and adiponectin, and also a number of other key inflammatory proteins, particularly cytokines and chemokines [1]. The cytokines and chemokines encompass interleukin-1(3 (EL-1 (3), IL-6, DL-10, TNFa, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF). Other major inflammation-related adipokines include nerve growth factor (NGF), and acute phase proteins such as serum amyloid A and haptoglobin. In addition, adipocytes secrete plasminogen activator inhibitor-1 (PAI-1), which is an important thrombotic factor as well as an acute phase protein. 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

Vertex also put in clinical trial VX-765, another caspase-1 -specific, YVAD-derived peptidomimetic that is in vitro slightly more potent then pralnacasan (IC50 0.8 nM). Evaluation of VX-765 in a mouse model of oxazolone-induced dermatitis showed a dose-dependent (10-100 mg/kg) inhibition of ear inflammation. Consequently, VX-765 was enrolled in a 4-week phase Ila safety and pharmacokinetic study for psoriasis. However, Vertex has not communicated any results yet. 

In addition to binding of FceRII at the surface of B cells, IgE also binds FceRI at the surface of DCs and monocytes. This process increases the uptake of allergen by DCs and the subsequent presentation to specific Th cells, which drive the late phase of the allergic inflammation [3,144]. 

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. 

Gabay C, Kushner I Acute-phase proteins and other systemic responses to inflammation. New Engl J Med 1999 340 448. 

Room temperature ionic liquids (RTILs), such as those based on A,A-dialkylimidazolium ions, are gaining importance (Bradley, 1999). The ionic liquids do not evaporate easily and thus there are no noxious fumes. They are also non-inflammable. Ionic liquids dissolve catalysts that are insoluble in conventional organic chemicals. IFP France has developed these solvents for dimerization, hydrogenation, isomerization, and hydroformylation reactions without conventional solvents. For butene dimerization a commercial process exists. RTILs form biphasic systems with the catalyst in the RTIL phase, which is immiscible with the reactants and products. This system is capable of being extended to a list of organometallic catalysts. Industrial Friedel-Crafts reactions, such as acylations, have been conducted and a fragrance molecule tra.seolide has been produced in 99% yield (Bradley, 1999). 

The combustion of a chemical substance takes place in the gaseous phase except with metals and metalloids where combustion takes place in the solid phase. This impiies that a soiid or a liquid inflammable chemical has the ability to vapourise in order to buiid an inflammable vapour-air mixture. The two indicative parameters are the boiling point and, most important, the vapour pressure of the liquid. 

On the other hand, two-phase systems have potential disadvantages. Biocatalyst inhibition or denaturation may occur in contact with organic solvent dissolved in the aqueous phase or at the organic-aqueous interface. The system may be complex and inflammable. 

Iwamura and Ueda [386] described compound (611) as a CB2 selective inverse agonist in a patent application. The potential therapeutic roles of CB2 antagonists are not clearly defined at the moment, although roles in regulation of the immune system and inflammation have been widely proposed. This patent application describes that activity of compound (611) in a mouse model of asthma, in which the compound suppressed immediate and late-phase asthmatic response and airway hyper-responsiveness. 

In the late phase response, activated airway cells release inflammatory cytokines and chemokines, recruiting inflammatory cells into the lungs. The late phase response occurs 4 to 6 hours after the initial allergen challenge and results in a less intense bronchoconstriction as well as increased airway hyperresponsiveness and airway inflammation.6... 

Shirley, NY) sodium ferric gluconate (Ferrlecit by Watson Pharmaceuticals, Inc., Corona, CA) and iron sucrose (Venofer by American Reagent, Inc., Shirley, NY). Initiation of IV iron should be based on evaluation of iron stores. A serum ferritin level less than 100 ng/mL in conjunction with a TSAT level less than 20% indicates absolute iron deficiency and is a clear indication for the need for iron replacement.31 When TSAT is less than 20% in conjunction with normal or elevated serum ferritin levels, treatment should be based on the clinical picture of the patient, as serum ferritin is an acute phase reactant, which may become elevated with inflammation and stress. Iron supplementation may be indicated if Hgb levels are below the goal level. 

Heat should not be applied during the acute injury phase (the first 48 hours) because it promotes swelling and inflammation. 

---