Inflammatory properties

Dibenzo[/),/]thiepin-10(l 1H)-one (1) is an important synthon for the transformation of thiepins into other heterocycles. Oxidation with selenium(IV) oxide gives dibenzo[7>,/]thiepin-10,l 1-dionc (2), in 45% yield,38 which can be condensed with a series of benzaldchydes in the presence of ammonium acetate to provide the substituted 2-aryldibenzo[2,3 6,7]thiepino[4,5-t/]imidazoles 3, known to have anti-inflammatory properties.38... 

The second group of non-opioid analgesics, which are not classified as NSAIDs, consists of substances that lack anti-inflammatory properties, such as phenazones, metamizole (dipyrone) and paracetamol. Their molecules are neutral or weakly basic, have no hydrophilic... 

Rheumatoid Arthritis. Figure 2 The concept of a cytokine dysequilibrium. Many cytokines are detectable in rheumatoid synovial tissues, including those with predominantly anti-inflammatory properties. But the net effect is a dominance of proinflammatory activity. 

Acetaminophen is a pain reliever similar to aspirin, but it does not have aspirin s anti-inflammatory properties—or its undesirable effects... 

Although atherosclerosis and rheumatoid arthritis (RA) are distinct disease states, both disorders are chronic inflammatory conditions and may have common mechanisms of disease perpetuation. At sites of inflammation, such as the arterial intima undergoing atherogen-esis or the rheumatoid joint, oxygen radicals, in the presence of transition-metal ions, may initiate the peroxidation of low-density lipoprotein (LDL) to produce oxidatively modified LDL (ox-LDL). Ox-LDL has several pro-inflammatory properties and may contribute to the formation of arterial lesions (Steinberg et /., 1989). Increased levels of lipid peroxidation products have been detected in inflammatory synovial fluid (Rowley et /., 1984 Winyard et al., 1987a Merry et al., 1991 Selley et al., 1992 detailed below), but the potential pro-inflammatory role of ox-LDL in the rheumatoid joint has not been considered. We hypothesize that the oxidation of LDL within the inflamed rheumatoid joint plays a pro-inflammatory role just as ox-LDL has the identical capacity within the arterial intima in atherosclerosis. 

In contrast to MDA and hydroxynonenai, other aldehyde products of lipid peroxidation are hydrophobic and remain closely associated with LDL to accumulate to mil-limolar concentrations. Aldehydes at these elevated levels react with the protein portion of the LDL molecule, apolipoprotein B (apoB). Accumulated aldehydes bind the free amino groups from lysine residues in addition to other functional groups (-OH, -SH) on the apoB polypeptide. Consequently, the protein takes on a net negative charge and complete structural rearrangement results in the formation of ox-LDL. ox-LDL is no longer recognized by the LDL receptor, and has several pro-inflammatory properties (discussed below). 

Spyriounis, D.M., Tani, E., Rekka, E., Demopoulos, V.J. and Kourounakis, P.N. (1993). Novel AT-substituted 3-aminosteroids which exhibit anti-inflammatory properties and influence free radical processes. Eur. J. Med. Chem. 28, 521-525. 

In the early clinical trials of Pravadoline (248), the Sterling-Winthrop Research group observed CNS side effects. In an effort to circumvent these issues, indenes were explored as an alternative core [197]. The rationale behind this approach came from the observation that sulindac (308), an indene analogue of indomethacin (309), had anti-inflammatory properties comparable to (309) but without the CNS-associated side effects. 

Corticosteroids have potent anti-inflammatory properties and are used in active IBD to rapidly suppress inflammation. Corticosteroids have favorable effects in modulating several cell types involved in the inflammatory process.20,21 They may be administered systemically or delivered locally to the site of action by altering the drug formulation (Table 16-2). Because these drugs usually improve symptoms and disease severity rapidly, they should be restricted to short-term management of active disease. Long-term use of systemic corticosteroids is... 

Retinoids, which are highly effective in the treatment of acne, stimulate epithelial cell turnover and aid in unclogging blocked pores. Retinoids also exhibit anti-inflammatory properties through the inhibition of neutrophil and monocyte chemotaxis.8 Because of these comedolytic and antiinflammatory effects, topical retinoids are recommended as first-line treatment for mild to moderate comedonal and inflammatory acne.3 While success is seen with monotherapy, using a retinoid in combination with benzoyl peroxide or topical antibacterials is also an appropriate and effective therapeutic treatment option.3 Tretinoin, adapalene, and tazarotene are topical retinoids available for use in the treatment of acne. Table 62-2 describes the strengths and formulations of these agents. 

With antibacterial and anti-inflammatory properties, and the ability to stabilize keratinization, azelaic acid is an effective alternative in the treatment of mild to moderate acne in patients who cannot tolerate benzoyl peroxide or topical retinoids.3,21 It also has a hypopigmentation effect that may prove effective in patients who are prone to post-inflammatory hyperpigmentation resulting from acne.22... 

De Klerck B, Geboes L, Hatse S, et al. Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis. Arthritis Res Ther 2005 7(6) R1208-1220. 

McQuibban GA, Gong JH, Wong JP, Wallace JL, Clark-Lewis I, Overall CM. Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood 2002 100(4) 1160-1167. 

Elder blossoms, eyebright (Euphrasia officinalis) and goldenrod herb make a beneficial infusion to treat hay fever due to its anti-inflammatory properties. 

Vascular Effects of Complement Activation. During complement activation a number of complement fragments (anaphylatoxins), which are polypeptides with inflammatory properties, are released. The anaphylatoxins C3a and C5a induce smooth muscle contraction and enhance vascular permeability (H31). The most pronounced activation of complement with the formation of anaphylatoxins and terminal C5-9 complexes has been observed in septic shock (B29, B30, P2). Studies indicate that there is a relation between high concentrations of anaphylatoxins and C5-9 complexes and the development of ARDS or MODS in patients with sepsis (H10). 

The family Aristolochiaceae is a family of herbaceous plants often used in Asia and the Pacific to counteract snake poisoning, promote urination and menses, mitigate stomachache, and treat dropsy and skin diseases. During the past 20 years, members of this family, especially from the genus Aristolochia have attracted much interest and has been the subject of numerous chemical and pharmacological studies. The anti-inflammatory property of Aristolochia species is probably the result of a direct... 

A significant advance in the understanding of the anti-inflammatory properties of Bupleurum fruticescens has been provided by Prieto et al. (36). The showed that a methanol extract from the aerial parts had a significant effect on 5-lipoxygenase activity, inhibiting both LTB4 and 5(S)-HETE production, with IC50 values of 112 and 95 (xg/mL, respectively. At concentrations of 200 (Xg/mL, the extract inhibited COX-1 (90%) and elastase activities (54%). What are the principles involved here, saponin ... 

Sigesbeckia glabrescens Mak., or hi chum (Korean Fig. 21), is used in Korea to treat liver and kidney diseases, asthma, allergic disorders, costiveness, deafness, and blindness. In China, the plant is prescribed for rheumatic pain, numbness, weak bones, and to wash boils. The anti-inflammatory property of Sigesbeckia glabrescens Mak. is... 

The plant has been used in traditional Korean herbal medicine for its antipyretic, analgesic, and anti-inflammatory properties vermifuge. 

The plant is strongly aromatic on account of an essential oil which comprises cis-a-ocimene (25.11%), 3,7-dimethyl-l,6-octadien-3 ol (16.85%), and trans-nerolidol (13.89%), hence the use of the plant in aromatherapy. A methanolic extract of bark of Litsea cubeba (Lour.) Pers. and its fractions (0.01 mg/mL) from bark inhibit NO and PGE2 production in LPS-activated RAW 264.7 macrophages without significant cytotoxicity at less than 0.01 mg/mL concentration. The methanol extract decreased the enzymatic activity of myeloperoxidase (0.05 mg/mL). These findings suggest that L. cubeba is beneficial for inflammatory conditions and may contain compound(s) with anti-inflammatory properties (63). Can we expect the vasorelaxant laurotetanine (64) isolated from the plant to exert such activity ... 

Olajide OA, Okpako DT, Makinde JM. Anti-inflammatory properties of Bridelia ferrug-inea stem bark. Inhibition of lipopolysaccaride-induced septic shock and vascular permeability. J Ethnopharmacol 1999 88 221-224. 

In China, the plant is used to treat rheumatic inflammation. The anti-inflammatory property is substantiated, and a surprising amount of evidence is available. Note that the main anti-inflammatory principle of Tripterygium uiildfordii is a diterpene triepoxide known as triptolide, which posseses potent anti-inflammatory and immunosuppressive properties (103,104). 

Thus, the tetravalency, anti-inflammatory properties and molecular stability of slgA make it particularly suitable for protective passive immunity when applied to mucosal surfaces. To date, the clinical evaluation of slgA protection in humans and animal models has been very limited. Indeed most studies have employed monomeric IgA monoclonal antibodies [3,15]. Hence, differences in IgA and IgG protective activities at the mucosal level have often not been observed [15]. Only a few studies have demonstrated the superior activity of polymeric IgA or slgA compared with monomeric IgG or IgA [16]. In order to determine the efficacy of slgA, future animal experiments and clinical trials are needed to compare the activities of IgG monoclonal antibodies and their slgA counterparts. The ability to engineer slgAs in plants will allow these comparisons to be made [17]. 

The purified product is presented as a solution and contains sodium citrate, EDTA, sodium chloride and polysorbate 80 as excipients. A daily (s.c.) injection of 100 mg is recommended for patients with rheumatoid arthritis. This inflammatory condition is (not surprisingly) characterized by the presence of high levels of IL-1 in the synovial fluid of affected joints. In addition to its pro-inflammatory properties, IL-1 also mediates additional negative influences on the joint/bone, including promoting cartilage degradation and stimulation of bone resorption. 

It was initially argued that the best potential PTK inhibitors would be compounds that compete for the substrate in the kinase binding domain. It was argued that such compounds would be less toxic than ATP mimics since they bind to those domains at the kinase site that are less conserved than the substrate binding domains. Indeed tyrphostins like AG 490 which blocks Jak-2 [10] and AG 556 which possesses anti-inflammatory properties have been shown to be highly non-toxic in vivo [34-37]. 

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