Inflammation. Inflammation is the process of activation of the immune system in the interest of self- preservation. The inflammatory response can occur over a short period of time (acute) or can persist with long course (chronic). Key aspects involved in the inflammatory response are the production of cytokines (e.g. interleukin- [IL] 1, 6, 4, 10, tumor necrosis factor-alpha [TNF-α]) acute phase proteins (e.g. C-reactive protein [CRP]) chemokines and adhesion molecules (Xxxx, 1995; G. E. Xxxxxx, Xxxxxxx, Xxxxxx, Xxxxxxxxx, & Xxxxx, 2002; Xxxxxxxxx, Xxxxxx, et al., 2001). Activation of the immune response leads to the production of cytokines, pro- and anti- inflammatory, which in turn influence pathophysiological domains such as neuroendocrine function, neurotransmitter metabolism and regional brain activity (Xxxxxxx, X’Xxxxxx, Xxxxxx, Xxxxxxx, & Xxxxxx, 2008; Xxxxxxxxx, Xxxxxxx, & Xxxx, 2005).
Inflammation. Offspring exposure to depression in utero will be associated with elevated inflammation at 25 years.
Inflammation. Inflammation is known to play a critical role in production of ROS and initiation of oxidative stress [11]. Activated neutrophils can kill bacteria by imposing severe oxidative stress, therefore, if the number of activated cells is large and/or inflammation goes on for long time, serious damage may occur [67]. In 1863 Virchow hypothesized that cancer originates at the sites of inflammation. At present, there seems to be a consensus that chronic inflammation may serve as a critical component of tumor development and progression [68]. Interaction of cellular immune system with antigens generates ROS and triggers production of pro-inflammatory cytokines and chemokines, which then induce production of ROS [69, 70]. Conversely, oxidative stress can stimulate inflammatory response by activating a variety of transcription factors, such as NF-kB, AP-1, and p53, which then lead to expression of inflammatory cytokines and chemokines [1, 71]. Thus, inflammation is both a cause and a consequence of oxidative stress. Antioxidants, such as vitamin C and β-carotene, have been known to possess anti-inflammatory properties [72-74]. Carotenoids are a group of lipid soluble antioxidants found in yellow and green vegetables such as carrots, spinach, and sweet potatoes. The major dietary carotenoids include α-carotene, β-carotene, lycopene, lutein, β-cryptoxanthin, and zeaxanthin. Carotenoids are known to be efficient scavengers of free radicals, and thus play an important role in preventing lipid peroxidation [75]. The antioxidant property of carotenoids is mainly due to their conjugated double-bonded structure that allows delocalizing unpaired electrons [76]. Carotenoids react with free radicals through radical addition, hydrogen abstraction from carotenoids, or electron-transfer reaction [77]. In addition to their direct antioxidant action certain carotenoids also act as precursors of other more powerful antioxidants [78]. Vitamin C, also known as ascorbic acid, is a major aqueous-phase antioxidant. Under physiological conditions, it functions as a potent free radical scavenger in the plasma. [79, 80]. The antioxidant property of vitamin C is attributed to its ability to form relatively stable ascorbate radicals [81]. Humans normally acquire vitamin C from a variety of dietary sources, such as acid fruits and green vegetables [82, 83].
Inflammation. In order to qualify as a Novel Validated Target such Validated Target shall be reasonably believed to lead to a valid and enforceable patent in the United States as determined in good faith by Joint Management Team.
Inflammation. The inflammatory response is essential for defense against harmful micro- organisms and for the repair of damaged tissues. The failure of the body's control mechanisms regulating inflammatory response occurs in conditions such as rheumatoid arthritis, acute respiratory distress syndrome and asthma. Tumor necrosis factor binding protein ("TNFbp") and interleukin-1 receptor antagonist ("IL-1ra") were two product candidates added to the Company's inflammation research program through the acquisition of Synergen (see "Joint Ventures and Business Relationships--Other business relationships"). A human clinical trial for TNFbp was completed for possible use in the treatment of rheumatoid arthritis. Because of potential issues with immunogenicity, a second generation molecule, soluble tumor necrosis factor- receptor I ("sTNF-RI"), was developed, and the Company does not intend to pursue further development of the first generation TNFbp. A phase 1 study of sTNF-RI in patients with rheumatoid arthritis has been completed. A phase 2 clinical trial of IL-1ra in combination with methotrexate in patients with rheumatoid arthritis has completed enrollment. The Company is also researching second generation molecules and sustained duration formulations which have demonstrated some additional benefit in preclinical studies over the first generation product candidate. Phase 1 studies of IL-1ra delivered by continuous infusion have been completed. In September 1997, Amgen announced that it was seeking a corporate partner for its inflammation research and development programs, located in Boulder, Colorado. Following an approximate six month period during which Amgen considered a number of corporate partnering alternatives, the Company announced in April 1998 that it had decided to retain its principal product candidates, sTNF-RI and IL-1ra, and relocated their respective development programs to Thousand Oaks. Amgen discontinued the discovery research programs. Joint Ventures and Business Relationships The Company generally intends to self-market its products. From time to time it may supplement this effort by using joint ventures and other business relationships to provide additional marketing and product development capabilities in certain countries. In addition to internal research and development efforts, the Company has established external research collaborations and has acquired certain product and technology rights. Amgen has established the relationships described belo...
