Disease progression

In recent years increasing attention has been paid to the possibility of delaying or even reversing the memory loss that accompanies old age or the more tragic loss of human capabilities associated with premature senility - Alzheimer s disease. Progress is hampered by the difficulty of identifying suitable animal tests, and there is presently no reliable therapy. 

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. 

Amyotropic lateral sclerosis (ALS) 3. AEA and 2-AG increase in the spinal cord of SOD1 transgenic mice, a model of ALS, to inhibit disease progress 3. CB2 receptor agonists or inhibitors of degradation... 

Anticytokine antibodies Infliximab Chimeric (mouse/human) monoclonal antibody against TNEa. Effective in the treatment of severe forms of rheumatoid arthritis where it can halt disease progression, or inflammatory bowel disease (EBD). 

Although there has been substantial success using IFN for the treatment of some cancels, until this point, the great majority of tumors are resistant or show an initial moderate response soon followed by disease progression under treatment. One likely reason for resistance is the progredient loss of susceptibility to IFN, which may be caused by downregulation of IFN receptors or perturbation of intracellular DFN-signaling pathways, a phenomenon also known from in vitro studies. 

In a proportion of patients systemic and extra-articular features may be observed during the course of the disease (and rarely prior to joint disease). These include anaemia, weight loss, vasculitis, serositis, nodules in subcutaneous, pulmonary and sclera tissues, mononeuritis multiplex, and interstitial inflammation in lungs as well as in exocrine salivary and lacrimal tissue. However, these systemic manifestations occur relatively late in the disease progression. 

During early treatment witii levodopa and carbidopa, adverse reactions are usually not a problem. But as the disease progresses, die response to die drug may become less, and the period of time tiiat each dose is effective begins to decrease, leading to more frequent doses, and more adverse reactions. 

Env sequences both temporally and between patients. Two drugs that target HIV-1 entry, enfuvirtide and maraviroc, are now licensed for treatment of HIV-1 infection. The efficacy of these drugs validates entry as a point of intervention in viral hfe cycles and, in the context of HIV treatment, contributes to the growing armamentarium of antivirals which, in multidrug combinations, can effectively inhibit viral replication and prevent disease progression. 

Chan PL, Holford NH. Drug treatment effects on disease progression. Annu Rev Pharmacol Toxicol 2001 41 625-59. 

Li M, Song R, Masciotra S, Soriano V, Spira TJ, Lai RB, Yang C (2005) Association of CCR5 human haplogroup E with rapid HIV type 1 disease progression. AIDS Res Hum Retroviruses 21 111-115... 

McDermott DH, Zimmerman PA, Guignard F, Kleeberger CA, Lehman SF, Murphy PM (1998) CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS). Lancet 352 866-870... 

Singh KK, Hughes MD, Chen J, Spector SA (2005) Genetic polymorphisms in CX3CR1 predict HIV-1 disease progression in children independently of CD4-I- lymphocyte count and HIV-1 RNA load. J Infect Dis 191 1971-1980... 

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