Australia
In the past, Australia has used British and American terms interchangeably, including "mental retardation" and "mental handicap". Today, "intellectual disability" is the preferred and more commonly used descriptor. Society and culture
People with intellectual disabilities are often not seen as full citizens of society. Person-centered planning and approaches are seen as methods of addressing the continued labeling and exclusion of socially devalued people, such as people with disabilities, encouraging a focus on the person as someone with capacities and gifts as well as support needs. The self-advocacy movement promotes the right of self-determination and self-direction by people with intellectual disabilities, which means allowing them to make decisions about their own lives. Until the middle of the 20th century, people with intellectual disabilities were routinely excluded from public education, or educated away from other typically developing children. Compared to peers who were segregated in special schools, students who are mainstreamed or included in regular classrooms report similar levels of stigma and social self-conception, but more ambitious plans for employment. As adults, they may live independently, with family members, or in different types of institutions organized to support people with disabilities. About 8% currently live in an institution or a group home.In the United States, the average lifetime cost of a person with an intellectual disability amounts to $223,000 per person, in 2003 US dollars, for direct costs such as medical and educational expenses. The indirect costs were estimated at $771,000, due to shorter lifespans and lower than average economic productivity.
Mechanism of action
GTN is a prodrug which must be denitrated, with the nitrite anion or a related species further reduced to produce the active metabolite nitric oxide (NO). Organic nitrates that undergo these two steps within the body are called nitrovasodilators, and the denitration and reduction occur via a variety of mechanisms. The mechanism by which such nitrates produce NO is widely disputed. Some believe that organic nitrates produce NO by reacting with sulfhydryl groups, while others believe that enzymes such as glutathione S-transferases, cytochrome P450 (CYP), and xanthine oxidoreductase are the primary source of GTN bioactivation. In recent years, a great deal of evidence has been produced that supports the conclusion that GTNs clinically relevant denitration and reduction produce 1,2-glyceryl dinitrate (GDN) and NO, and that this reaction is catalysed by mitochondrial aldehyde dehydrogenase (ALDH2 or mtALDH). The NO produced by this process is a potent activator of guanylyl cyclase (GC) by heme-dependent mechanisms; this activation results in formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). Among other roles, cGMP serves as a substrate for a cGMP-dependent protein kinase that activates myosin light chain phosphatase. Thus, production of NO from exogenous sources such as GTN increases the level of cGMP within the cell, and stimulates dephosphorylation of myosin, which initiates relaxation of smooth muscle cells in blood vessels.