Free Radical Generation by Selenium Compounds and Their Prooxidant Toxicity

Selemum (Se) and many of its compounds are among the most toxic of nutrients. Selenium toxicity was first described in range animals in the western United States in the 1930's which consumed' selenium accumulator' plants of the genus Astragalus, Xylorrhiza,Oonopsis, and Stanleya. Selenites and selenates from the soil accumulate in these plants primarily as methylated selenium compounds and plants evolve dimethyldiselenide and dimethyselenide.Dietary selenium, primarily as selenomethionine and selenocysteine for humans fulfill the dietary requirement for selenoenzymes and proteins. In humans and animals excessive dietary selenium may be toxic. In vitro, selenium compounds such as selenite, selenium dioxide and diselenides react with thiols, such as glutathione, producing superoxide and other reactive oxygen species. This catalytic reaction of selenium compounds with thiols likely accounts for selenium toxicity to cells ex vivo and in vivo where the major glutathione producing organ,the liver, is also the major target organ of selenium toxicity.Selenium enzymes and selenoethers that do not readily form a selenide (RSe-) anion and compounds such as Ebselen where selenium is sequestered, are not toxic. Methylation of selenium by both plants and animals serves to detoxify selenium by generating methylselenides. Alternatively, full reduction of Se to elemental selenium (Se0) as done by some bacteria and the formation of heavy metal selenides such as Ag2Se or Hg2Se, results in a non-catalytic nontoxic form of selenium.This catalytic prooxidant attribute of some selenium compounds appears to account for its toxicity when such activity exceeds plant and animal methylation reactions and antioxidant defenses. This prooxidant activity may also account for cellular apoptosis and may provide a useful pharmaceutical application for selenium compounds as antibacterial, antiviral, antifungal and anticancer agents

Induced pluripotent stem cells

Induced pluripotent stem （iPS） cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic ceil nuclear transfer （SCNT） has been ineffective in humans. Recent discoveries show that human fibroblasls can be reprogrammed by a transient over expression of a small number of genes; they can undergo induced pluripotency, iPS were first produced in 2006. By 2008, work was underway to remove the potential oncogenes from their structure. In 2009, protein iPS （piPS） cells were discovered. Surface markers and reporter genes play an important role in stem cell research. Clinical applications include generation of self renewing stem cells, tissue replacement and many more. Stem cell therapy has the ability to dramatically change the treatment of human diseases.

The urgent need for more potent antiretroviral therapy in low-income countries to achieve UNAIDS 90-90-90 and complete eradication of AIDS by 2030

Background:Over 90%of Human Immunodeficiency Virus(HIV)infected individuals will be on treatment by 2020under UNAIDS 90-90-90 global targets.Under World Health Organisation(WHO)"Treat All"approach,this number will be approximately 36.4 million people with over 98%in low-income countries(LICs).Main body:Pretreatment drug resistance(PDR)largely driven by frequently use of non-nucleoside reverse transcriptase inhibitors(NNRTIs),efavirenz and nevirapine,has been increasing with roll-out of combined antiretroviral therapy(cART)with 29%annual increase in some LICs countries.PDR has exceeded 10%in most LICs which warrants change of first line regimen to more robust classes under WHO recommendations.If no change in regimens is enforced in LICs,it’s estimated that over 16%of total deaths,9%of new infections,and 8%of total cART costs will be contributed by HIV drug resistance by 2030.Less than optimal adherence,and adverse side effects associated with currently available drug regimens,all pose a great threat to achievement of 90%viral suppression and elimination of AIDS as a public health threat by 2030.This calls for urgent introduction of policies that advocate for voluntary and compulsory drug licensing of new more potent drugs which should also emphasize universal access of these drugs to all individuals worldwide.Conclusions:The achievement of United Nations Programme on HIV and AIDS 2020 and 2030 targets in LICs depends on access to active cART with higher genetic barrier to drug resistance,better safety,and tolerability profiles.It’s also imperative to strengthen quality service delivery in terms of retention of patients to treatment,support for adherence to cART,patient follow up and adequate drug stocks to help achieve a free AIDS generation.