Zalcitabine
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Zalcitabine
Zalcitabine (2′-3′-dideoxycytidine, ddC), also called dideoxycytidine, is a nucleoside analog reverse-transcriptase inhibitor (NRTI) sold under the trade name Hivid. Zalcitabine was the third antiretroviral to be approved by the Food and Drug Administration (FDA) for the treatment of HIV/AIDS. It is used as part of a combination regimen. Zalcitabine appears less potent than some other nucleoside RTIs, has an inconvenient three-times daily frequency and is associated with serious adverse events. For these reasons it is now rarely used to treat human immunodeficiency virus (HIV), and it has even been removed from pharmacies entirely in some countries. History Zalcitabine was first synthesized in the 1960s by Jerome HorwitzOral account of the history of AZT, d4T and ddC by Jerome Horwitz and Hiroaki Mitsuya in the documentary filI am alive today - History of an AIDS drug and subsequently developed as an anti-HIV agent by Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan at the ...
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Hiroaki Mitsuya
is a Japanese virologist famous for his role in discovery of the anti-HIV drug zidovudine (AZT) as well as other anti-AIDS drugs including didanosine (ddI) and zalcitabine (ddC). Mitsuya was born in Sasebo, Nagasaki and received his M.D. and Ph.D. from Kumamoto University. He joined the American National Cancer Institute in Bethesda, Maryland, in 1982, working initially on Human T-lymphotropic virus 1 before switching his attention to HIV. His identification of AZT as an anti-HIV drug, as well as the anti-HIV properties of didanosine and zalcitabine, was made in 1985. He was appointed Professor of Hematology, Rheumatology and Clinical Immunology at Kumamoto University Graduate School of Medical And Pharmaceutical Sciences. In December, 2006, he was awarded the first NIH The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health ...
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Reverse-transcriptase Inhibitor
Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs Enzyme inhibition, inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses. Mechanism of action When HIV infects a cell, reverse transcriptase copies the viral single stranded RNA genome into a double-stranded viral DNA. The viral DNA is then integrated into the host chromosomal DNA, which then allows host cellular processes, such as transcription and translation, to reproduce the virus. RTIs block reverse transcriptase's enzymatic function and prevent completion of synthesis of the double-stranded viral DNA, thus preventing HIV from multiplying. A similar process occurs with other types of viruses. The hepatitis B virus, for example, carries its genetic material in the form of DNA, and employs an RNA-dependent DNA polymerase to replicate. Some of the same compou ...
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Didanosine
Didanosine (ddI, DDI), sold under the brand name Videx, is a medication used to treat HIV/AIDS. It is used in combination with other medications as part of highly active antiretroviral therapy (HAART). It is of the reverse-transcriptase inhibitor class. Didanosine was first described in 1975 and approved for use in the United States in 1991. Adverse effects The most common adverse events with didanosine are diarrhea, nausea, vomiting, abdominal pain, fever, headache, and rash. Peripheral neuropathy occurred in 21-26% of participants in key didanosine trials. Pancreatitis is rarely observed but has caused occasional fatalities, and has black box warning status. Other reported serious adverse events are retinal changes, optic neuritis and alterations of liver functions. The risk of some of these serious adverse events is increased by drinking alcohol. In February 2010, the United States Food and Drug Administration issued a statement that patients using didanosine (Videx) are a ...
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Robert Yarchoan
Robert Yarchoan (born 1950) is a medical researcher who played an important role in the development of the first effective drugs for AIDS. He is the Chief of the HIV and AIDS Malignancy Branch in the NCI and also coordinates HIV/AIDS malignancy research throughout the NCI as director of the Office of HIV and AIDS Malignancy (OHAM). Education and career Dr. Yarchoan was raised in Oceanside, New York and graduated from Amherst College in 1971. He subsequently received his M.D. from the University of Pennsylvania and completed an internship and residency in internal medicine at the University of Minnesota and a fellowship in Immunology in the Metabolism Branch of the NCI. After completing his training he joined the laboratory of Dr. Samuel Broder. In 1991 he was appointed to be a Section Chief of the Medicine Branch and in 1996 he named chief of the newly formed HIV and AIDS Malignancy Branch. Dr. Yarchoan was also appointed to be the first director of the NCI Office of HIV and AI ...
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Hoffmann-La Roche
F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX Swiss Exchange. The company headquarters are located in Basel. Roche is the fifth largest pharmaceutical company in the world by revenue, and the leading provider of cancer treatments globally. The company controls the American biotechnology company Genentech, which is a wholly owned affiliate, and the Japanese biotechnology company Chugai Pharmaceuticals, as well as the United States-based companies Ventana and Foundation Medicine. Roche's revenues during fiscal year 2020 were 58.32 billion Swiss francs. Descendants of the founding Hoffmann and Oeri families own slightly over half of the bearer shares with voting rights (a pool of family shareholders 45%, and Maja Oeri a further 5% apart), with Swiss pharma firm Novartis owning a furth ...
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Jerome Horwitz
Jerome Phillip Horwitz (January 16, 1919 – September 6, 2012) was an American scientist; his affiliations included the Barbara Ann Karmanos Cancer Institute, the Wayne State University School of Medicine and the Michigan Cancer Foundation. Background Horwitz was a Jewish Detroit native and 1937 graduate of Central High School. He earned his bachelor's and master's degrees in chemistry from the University of Detroit; his doctorate in chemistry came from the University of Michigan. He completed his post-doctoral training at Northwestern University and the University of Michigan Clinical breakthroughs In 1964, while conducting research for the Michigan Cancer Foundation, Horwitz synthesized a compound that was to become known as zidovudine (AZT) - an antiviral drug used to treat HIV patients; Zidovudine was initially developed as a treatment for cancer. Horwitz was also first to synthesize stavudine (d4T) and zalcitabine (ddC) - two other reverse-transcriptase inhibito ...
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Samuel Broder
Samuel Broder spent his childhood in Poland, in a group of Jewish guerrillas threatened by the Nazis. He emigrated to the United States with a group of Polish survivors and settled with his parents in an industrial neighborhood in Detroit, where they ran a snack bar that was razed to the ground during the riots in 1968 for the assassination of Martin Luther King. Broder didn’t like to work there, he had different goals. He thought that in science he could succeed without belonging to a high socioeconomic class, so he began to get good grades in science subjects and got a scholarship to Michigan State University. He was a co-developer of some of the first effective drugs for the treatment of AIDS and was Director of the National Cancer Institute (NCI) from 1989 to 1995. During the first years of the AIDS epidemic, he co-developed zidovudine (AZT), didanosine (ddI), and zalcitabine (ddC), which were the first effective drugs licensed for the treatment of AIDS. In 1989, he wa ...
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Hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy groups. Both the negatively charged anion , called hydroxide, and the neutral radical , known as the hydroxyl radical, consist of an unbonded hydroxy group. According to IUPAC definitions, the term ''hydroxyl'' refers to the hydroxyl radical () only, while the functional group is called a ''hydroxy group''. Properties Water, alcohols, carboxylic acids, and many other hydroxy-containing compounds can be readily deprotonated due to a large difference between the electronegativity of oxygen (3.5) and that of hydrogen (2.1). Hydroxy-containing compounds engage in intermolecular hydrogen bonding increasing the electrostatic attraction between molecules and thus to higher boiling and melting points than found for compounds that lack this f ...
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Hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic, and highly combustible. Hydrogen is the most abundant chemical substance in the universe, constituting roughly 75% of all normal matter.However, most of the universe's mass is not in the form of baryons or chemical elements. See dark matter and dark energy. Stars such as the Sun are mainly composed of hydrogen in the plasma state. Most of the hydrogen on Earth exists in molecular forms such as water and organic compounds. For the most common isotope of hydrogen (symbol 1H) each atom has one proton, one electron, and no neutrons. In the early universe, the formation of protons, the nuclei of hydrogen, occurred during the first second after the Big Bang. The emergence of neutral hydrogen atoms throughout the universe occurred about 370,000 ...
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T Cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 or ...
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Reverse Transcriptase
A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, by retrotransposon mobile genetic elements to proliferate within the host genome, and by eukaryotic cells to extend the telomeres at the ends of their linear chromosomes. Contrary to a widely held belief, the process does not violate the flows of genetic information as described by the classical central dogma, as transfers of information from RNA to DNA are explicitly held possible. Retroviral RT has three sequential biochemical activities: RNA-dependent DNA polymerase activity, ribonuclease H (RNase H), and DNA-dependent DNA polymerase activity. Collectively, these activities enable the enzyme to convert single-stranded RNA into double-stranded cDNA. In retroviruses and retrotransposons, this cDNA can then integrate into the host genom ...
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Liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is located in the quadrant (anatomy), right upper quadrant of the abdomen, below the thoracic diaphragm, diaphragm. Its other roles in metabolism include the regulation of Glycogen, glycogen storage, decomposition of red blood cells, and the production of hormones. The liver is an accessory digestive organ that produces bile, an alkaline fluid containing cholesterol and bile acids, which helps the fatty acid degradation, breakdown of fat. The gallbladder, a small pouch that sits just under the liver, stores bile produced by the liver which is later moved to the small intestine to complete digestion. The liver's highly specialized biological tissue, tissue, consisting mostly of hepatocytes, regulates a w ...
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