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Tofacitinib
Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular course juvenile idiopathic arthritis, and ulcerative colitis. It is a janus kinase (JAK) inhibitor, discovered and developed by the National Institutes of Health and Pfizer. Common side effects include diarrhea, headache, and high blood pressure. Serious side effects may include infections, cancer, and pulmonary embolism. In 2019, the safety committee of the European Medicines Agency began a review of tofacitinib and recommended that doctors temporarily not prescribe the 10 mg twice-daily dose to people at high risk for pulmonary embolism. The U.S. Food and Drug Administration (FDA) also released warnings about the risk of blood clots. An important side effect of Jakinibs is serious bacterial, mycobacterial, fungal and viral infections. In the phase III trials of tofacitinib among opportunistic infections ...
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Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves, and blood. This may result in a anemia, low red blood cell count, pleurisy, inflammation around the lungs, and pericarditis, inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months. While the cause of rheumatoid arthritis is not clear, it is believed to involve a combination of genetic and environmental factors. The underlying mechanism involves the body's immune system attacking the joints. This results in inflammation and thickening of the synovium, joint capsule. It also affects the und ...
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Ulcerative Colitis
Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood ( hematochezia). Weight loss, fever, and anemia may also occur. Often, symptoms come on slowly and can range from mild to severe. Symptoms typically occur intermittently with periods of no symptoms between flares. Complications may include abnormal dilation of the colon ( megacolon), inflammation of the eye, joints, or liver, and colon cancer. The cause of UC is unknown. Theories involve immune system dysfunction, genetics, changes in the normal gut bacteria, and environmental factors. Rates tend to be higher in the developed world with some proposing this to be the result of less exposure to intestinal infections, or to a Western diet and lifestyle. The remova ...
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Pfizer
Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 1849 in New York by German entrepreneurs Charles Pfizer (1824–1906) and Charles F. Erhart (1821–1891), Pfizer is one of the oldest pharmaceutical companies in North America. Pfizer develops and produces medicines and vaccines for immunology, oncology, cardiology, endocrinology, and neurology. The company's largest products by sales are the Pfizer–BioNTech COVID-19 vaccine ($11 billion in 2023 revenues), apixaban ($6 billion in 2023 revenues), a pneumococcal conjugate vaccine ($6 billion in 2023 revenues), palbociclib ($4 billion in 2023 revenues), and tafamidis ($3 billion in 2023 revenues). In 2023, 46% of the company's revenues came from the United States, 6% came from Japan, and 48% came from other countries. Pfizer has been a publi ...
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Janus Kinase
Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 and 2 (since they were just two of many discoveries in a PCR-based screen of kinases), but were ultimately published as "Janus kinase". The name is taken from the two-faced Roman god of beginnings, endings and duality, Janus, because the JAKs possess two near-identical phosphate-transferring domains. One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first. Family The four JAK family members are: * Janus kinase 1 (JAK1) * Janus kinase 2 (JAK2) * Janus kinase 3 (JAK3) * Tyrosine kinase 2 (TYK2) Transgenic mice that do not express JAK1 have defective responses to some cytokines, such as interferon-gamma. JAK1 and JAK2 are involved in type II interferon (interferon-gamma) signalling, whereas JAK1 and TYK2 are involved in type I ...
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DMARDs
Disease-modifying antirheumatic drugs (DMARDs) comprise a category of otherwise unrelated disease-modifying drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is often used in contrast to nonsteroidal anti-inflammatory drugs (which refers to agents that treat the inflammation, but not the underlying cause) and steroids (which blunt the immune response but are insufficient to slow down the progression of the disease). The term "antirheumatic" can be used in similar contexts, but without making a claim about an effect on the disease course. Other terms that have historically been used to refer to the same group of drugs are "remission-inducing drugs" (RIDs) and "slow-acting antirheumatic drugs" (SAARDs). Terminology Although the use of the term DMARDs was first propagated in rheumatoid arthritis (hence their name), the term has come to pertain to many other diseases, such as Crohn's disease, lupus erythematosus, Sjögren syndrome, immun ...
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Psoriatic Arthritis
Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that may occur in some people affected by the autoimmune disease psoriasis. The classic features of psoriatic arthritis include dactylitis (sausage-like swelling of the fingers), skin lesions, and nail lesions. Lesions of the nails may include small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin lesions consistent with psoriasis (e.g., red, scaly, and itchy plaques) frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy. Genetics are thought to be strongly involved in the development of psoriatic arthritis. Obesity and certain forms of psoriasis are thought to increase the risk. Psoriatic arthritis affects up to 30% of people with psoriasis. It occurs in both children and adults. Some people with Ps ...
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Janus Kinase
Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 and 2 (since they were just two of many discoveries in a PCR-based screen of kinases), but were ultimately published as "Janus kinase". The name is taken from the two-faced Roman god of beginnings, endings and duality, Janus, because the JAKs possess two near-identical phosphate-transferring domains. One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first. Family The four JAK family members are: * Janus kinase 1 (JAK1) * Janus kinase 2 (JAK2) * Janus kinase 3 (JAK3) * Tyrosine kinase 2 (TYK2) Transgenic mice that do not express JAK1 have defective responses to some cytokines, such as interferon-gamma. JAK1 and JAK2 are involved in type II interferon (interferon-gamma) signalling, whereas JAK1 and TYK2 are involved in type I ...
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Methotrexate
Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given Oral administration, by mouth or by injection. Common side effects include nausea, feeling tired, fever, increased risk of infection, leukopenia, low white blood cell counts, and ulcerative stomatitis, breakdown of the skin inside the mouth. Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes. People on long-term treatment should be regularly checked for side effects. It is not safe during breastfeeding. In those with kidney problems, lower doses may be needed. It ...
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Efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made between efficacy and effectiveness. The word ''efficacy'' is used in pharmacology and medicine to refer both to the maximum response achievable from a pharmaceutical drug in research settings, and to the capacity for sufficient therapeutic effect or beneficial change in clinical settings. Pharmacology In pharmacology, efficacy () is the maximum response achievable from an applied or dosed agent, for instance, a small molecule drug. Intrinsic activity is a relative term for a drug's efficacy relative to a drug with the highest observed efficacy. It is a purely descriptive term that has little or no mechanistic interpretation. In order for a drug to have an effect, it needs to bind to its target, and then to affect the function of this tar ...
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Carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, Genetics, genetic, and Epigenetics, epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all Tissue (biology), tissues and under a variety of circumstances. Normally, the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and Organ (anatomy), organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and Epigenetics, epimutations that lead to cancer disrupt these orderly processes by interfering with the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division ...
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Fertility
Fertility in colloquial terms refers the ability to have offspring. In demographic contexts, fertility refers to the actual production of offspring, rather than the physical capability to reproduce, which is termed fecundity. The fertility rate is the average number of children born during an individual's lifetime. In medicine, fertility refers to the ability to have children, and infertility refers to difficulty in reproducing naturally. In general, infertility or subfertility in humans is defined as not being able to conceive a child after one year (or longer) of unprotected sex. The antithesis of ''fertility'' is infertility, while the antithesis of ''fecundity'' is sterility. Demography In demographic contexts, fertility refers to the actual production of offspring, rather than the physical capability to produce which is termed fecundity. While fertility can be measured, fecundity cannot be. Demographers measure the fertility rate in a variety of ways, which can be broa ...
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Mutagenesis
Mutagenesis () is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures. A mutagen is a mutation-causing agent, be it chemical or physical, which results in an increased rate of mutations in an organism's genetic code. In nature mutagenesis can lead to cancer and various heritable diseases, and it is also a driving force of evolution. Mutagenesis as a science was developed based on work done by Hermann Muller, Charlotte Auerbach and J. M. Robson in the first half of the 20th century. History DNA may be modified, either naturally or artificially, by a number of physical, chemical and biological agents, resulting in mutations. Hermann Muller found that "high temperatures" have the ability to mutate genes in the early 1920s, and in 1927, demonstrated a causal link to mutation upon experimen ...
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