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Activated Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintaining the permeability of blood vessel walls in humans and other animals. Activated protein C (APC) performs these operations primarily by proteolytically inactivating proteins Factor Va and Factor VIIIa. APC is classified as a serine protease since it contains a residue of serine in its active site. In humans, protein C is encoded by the ''PROC'' gene, which is found on chromosome 2. The zymogenic form of protein C is a vitamin K-dependent glycoprotein that circulates in blood plasma. Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a disulfide bond. The protein C zymogen is activated when it binds to thrombin, another protein heavily involved in coagulation, and protein C's a ...
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Zymogen
In biochemistry, a zymogen (), also called a proenzyme (), is an inactive precursor of an enzyme. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the active site) for it to become an active enzyme. The biochemical change usually occurs in Golgi bodies, where a specific part of the precursor enzyme is cleaved in order to activate it. The inactivating piece which is cleaved off can be a peptide unit, or can be independently-folding domains comprising more than 100 residues. Although they limit the enzyme's ability, these N-terminal extensions of the enzyme or a “prosegment” often aid in the stabilization and folding of the enzyme they inhibit. The pancreas secretes zymogens partly to prevent the enzymes from digesting proteins in the cells in which they are synthesised. Enzymes like pepsin are created in the form of pepsinogen, an inactive zymogen. Pepsinogen is activated when chief ce ...
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Disulfide Bond
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In biology, disulfide bridges formed between thiol groups in two cysteine residues are an important component of the secondary and tertiary structure of proteins. ''Persulfide'' usually refers to compounds. In inorganic chemistry disulfide usually refers to the corresponding anion (−S−S−). Organic disulfides Symmetrical disulfides are compounds of the formula . Most disulfides encountered in organo sulfur chemistry are symmetrical disulfides. Unsymmetrical disulfides (also called heterodisulfides) are compounds of the formula . They are less common in organic chemistry, but most disulfides in nature are unsymmetrical. Properties The disulfide bonds are strong, with a typical bond dissociation energy of 60 kcal/mol (251& ...
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Cochrane Review
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients and policy makers. It includes 53 review groups that are based at research institutions worldwide. Cochrane has approximately 30,000 volunteer experts from around the world. The group conducts systematic reviews of health-care interventions and diagnostic tests and publishes them in the Cochrane Library. According to the Library, articles are available via one-click access, but some require paid subscription or registration before reading. A few reviews, in occupational health for example, incorporate results from non-randomised observational studies as well as controlled before–after (CBA) studies and interrupted time-series studies. History Cochrane, previously known as the Cochrane Collaboration, was founded in 1 ...
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Surviving Sepsis Campaign
The Surviving Sepsis Campaign (SSC) is a global initiative to bring together professional organizations in reducing mortality from sepsis. The purpose of the SSC is to create an international collaborative effort to improve the treatment of sepsis and reduce the high mortality rate associated with the condition. The Surviving Sepsis Campaign and the Institute for Healthcare Improvement have teamed up to achieve a 25 percent reduction in sepsis mortality by 2009. The guidelines were updated in 2016 and again in 2021. Relevance Mortality associated with severe sepsis remains high at 30-50%. When shock is present, mortality is reported to be even higher at around 50-60%. Approximately 1400 people die from sepsis each day throughout the world. In the U.S. there are approximately 750,000 new sepsis cases each year, with at least 210,000 fatalities and this is reported to be same throughout Europe. As medicine becomes more advanced, with invasive procedures and immunosuppression, th ...
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Sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is followed by suppression of the immune system. Common signs and symptoms include fever, tachycardia, increased heart rate, hyperventilation, increased breathing rate, and mental confusion, confusion. There may also be symptoms related to a specific infection, such as a cough with pneumonia, or dysuria, painful urination with a pyelonephritis, kidney infection. The very young, old, and people with a immunodeficiency, weakened immune system may have no symptoms of a specific infection, and the hypothermia, body temperature may be low or normal instead of having a fever. Severe sepsis causes organ dysfunction, poor organ function or blood flow. The presence of Hypotension, low blood pressure, high blood Lactic acid, lactate, or Oliguria, low urine o ...
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Eli Lilly And Company
Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel Eli Lilly, a pharmaceutical chemist and veteran of the American Civil War. As of 2022, Lilly is known for its clinical depression drugs Prozac ( fluoxetine) (1986) and Cymbalta (duloxetine) (2004) and its antipsychotic medication Zyprexa (olanzapine) (1996), although its primary revenue drivers are the diabetes drugs Humalog (insulin lispro) (1996) and Trulicity (dulaglutide) (2014). Lilly's achievements include being the first company to mass-produce the polio vaccine developed by Jonas Salk, and insulin. It was one of the first pharmaceutical companies to produce human insulin using recombinant DNA including Humulin ( insulin medication), Humalog (insulin lispro), and the first approved biosimilar insulin product in the US, Basaglar ( ...
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Drotrecogin Alfa
Drotrecogin alfa (activated) (Xigris, marketed by Eli Lilly and Company) is a recombinant form of human activated protein C that has anti-thrombotic, anti-inflammatory, and profibrinolytic properties. Drotrecogin alpha (activated) belongs to the class of serine proteases. Drotrecogin alfa has not been found to improve outcomes in people with severe sepsis. The manufacturer's aggressive strategies in marketing its use in severe sepsis have been criticized. On October 25, 2011, Eli Lilly & Co. withdrew Xigris from the market after a major study showed no efficacy for the treatment of sepsis. Medical uses Drotrecogin alfa does not improve mortality in severe sepsis or septic shock but does increase bleeding risks. Therefore, a 2012 Cochrane review recommended that clinicians and policymakers not recommend its use and Eli Lilly has announced the discontinuation of all clinical trials. Risks and contraindications Contraindications The following patients should not receive drotrecog ...
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Recombinant DNA
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be found in the genome. Recombinant DNA is the general name for a piece of DNA that has been created by combining at least two fragments from two different sources. Recombinant DNA is possible because DNA molecules from all organisms share the same chemical structure, and differ only in the nucleotide sequence within that identical overall structure. Recombinant DNA molecules are sometimes called chimeric DNA, because they can be made of material from two different species, like the mythical chimera. R-DNA technology uses palindromic sequences and leads to the production of sticky and blunt ends. The DNA sequences used in the construction of recombinant DNA molecules can originate from any species. For example, plant DNA may be joined to bacter ...
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Thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus. Thrombosis may occur in veins (venous thrombosis) or in arteries (arterial thrombosis). Venous thrombosis (sometimes called DVT, deep vein thrombosis) leads to a blood clot in the affected part of the body, while arterial thrombosis (and, rarely, severe venous thrombosis) affects the blood supply and leads to damage of the tissue supplied by that artery (ischemia and necrosis). A piece of either an arterial or a venous thrombus can break off as an embolus, which could ...
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Activated Protein C Resistance
Activated protein C resistance (APCR) is a hypercoagulability (an increased tendency of the blood to clot) characterized by a lack of a response to activated protein C (APC), which normally helps prevent blood from clotting excessively. This results in an increased risk of venous thrombosis (blood clots in veins), which resulting in medical conditions such as deep vein thrombosis (usually in the leg) and pulmonary embolism (in the lung, which can cause death). The most common cause of hereditary APC resistance is factor V Leiden mutation. Presentation Associated conditions An estimated 64 percent of patients with venous thromboembolism may have APC resistance. Genetics The disorder can be acquired or inherited, the hereditary form having an autosomal dominant inheritance pattern. Pathophysiology APC (with protein S as a cofactor) degrades Factor Va and Factor VIIIa. APC resistance is the inability of protein C to cleave Factor Va and/or Factor VIIIa, which allows for longer dur ...
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Anticoagulant
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they help keep the bite area unclotted long enough for the animal to obtain some blood. As a class of medications, anticoagulants are used in therapy for thrombotic disorders. Oral anticoagulants (OACs) are taken by many people in pill or tablet form, and various intravenous anticoagulant dosage forms are used in hospitals. Some anticoagulants are used in medical equipment, such as sample tubes, blood transfusion bags, heart–lung machines, and dialysis equipment. One of the first anticoagulants, warfarin, was initially approved as a rodenticide. Anticoagulants are closely related to antiplatelet drugs and thrombolytic drugs by manipulating the various pathways of blood coagulation. Specifically, antiplatelet drugs inhibit platelet agg ...
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White Blood Cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from multipotent cells in the bone marrow known as hematopoietic stem cells. Leukocytes are found throughout the body, including the blood and lymphatic system. All white blood cells have cell nucleus, nuclei, which distinguishes them from the other blood cells, the anucleated red blood cells (RBCs) and platelets. The different white blood cells are usually classified by cell division, cell lineage (myelocyte, myeloid cells or lymphocyte, lymphoid cells). White blood cells are part of the body's immune system. They help the body fight infection and other diseases. Types of white blood cells are granulocytes (neutrophils, eosinophils, and basophils), and agranulocytes (monocytes, and lymphocytes (T cells and B cells)). Myeloid cells ...
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