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Lanadelumab
Lanadelumab, sold under the brand name Takhzyro, is a human monoclonal antibody (class IgG1 kappa) that targets plasma kallikrein (pKal) in order to promote prevention of angioedema in people with hereditary angioedema. Lanadelumab, was approved in the United States as the first monoclonal antibody indicated for prophylactic treatment to prevent hereditary angioedema attacks. Lanadelumab is the first treatment for hereditary angioedema prevention made by using cells within a lab, not human plasma. Common side effects include pain associated with injection site reactions, injection site bruising, upper respiratory infection, headache, rash, myalgia, dizziness, and diarrhea. The US Food and Drug Administration approved the use of lanadelumab in August 2018, for people that are 12 years and older and have either type I or type II hereditary angioedema. Medical uses In the United States, lanadelumab is indicated for the prophylaxis of hereditary angioedema attacks. Adverse e ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hereditary Angioedema
Hereditary angioedema (HAE) is a disorder that results in recurrent attacks of severe swelling. The swelling most commonly affects the arms, legs, face, intestinal tract, and airway. If the intestinal tract is affected, abdominal pain and vomiting may occur. Swelling of the airway can result in its obstruction and trouble breathing. Without preventive treatment, attacks typically occur every two weeks and last for a few days. There are three main types of HAE. Types I and II are caused by a mutation in the '' SERPING1'' gene, which encodes the C1 inhibitor protein, and type III now called HAE with Normal C1 esterase(HAE nl C1). Six known mutations are described in the literature under the type 3 HAE. The result is increased levels of bradykinin, which promotes swelling. The condition may be inherited in an autosomal dominant manner or occur as a new mutation. Triggers for an attack may include minor trauma or stress, but attacks often occur without any obvious preceding even ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Angioedema
Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are swelling within the upper skin. Onset is typically over minutes to hours. The underlying mechanism typically involves histamine or bradykinin. The version related to histamine is due to an allergic reaction to agents such as insect bites, foods, or medications. The version related to bradykinin may occur due to an inherited problem known as C1 esterase inhibitor deficiency, medications known as angiotensin-converting enzyme inhibitors, or a lymphoproliferative disorder. Treatment to protect the airway may include intubation or cricothyroidotomy. Histamine-related angioedema can be treated with antihistamines, corticosteroids, and epinephrine. In those with bradykinin-related disease a C1 esterase inhibitor, ecallantide, or icati ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Kallikrein
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein (encoded by ''KLKB1 gene'') has no known paralogue, while tissue kallikrein-related peptidases (''KLKs'') encode a family of fifteen closely related serine proteases. These genes are localised to chromosome Chromosome 19 (human), 19q13, forming the largest contiguous cluster of proteases within the human genome. Kallikreins are responsible for the coordination of various physiological functions including blood pressure, semen liquefaction and skin desquamation. Occurrence In 1934, Eugen Werle reported finding a substance in the pancreas of humans and various animals in such large amounts that the pancreas could be taken for its site of origin. He named it kallikrein, by derivation from the Greek word καλλίκρεας (''kallíkreas'') 'pancreas'. Since then, similar enzymes have been found in the biological fluids of humans and other mammals, as we ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
C1-inhibitor
C1-inhibitor (C1-inh, C1 esterase inhibitor) is a protease inhibitor belonging to the serpin superfamily. Its main function is the inhibition of the complement system (C1r, C1s) to prevent spontaneous activation but also as the major regulator of the contact system (PK, FXIIa, and FXIa). Proteomics C1-inhibitor is the largest member among the ''serpin'' superfamily of proteins. It can be noted that, unlike most family members, C1-inhibitor has a 2- domain structure. The C-terminal serpin domain is similar to other serpins, which is the part of C1-inhibitor that provides the inhibitory activity. The N-terminal domain (also some times referred to as the ''N-terminal tail'') is not essential for C1-inhibitor to inhibit proteases. This domain has no similarity to other proteins. C1-inhibitor is highly glycosylated, bearing both ''N''- and ''O''-glycans. N-terminal domain is especially heavily glycosylated. Role in disease Deficiency of this protein is associated with here ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks Covalent bond, bonds. Proteases are involved in numerous biological pathways, including Digestion#Protein digestion, digestion of ingested proteins, protein catabolism (breakdown of old proteins), and cell signaling. In the absence of functional accelerants, proteolysis would be very slow, taking hundreds of years. Proteases can be found in all forms of life and viruses. They have independently convergent evolution, evolved multiple times, and different classes of protease can perform the same reaction by completely different catalytic mechanisms. Classification Based on catalytic residue Proteases can be classified into seven broad ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Kininogen
Kininogens are Protein precursor, precursor proteins for Kinin, kinins, biologically active Peptide, polypeptides involved in blood coagulation, vasodilation, smooth muscle contraction, Inflammation, inflammatory regulation, and the regulation of the Circulatory system, cardiovascular and Kidney, renal systems. Types of kininogen There are two main types of kininogen (KNG), High-molecular-weight kininogen, high-molecular-weight-kininogen and Low-molecular-weight kininogen, low-molecular-weight-kininogen, with a third type – T-kininogen – only found in rats but not humans. High molecular weight kininogen High-molecular-weight-kininogen (HK) is a non-enzymatic Cofactor (biochemistry), cofactor involved in the kinin-kallikrein system, which plays a role in blood coagulation, blood pressure regulation, and inflammation. It is synthesized in endothelial cells and is produced mostly by the liver. It is also a precursor protein for bradykinin. Low molecular weight kininogen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bradykinin
Bradykinin (BK) (from Greek ''brady-'' 'slow' + ''-kinin'', ''kīn(eîn)'' 'to move') is a peptide that promotes inflammation. It causes arterioles to dilate (enlarge) via the release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor and makes veins constrict, via prostaglandin F2, thereby leading to leakage into capillary beds, due to the increased pressure in the capillaries. Bradykinin consists of nine amino acids, and is a physiologically and pharmacologically active peptide of the kinin group of proteins. A class of drugs called angiotensin-converting-enzyme inhibitors (ACE inhibitors) increase bradykinin levels by inhibiting its degradation, thereby increasing its blood pressure lowering effect. ACE inhibitors are FDA approved for the treatment of hypertension and heart failure. Structure Bradykinin, sometimes referred to as BK, is a 9–amino acid Translation (genetics), peptide chain. The amino acid sequence of bradykinin is: arginine, Arg-pr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vasodilation
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels. When blood vessels dilate, the flow of blood is increased due to a decrease in vascular resistance and increase in cardiac output. Vascular resistance is the amount of force circulating blood must overcome in order to allow perfusion of body tissues. Narrow vessels create more vascular resista ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Clinical Trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, pharmaceutical drug, drugs, medical nutrition therapy, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received institutional review board, health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small Pilot experiment, pi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vasodilation
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels. When blood vessels dilate, the flow of blood is increased due to a decrease in vascular resistance and increase in cardiac output. Vascular resistance is the amount of force circulating blood must overcome in order to allow perfusion of body tissues. Narrow vessels create more vascular resista ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vascular Permeability
Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the permeability of a blood vessel wall–in other words, the blood vessel wall's capacity to allow for the flow of small molecules (such as drugs, nutrients, water, or ions) or even whole cells (such as lymphocytes on their way to a site of inflammation) in and out of the vessel. Blood vessel walls are lined by a single layer of endothelial cells. The gaps between endothelial cells (cell junctions) are strictly regulated depending on the type and physiological state of the tissue. There are several techniques to measure vascular permeability to certain molecules. For instance, the cannulation of a single microvessel with a micropipette: the microvessel is perfused with a certain pressure, occluded downstream, and then the velocity of some cells will be related to the permeability.Michel, C. C., Mason, J. C., Curry, F. E. & Tooke, J. E. Development of Landis Techn ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
