I mispronounce or stumble over words — anastomosis, extravasation, Gastrografin — that seem foreign.
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Complications related to extravasation are possible with any medication. Since Vesicants are blistering agents, extravasation may lead to irreversible tissue injury. Extravasation is particularly serious during chemotherapy, since chemotherapy medications are highly toxic.
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Oral mucocele is a clinical term for two related phenomena: mucus extravasation phenomenon and mucous retention cyst. Other names include mucous extravasation cyst, mucous cyst of the oral mucosa, and mucous retention and extravasation phenomena. Mucous extravasation phenomenon is a swelling of connective tissue consisting of a collection of fluid called mucus. This occurs because of a ruptured salivary gland duct usually caused by local trauma (damage) in the case of mucous extravasation phenomenon and an obstructed or ruptured salivary duct (parotid duct) in the case of a mucus retention cyst.
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Both mucous retention and extravasation phenomena are classified as salivary gland disorders.
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Shoulder arthroscopy is typically limited to about 90-120 minutes before the swelling from fluid extravasation interferes with the procedure, and presents a potential risk to the patient. Typically, fluid extravasation is managed by controlling fluid pressure, or hastening the procedure. Arthroscopic instrumentation such as the newer Extravastat devices to drain extravasated fluid from the soft tissue during shoulder and hip arthroscopy has been reported to be beneficial in reducing fluid extravasation and swelling.
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The non-contrast images facilitate the differentiation of active extravasation or acute bleeding from vascular calcifications.
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While initial adhesion indicates the start of lymphocyte homing, there is regulation of each step of extravasation.
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The United States Food and Drug Administration has also approved a dexrazoxane for use as a treatment of extravasation resulting from IV anthracycline chemotherapy.Totect label on FDA's website Extravasation is an adverse event in which chemotherapies containing anthracylines leak out of the blood vessel and necrotize the surrounding tissue.
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Extravasation of urine due to blunt renal trauma or ureteral obstruction can lead to the formation of an urinoma.
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Hyaluronidase is also used for extravasation of hyperosmolar solutions. Hyaluronidase is used by plastic surgeons and dermatologists to reverse the effects of hyaluronic acid injections used as dermal fillers whenever the patient receiving the injections is unhappy with the results. Besides, hyaluronidase is a recommended antidote for vinca alkaloid overdose or extravasation.
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Milder consequences of extravasation include irritation, characterized by symptoms of pain and inflammation, with the clinical signs of warmth, erythema, or tenderness.
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Complications of using an irrigation system is that fluid extravasation into the soft tissues of the forearm can result in a compartment syndrome.
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Common adverse drug reaction includes bone marrow suppression, fatigue, hair loss, mouth ulcer, loss of appetite and diarrhea. Actinomycin is a vesicant, if extravasation occurs.
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If extravasation occurs local tissue death may result. The medication phentolamine can be injected at the site to try to decrease the risk of tissue death.
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Outside of the evaluation of masses, delayed phase images can be used in the evaluation of active vascular extravasation in trauma patients, vascular malformations, and aneurysm disruption.
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Angiopellosis allows for the extravasation of multiple cells during a single event. The blood vessel will actively remodel around a cluster/group of cells and allow the cells to exit in a single event. Diapedesis only allows for a single white blood cell to migrate across the blood vessel wall at a time. Although multiple white blood cells can leave simultaneously, they all elicit separate diapedesis extravasation events.
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This is transmitted to the atrium. On the left side of the heart, the increased pressure is transmitted to the pulmonary vasculature, and the resultant hydrostatic pressure favors extravasation of fluid into the lung parenchyma, causing pulmonary edema. On the right side of the heart, the increased pressure is transmitted to the systemic venous circulation and systemic capillary beds, favoring extravasation of fluid into the tissues of target organs and extremities, resulting in dependent peripheral edema.
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Extravasation may also refer to the leakage of infused substances from the vasculature into the subcutaneous tissue. The leakage of high-osmolarity solutions or chemotherapy agents can result in significant tissue destruction and significant complications.
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Extravasation is the leakage of intravenously (IV) infused, and potentially damaging, medications into the extravascular tissue around the site of infusion. The leakage can occur through brittle veins in the elderly, through previous venipuncture access, or through direct leakage from wrongly positioned venous access devices. When the leakage is not of harmful consequence it is known as infiltration. Extravasation of medication during intravenous therapy is an adverse event related to therapy that, depending on the medication, amount of exposure, and location, can potentially cause serious injury and permanent harm, such as tissue necrosis.
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Extravasation of urine refers to the condition where an interruption of the urethra leads to a collection of urine in other cavities, such as the scrotum or the penis in males. It can be associated with a calculus.
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119 This secondary injury can contribute heavily to long term loss of function and disability.Noble LJ, Wrathall JR. Distribution and time course of protein extravasation in the rat spinal cord after contusive injury. Brain Res 1989;482:57–66.
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Hemodynamically-stable individuals should undergo further radiographic assessment. Abdominal computed tomography (CT) with contrast can detect retroperitoneal hematomas, renal lacerations, urinary extravasation, and renal arterial and venous injuries. A repeat scan ten minutes after the first is recommended.
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Due to the invasive nature of invadopodia in cancer cells, research has focused on targeting invadopodia as a potential therapeutic target to inhibit metastasis. Inhibiting invadopodia formation by targeting Src kinase with Saracatanib in a chicken model system showed a decreased incidence of invadopodia and decreased cancer extravasation. In mice, inhibiting invadopodia formation directly, through RNAi against tks4 or tks5, significantly reduced cancer extravasation. Screening for drug activators and inhibitors of invadopodia revealed that Cdc5 can be a target for inhibiting invadopodia formation and also that, paradoxically, paclitaxel, a drug commonly used to treat cancer, induces invadopodia formation.
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An injury to the urethra leaving Buck's fascia intact results in a collection of urine (extravasation) limited to the penis, deep to Buck's fascia. However, if the injury to the bulb of the penis results in urethral injury accompanying a tear of the Buck's fascia, then extravasated blood and urine would accumulate in the superficial perineal space, passing into the penis (outer to Buck's fascia) as well as the scrotum and lower anterior abdominal wall. Extravasation of urine involving a compromised Buck's fascia can be appreciated clinically by blood collecting in the superficial pouch, resulting in a 'butterfly'-shaped region around the penis.
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The size of the nanoparticle (20-50 nm in diameter) facilitates its extravasation in the more leaky vessels of tumors via the enhanced permeability and retention effect and as a result, the anticancer drug is enhanced and retained in the tumor tissue.
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Acute care of a hemodynamically unstable trauma patient is never an ideal task. The emphasis is on stopping blood extravasation and hemodynamic stabilisation without delay, despite if it is pre-hospital, in the emergency department or in a hybrid operating suite. REBOA, also called Aortic Balloon Occlusion (ABO), is a powerful endovascular tool that inflates an intra-aortic balloon occluding the lumen of the vessel and decreased or completely prevents blood flow to the more distal parts. If inflated in the aorta proximal to the identified source of bleeding it may help to diminish or stop blood extravasation, also potentially aiding to increase cardiac afterload.
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Pathogenic influence was attributed also to the extravasation of other blood born substances such as hemosiderin or iron. Iron from hemoglobin, a molecule in red blood cells, can lead to the formation of free radicals that damage cell membranes; this process has been linked to epileptogenesis.
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Extravasation of intravenous sodium bicarbonate has been reported to cause chemical cellulitis because of its alkalinity, resulting in tissue necrosis, ulceration and/or sloughing at the site of infiltration. This condition is managed by prompt elevation of the part, warmth and local injection of lidocaine or hyaluronidase.
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Perforations can be closed with absorbable sutures. The suprapubic cystostomy remains in place for three months. Incomplete urethral disruptions heal spontaneously and the suprapubic cystostomy can be removed after three weeks for these injuries. Before removing a cystostomy, a voiding cystourethrography should demonstrate no urine extravasation.
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Goldberger's War (1st ed.). New York: Hill and Wang. pp. 68–71. . Also in 1901, Schamberg described a peculiar progressive pigmentary dermatosis caused by extravasation of blood from the capillaries in the skin. It is most common in the lower extremities, but its underlying etiology has not been firmly established.
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At high stresses, the binding affinities are still reduced because the selectin-ligand bond is still a normal slip bond. It is thought that this shear stress threshold helps select for the right diameter of blood vessels to initiate leukocyte extravasation, and may also help prevent inappropriate leukocyte aggregation during vascular stasis.
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Carmeliet P, et al., Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGFmediated endothelial survival and angiogenesis. Cell. 1999; 98: 147–57.Carmeliet P, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med.
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Extravasation of irrigation fluid is the unintended migration of irrigation fluid (e.g. saline) introduced into a human body. This may occur in a number of types of endoscopic surgery, such as minimally invasive orthopedic surgery, i.e. arthroscopy, TURP (trans-urethral resection of the prostate) and TCRE (trans- cervical resection of the endometrium).
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Leukocytes or white blood cells destroy abnormal cells and also provide protection against bacteria and other foreign matter. These interactions are transitory in nature but are crucial as an immediate immune response. To fight infection, leukocytes must move from the blood into the affected tissues. This movement into tissues is called extravasation.
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HEVs develop from cytokine production after exposure to antigen and express adhesion molecules from the selectin family, mucin-like family, and the Ig superfamily. Naive lymphocyte extravasation into Peyer’s patches is often mediated by L-selectin and limited expression of α4 integrins and other homing receptors prevents these lymphocytes from accessing mucosal effector tissue.
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This may occur subsequent to blood–brain barrier failure, and lead to extravasation of serum components into the brain that are potentially toxic. Lacunar infarction could thus occur in this way, and the narrowing – the hallmark feature of lipohyalinosis – may merely be a feature of the swelling occurring around it that squeezes on the structure.
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Patients can have pain secondary to uterine contractions, uterine tetany or localized uterine tenderness. Signs can also be due to abruptio placentae including uterine hypertonus, fetal distress, fetal death, and rarely, hypovolemic shock (shock secondary to severe blood loss). The uterus may adopt a bluish/purplish, mottled appearance due to extravasation of blood into uterine muscle.
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Angiopellosis extravasation occurs as a means for cells that are not native to the circulation to exit. This includes adult stem cells that are injected intravenously for therapies. Cells that are normally found in circulation (i.e. blood cells) either extravasate through diapedesis (white blood cells), or do not extravasate and remain in circulation (red blood cells).
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Granzyme B can degrade many proteins in the extracellular matrix (ECM) including fibronectin, vitronectin and aggrecan. Cleavage can cause cell death by anoikis and release alarmins from the ECM inducing inflammation. Fragments of fibronectin can attract neutrophils and stimulate MMP expression from chondrocytes. Basophils secrete granzyme B to degrade endothelial cell-cell contacts allowing extravasation to sites of inflammation.
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ICAM-1 promotes the extravasation and activation of leukocytes (white blood cells), which is part of the inflammation process. Alicaforsen inhibits the activity of ICAM-1 protein by degrading mRNA coding for it via an RNase-H based mechanism. It appears to have better efficacy as a topical medication than via systemic administration which is typical of antisense drugs.
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There was no recent external injury save to the neck. The > body being washed more thoroughly I could see some healing sores. The lobe > of the left ear was torn as if from the removal or wearing through of an > earring, but it was thoroughly healed. On removing the scalp there was no > sign of extravasation of blood.
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A microscope picture of a cell's invadopodium. Courtesy M.C. Farach-Carson. Invadopodia are actin-rich protrusions of the plasma membrane that are associated with degradation of the extracellular matrix in cancer invasiveness and metastasis. Very similar to podosomes, invadopodia are found in invasive cancer cells and are important for their ability to invade through the extracellular matrix, especially in cancer cell extravasation.
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Vitreous hemorrhage is the extravasation, or leakage, of blood into the areas in and around the vitreous humor of the eye. The vitreous humor is the clear gel that fills the space between the lens and the retina of the eye. A variety of conditions can result in blood leaking into the vitreous humor, which can cause impaired vision, floaters, and photopsia.
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Embolization is a minimally invasive technique used in EVTM of selected hemodynamically unstable patients with both traumatic and non-traumatic injuries. It is the artificial creation of a thrombus by the introduction of various substances to intentionally occlude a vessel with the aim to stop or diminish blood extravasation and is a critical part of the modern management of arterial injuries.
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Anthracyclines are a class of drugs that are among the most commonly used agents in the treatment of cancer. Doxorubicin, the first anthracycline to gain approval, has demonstrated efficacy in a wide variety of cancers including breast cancer, lung cancer, sarcomas, and lymphomas. However, doxorubicin is associated with side effects such as myelosuppression, gastrointestinal disorders, mucositis, stomatitis, cumulative cardiotoxicity and extravasation.
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Battle's sign, also known as mastoid ecchymosis, is an indication of fracture of middle cranial fossa of the skull. These fractures may be associated with underlying brain trauma. Battle's sign consists of bruising over the mastoid process as a result of extravasation of blood along the path of the posterior auricular artery. The sign is named after William Henry Battle.
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Cell-surface sialylation has been implicated in cell–to-cell interactions, and over- expression of a brain sialyltransferase in breast-cancer cells is a mechanism highlighting the role of cell-surface glycosylation in organ-specific metastatic interactions. Breast-cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of BBB-crossing and brain colonization.
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Infection, phlebitis, extravasation, infiltration, air embolism, hemorrhage (bleeding) and formation of a hematoma (bruise) may occur. Because of the risk of insertion-site infection the CDC advises in their guideline that the catheter needs to be replaced every 96 hours. However, the need to replace these catheters routinely is debated. Expert management has been shown to reduce the complications of peripheral lines.
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Heparanase has endoglycosidase activity and cleaves polymeric heparan sulfate molecules at sites which are internal within the polymeric chain. The enzyme degrades the heparan sulfate scaffold of the basement membrane and extracellular matrix. It is also associated with the inflammatory process, by allowing the extravasation of activated T lymphocytes. In ocular surface physiology this activity functions as an off/on switch for the prosecretory mitogen lacritin.
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Features of vascular injury are shown including fibrinoid necrosis (asterisks) and erytrocyt extravasation (solid arrows). The diagnostic testing for vasculitis should be guided by the patient's history and physical exam. The clinician should ask about the duration, onset, and presence any associated symptoms such as weight loss or fatigue (that would indicate a systemic cause). It is important to distinguish between IgA and non-IgA vasculitis.
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Without annexin A-I in mediating this response, neutrophil extravasation is highly active and worsens the inflammatory response in damaged or infected tissues. Annexin A-I has also been implicated in apoptotic mechanisms in the cell. When expressed on the surface of neutrophils, annexin A-I promotes pro-apoptotic mechanisms. Alternatively, when expressed on the cell surface, annexin A-I promotes the removal of cells that have undergone apoptosis.
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Intravasation is the invasion of cancer cells through the basement membrane into a blood or lymphatic vessel. Intravasation is one of several carcinogenic events that initiate the escape of cancerous cells from their primary sites. Other mechanisms include invasion through basement membranes, extravasation, and colonization of distant metastatic sites. Cancer cell chemotaxis also relies on this migratory behavior to arrive at a secondary destination designated for cancer cell colonization.
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Substance P (SP) is a neuropeptide produced by capsaicin neuron cell bodies (localized in trigeminal ganglia and dorsal root) and plays a major role in dental pain and inflammation. Other peptides include cGRP, galanin, somatostatin, and neurokinin A-B. The biological effects of SP are expressed by the binding of specific G protein- coupled NK receptors. Interaction with SP receptors induces vasodilation and allows for plasma extravasation and mastocyte degranulation.
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Endothelial cells possess a large number of OSM receptors. Stimulation of a primary endothelial culture (HUVEC) with hOSM results in delayed but prolonged upregulation of P-selectin, which facilitates leukocyte adhesion and rolling, necessary for their extravasation. OSM also promotes the production of IL-6 from these cells. As mentioned above the action of OSM as a quencher of the inflammatory response is by no means established yet.
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As part of a disease process, infiltration is sometimes used to define the invasion of cancer cells into the underlying matrix or the blood vessels. Similarly, the term may describe the deposition of amyloid protein. During leukocyte extravasation, white blood cells move in response to cytokines from within the blood, into the diseased or infected tissues, usually in the same direction as a chemical gradientKumar et al. 2014, p.
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The selectins and selectin ligands determine the organ selectivity of metastasis. Several factors may explain the seed and soil theory or homing of metastasis. In particular, genetic regulation and activation of specific chemokines, cytokines and proteases may direct metastasis to a preferred organ. In fact, the extravasation of circulating tumor cells in the host organ requires successive adhesive interactions between endothelial cells and their ligands or counter-receptors present on the cancer cells.
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Bursae are readily inflamed when irritated, as their walls are very thin. Along with the pes anserine bursa, the prepatellar bursa is one of the most common bursae to cause knee pain when inflamed. Prepatellar bursitis is caused by either a single instance of acute trauma to the knee, or repeated minor trauma to the knee. The trauma can cause extravasation of nearby fluids into the bursa, which stimulates an inflammatory response.
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Phentolamine should only be given to patients who do not fully respond to benzodiazepines, nitroglycerin, and calcium channel blockers. When given by injection it causes blood vessels to dilate, thereby increasing blood flow. When injected into the penis (intracavernosal), it increases blood flow to the penis, which results in an erection. It may be stored in crash carts to counteract severe peripheral vasoconstriction secondary to extravasation of peripherally placed vasopressor infusions, typically of norepinephrine.
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Purple glove syndrome is caused by the intravenous anticonvulsant phenytoin. This medication has many already established neurological side effects, however glove syndrome is a rare, but very serious adverse effect that may lead to limb amputations. This may occur due to the administration of phenytoin with or without extravasation. The defining characteristic is a purplish to black discoloration of the extremity followed by peripheral edema and pain distal to the site of infusion.
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36, in a process called chemotaxis. The presence of lymphocytes in tissue in greater than normal numbers is likewise called infiltration. As part of medical intervention, local anaesthetics may be injected at more than one point so as to infiltrate an area prior to a surgical procedure. However, the term may also apply to unintended iatrogenic leakage of fluids from phlebotomy or intravenous drug delivery procedures, a process also known as extravasation or "tissuing".
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As part of the reaction of the body to the surgical wounds of vasectomy, the body produces hard scar-like tissue. Clamping the vas deferens can produce muscle disruption and fibrosis. As the diameter of the vas lumen is less than the thickness of the wall, the thick muscle layers can easily become disrupted, leading to sperm accumulation and extravasation. Cysts often form from the fluid that spreads between the muscle layers.
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MMPs and NO induce vasodilation in the cerebral vasculature. Cytokines induce capillary wall changes in the blood brain barrier, which leads to expression of more leukocyte receptors, thus increasing white blood cell binding and extravasation. The barrier that the meninges create between the brain and the bloodstream are what normally protect the brain from the body's immune system. Damage to the meninges and endothelial cells increases cytotoxic reactive oxygen species production, which damages pathogens as well as nearby cells.
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It has also been proven to be a tumor suppressor for some tumors. It probably is aided by its action in upregulating thrombospondin, SPARC (osteonectin), and fibronectin. However it has also been speculated to aid in extravasation in circulating melanoma cells. In case of prostate cancer it has been shown to be expressed in cancer associated stroma but not in normal stroma and has been suggested to be of potential help for cancer specific drug targeting .
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Metastasis is common in the late stages of cancer and it can occur via the blood or the lymphatic system or both. The typical steps in metastasis are local invasion, intravasation into the blood or lymph, circulation through the body, extravasation into the new tissue, proliferation and angiogenesis. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the lungs, liver, brain and the bones.
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The ITGB2 protein product is CD18. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain, and are crucial for cells to be able to efficiently bind to the extracellular matrix. This is especially important for neutrophils, as cellular adhesion plays a large role in extravasation from the blood vessels. A given chain may combine with multiple partners resulting in different integrins. The known binding partners of CD18 are CD11a, CD11b, CD11c and CD11d.
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A urinoma is the result of a breach of the integrity of the pelvis or calices of the kidney or of the ureter. The urine collection in the perirenal fat causes an inflammatory response with lipolysis resulting in its fibrous encapsulation. Urinomas are usually caused by blunt trauma to the kidneys. While extravasation of urine is common as a result a severe blunt trauma (2-18%), spontaneous resolution is typical, and urinoma formation develops only in few instances.
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Typical external symptoms include exophthalmia and the presence of hemorrhages in the periorbital and intraocular area, the base of fins, the perianal region, the opercula and the buccal region. In further studies, swollen abdomens and anal prolapsus have been observed. Due to infection, fish have produced lesions in the vascular endothelium that cause blood extravasation, leading to hemorrhages and petechiae at the surface of internal organs. The main organs affected are the spleen, liver, brain, stomach, kidney and heart.
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A complement receptor is a membrane-bound receptor belonging to the complement system, which is part of the innate immune system. Complement receptors bind effector protein fragments that are produced in response to antigen-antibody complexes or damage-associated molecules. Complement receptor activation contributes to the regulation of inflammation, leukocyte extravasation, and phagocytosis; it also contributes to the adaptive immune response. Different complement receptors can participate in either the classical complement pathway, the alternative complement pathway, or both.
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Injections also cause localized bleeding, which may lead to a hematoma. Intravenous injections may also cause phlebitis, especially when multiple injections are given in a vein over a short period of time. Infiltration and extravasation may also occur when a medication intended to be injected into a vein is inadvertently injected into surrounding tissues. Those who are afraid of needles may also experience fainting at the sight of a needle, or before or after an injection.
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The precise cause of amyloid purpura is unknown, but several mechanisms are thought to contribute. One may be a decrease in the level of circulating factor X, a clotting factor necessary for coagulation. The proposed mechanism for this decrease in factor X is that circulating amyloid fibrils bind and inactivate factor X. Another contributing factor may be enhanced fibrinolysis, the breakdown of clots. Subendothelial deposits of amyloid may weaken blood vessels and lead to the extravasation of blood.
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Atherosclerosis is the result of an inflammatory response to lipid-mediated vascular damage. It has been identified that cytokines such as TNF-α induce the expression of pro-inflammatory genes to synthesize leukocyte adhesion molecules and chemokines. Endothelial cells highly express MAP4K4 and recent studies have reported that MAP4K4 enhances endothelial permeability. This consequently contributes to the development of atherosclerosis due to the promotion of leukocyte extravasation, transport of oxidized lipids and the formation of plaques.
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This buildup of irrigation fluid in the soft tissue may cause edema. This swelling can interfere with the arthroscopic procedure by collapsing the surgical space, or migrating into the patient's neck and causing airway blockage. In hip arthroscopy, a feared complication is abdominal flooding where the irrigation fluid leaks from the hip joint capsule and drains into the abdominal cavity. Risk factors for fluid extravasation include procedure length (> 90-120 min), obesity, and age (> 45-50) with accompanying lack of muscle tone.
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Sialyl- Lewisx plays a critical role in cancer metastasis, facilitating the extravasation of cancer cells out of the bloodstream while they are moving through the body. Its expression is related to tumor stage, recurrence, and overall patient survival. Therefore, sialyl Lewis x is being used as a target in studies to fight tumors and cancer cell growth. It has been shown that there is frequent overexpression of sialyl Lewis x on cancer cells and is found on both N-glycan and O-glycans.
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These criteria were then validated in 56 consecutive patients retrospectively and appear to reliably predict the need for invasive management in patients with blunt injury to the spleen (sensitivity of 100%, specificity 88%, overall accuracy was 93%). The study suggested that the following three CT findings correlate with the need for intervention: #Devascularization or laceration involving 50% or more of the splenic parenchyma #Contrast blush greater than one centimeter in diameter (from active extravasation of IV contrast or pseudoaneurysm formation) #A large hemoperitoneum.
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Viel is co-author of The Inner Life of the Cell, an 8.5-minute 3D computer graphics animation illustrating the molecular mechanisms that occur when a white blood cell in the blood vessels of the human body is activated by inflammation (Leukocyte extravasation). It shows how a white blood cell rolls along the inner surface of the capillary, flattens out, and squeezes through the cells of the capillary wall to the site of inflammation where it contributes to the immune reaction.
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Preclinical evidence suggests that, during a migraine, activated primary sensory neurons (meningeal nociceptors) in the trigeminal ganglion release CGRP from their peripherally projecting nerve endings located within the meninges. This CGRP then binds to and activates CGRP receptors located around meningeal vessels, causing vasodilation, mast cell degranulation, and plasma extravasation. Human observations have further implicated the role of CGRP in the pathophysiology of migraine. Activation of primary sensory neurons in the trigeminal vascular system in humans can cause the release of CGRP.
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Causes of unconjugated hyperbilirubinemia are divided into three main categories, namely, excessive bilirubin synthesis, liver bilirubin uptake malfunction, and bilirubin conjugation compromise. As to excessive bilirubin synthesis, both intravascular hemolysis and extravascular hemolysis can involve in the pathophysiology. Additionally, dyserythropoiesis and extravasation of blood into tissues such as angioedema and edema can also lead to indirect hyperbilirubinemia, along with heart failure, medication-induced, ethinyl estradiol, chronic hepatitis, and cirrhosis that are, otherwise, attributed to hepatic bilirubin mal-uptake and bilirubin conjugation compromise, respectively.
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The EPR effect is further enhanced by many pathophysiological factors involved in enhancement of the extravasation of macromolecules in solid tumor tissues. For instance, bradykinin, nitric oxide / peroxynitrite, prostaglandins, vascular permeability factor (also known as vascular endothelial growth factor VEGF), tumor necrosis factor and others. One factor that leads to the increased retention is the lack of lymphatics around the tumor region which would filter out such particles under normal conditions. The EPR effect is usually employed to describe nanoparticle and liposome delivery to cancer tissue.
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Annexin A-I seems to be one of the most heavily involved annexins in anti- inflammatory responses. Upon infection or damage to tissues, annexin A-I is believed to reduce inflammation of tissues by interacting with annexin A-I receptors on leukocytes. In turn, the activation of these receptors functions to send the leukocytes to the site of infection and target the source of inflammation directly. As a result, this inhibits leukocyte (specifically neutrophils) extravasation and down regulates the magnitude of the inflammatory response.
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For continuous, frequent or prolonged intravenous chemotherapy administration, various systems may be surgically inserted into the vasculature to maintain access. Commonly used systems are the Hickman line, the Port-a-Cath, and the PICC line. These have a lower infection risk, are much less prone to phlebitis or extravasation, and eliminate the need for repeated insertion of peripheral cannulae. Isolated limb perfusion (often used in melanoma), or isolated infusion of chemotherapy into the liver or the lung have been used to treat some tumors.
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JAML or Junctional Adhesion Molecule-Like, or AMICA1 is a JAM transmembrane protein family member. It is composed of two extracellular immunoglobulin-like domains, a membrane-spanning region, and a cytoplasmic tail involved in activation signaling. A known ligand of JAML is Coxsackie virus and Adenovirus Receptor (CXADR in humans and CAR in mice) which has been shown to localize to the tight junctions of epithelial cells. JAML-mediated activation of CAR is required for neutrophil extravasation in addition to other leukocyte/epithelial cell interaction models.
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Metastasis is the leading cause of mortality in cancer patients; it relies on the ability of cancer cells to degrade the surrounding extracellular matrix and invade other tissues. The mechanisms of this process are still not completely understood, and because of the invasive properties of invadopodia, they have been investigated in this context. Indeed, invadopodia have been implicated in many cancers and cancer cells. Increased invasiveness of cancer cells correlates with invadopodia presence, and cancer cells have been observed to project them into the endothelium of blood vessels during extravasation, an important step in metastasis.
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Since the adhesion of several cancer cells to endothelium requires the presence of endothelial selectins as well as sialyl Lewis carbohydrates on cancer cells, the degree of expression of selectins on the vascular wall and the presence of the appropriate ligand on cancer cells are determinant for their adhesion and extravasation into a specific organ. The differential selectin expression profile on endothelium and the specific interactions of selectins expressed by endothelial cells of potential target organs and their ligands expressed on cancer cells are major determinants that underlie the organ-specific distribution of metastases.
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Based on the degree and type of local effect, bites can be divided into two symptomatic categories: those with little or no surface extravasation, and those with hemorrhages evident as ecchymosis, bleeding and swelling. In both cases there is severe pain and tenderness, but in the latter there is widespread superficial or deep necrosis and compartment syndrome. Serious bites cause limbs to become immovably flexed as a result of significant hemorrhage or coagulation in the affected muscles. Residual induration, however, is rare and usually these areas completely resolve.
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Sialyl Lewis X is also one of the most important blood group antigens and is displayed on the terminus of glycolipids that are present on the cell surface. The sialyl Lewis X determinant, E-selectin ligand carbohydrate structure, is constitutively expressed on granulocytes and monocytes and mediates inflammatory extravasation of these cells. Resting T- and B-lymphocytes lack its expression and are induced to strongly express sialyl Lewis X upon activation. The sialyl Lewis X determinant is expressed preferentially on activated Th1 cells but not on Th2 cells.
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In 2006, XVIVO released The Inner Life of the Cell, an 8.5 minute 3D computer graphics animation depicting the molecular processes of a white blood cell during leukocyte extravasation. The concepts and scientific knowledge for the film were given by Robert Lue, director of life sciences education, and Alain Viel, director of undergraduate research at Harvard University. The film was commissioned by Robert Lue to become part of the molecular and cellular biology department’s learning program, Bio Visions. XVIVO’s John Liebler was the lead animator for the project.
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Evidence does not support a benefit of kyphoplasty over vertebroplasty with respect to pain, but the procedures may differ in restoring lost vertebral height, and in safety issues like cement extravasation (leakage). As with vertebroplasty, several unblinded studies have suggested a benefit from balloon kyphoplasty. , no blinded studies have been performed, and since the procedure is a derivative of vertebroplasty, the unsuccessful results of these blinded studies have cast doubt upon the benefit of kyphoplasty generally. Some vertebroplasty practitioners and some health care professional organizations continue to advocate for the procedure.
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Because the activity of fibroblasts and epithelial cells requires oxygen and nutrients, angiogenesis is imperative for other stages in wound healing, like epidermal and fibroblast migration. The tissue in which angiogenesis has occurred typically looks red (is erythematous) due to the presence of capillaries. Angiogenesis occurs in overlapping phases in response to inflammation: #Latent period: During the haemostatic and inflammatory phase of the wound healing process, vasodilation and permeabilisation allow leukocyte extravasation and phagocytic debridement and decontamination of the wound area. Tissue swelling aids later angiogenesis by expanding and loosening the existing collagenous extracellular matrix.
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The rolling mechanism helps the L-selectin molecules on the surface of naive T cells to weakly interact with GlyCAM-1 and CD34 molecules on HEV cells. The chemokine CCL21 then binds to its receptor CCR7 expressed on the T cell. This binding induces a conformational change in the LFA-1 molecule causing it to bind tightly to ICAM-1. This tight binding stops further movement of the T cell which can then move between HEV cells into the lymph node by a process termed 'diapedesis' (or extravasation).
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Continued work led to the development of sumatriptan, now known as the first 5-HT1 agonist, selective for the 5-HT1D/B receptors and also the 5-HT1F receptor with less affinity. By 1991 sumatriptan became available in clinical use in the Netherlands and in the US in 1993. However, there was always a debate about its mechanism of action, and it still remains unclear today. Later, Mike Moskowitz proposed a theory about "neuronal extravasation", and this was the first clue that sumatriptan might have a direct neuronal effect in migraine attacks.
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About 100 mg are thought to be enough to kill a healthy adult human male, with death occurring after 25 hours. In humans, bites from this species can produce severe local and systemic symptoms. Based on the degree and type of local effect, bites can be divided into two symptomatic categories - those with little or no surface extravasation, and those with hemorrhages evident as ecchymosis, bleeding, and swelling. In both cases, severe pain and tenderness occur, but in the latter, widespread superficial or deep necrosis and compartment syndrome are seen.
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Studies show a moderate neutrophilia (less than 50%), elevated ESR (greater than 30 mm/h) (90%), and a slight increase in alkaline phosphatase (83%). Skin biopsy shows a papillary and mid-dermal mixed infiltrate of polymorphonuclear leukocytes with nuclear fragmentation and histiocytic cells. The infiltrate is predominantly perivascular with endothelial-cell swelling in some vessels, but vasculitic changes (blood clots; deposition of fibrin, complement, or immunoglobulins within the vessel walls; red blood cell extravasation;inflammatory infiltration of vascular walls) are absent in early lesions.Perivasculitis occurs secondarily, because of cytokines released by the lesional neutrophils.
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Pulmonary capillary pressures in this level cause an imbalance between the hydrostatic pressure and the oncotic pressure, leading to extravasation of fluid from the vascular tree and pooling of fluid in the lungs (congestive heart failure causing pulmonary edema). The constant pressure overload of the left atrium will cause the left atrium to increase in size. As the left atrium increases in size, it becomes more prone to develop atrial fibrillation (AF). When atrial fibrillation develops, the atrial kick is lost (since it is due to the normal atrial contraction).
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ICAM-1 propagates an inflammatory response promoting the extravasation and activation of leukocytes (white blood cells) into inflamed tissue. Increased expression of ICAM-1 has been observed within the inflamed intestinal mucosa of ulcerative colitis, pouchitis and Crohn's sufferers where ICAM-1 over production correlated with disease activity. This suggests that ICAM-1 is a potential therapeutic target in the treatment of these diseases. Cannabinoid CB2 receptor agonists are found to decrease the induction of ICAM-1 and VCAM-1 surface expression in human brain tissues and primary human brain endothelial cells (BMVEC) exposed to various pro-inflammatory mediators.
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At the same time, the G-protein subunit Gα directly activates an enzyme called protein tyrosine kinase (PTK), which phosphorylates serine and threonine residues in the tail of the chemokine receptor, causing its desensitisation or inactivation. The initiated MAP kinase pathway activates specific cellular mechanisms involved in chemotaxis, degranulation, release of superoxide anions, and changes in the avidity of cell adhesion molecules called integrins. Chemokines and their receptors play a crucial role in cancer metastasis as they are involved in extravasation, migration, micrometastasis, and angiogenesis. This role of chemokine is strikingly similar to their normal function of localizing leukocytes to an inflammatory site.
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Following cell activation (for example, by neutrophil adhesion to endothelial-cell monolayers), annexin A1 is promptly mobilized to the cell surface and secreted. Annexin A1 promotes neutrophil detachment and apoptosis, and phagocytosis of apoptotic neutrophils by macrophages. On the other hand, it reduces the tendency of neutrophils to penetrate the endothelium of blood vessels. In vitro and in vivo analyses show that exogenous and endogenous annexin A1 counter-regulate the activities of innate immune cells, particularly extravasation and the generation of proinflammatory mediators, which ensures that a sufficient level of activation is reached but not exceeded.
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HAS can play roles in all of the stages of cancer metastasis. By producing anti-adhesive HA, HAS can allow tumor cells to release from the primary tumor mass and if HA associates with receptors such as CD44, the activation of Rho GTPases can promote EMT of the cancer cells. During the processes of intravasation or extravasation, the interaction of HAS produced HA with receptors such as CD44 or RHAMM promote the cell changes that allow for the cancer cells to infiltrate the vascular or lymphatic systems. While traveling in these systems, HA produced by HAS protects the cancer cell from physical damage.
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Macrophages that reside in adult healthy tissues either derive from circulating monocytes or are established before birth and then maintained during adult life independently of monocytes. By contrast, most of the macrophages that accumulate at diseased sites typically derive from circulating monocytes. When a monocyte enters damaged tissue through the endothelium of a blood vessel, a process known as leukocyte extravasation, it undergoes a series of changes to become a macrophage. Monocytes are attracted to a damaged site by chemical substances through chemotaxis, triggered by a range of stimuli including damaged cells, pathogens and cytokines released by macrophages already at the site.
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Angiopellosis (cell extravasation) is the movement of cells out of the circulatory system into the surrounding tissue. This process is specific to non-leukocytic cells, as leukocytes (white blood cells) utilize diapedesis for movement out of circulation. Angiopellosis was discovered by studying how stem cells reach damaged tissue when injected or infused into the blood stream. Recently, it was found that circulating tumor cells (CTCs) also possess the ability to exit blood vessels through angiopellosis during the metastasis process Angiopellosis involves recognition of cells by the blood vessel wall (endothelial cells), and then the active remolding of the blood vessel to allow the cell to exit.
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Notably, because of its potential in relevant antimicrobial, anti-tumor cell, and/or consumption of amino acids, the interest of researching sv-LAAOs has begun to grow. Many authors have investigated the mechanism of antibacterial action of sv-LAAO. It is well established that sv- LAAO kills and breaks down bacteria by the H2O2 that is produced as a result of the oxidation reaction occurring in the surrounding environment. In one case study, it was reported that the sv-LAAO (isolated from C. durissus cascavella venom) caused the rupture of bacteria membranes while promoting extravasation, or leakage, of plasmatic contents out of the cellular structure.
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CP-122,288 is a drug which acts as a potent and selective agonist for the 5-HT1B, 5-HT1D and 5-HT1F serotonin receptor subtypes. It is a derivative of the migraine medication sumatriptan, but while CP-122,288 is 40,000 times more potent than sumatriptan as an inhibitor of neurogenic inflammation and plasma protein extravasation, it is only twice as potent as a constrictor of blood vessels. In human trials, CP-122,288 was not found to be effective as a treatment for migraine, but its selectivity for neurogenic anti-inflammatory action over vasoconstriction has made it useful for research into the underlying causes of migraine.
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Non contrasted CT scans might show an intimal flap, periaortic hematoma, luminal filling defect, aortic contour abnormality, pseudoaneurysm, contained rupture, vessel wall disruption, active extravasation of intravenous contrast from the aorta and is therefore useful to assess for minimal aortic injury. Trans esophageal echos are useful in patients that are hemodynamically unstable, but the sensitivity and specificity of this study varies based on clinical user. The trans esophageal echo relies on placement an ultrasound probe into the patient's esophagus in order to get an ultrasound of the heart. If esophageal injury is expected, the patient has a facial injury, or if the patient has difficulty maintaining their away then the trans esophageal echo is contraindicated.
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Although Lewis observed vasodilation that could be explained by axon reflex, there was not yet direct evidence explaining the branching of nerves from the center of an axon rather than a cell body or which chemical agents were responsible for the goose bump, red line, and dilated blood vessel symptoms. In the 1960s, scientists A. Janscó-Gabor and J. Szolcsányi demonstrated that when irritant chemicals and electrical stimulants are applied to the skin, cutaneous nocireceptors are stimulated. These pain sensors send signals to neighboring tissues resulting in extravasation, also known as leakage from the blood vessels. This response is similar to Lewis’s research with vasodilation as both rely on an intact sensory nerve supply that affect neighboring tissues.
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Unlike ultrasound examination (FAST), CT provides anatomic and functional information that allows for accurate grading of the injury which is partly responsible for a growing trend toward conservative management (intravenous fluids, close monitoring, watchful waiting) of renal trauma. Conservative management does not apply in situations where extensive urinary extravasation or devitalized areas of renal parenchyma are found and especially if associated with injuries to other abdominal organs; these cases are complication-prone and much more likely to require surgery. That being said, a retrospective study suggests that primary conservative treatment of blunt kidney rupture seems to lead to less surgery, especially less open surgery, and less blood and renal parenchyma loss, compared to a strategy of initial surgery.
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Integrins have two main functions, attachment of the cells to the ECM and signal transduction from the ECM to the cells. They are also involved in a wide range of other biological activities, including extravasation, cell-to- cell adhesion, cell migration, and as receptors for certain viruses, such as adenovirus, echovirus, hantavirus, and foot-and-mouth disease, polio virus and other viruses. A prominent function of the integrins is seen in the molecule GpIIb/IIIa, an integrin on the surface of blood platelets (thrombocytes) responsible for attachment to fibrin within a developing blood clot. This molecule dramatically increases its binding affinity for fibrin/fibrinogen through association of platelets with exposed collagens in the wound site.
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The Inner Life of the Cell is an 8.5-minute 3D computer graphics animation illustrating the molecular mechanisms that occur when a white blood cell in the blood vessels of the human body is activated by inflammation (Leukocyte extravasation). It shows how a white blood cell rolls along the inner surface of the capillary, flattens out, and squeezes through the cells of the capillary wall to the site of inflammation where it contributes to the immune reaction. When teaching biology, professors will often generate 3D animations to demonstrate certain concepts to their students in a much more visual way than would otherwise be possible. In the case of The Inner Life of the Cell the creators aimed for a more cinematic, as opposed to academic, feel.
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A catheter with a diameter of less than 2 mm is inserted at the base of the foot (femoral artery) or the artery in the wrist (radial artery). The tip of the catheter is inserted into the orifice of the bronchial artery (normally smaller than 1 mm) or other non-bronchial hemoptysis-related arteries. Contrast agent is injected through the catheter, and when abnormal findings are observed, such as systemic–pulmonary shunts, proliferations of the capillary vessels, or extravasation of the contrast medium to the lung tissues, they were super selectively embolized using the 3 Fr microcatheter system. A thinner microcatheter (about 0.8 mm) is passed through the catheter into the blood vessel, and then, embolic material is injected into the appropriate site.
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Activated protein C binds to endothelial protein C receptor and subsequently cleaves the endothelial cell protease activated receptor-1, not only altering coagulation profiles but down-regulating pro- inflammatory and pro-apoptotic mediators, up-regulation of anti-inflammatory and anti-apoptotic pathways and stabilization of the endothelial cell barrier functions. Systemic coagulation activation may lead to depletion of circulating coagulation factors and platelets, which subsequently lead to bleeding. In early purpura fulminans, lesion progression correlates with the histological appearance of blockage of small skin blood vessels with blood clots causing capillary dilation and congestion with red blood cells. In later stage lesions, there is irreversible endothelial ischaemic injury with extravasation of blood cells into the dermis and gangrenous necrosis, sometimes with secondary infection.
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This triggers the activation of integrins from the cancer cells allowing their firmer adhesion to members of the Ig-CAM family such as ICAM, initiating the transendothelial migration and extravasation processes.[72] The appropriate set of endothelial receptors is sometimes not expressed constitutively and the cancer cells have to trigger their expression. In this context, the culture supernatants of cancer cells can trigger the expression of E- selectin by endothelial cells suggesting that cancer cells may release by themselves cytokines such as TNF-α, IL-1β or INF-γ that will directly activate endothelial cells to express E-selectin, P-selectin, ICAM-2 or VCAM. On the other hand, several studies further show that cancer cells may initiate the expression of endothelial adhesion molecules in a more indirect ways.
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Helminthic therapy using the whipworm Trichuris suis has been shown in a randomized control trial from Iowa to show benefit in people with ulcerative colitis. The therapy tests the hygiene hypothesis which argues that the absence of helminths in the colons of people in the developed world may lead to inflammation. Both helminthic therapy and fecal microbiota transplant induce a characteristic Th2 white cell response in the diseased areas, which was unexpected given that ulcerative colitis was thought to involve Th2 overproduction. Alicaforsen is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human ICAM-1 messenger RNA through Watson-Crick base pair interactions in order to subdue expression of ICAM-1. ICAM-1 propagates an inflammatory response promoting the extravasation and activation of leukocytes (white blood cells) into inflamed tissue.
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In humans, lack of functional CD18 causes Leukocyte Adhesion Deficiency, a disease defined by a lack of leukocyte extravasation from blood into tissues, which is the inability of circulating leukocytes to respond to foreign bodies present in the tissue. This subsequently reduces the ability of the individual's immune system to fight off infection, making them more susceptible to foreign infection than those with functional CD18 proteins. The beta 2 integrins have also been found in a soluble form, meaning they are not anchored into the plasma membrane of the cell, but rather exist outside of the cell in the plasma, and are capable of ligand binding. The soluble beta 2 integrins are ligand binding and plasma levels are inversely associated with disease activity in the autoimmune disease spondyloarthritis.
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Butcher and his research team study the trafficking of white blood cells (lymphocytes, dendritic cells, monocytes, etc.), including their interactions with the endothelial lining of blood vessels at sites of leukocyte extravasation, and their chemotactic responses in tissues. These events regulate immune responses by controlling the access of leukocytes to sites of inflammatory or immune reaction in the body. He and his research team have shown that lymphocytes use a variety of different adhesion molecules or "homing receptors" to recognize organ (and/or inflammation)-specific vascular ligands or "addressins" that define the tissue position (address) of blood vessels in the body. Their studies have shown that these adhesion receptors act coordinately with G protein-linked serpentine chemoattractant receptors in a multi-step process that controls the specificity and provides combinatorial diversity in leukocyte trafficking.
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With the roles of ICAM-1 in cell-cell adhesion, extravasation, and infection more fully understood, a potential role for ICAM-1 in signal transduction was hypothesized. Most of the work involving ICAM-1 in recent years has focused on this central question as well as related questions. Researchers reasoned that, should ICAM-1 signal transduction prove to occur, it would be necessary to identify the mechanism of that signaling, the conditions and environment in which the signaling would occur, and the biological endpoints of any signaling cascades involved. Beyond its classically described functions as an adhesion and viral entry molecule, ICAM-1 has now been characterized convincingly as possessing a role in signal transduction. Furthermore, the signal-transducing functions of ICAM-1 seem to be associated primarily with proinflammatory pathways.
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Lymphocyte homing occurs in four steps leading to extravasation into target tissue; Rolling, activation, activation-dependent “arrest”, and diapedesis. Mediated by lymphocyte receptors and vascular ligand interactions, “tethering” is a reversible linkage that leads to either rolling along the vessel wall or transient immediate arrest. L-selectin is able to mediate vessel adhesion whereas α4 integrins, α4β1 or α4β7, can perform primary or secondary adhesion through a stronger tethering and even contribute to transendothelial migration of lymphocytes. L-selectin, for example, is also able to be cleaved by an enzyme, ensuring proper binding of lymphocytes and allowing release of non-target cells. While attached to the vessel, lymphocytes test target tissue for chemokines and pro-adhesive factors that then prompt “arrest.” In addition to α4 integrins, LFA-1 and Mac-1 mediate the prevention of lymphocyte transendothelial migration into target tissues.
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This study took special note of the fact that perlecan upregulation occurred even before that of heparanase, an essential protein involved in the process of extravasation. In ovarian cancer as in other cancers, perlecan expression occurs differently throughout progression of the disease. Perlecan staining is lost in ovarian basement membrane that has been breached by an invasive adenocarcinoma, which is in contrast to perlecan staining in the basement membranes of normal ovaries and those with benign tumors, where basement membrane is homogeneous and very similar in composition to that in other normal tissues. This is consistent with other results showing loss of perlecan in basement membranes affected by invasive cervical cancer spreading to the pelvic lymph nodes, which comes as no surprise due to the correlation of elevated levels of heparanase mRNA expression with invasion of similar cervical carcinoma.
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Lipoplatin evades immune surveillance thus escaping clearance from macrophages, circulates for long periods in body fluids after intravenous administration with a half-life of ~120 h, and extravasates through the compromised endothelium of the vasculature in tumors created during the process of neoangiogenesis Extravasation Figure. Thus, lipoplatin nanoparticles are concentrated to the primary tumor and metastases. Human studies have shown 40- to 200-fold higher platinum concentration compared to the adjacent normal tissue in specimens from human biopsies 20 post-infusion of the drug. Lipoplatin nanoparticles once inside the tumor cell mass can fuse with the cell membrane because of the presence of the fusogenic lipid DPPG in their lipid bilayer; an alternative mechanism proposed is that lipoplatin is taken by endocytosis by tumor cells as shown from lipoplatin containing fluorescent lipids and imaging of the tumor cells in culture thus treated with fluorescent microscopy.
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Systemic capillary leak syndrome (SCLS, or Clarkson's disease), or primary capillary leak syndrome, is a rare, grave and episodic medical condition observed largely in otherwise healthy individuals mostly in middle age. It is characterized by self-reversing episodes during which the endothelial cells which line the capillaries, usually of the extremities, separate for one to three days, causing a leakage of plasma mainly into the muscle compartments of the arms and legs. The abdomen, the central nervous system, and the organs (including the lungs) are typically spared, but the extravasation in the extremities is sufficiently massive to cause circulatory shock and compartment syndromes, with a dangerous hypotension (low blood pressure), hemoconcentration (thickening of the blood) and hypoalbuminemia (drop in albumin, a major protein) in the absence of other causes for such abnormalities. SCLS is thus a limb- and life-threatening illness, because each episode has the potential to cause damage to limb muscles and nerves, as well as to vital organs due to limited perfusion.
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High endothelial venules (HEV) are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thinner endothelial cells found in regular venules. HEVs enable lymphocytes circulating in the blood to directly enter a lymph node (by crossing through the HEV). Table 14-1 In humans, HEVs are found in all secondary lymphoid organs (with the exception of spleen, where blood exits through open arterioles and enters the red pulp), including hundreds of lymph nodes dispersed in the body, tonsils and adenoids in the pharynx, Peyer's patches (PIs) in the small intestine, appendix, and small aggregates of lymphoid tissue in the stomach and large intestine. In contrast to the endothelial cells from other vessels, the high endothelial cells of HEVs have a distinctive appearance, consisting of a cuboidal morphology and with various receptors to interact with leukocytes (express specialized ligands for lymphocytes and are able to support high levels of lymphocyte extravasation).
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The results of numerous experimental and clinical studies of malignant neoplasms have indicated that invasive growth and metastasis are the main manifestations of tumor progression, which represent two closely related processes. A malignant tumor is characterized by the possibility to implement such a biological phenomenon as the metastatic cascade that is a unique multi-stage “program” where cell invasion is a trigger and a key factor for further cancer progression and metastasis in distant organs and tissues. Massive metastatic lesions lead to the development of severe organ failure and, therefore, a patient’s death. The range between “end” points of a complex invasive metastatic process –invasion of the primary tumor into surrounding tissues and the formation of metastatic foci –comprises several stages, the passage of which is strictly necessary for the successful development and subsequent progression of tumor growth: intravasation, survival and presence in the systemic circulation, extravasation with subsequent colonization of organs by tumor cells, and the formation of clinically detectable metastasis.
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12(S)-HpETE, 12(R)-HETE, racemic mixtures of these 12-HETEs, and/or 12-oxo-ETE stimulate: a) the directed migration (chemotaxis) of human, rat, and rabbit neutrophils as well as rabbit macrophages; b) human neutrophils to adhere to each other (i.e. aggregate) and in cooperation with Tumor necrosis factor alpha or Platelet-activating factor, to release their granule-bound enzymes; c) the binding of human vascular epithelial cells to human monocytes; d) DNA synthesis and mitogenesis in the immortalized human keratinocyte cell line HaCaT; and e) when injected in the skin of human volunteers, the extravasation and local accumulation of circulating blood neutrophils and mononuclear cells. These results suggest these metabolites contribute to the inflammation that occurs as sites where they are formed in abnormal amounts such as in human rheumatoid arthritis, Inflammatory bowel disease, Contact dermatitis, psoriasis, various forms of Ichthyosis including Congenital ichthyosiform erythroderma, and corneal inflammatory diseases. Since BLT2 appears to mediate the responses of leukocytes to 12(S)-HpETE, 12(S)-HETE, 12(R)-HETE, and 12-oxo-ETE but GPR31 is expressed by various other cells (e.g.
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ICAM-1 and soluble ICAM-1 have antagonistic effects on the tight junctions forming the blood-testis barrier, thus playing a major role in spermatogenesis. The presence of heavy glycosylation and other structural characteristics of ICAM-1 lend the protein binding sites for numerous ligands. ICAM-1 possesses binding sites for a number of immune-associated ligands. Notably, ICAM-1 binds to _mac_ rophage adhesion ligand- _1_ (Mac-1; ITGB2 / ITGAM), _l_ eukocyte _f_ unction associated _a_ ntigen- _1_ (LFA-1), and fibrinogen. These three proteins are generally expressed on endothelial cells and leukocytes, and they bind to ICAM-1 to facilitate transmigration of leukocytes across vascular endothelia in processes such as extravasation and the inflammatory response. As a result of these binding characteristics, ICAM-1 has classically been assigned the function of intercellular adhesion. Researchers began to question the role of ICAM-1 as a simple adhesion molecule upon discovering that ICAM-1 serves as the binding site for entry of the major group of human rhinovirus (HRV) into various cell types. ICAM-1 also became known for its affinity for plasmodium falciparum-infected erythrocytes (PFIE), providing more of a role for ICAM-1 in infectious disease.
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