Misplaced Pages

#92907

83-496: It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions. Serum concentration of VEGF is high in bronchial asthma and diabetes mellitus . VEGF's normal function is to create new blood vessels during embryonic development , new blood vessels after injury, muscle following exercise, and new vessels ( collateral circulation ) to bypass blocked vessels. It can contribute to disease. Solid cancers cannot grow beyond

166-578: A cell to survive, move, or further differentiate. Hence, VEGF is a potential target for the treatment of cancer . The first anti-VEGF drug, a monoclonal antibody named bevacizumab , was approved in 2004. Approximately 10–15% of patients benefit from bevacizumab therapy; however, biomarkers for bevacizumab efficacy are not yet known. Current studies show that VEGFs are not the only promoters of angiogenesis. In particular, FGF2 and HGF are potent angiogenic factors. Patients suffering from pulmonary emphysema have been found to have decreased levels of VEGF in

249-441: A tyrosine kinase pathway leading to angiogenesis. The expression of angiopoietin-2 in the absence of VEGF leads to endothelial cell death and vascular regression. Conversely, a German study done in vivo found that VEGF concentrations actually decreased after a 25% reduction in oxygen intake for 30 minutes. HIF1 alpha and HIF1 beta are constantly being produced but HIF1 alpha is highly O 2 labile, so, in aerobic conditions, it

332-469: A vascular permeability factor secreted by tumors in guinea pigs and hamsters. In 1989 Ferrara and Henzel described an identical factor in bovine pituitary follicular cells which they purified, cloned and named VEGF. A similar VEGF alternative splicing was discovered by Tischer et al. in 1991. Between 1996 and 1997, Christinger and De Vos obtained the crystal structure of VEGF, first at 2.5 Å resolution and later at 1.9 Å. Fms-like tyrosine kinase-1 (flt-1)

415-406: A combination of factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. There is limited evidence to guide possible approaches to reducing autumn exacerbations, but while costly, seasonal omalizumab treatment from four to six weeks before school return may reduce autumn asthma exacerbations. Asthma is the result of chronic inflammation of

498-456: A common cause of acute attacks in women and children. Both viral and bacterial infections of the upper respiratory tract can worsen the disease. Psychological stress may worsen symptoms – it is thought that stress alters the immune system and thus increases the airway inflammatory response to allergens and irritants. Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school. This might reflect

581-413: A few times a day or a few times per week. Depending on the person, asthma symptoms may become worse at night or with exercise. Asthma is thought to be caused by a combination of genetic and environmental factors . Environmental factors include exposure to air pollution and allergens . Other potential triggers include medications such as aspirin and beta blockers . Diagnosis is usually based on

664-521: A limited size without an adequate blood supply; cancers that can express VEGF are able to grow and metastasize. Overexpression of VEGF can cause vascular disease in the retina of the eye and other parts of the body. Drugs such as aflibercept , bevacizumab , ranibizumab , and pegaptanib can inhibit VEGF and control or slow those diseases. In 1970, Judah Folkman et al . described a factor secreted by tumors causing angiogenesis and called it tumor angiogenesis factor . In 1983 Senger et al. identified

747-412: A person's asthma is controlled. The methacholine challenge involves the inhalation of increasing concentrations of a substance that causes airway narrowing in those predisposed. If negative it means that a person does not have asthma; if positive, however, it is not specific for the disease. Other supportive evidence includes: a ≥20% difference in peak expiratory flow rate on at least three days in

830-413: A significantly higher risk compared to randomly selected controls ( odds ratio 7.2, 95% confidence interval 5.2–10). Asthma phenotyping and endotyping has emerged as a novel approach to asthma classification inspired by precision medicine which separates the clinical presentations of asthma, or asthma phenotypes, from their underlying causes, or asthma endotypes. The best-supported endotypic distinction

913-529: A single transmembrane spanning region, and an intracellular portion containing a split tyrosine-kinase domain. VEGF-A binds to VEGFR-1 ( Flt-1 ) and VEGFR-2 ( KDR/Flk-1 ). VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF. The function of VEGFR-1 is less well-defined, although it is thought to modulate VEGFR-2 signaling. Another function of VEGFR-1 may be to act as a dummy/decoy receptor, sequestering VEGF from VEGFR-2 binding (this appears to be particularly important during vasculogenesis in

SECTION 10

#1732793991093

996-446: A split tyrosine-kinase domain. VEGF-A binds to VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF. The function of VEGFR-1 is less well defined, although it is thought to modulate VEGFR-2 signaling. Another function of VEGFR-1 is to act as a dummy/decoy receptor, sequestering VEGF from VEGFR-2 binding (this appears to be particularly important during vasculogenesis in

1079-585: A third of people. This may be even more common in some ethnic groups such as the Japanese and those with aspirin-exacerbated respiratory disease. Other studies have found improvement in asthmatic symptoms from alcohol. Non-atopic asthma, also known as intrinsic or non-allergic, makes up between 10 and 33% of cases. There is negative skin test to common inhalant allergens. Often it starts later in life, and women are more commonly affected than men. Usual treatments may not work as well. The concept that "non-atopic"

1162-429: A trigger for asthma; formaldehyde exposure, for example, has a positive association. Phthalates in certain types of PVC are associated with asthma in both children and adults. While exposure to pesticides is linked to the development of asthma, a cause and effect relationship has yet to be established. A meta-analysis concluded gas stoves are a major risk factor for asthma, finding around one in eight cases in

1245-432: A week for at least two weeks, a ≥20% improvement of peak flow following treatment with either salbutamol, inhaled corticosteroids or prednisone, or a ≥20% decrease in peak flow following exposure to a trigger. Testing peak expiratory flow is more variable than spirometry, however, and thus not recommended for routine diagnosis. It may be useful for daily self-monitoring in those with moderate to severe disease and for checking

1328-527: Is a common long-term inflammatory disease of the airways of the lungs . Asthma occurs when allergens , pollen , dust, or other particles, are inhaled into the lungs, causing the bronchioles to constrict and produce mucus, which then restricts oxygen flow to the alveoli . It is characterized by variable and recurring symptoms, reversible airflow obstruction , and easily triggered bronchospasms . Symptoms include episodes of wheezing , coughing , chest tightness, and shortness of breath . These may occur

1411-1016: Is a commonly reported occupational disease . Many cases, however, are not reported or recognized as such. It is estimated that 5–25% of asthma cases in adults are work-related. A few hundred different agents have been implicated, with the most common being isocyanates , grain and wood dust, colophony , soldering flux , latex , animals, and aldehydes . The employment associated with the highest risk of problems include those who spray paint , bakers and those who process food, nurses, chemical workers, those who work with animals, welders , hairdressers and timber workers. Aspirin-exacerbated respiratory disease (AERD), also known as aspirin -induced asthma, affects up to 9% of asthmatics. AERD consists of asthma, nasal polyps, sinus disease, and respiratory reactions to aspirin and other NSAID medications (such as ibuprofen and naproxen). People often also develop loss of smell and most experience respiratory reactions to alcohol. Alcohol may worsen asthmatic symptoms in up to

1494-429: Is a history of atopic disease ; with asthma occurring at a much greater rate in those who have either eczema or hay fever . Asthma has been associated with eosinophilic granulomatosis with polyangiitis (formerly known as Churg–Strauss syndrome), an autoimmune disease and vasculitis . Individuals with certain types of urticaria may also experience symptoms of asthma. There is a correlation between obesity and

1577-456: Is a kind of asthma distinguishable by recurrent, severe attacks. Type 1 brittle asthma is a disease with wide peak flow variability, despite intense medication. Type 2 brittle asthma is background well-controlled asthma with sudden severe exacerbations. Exercise can trigger bronchoconstriction both in people with or without asthma. It occurs in most people with asthma and up to 20% of people without asthma. Exercise-induced bronchoconstriction

1660-503: Is a specific single nucleotide polymorphism in the CD14 region and exposure to endotoxin (a bacterial product). Endotoxin exposure can come from several environmental sources including tobacco smoke, dogs, and farms. Risk for asthma, then, is determined by both a person's genetics and the level of endotoxin exposure. A triad of atopic eczema , allergic rhinitis and asthma is called atopy. The strongest risk factor for developing asthma

1743-499: Is a well-recognized condition, there is not one universal agreed-upon definition. It is defined by the Global Initiative for Asthma as "a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing particularly at night or in

SECTION 20

#1732793991093

1826-732: Is affected, the probability of the other having the disease is approximately 25%. By the end of 2005, 25 genes had been associated with asthma in six or more separate populations, including GSTM1 , IL10 , CTLA-4 , SPINK5 , LTC4S , IL4R and ADAM33 , among others. Many of these genes are related to the immune system or modulating inflammation. Even among this list of genes supported by highly replicated studies, results have not been consistent among all populations tested. In 2006 over 100 genes were associated with asthma in one genetic association study alone; more continue to be found. Some genetic variants may only cause asthma when they are combined with specific environmental exposures. An example

1909-668: Is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor. There are multiple isoforms of VEGF-A that result from alternative splicing of mRNA from a single, 8- exon VEGFA gene. These are classified into two groups which are referred to according to their terminal exon (exon 8) splice site: the proximal splice site (denoted VEGF xxx ) or distal splice site (VEGF xxx b). In addition, alternate splicing of exon 6 and 7 alters their heparin -binding affinity and amino acid number (in humans: VEGF 121 , VEGF 121 b, VEGF 145 , VEGF 165 , VEGF 165 b, VEGF 189 , VEGF 206 ;

1992-443: Is also important in diabetic retinopathy (DR). The microcirculatory problems in the retina of people with diabetes can cause retinal ischaemia, which results in the release of VEGF-A, and a switch in the balance of pro-angiogenic VEGF xxx isoforms over the normally expressed VEGF xxx b isoforms. VEGF xxx may then cause the creation of new blood vessels in the retina and elsewhere in the eye, heralding changes that may threaten

2075-561: Is an important signaling protein involved in both vasculogenesis (the formation of the circulatory system ) and angiogenesis (the growth of blood vessels from pre-existing vasculature). As its name implies, VEGF activity is restricted mainly to cells of the vascular endothelium , although it does have effects on a limited number of other cell types (e.g. stimulation monocyte / macrophage migration). In vitro , VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration . VEGF also enhances microvascular permeability and

2158-594: Is associated with a greater risk of asthma-like symptoms. Low air quality from environmental factors such as traffic pollution or high ozone levels has been associated with both asthma development and increased asthma severity. Over half of cases in children in the United States occur in areas when air quality is below the EPA standards. Low air quality is more common in low-income and minority communities. Exposure to indoor volatile organic compounds may be

2241-500: Is associated with an increased risk of asthma in the child. Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma. Different individuals react to various factors in different ways. Most individuals can develop severe exacerbation from a number of triggering agents. Home factors that can lead to exacerbation of asthma include dust , animal dander (especially cat and dog hair), cockroach allergens and mold . Perfumes are

2324-504: Is associated with exposure to indoor allergens. Common indoor allergens include dust mites , cockroaches , animal dander (fragments of fur or feathers), and mould. Efforts to decrease dust mites have been found to be ineffective on symptoms in sensitized subjects. Weak evidence suggests that efforts to decrease mould by repairing buildings may help improve asthma symptoms in adults. Certain viral respiratory infections, such as respiratory syncytial virus and rhinovirus , may increase

2407-435: Is attributed to the lack of healthy bacterial colonization that the newborn would have acquired from passage through the birth canal. There is a link between asthma and the degree of affluence which may be related to the hygiene hypothesis as less affluent individuals often have more exposure to bacteria and viruses. Family history is a risk factor for asthma, with many different genes being implicated. If one identical twin

2490-977: Is believed that the recent increased rates of asthma are due to changing epigenetics ( heritable factors other than those related to the DNA sequence ) and a changing living environment. Asthma that starts before the age of 12 years old is more likely due to genetic influence, while onset after age 12 is more likely due to environmental influence. Many environmental factors have been associated with asthma's development and exacerbation, including allergens, air pollution, and other environmental chemicals. There are some substances that are known to cause asthma in exposed people and they are called asthmagens . Some common asthmagens include ammonia, latex, pesticides, solder and welding fumes, metal or wood dusts, spraying of isocyanate paint in vehicle repair, formaldehyde, glutaraldehyde, anhydrides, glues, dyes, metal working fluids, oil mists, moulds. Smoking during pregnancy and after delivery

2573-427: Is classified based on severity, at the moment there is no clear method for classifying different subgroups of asthma beyond this system. Finding ways to identify subgroups that respond well to different types of treatments is a current critical goal of asthma research. Recently, asthma has been classified based on whether it is associated with type 2 or non–type 2 inflammation. This approach to immunologic classification

Vascular endothelial growth factor - Misplaced Pages Continue

2656-437: Is common in professional athletes. The highest rates are among cyclists (up to 45%), swimmers, and cross-country skiers. While it may occur with any weather conditions, it is more common when it is dry and cold. Inhaled beta 2 agonists do not appear to improve athletic performance among those without asthma; however, oral doses may improve endurance and strength. Asthma as a result of (or worsened by) workplace exposures

2739-464: Is commonly referred to as an asthma attack . The classic symptoms are shortness of breath , wheezing , and chest tightness . The wheezing is most often when breathing out. While these are the primary symptoms of asthma, some people present primarily with coughing , and in severe cases, air motion may be significantly impaired such that no wheezing is heard. In children, chest pain is often present. Signs occurring during an asthma attack include

2822-430: Is correlated with more exposure to cigarette smoke, an older age, less symptom reversibility after bronchodilator administration, and decreased likelihood of family history of atopy. The evidence for the effectiveness of measures to prevent the development of asthma is weak. The World Health Organization recommends decreasing risk factors such as tobacco smoke, air pollution, chemical irritants including perfume , and

2905-470: Is degraded. When the cell becomes hypoxic, HIF1 alpha persists and the HIF1alpha/beta complex stimulates VEGF release. the combined use of microvesicles and 5-FU resulted in enhanced chemosensitivity of squamous cell carcinoma cells more than the use of either 5-FU or microvesicle alone. In addition, down regulation of VEGF gene expression was associated with decreased CD1 gene expression. VEGF-A and

2988-436: Is driven by a developing understanding of the underlying immune processes and by the development of therapeutic approaches that target type 2 inflammation. Although asthma is a chronic obstructive condition, it is not considered as a part of chronic obstructive pulmonary disease , as this term refers specifically to combinations of disease that are irreversible such as bronchiectasis and emphysema . Unlike these diseases,

3071-399: Is insufficient, the use of medication is recommended. Pharmaceutical drugs are selected based on, among other things, the severity of illness and the frequency of symptoms. Specific medications for asthma are broadly classified into fast-acting and long-acting categories. The medications listed below have demonstrated efficacy in improving asthma symptoms; however, real world use-effectiveness

3154-537: Is limited as around half of people with asthma worldwide remain sub-optimally controlled, even when treated. People with asthma may remain sub-optimally controlled either because optimum doses of asthma medications do not work (called "refractory" asthma) or because individuals are either unable (e.g. inability to afford treatment, poor inhaler technique) or unwilling (e.g., wish to avoid side effects of corticosteroids) to take optimum doses of prescribed asthma medications (called "difficult to treat" asthma). In practice, it

3237-408: Is no known cure for asthma, but it can be controlled. Symptoms can be prevented by avoiding triggers, such as allergens and respiratory irritants , and suppressed with the use of inhaled corticosteroids . Long-acting beta agonists (LABA) or antileukotriene agents may be used in addition to inhaled corticosteroids if asthma symptoms remain uncontrolled. Treatment of rapidly worsening symptoms

3320-434: Is not known whether asthma causes psychological problems or psychological problems lead to asthma. Current asthma, but not former asthma, is associated with increased all-cause mortality, heart disease mortality, and chronic lower respiratory tract disease mortality. Asthma, particularly severe asthma, is strongly associated with development of chronic obstructive pulmonary disease (COPD). Those with asthma, especially if it

3403-452: Is not possible to distinguish "refractory" from "difficult to treat" categories for patients who have never taken optimum doses of asthma medications. A related issue is that the asthma efficacy trials upon which the pharmacological treatment guidelines are based have systematically excluded the majority of people with asthma. For example, asthma efficacy treatment trials always exclude otherwise eligible people who smoke, and smoking diminishes

Vascular endothelial growth factor - Misplaced Pages Continue

3486-478: Is poorly controlled, are at increased risk for radiocontrast reactions. Cavities occur more often in people with asthma. This may be related to the effect of beta 2 -adrenergic agonists decreasing saliva. These medications may also increase the risk of dental erosions . Asthma is caused by a combination of complex and incompletely understood environmental and genetic interactions. These influence both its severity and its responsiveness to treatment. It

3569-552: Is sometimes referred to as vascular permeability factor. All members of the VEGF family stimulate cellular responses by binding to tyrosine kinase receptors (the VEGFRs) on the cell surface, causing them to dimerize and become activated through transphosphorylation . The VEGF receptors have an extracellular portion consisting of 7 immunoglobulin -like domains, a single transmembrane spanning region and an intracellular portion containing

3652-421: Is supportive of the diagnosis. It however may be normal in those with a history of mild asthma, not currently acting up. As caffeine is a bronchodilator in people with asthma, the use of caffeine before a lung function test may interfere with the results. Single-breath diffusing capacity can help differentiate asthma from COPD . It is reasonable to perform spirometry every one or two years to follow how well

3735-412: Is synonymous with "non-allergic" is called into question by epidemiological data that the prevalence of asthma is closely related to the serum IgE level standardized for age and sex (P<0.0001), indicating that asthma is almost always associated with some sort of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in

3818-722: Is the type 2-high/type 2-low distinction. Classification based on type 2 inflammation is useful in predicting which patients will benefit from targeted biologic therapy . Many other conditions can cause symptoms similar to those of asthma. In children, symptoms may be due to other upper airway diseases such as allergic rhinitis and sinusitis , as well as other causes of airway obstruction including foreign body aspiration , tracheal stenosis , laryngotracheomalacia , vascular rings , enlarged lymph nodes or neck masses. Bronchiolitis and other viral infections may also produce wheezing. According to European Respiratory Society , it may not be suitable to label wheezing preschool children with

3901-482: Is then used to confirm the diagnosis. In children under the age of six the diagnosis is more difficult as they are too young for spirometry. Spirometry is recommended to aid in diagnosis and management. It is the single best test for asthma. If the FEV 1 measured by this technique improves more than 12% and increases by at least 200 millilitres following administration of a bronchodilator such as salbutamol , this

3984-423: Is usually with an inhaled short-acting beta 2 agonist such as salbutamol and corticosteroids taken by mouth. In very severe cases, intravenous corticosteroids, magnesium sulfate , and hospitalization may be required. In 2019 asthma affected approximately 262 million people and caused approximately 461,000 deaths. Most of the deaths occurred in the developing world . Asthma often begins in childhood, and

4067-414: The conducting zone of the airways (most especially the bronchi and bronchioles ), which subsequently results in increased contractability of the surrounding smooth muscles . This among other factors leads to bouts of narrowing of the airway and the classic symptoms of wheezing. The narrowing is typically reversible with or without treatment. Occasionally the airways themselves change. Typical changes in

4150-423: The "infectious asthma" (IA) syndrome, or as "asthma associated with infection" (AAWI) to distinguish infection-associated asthma initiation from the well known association of respiratory infections with asthma exacerbations. Reported clinical prevalences of IA for adults range from around 40% in a primary care practice to 70% in a speciality practice treating mainly severe asthma patients. Additional information on

4233-433: The U.S. could be attributed to these. The majority of the evidence does not support a causal role between paracetamol (acetaminophen) or antibiotic use and asthma. A 2014 systematic review found that the association between paracetamol use and asthma disappeared when respiratory infections were taken into account. Maternal psychological stress during pregnancy is a risk factor for the child to develop asthma. Asthma

SECTION 50

#1732793991093

4316-471: The age of 65, most people with obstructive airway disease will have asthma and COPD. In this setting, COPD can be differentiated by increased airway neutrophils, abnormally increased wall thickness, and increased smooth muscle in the bronchi. However, this level of investigation is not performed due to COPD and asthma sharing similar principles of management: corticosteroids, long-acting beta-agonists, and smoking cessation. It closely resembles asthma in symptoms,

4399-616: The airway obstruction in asthma is usually reversible; however, if left untreated, the chronic inflammation from asthma can lead the lungs to become irreversibly obstructed due to airway remodelling. In contrast to emphysema, asthma affects the bronchi, not the alveoli . The combination of asthma with a component of irreversible airway obstruction has been termed the asthma-chronic obstructive disease (COPD) overlap syndrome (ACOS) . Compared to other people with "pure" asthma or COPD, people with ACOS exhibit increased morbidity, mortality and possibly more comorbidities. An acute asthma exacerbation

4482-466: The airways include an increase in eosinophils and thickening of the lamina reticularis . Chronically the airways' smooth muscle may increase in size along with an increase in the numbers of mucous glands. Other cell types involved include T lymphocytes , macrophages , and neutrophils . There may also be involvement of other components of the immune system , including cytokines , chemokines , histamine , and leukotrienes among others. While asthma

4565-575: The battery of aeroallergens studied (the "missing antigen(s)" hypothesis). For example, an updated systematic review and meta-analysis of population-attributable risk (PAR) of Chlamydia pneumoniae biomarkers in chronic asthma found that the PAR for C. pneumoniae -specific IgE was 47%. Infectious asthma is an easily identified clinical presentation. When queried, asthma patients may report that their first asthma symptoms began after an acute lower respiratory tract illness. This type of history has been labelled

4648-703: The cell surface, enhancing their ability to bind and activate the VEGF receptors (VEGFRs). Recently, VEGF-C has been shown to be an important inducer of neurogenesis in the murine subventricular zone, without exerting angiogenic effects. All members of the VEGF family stimulate cellular responses by binding to tyrosine kinase receptors (the VEGFRs ) on the cell surface, causing them to dimerize and become activated through transphosphorylation , although to different sites, times, and extents. The VEGF receptors have an extracellular portion consisting of 7 immunoglobulin-like domains,

4731-431: The clinical prevalence of IA in adult-onset asthma is unavailable because clinicians are not trained to elicit this type of history routinely, and recollection in child-onset asthma is challenging. A population-based incident case-control study in a geographically defined area of Finland reported that 35.8% of new-onset asthma cases had experienced acute bronchitis or pneumonia in the year preceding asthma onset, representing

4814-530: The corresponding receptors are rapidly up-regulated after traumatic injury of the central nervous system (CNS). VEGF-A is highly expressed in the acute and sub-acute stages of CNS injury, but the protein expression declines over time. This time-span of VEGF-A expression corresponds with the endogenous re-vascularization capacity after injury. This would suggest that VEGF-A / VEGF 165 could be used as target to promote angiogenesis after traumatic CNS injuries. However, there are contradicting scientific reports about

4897-421: The development of asthma, but exposure at an older age may provoke bronchoconstriction. Evidence supporting the hygiene hypothesis includes lower rates of asthma on farms and in households with pets. Use of antibiotics in early life has been linked to the development of asthma. Also, delivery via caesarean section is associated with an increased risk (estimated at 20–80%) of asthma – this increased risk

4980-546: The early morning. These episodes are usually associated with widespread but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment". There is currently no precise test for the diagnosis, which is typically based on the pattern of symptoms and response to therapy over time. Asthma may be suspected if there is a history of recurrent wheezing, coughing or difficulty breathing and these symptoms occur or worsen due to exercise, viral infections, allergens or air pollution. Spirometry

5063-455: The effectiveness of new medications. It may also be helpful in guiding treatment in those with acute exacerbations. Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in one second (FEV 1 ), and peak expiratory flow rate . Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic), based on whether symptoms are precipitated by allergens (atopic) or not (non-atopic). While asthma

SECTION 60

#1732793991093

5146-585: The effects of VEGF-A treatments in CNS injury models. Although it has not been associated as a biomarker for the diagnosis of acute ischemic stroke , high levels of serum VEGF in the first 48 hours after an cerebral infarct have been associated with a poor prognosis after 6 months and 2 years. VEGF-A has been implicated with poor prognosis in breast cancer . Numerous studies show a decreased overall survival and disease-free survival in those tumors overexpressing VEGF. The overexpression of VEGF-A may be an early step in

5229-471: The efficacy of inhaled corticosteroids, the mainstay of asthma control management. VEGF receptors VEGF receptors ( VEGFRs ) are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Depending on alternative splicing , they may be membrane-bound (mbVEGFR) or soluble (sVEGFR). Inhibitors of VEGFR are used in the treatment of cancer . Vascular endothelial growth factor (VEGF)

5312-639: The embryo). In fact, an alternatively spliced form of VEGFR-1 (sFlt1) is not a membrane bound protein but is secreted and functions primarily as a decoy. A third receptor has been discovered (VEGFR-3), however, VEGF-A is not a ligand for this receptor. VEGFR-3 mediates lymphangiogenesis in response to VEGF-C and VEGF-D. In addition to binding to VEGFRs, VEGF binds to receptor complexes consisting of both neuropilins and VEGFRs. This receptor complex has increased VEGF signalling activity in endothelial cells ( blood vessels ). Neuropilins (NRP) are pleiotropic receptors and therefore other molecules may interfere with

5395-899: The embryo). VEGF-C and VEGF-D, but not VEGF-A, are ligands for a third receptor ( VEGFR-3/Flt4 ), which mediates lymphangiogenesis . The receptor (VEGFR3) is the site of binding of main ligands (VEGFC and VEGFD), which mediates perpetual action and function of ligands on target cells. Vascular endothelial growth factor-C can stimulate lymphangiogenesis (via VEGFR3) and angiogenesis via VEGFR2. Vascular endothelial growth factor-R3 has been detected in lymphatic endothelial cells in CL of many species, cattle, buffalo and primate. In addition to binding to VEGFRs , VEGF binds to receptor complexes consisting of both neuropilins and VEGFRs. This receptor complex has increased VEGF signalling activity in endothelial cells ( blood vessels ). Neuropilins (NRP) are pleiotropic receptors and therefore other molecules may interfere with

5478-451: The home if a person has allergic symptoms to said pet. Dietary restrictions during pregnancy or when breastfeeding have not been found to be effective at preventing asthma in children and are not recommended. Omega-3 consumption, Mediterranean diet and antioxidants have been suggested by some studies to potentially help prevent crises but the evidence is still inconclusive. Reducing or eliminating compounds known to sensitive people from

5561-422: The number of lower respiratory infections . Other efforts that show promise include: limiting smoke exposure in utero , breastfeeding , and increased exposure to daycare or large families, but none are well supported enough to be recommended for this indication. Early pet exposure may be useful. Results from exposure to pets at other times are inconclusive and it is only recommended that pets be removed from

5644-404: The pattern of symptoms, response to therapy over time, and spirometry lung function testing. Asthma is classified according to the frequency of symptoms of forced expiratory volume in one second (FEV 1 ), and peak expiratory flow rate . It may also be classified as atopic or non-atopic, where atopy refers to a predisposition toward developing a type 1 hypersensitivity reaction. There

5727-525: The predicted best. Moderate is defined as between 80 and 200 L/min, or 25% and 50% of the predicted best, while severe is defined as ≤ 80 L/min, or ≤25% of the predicted best. Acute severe asthma , previously known as status asthmaticus, is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators and corticosteroids. Half of cases are due to infections with others caused by allergen, air pollution, or insufficient or inappropriate medication use. Brittle asthma

5810-408: The process of metastasis , a step that is involved in the "angiogenic" switch. Although VEGF-A has been correlated with poor survival, its exact mechanism of action in the progression of tumors remains unclear. VEGF-A is also released in rheumatoid arthritis in response to TNF-α , increasing endothelial permeability and swelling and also stimulating angiogenesis (formation of capillaries). VEGF-A

5893-559: The pulmonary arteries. VEGF-D has also been shown to be over expressed in lymphangioleiomyomatosis and is currently used as a diagnostic biomarker in the treatment of this rare disease. In the kidney , increased expression of VEGF-A in glomeruli directly causes the glomerular hypertrophy that is associated with proteinuria. VEGF alterations can be predictive of early-onset pre-eclampsia . Gene therapies for refractory angina establish expression of VEGF in epicardial cells to promote angiogenesis. Bronchial asthma Asthma

5976-504: The rates have increased significantly since the 1960s. Asthma was recognized as early as Ancient Egypt . The word asthma is from the Greek ἆσθμα , âsthma , which means 'panting'. Asthma is characterized by recurrent episodes of wheezing , shortness of breath , chest tightness , and coughing . Sputum may be produced from the lung by coughing but is often hard to bring up. During recovery from an asthma attack (exacerbation) ,

6059-653: The risk of asthma with both having increased in recent years. Several factors may be at play including decreased respiratory function due to a buildup of fat and the fact that adipose tissue leads to a pro-inflammatory state. Beta blocker medications such as propranolol can trigger asthma in those who are susceptible. Cardioselective beta-blockers , however, appear safe in those with mild or moderate disease. Other medications that can cause problems in asthmatics are angiotensin-converting enzyme inhibitors , aspirin , and NSAIDs . Use of acid-suppressing medication ( proton pump inhibitors and H2 blockers ) during pregnancy

6142-550: The risk of developing asthma when acquired as young children. Certain other infections, however, may decrease the risk. The hygiene hypothesis attempts to explain the increased rates of asthma worldwide as a direct and unintended result of reduced exposure, during childhood, to non-pathogenic bacteria and viruses. It has been proposed that the reduced exposure to bacteria and viruses is due, in part, to increased cleanliness and decreased family size in modern societies. Exposure to bacterial endotoxin in early childhood may prevent

6225-519: The rodent orthologs of these proteins contain one fewer amino acids). These domains have important functional consequences for the VEGF splice variants, as the terminal (exon 8) splice site determines whether the proteins are pro-angiogenic (proximal splice site, expressed during angiogenesis) or anti-angiogenic (distal splice site, expressed in normal tissues). In addition, inclusion or exclusion of exons 6 and 7 mediate interactions with heparan sulfate proteoglycans (HSPGs) and neuropilin co-receptors on

6308-543: The sight. VEGF-A plays a role in the disease pathology of the wet form age-related macular degeneration (AMD), which is the leading cause of blindness for the elderly of the industrialized world. The vascular pathology of AMD shares certain similarities with diabetic retinopathy, although the cause of disease and the typical source of neovascularization differs between the two diseases. VEGF-D serum levels are significantly elevated in patients with angiosarcoma . Once released, VEGF-A may elicit several responses. It may cause

6391-615: The signalling of the NRP/VEGFR receptor complexes. For example, Class 3 semaphorins compete with VEGF 165 for NRP binding and could therefore regulate VEGF-mediated angiogenesis . VEGF-A production can be induced in a cell that is not receiving enough oxygen . When a cell is deficient in oxygen, it produces HIF, hypoxia-inducible factor , a transcription factor. HIF stimulates the release of VEGF-A, among other functions (including modulation of erythropoiesis). Circulating VEGF-A then binds to VEGF receptors on endothelial cells, triggering

6474-692: The sputum may appear pus-like due to high levels of white blood cells called eosinophils . Symptoms are usually worse at night and in the early morning or in response to exercise or cold air. Some people with asthma rarely experience symptoms, usually in response to triggers, whereas others may react frequently and readily and experience persistent symptoms. A number of other health conditions occur more frequently in people with asthma, including gastroesophageal reflux disease (GERD), rhinosinusitis , and obstructive sleep apnea . Psychological disorders are also more common, with anxiety disorders occurring in between 16 and 52% and mood disorders in 14–41%. It

6557-424: The term asthma because there is lack of clinical data on inflammation in airways. In adults, COPD , congestive heart failure , airway masses, as well as drug-induced coughing due to ACE inhibitors may cause similar symptoms. In both populations vocal cord dysfunction may present similarly. Chronic obstructive pulmonary disease can coexist with asthma and can occur as a complication of chronic asthma. After

6640-413: The use of accessory muscles of respiration ( sternocleidomastoid and scalene muscles of the neck), there may be a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest. A blue colour of the skin and nails may occur from lack of oxygen. In a mild exacerbation the peak expiratory flow rate (PEFR) is ≥200 L/min, or ≥50% of

6723-583: The workplace may be effective. It is not clear if annual influenza vaccinations affect the risk of exacerbations. Immunization, however, is recommended by the World Health Organization. Smoking bans are effective in decreasing exacerbations of asthma. While there is no cure for asthma, symptoms can typically be improved. The most effective treatment for asthma is identifying triggers, such as cigarette smoke , pets or other allergens, and eliminating exposure to them. If trigger avoidance

6806-529: Was known as VEGF. A number of VEGF-related proteins encoded by viruses ( VEGF-E ) and in the venom of some snakes ( VEGF-F ) have also been discovered. Activity of VEGF-A, as its name implies, has been studied mostly on cells of the vascular endothelium , although it does have effects on a number of other cell types (e.g., stimulation monocyte / macrophage migration, neurons, cancer cells, kidney epithelial cells). In vitro, VEGF-A has been shown to stimulate endothelial cell mitogenesis and cell migration . VEGF-A

6889-459: Was shown to be a VEGF receptor by Ferrara et al. in 1992. The kinase insert domain receptor (KDR) was shown to be a VEGF receptor by Terman et al. in 1992 as well. In 1998, neuropilin 1 and neuropilin 2 were shown to act as VEGF receptors. In mammals, the VEGF family comprises five members: VEGF-A , placenta growth factor ( PGF ), VEGF-B , VEGF-C and VEGF-D . The latter members were discovered after VEGF-A; before their discovery, VEGF-A

#92907