Meningitis
Meningitis is an inflammation of the membranes that surround the brain and spinal cord (these membranes are also known as meninges). Meningitis is most commonly caused by infections with various pathogens, examples of which are Streptococcus pneumoniae and Haemophilus influenzae. When the meninges are inflamed, the blood-brain barrier may be disrupted. This disruption may increase the penetration of various substances (including either toxins or antibiotics) into the brain. Antibiotics used to treat meningitis may aggravate the inflammatory response of the central nervous system by releasing neurotoxins from the cell walls of bacteria-like lipopolysaccharide (LPS) [9] Treatment with third-generation or fourth-generation cephalosporin is usually preferred.
Epilepsy
Epilepsy is a common neurological disease that is characterized by recurrent and sometimes untreatable seizures. Several clinical and experimental data have implicated the failure of blood-brain barrier function in triggering chronic or acute seizures,[10][11] some studies implicate the interactions between a common blood protein - albumin and astrocytes.[12] These findings have shown that acute seizures are a predictable consequence of disruption of the BBB by either artificial or inflammatory mechanisms. In addition, expression of drug resistance molecules and transporters at the BBB are a significant mechanism of resistance to commonly used anti-epileptic drugs.[13]
Multiple sclerosis (MS)
Multiple sclerosis (MS) is considered to be an auto-immune and neurodegenerative disorder in which the immune system attacks the myelin that protects and electrically insulates the neurons of the central and peripheral nervous systems. Normally, a person's nervous system would be inaccessible to the white blood cells due to the blood-brain barrier. However, it has been shown using Magnetic Resonance Imaging, that when a person is undergoing an MS "attack," the blood-brain barrier has broken down in a section of the brain or spinal cord, allowing white blood cells called T lymphocytes to cross over and attack the myelin. It has sometimes been suggested that, rather than being a disease of the immune system, MS is a disease of the blood-brain barrier.[14] A recent study suggests that the weakening of the blood-brain barrier is a result of a disturbance in the endothelial cells on the inside of the blood vessel, due to which the production of the protein P-glycoprotein is not working well.
There are currently active investigations into treatments for a compromised blood-brain barrier. It is believed that oxidative stress plays an important role into the breakdown of the barrier. Anti-oxidants such as lipoic acid may be able to stabilize a weakening blood-brain barrier.[15]
Neuromyelitis optica
Neuromyelitis optica, also known as Devic's disease, is similar to and is often confused with multiple sclerosis. Among other differences from MS, a different target of the autoimmune response has been identified. Patients with neuromyelitis optica have high levels of antibodies against a protein called aquaporin 4 (a component of the astrocytic foot processes in the blood-brain barrier).[16]
Late-stage neurological trypanosomiasis (Sleeping sickness)
Late-stage neurological trypanosomiasis, or sleeping sickness, is a condition in which trypanosoma protozoa are found in brain tissue. It is not yet known how the parasites infect the brain from the blood, but it is suspected that they cross through the choroid plexus, a circumventricular organ.
Progressive multifocal leukoencephalopathy (PML)
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system that is caused by reactivation of a latent papovavirus (the JC polyomavirus) infection, that can cross the BBB. It affects immune-compromised patients and it is usually seen with patients suffering from AIDS.
[edit] De Vivo disease
De Vivo disease (also known as GLUT1 deficiency syndrome) is a rare condition caused by inadequate transportation of the sugar, glucose, across the blood-brain barrier, resulting in mental retardation and other neurological problems. Genetic defects in glucose transporter type 1 (GLUT1) appears to be the primary cause of De Vivo disease.[17][18]
Alzheimer's Disease
Some new evidence indicates [19] that disruption of the blood-brain barrier in Alzheimer's Disease patients allows blood plasma containing amyloid beta (Aβ) to enter the brain where the Aβ adheres preferentially to the surface of astrocytes. These findings have led to the hypotheses that (1) breakdown of the blood-brain barrier allows access of neuron-binding autoantibodies and soluble exogenous Aβ42 to brain neurons and (2) binding of these auto-antibodies to neurons triggers and/or facilitates the internalization and accumulation of cell surface-bound Aβ42 in vulnerable neurons through their natural tendency to clear surface-bound autoantibodies via endocytosis. Eventually the astrocyte is overwhelmed, dies, ruptures, and disintegrates, leaving behind the insoluble Aβ42 plaque. Thus, in some patients, Alzheimer’s disease may be caused (or more likely, aggravated) by a breakdown in the blood-brain barrier. [1]
The herpes virus produces the amyloid beta (Aβ), and this virus has been found to be the pathogen responsible for being a major cause of the disease. [2]
HIV Encephalitis
It is believed [20] that latent HIV can cross the blood-brain barrier inside circulating monocytes in the bloodstream ("Trojan horse theory") within the first 14 days of infection. Once inside, these monocytes become activated and are transformed into macrophages. Activated macrophages release virions into the brain tissue proximate to brain microvessels. These viral particles likely attract the attention of sentinel brain microglia and perivascular macrophages initiating an inflammatory cascade that may cause a series of intracellular signaling in brain microvascular endothelial cells and damage the functional and structural integrity of the BBB. This inflammation is HIV encephalitis (HIVE). Instances of HIVE probably occur throughout the course of AIDS and are a precursor for HIV-associated dementia (HAD). The premier model for studying HIV and HIVE is the simian model.
References
^ Hamilton RD, Foss AJ, Leach L (2007). "Establishment of a human in vitro model of the outer blood-retinal barrier". Journal of Anatomy 211: 707. doi:10.1111/j.1469-7580.2007.00812.x. PMID 17922819.
^ Pritchard, Thomas C.; Alloway, Kevin Douglas (1999) (Google books preview). Medical Neuroscience. Hayes Barton Press. pp. 76–77. ISBN 1889325295. http://books.google.com/books?id=m7Y80PcFHtsC&printsec=frontcover#PPA76,M1. Retrieved 2009-02-08.
^ Gilgun-Sherki, Yossi; Melamed, Eldad and Offen, Daniel.(2001). Neuropharmacology. Volume 40, Issue 8, June 2001, Pages 959-975. doi:10.1016/S0028-3908(01)00019-3
^ Lina Stern: Science and fate by A.A. Vein. Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
^ Silva, GA (December 2008). "Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS". BMC Neuroscience 9 (Suppl. 3): S4. doi:10.1186/1471-2202-9-S3-S4. PMID 19091001. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19091001.
^ Brigger I, Morizet J, Aubert G, et al. (December 2002). "Poly(ethylene glycol)-coated hexadecylcyanoacrylate nanospheres display a combined effect for brain tumor targeting". J. Pharmacol. Exp. Ther. 303 (3): 928–36. doi:10.1124/jpet.102.039669. PMID 12438511.
^ Hashizume, H; Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, Jain RK, McDonald DM (April 2000). "Openings between defective endothelial cells explain tumor vessel leakiness". American Journal of Pathology 156 (4): 1363–1380. PMID 10751361.
^ Schneider, SW; Ludwig T, Tatenhorst L, Braune S, Oberleithner H, Senner V, Paulus W (March 2004). "Glioblastoma cells release factors that disrupt blood-brain barrier features". Acta Neuropathologica 107 (3): 272–276. doi:10.1007/s00401-003-0810-2. PMID 14730455.
^ Beam, TR Jr.; Allen, JC (December 1977). "Blood, brain, and cerebrospinal fluid concentrations of several antibiotics in rabbits with intact and inflamed meninges". Antimicrobial agents and chemotherapy 12 (6): 710–6. PMID 931369.
^ E. Oby and D. Janigro, The Blood-brain barrier and epilepsy. Epilepsia. 2006 Nov;47(11):1761-74
^ Marchi,N. et al. Seizure-Promoting Effect of Blood-Brain Barrier Disruption. Epilepsia 48(4), 732-742 (2007). Seiffert,E. et al. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J. Neurosci. 24, 7829-7836 (2004). Uva,L. et al. Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood-brain barrier permeability. Neuroscience (2007). van Vliet,E.A. et al. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 130, 521-534 (2007).
^ Ivens S, Kaufer D, Flores LP, Bechmann I, Zumsteg D, Tomkins O et al. (2007). "TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis.". Brain 130 (Pt 2): 535–47. doi:10.1093/brain/awl317. PMID 17121744. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17121744.
^ Awasthi,S. et al. RLIP76, a non-ABC transporter, and drug resistance in epilepsy. BMC. Neurosci. 6, 61 (2005). Loscher,W. & Potschka,H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat. Rev. Neurosci. 6, 591-602 (2005).
^ Waubant E (2006). "Biomarkers indicative of blood-brain barrier disruption in multiple sclerosis". Disease Markers 22 (4): 235–44. PMID 17124345. http://iospress.metapress.com/openurl.asp?genre=article&issn=0278-0240&volume=22&issue=4&spage=235.
^ Schreibelt G, Musters RJ, Reijerkerk A, et al. (August 2006). "Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity". J. Immunol. 177 (4): 2630–7. PMID 16888025. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16888025.
^ Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (August 2005). "IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel". J. Exp. Med. 202 (4): 473–7. doi:10.1084/jem.20050304. PMID 16087714.
^ Pascual, JM; Wang D, Lecumberri B, Yang H, Mao X, Yang R, De Vivo DC (May 2004). "GLUT1 deficiency and other glucose transporter diseases". European journal of endocrinology 150 (5): 627–33. doi:10.1530/eje.0.1500627. PMID 15132717.
^ Klepper, J; Voit T (June 2002). "Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain-- a review". European journal of pediatrics 161 (6): 295–304. doi:10.1007/s00431-002-0939-3. PMID 12029447.
^ Microvascular injury and blood–brain barrier leakage in Alzheimer’s disease - Zipser et al 2006
^ http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.neuro.25.112701.142822?cookieSet=1
Monday, June 28, 2010
Diseases involving the blood-brain barrier
Meningitis
Meningitis is an inflammation of the membranes that surround the brain and spinal cord (these membranes are also known as meninges). Meningitis is most commonly caused by infections with various pathogens, examples of which are Streptococcus pneumoniae and Haemophilus influenzae. When the meninges are inflamed, the blood-brain barrier may be disrupted. This disruption may increase the penetration of various substances (including either toxins or antibiotics) into the brain. Antibiotics used to treat meningitis may aggravate the inflammatory response of the central nervous system by releasing neurotoxins from the cell walls of bacteria-like lipopolysaccharide (LPS) [9] Treatment with third-generation or fourth-generation cephalosporin is usually preferred.
Epilepsy
Epilepsy is a common neurological disease that is characterized by recurrent and sometimes untreatable seizures. Several clinical and experimental data have implicated the failure of blood-brain barrier function in triggering chronic or acute seizures,[10][11] some studies implicate the interactions between a common blood protein - albumin and astrocytes.[12] These findings have shown that acute seizures are a predictable consequence of disruption of the BBB by either artificial or inflammatory mechanisms. In addition, expression of drug resistance molecules and transporters at the BBB are a significant mechanism of resistance to commonly used anti-epileptic drugs.[13]
Multiple sclerosis (MS)
Multiple sclerosis (MS) is considered to be an auto-immune and neurodegenerative disorder in which the immune system attacks the myelin that protects and electrically insulates the neurons of the central and peripheral nervous systems. Normally, a person's nervous system would be inaccessible to the white blood cells due to the blood-brain barrier. However, it has been shown using Magnetic Resonance Imaging, that when a person is undergoing an MS "attack," the blood-brain barrier has broken down in a section of the brain or spinal cord, allowing white blood cells called T lymphocytes to cross over and attack the myelin. It has sometimes been suggested that, rather than being a disease of the immune system, MS is a disease of the blood-brain barrier.[14] A recent study suggests that the weakening of the blood-brain barrier is a result of a disturbance in the endothelial cells on the inside of the blood vessel, due to which the production of the protein P-glycoprotein is not working well.
There are currently active investigations into treatments for a compromised blood-brain barrier. It is believed that oxidative stress plays an important role into the breakdown of the barrier. Anti-oxidants such as lipoic acid may be able to stabilize a weakening blood-brain barrier.[15]
Neuromyelitis optica
Neuromyelitis optica, also known as Devic's disease, is similar to and is often confused with multiple sclerosis. Among other differences from MS, a different target of the autoimmune response has been identified. Patients with neuromyelitis optica have high levels of antibodies against a protein called aquaporin 4 (a component of the astrocytic foot processes in the blood-brain barrier).[16]
Late-stage neurological trypanosomiasis (Sleeping sickness)
Late-stage neurological trypanosomiasis, or sleeping sickness, is a condition in which trypanosoma protozoa are found in brain tissue. It is not yet known how the parasites infect the brain from the blood, but it is suspected that they cross through the choroid plexus, a circumventricular organ.
Progressive multifocal leukoencephalopathy (PML)
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system that is caused by reactivation of a latent papovavirus (the JC polyomavirus) infection, that can cross the BBB. It affects immune-compromised patients and it is usually seen with patients suffering from AIDS.
[edit] De Vivo disease
De Vivo disease (also known as GLUT1 deficiency syndrome) is a rare condition caused by inadequate transportation of the sugar, glucose, across the blood-brain barrier, resulting in mental retardation and other neurological problems. Genetic defects in glucose transporter type 1 (GLUT1) appears to be the primary cause of De Vivo disease.[17][18]
Alzheimer's Disease
Some new evidence indicates [19] that disruption of the blood-brain barrier in Alzheimer's Disease patients allows blood plasma containing amyloid beta (Aβ) to enter the brain where the Aβ adheres preferentially to the surface of astrocytes. These findings have led to the hypotheses that (1) breakdown of the blood-brain barrier allows access of neuron-binding autoantibodies and soluble exogenous Aβ42 to brain neurons and (2) binding of these auto-antibodies to neurons triggers and/or facilitates the internalization and accumulation of cell surface-bound Aβ42 in vulnerable neurons through their natural tendency to clear surface-bound autoantibodies via endocytosis. Eventually the astrocyte is overwhelmed, dies, ruptures, and disintegrates, leaving behind the insoluble Aβ42 plaque. Thus, in some patients, Alzheimer’s disease may be caused (or more likely, aggravated) by a breakdown in the blood-brain barrier. [1]
The herpes virus produces the amyloid beta (Aβ), and this virus has been found to be the pathogen responsible for being a major cause of the disease. [2]
HIV Encephalitis
It is believed [20] that latent HIV can cross the blood-brain barrier inside circulating monocytes in the bloodstream ("Trojan horse theory") within the first 14 days of infection. Once inside, these monocytes become activated and are transformed into macrophages. Activated macrophages release virions into the brain tissue proximate to brain microvessels. These viral particles likely attract the attention of sentinel brain microglia and perivascular macrophages initiating an inflammatory cascade that may cause a series of intracellular signaling in brain microvascular endothelial cells and damage the functional and structural integrity of the BBB. This inflammation is HIV encephalitis (HIVE). Instances of HIVE probably occur throughout the course of AIDS and are a precursor for HIV-associated dementia (HAD). The premier model for studying HIV and HIVE is the simian model.
References
^ Hamilton RD, Foss AJ, Leach L (2007). "Establishment of a human in vitro model of the outer blood-retinal barrier". Journal of Anatomy 211: 707. doi:10.1111/j.1469-7580.2007.00812.x. PMID 17922819.
^ Pritchard, Thomas C.; Alloway, Kevin Douglas (1999) (Google books preview). Medical Neuroscience. Hayes Barton Press. pp. 76–77. ISBN 1889325295. http://books.google.com/books?id=m7Y80PcFHtsC&printsec=frontcover#PPA76,M1. Retrieved 2009-02-08.
^ Gilgun-Sherki, Yossi; Melamed, Eldad and Offen, Daniel.(2001). Neuropharmacology. Volume 40, Issue 8, June 2001, Pages 959-975. doi:10.1016/S0028-3908(01)00019-3
^ Lina Stern: Science and fate by A.A. Vein. Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
^ Silva, GA (December 2008). "Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS". BMC Neuroscience 9 (Suppl. 3): S4. doi:10.1186/1471-2202-9-S3-S4. PMID 19091001. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19091001.
^ Brigger I, Morizet J, Aubert G, et al. (December 2002). "Poly(ethylene glycol)-coated hexadecylcyanoacrylate nanospheres display a combined effect for brain tumor targeting". J. Pharmacol. Exp. Ther. 303 (3): 928–36. doi:10.1124/jpet.102.039669. PMID 12438511.
^ Hashizume, H; Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, Jain RK, McDonald DM (April 2000). "Openings between defective endothelial cells explain tumor vessel leakiness". American Journal of Pathology 156 (4): 1363–1380. PMID 10751361.
^ Schneider, SW; Ludwig T, Tatenhorst L, Braune S, Oberleithner H, Senner V, Paulus W (March 2004). "Glioblastoma cells release factors that disrupt blood-brain barrier features". Acta Neuropathologica 107 (3): 272–276. doi:10.1007/s00401-003-0810-2. PMID 14730455.
^ Beam, TR Jr.; Allen, JC (December 1977). "Blood, brain, and cerebrospinal fluid concentrations of several antibiotics in rabbits with intact and inflamed meninges". Antimicrobial agents and chemotherapy 12 (6): 710–6. PMID 931369.
^ E. Oby and D. Janigro, The Blood-brain barrier and epilepsy. Epilepsia. 2006 Nov;47(11):1761-74
^ Marchi,N. et al. Seizure-Promoting Effect of Blood-Brain Barrier Disruption. Epilepsia 48(4), 732-742 (2007). Seiffert,E. et al. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J. Neurosci. 24, 7829-7836 (2004). Uva,L. et al. Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood-brain barrier permeability. Neuroscience (2007). van Vliet,E.A. et al. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 130, 521-534 (2007).
^ Ivens S, Kaufer D, Flores LP, Bechmann I, Zumsteg D, Tomkins O et al. (2007). "TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis.". Brain 130 (Pt 2): 535–47. doi:10.1093/brain/awl317. PMID 17121744. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17121744.
^ Awasthi,S. et al. RLIP76, a non-ABC transporter, and drug resistance in epilepsy. BMC. Neurosci. 6, 61 (2005). Loscher,W. & Potschka,H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat. Rev. Neurosci. 6, 591-602 (2005).
^ Waubant E (2006). "Biomarkers indicative of blood-brain barrier disruption in multiple sclerosis". Disease Markers 22 (4): 235–44. PMID 17124345. http://iospress.metapress.com/openurl.asp?genre=article&issn=0278-0240&volume=22&issue=4&spage=235.
^ Schreibelt G, Musters RJ, Reijerkerk A, et al. (August 2006). "Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity". J. Immunol. 177 (4): 2630–7. PMID 16888025. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16888025.
^ Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (August 2005). "IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel". J. Exp. Med. 202 (4): 473–7. doi:10.1084/jem.20050304. PMID 16087714.
^ Pascual, JM; Wang D, Lecumberri B, Yang H, Mao X, Yang R, De Vivo DC (May 2004). "GLUT1 deficiency and other glucose transporter diseases". European journal of endocrinology 150 (5): 627–33. doi:10.1530/eje.0.1500627. PMID 15132717.
^ Klepper, J; Voit T (June 2002). "Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain-- a review". European journal of pediatrics 161 (6): 295–304. doi:10.1007/s00431-002-0939-3. PMID 12029447.
^ Microvascular injury and blood–brain barrier leakage in Alzheimer’s disease - Zipser et al 2006
^ http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.neuro.25.112701.142822?cookieSet=1
Meningitis is an inflammation of the membranes that surround the brain and spinal cord (these membranes are also known as meninges). Meningitis is most commonly caused by infections with various pathogens, examples of which are Streptococcus pneumoniae and Haemophilus influenzae. When the meninges are inflamed, the blood-brain barrier may be disrupted. This disruption may increase the penetration of various substances (including either toxins or antibiotics) into the brain. Antibiotics used to treat meningitis may aggravate the inflammatory response of the central nervous system by releasing neurotoxins from the cell walls of bacteria-like lipopolysaccharide (LPS) [9] Treatment with third-generation or fourth-generation cephalosporin is usually preferred.
Epilepsy
Epilepsy is a common neurological disease that is characterized by recurrent and sometimes untreatable seizures. Several clinical and experimental data have implicated the failure of blood-brain barrier function in triggering chronic or acute seizures,[10][11] some studies implicate the interactions between a common blood protein - albumin and astrocytes.[12] These findings have shown that acute seizures are a predictable consequence of disruption of the BBB by either artificial or inflammatory mechanisms. In addition, expression of drug resistance molecules and transporters at the BBB are a significant mechanism of resistance to commonly used anti-epileptic drugs.[13]
Multiple sclerosis (MS)
Multiple sclerosis (MS) is considered to be an auto-immune and neurodegenerative disorder in which the immune system attacks the myelin that protects and electrically insulates the neurons of the central and peripheral nervous systems. Normally, a person's nervous system would be inaccessible to the white blood cells due to the blood-brain barrier. However, it has been shown using Magnetic Resonance Imaging, that when a person is undergoing an MS "attack," the blood-brain barrier has broken down in a section of the brain or spinal cord, allowing white blood cells called T lymphocytes to cross over and attack the myelin. It has sometimes been suggested that, rather than being a disease of the immune system, MS is a disease of the blood-brain barrier.[14] A recent study suggests that the weakening of the blood-brain barrier is a result of a disturbance in the endothelial cells on the inside of the blood vessel, due to which the production of the protein P-glycoprotein is not working well.
There are currently active investigations into treatments for a compromised blood-brain barrier. It is believed that oxidative stress plays an important role into the breakdown of the barrier. Anti-oxidants such as lipoic acid may be able to stabilize a weakening blood-brain barrier.[15]
Neuromyelitis optica
Neuromyelitis optica, also known as Devic's disease, is similar to and is often confused with multiple sclerosis. Among other differences from MS, a different target of the autoimmune response has been identified. Patients with neuromyelitis optica have high levels of antibodies against a protein called aquaporin 4 (a component of the astrocytic foot processes in the blood-brain barrier).[16]
Late-stage neurological trypanosomiasis (Sleeping sickness)
Late-stage neurological trypanosomiasis, or sleeping sickness, is a condition in which trypanosoma protozoa are found in brain tissue. It is not yet known how the parasites infect the brain from the blood, but it is suspected that they cross through the choroid plexus, a circumventricular organ.
Progressive multifocal leukoencephalopathy (PML)
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system that is caused by reactivation of a latent papovavirus (the JC polyomavirus) infection, that can cross the BBB. It affects immune-compromised patients and it is usually seen with patients suffering from AIDS.
[edit] De Vivo disease
De Vivo disease (also known as GLUT1 deficiency syndrome) is a rare condition caused by inadequate transportation of the sugar, glucose, across the blood-brain barrier, resulting in mental retardation and other neurological problems. Genetic defects in glucose transporter type 1 (GLUT1) appears to be the primary cause of De Vivo disease.[17][18]
Alzheimer's Disease
Some new evidence indicates [19] that disruption of the blood-brain barrier in Alzheimer's Disease patients allows blood plasma containing amyloid beta (Aβ) to enter the brain where the Aβ adheres preferentially to the surface of astrocytes. These findings have led to the hypotheses that (1) breakdown of the blood-brain barrier allows access of neuron-binding autoantibodies and soluble exogenous Aβ42 to brain neurons and (2) binding of these auto-antibodies to neurons triggers and/or facilitates the internalization and accumulation of cell surface-bound Aβ42 in vulnerable neurons through their natural tendency to clear surface-bound autoantibodies via endocytosis. Eventually the astrocyte is overwhelmed, dies, ruptures, and disintegrates, leaving behind the insoluble Aβ42 plaque. Thus, in some patients, Alzheimer’s disease may be caused (or more likely, aggravated) by a breakdown in the blood-brain barrier. [1]
The herpes virus produces the amyloid beta (Aβ), and this virus has been found to be the pathogen responsible for being a major cause of the disease. [2]
HIV Encephalitis
It is believed [20] that latent HIV can cross the blood-brain barrier inside circulating monocytes in the bloodstream ("Trojan horse theory") within the first 14 days of infection. Once inside, these monocytes become activated and are transformed into macrophages. Activated macrophages release virions into the brain tissue proximate to brain microvessels. These viral particles likely attract the attention of sentinel brain microglia and perivascular macrophages initiating an inflammatory cascade that may cause a series of intracellular signaling in brain microvascular endothelial cells and damage the functional and structural integrity of the BBB. This inflammation is HIV encephalitis (HIVE). Instances of HIVE probably occur throughout the course of AIDS and are a precursor for HIV-associated dementia (HAD). The premier model for studying HIV and HIVE is the simian model.
References
^ Hamilton RD, Foss AJ, Leach L (2007). "Establishment of a human in vitro model of the outer blood-retinal barrier". Journal of Anatomy 211: 707. doi:10.1111/j.1469-7580.2007.00812.x. PMID 17922819.
^ Pritchard, Thomas C.; Alloway, Kevin Douglas (1999) (Google books preview). Medical Neuroscience. Hayes Barton Press. pp. 76–77. ISBN 1889325295. http://books.google.com/books?id=m7Y80PcFHtsC&printsec=frontcover#PPA76,M1. Retrieved 2009-02-08.
^ Gilgun-Sherki, Yossi; Melamed, Eldad and Offen, Daniel.(2001). Neuropharmacology. Volume 40, Issue 8, June 2001, Pages 959-975. doi:10.1016/S0028-3908(01)00019-3
^ Lina Stern: Science and fate by A.A. Vein. Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
^ Silva, GA (December 2008). "Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS". BMC Neuroscience 9 (Suppl. 3): S4. doi:10.1186/1471-2202-9-S3-S4. PMID 19091001. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19091001.
^ Brigger I, Morizet J, Aubert G, et al. (December 2002). "Poly(ethylene glycol)-coated hexadecylcyanoacrylate nanospheres display a combined effect for brain tumor targeting". J. Pharmacol. Exp. Ther. 303 (3): 928–36. doi:10.1124/jpet.102.039669. PMID 12438511.
^ Hashizume, H; Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, Jain RK, McDonald DM (April 2000). "Openings between defective endothelial cells explain tumor vessel leakiness". American Journal of Pathology 156 (4): 1363–1380. PMID 10751361.
^ Schneider, SW; Ludwig T, Tatenhorst L, Braune S, Oberleithner H, Senner V, Paulus W (March 2004). "Glioblastoma cells release factors that disrupt blood-brain barrier features". Acta Neuropathologica 107 (3): 272–276. doi:10.1007/s00401-003-0810-2. PMID 14730455.
^ Beam, TR Jr.; Allen, JC (December 1977). "Blood, brain, and cerebrospinal fluid concentrations of several antibiotics in rabbits with intact and inflamed meninges". Antimicrobial agents and chemotherapy 12 (6): 710–6. PMID 931369.
^ E. Oby and D. Janigro, The Blood-brain barrier and epilepsy. Epilepsia. 2006 Nov;47(11):1761-74
^ Marchi,N. et al. Seizure-Promoting Effect of Blood-Brain Barrier Disruption. Epilepsia 48(4), 732-742 (2007). Seiffert,E. et al. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J. Neurosci. 24, 7829-7836 (2004). Uva,L. et al. Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood-brain barrier permeability. Neuroscience (2007). van Vliet,E.A. et al. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 130, 521-534 (2007).
^ Ivens S, Kaufer D, Flores LP, Bechmann I, Zumsteg D, Tomkins O et al. (2007). "TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis.". Brain 130 (Pt 2): 535–47. doi:10.1093/brain/awl317. PMID 17121744. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17121744.
^ Awasthi,S. et al. RLIP76, a non-ABC transporter, and drug resistance in epilepsy. BMC. Neurosci. 6, 61 (2005). Loscher,W. & Potschka,H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat. Rev. Neurosci. 6, 591-602 (2005).
^ Waubant E (2006). "Biomarkers indicative of blood-brain barrier disruption in multiple sclerosis". Disease Markers 22 (4): 235–44. PMID 17124345. http://iospress.metapress.com/openurl.asp?genre=article&issn=0278-0240&volume=22&issue=4&spage=235.
^ Schreibelt G, Musters RJ, Reijerkerk A, et al. (August 2006). "Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity". J. Immunol. 177 (4): 2630–7. PMID 16888025. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16888025.
^ Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (August 2005). "IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel". J. Exp. Med. 202 (4): 473–7. doi:10.1084/jem.20050304. PMID 16087714.
^ Pascual, JM; Wang D, Lecumberri B, Yang H, Mao X, Yang R, De Vivo DC (May 2004). "GLUT1 deficiency and other glucose transporter diseases". European journal of endocrinology 150 (5): 627–33. doi:10.1530/eje.0.1500627. PMID 15132717.
^ Klepper, J; Voit T (June 2002). "Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain-- a review". European journal of pediatrics 161 (6): 295–304. doi:10.1007/s00431-002-0939-3. PMID 12029447.
^ Microvascular injury and blood–brain barrier leakage in Alzheimer’s disease - Zipser et al 2006
^ http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.neuro.25.112701.142822?cookieSet=1
Blood-brain barrier
The blood-brain barrier (BBB) is a separation of circulating blood and cerebrospinal fluid (CSF) in the central nervous system (CNS). It occurs along all capillaries and consists of tight junctions around the capillaries that don't exist in normal circulation. Endothelial cells restrict the diffusion of microscopic objects (e.g. bacteria) and large or hydrophilic molecules into the CSF, while allowing the diffusion of small hydrophobic molecules (O2, hormones, CO2). Cells of the barrier actively transport metabolic products such as glucose across the barrier with specific proteins.
Physiology
This "barrier" results from the selectivity of the tight junctions between endothelial cells in CNS vessels that restricts the passage of solutes. At the interface between blood and the brain, endothelial cells are stitched together by these tight junctions, which are composed of smaller subunits, frequently biochemical dimers, that are transmembrane proteins such as occludin, claudins, junctional adhesion molecule (JAM), or ESAM, for example. Each of these transmembrane proteins is anchored into the endothelial cells by another protein complex that includes zo-1 and associated proteins.
The blood-brain barrier is composed of high-density cells restricting passage of substances from the bloodstream much more than endothelial cells in capillaries elsewhere in the body. Astrocyte cell projections called astrocytic feet (also known as "glia limitans") surround the endothelial cells of the BBB, providing biochemical support to those cells. The BBB is distinct from the quite similar blood-cerebrospinal fluid barrier, which is a function of the choroidal cells of the choroid plexus, and from the blood-retinal barrier, which can be considered a part of the whole realm of such barriers.[1]
Several areas of the human brain are not "behind" the BBB. These include the circumventricular organs. One example of this is the pineal gland, which secretes the hormone melatonin "directly into the systemic circulation"[2] as this hormone can pass through the blood-brain barrier.[3]
The blood-brain barrier is composed of high-density cells restricting passage of substances from the bloodstream much more than endothelial cells in capillaries elsewhere in the body. Astrocyte cell projections called astrocytic feet (also known as "glia limitans") surround the endothelial cells of the BBB, providing biochemical support to those cells. The BBB is distinct from the quite similar blood-cerebrospinal fluid barrier, which is a function of the choroidal cells of the choroid plexus, and from the blood-retinal barrier, which can be considered a part of the whole realm of such barriers.[1]
Several areas of the human brain are not "behind" the BBB. These include the circumventricular organs. One example of this is the pineal gland, which secretes the hormone melatonin "directly into the systemic circulation"[2] as this hormone can pass through the blood-brain barrier.[3]
Crystal Mall (British Columbia)
Crystal Mall was established in 2000.[1] By the number of retailers, it is the largest Asian mall in Western Canada with more than 200 stores. Despite the number of stores, operation hours are not standardized which may create inconvenience for the shoppers. The largest Asian mall by square feet is the Aberdeen Centre in Richmond, British Columbia. Crystal Mall also has a food fair with more than 20 food vendors which often offer cheap lunch or dinner combinations with average price being less than five dollars. There are several popular bubble tea shops as well. The mall also has a traditional Chinese open market. The mall has 950 parking stalls in its 4-level underground parking, although a small section is reserved for hotel customers only. The underground parking is constructed in a circular direction just like the mall itself. The parking lot is regularly patrolled.[2] Occasionally, the mall will host events such as for Christmas, New Years, Chinese New Years, or a contest called Crystal Cover Girl
Water-cement ratio
Water-cement ratio is the ratio of weight of water to the weight of cement used in a concrete mix. It has an important influence on the quality of concrete produced. A lower water-cement ratio leads to higher strength and durability, but may make the mix more difficult to place. Placement difficulties can be resolved by using plasticizer. The water-cement ratio is independent of the total cement content (and the total water content) of a concrete mix.
Often, the water to cement ratio is characterized as the water to cement plus pozzolan ratio, w/(c+p). The pozzolan is typically a fly ash, or blast furnace slag. It can include a number of other materials, such as silica fume, rice hull ash or natural pozzolans. The addition of pozzolans will influence the strength gain of the concrete.
The concept of water-cement ratio was developed by Duff A. Abrams and first published in 1918.
Concrete hardens as a result of the chemical reaction between cement and water (known as hydration). For every 4 lbs of cement, 1 lb of water is needed to fully complete the reaction. This results in a water-cement ratio of 1:4 or 20% (1/1+4). In reality, a mix formed with 20% water is too dry and does not flow well enough to be placed, and some of the water is taken up by the sand and stone and is not available to participate in the hydration reaction. So more water is used than is technically necessary to react with the cement. More typical Water-Cement ratios of 35% to 40% are used, along with a plasticizer.
Too much water will result in settling and segregation of the sand/stone components (more sand in the top layers because the stone will settle at the bottom). Also, any water that is not consumed by the hydration reaction will eventually leave the concrete as it hardens, resulting in microscopic pores or holes that will reduce the final strength of the concrete (but interestingly - microscopic pores or holes are desired in outdoor concrete that gets wet while experiencing low temperatures resulting in freeze-thaw cycles. For flatwork (driveways, steps, sidewalks, etc) an air-entrainment agent is added to create small bubbles in the concrete. This helps the finished, hardened concrete resist fracturing caused by freeze-thaw temperature cycling. Finished, hardened concrete can be as much as 6% air (by volume) because of this.
And finally, a mix with too much water will experience more shrinkage as the excess water leaves, resulting in internal cracks and visible fractures (particularly around inside corners) which again will reduce the final strength. Anyone who has set wooden fence posts in concrete piers will probably notice cracks radiating from the corners of the post. This can be reduced by keeping the water to an absolute minimum.
Often, the water to cement ratio is characterized as the water to cement plus pozzolan ratio, w/(c+p). The pozzolan is typically a fly ash, or blast furnace slag. It can include a number of other materials, such as silica fume, rice hull ash or natural pozzolans. The addition of pozzolans will influence the strength gain of the concrete.
The concept of water-cement ratio was developed by Duff A. Abrams and first published in 1918.
Concrete hardens as a result of the chemical reaction between cement and water (known as hydration). For every 4 lbs of cement, 1 lb of water is needed to fully complete the reaction. This results in a water-cement ratio of 1:4 or 20% (1/1+4). In reality, a mix formed with 20% water is too dry and does not flow well enough to be placed, and some of the water is taken up by the sand and stone and is not available to participate in the hydration reaction. So more water is used than is technically necessary to react with the cement. More typical Water-Cement ratios of 35% to 40% are used, along with a plasticizer.
Too much water will result in settling and segregation of the sand/stone components (more sand in the top layers because the stone will settle at the bottom). Also, any water that is not consumed by the hydration reaction will eventually leave the concrete as it hardens, resulting in microscopic pores or holes that will reduce the final strength of the concrete (but interestingly - microscopic pores or holes are desired in outdoor concrete that gets wet while experiencing low temperatures resulting in freeze-thaw cycles. For flatwork (driveways, steps, sidewalks, etc) an air-entrainment agent is added to create small bubbles in the concrete. This helps the finished, hardened concrete resist fracturing caused by freeze-thaw temperature cycling. Finished, hardened concrete can be as much as 6% air (by volume) because of this.
And finally, a mix with too much water will experience more shrinkage as the excess water leaves, resulting in internal cracks and visible fractures (particularly around inside corners) which again will reduce the final strength. Anyone who has set wooden fence posts in concrete piers will probably notice cracks radiating from the corners of the post. This can be reduced by keeping the water to an absolute minimum.
Sources of Air pollution
Main article: AP 42 Compilation of Air Pollutant Emission Factors
Dust storm approaching Stratford, Texas
Controlled burning of a field outside of Statesboro, Georgia in preparation for spring planting
Sources of air pollution refer to the various locations, activities or factors which are responsible for the releasing of pollutants in the atmosphere. These sources can be classified into two major categories which are:
Anthropogenic sources (human activity) mostly related to burning different kinds of fuel
"Stationary Sources" include smoke stacks of power plants, manufacturing facilities (factories) and waste incinerators, as well as furnaces and other types of fuel-burning heating devices
"Mobile Sources" include motor vehicles, marine vessels, aircraft and the effect of sound etc.
Chemicals, dust and controlled burn practices in agriculture and forestry management. Controlled or prescribed burning is a technique sometimes used in forest management, farming, prairie restoration or greenhouse gas abatement. Fire is a natural part of both forest and grassland ecology and controlled fire can be a tool for foresters. Controlled burning stimulates the germination of some desirable forest trees, thus renewing the forest.
Fumes from paint, hair spray, varnish, aerosol sprays and other solvents
Waste deposition in landfills, which generate methane.Methane is not toxic; however, it is highly flammable and may form explosive mixtures with air. Methane is also an asphyxiant and may displace oxygen in an enclosed space. Asphyxia or suffocation may result if the oxygen concentration is reduced to below 19.5% by displacement
Military, such as nuclear weapons, toxic gases, germ warfare and rocketry
Natural sources
Dust from natural sources, usually large areas of land with little or no vegetation.
Methane, emitted by the digestion of food by animals, for example cattle.
Radon gas from radioactive decay within the Earth's crust. Radon is a colorless, odorless, naturally occurring, radioactive noble gas that is formed from the decay of radium. It is considered to be a health hazard. Radon gas from natural sources can accumulate in buildings, especially in confined areas such as the basement and it is the second most frequent cause of lung cancer, after cigarette smoking.
Smoke and carbon monoxide from wildfires.
Volcanic activity, which produce sulfur, chlorine, and ash particulates.
Emission factors
Main article: AP 42 Compilation of Air Pollutant Emission Factors
Air pollutant emission factors are representative values that attempt to relate the quantity of a pollutant released to the ambient air with an activity associated with the release of that pollutant. These factors are usually expressed as the weight of pollutant divided by a unit weight, volume, distance, or duration of the activity emitting the pollutant (e.g., kilograms of particulate emitted per megagram of coal burned). Such factors facilitate estimation of emissions from various sources of air pollution. In most cases, these factors are simply averages of all available data of acceptable quality, and are generally assumed to be representative of long-term averages.
The United States Environmental Protection Agency has published a compilation of air pollutant emission factors for a multitude of industrial sources.[5] The United Kingdom, Australia, Canada and many other countries have published similar compilations, as well as the European Environment Agency.[6][7][8][9][10]
Indoor air quality (IAQ)
Main article: Indoor air quality
A lack of ventilation indoors concentrates air pollution where people often spend the majority of their time. Radon (Rn) gas, a carcinogen, is exuded from the Earth in certain locations and trapped inside houses. Building materials including carpeting and plywood emit formaldehyde (H2CO) gas. Paint and solvents give off volatile organic compounds (VOCs) as they dry. Lead paint can degenerate into dust and be inhaled. Intentional air pollution is introduced with the use of air fresheners, incense, and other scented items. Controlled wood fires in stoves and fireplaces can add significant amounts of smoke particulates into the air, inside and out[11]. Indoor pollution fatalities may be caused by using pesticides and other chemical sprays indoors without proper ventilation.
Carbon monoxide (CO) poisoning and fatalities are often caused by faulty vents and chimneys, or by the burning of charcoal indoors. Chronic carbon monoxide poisoning can result even from poorly adjusted pilot lights. Traps are built into all domestic plumbing to keep sewer gas, hydrogen sulfide, out of interiors. Clothing emits tetrachloroethylene, or other dry cleaning fluids, for days after dry cleaning.
Though its use has now been banned in many countries, the extensive use of asbestos in industrial and domestic environments in the past has left a potentially very dangerous material in many localities. Asbestosis is a chronic inflammatory medical condition affecting the tissue of the lungs. It occurs after long-term, heavy exposure to asbestos from asbestos-containing materials in structures. Sufferers have severe dyspnea (shortness of breath) and are at an increased risk regarding several different types of lung cancer. As clear explanations are not always stressed in non-technical literature, care should be taken to distinguish between several forms of relevant diseases. According to the World Health Organisation (WHO), these may defined as; asbestosis, lung cancer, and mesothelioma (generally a very rare form of cancer, when more widespread it is almost always associated with prolonged exposure to asbestos).
Biological sources of air pollution are also found indoors, as gases and airborne particulates. Pets produce dander, people produce dust from minute skin flakes and decomposed hair, dust mites in bedding, carpeting and furniture produce enzymes and micrometre-sized fecal droppings, inhabitants emit methane, mold forms in walls and generates mycotoxins and spores, air conditioning systems can incubate Legionnaires' disease and mold, and houseplants, soil and surrounding gardens can produce pollen, dust, and mold. Indoors, the lack of air circulation allows these airborne pollutants to accumulate more than they would otherwise occur in nature.
Health effects
The World Health Organization states that 2.4 million people die each year from causes directly attributable to air pollution, with 1.5 million of these deaths attributable to indoor air pollution.[12] "Epidemiological studies suggest that more than 500,000 Americans die each year from cardiopulmonary disease linked to breathing fine particle air pollution. . ."[13] A study by the University of Birmingham has shown a strong correlation between pneumonia related deaths and air pollution from motor vehicles.[14] Worldwide more deaths per year are linked to air pollution than to automobile accidents.[citation needed] Published in 2005 suggests that 310,000 Europeans die from air pollution annually.[citation needed] Direct causes of air pollution related deaths include aggravated asthma, bronchitis, emphysema, lung and heart diseases, and respiratory allergies.[citation needed] The US EPA estimates that a proposed set of changes in diesel engine technology (Tier 2) could result in 12,000 fewer premature mortalities, 15,000 fewer heart attacks, 6,000 fewer emergency room visits by children with asthma, and 8,900 fewer respiratory-related hospital admissions each year in the United States.[citation needed]
The worst short term civilian pollution crisis in India was the 1984 Bhopal Disaster.[15] Leaked industrial vapors from the Union Carbide factory, belonging to Union Carbide, Inc., U.S.A., killed more than 2,000 people outright and injured anywhere from 150,000 to 600,000 others, some 6,000 of whom would later die from their injuries.[citation needed] The United Kingdom suffered its worst air pollution event when the December 4 Great Smog of 1952 formed over London. In six days more than 4,000 died, and 8,000 more died within the following months.[citation needed] An accidental leak of anthrax spores from a biological warfare laboratory in the former USSR in 1979 near Sverdlovsk is believed to have been the cause of hundreds of civilian deaths.[citation needed] The worst single incident of air pollution to occur in the United States of America occurred in Donora, Pennsylvania in late October, 1948, when 20 people died and over 7,000 were injured.[16]
The health effects caused by air pollutants may range from subtle biochemical and physiological changes to difficulty in breathing, wheezing, coughing and aggravation of existing respiratory and cardiac conditions. These effects can result in increased medication use, increased doctor or emergency room visits, more hospital admissions and premature death. The human health effects of poor air quality are far reaching, but principally affect the body's respiratory system and the cardiovascular system. Individual reactions to air pollutants depend on the type of pollutant a person is exposed to, the degree of exposure, the individual's health status and genetics.[citation needed]
A new economic study of the health impacts and associated costs of air pollution in the Los Angeles Basin and San Joaquin Valley of Southern California shows that more than 3800 people die prematurely (approximately 14 years earlier than normal) each year because air pollution levels violate federal standards. The number of annual premature deaths is considerably higher than the fatalities related to auto collisions in the same area, which average fewer than 2,000 per year [17].
Diesel exhaust (DE) is a major contributor to combustion derived particulate matter air pollution. In several human experimental studies, using a well validated exposure chamber setup, DE has been linked to acute vascular dysfunction and increased thrombus formation.[18][19] This serves as a plausible mechanistic link between the previously described association between particulate matter air pollution and increased cardiovascular morbidity and mortality.
Effects on cystic fibrosis
Main article: Cystic fibrosis
A study from 1999 to 2000 by the University of Washington showed that patients near and around particulate matter air pollution had an increased risk of pulmonary exacerbations and decrease in lung function.[20] Patients were examined before the study for amounts of specific pollutants like Pseudomonas aeruginosa or Burkholderia cenocepacia as well as their socioeconomic standing. Participants involved in the study were located in the United States in close proximity to an Environmental Protection Agency.[clarification needed] During the time of the study 117 deaths were associated with air pollution. A trend was noticed that patients living closer or in large metropolitan areas to be close to medical help also had higher level of pollutants found in their system because of more emissions in larger cities. With cystic fibrosis patients already being born with decreased lung function everyday pollutants such as smoke emissions from automobiles, tobacco smoke and improper use of indoor heating devices could add to the disintegration of lung function.[21]
Effects on COPD
Main article: Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) include diseases such as chronic bronchitis, emphysema, and some forms of asthma.[22]
A study conducted in 1960-1961 in the wake of the Great Smog of 1952 compared 293 London residents with 477 residents of Gloucester, Peterborough, and Norwich, three towns with low reported death rates from chronic bronchitis. All subjects were male postal truck drivers aged 40 to 59. Compared to the subjects from the outlying towns, the London subjects exhibited more severe respiratory symptoms (including cough, phlegm, and dyspnea), reduced lung function (FEV1 and peak flow rate), and increased sputum production and purulence. The differences were more pronounced for subjects aged 50 to 59. The study controlled for age and smoking habits, so concluded that air pollution was the most likely cause of the observed differences.[23]
It is believed that much like cystic fibrosis, by living in a more urban environment serious health hazards become more apparent. Studies have shown that in urban areas patients suffer mucus hypersecretion, lower levels of lung function, and more self diagnosis of chronic bronchitis and emphysema.[24]
The Great Smog of 1952
Main article: Great Smog of 1952
The Great Smog of 1952 in London.
Early in December 1952, a cold fog descended upon London. Because of the cold, Londoners began to burn more coal than usual. The resulting air pollution was trapped by the inversion layer formed by the dense mass of cold air. Concentrations of pollutants, coal smoke in particular, built up dramatically. The problem was made worse by use of low-quality, high-sulphur coal for home heating in London in order to permit export of higher-quality coal, because of the country's tenuous postwar economic situation. The "fog", or smog, was so thick that driving became difficult or impossible.[25]. The extreme reduction in visibility was accompanied by an increase in criminal activity as well as transportation delays and a virtual shut down of the city. During the 4 day period of fog, at least 4,000 people died as a direct result of the weather.[26]
Effects on children
Cities around the world with high exposure to air pollutants have the possibility of children living within them to develop asthma, pneumonia and other lower respiratory infections as well as a low initial birth rate. Protective measures to ensure the youths' health are being taken in cities such as New Delhi, India where buses now use compressed natural gas to help eliminate the “pea-soup” smog.[27] Research by the World Health Organization shows there is the greatest concentration of particulate matter particles in countries with low economic world power and high poverty and population rates. Examples of these countries include Egypt, Sudan, Mongolia, and Indonesia. The Clean Air Act was passed in 1970, however in 2002 at least 146 million Americans were living in areas that did not meet at least one of the “criteria pollutants” laid out in the 1997 National Ambient Air Quality Standards.[28] Those pollutants included: ozone, particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide, and lead. Because children are outdoors more and have higher minute ventilation they are more susceptible to the dangers of air pollution.
Health effects in relatively "clean" areas
Even in areas with relatively low levels of air pollution, public health effects can be substantial and costly. This is because effects can occur at very low levels and a large number of people can potentially breathe in such pollutants. A 2005 scientific study for the British Columbia Lung Association showed that a 1% improvement in ambient PM2.5 and ozone concentrations will produce a $29 million in annual savings in the region in 2010[29]. This finding is based on health valuation of lethal (mortality) and sub-lethal (morbidity) effects
Dust storm approaching Stratford, Texas
Controlled burning of a field outside of Statesboro, Georgia in preparation for spring planting
Sources of air pollution refer to the various locations, activities or factors which are responsible for the releasing of pollutants in the atmosphere. These sources can be classified into two major categories which are:
Anthropogenic sources (human activity) mostly related to burning different kinds of fuel
"Stationary Sources" include smoke stacks of power plants, manufacturing facilities (factories) and waste incinerators, as well as furnaces and other types of fuel-burning heating devices
"Mobile Sources" include motor vehicles, marine vessels, aircraft and the effect of sound etc.
Chemicals, dust and controlled burn practices in agriculture and forestry management. Controlled or prescribed burning is a technique sometimes used in forest management, farming, prairie restoration or greenhouse gas abatement. Fire is a natural part of both forest and grassland ecology and controlled fire can be a tool for foresters. Controlled burning stimulates the germination of some desirable forest trees, thus renewing the forest.
Fumes from paint, hair spray, varnish, aerosol sprays and other solvents
Waste deposition in landfills, which generate methane.Methane is not toxic; however, it is highly flammable and may form explosive mixtures with air. Methane is also an asphyxiant and may displace oxygen in an enclosed space. Asphyxia or suffocation may result if the oxygen concentration is reduced to below 19.5% by displacement
Military, such as nuclear weapons, toxic gases, germ warfare and rocketry
Natural sources
Dust from natural sources, usually large areas of land with little or no vegetation.
Methane, emitted by the digestion of food by animals, for example cattle.
Radon gas from radioactive decay within the Earth's crust. Radon is a colorless, odorless, naturally occurring, radioactive noble gas that is formed from the decay of radium. It is considered to be a health hazard. Radon gas from natural sources can accumulate in buildings, especially in confined areas such as the basement and it is the second most frequent cause of lung cancer, after cigarette smoking.
Smoke and carbon monoxide from wildfires.
Volcanic activity, which produce sulfur, chlorine, and ash particulates.
Emission factors
Main article: AP 42 Compilation of Air Pollutant Emission Factors
Air pollutant emission factors are representative values that attempt to relate the quantity of a pollutant released to the ambient air with an activity associated with the release of that pollutant. These factors are usually expressed as the weight of pollutant divided by a unit weight, volume, distance, or duration of the activity emitting the pollutant (e.g., kilograms of particulate emitted per megagram of coal burned). Such factors facilitate estimation of emissions from various sources of air pollution. In most cases, these factors are simply averages of all available data of acceptable quality, and are generally assumed to be representative of long-term averages.
The United States Environmental Protection Agency has published a compilation of air pollutant emission factors for a multitude of industrial sources.[5] The United Kingdom, Australia, Canada and many other countries have published similar compilations, as well as the European Environment Agency.[6][7][8][9][10]
Indoor air quality (IAQ)
Main article: Indoor air quality
A lack of ventilation indoors concentrates air pollution where people often spend the majority of their time. Radon (Rn) gas, a carcinogen, is exuded from the Earth in certain locations and trapped inside houses. Building materials including carpeting and plywood emit formaldehyde (H2CO) gas. Paint and solvents give off volatile organic compounds (VOCs) as they dry. Lead paint can degenerate into dust and be inhaled. Intentional air pollution is introduced with the use of air fresheners, incense, and other scented items. Controlled wood fires in stoves and fireplaces can add significant amounts of smoke particulates into the air, inside and out[11]. Indoor pollution fatalities may be caused by using pesticides and other chemical sprays indoors without proper ventilation.
Carbon monoxide (CO) poisoning and fatalities are often caused by faulty vents and chimneys, or by the burning of charcoal indoors. Chronic carbon monoxide poisoning can result even from poorly adjusted pilot lights. Traps are built into all domestic plumbing to keep sewer gas, hydrogen sulfide, out of interiors. Clothing emits tetrachloroethylene, or other dry cleaning fluids, for days after dry cleaning.
Though its use has now been banned in many countries, the extensive use of asbestos in industrial and domestic environments in the past has left a potentially very dangerous material in many localities. Asbestosis is a chronic inflammatory medical condition affecting the tissue of the lungs. It occurs after long-term, heavy exposure to asbestos from asbestos-containing materials in structures. Sufferers have severe dyspnea (shortness of breath) and are at an increased risk regarding several different types of lung cancer. As clear explanations are not always stressed in non-technical literature, care should be taken to distinguish between several forms of relevant diseases. According to the World Health Organisation (WHO), these may defined as; asbestosis, lung cancer, and mesothelioma (generally a very rare form of cancer, when more widespread it is almost always associated with prolonged exposure to asbestos).
Biological sources of air pollution are also found indoors, as gases and airborne particulates. Pets produce dander, people produce dust from minute skin flakes and decomposed hair, dust mites in bedding, carpeting and furniture produce enzymes and micrometre-sized fecal droppings, inhabitants emit methane, mold forms in walls and generates mycotoxins and spores, air conditioning systems can incubate Legionnaires' disease and mold, and houseplants, soil and surrounding gardens can produce pollen, dust, and mold. Indoors, the lack of air circulation allows these airborne pollutants to accumulate more than they would otherwise occur in nature.
Health effects
The World Health Organization states that 2.4 million people die each year from causes directly attributable to air pollution, with 1.5 million of these deaths attributable to indoor air pollution.[12] "Epidemiological studies suggest that more than 500,000 Americans die each year from cardiopulmonary disease linked to breathing fine particle air pollution. . ."[13] A study by the University of Birmingham has shown a strong correlation between pneumonia related deaths and air pollution from motor vehicles.[14] Worldwide more deaths per year are linked to air pollution than to automobile accidents.[citation needed] Published in 2005 suggests that 310,000 Europeans die from air pollution annually.[citation needed] Direct causes of air pollution related deaths include aggravated asthma, bronchitis, emphysema, lung and heart diseases, and respiratory allergies.[citation needed] The US EPA estimates that a proposed set of changes in diesel engine technology (Tier 2) could result in 12,000 fewer premature mortalities, 15,000 fewer heart attacks, 6,000 fewer emergency room visits by children with asthma, and 8,900 fewer respiratory-related hospital admissions each year in the United States.[citation needed]
The worst short term civilian pollution crisis in India was the 1984 Bhopal Disaster.[15] Leaked industrial vapors from the Union Carbide factory, belonging to Union Carbide, Inc., U.S.A., killed more than 2,000 people outright and injured anywhere from 150,000 to 600,000 others, some 6,000 of whom would later die from their injuries.[citation needed] The United Kingdom suffered its worst air pollution event when the December 4 Great Smog of 1952 formed over London. In six days more than 4,000 died, and 8,000 more died within the following months.[citation needed] An accidental leak of anthrax spores from a biological warfare laboratory in the former USSR in 1979 near Sverdlovsk is believed to have been the cause of hundreds of civilian deaths.[citation needed] The worst single incident of air pollution to occur in the United States of America occurred in Donora, Pennsylvania in late October, 1948, when 20 people died and over 7,000 were injured.[16]
The health effects caused by air pollutants may range from subtle biochemical and physiological changes to difficulty in breathing, wheezing, coughing and aggravation of existing respiratory and cardiac conditions. These effects can result in increased medication use, increased doctor or emergency room visits, more hospital admissions and premature death. The human health effects of poor air quality are far reaching, but principally affect the body's respiratory system and the cardiovascular system. Individual reactions to air pollutants depend on the type of pollutant a person is exposed to, the degree of exposure, the individual's health status and genetics.[citation needed]
A new economic study of the health impacts and associated costs of air pollution in the Los Angeles Basin and San Joaquin Valley of Southern California shows that more than 3800 people die prematurely (approximately 14 years earlier than normal) each year because air pollution levels violate federal standards. The number of annual premature deaths is considerably higher than the fatalities related to auto collisions in the same area, which average fewer than 2,000 per year [17].
Diesel exhaust (DE) is a major contributor to combustion derived particulate matter air pollution. In several human experimental studies, using a well validated exposure chamber setup, DE has been linked to acute vascular dysfunction and increased thrombus formation.[18][19] This serves as a plausible mechanistic link between the previously described association between particulate matter air pollution and increased cardiovascular morbidity and mortality.
Effects on cystic fibrosis
Main article: Cystic fibrosis
A study from 1999 to 2000 by the University of Washington showed that patients near and around particulate matter air pollution had an increased risk of pulmonary exacerbations and decrease in lung function.[20] Patients were examined before the study for amounts of specific pollutants like Pseudomonas aeruginosa or Burkholderia cenocepacia as well as their socioeconomic standing. Participants involved in the study were located in the United States in close proximity to an Environmental Protection Agency.[clarification needed] During the time of the study 117 deaths were associated with air pollution. A trend was noticed that patients living closer or in large metropolitan areas to be close to medical help also had higher level of pollutants found in their system because of more emissions in larger cities. With cystic fibrosis patients already being born with decreased lung function everyday pollutants such as smoke emissions from automobiles, tobacco smoke and improper use of indoor heating devices could add to the disintegration of lung function.[21]
Effects on COPD
Main article: Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) include diseases such as chronic bronchitis, emphysema, and some forms of asthma.[22]
A study conducted in 1960-1961 in the wake of the Great Smog of 1952 compared 293 London residents with 477 residents of Gloucester, Peterborough, and Norwich, three towns with low reported death rates from chronic bronchitis. All subjects were male postal truck drivers aged 40 to 59. Compared to the subjects from the outlying towns, the London subjects exhibited more severe respiratory symptoms (including cough, phlegm, and dyspnea), reduced lung function (FEV1 and peak flow rate), and increased sputum production and purulence. The differences were more pronounced for subjects aged 50 to 59. The study controlled for age and smoking habits, so concluded that air pollution was the most likely cause of the observed differences.[23]
It is believed that much like cystic fibrosis, by living in a more urban environment serious health hazards become more apparent. Studies have shown that in urban areas patients suffer mucus hypersecretion, lower levels of lung function, and more self diagnosis of chronic bronchitis and emphysema.[24]
The Great Smog of 1952
Main article: Great Smog of 1952
The Great Smog of 1952 in London.
Early in December 1952, a cold fog descended upon London. Because of the cold, Londoners began to burn more coal than usual. The resulting air pollution was trapped by the inversion layer formed by the dense mass of cold air. Concentrations of pollutants, coal smoke in particular, built up dramatically. The problem was made worse by use of low-quality, high-sulphur coal for home heating in London in order to permit export of higher-quality coal, because of the country's tenuous postwar economic situation. The "fog", or smog, was so thick that driving became difficult or impossible.[25]. The extreme reduction in visibility was accompanied by an increase in criminal activity as well as transportation delays and a virtual shut down of the city. During the 4 day period of fog, at least 4,000 people died as a direct result of the weather.[26]
Effects on children
Cities around the world with high exposure to air pollutants have the possibility of children living within them to develop asthma, pneumonia and other lower respiratory infections as well as a low initial birth rate. Protective measures to ensure the youths' health are being taken in cities such as New Delhi, India where buses now use compressed natural gas to help eliminate the “pea-soup” smog.[27] Research by the World Health Organization shows there is the greatest concentration of particulate matter particles in countries with low economic world power and high poverty and population rates. Examples of these countries include Egypt, Sudan, Mongolia, and Indonesia. The Clean Air Act was passed in 1970, however in 2002 at least 146 million Americans were living in areas that did not meet at least one of the “criteria pollutants” laid out in the 1997 National Ambient Air Quality Standards.[28] Those pollutants included: ozone, particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide, and lead. Because children are outdoors more and have higher minute ventilation they are more susceptible to the dangers of air pollution.
Health effects in relatively "clean" areas
Even in areas with relatively low levels of air pollution, public health effects can be substantial and costly. This is because effects can occur at very low levels and a large number of people can potentially breathe in such pollutants. A 2005 scientific study for the British Columbia Lung Association showed that a 1% improvement in ambient PM2.5 and ozone concentrations will produce a $29 million in annual savings in the region in 2010[29]. This finding is based on health valuation of lethal (mortality) and sub-lethal (morbidity) effects
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