Sandbox Reserved 686 - Revision history

Student at 22:43, 3 May 2013

Student — Fri, 03 May 2013 22:43:41 GMT

←Older revision		Revision as of 22:43, 3 May 2013
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	With the channel stabilized in the open conformation by Ivermectin, chloride ions can freely flow into the cell. When the chloride ions are continually flowing, the polarization of the membrane is lost. This is how the parasitic microfilariae are killed. Their neurotransmission is severely inhibited. The microfilariae eventually die of flaccid paralysis. Ivermectin is often prescribed along with doxycycline in order to kill the ''Wolbachia'', as well.		With the channel stabilized in the open conformation by Ivermectin, chloride ions can freely flow into the cell. When the chloride ions are continually flowing, the polarization of the membrane is lost. This is how the parasitic microfilariae are killed. Their neurotransmission is severely inhibited. The microfilariae eventually die of flaccid paralysis. Ivermectin is often prescribed along with doxycycline in order to kill the ''Wolbachia'', as well.
		+
		+	===References===
		+
		+	<small>Andre, Amelie Saint, et al. "The Role of Endosymbiotic Wolbachia Bacteria in the Pathogenesis of River Blindness." Science 8 Mar. 2002: 1892-95. Web. 27 Apr. 2013. <http://www.sciencemag.org>.</small>
		+
		+	<small>Ardelli, B. F. "Transport proteins of the ABC systems superfamily and their role in drug action and resistance in nematodes." Parasitology International (2013): n. pag. Academic Search Complete. Web. 20 Apr. 2013.</small>
		+
		+	<small>Canga, Aranzazu Gonzalez, et al. "The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review." The American Association of Pharmaceutical Scientists Journal 10.1 (2007): 42-46. Google Scholar. Web. 24 Apr. 2013.</small>
		+
		+	<small>Geary, Timothy G. "Ivermectin 20 years on: maturation of a wonder drug." Trends in Parasitology 21.11 (2008): 530-32. PubMed. Web. 23 Apr. 2013. <http://www.sciencedirect.com>.</small>
		+
		+	<small>Gillette-Ferguson, Illona, et al. "Wolbachia- and Onchocerca volvulus-Induced Keratitis (River Blindness) Is Dependent on Myeloid Differentiation Factor 88." Infection and Immunity 74.4 (2006): 2442-45. Google Scholar. Web. 26 Apr. 2013.</small>
		+
		+	<small>Goa, Karen L., Donna McTavish, and Stephen P. Clissold. "Ivermectin." Drugs 42.4 (1991): 640-58. Google Scholar. Web. 27 Apr. 2013.</small>
		+
		+	<small>Hibbs, Ryan E., and Eric Gouaux. "Principles of activation and permeation in an anion-selective Cys-loop receptor." Nature 474 (2011): 54-60. PubMed. Web. 12 Apr. 2013.</small>
		+
		+	<small>"Ivermectin." Wikipedia. Wikipedia, n.d. Web. 27 Apr. 2013. <https://en.wikipedia.org/wiki/Ivermectin>.</small>
		+
		+	<small>Lynagh, Timothy, et al. "Molecular Determinants of Ivermectin Sensitivity at the Glycine Receptor Chloride Channel." Journal of Biological Chemistry 286.51 (2011): 43913-24. PubMed. Web. 23 Apr. 2013.</small>
		+
		+	<small>"Onchocerciasis." Centers for Disease Control and Prevention. USA.gov, n.d. Web. 24 Apr. 2013. <http://www.cdc.gov/parasites/onchocerciasis/gen_info/faqs.html>.</small>
		+
		+	<small>Silberberg, Shai D., Mufeng Li, and Kenton J. Swartz. "Ivermectin Interaction with Transmembrane Helices Reveals Widespread Rearrangements during Opening of P2X Receptor Channels." Neuron 54 (2007): 263-74. Google Scholar. Web. 20 Apr. 2013.</small>

Student at 22:33, 3 May 2013

Student — Fri, 03 May 2013 22:33:04 GMT

←Older revision		Revision as of 22:33, 3 May 2013
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	==Mechanism==		==Mechanism==

-	The <scene name='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2'>glutamate-gated chloride channel</scene> is made up of <scene name='Sandbox_Reserved_686/~~5_subunits_no_fab_cl~~/2'>five homologous subunits</scene>, as displayed by the different colorings. All the subunits are conserved structurally, but not necessarily in their amino acid sequence. Each monomer has <scene name='Sandbox_Reserved_686/Secondary_structures/2'>two domains</scene>. The extracellular domain is mainly β-pleated sheets, shown pink in the structure. The transmembrane portion of the ion channel, on each monomer, has four α-helices, colored blue.	+	The <scene name='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2'>glutamate-gated chloride channel</scene> is made up of <scene name='Sandbox_Reserved_686/Five_homologous_subunits/1'>five homologous subunits</scene>, as displayed by the different colorings. All the subunits are conserved structurally, but not necessarily in their amino acid sequence. Each monomer has <scene name='Sandbox_Reserved_686/Secondary_structures/2'>two domains</scene>. The extracellular domain is mainly β-pleated sheets, shown pink in the structure. The transmembrane portion of the ion channel, on each monomer, has four α-helices, colored blue. The α-helical portion of the subunit would not be accessible to solvent. The accessibility is not able to be shown in the 3D imagery.

	Ivermectin interacts within the lipid bilayer on the extracellular half. It inserts itself <scene name='Sandbox_Reserved_686/Between_subunits/1'>between two subunits</scene>, in the α-helices, to stabilize the open conformation of the ion channel (Ivermectin is brown, between a pink and tan subunit). There is a slight gapping evident between the two subunits, confirming that Ivermectin is opening up the channel. It is thought that the <scene name='Sandbox_Reserved_686/Serine_interaction/2'>interaction between serine 260 and Ivermectin</scene> is important in pulling those subunits open. With the subunits spread apart, the channel stays open longer, and has a higher affinity for glutamate.		Ivermectin interacts within the lipid bilayer on the extracellular half. It inserts itself <scene name='Sandbox_Reserved_686/Between_subunits/1'>between two subunits</scene>, in the α-helices, to stabilize the open conformation of the ion channel (Ivermectin is brown, between a pink and tan subunit). There is a slight gapping evident between the two subunits, confirming that Ivermectin is opening up the channel. It is thought that the <scene name='Sandbox_Reserved_686/Serine_interaction/2'>interaction between serine 260 and Ivermectin</scene> is important in pulling those subunits open. With the subunits spread apart, the channel stays open longer, and has a higher affinity for glutamate.

	With the channel stabilized in the open conformation by Ivermectin, chloride ions can freely flow into the cell. When the chloride ions are continually flowing, the polarization of the membrane is lost. This is how the parasitic microfilariae are killed. Their neurotransmission is severely inhibited. The microfilariae eventually die of flaccid paralysis. Ivermectin is often prescribed along with doxycycline in order to kill the ''Wolbachia'', as well.		With the channel stabilized in the open conformation by Ivermectin, chloride ions can freely flow into the cell. When the chloride ions are continually flowing, the polarization of the membrane is lost. This is how the parasitic microfilariae are killed. Their neurotransmission is severely inhibited. The microfilariae eventually die of flaccid paralysis. Ivermectin is often prescribed along with doxycycline in order to kill the ''Wolbachia'', as well.

Student at 22:22, 3 May 2013

Student — Fri, 03 May 2013 22:22:29 GMT

←Older revision		Revision as of 22:22, 3 May 2013
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	The <scene name='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2'>glutamate-gated chloride channel</scene> is made up of <scene name='Sandbox_Reserved_686/5_subunits_no_fab_cl/2'>five homologous subunits</scene>, as displayed by the different colorings. All the subunits are conserved structurally, but not necessarily in their amino acid sequence. Each monomer has <scene name='Sandbox_Reserved_686/Secondary_structures/2'>two domains</scene>. The extracellular domain is mainly β-pleated sheets, shown pink in the structure. The transmembrane portion of the ion channel, on each monomer, has four α-helices, colored blue.		The <scene name='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2'>glutamate-gated chloride channel</scene> is made up of <scene name='Sandbox_Reserved_686/5_subunits_no_fab_cl/2'>five homologous subunits</scene>, as displayed by the different colorings. All the subunits are conserved structurally, but not necessarily in their amino acid sequence. Each monomer has <scene name='Sandbox_Reserved_686/Secondary_structures/2'>two domains</scene>. The extracellular domain is mainly β-pleated sheets, shown pink in the structure. The transmembrane portion of the ion channel, on each monomer, has four α-helices, colored blue.

-	Ivermectin interacts within the lipid bilayer on the extracellular half. It inserts itself <scene name='Sandbox_Reserved_686/Between_subunits/1'>between two subunits</scene>, in the α-helices, to stabilize the open conformation of the ion channel (Ivermectin is brown, between a pink and tan subunit). There is a slight gapping evident between the two subunits, confirming that Ivermectin is opening up the channel. It is thought that the <scene name='Sandbox_Reserved_686/Serine_interaction/2'>interaction between serine 260 and Ivermectin</scene> is important in pulling those ~~subinits~~ open.	+	Ivermectin interacts within the lipid bilayer on the extracellular half. It inserts itself <scene name='Sandbox_Reserved_686/Between_subunits/1'>between two subunits</scene>, in the α-helices, to stabilize the open conformation of the ion channel (Ivermectin is brown, between a pink and tan subunit). There is a slight gapping evident between the two subunits, confirming that Ivermectin is opening up the channel. It is thought that the <scene name='Sandbox_Reserved_686/Serine_interaction/2'>interaction between serine 260 and Ivermectin</scene> is important in pulling those subunits open. With the subunits spread apart, the channel stays open longer, and has a higher affinity for glutamate.
		+
		+	With the channel stabilized in the open conformation by Ivermectin, chloride ions can freely flow into the cell. When the chloride ions are continually flowing, the polarization of the membrane is lost. This is how the parasitic microfilariae are killed. Their neurotransmission is severely inhibited. The microfilariae eventually die of flaccid paralysis. Ivermectin is often prescribed along with doxycycline in order to kill the ''Wolbachia'', as well.

Student at 22:13, 3 May 2013

Student — Fri, 03 May 2013 22:13:17 GMT

←Older revision		Revision as of 22:13, 3 May 2013
Line 13:		Line 13:
	==Mechanism==		==Mechanism==

-	The <scene name='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2'>glutamate-gated chloride channel</scene> is made up of <scene name='Sandbox_Reserved_686/5_subunits_no_fab_cl/2'>five homologous subunits</scene>, as displayed by the different colorings. All the subunits are conserved structurally, but not necessarily in their amino acid sequence. Each monomer has <scene name='Sandbox_Reserved_686/~~Full_basic_only_ivm_second_str~~/1'>two domains</scene>.	+	The <scene name='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2'>glutamate-gated chloride channel</scene> is made up of <scene name='Sandbox_Reserved_686/5_subunits_no_fab_cl/2'>five homologous subunits</scene>, as displayed by the different colorings. All the subunits are conserved structurally, but not necessarily in their amino acid sequence. Each monomer has <scene name='Sandbox_Reserved_686/Secondary_structures/2'>two domains</scene>. The extracellular domain is mainly β-pleated sheets, shown pink in the structure. The transmembrane portion of the ion channel, on each monomer, has four α-helices, colored blue.

-		+	Ivermectin interacts within the lipid bilayer on the extracellular half. It inserts itself <scene name='Sandbox_Reserved_686/Between_subunits/1'>between two subunits</scene>, in the α-helices, to stabilize the open conformation of the ion channel (Ivermectin is brown, between a pink and tan subunit). There is a slight gapping evident between the two subunits, confirming that Ivermectin is opening up the channel. It is thought that the <scene name='Sandbox_Reserved_686/Serine_interaction/2'>interaction between serine 260 and Ivermectin</scene> is important in pulling those subinits open.
-		+
-	<scene name='Sandbox_Reserved_686/~~Ivm_between_2_subunits~~/1'>in between</scene>	+

Student at 21:38, 3 May 2013

Student — Fri, 03 May 2013 21:38:08 GMT

←Older revision		Revision as of 21:38, 3 May 2013
Line 7:		Line 7:
	==Background==		==Background==

-	Ivermectin is an important pharmaceutical, used mainly as an anti-helminthic agent. It is a macrocyclic lactone, evidenced by its structure above, and a member of the larger category of avermectins. One of the most common ways Ivermectin is used, is to treat Onchocerciasis. Onchocerciasis, better known as River Blindness, is the second leading cause of infectious blindness in the world.	+	Ivermectin is an important pharmaceutical, used mainly as an anti-helminthic agent. It is a macrocyclic lactone, evidenced by its structure above, and a member of the larger category of avermectins. Ivermectin was discovered from ''Streptomyces avermitilis''. One of the most common ways Ivermectin is used, is to treat Onchocerciasis. Onchocerciasis, better known as River Blindness, is the second leading cause of infectious blindness in the world.

	''O. volvulus'' and ''Wolbachia'' are the infectious agents involved in this disease. ''Wolbachia'', the bacterial symbiont of ''O. volvulus'', is released when the worm dies and causes inflammation and keratitis. Ivermectin work to kills the ''O. volvulus'' microfilariae and prevent the female macrofilariae from producing more microfilariae. The drug interacts with the glutamate-gated chloride channel to accomplish this.		''O. volvulus'' and ''Wolbachia'' are the infectious agents involved in this disease. ''Wolbachia'', the bacterial symbiont of ''O. volvulus'', is released when the worm dies and causes inflammation and keratitis. Ivermectin work to kills the ''O. volvulus'' microfilariae and prevent the female macrofilariae from producing more microfilariae. The drug interacts with the glutamate-gated chloride channel to accomplish this.
Line 13:		Line 13:
	==Mechanism==		==Mechanism==

		+	The <scene name='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2'>glutamate-gated chloride channel</scene> is made up of <scene name='Sandbox_Reserved_686/5_subunits_no_fab_cl/2'>five homologous subunits</scene>, as displayed by the different colorings. All the subunits are conserved structurally, but not necessarily in their amino acid sequence. Each monomer has <scene name='Sandbox_Reserved_686/Full_basic_only_ivm_second_str/1'>two domains</scene>.



-	<scene name='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2'>Protein structure as crystallized</scene>
-	<scene name='Sandbox_Reserved_686/5_subunits_no_fab_cl/2'>5 parts</scene>
	<scene name='Sandbox_Reserved_686/Ivm_between_2_subunits/1'>in between</scene>		<scene name='Sandbox_Reserved_686/Ivm_between_2_subunits/1'>in between</scene>
-	<scene name='Sandbox_Reserved_686/Full_basic_only_ivm_second_str/1'>Secondary Structure</scene>

Student at 19:38, 3 May 2013

Student — Fri, 03 May 2013 19:38:13 GMT

←Older revision		Revision as of 19:38, 3 May 2013
Line 7:		Line 7:
	==Background==		==Background==

-	Ivermectin is an important pharmaceutical, used mainly as an anti-helminthic agent. It is a member of the larger category of avermectins. One of the most common ways Ivermectin is used, is to treat Onchocerciasis. Onchocerciasis, better known as River Blindness,	+	Ivermectin is an important pharmaceutical, used mainly as an anti-helminthic agent. It is a macrocyclic lactone, evidenced by its structure above, and a member of the larger category of avermectins. One of the most common ways Ivermectin is used, is to treat Onchocerciasis. Onchocerciasis, better known as River Blindness, is the second leading cause of infectious blindness in the world.
		+
		+	''O. volvulus'' and ''Wolbachia'' are the infectious agents involved in this disease. ''Wolbachia'', the bacterial symbiont of ''O. volvulus'', is released when the worm dies and causes inflammation and keratitis. Ivermectin work to kills the ''O. volvulus'' microfilariae and prevent the female macrofilariae from producing more microfilariae. The drug interacts with the glutamate-gated chloride channel to accomplish this.
		+
		+	==Mechanism==
		+
		+

Student at 04:06, 3 May 2013

Student — Fri, 03 May 2013 04:06:27 GMT

←Older revision		Revision as of 04:06, 3 May 2013
Line 7:		Line 7:
	==Background==		==Background==

-	~~[[Wikipedia:~~Ivermectin~~\|Ivermectin]]~~ is an important pharmaceutical, used mainly as an anti-helminthic agent. It is a member of the larger category of avermectins. One of the most common ways Ivermectin is used, is to treat ~~[[Wikipedia:Onchocerciasis\|~~Onchocerciasis]]. Onchocerciasis, better known as River Blindness,	+	Ivermectin is an important pharmaceutical, used mainly as an anti-helminthic agent. It is a member of the larger category of avermectins. One of the most common ways Ivermectin is used, is to treat Onchocerciasis. Onchocerciasis, better known as River Blindness,

Student at 03:58, 3 May 2013

Student — Fri, 03 May 2013 03:58:12 GMT

←Older revision		Revision as of 03:58, 3 May 2013
Line 7:		Line 7:
	==Background==		==Background==

-	[[Ivermectin]] is an important pharmaceutical, used mainly as an anti-helminthic agent. It is a member of the larger category of avermectins. One of the most common ways Ivermectin is used, is to treat [[Onchocerciasis]]. Onchocerciasis, better known as River Blindness,	+	[[Wikipedia:Ivermectin\|Ivermectin]] is an important pharmaceutical, used mainly as an anti-helminthic agent. It is a member of the larger category of avermectins. One of the most common ways Ivermectin is used, is to treat [[Wikipedia:Onchocerciasis\|Onchocerciasis]]. Onchocerciasis, better known as River Blindness,

Student at 03:54, 3 May 2013

Student — Fri, 03 May 2013 03:54:56 GMT

←Older revision		Revision as of 03:54, 3 May 2013
Line 7:		Line 7:
	==Background==		==Background==

-	Ivermectin is an important pharmaceutical, used mainly as an anti-helminthic agent.	+	[[Ivermectin]] is an important pharmaceutical, used mainly as an anti-helminthic agent. It is a member of the larger category of avermectins. One of the most common ways Ivermectin is used, is to treat [[Onchocerciasis]]. Onchocerciasis, better known as River Blindness,

Student at 03:49, 3 May 2013

Student — Fri, 03 May 2013 03:49:35 GMT

←Older revision		Revision as of 03:49, 3 May 2013
Line 3:		Line 3:
	<!-- PLEASE ADD YOUR CONTENT BELOW HERE -->		<!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
	=Ivermectin=		=Ivermectin=
-	[[Image:Ivermectin_skeletal.svg]]	+	[[Image:Ivermectin_skeletal.svg.png]]
	<Structure load='3RHW' size='500' frame='true' align='right' caption='Insert caption here' scene='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2' />		<Structure load='3RHW' size='500' frame='true' align='right' caption='Insert caption here' scene='Sandbox_Reserved_686/Full_basic_protein_only_ivm/2' />
	==Background==		==Background==