BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
N,N-deithyl-iododifluoroacetamide 1 reacted with alkenes,alkynes in aqueous aceto- nitrile solutions of sodium dithionite and sodium hydrogen carbonate at room temperature to give the corresponding adducts,thus consti...N,N-deithyl-iododifluoroacetamide 1 reacted with alkenes,alkynes in aqueous aceto- nitrile solutions of sodium dithionite and sodium hydrogen carbonate at room temperature to give the corresponding adducts,thus constituting a new method for introducing the CF_2 group into organic mol- ecules.Compound 1 reacted with conjugated olefins 2b,c to afford the iodine-free adducts 7b,c. The adducts 3d-f,from addition of 1 to alkenes 2d-f,could be converted into α,α-difluoro-γ- lactones 5d-f by treatment with silica gel.Compound 1 reacted with ethyl vinyl ether 2i to give aldehyde 8,and perfluoroalkyl or polyfluoroalkyl iodides reacted similarly.A radical mechanism was proposed for the addition reaction.Under the same condition,N,N-diethyl-bromodifluoroacetamide produced only the corresponding sulfinate Et_2NC(O)CF_2SO_2Na.展开更多
Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and dis...Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and disease,the search for new compounds that modulate these proteins is still relevant.Traditional medicine has long been a rich source of neuroactive compounds.For example,the indigenous Mapuche people have used the leaves and bark of the Drimys winteri tree for centuries to treat various diseases.Consequently,several studies have investigated the biological effects of compounds in Drimys winteri,highlighting sesquiterpenes such asα-humulene,drimenin,polygodial,andα-,β-,γ-eudesmol.However,there is currently no literature review focusing on the ability of these sesquiterpenes to modulate ion channels.This review summarizes the current knowledge about neuroactive compounds found in Drimys winteri,with special emphasis on their direct actions on neuronal ion channels.Several Drimys winteri sesquiterpenes modulate a diverse array of neuronal ion channels,including transient receptor potential channels,gamma-aminobutyric acid A receptors,nicotinic acetylcholine receptors,and voltage-dependent Ca^(2+)and Na^(+)channels.Interestingly,the modulation of these molecular targets by Drimys winteri sesquiterpenes correlates with their therapeutic actions.The promiscuous pharmacological profile of Drimys winteri sesquiterpenes suggests they modulate multiple protein targets in vivo,making them potentially useful for treating complex,multifactorial diseases.Further studies at the molecular level may aid in developing multitargeted drugs with enhanced therapeutic effects.展开更多
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
文摘N,N-deithyl-iododifluoroacetamide 1 reacted with alkenes,alkynes in aqueous aceto- nitrile solutions of sodium dithionite and sodium hydrogen carbonate at room temperature to give the corresponding adducts,thus constituting a new method for introducing the CF_2 group into organic mol- ecules.Compound 1 reacted with conjugated olefins 2b,c to afford the iodine-free adducts 7b,c. The adducts 3d-f,from addition of 1 to alkenes 2d-f,could be converted into α,α-difluoro-γ- lactones 5d-f by treatment with silica gel.Compound 1 reacted with ethyl vinyl ether 2i to give aldehyde 8,and perfluoroalkyl or polyfluoroalkyl iodides reacted similarly.A radical mechanism was proposed for the addition reaction.Under the same condition,N,N-diethyl-bromodifluoroacetamide produced only the corresponding sulfinate Et_2NC(O)CF_2SO_2Na.
基金supported by ANID-FONDECYT 1200908(to JF),ANID-FONDECYT 1211082 and 1250856(to GEY)by the Millennium Nucleus for the Study of Pain NCN19_038(Mi Nu SPain)(to GEY)funded by the ANID scholarship 21201176。
文摘Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and disease,the search for new compounds that modulate these proteins is still relevant.Traditional medicine has long been a rich source of neuroactive compounds.For example,the indigenous Mapuche people have used the leaves and bark of the Drimys winteri tree for centuries to treat various diseases.Consequently,several studies have investigated the biological effects of compounds in Drimys winteri,highlighting sesquiterpenes such asα-humulene,drimenin,polygodial,andα-,β-,γ-eudesmol.However,there is currently no literature review focusing on the ability of these sesquiterpenes to modulate ion channels.This review summarizes the current knowledge about neuroactive compounds found in Drimys winteri,with special emphasis on their direct actions on neuronal ion channels.Several Drimys winteri sesquiterpenes modulate a diverse array of neuronal ion channels,including transient receptor potential channels,gamma-aminobutyric acid A receptors,nicotinic acetylcholine receptors,and voltage-dependent Ca^(2+)and Na^(+)channels.Interestingly,the modulation of these molecular targets by Drimys winteri sesquiterpenes correlates with their therapeutic actions.The promiscuous pharmacological profile of Drimys winteri sesquiterpenes suggests they modulate multiple protein targets in vivo,making them potentially useful for treating complex,multifactorial diseases.Further studies at the molecular level may aid in developing multitargeted drugs with enhanced therapeutic effects.
