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3- antidotes against organophosphate intoxication
antagonist. Dases of0 or90 m+.9 wdr~administerdddrilyb~gavaps for 26 wwks. JGA hvpertrcchvwas accarem in histabcical sectbnr. lmmunohistochemislwend in situ hvtfldizstbn demc&raled on irv crease in Ihc number of renirwMtainiOg ccl15in bcth the Merant ar. and the intdcbular art&a. In concbrbn. JGA hypsrlmphq cawed as a result ct anta9onism of the angbtsnsin II recspto~ AsSOclatedvdthJGA hyportmphywasbcr(laSBdaxperrbn of bcathrenin and tenin mRNA. indicadvaof mimulatedrenin synthssiscaused bv an sxag9erated pharmacologicd rasponsa of renin-sacretingcelh to the 10950, ‘aedback inhibitb” byangbtansin II
and H22 oniv 18%. mapstiNstv Both compoundsrestcred completely lull naromuscularMack inducedwth TMPhF. &ww&:
orgwophosphais intaication: antiioles; ChE rcactivatcrs
teibtos
&ww&r renin
angictensin II antagonism: juxtaglocwubr
apparatus;
bony! (Kksuhstituted bispywdwwmmorwxmds wth ‘&tr&e as shown kbwwer~investig~tsdforlheirpharmaoobgicalandantidc~l prcperties in ordflr to ‘olbw Ihe str”ct”re-ac”“Ly relationships(SAR,.
G.ph Dragval.kf. Babiclwva.A.Ya. Podwshnisk.A.G. Pato~. Irrsrilvtsoftlo& nrmeds@wMcMd L.1..llk&ne. Kiev Epwide materials are widely used for equipmanl and capacities protecl~oninfcodindustrv.Oneofthemontim~onamccmwnentotthess roarings is epichbmh~flrinIEClH). Till n&ccbrim& mathods werez used for datarminaricncf trace quumitios of EClH in water wrlutbns. !A’@studii characteristbsof EC1Ii in dKferantmedia imitatingfood prodwas It is ahorn that in acid Comahina ~o!Utlom ECtH turris into dichbrchydrin dependiw on time. Gss-chiomatwraphii methods w8re efaborated,or determbatbn Of tb%e Subfllrv%s. The e,,ance of this m&cd ccmists in imenctbn with chbmhydrb cr brcmhydrii acids lar obtaining of EClH derivative.?. which are then conesntraied and determined. Fer increasing of id+RYIEdlH)nraIlability chrcmal~ graphic chanctaristbr of sanw glvDerclderfvatiws cn two tobmns of diiennt polarity were detarmined using ftamebnizatbn and permawnt recombinaticawbc~ detectors. EClH and its daivstivas determinatbn limit b c.Ol~.MI1 mgMm3 dapendicg on deriativas structure and detactom applied
LOM of the cor”c+wndsfor 24 h wore betwee” SOand 198 rraRc in formatiOn of air snvimnmsm quality onthe bwaoreysd objects of wooden hcurebuildinrr a leadiic rM bebncs to some cc_ric material* and ihe con&tiins L&sodWI theiatter ones &&ced tih appkcatbn of earbcmidcfcnaldshyda resins. We have c&&d outscmehyp[enlcsv-cnide~npindwrair~lutioncf named abii. located in S~twua rwbnr. Accountin fcrmuls compass ticncf chipboards.foam plastb utilizedintkmwcodenhouoesbuilding formaldehydeccment in the indoor air was d6lermined. For lhls three m&cdsof the indlrafed pallufant testktg wxe us& photcccbrimmrb (with acstv(acetone solution). gas chmmatagrahic (formetdshyds reacrbn with 2. 4.dinitrcchenYlhvdrazfn~Lthirrlavar chromatccrachv +zxmvenioninto tormaldi&d&~FCrfd8~e &msnt in the%& air was idenUfiedto be axceeded in the maiorii of casas l~fold. Asa result of curtsrtsthag~?rchmrmtopraphictschniquawasfound to bsmcreprbritatii in twmsldehydedotermindlbn, Hcwcver. white conductingthe field-kindruwys. the phctcccbrimetric test was estimated M a swc&ul ens.
ttw
the IaM. IbM &bstiiutbn. Best reslcratbn cf neuromuscularblock induced by 1.22.1rimetfiylpm~meth~ph~phonotlw~datw ITMPHFt was achiid with (bYM detivativas. Antxbtal atlactivanasa of th8 oxinws against TMPhF-poisoning was in the same order for all ccmpounds tested but ntb5t pmnounced by la)2 CC. The resultsobtained ~os_tramadifferent mechanwns cl antidata, act,on of ,a)2 and ,#-I &words: craanophosphate ~rdcxic~ticn:antidotes:ChE reaetfvators: structurp-aciitity relationships
The “H”-s&-s oximeseonsiPtof modifiad bisppyridinium mcmo~xlme and were suparior tc other conventional cholinesterase r(~ftiialcrs in the treatmknt cl intoxbatbns with highly tcnb crgac+msphates such 1. 2. 2-trimethvlpropyl methvlph~phonofluoridsls (TMPhFl. Two of these axime4bi~2-hydrc~imin~~~~imum-l-mathyl) ether diibdlde lH221 and 12.~rcxvimlnwnethyl-~idinium-1.melhyll 13h~ro~mimme~ylpyrMin~~m.l-me~yl~ ether diiodida IH23). were sVntheri~ld~ndstudisdtwtheirpharmaoolopicalandantido~alpmperices LDSDaner i p. applitatbn in mice cf H22 and H23 were 192 and 142 ma&! b.w.. respectively.Both compamds inhibid in vitroacetyfchO(~rwsterass lAChE)actwity- IC50 wsreO.29.dO.15 mmcbs,l lo, H22acdH23.mspactiue~. OnlyH23passssMda~ickeholinolylhicsc. ti& after swam of rat leum induced in via0 with acetvfchclina H22 and srpecitlly H23 were more effectivethan toxcgonin’altar imcxbrtica withTMPhF and itoprodmelhylphoDphoroflwridats(~PMPhF). H23 reactiMted !n vitro 70% of AChE-activity,inhibited with CPMPhF,
The prssanr ~Cutfvinvestigatedthe &fact of long4Crm administratbn of cardioprctectivedrug aobadina ISTB) to dams cn selectivepanma~rs~tsponlaneousbehaviouroftheiroffspringinopnfield(fnqusn~~ and durationof grccming. frequencyof motor and vwtbat expbramry aclivifK durationcfacriwttyandimmaksibty)iest%dC~~ dayBoot ags.Ths lnatment of dams with ST6 si@csmfy ~ncressedspmanwur mw tar activityct cffspriw in bath sexes. The other parameterswre not alfected. with exceptionof a significant increasein theirequencyarr.i duratiin cf grcuming in femabs compared to males fmm STB treated dams. Keywcnls:stobadine; opontaw~us behavi~ur;rat; offspring
and H22 oniv 18%. mapstiNstv Both compoundsrestcred completely lull naromuscularMack inducedwth TMPhF. &ww&:
orgwophosphais intaication: antiioles; ChE rcactivatcrs
teibtos
&ww&r renin
angictensin II antagonism: juxtaglocwubr
apparatus;
bony! (Kksuhstituted bispywdwwmmorwxmds wth ‘&tr&e as shown kbwwer~investig~tsdforlheirpharmaoobgicalandantidc~l prcperties in ordflr to ‘olbw Ihe str”ct”re-ac”“Ly relationships(SAR,.
G.ph Dragval.kf. Babiclwva.A.Ya. Podwshnisk.A.G. Pato~. Irrsrilvtsoftlo& nrmeds@wMcMd L.1..llk&ne. Kiev Epwide materials are widely used for equipmanl and capacities protecl~oninfcodindustrv.Oneofthemontim~onamccmwnentotthess roarings is epichbmh~flrinIEClH). Till n&ccbrim& mathods werez used for datarminaricncf trace quumitios of EClH in water wrlutbns. !A’@studii characteristbsof EC1Ii in dKferantmedia imitatingfood prodwas It is ahorn that in acid Comahina ~o!Utlom ECtH turris into dichbrchydrin dependiw on time. Gss-chiomatwraphii methods w8re efaborated,or determbatbn Of tb%e Subfllrv%s. The e,,ance of this m&cd ccmists in imenctbn with chbmhydrb cr brcmhydrii acids lar obtaining of EClH derivative.?. which are then conesntraied and determined. Fer increasing of id+RYIEdlH)nraIlability chrcmal~ graphic chanctaristbr of sanw glvDerclderfvatiws cn two tobmns of diiennt polarity were detarmined using ftamebnizatbn and permawnt recombinaticawbc~ detectors. EClH and its daivstivas determinatbn limit b c.Ol~.MI1 mgMm3 dapendicg on deriativas structure and detactom applied
LOM of the cor”c+wndsfor 24 h wore betwee” SOand 198 rraRc in formatiOn of air snvimnmsm quality onthe bwaoreysd objects of wooden hcurebuildinrr a leadiic rM bebncs to some cc_ric material* and ihe con&tiins L&sodWI theiatter ones &&ced tih appkcatbn of earbcmidcfcnaldshyda resins. We have c&&d outscmehyp[enlcsv-cnide~npindwrair~lutioncf named abii. located in S~twua rwbnr. Accountin fcrmuls compass ticncf chipboards.foam plastb utilizedintkmwcodenhouoesbuilding formaldehydeccment in the indoor air was d6lermined. For lhls three m&cdsof the indlrafed pallufant testktg wxe us& photcccbrimmrb (with acstv(acetone solution). gas chmmatagrahic (formetdshyds reacrbn with 2. 4.dinitrcchenYlhvdrazfn~Lthirrlavar chromatccrachv +zxmvenioninto tormaldi&d&~FCrfd8~e &msnt in the%& air was idenUfiedto be axceeded in the maiorii of casas l~fold. Asa result of curtsrtsthag~?rchmrmtopraphictschniquawasfound to bsmcreprbritatii in twmsldehydedotermindlbn, Hcwcver. white conductingthe field-kindruwys. the phctcccbrimetric test was estimated M a swc&ul ens.
ttw
the IaM. IbM &bstiiutbn. Best reslcratbn cf neuromuscularblock induced by 1.22.1rimetfiylpm~meth~ph~phonotlw~datw ITMPHFt was achiid with (bYM detivativas. Antxbtal atlactivanasa of th8 oxinws against TMPhF-poisoning was in the same order for all ccmpounds tested but ntb5t pmnounced by la)2 CC. The resultsobtained ~os_tramadifferent mechanwns cl antidata, act,on of ,a)2 and ,#-I &words: craanophosphate ~rdcxic~ticn:antidotes:ChE reaetfvators: structurp-aciitity relationships
The “H”-s&-s oximeseonsiPtof modifiad bisppyridinium mcmo~xlme and were suparior tc other conventional cholinesterase r(~ftiialcrs in the treatmknt cl intoxbatbns with highly tcnb crgac+msphates such 1. 2. 2-trimethvlpropyl methvlph~phonofluoridsls (TMPhFl. Two of these axime4bi~2-hydrc~imin~~~~imum-l-mathyl) ether diibdlde lH221 and 12.~rcxvimlnwnethyl-~idinium-1.melhyll 13h~ro~mimme~ylpyrMin~~m.l-me~yl~ ether diiodida IH23). were sVntheri~ld~ndstudisdtwtheirpharmaoolopicalandantido~alpmperices LDSDaner i p. applitatbn in mice cf H22 and H23 were 192 and 142 ma&! b.w.. respectively.Both compamds inhibid in vitroacetyfchO(~rwsterass lAChE)actwity- IC50 wsreO.29.dO.15 mmcbs,l lo, H22acdH23.mspactiue~. OnlyH23passssMda~ickeholinolylhicsc. ti& after swam of rat leum induced in via0 with acetvfchclina H22 and srpecitlly H23 were more effectivethan toxcgonin’altar imcxbrtica withTMPhF and itoprodmelhylphoDphoroflwridats(~PMPhF). H23 reactiMted !n vitro 70% of AChE-activity,inhibited with CPMPhF,
The prssanr ~Cutfvinvestigatedthe &fact of long4Crm administratbn of cardioprctectivedrug aobadina ISTB) to dams cn selectivepanma~rs~tsponlaneousbehaviouroftheiroffspringinopnfield(fnqusn~~ and durationof grccming. frequencyof motor and vwtbat expbramry aclivifK durationcfacriwttyandimmaksibty)iest%dC~~ dayBoot ags.Ths lnatment of dams with ST6 si@csmfy ~ncressedspmanwur mw tar activityct cffspriw in bath sexes. The other parameterswre not alfected. with exceptionof a significant increasein theirequencyarr.i duratiin cf grcuming in femabs compared to males fmm STB treated dams. Keywcnls:stobadine; opontaw~us behavi~ur;rat; offspring