oxygen kinetics Dotaz Zobrazit nápovědu
Stobadín, (-)-cis - 2,8-dimetyl - 2,3,4,4a,5,9b-hexahydro-lH - pyridol[4,3b]-indol je látka s potenciálnym antiarytmickým, antihistamínovým, anestetickým, antiulceróznym a významným antioxidačným účinkom. N5-acylsubstitúciou stobadínu boli pripravené deriváty, ktoré predstavujú prodrug formy aktívnej substancie - stobadínu - pričom sa predpokladá, že sa v organizme budú hydrolyzovať a aktívna látka sa bude uvoľňovať vo vyšších koncentráciách v rôznych biologických tkarúvách. Predkladaná práca sa zaoberá sledovanímkinetikyhydrolýzy 13 acylderivátov stobadínu v prostredí 0,1 molA hydroxidu sodného pri teplote 70 'C spektrofotometricky v UF oblasti spektra. Stanovené rýchlostné konštant>ty sa korelovali s dĺžkou postranného acylového reťazca a hodnotami pKa študovaných látok.
Stobadin, (-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-lH-pyridol[4,3b]-indol is a compound with a potential antiarrhythmic, antihistamine, anaesthetic, antiulcerous, and marked antioxidative effect. N5-acylsubstitution of stobadin yielded derivatives, which represent prodrug forms of the active principle - stobadin, and it is assumed that they will be hydrolysed in the organism and the active principle will be released in higher concentrations in various biological tissues. The present paper deals with the investigation of the kinetics of hydrolysis of 13 stobadin acylderivatives in a medium of 0.1 molA of sodium hydroxide at 70 °C, employing spectrophotometry in the UV region of the spectrum. The determined rate constants were correlated with the length of the side acyl chain and the pKa values of the compounds under study.
[1st ed.] XXVIII, 377 s. : obr., tab., grafy ; 25 cm
- MeSH
- fyziologie buňky MeSH
- fyziologie krevního oběhu a dýchání MeSH
- kinetika MeSH
- kyslík fyziologie MeSH
- Publikační typ
- kongresy MeSH
- sborníky MeSH
- Konspekt
- Fyziologie člověka a srovnávací fyziologie
- NLK Obory
- fyziologie
Stobadín, (-)-cis-2,8-dimetyl-2,3,4,4a,5,9b-hexahydro-lH-pyrido[4,3b]-indol, je látka s potenciálnym antiarytmickým a antihypoxickým účinkom, u ktorej bol zistený aj výrazný účinok na vychytávanie voľných kyslíkových radikálov. Pripravili sa acylderiváty stobadínu a predpokladá sa, že aktívne liečivo sa z nich uvoľní hydrolýzou v rôznych biologických tkanivách. V práci sledujeme kinetiku kyslej hydrolýzy 13 acylderivátov stobadínu. Rozklad látok sme študovali v prostredí kyseliny chlorovodíkovej 0,1 mol.l-1 pri 20 a 70 °C spektrofotometricky v UF oblasti a stanovili sme rýchlostné konštanty hydrolýzy. Metódami tenkovrstvovej a plynovej chromatografie sme potvrdili, že hydrolýzou sa z prodrug formy uvoľní stobadín.
Stobadine, (-)-cis-2,8-dimethyl-2,3,4,4a,5,9a-hexahydro-lH-pyrido[4,3b]-indole, is a substance with potential antiarrhythmic and antihypoxic effects, in which also a marked effect on scavengers of free oxygen radicals was found. Stobadine acylderivatives were prepared and it is assumed that the active principle will be released from them by hydrolysing in various biological tissues. The present paper examines the kinetics of acid hydrolysis of 13 stobadine derivatives. Decomposition of substances was studied in the medium of hydrochloric acid 0.1 ml.l-l at 20 and 70 °C spectrophotometrically in the UV region and rate constants of hydrolysis were determined. The methods of thin-layer and gas chromatography confirmed that stobadine is released from the prodrug form.
- Klíčová slova
- STOBADIN,
- MeSH
- antiarytmika MeSH
- antioxidancia MeSH
- hydrolýza MeSH
- karboliny farmakokinetika MeSH
- scavengery volných radikálů MeSH
KEY POINTS: Spinal treatment can restore diaphragm function in all animals 1 month following C2 hemisection induced paralysis. Greater recovery occurs the longer after injury the treatment is applied. Through advanced assessment of muscle mechanics, innovative histology and oxygen tension modelling, we have comprehensively characterized in vivo diaphragm function and phenotype. Muscle work loops reveal a significant deficit in diaphragm functional properties following chronic injury and paralysis, which are normalized following restored muscle activity caused by plasticity-induced spinal reconnection. Injury causes global and local alterations in diaphragm muscle vascular supply, limiting oxygen diffusion and disturbing function. Restoration of muscle activity reverses these alterations, restoring oxygen supply to the tissue and enabling recovery of muscle functional properties. There remain metabolic deficits following restoration of diaphragm activity, probably explaining only partial functional recovery. We hypothesize that these deficits need to be resolved to restore complete respiratory motor function. ABSTRACT: Months after spinal cord injury (SCI), respiratory deficits remain the primary cause of morbidity and mortality for patients. It is possible to induce partial respiratory motor functional recovery in chronic SCI following 2 weeks of spinal neuroplasticity. However, the peripheral mechanisms underpinning this recovery are largely unknown, limiting development of new clinical treatments with potential for complete functional restoration. Utilizing a rat hemisection model, diaphragm function and paralysis was assessed and recovered at chronic time points following trauma through chondroitinase ABC induced neuroplasticity. We simulated the diaphragm's in vivo cyclical length change and activity patterns using the work loop technique at the same time as assessing global and local measures of the muscles histology to quantify changes in muscle phenotype, microvascular composition, and oxidative capacity following injury and recovery. These data were fed into a physiologically informed model of tissue oxygen transport. We demonstrate that hemidiaphragm paralysis causes muscle fibre hypertrophy, maintaining global oxygen supply, although it alters isolated muscle kinetics, limiting respiratory function. Treatment induced recovery of respiratory activity normalized these effects, increasing oxygen supply, restoring optimal diaphragm functional properties. However, metabolic demands of the diaphragm were significantly reduced following both injury and recovery, potentially limiting restoration of normal muscle performance. The mechanism of rapid respiratory muscle recovery following spinal trauma occurs through oxygen transport, metabolic demand and functional dynamics of striated muscle. Overall, these data support a systems-wide approach to the treatment of SCI, and identify new targets to mediate complete respiratory recovery.
- MeSH
- bránice * MeSH
- kinetika MeSH
- krysa rodu rattus MeSH
- kyslík MeSH
- lidé MeSH
- mícha MeSH
- nervus phrenicus MeSH
- obnova funkce MeSH
- poranění míchy * MeSH
- potkani Sprague-Dawley MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- nemoci z povolání MeSH
- oxymetrie metody MeSH
- silikóza MeSH
- spirometrie MeSH
- Publikační typ
- srovnávací studie MeSH
Pyridoindolový derivát stobadín, [(-)-cis-2,8-dimetyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3b]-indol]je perspektívne antiarytmikum, antihistaminikum, anestetikum, antiulcerózum so schopnosťou vychytávať voľné kyslíkové radikály. Boli pripravené prodrug formy – N(5) - acylsubstituovaný stobadín – aktívnej substancie – stobadínu – pričom sa predpokladá, že sa v organizme budúhydrolyzovať a aktívna látka sa bude uvoľňovať vo vyšších koncentráciách v rôznych biologických tkanivách. Predkladaná práca sa zaoberá sledovaním kinetiky hydrolýzy 13 acylderivátov stobadínuv prostredí tlmivého roztoku o pH 7 pri teplote 70 °C a 75 °C spektrofotometricky v UF oblastispektra. Stanovené rýchlostné konštanty sa korelovali s dĺžkou postranného acylového reťazcaa hodnotami pKa študovaných látok. Stanovil sa profil log k – pH látok.
The pyridoindole derivative stobadin, [(-)-cis-2,8-dimetyl-2,3,4,4a,5,9b-hexahydro-lH-pyrido[4,3b]-indole] is a perspective antiarrhythmic, antihistamine, anaesthetic, antiulcerous drug capable of extinguishing free oxygen radical. Its prodrug forms - N(5)' acyl-substituted stobadine - of the active substance - stobadine - have been prepared and it is assumed that the will be hydrolyzed in the organism and the active substance will be released in higher concentrations in different biological tissues. The present paper is concerned with the investigation of the kinetics of the hydrolysis of 13 acyl derivatives of stobadine in the medium of a buffer solution of pH 7 at temperatures of 70 °C and 75 °C spectrophotometrically in the UV regioi ion of the spectrum. The determined rate constants were correlated with the length of the side acyl chain and the pKa values of the drugs under study. The profile of log k - pH of substances was determined.
