33 research outputs found
Mitochondriotropic and Cardioprotective Effects of Triphenylphosphonium-Conjugated Derivatives of the Diterpenoid Isosteviol
Mitochondria play a crucial role in the cell fate; in particular, reducing the accumulation of calcium in the mitochondrial matrix offers cardioprotection. This affect is achieved by a mild depolarization of the mitochondrial membrane potential, which prevents the assembly and opening of the mitochondrial permeability transition pore. For this reason, mitochondria are an attractive target for pharmacological interventions that prevent ischaemia/reperfusion injury. Isosteviol is a diterpenoid created from the acid hydrolysis of Steviarebaudiana Bertoni (fam. Asteraceae) glycosides that has shown protective effects against ischaemia/reperfusion injury, which are likely mediated through the activation of mitochondrial adenosine tri-phosphate (ATP)-sensitive potassium (mitoKATP) channels. Some triphenylphosphonium (triPP)-conjugated derivatives of isosteviol have been developed, and to evaluate the possible pharmacological benefits that result from these synthetic modifications, in this study, the mitochondriotropic properties of isosteviol and several triPP-conjugates were investigated in rat cardiac mitochondria and in the rat heart cell line H9c2. This study's main findings highlight the ability of isosteviol to depolarize the mitochondrial membrane potential and reduce calcium uptake by the mitochondria, which are typical functions of mitochondrial potassium channel openings. Moreover, triPP-conjugated derivatives showed a similar behavior to isosteviol but at lower concentrations, indicative of their improved uptake into the mitochondrial matrix. Finally, the cardioprotective property of a selected triPP-conjugated derivative was demonstrated in an in vivo model of acute myocardial infarct
ΠΠΠΠΠΠ§ΠΠ‘ΠΠΠ Π‘ΠΠ£Π§ΠΠ ΠΠΠΠΠΠΠ‘ΠΠ£ΠΠ―Π ΠΠΠΠ ΠΠΠ§ΠΠΠΠ― ΠΠΠ‘Π’Π’Π ΠΠΠΠΠ’ΠΠ§ΠΠ‘ΠΠΠ ΠΠΠΠΠ ΠΠΠΠ« ΠΠΠ§ΠΠ§ΠΠΠ ΠΠ Π’ΠΠ ΠΠ
Introduction. Aneurysm of renal artery is a rare and complex pathology of renal bloodstream. Large percentage of observations show that renal artery aneurysms are iatrogenic and happen due to urological interventions. Traumatic aneurysms are much less frequent. By the nature of the blood supply arterial aneurysms are subdiveded into those, which occur when the injured organ is only artery and arteriovenous aneurysms that occur while an artery is damaged along with the accompanying veins. Aneurysms may be treated only surgically, and the only exception is pregnancy. It is possible to use the open treatment option such as aneurysm resection with prosthetics, reanastomosing or its collateral plastics of the renal artery; exclusion of aneurysm with shunting of renal artery or its branches; resection of aneurysm with anastomosing of artery with azygos splanchnic arteries; complex reconstruction using autovein or internal iliac artery segment; including kidney resection at local infarction or nephrectomy in the case of evident nephrosclerosis.Materials and methods. This paper presents a clinical case of successful minimally invasive surgical treatment of traumatic aneurysm of renal artery. It was carried out through stenting of the right lowpolar renal artery: a coronary sheath was used to transfuse and implant the Explorer-Itgimedical Aneugraft 3.0 * 18.0 mm graft-system; the stent-graft was implanted into the right lowpolar renal artery so that it covers the aneurysm ostium. Results. The above case shows the possibility to successfully apply the endovascular method to treat posttraumatic aneurysms of renal arteries with derivative circulation.Conclusion. This technique can be safely and successfully used as an alternative to the traditional Β«openΒ» surgery, as it is minimally invasive, and allows performing a complete blockade of the pathological blood flow and to avoid an additional operating trauma and compromenation of distal branches.Β ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΠ½Π΅Π²ΡΠΈΠ·ΠΌΠ° ΠΏΠΎΡΠ΅ΡΠ½ΡΡ
Π°ΡΡΠ΅ΡΠΈΠΉ β ΡΠ΅Π΄ΠΊΠ°Ρ ΠΈ ΡΠ»ΠΎΠΆΠ½Π°Ρ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡ ΡΠΎΡΡΠ΄ΠΈΡΡΠΎΠ³ΠΎ ΡΡΡΠ»Π° ΠΏΠΎΡΠΊΠΈ. Π Π±ΠΎΠ»ΡΡΠΎΠΌ ΠΏΡΠΎΡΠ΅Π½ΡΠ΅ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΠΉ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌΡ ΠΏΠΎΡΠ΅ΡΠ½ΡΡ
Π°ΡΡΠ΅ΡΠΈΠΉ ΡΠ²Π»ΡΡΡΡΡ ΡΡΡΠΎΠ³Π΅Π½Π½ΡΠΌΠΈ, Π²ΠΎΠ·Π½ΠΈΠΊΠ°ΡΡΠΈΠΌΠΈ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΈΠ½ΡΠ΅ΡΠ²Π΅Π½ΡΠΈΠΎΠ½Π½ΡΡ
ΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π²ΠΌΠ΅ΡΠ°ΡΠ΅Π»ΡΡΡΠ². Π’ΡΠ°Π²ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌΡ Π²ΡΡΡΠ΅ΡΠ°ΡΡΡΡ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΡΠ΅ΠΆΠ΅. ΠΠΎ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΡ ΠΊΡΠΎΠ²ΠΎΡΠ½Π°Π±ΠΆΠ΅Π½ΠΈΡ ΡΠ°Π·Π»ΠΈΡΠ°ΡΡ Π°ΡΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΠ΅ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌΡ, Π²ΠΎΠ·Π½ΠΈΠΊΠ°ΡΡΠΈΠ΅ ΠΏΡΠΈ ΡΠ°Π½Π΅Π½ΠΈΠΈ ΡΠΎΠ»ΡΠΊΠΎ Π°ΡΡΠ΅ΡΠΈΠΈ, ΠΈ Π°ΡΡΠ΅ΡΠΈΠΎΠ²Π΅Π½ΠΎΠ·Π½ΡΠ΅ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌΡ, Π²ΠΎΠ·Π½ΠΈΠΊΠ°ΡΡΠΈΠ΅ ΠΏΡΠΈ ΠΎΠ΄Π½ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΌ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΠΈ Π°ΡΡΠ΅ΡΠΈΠΈ ΠΈ ΡΠΎΠΏΡΡΡΡΠ²ΡΡΡΠ΅ΠΉ Π²Π΅Π½Ρ. ΠΠ΅ΡΠ΅Π½ΠΈΠ΅ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎ ΡΠΎΠ»ΡΠΊΠΎ Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΠΏΠΎΡΠΎΠ±ΠΎΠΌ, ΠΈΡΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅ΠΌ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠΎΠ»ΡΠΊΠΎ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΡΡΡ. ΠΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΎΡΠΊΡΡΡΡΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π»Π΅ΡΠ΅Π½ΠΈΡ, ΡΠ°ΠΊΠΈΡ
ΠΊΠ°ΠΊ ΡΠ΅Π·Π΅ΠΊΡΠΈΡ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌΡ Ρ ΠΏΡΠΎΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ, ΡΠ΅Π°Π½Π°ΡΡΠΎΠΌΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΈΠ»ΠΈ Π΅Π΅ Π±ΠΎΠΊΠΎΠ²ΠΎΠΉ ΠΏΠ»Π°ΡΡΠΈΠΊΠΎΠΉ ΠΏΠΎΡΠ΅ΡΠ½ΠΎΠΉ Π°ΡΡΠ΅ΡΠΈΠΈ; Π²ΡΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌΡ Ρ ΡΡΠ½ΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΠΎΡΠ΅ΡΠ½ΠΎΠΉ Π°ΡΡΠ΅ΡΠΈΠΈ ΠΈΠ»ΠΈ Π΅Π΅ Π²Π΅ΡΠ²Π΅ΠΉ; ΡΠ΅Π·Π΅ΠΊΡΠΈΡ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌΡ Ρ Π°Π½Π°ΡΡΠΎΠΌΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°ΡΡΠ΅ΡΠΈΠΈ Ρ Π½Π΅ΠΏΠ°ΡΠ½ΡΠΌΠΈ Π²ΠΈΡΡΠ΅ΡΠ°Π»ΡΠ½ΡΠΌΠΈ Π°ΡΡΠ΅ΡΠΈΡΠΌΠΈ; ΡΠ»ΠΎΠΆΠ½ΡΠ΅ ΡΠ΅ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°ΡΡΠΎΠ²Π΅Π½Ρ ΠΈΠ»ΠΈ ΡΠ΅Π³ΠΌΠ΅Π½ΡΠ° Π²Π½ΡΡΡΠ΅Π½Π½Π΅ΠΉ ΠΏΠΎΠ΄Π²Π·Π΄ΠΎΡΠ½ΠΎΠΉ Π°ΡΡΠ΅ΡΠΈΠΈ; Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠ΅Π·Π΅ΠΊΡΠΈΠΈ ΠΏΠΎΡΠΊΠΈ ΠΏΡΠΈ Π»ΠΎΠΊΠ°Π»ΡΠ½ΠΎΠΌ ΠΈΠ½ΡΠ°ΡΠΊΡΠ΅ ΠΈΠ»ΠΈ Π½Π΅ΡΡΡΠΊΡΠΎΠΌΠΈΠΈ Π² ΡΠ»ΡΡΠ°Π΅ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΠ³ΠΎ Π½Π΅ΡΡΠΎΡΠΊΠ»Π΅ΡΠΎΠ·Π°.Β ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠ»ΡΡΠ°ΠΉ ΡΡΠΏΠ΅ΡΠ½ΠΎΠ³ΠΎ ΠΌΠ°Π»ΠΎΠΈΠ½Π²Π°Π·ΠΈΠ²Π½ΠΎΠ³ΠΎ Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π»Π΅ΡΠ΅Π½ΠΈΡ ΡΡΠ°Π²ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌΡ ΠΏΠΎΡΠ΅ΡΠ½ΠΎΠΉ Π°ΡΡΠ΅ΡΠΈΠΈ. ΠΠ»Ρ ΡΡΠΎΠ³ΠΎ Π²ΡΠΏΠΎΠ»Π½Π΅Π½ΠΎ ΡΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠ°Π²ΠΎΠΉ Π½ΠΈΠΆΠ½Π΅ΠΏΠΎΠ»ΡΡΠ½ΠΎΠΉ ΠΏΠΎΡΠ΅ΡΠ½ΠΎΠΉ Π°ΡΡΠ΅ΡΠΈΠΈ: ΠΏΠΎ ΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΠΎΠΌΡ ΠΏΡΠΎΠ²ΠΎΠ΄Π½ΠΈΠΊΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π° ΠΈ ΠΈΠΌΠΏΠ»Π°Π½ΡΠΈΡΠΎΠ²Π°Π½Π° Π³ΡΠ°ΡΡ-ΡΠΈΡΡΠ΅ΠΌΠ° Itgimedical Aneugraft 3,0*18,0 ΠΌΠΌ β ΡΡΠ΅Π½Ρ-Π³ΡΠ°ΡΡ ΠΈΠΌΠΏΠ»Π°Π½ΡΠΈΡΠΎΠ²Π°Π½ Π² Π½ΠΈΠΆΠ½Π΅ΠΏΠΎΠ»ΡΡΠ½ΡΡ ΠΏΡΠ°Π²ΡΡ ΠΏΠΎΡΠ΅ΡΠ½ΡΡ Π°ΡΡΠ΅ΡΠΈΡ Ρ ΠΏΠ΅ΡΠ΅ΠΊΡΡΡΠΈΠ΅ΠΌ ΡΠ΅ΠΉΠΊΠΈ Π°Π½Π΅Π²ΡΠΈΠ·ΠΌΡ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΠΈΠ²Π΅Π΄Π΅Π½Π½ΡΠΉ ΡΠ»ΡΡΠ°ΠΉ ΠΏΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΡΠΏΠ΅ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠ½Π΄ΠΎΠ²Π°ΡΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ ΠΌΠ΅ΡΠΎΠ΄Π° Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΠΎΡΡΡΡΠ°Π²ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π°Π½Π΅Π²ΡΠΈΠ·ΠΌ ΠΏΠΎΡΠ΅ΡΠ½ΡΡ
Π°ΡΡΠ΅ΡΠΈΠΉ Ρ Π°ΡΡΠ΅ΡΠΈΠΎΠ²Π΅Π½ΠΎΠ·Π½ΡΠΌ ΡΠ±ΡΠΎΡΠΎΠΌ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ°Π½Π½Π°Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° ΠΌΠΎΠΆΠ΅Ρ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎ ΠΈ Ρ ΡΡΠΏΠ΅Ρ
ΠΎΠΌ ΠΏΡΠΈΠΌΠ΅Π½ΡΡΡΡΡ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ Π°Π»ΡΡΠ΅ΡΠ½Π°ΡΠΈΠ²Ρ ΡΡΠ°Π΄ΠΈΡΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ Β«ΠΎΡΠΊΡΡΡΠΎΠ³ΠΎΒ» Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π²ΠΌΠ΅ΡΠ°ΡΠ΅Π»ΡΡΡΠ²Π°, ΠΏΠΎΡΠΊΠΎΠ»ΡΠΊΡ ΠΎΠ½Π° ΠΌΠ°Π»ΠΎΠΈΠ½Π²Π°Π·ΠΈΠ²Π½Π°, ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ Π²ΡΠΏΠΎΠ»Π½ΡΡΡ ΠΏΠΎΠ»Π½ΡΡ Π±Π»ΠΎΠΊΠ°Π΄Ρ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΊΡΠΎΠ²ΠΎΡΠΎΠΊΠ°, ΠΈΠ·Π±Π΅Π³Π°ΡΡ Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΡΠ°Π²ΠΌΡ ΠΈ ΠΊΠΎΠΌΠΏΡΠΎΠΌΠ΅ΡΠ°ΡΠΈΠΈ Π΄ΠΈΡΡΠ°Π»ΡΠ½ΡΡ
Π²Π΅ΡΠ²Π΅ΠΉ.
Antiviral nucleoside analogs
[Figure not available: see fulltext.] The minireview surveys the modification of native nucleosides as a result of which huge libraries of nucleoside analogs of various structures were synthesized. Particular attention is paid to the synthesis of the so-called prodrug forms of nucleoside analogs which ensure their penetration into the cell and metabolism to active 5'-triphosphate derivatives. All the best known antiviral cyclic nucleoside analogs approved for the treatment of HIV infections, hepatitis B, C, and influenza since the 1960s, as well as those in various stages of clinical trials in recent years, are listed. Nucleoside analogs that have shown the ability to inhibit the replication of SARS-CoV and MERS-CoV are discussed, including remdesivir, approved by the FDA for emergency use in the fight against COVID-19
THE CONFORMATION ANALYSIS OF DERIVATIVES 1,2-DISUBSTITUTE ETHANES WITH SEVERAL AXES OF THE INTERNAL ROTATION
Using the complex of the experimental and theoretical methods, the conformation analysis of the purposefully synthesized derivatives of 1,2-disubstitute ethanes with several axes of the internal rotation, containing in its orders the physiologically active compounds in the different aggregate states, has been performed. The tendencies of influence of interaction of the vicinal and more distant substitutes (Ar, Htr, N, N*99+, O, S, CN) have been established of the central bond C-C ethane fragment for the conformation of the molecule as a whole; first, the possibility of realization of the sterically overloaded conformers with the screened couples in 1,3-position, stabilization of which can't be explained with the intramolecular hydrogen connection. The laws of orientation of the plane of the aromatic cycle relative the couple of the C-C ethane fragment, containing the different functional groups, have been shown. The obtained data about the spatial structure have allowed to explain the activity of the investigated physiologically active compounds in relation of the different biotargets, including the unique inhibiting properties 1-N-benzyldiethylammonium-2-alkyluracylil-ethanes in relation to acetyl-cholinesterase. On the base of the sugested model of the molecules recognition image of these substrates by the allosteric areas of the ferment, the synthesis of the more perspective physiologically active compounds of the pyrimidine order is possible.Available from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio