scholarly journals Influence of the new tiazoloindole derivative on the organism resistance to hypoxia in the early and late periods of preconditioning

2014 ◽  
Vol 12 (4) ◽  
pp. 54-57
Author(s):  
Olga Sergeevna Levchenkova ◽  
Vasiliy Egorovich Novikov ◽  
Vera Vasil'yevna Marysheva
Keyword(s):  
Early Phase ◽  
Hypobaric Hypoxia ◽  
Acute Hypoxia ◽  
Late Phase ◽  
Animal Life ◽  
Resistance To Hypoxia ◽  
Hypoxia With Hypercapnia

The aim of this investigation was to study an ability of tiazoloindole derivative encoded VM-606 to influence the lifespan of mice in experimental acute hypoxia with hypercapnia and hypobaric hypoxia in early and late phase of preconditioning. It was found that the use of VM- 606 in dose of 50 mg/kg leads to significant increase in the duration of animal life in case of subsequent acute hypoxia in early phase of preconditioning, but doesn’t produce effect in the late phase of preconditioning.

scholarly journals Influence of the new tiazoloindole derivative on organism resistance to hypoxia in the early and late periodsof preconditioning

2015 ◽  
Vol 13 (1) ◽  
pp. 52-55
Author(s):  
Ol'ga Sergeevna Levchenkova ◽  
Vasiliy Egorovich Novikov ◽  
Vera Vasil'yevna Marysheva
Keyword(s):  
Early Phase ◽  
Hypobaric Hypoxia ◽  
Acute Hypoxia ◽  
Late Phase ◽  
Animal Life ◽  
Resistance To Hypoxia ◽  
Hypoxia With Hypercapnia

The aim of this investigation was to study an ability of tiazoloindole derivative encoded VM-606 to influence the lifespan of mice in experimental acute hypoxia with hypercapnia and hypobaric hypoxia in early and late phase of preconditioning. It was found that the use of VM-606 in dose of 50 mg/kg leads to significant increase in the duration of animal life in case of subsequent acute hypoxia in early phase of preconditioning, but doesn’t produce effect in the late phase of preconditioning.

scholarly journals Potentiation of the hypoxic preconditioning effect by antihypoxants

2019 ◽  
Vol 17 (1) ◽  
pp. 37-44
Author(s):  
Vasiliy E. Novikov ◽  
Olga S. Levchenkova ◽  
Elena I. Klimkina ◽  
Konstantin N. Kulagin
Keyword(s):  
Hypobaric Hypoxia ◽  
Carotid Arteries ◽  
Acute Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Experimental Models ◽  
Hypoxic Preconditioning ◽  
Acute Hypobaric Hypoxia ◽  
Hypoxia With Hypercapnia ◽  
The Common ◽  
Common Carotid Arteries

The development of effective methods to increase the organism resistance to hypoxia is an important task of current medicine. One of such methods is preconditioning, as a result of which, a potent mobilization of the adaptive organism abilities occurs under a preconditioning factor action. Aim. To study the possibility of potentiating of the hypoxic preconditioning effect with help of antihypoxants. Methods. Evaluation of the effectiveness of combined preconditioning (antihypoxants + moderate hypobaric hypoxia) was performed on experimental models of acute hypoxia with hypercapnia, acute hypobaric hypoxia in mice, and bilateral occlusion of the common carotid arteries in rats. Investigated antihypoxants are amtizol, hypoxen, cobazole, metaprot, mexidol, mildronate, substances under the codes VM-606, pQ-4 and pQ-1104. Results. PreC with use of amtizol at dose 25 mg/kg, cobazole at dose 30 mg/kg, VM-606, pQ-4 and pQ-1104 at doses 50 mg/kg in combination with moderate hypoxia increased the lifespan of mice in acute hypoxia with hypercapniamodel and acute hypobaric hypoxia from 57 to 170%. Combined preconditioning with amtizol, cobazole and pQ-4 significantly increased the survival rate of rats in cerebral ischemia, amtizol and pQ-4 reduced neurological deficiency in the post ischemic period as well. Conclusion. Antitipoxants as amtizol, cobazole, VM-606, pQ-4, pQ-1104 potentiate the hypoxic preconditioning effect on acute hypoxia with hypercapnia, acute hypobaric hypoxia and occlusion of the common carotid arteries models, the most significant effect was noted for amtizol and pQ-4. Signal role in the adaptation induction to hypoxia and ischemia by combined preconditioning with use of antihypoxants hypoxia-inducible factor HIF-1α can play.

scholarly journals THE COMPARATIVE STUDYING OF ANTI-HYPOXEMIC ACTIVITY OF COMPLEX OF ZINC ACETATE WITH N-PROPARGYLIMIDAZOLE AND 3-HYDROXYPYRIDINE

2017 ◽  
Vol 23 (3) ◽  
pp. 148-151
Author(s):  
S. A Shakhmardanova ◽  
P. A Galenko-Yaroshevsky ◽  
L. N Parshina ◽  
B. A Trofimov ◽  
V. V Tarasov ◽  
...  
Keyword(s):  
Zinc Acetate ◽  
Hypobaric Hypoxia ◽  
Large Range ◽  
Narrow Range ◽  
Acute Hypoxia ◽  
Comparative Investigation ◽  
Complex Compounds ◽  
Control Groups ◽  
Acute Hypobaric Hypoxia ◽  
Hypoxia With Hypercapnia

The pharmacotherapy of hypoxia is an important task of modern experimental and clinical pharmacology. The medications with anti-hypoxic effect implemented into clinical practice unfortunately do not meet requirements of physicians due to poor efficiency, narrow range of active dosages and undesirable side effects. The complexes of zinc with N-alkenylimidazole demonstrated anti-hypoxic activity at various models of acute hypoxia within large range of dosage. Therefore, further studying of zinc-contained compounds as possible correctors of hypoxia is of particular interest. The experiments with white nonlinear male mice were used for comparative investigation of ant-hypoxic effect of complex compounds of zinc acetate with N-propargylimidazole and 3-hydroxipyridine, including complexes immobilized on sulfated arabinogalaсtan and also well-known anti-hypoxants and/or anti-oxidants: etomerzol, mexidol, nooglutil and hypoxen. It is demonstrated that anti-hypoxic effect of complex of zinc acetate with N-propargylimidazolein conditions of acute hypobaric hypoxia, acute hypoxia with hypercapnia acute hematic hypoxia by width of active dosages (1-100 mg/kg, intraperitoneally) and degree of expression (19-317% in comparison with control groups of animals) excels the similar effect in well-known anti-hypoxants and/or anti-oxidants: etomerzol (25-100 mg/kg, intraperitoneally), mexidol (100 mk per kg, intraperitoneally), nooglutil (25-100 mg/kg, intraperitoneally) and hypoxen (50-150 mg/kg, intraperitoneally). The protective effect of complex of zinc acetate with 3-hydroxipyridine by width of active dosages (25-100 mg/kg, intraperitoneally) and degree of expression (27-167% in comparison with control groups of animals) in conditions of exogenous hypoxia (acute hypobaric hypoxia and acute hypoxia with hypercapnia) excels similar effect of etomerzol and mexidol ans is comparable with effect of nooglutil and hypoxen. The complexes immobilized on sulfated arabinogalactan were ineffective.

Continuous Adaptation of Rats to Hypobaric Hypoxia Prevents Stressor Hyperglycemia and Optimizes Mitochondrial Respiration in Acute Hypoxia

2013 ◽  
Vol 4 (2) ◽  
pp. 137-147
Author(s):  
Vladimir I. Portnichenko ◽  
Valentina I. Nosar ◽  
Alla M. Sydorenko ◽  
Alla G. Portnychenko ◽  
Irina N. Mankovska
Keyword(s):  
Mitochondrial Respiration ◽  
Hypobaric Hypoxia ◽  
Acute Hypoxia

Improved Stage Categorization of PTZ-Induced Kindling and Late Enhanced Neurogenesis in PTZ Kindled Mice

2019 ◽  
Vol 8 ◽  
pp. 1511
Author(s):  
Marzieh Shahpari ◽  
Hadi Aligholi ◽  
Mohammad Reza Namavar ◽  
Farzaneh Vafaee ◽  
Masoumeh Emamghoreishi
Keyword(s):  
Subventricular Zone ◽  
Early Phase ◽  
Hind Limb ◽  
Late Phase ◽  
The Other ◽  
Myoclonic Jerk ◽  
Ptz Kindling ◽  
First Occurrence ◽  
Tonic Extension ◽  
Behavioral Index

Background: There is no universally accepted behavioral scoring to define the early development of phenothiazine (PTZ) kindling. Therefore, studies investigating alterations of neurogenesis in the PTZ model were mainly focused on full kindled animals rather than early stages of kindling. This study aimed to determine an appropriate behavioral index for categorizing stages of PTZ kindling progress and to evaluate neurogenesis during PTZ kindling. Materials and Methods: Twenty-four mice were intraperitoneally injected with a sub convulsive dose of PTZ (40mg/kg) every other day until they became full kindled. The first occurrence of different seizure behaviors and their durations were recorded during kindling development, and the different stages of kindling were categorized. Neurogenesis was evaluated in the lateral subventricular zone (SVZ) at each stage of kindling by immunofluorescence staining. Results: First occurrence of restlessness, motionless staring, hind limb tonic extension, Straub’s tail, myoclonic jerk, and tonic-clonic were sequentially observed in more than 80% of animals with increasing PTZ injections. The duration of the myoclonic jerk was significantly longer than the other seizure behaviors. The significantly higher percentage of BrdU-positive cells was found in SVZ of mice showing tonic-clonic in comparison to other seizure behaviors. Conclusion: A hierarchy behavior was observed during the kindling process when considering the first occurrence of seizure behaviors. We defined the first occurrence of restlessness, motionless, hind limb tonic extension and Straub’s tail behaviors as an early phase, myoclonic jerk as a borderline phase and tonic-clonic as a late phase of PTZ-induced kindling. Our results indicated an enhanced SVZ neurogenesis at the late phase of kindling. [GMJ.2019;8:e1511]

The Time-Course of Changes in the State of Brain Monoaminergic Systems of Mice Under the Acute Hypoxia with Hypercapnia

2020 ◽  
Vol 14 (2) ◽  
pp. 136-149
Author(s):  
I. V. Karpova ◽  
V. V. Mikheev ◽  
V. V. Marysheva ◽  
N. A. Kuritcyna ◽  
E. R. Bychkov ◽  
...  
Keyword(s):  
Time Course ◽  
Acute Hypoxia ◽  
The State ◽  
Hypoxia With Hypercapnia

Nucleolin Improves Heart Function During Recovery From Myocardial Infarction by Modulating Macrophage Polarization

2021 ◽  
pp. 107424842198957
Author(s):  
Yuting Tang ◽  
Xiaofang Lin ◽  
Cheng Chen ◽  
Zhongyi Tong ◽  
Hui Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Early Phase ◽  
Heart Function ◽  
Macrophage Polarization ◽  
Late Phase ◽  
Macrophage Infiltration ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization ◽  
Nucleolin Expression

Background: Nucleolin has multiple functions within cell survival and proliferation pathways. Our previous studies have revealed that nucleolin can significantly reduce myocardial ischemia-reperfusion injury by promoting myocardial angiogenesis and reducing myocardial apoptosis. In this study, we attempted to determine the role of nucleolin in myocardial infarction (MI) injury recovery and the underlying mechanism. Methods: Male BALB/c mice aged 6–8 weeks were used to set up MI models by ligating the left anterior descending coronary artery. Nucleolin expression in the heart was downregulated by intramyocardial injection of a lentiviral vector expressing nucleolin-specific small interfering RNA. Macrophage infiltration and polarization were measured by real-time polymerase chain reaction, flow cytometry, and immunofluorescence. Cytokines were detected by enzyme-linked immunosorbent assay. Results: Nucleolin expression in myocardium after MI induction decreased a lot at early phase and elevated at late phase. Nucleolin knockdown impaired heart systolic and diastolic functions and decreased the survival rate after MI. Macrophage infiltration increased in the myocardium after MI. Most macrophages belonged to the M1 phenotype at early phase (2 days) and the M2 phenotype increased greatly at late phase after MI. Nucleolin knockdown in the myocardium led to a decrease in M2 macrophage polarization with no effect on macrophage infiltration after MI. Furthermore, Notch3 and STAT6, key regulators of M2 macrophage polarization, were upregulated by nucleolin in RAW 264.7 macrophages. Conclusions: Lack of nucleolin impaired heart function during recovery after MI by reducing M2 macrophage polarization. This finding probably points to a new therapeutic option for ischemic heart disease.

scholarly journals AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takao Watanabe ◽  
Yoshio Tokumoto ◽  
Kouji Joko ◽  
Kojiro Michitaka ◽  
Norio Horiike ◽  
...  
Keyword(s):  
Risk Factors ◽  
Confidence Interval ◽  
Early Phase ◽  
Late Phase ◽  
Previous History ◽  
Late Recurrence ◽  
Early Recurrence ◽  
Hazard Ratio ◽  
Post Treatment ◽  
Hcc Recurrence

Abstract Background An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. Methods Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as ‘early recurrence’, and recurrence more than 1 year after as ‘late recurrence’. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. Results Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026–1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. Conclusion Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

Alternative poly(A) site utilization during adenovirus infection coincides with a decrease in the activity of a poly(A) site processing factor

1993 ◽  
Vol 13 (4) ◽  
pp. 2411-2419
Author(s):  
K P Mann ◽  
E A Weiss ◽  
J R Nevins
Keyword(s):  
Early Phase ◽  
Late Phase ◽  
Transcription Unit ◽  
Adenovirus Infection ◽  
Processing Factor ◽  
Proximal Half ◽  
Rate Determining Step ◽  
Frequency Of Use ◽  
Late Transcription ◽  
A Site

The recognition and processing of a pre-mRNA to create a poly(A) addition site, a necessary step in mRNA biogenesis, can also be a regulatory event in instances in which the frequency of use of a poly(A) site varies. One such case is found during the course of an adenovirus infection. Five poly(A) sites are utilized within the major late transcription unit to produce more than 20 distinct mRNAs during the late phase of infection. The proximal half of the major late transcription unit is also expressed during the early phase of a viral infection. During this early phase of expression, the L1 poly(A) site is used three times more frequently than the L3 poly(A) site. In contrast, the L3 site is used three times more frequently than the L1 site during the late phase of infection. Recent experiments have suggested that the recognition of the poly(A) site GU-rich downstream element by the CF1 processing factor may be a rate-determining step in poly(A) site selection. We demonstrate that the interaction of CF1 with the L1 poly(A) site is less stable than the interaction of CF1 with the L3 poly(A) site. We also find that there is a substantial decrease in the level of CF1 activity when an adenovirus infection proceeds to the late phase. We suggest that this reduction in CF1 activity, coupled with the relative instability of the interaction with the L1 poly(A) site, contributes to the reduced use of the L1 poly(A) site during the late stage of an adenovirus infection.

Evaluation of the activity of antihypoxants with an isothiourea structure in a model of hypercapnic hypoxia with a shutdown of the cerebral hemispheres

2021 ◽  
Vol 19 (1) ◽  
pp. 55-63
Author(s):  
Vera V. Marysheva ◽  
Vladimir V. Mikheev ◽  
Petr D. Shabanov
Keyword(s):  
Acute Hypoxia ◽  
Life Time ◽  
The Body ◽  
Cerebral Hemispheres ◽  
Antihypoxic Activity ◽  
Hypoxic Episode ◽  
Hypoxia With Hypercapnia ◽  
Hypercapnic Hypoxia ◽  
Outbred Mice ◽  
The Brain

PURPOSE: To study the effect of amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one from the hemispheres, as well as both hemispheres of the brain. METHODS: A model of acute hypoxia with hypercapnia (canned hypoxia) was used in mice of the same mass, the lifespan of all animals was determined. Temporary shutdown of the cortex of one of the hemispheres or both hemispheres was achieved by epidural application of filter paper moistened with 25% potassium chloride solution, creating a spreading depression according to Leao. Amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) at equimolar doses of 25, 32.5, and 50 mg/kg, respectively were used as pharmacological analyzers, the compounds were injected intraperitoneally 30 min before the hypoxic episode. RESULTS: It was shown that, in contrast to amtizol, 2-ABT and VM-606 increase the life time of experimental animals when any hemisphere is turned off. The use of drugs when both hemispheres were turned off revealed that amtizol has approximately equal effect on the brain and the rest of the body, in 2-ABT antihypoxic activity is 1/3 associated with the brain, in VM-606 exclusively with the brain. CONCLUSION: The experimental model used in this work makes it possible to quite easily evaluate the effect of either one drug or compare several drugs, their role in the functioning of the cerebral hemispheres, on which part of the sample highly resistant or low resistant to hypoxia they have the greatest effect.

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