scholarly journals Effect of Chronic Administration of 5-(3-chlorophenyl)-4-Hexyl-2,4 -Dihydro-3H-1,2,4-Triazole-3-Thione (TP-315)—A New Anticonvulsant Drug Candidate—On Living Organisms

2021 ◽  
Vol 22 (7) ◽  
pp. 3358
Author(s):  
Anna Makuch-Kocka ◽  
Marta Andres-Mach ◽  
Mirosław Zagaja ◽  
Anna Śmiech ◽  
Magdalena Pizoń ◽  
...  
Keyword(s):  
Hematological Parameters ◽  
Anticonvulsant Drug ◽  
Living Organism ◽  
Drug Candidate ◽  
In Vitro Tests ◽  
Maximal Electroshock ◽  
Tp 315 ◽  
The Impact ◽  
Chronic Use

About 70 million people suffer from epilepsy—a chronic neurodegenerative disease. In most cases, the cause of the disease is unknown, but epilepsy can also develop as the result of a stroke, trauma to the brain, or the use of psychotropic substances. The treatment of epilepsy is mainly based on the administration of anticonvulsants, which the patient must most often use throughout their life. Despite significant progress in research on antiepileptic drugs, about 30% of patients still have drug-resistant epilepsy, which is insensitive to pharmacotherapy used so far. In our recent studies, we have shown that 4-alkyl-5-aryl-1,2,4-triazole-3-thiones act on the voltage-gated sodium channels and exhibit anticonvulsant activity in an MES (maximal electroshock-induced seizure) and 6Hz test in mice. Previous studies have shown their beneficial toxic and pharmacological profile, but their effect on a living organism during chronic use is still unknown. In the presented study, on the basis of the previously conducted tests and the PAMPA (parallel artificial membrane permeability assay) BBB (blood–brain barrier) test, we selected one 1,2,4-triazole-3-thione derivative—TP-315—for further studies aimed at assessing the impact of its chronic use on a living organism. After long-term administration of TP-315 to Albino Swiss mice, its effect on the functional parameters of internal organs was assessed by performing biochemical, morphological, and histopathological examinations. It was also determined whether the tested compound inhibits selected isoforms of the CYP450 enzyme system. On the basis of the conducted tests, it was found that TP-315 does not show nephrotoxic nor hepatotoxic effects and does not cause changes in hematological parameters. In vitro tests showed that TP-315 did not inhibit CYP2B6, CYP2D6, CYP3A4, or CYP3A5 enzymes at the concentration found in the serum of mice subjected to long-term exposure to this compound.

scholarly journals Effect of long-term administration of a novel anticonvulsant drug candidate (TP-315) on living organism

2020 ◽  
Author(s):  
Anna Makuch-Kocka ◽  
Marta Andres-Mach ◽  
Mirosław Zagaja ◽  
Anna Śmiech ◽  
Magdalena Pizoń ◽  
...  
Keyword(s):  
Anticonvulsant Drug ◽  
Living Organism ◽  
Drug Candidate ◽  
Tp 315 ◽  
Term Administration

scholarly journals A study on the distribution of 85Sr and 134Cs radionuclides after total body irradiation

2020 ◽  
Vol 35 (4) ◽  
pp. 361-371
Author(s):  
Marketa Nemcova ◽  
Lenka Andrejsova ◽  
Anna Lierova ◽  
Marcela Jelicova ◽  
Zuzana Sinkorova ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Retention Rate ◽  
Accumulation Rate ◽  
Hematological Parameters ◽  
Elimination Rate ◽  
Living Organism ◽  
Minimal Effect ◽  
Total Body ◽  
The Impact ◽  
Kinetics Of

The kinetics of strontium, 85Sr, and cesium, 134Cs, were evaluated in a mouse experimental model to determine the impact of these radionuclides on a living organism concerning total body irradiation. Our study demonstrates that the elimination rate of 134Cs from the skeleton and teeth is influenced by total body irradiation and the presence of 85Sr. Higher accumulation and faster 134Cs elimination rates were observed in the skeleton and teeth of mice administrated with a mixture of 134Cs + 85Sr radionuclides. Regarding 85Sr, only a minimal effect was observed on its accumulation rate in skeleton, teeth, and muscle in total body irradiation mice. The effect of the 85Sr + 134Cs radionuclide mix on the accumulation of 85Sr was more apparent in teeth, showing a higher retention rate after 10-24 days of administration in non-irradiated mice. The evaluation of the kinetics of these radionuclides provided much-needed insight on their effects during the first two months after exposure, demonstrating that the accumulation rate of 85Sr is greater than that of 134Cs. Further, the elimination rate of the former is slower in comparison to the latter. Interestingly, total body irradiation has a greater effect on the hematological parameters of the mice blood than the radionuclides alone.

Analysing the impact of a guideline for the use of new potassium binders for treatment of chronic hyperkalaemia to maximise inhibition of renin–angiotensin–aldosterone system (RAAS) within the general nephrology clinic?

2020 ◽  
Author(s):  
Priyank Patel ◽  
Andrew Frankel
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Ckd Stage ◽  
The Mean ◽  
Potassium Binders ◽  
The Impact ◽  
Chronic Use

Abstract Background Renin–angiotensin–aldosterone system (RAAS) inhibitors provide significant cardiorenal benefits with improved long-term outcomes for patients. This is most significant for patients receiving maximal RAAS inhibition, but some patients are unable to tolerate this therapy because of hyperkalaemia. Recently published National Institute for Health and Care Excellence (NICE) technology appraisal guidance recommended using sodium zirconium cyclosilicate (SZC) and patiromer for patients with chronic kidney disease (CKD) stage 3b to 5 or heart failure with reduced ejection fraction, who are not taking an optimised dosage of RAAS inhibitor because of hyperkalaemia. Objective Determine the impact of a locally produced guideline on effective implementation of NICE recommendation for use of SZC or patiromer to help maximise inhibition of the renin–angiotensin–aldosterone system within the general nephrology clinic. Methods A local guideline to practically support the implementation of recommendations made by NICE in the chronic use of new potassium binders was produced. One hundred sequential patients in a general nephrology clinic with non-immune chronic kidney disease (CKD 3 to 5) had their electronic records reviewed. Those with an indication for RAAS inhibition were identified. Results Of the 100 consecutive patients audited, 46 were female and 54 were male. The mean age of these patients was 64 and the mean estimated glomerular filtration rate (eGFR) was 33. Sixty-eight patients had an indication for being on RAAS inhibition with only 10 on maximal doses. Of the remaining 58 patients, 26 (45%) were limited by hyperkalaemia. Of these 26 patients, 12 of these patients (46%) had hyperkalaemia associated with an episode of acute kidney injury (AKI). Therefore, 14% of patients attending a general nephrology clinic were identified suitable for SZC and patiromer. Conclusions A significant proportion (14%) of unselected patients attending a general nephrology clinic were not on optimum RAAS inhibition due to hyperkalaemia. These patients would meet the criteria established within a working guideline for the implementation of the chronic use of SZC or patiromer and are likely to attain prognostic long-term benefit by using these new potassium binders to maximise RAAS inhibition. This analysis has implications for renal centres across the UK.

Suppressed, but Not Forgotten

2011 ◽  
Vol 70 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Beat Meier ◽  
Anja König ◽  
Samuel Parak ◽  
Katharina Henke
Keyword(s):  
Memory Trace ◽  
Thought Suppression ◽  
Test Phase ◽  
Indirect Test ◽  
Final Test ◽  
Test Experiment ◽  
And Control ◽  
Cue Words ◽  
The Impact

This study investigates the impact of thought suppression over a 1-week interval. In two experiments with 80 university students each, we used the think/no-think paradigm in which participants initially learn a list of word pairs (cue-target associations). Then they were presented with some of the cue words again and should either respond with the target word or avoid thinking about it. In the final test phase, their memory for the initially learned cue-target pairs was tested. In Experiment 1, type of memory test was manipulated (i.e., direct vs. indirect). In Experiment 2, type of no-think instructions was manipulated (i.e., suppress vs. substitute). Overall, our results showed poorer memory for no-think and control items compared to think items across all experiments and conditions. Critically, however, more no-think than control items were remembered after the 1-week interval in the direct, but not in the indirect test (Experiment 1) and with thought suppression, but not thought substitution instructions (Experiment 2). We suggest that during thought suppression a brief reactivation of the learned association may lead to reconsolidation of the memory trace and hence to better retrieval of suppressed than control items in the long term.

Examining the Impact of the Disabled Youth Peer Development Initiative: What are the Long-Term Outcomes?

2003 ◽  
Author(s):  
Teresa Garate-Serafini ◽  
Jose Mendez ◽  
Patty Arriaga ◽  
Larry Labiak ◽  
Carol Reynolds
Keyword(s):  
Long Term Outcomes ◽  
The Disabled ◽  
The Impact

The Impact of Different Treatments on Long-Term Symptoms in Vestibular Schwannoma

2014 ◽  
Vol 75 (S 02) ◽  
Author(s):  
Morten Lund-Johansen ◽  
Øystein Tveiten ◽  
Monica Finnkirk ◽  
Erling Myrseth ◽  
Frederik Goplen ◽  
...  
Keyword(s):  
Vestibular Schwannoma ◽  
The Impact

The influence of inflation targeting on the pass-through effect of the exchange rate

2018 ◽  
pp. 70-84
Author(s):  
Ph. S. Kartaev ◽  
Yu. I. Yakimova
Keyword(s):  
Developing Countries ◽  
Monetary Policy ◽  
Exchange Rate ◽  
Inflation Targeting ◽  
Policy Regime ◽  
Short And Long Term ◽  
The Exchange Rate ◽  
Pass Through ◽  
The Impact

The paper studies the impact of the transition to the inflation targeting regime on the magnitude of the pass-through effect of the exchange rate to prices. We analyze cross-country panel data on developed and developing countries. It is shown that the transition to this regime of monetary policy contributes to a significant reduction in both the short- and long-term pass-through effects. This decline is stronger in developing countries. We identify the main channels that ensure the influence of the monetary policy regime on the pass-through effect, and examine their performance. In addition, we analyze the data of time series for Russia. It was concluded that even there the transition to inflation targeting led to a decrease in the dependence of the level of inflation on fluctuations in the ruble exchange rate.

Secular stagnation in the modern world

2018 ◽  
pp. 125-141 ◽  
Author(s):  
S. M. Drobyshevsky ◽  
P. V. Trunin ◽  
A. V. Bozhechkova
Keyword(s):  
Public Debt ◽  
Capital Accumulation ◽  
Technological Development ◽  
Japanese Economy ◽  
Modern World ◽  
Key Factors ◽  
Destruction Process ◽  
Secular Stagnation ◽  
The Impact

The paper studies the factors of secular stagnation. Key factors of long-term slowdown in economic growth include the slowdown of technological development, aging population, human capital accumulation limits, high public debt, creative destruction process violation etc. The authors analyze key theoretical aspects of long-term stagnation and study the impact of these factors on Japanies economy. The authors conclude that most of the factors have significant influence on the Japanese economy for recent decades, but they cannot explain all dynamics. For Russia, on the contrary, we do not see any grounds for considering the decline in the economy since 2013 as an episode of secular stagnation.

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