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RISS 인기검색어
- 검색키워드
- 저자 : Zsolt (검색결과 38 건)
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Differential effects of sodium channel blockers on in vitro induced epileptiform activities
Zsolt Ga´ ll,Ka´roly Orba´n-Kis,Tibor Szila´gyi 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.1
Antiepileptic drugs act on voltage gated sodiumchannels in many different ways: rufinamide is thought toinfluence the fast inactivation, so its anticonvulsant actioncould be similar to carbamazepine, whereas lacosamideenhances the slow inactivation; however some antidepressantswere also described to act in the same way. Rufinamide,lacosamide, carbamazepine, fluoxetine andimipramine were tested using in vitro models of epileptiformactivities. Extracellular local field potentials were recordedusing hippocampal slices from immature rats and the patternof epileptiform activities was analyzed. Seizure-like events(SLE), but not interictal bursts were sensitive to AEDs’action. Rufinamide increased interictal periods by prolongingpreictal phase and reducing SLE duration, and was theonly tested AED which reduced SLE frequency. Lacosamide’seffect resembled that of fluoxetine in the low-Mg2?model: both drugs reduced markedly the SLE duration, butincreased their frequency. Imipramine and fluoxetine irreversiblysuppressed SLE in all slices. Some proconvulsivetype of action on SLEs such as increasing preictal neuronalactivity by rufinamide and increasing SLE frequency bylacosamide, fluoxetine and carbamazepine, were alsoobserved. Newer drugs were more efficient than carbamazepine,and the anticonvulsant action of antidepressantson in vitro epileptiform activities may seem somewhatsurprising.
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Distribution of lacosamide in the rat brain assessed by in vitro slice technique
Zsolt Ga´ ll,Szende Vancea 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.1
Lacosamide is a newer anticonvulsant and is theonly one that enhances the slow inactivation of voltagegated sodium channels. It is also claimed to have diseasemodifyingpotential, but its pharmacokinetic propertieshave been much less discussed in the literature. In rats,lacosamide shows restricted distribution to tissues, and thebrain-to-plasma partition coefficient (Kp) is only 0.553. Inthis study, the brain disposition of lacosamide was evaluatedin rat brains, and its neuropharmacokinetic parameters(i.e., protein binding and intracellular accumulation) wereassessed using in vitro methods. Brain slice experimentsand brain homogenate binding studies were performed forseveral drugs acting on the central nervous system, anddrugs were assayed by using a liquid chromatography-massspectrometry system. By applying a combined approach, itwas found that (1) the unbound volume of distribution inthe brain for lacosamide (Vu,brain = 1.37) was lower thanthat of other classical anticonvulsants; (2) the unboundfraction of lacosamide in the brain (0.899) was slightlylower than its unbound fraction in plasma (0.96); (3) theunbound intracellular-to-extracellular concentration ratioof lacosamide was 1.233, meaning that lacosamide wasaccumulated in the intracellular space because of itsphysicochemical properties and zwitterionic structure; and(4) the unbound brain-to-plasma concentration ratio oflacosamide was lower than the total brain-to-plasma concentrationratio (Kp,uu,brain = 0.42 vs. Kp = 0.553). Inconclusion, the limited brain distribution of lacosamide isnot related to its nonspecific protein-binding capacity;rather, an active transport mechanism across the blood–brain barrier may be involved, which reduces the anticonvulsantand/or antiepileptogenic actions of this drug.
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Simulation of photonic crystal waveguides with dispersion
Zsolt Szabo,Gyorgy Kadar,Janos Balazs 한국물리학회 2006 Current Applied Physics Vol.6 No.2
In this paper the nite dierence time domain (FDTD) method is applied to calculate the wave propagation in two dimensionalphotonic crystal optical waveguides and to determine the energy distribution along the propagation path. The band structure isdetermined taking into account the frequency dependence of the dielectric permittivity. Two dimensional photonic crystals basedon bulk and porous silicon material were investigated and a gradual decrease of the averaged energy was found.
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Recent Advances in the Neoadjuvant Treatment of Breast Cancer
Gábor Rubovszky,Zsolt Horváth 한국유방암학회 2017 Journal of breast cancer Vol.20 No.2
In the last few decades, neoadjuvant therapy for breast cancer has gained considerable therapeutic importance. Despite extensive clinical investigations, it has not yet been clarified whether neoadjuvant therapy would result in improved survival in comparison with the standard adjuvant setting in any subgroups of patients with breast cancer. Chemotherapy is especially effective in the treatment of endocrine insensitive tumors, and such therapeutic benefit can be assumed for patients with triple-negative, or hormone receptor-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, dose escalation, modification of the therapeutic regimens according to early tumor response, as well as the optimal sequence of administration are still matters of debate. There is a current debate between clinical experts regarding the concomitant and sequential administration of carboplatin and capecitabine, respectively, as part of the standard neoadjuvant treatment, as well as the use of bevacizumab, as part of the preoperative treatment. In case of HER2 positive tumors, an anti-HER2 agent can be administered as part of the preoperative treatment, and according to preliminary clinical data, dual HER2 blockade can also be reasonable. Further, chemotherapy-free regimens can be justified in highly endocrine sensitive tumors, while immune modulating agents may also gain particular importance in the case of certain subtypes of breast cancer. Several small-molecule targeted therapies are under clinical investigation and are expected to provide new neoadjuvant treatment options. However, novel, more predictive biomarkers are required for further evaluation of the neoadjuvant therapies, as well as the effect of novel targeted agents intended to be incorporated into neoadjuvant therapy.
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Role of Glutathione Redox System on the T-2 Toxin Tolerance of Pheasant (Phasianus colchicus)
Csaba Fernye,Zsolt Ancsin,Andrea Bocsai,Krisztian Balogh,Miklos Mezes,Marta Erdelyi 한국독성학회 2018 Toxicological Research Vol.34 No.3
The purpose of the present study was to evaluate the effects of different dietary concentrations of T-2 toxin on blood plasma protein content, lipid peroxidation and glutathione redox system of pheasant (Phasianus colchicus). A total of 320 one-day-old female pheasants were randomly assigned to four treatment groups fed with a diet contaminated with different concentrations of T-2 toxin (control, 4 ㎎/㎏, 8 ㎎/㎏ and 16 ㎎/㎏). Birds were sacrificed at early (12, 24 and 72 hr) and late (1, 2 and 3 weeks) stages of the experiment to demonstrate the effect of T-2 toxin on lipid peroxidation and glutathione redox status in different tissues. Feed refusal and impaired growth were observed with dose dependent manner. Lipid-peroxidation was not induced in the liver, while the glutathione redox system was activated partly in the liver, but primarily in the blood plasma. Glutathione peroxidase activity has changed parallel with reduced glutathione concentration in all tissues. Based on our results, pheasants seem to have higher tolerance to T-2 toxin than other avian species, and glutathione redox system might contribute in some extent to this higher tolerance, in particular against free-radical mediated oxidative damage of tissues, such as liver.
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Csaba Fernye,Zsolt Ancsin,Márta Erdélyi,Miklós Mézes,Krisztián Balogh 한국독성학회 2020 Toxicological Research Vol.36 No.2
There are only a few reports on the effects of mycotoxins on pheasant (Phasianus colchicus) and the susceptibility to deoxynivalenol of these birds have never been reported before. The present experiment focuses to investigate the effects of different dietary concentrations of deoxynivalenol on blood plasma protein content, some parameters of lipid peroxidation and glutathione redox system and on the performance of pheasant chicks. A total of 320 1-day-old female pheasants were randomly assigned to four treatment groups fed with a diet contaminated with deoxynivalenol (control, 5.11 mg/kg, 11.68 mg/kg and 16.89 mg/kg). Birds were sacrificed at early (12, 24 and 72 h) and late (1, 2 and 3 weeks) stages of the experiment to demonstrate the oxidative stress-inducing effect of deoxynivalenol. Feed refusal was dose dependent, especially in the last third of the trial, but only minor body weight gain decrease was found. Lipid-peroxidation parameters did not show dose-dependent effect, except in blood plasma during the early stage of the trial. The glutathione redox system, reduced glutathione content and glutathione peroxidase activity, was activated in the liver, but primarily in the blood plasma. Glutathione peroxidase activity has changed parallel with reduced glutathione concentration in all tissues. Comparing our results with literature data, pheasants seem to have the same or higher tolerance to deoxynivalenol than other avian species, and glutathione redox system might contribute in some extent to this tolerance, as effective antioxidant defence against oxidative stress.
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