Huba Kalasz - Academia.edu (original) (raw)

Papers by Huba Kalasz

Current Medicinal Chemistry, Apr 1, 2013

K203 is an experimental bis-pyridinium mono-aldoxime type cholinesterase reactivator of potential... more K203 is an experimental bis-pyridinium mono-aldoxime type cholinesterase reactivator of potential use in organophosphate/ organophosphonate poisoning. Pharmacokinetics of K203 were examined in Wistar rats and beagle dogs using ion-pair HPLC. Serum and cerebrospinal fluid concentrations of K203 were determined using ion-pair reversedphase chromatography on octadecyl silica column. HPLC with ultraviolet detection was used for determination of serum concentration of K203 higher than 0.1 μg/mL while its low concentrations in cerebrospinal fluid required electrochemical detection (0.015 through 4 μg/mL range). In rats the serum levels of K203 followed zero order pharmacokinetics from 15 to 120 minutes post administration. Zero order pharmacokinetics was also observed in beagle dogs after low dose (15 μmol/kg) of K203 administration. High dose administration (250 μmol/kg) led to subsequent hindered elimination from both cerebrospinal fluid and serum.

Acta Chromatographica, Dec 1, 2008

The pharmacokinetics of K-203, a recently synthesized bis-pyridinium aldoxime, have been investig... more The pharmacokinetics of K-203, a recently synthesized bis-pyridinium aldoxime, have been investigated by reversed-phase HPLC. The K-203 content of serum samples was monitored by HPLC with ultraviolet absorbance detection at 286 nm. The low concentration of K-203 in samples of brain, eyes, and cerebrospinal fluid was also determined by HPLC; quantitative evaluation was possible by use of an amperometric detector.

Bis-pyridinium mono-aldoxime (BPMA) compounds are potential antidotes against organophosphorus in... more Bis-pyridinium mono-aldoxime (BPMA) compounds are potential antidotes against organophosphorus inhibitors of either acetylcholinesterase or these of butyrylcholinesterase. From the points of drug distribution and pharmacokinetics essential characteristics were determined (concentration versus time curves). Experimental results of pharmacokinetics of BPMA will be detailed with special focus on drug distribution and HPLC analysis of oxime K117. The concentration of BPMAs decreases fast in the body of rats, and thus they fulfil the basic requirement for antidotes: elimination should be as fast as possible. Their elimination curve should be characterized by the term "tenth-life" rather than half-life. BPMA compounds penetrate into the brain in considerable amounts of their concentration in the serum. As blood-brain penetration can have vital importance, time of the maximum extent of blood-brain barrier should also be conceived as a novel pharmacokinetic parameter.

Molecules, 2020

Our aim was to find chlorine-substituted antidotes against organophosphate poisoning and compare ... more Our aim was to find chlorine-substituted antidotes against organophosphate poisoning and compare their pharmacokinetics to their parent compound, K-203. White male Wistar rats were intramuscularly injected with K-203, K-867 or K-870. Serum, brain, kidneys, liver, lung, eyes, and testes tissues were taken after 5, 15, 30, 60, and 120 min and analyzed using reversed-phase high-performance liquid chromatography. K-203, K-867, or K-870 was present in every tissue that was analyzed, including the serum, the eyes, testes, liver, kidneys, lungs, and the brain. The serum levels of K-867 and K-870 (chlorine-substituted derivatives of K-203) were nearly constant between 15 and 30 min, while their parent compound (K-203) showed peak level at 15 min after the administration of 30 µmol/rat. Neither K-203, nor K-867 or K-870 were toxic at a dose of 100 µmol/200 g in rats. Chlorine-substitution of K-867 and K-870 produced limited absorbance and distribution compared to their parent compound, K203.

The Open Medicinal Chemistry Journal, 2019

Background: Bis-pyridinium aldoximes are reactivators of the paraoxon-inhibited butyrylcholineste... more Background: Bis-pyridinium aldoximes are reactivators of the paraoxon-inhibited butyrylcholinesterase enzyme. Paraoxon is the active product of parathion, a widely used insecticide. Objective: The objective of this study is to examine the dose-dependent distribution of K117, a bis-pyridinium aldoxime in rat tissues. Materials and Methods: White male Wistar rats were intramuscularly injected with various doses of K117; the animals were sacrificed 30 minutes after injections. The dose-dependent body distribution of K117 was determined using reversed-phase HPLC. Results: Dose-dependent distribution of K117 in body tissues was linear in the serum and other body tissues throughout the whole range of the concentrations studied. However, the of distribution was not observed in the brain and cerebrospinal fluid, especially with high doses. Conclusion: The body distribution of K117 significantly depends on doses used, the p-value is: 500 nmol, i.m., when applied in the range of 100 to 10,000...

The Open Medicinal Chemistry Journal, 2020

Background: Our recent work has been treating the pharmacokinetics of pyridinium aldoximes of var... more Background: Our recent work has been treating the pharmacokinetics of pyridinium aldoximes of various structures including their time-dependent distribution in the body of male rats and also the extent of blood-brain-barrier penetration. Objective: Our overall aim was to find a proper antidote in organophosphate poisoning with fast elimination. Methods: White male Wistar rats were intramuscularly injected with the aqueous solution of 3 µmol of K-347. The animals were sacrificed at different time periods following treatment; various tissues and body fluids were taken and homogenised. The level of K-347 was determined using reversed-phase HPLC. Dose-dependence of tissue level was also determined by using various doses, 3 µmol through 100 µmol of K-347. Results: The serum level of K-347 showed a definitely fast decline. K347 did not have any effect on Gram-positive and Gram-negative bacteria that we tested. Conclusion: The kinetics of K-347 showed an extremely fast offset, even in comp...

Acta Biologica Hungarica

Microsomal oxidation of exogenic compounds yields efferent metabolites with small molecular size.... more Microsomal oxidation of exogenic compounds yields efferent metabolites with small molecular size. N-demethylation results in formaldehyde generation in addition to the nor-compound. Interesting changes in the level of formaldehyde elimination were observed after a single dose of either ( )-deprenyl or (+)-deprenyl. Urine elimination of the generated formaldehyde was determined using thin-layer chromatography after derivatization with dimedone.

Molecular and Cellular Biochemistry, 2021

Allium species, belonging to Alliaceae family, are among the oldest cultivated vegetables used as... more Allium species, belonging to Alliaceae family, are among the oldest cultivated vegetables used as food. Garlic, onions, leeks and chives, which belong to this family, have been reported to have medicinal properties. The Allium species constituents have been shown to have antibacterial and antioxidant activities, and, in addition, other biological properties. These activities are related to their rich organosulfur compounds. These organosulfur compounds are believed to prevent the development of cancer, cardiovascular, neurological, diabetes, liver diseases as well as allergy and arthritis. There have also been reports on toxicities of these compounds. The major active compounds of Allium species includes, diallyl disulfide, diallyl trisulfide, diallyl sulfide, dipropyl disulfide, dipropyl trisulfide, 1-propenylpropyl disulfide, allyl methyl disulfide and dimethyl disulfide. The aim of this review is to focus on a variety of experimental and clinical reports on the effectiveness, toxicities and possible mechanisms of actions of the active compounds of garlic, onions, leek and chives.

Abstract: Peroxisome proliferator-activated receptor (PPAR) agonists are used as adjunct therapy ... more Abstract: Peroxisome proliferator-activated receptor (PPAR) agonists are used as adjunct therapy in the treatment of diabetes mellitus. Fibrates, including fenofibrate, gemfibrozil, benzafibrate, ciprofibrate, and clofibrate act on PPAR alpha to reduce the level of hypertriglyceridemia. However, agonists (ligands) of PPAR-beta/delta receptors, such as tesaglitazar, muraglitazar, ragaglitazar, imiglitazar, aleglitazar, alter the body's energy substrate preference from glucose to lipids and hence contribute to the reduction of blood glucose level. Glitazones or thiazolidinediones on the other hand, bind to PPAR-gamma receptors located in the nuclei of cells. Activation of PPAR-gamma receptors leads to a decrease in insulin resistance and modification of adipocyte metabolism. They reduce hyperlipidaemia by increasing the level of ATPbinding cassette A1, which modifies extra-hepatic cholesterol into HDL. Dual or pan PPAR ligands stimulate two or more isoforms of PPAR and thereby re...

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The open medicinal chemistry journal, 2018

Tinuvin 770 [bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate, Ciba-Geigy, Basel, Switzerland] is ... more Tinuvin 770 [bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate, Ciba-Geigy, Basel, Switzerland] is a UV light stabilizer that is a component of many plastic materials used world-wide in the medical and food industries. We report on the acute hemodynamic effects of Tinuvin 770 examined in dogs. Tinuvin 770 was dissolved in a mixture of saline and ethanol (1:1 v/v) and was administered to 12 intravenously narcotized and respirated dogs in increasing doses (T1-T7: 1, 3.3, 6.6, 10, 33.3, 66.6 and 100 mg, respectively). The doses were given as bolus injections over a three minute period, and the effects were recorded for 12 minutes. The vehicle was used as a control. Hemodynamic parameters (heart rate, blood pressure, end-diastolic pressure, dp/dt, cardiac output) and ECG were monitored continously. At doses T1-T4, systolic and diastolic blood pressures, mean pressure and ventricular contractility were significantly decreased without significant changes in cardiac output, heart rate, or PQ...

The open medicinal chemistry journal, 2017

Selegiline is used to treat Parkinsonian patients. Other indications of its use have recently bee... more Selegiline is used to treat Parkinsonian patients. Other indications of its use have recently been discovered. Scouting special and beneficial side effects of selegiline treatment. Two-year old male Wistar rats were daily treated with 0.25 mg/kg of selegiline s.c. (subcutaneous injection). The rats were sacrificed following a four-weeks' treatment. Mass of testes, number of sperms, progressive motility of sperms, and their viability definitely increased. Selegiline can successfully be used to stop/counterbalance certain symptoms of aging.

The Open Medicinal Chemistry Journal, 2017

Background:Selegiline [(-)-deprenyl] is widely used for the treatment of Parkinson’s disease in h... more Background:Selegiline [(-)-deprenyl] is widely used for the treatment of Parkinson’s disease in humans.Objective:Time-dependence of tissue distribution of selegiline following per os administration to rats.Method:Oral administration of radiolabeled selegiline to rats resulted in a pattern of tissue distribution similar to that following intraperitoneal injection. Analyses were done using both reversed-phase HPLC and also by counting radioactivity in various body compartments of rats.Results:As a consequence of oral administration of 30 mg/kg of selegiline, its level in the stomach was extremely high (179.57 µg/g tissue through 54.67 µg/g at 15 min to 120 min), that is one magnitude higher than that in the serum level. High selegiline concentrations were also detected in the lacrimal glands (7.45 µg/g), kidneys (6.87 µg/g), livers (6.01 µg/g) and lungs (3.47 µg/g) after 30 minutes of application, which were higher than after intraperitoneal injections.Conclusion:The relatively high t...

Toxicology Mechanisms and Methods, 2017

In silico and in vitro evaluation of two novel oximes (K378 and K727) in comparison to K27 and pr... more In silico and in vitro evaluation of two novel oximes (K378 and K727) in comparison to K27 and pralidoxime against paraoxon-ethyl intoxication.

Expert opinion on biological therapy, Aug 1, 2017

The number of people with diabetes mellitus (DM) is estimated to exceed 640 million by the year 2... more The number of people with diabetes mellitus (DM) is estimated to exceed 640 million by the year 2040. Diabetic foot ulcer (DFU) is a debilitating illness that affects more than 2% of DM patients. DFU is caused by DM-induced neural and vascular lesions leading to a reduced sensation and microcirculation. The increase in the prevalence of DFU has prompted researchers to find new therapies for the management of DFU. Areas covered: This review presents the current status of novel biological therapies used in the treatment of DFU. Literature information and data analysis were collected from PubMed, the website of the American Diabetes Association, and ClinicalTrials.gov. The keywords used in the search were: DM, DFU, complications of DM. Expert opinion: Many biological agents have been investigated in a bid to find an effective therapy for DFU. These include growth factors (platelet-derived growth factor, vascular endothelial growth factor etc), stem cells (epithelial progenitor-, adipos...

Lc Gc North America, 2001

This installment of Milestones in Chromatography surveys the evolution of thin-layer chromatograp... more This installment of Milestones in Chromatography surveys the evolution of thin-layer chromatography and compares the technique with high performance liquid chromatography.

Lc Gc North America, 2002

This article summarizes the application of thin-layer chromatography (TLC) to the separation and ... more This article summarizes the application of thin-layer chromatography (TLC) to the separation and analysis of pharmaceuticals. The vast majority of applied methods involve classic TLC; however, both forced-flow TLC and planar electrophoresis are becoming more important. The authors describe the main practices of TLC, its associated detection methods, and a selection of applications