Jiri Kukacka

Utilizing of Adsorptive Transfer Stripping Technique Brdicka Reaction for Determination of Metallothioneins Level in Melanoma Cells, Blood Serum and Tissues.

In the paper we utilized the adsorptive transfer stripping differential pulse voltammetry Brdicka reaction for the determination of metallothioneins (MT) in melanoma cells, animal melanoma tissues (MeLiM miniature pig) and blood serum of patients with malignant melanoma. Primarily we attempted to investigate the influence of dilution of real sample on MT electrochemical response. Dilution of samples of 1 000 times was chosen the most suitable for determination of MT level in biological samples. Then we quantified the MT level in the melanoma cells, the animal melanoma tissues and the blood serum samples. The MT content in the cells varied within the range from 4.2 to 11.2 μM. At animal melanoma tissues (melanomas localized on abdomen, back limb and dorsum) the highest content of MT was determined in the tumour sampled on the back of the animal and was nearly 500 μg of MTs per gram of a tissue. We also quantified content of MT in metastases, which was found in liver, spleen and lymph nodes. Moreover the average MT level in the blood serum samples from patients with melanoma was 3.0 ± 0.8 μM. MT levels determined at melanoma samples were significantly (p < 0.05) higher compared to control ones at cells, tissues and blood serum.

Behavioural breaks in the heterogeneous agent model: the impact of herding, overconfidence, and market sentiment

The main aim of this work is to incorporate selected findings from behavioural finance into a Heterogeneous Agent Model using the Brock and Hommes (1998) [34] framework. Behavioural patterns are injected into an asset pricing framework through the so-called ‘Break Point Date’, which allows us to examine their direct impact. In particular, we analyse the dynamics of the model around the behavioural break. Price behaviour of 30 Dow Jones Industrial Average constituents covering five particularly turbulent US stock market periods reveals interesting patterns in this aspect. To replicate it, we apply numerical analysis using the Heterogeneous Agent Model extended with the selected findings from behavioural finance: herding, overconfidence, and market sentiment. We show that these behavioural breaks can be well modelled via the Heterogeneous Agent Model framework and they extend the original model considerably. Various modifications lead to significantly different results and model with behavioural breaks is also able to partially replicate price behaviour found in the data during turbulent stock market periods.

Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial)

BackgroundStatins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS.MethodsThe trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy.ResultsWe did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037).ConclusionsThis study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS.Trial registrationNCT00171275

Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin

Background and objective:  Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient’s glomerular filtration rate (GFR). The aim of the study was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N‐acetyl‐β‐d glucosaminidase (NAG), creatinine level and creatinine clearance].

An Adsorptive Transfer Technique Coupled with Brdicka Reaction to Reveal the Importance of Metallothionein in Chemotherapy with Platinum Based Cytostatics

The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug.

Intravitreal carboplatin concentration and area under concentration versus time curve after intravitreal and periocular delivery.

Purpose. To determine platinum (Pt) concentrations and area under the concentration versus time curve (AUC) of the vitreous humor after periocular or transcorneal intravitreal administration of carboplatin in rabbits. Methods. Eighteen albino rabbits were included in an in vivo experiment. Each animal received a single dose of either 30 mg of carboplatin by periocular injection (POI30 group: n=6) or 15 mg by periocular injection (POI15 group: n=6), or 0.05 mg by transcorneal intravitreal injection (TII group: n=6), respectively, into the right eye. Vitreous humor from the right eyes and plasma samples were collected post dose at 1, 2, 6, 24, 48, 168, and 336 hours or 448 hours, respectively. Flameless atomic absorption spectroscopy was employed to analyze total platinum concentrations in blood and vitreous humor. AUC was calculated using the trapezoidal rule. Results. Pt concentration was mostly <1 mg/L (0–3.15 mg/L) in the vitreous humor samples and ≥2 mg/L (2.33–7.3 mg/L) in the blood samples 1 hour after administration in POI groups. Markedly higher Pt concentrations were found 1 hour after intravitreal (TII) administration (10.285–66.759 mg/L) and decreased below 1 mg/L no less than 168 hours after administration. The mean AUC for Pt in vitreous humor was significantly lower (p=0.0001) after both POI30 and P0I15 administration compared to TII route (8.955 ± 2.464 mg/L/min). Conclusions. These findings proved that intravitreal carboplatin delivery enables the achievement of relatively stable concentrations and AUC of platinum in the rabbit vitreous humor. This moreover suggests that transcorneal intravitreal delivery of carboplatin aiming to treat retinoblastoma vitreous seeding is a promising mode of chemotherapy.

Realizing stock market crashes: stochastic cusp catastrophe model of returns under time-varying volatility

This paper develops a two-step estimation methodology, which allows us to apply catastrophe theory to stock market returns with time-varying volatility and model stock market crashes. Utilizing high frequency data, we estimate the daily realized volatility from the returns in the first step and use stochastic cusp catastrophe on data normalized by the estimated volatility in the second step to study possible discontinuities in markets. We support our methodology by simulations where we also discuss the importance of stochastic noise and volatility in deterministic cusp catastrophe model. The methodology is empirically tested on almost 27 years of U.S. stock market evolution covering several important recessions and crisis periods. Due to the very long sample period we also develop a rolling estimation approach and we find that while in the first half of the period stock markets showed marks of bifurcations, in the second half catastrophe theory was not able to confirm this behavior. Results suggest that the proposed methodology provides an important shift in application of catastrophe theory to stock markets.

The Impact of the Tobin Tax in a Heterogeneous Agent Model of the Foreign Exchange Market

We explore possible effects of a Tobin tax on exchange rate dynamics in a heterogeneous agent model. To assess the impact of the Tobin tax in this framework, we extend the model of De Grauwe and Grimaldi (Eur Econ Rev 50(1):1–33, 2006) by including transaction costs and perform numerical simulations. Motivated by the importance of the market microstructure, we choose to model the market as being cleared by a Walrasian auctioneer. This setting could more closely resemble the two-layered structure of foreign exchanges at daily frequency than a price impact function, which is often adopted in similar studies. We find that the Tobin tax can deliver a moderate reduction of return volatility and kurtosis. In addition, simulations indicate that the Tobin tax reduces the degree of mispricing in the time series, which is primarily achieved by eliminating long-lasting deviations from fundamental value.

No effect of high-doses-methotrexate treatment on serum cardiac troponin I levels in children.

Methotrexate (MTX) is an antifolate drug that inhibits dihydrofolate reductase, thereby depleting the cells of reduced folates, including 5-methyltetrahydrofolate. High-dose MTX therapy (HD-MTX), guided by serum concentration measurements, has an improved therapeutic outcome of patients suffering from acute lymphoblastic leukemia or osteosarcoma. Acute and chronic toxicity of MTX and the major metabolite 7-OH-MTX can limit therapeutic dose intensity and may lead to discontinuation of therapy. It was shown that 48-h plasma concentration >0.9 μmol/L is associated with high frequency of toxicity [1]. The chronic cardiac toxicity, with the development of left ventricular dysfunction, may be a late complication in patients treated with high-dose chemotherapy, especially when antracyclines are used. The acute cardiotoxicity of MTX and 7-OH-MTX is described in animal models [2], but in the pertinent literature no report has been found on the effects of MTX on heart in humans. The determination of cardiac troponin I (cTnI) has an accurate ability to detect minor myocardial damage. Increased serum cardiac troponin I may be considered a marker of cardiac toxicity (myonecrosis) induced by HD-MTX [3]. We analyzed 13 pediatric samples from 10 boys and 3 girls, mean (SD) age 8.8 ± 5.4 years, who had been treated with high-dose methotrexate (6 patients