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Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin (“Apodox” and “lip-8-dox”) and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC50) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC50 = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC50 was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP.

Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine). An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05). This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.

Polymers are currently widely used to replace a variety of natural materials with respect to their favourable physical and chemical properties, and due to their economic advantage. One of the most important branches of application of polymers is the production of different products for medical use. In this case, it is necessary to face a significant disadvantage of polymer products due to possible and very common colonization of the surface by various microorganisms that can pose a potential danger to the patient. One of the possible solutions is to prepare polymer with antibacterial/antimicrobial properties that is resistant to bacterial colonization. The aim of this study was to contribute to the development of antimicrobial polymeric material ideal for covering vascular implants with subsequent use in transplant surgery. Therefore, the complexes of polymeric substances (hyaluronic acid and chitosan) with silver nitrate or silver phosphate nanoparticles were created, and their effects on gram-positive bacterial culture of Staphylococcus aureus were monitored. Stages of formation of complexes of silver nitrate and silver phosphate nanoparticles with polymeric compounds were characterized using electrochemical and spectrophotometric methods. Furthermore, the antimicrobial activity of complexes was determined using the methods of determination of growth curves and zones of inhibition. The results of this study revealed that the complex of chitosan, with silver phosphate nanoparticles, was the most suitable in order to have an antibacterial effect on bacterial culture of Staphylococcus aureus. Formation of this complex was under way at low concentrations of chitosan. The results of electrochemical determination corresponded with the results of spectrophotometric methods and verified good interaction and formation of the complex. The complex has an outstanding antibacterial effect and this effect was of several orders higher compared to other investigated complexes.

Herein, we present a study focused on the determination of the influence of long-distance (53 km) bicycle riding on levels of chosen biochemical urinary and serum prostate cancer (PCa) biomarkers total prostate-specific antigen (tPSA), free PSA (fPSA) and sarcosine. Fourteen healthy participants with no evidence of prostate diseases, in the age range from 49–57 years with a median of 52 years, underwent physical exercise (mean race time of 150 20 min, elevation increase of 472 m) and pre- and post-ride blood/urine sampling. It was found that bicycle riding resulted in elevated serum uric acid (p = 0.001, median 271.76 vs. 308.44 mol/L pre- and post-ride, respectively), lactate (p = 0.01, median 2.98 vs. 4.8 mmol/L) and C-reactive protein (p = 0.01, 0.0–0.01 mg/L). It is noteworthy that our work supports the studies demonstrating an increased PSA after mechanical manipulation of the prostate. The subjects exhibited either significantly higher post-ride tPSA (p = 0.002, median 0.69 vs. 1.1 ng/mL pre- and post-ride, respectively) and fPSA (p = 0.028, median 0.25 vs. 0.35 ng/mL). Contrary to that, sarcosine levels were not significantly affected by physical exercise (p = 0.20, median 1.64 vs. 1.92 mol/mL for serum sarcosine, and p = 0.15, median 0.02 mol/mmol of creatinine vs. 0.01 mol/mmol of creatinine for urinary sarcosine). Taken together, our pilot study provides the first evidence that the potential biomarker of PCa—sarcosine does not have a drawback by means of a bicycle riding-induced false positivity, as was shown in the case of PSA. Uvádíme zde studii zaměřenou na stanovení vlivu jízd na kole do delších vzádelností (53 km) na úrovni vybrané biochemické moči a séra rakoviny prostaty (DPS) biomarker prostatický specifický antigen (tPSA), volné PSA (fPSA) a sarcosine. Čtrnáct zdravých účastníků bez známek onemocnění prostaty, ve věkovém rozmezí od 49-57 let s mediánem 52 let, podstoupili fyzickou aktivituí (střední doba závodu 150 20 min, převýšení 472 m) a odběr vzorků krve/moči před a po jízdě. Bylo zjištěno, že jízdy na kole ústí ve zvýšené serum kyseliny močové (p = 0,001, medián 271.76 vs. 308.44 mol/L před a po jízdě, respektive), laktát (p = 0,01, medián 2,98 versus 4,8 mmol/L) a C - reaktivního proteinu (p = 0,01, 0,0 – 0,01 mg/L). Stojí za zmínku,že naši práci podporuje studie, které prokazují zvýšené PSA po mechanické manipulaci s prostatou. Subjekty byly vystaveny buď podstatně vyšší post- jízdě tPSA (p = 0,002, medián 0,69 vs. 1,1 ng/mL, před a po jízdě, respektive) a fPSA (p = 0.028, medián 0,25-0,35 ng/mL). Na rozdíl od toho, úroveň sarkosinu nebyla výrazně ovlivněna fyzickou aktivitou. (p = 0,20, medián 1,64 vs. 1.92 mol/mL sérum sarcosine, a p = 0,15, medián0,02 mol/mmol kreatininu vs. 0,01 mol/mmol kreatininu za močového sarcosine). Čistě vazto našepilotní studie poukazuje na první důkazy, že potenciální biomarker DPS – sarcosine nemá záporné účinky při jízdě nakole tak jak bylo ukázáno v případě PSA.

V této práci jsme se zaměřili na rozdíly mezi bakteriálních kultur E. coli, získaných ze stěrů infekčních ran pacientů ve srovnání s laboratorním E. coli. Navíc blokování proteinu odpovědné za syntézu glutathion (-glutamyl-cystein synthasy GCL) za použití 10 mM buthionin sulfoximin byla zkoumána. Každý E. coli ukázala výrazné rozdíly v rezistenci vůči antibiotikům. Podle odhodlaný odolné, E. coli byly rozděleny do experimentálních skupin na základě statistického vyhodnocení jejich vlastností jako odolnější a citlivější. Tyto skupiny byly také použity pro nalezení rozdíly mezi nimi v závislosti na glutathion dráhy o rezistenci na antibiotika. Citlivější E. coli vykazovaly stejné kinetiky glutathionu syntézy zatímco blokuje GCL (km 0,1 um), ve srovnání s non-blokování. Kromě toho, nejčastější mutace v genech glutathion syntetázy, glutathion peroxidázy a glutathionreduktasy byly pozorovány v této skupině ve srovnání s laboratorní E. coli. Skupina "odolnější" E. coli vykazovaly rozdíly v km mezi 0,3 a 0,8 uM. Počet mutací ve srovnání s E. coli laboratoře byla podstatně nižší v porovnání s jinou skupinou. In this work, we focused on the differences between bacterial cultures of E. coli obtained from swabs of infectious wounds of patients compared to laboratory E. coli. In addition, blocking of the protein responsible for the synthesis of glutathione (-glutamylcysteine synthase—GCL) using 10 mM buthionine sulfoximine was investigated. Each E. coli showed significant differences in resistance to antibiotics. According to the etermined resistance, E. coli were divided into experimental groups based on a statistical evaluation of their properties as more resistant and more sensitive. These groups were also used for finding the differences in a dependence of the glutathione pathway on resistance to antibiotics. More sensitive E. coli showed the same kinetics of glutathione synthesis while blocking GCL (Km 0.1 M), as compared to non-blocking. In addition, the most frequent mutations in genes of glutathione synthetase, glutathione peroxidase and glutathione reductase were observed in this group compared to laboratory E.coli. The group of “more resistant” E. coli exhibited differences in Km between 0.3 and 0.8 M. The number of mutations compared to the laboratory E. coli was substantially lower compared to the other group.

Prostate cancer (CaP) is the most common type of tumour disease in men. Early diagnosis of cancer of the prostate is very important, because the sooner the cancer is detected, the better it is treated. According to that fact, there is great interest in the finding of new markers including amino acids, proteins or nucleic acids. Prostate specific antigen (PSA) is commonly used and is the most important biomarker of CaP. This marker can only be detected in blood and its sensitivity is approximately 80%. Moreover, early stages cannot be diagnosed using this protein. Currently, there does not exist a test for diagnosis of early stages of prostate cancer. This fact motivates us to find markers sensitive to the early stages of CaP, which are easily detected in body fluids including urine Rakovina prostaty (CaP) je nejčastějším typem nádorového onemocnění u mužů. Včasná diagnóza rakoviny prostaty, je velmi důležitá, protože čím dříve je rakovina zjištěna, tím lépe se léčí. Podle této skutečnosti, je velký zájem o nalazení nových markerů, včetně aminokyselin, proteinů a nukleových kyselin. Prostatický specifický antigen (PSA) je běžně používaný a je nejdůležitější biomarker u karcinomu prostaty. Tato značka může být detekována v krvi a jeho citlivost je přibližně 80%. Kromě toho, se v počátečních fázích nediagnostikuje s použitím tohoto proteinu. V současné době neexistuje test pro diagnostiku počátečních stadií rakoviny prostaty. Tato skutečnost nás motivuje najít markery citlivé na počáteční stadia karcinomu prostaty, které jsou snadno zjistitelné v tělních tekutinách, včetně moči.