Bioethical issues in the development of biopharmaceuticals

Development of biopharmaceuticals is a challenging issue in bioethics. Unlike conventional, small molecular weight drugs, biopharmaceuticals are proteins derived from DNA technology and hybrid techniques with complex three dimensional structures. Immunogenicity of biopharmaceuticals should always be tested in clinical settings due to low predictive value of preclinical animal models. However, non-human primates (NHP) and transgenic mice could be used to address certain aspects of immunogenicity. Substantial efforts have been made to reduce NHP use in biopharmaceutical drug development, e.g. study design improvements and changes in regulatory policy. In addition, several expert groups are active in this field (e.g. NC3Rs, BioSafe, and Biopharmaceutical Technical Group). Despite that, there is an increasing trend of use of NHP in preclinical safety testing of biopharmaceuticals, especially regarding monoclonal antibodies. Other potential bioethical issues related biopharmaceutical drug development are their cost/effectiveness ratio, clinical safety assessment, production of biosimilars, and comparison of their efficacy with placebo in countries without intention to market. Identification of the human genome has opened many new bioethical issues. Development of biopharmaceuticals is an important bioethical issue for several reasons. It connects all aspects of contemporary bioethics: bio­medicine (e.g. clinical trials in vulnerable subjects), animal welfare and the most recent ad­vances in biotechnology. In particular, biopharmaceutical drug development is a challenging issue regarding treatment of rare diseases

Zavisnost efikasnosti germanijumskih detektora od gustine uzoraka u spektrometriji gama zračenja

The effect of the density of environmental samples on the counting efficiency of Ge detectors used in gamma-spectrometry was studied. The dependence εff(ρ) was determined for two HPGe detectors (relative efficiencies 18% and 20%) using five radioactive standard reference materials (silicone resins, epoxy resin, milk powder, soil) with different matrix densities (0.45-1.22 g/cm3) in Marinelli beakers (V = 500 cm3). The dependence of efficiency vs. density was found to be linear and the regression parameters for energies in the range of 60-2000 keV were determined, too. The effect of variation in density on the counting efficiency of Ge detectors is dominant in the range of lower energies (60-600 keV) and de creases with energies in the higher energy range.Ispitivan je uticaj gustine uzoraka iz životne sredine na efikasnost brojanja germanijumskih detektora u spektrometriji gama zračenja. Zavisnost εff(ρ) određena je za dva HPGe detektora (relativnih efikasnosti 18% i 20%) za različite radioaktivne standardne referentne materijale (silikonske smole epoksi smolu, mleko u prahu, zemlju) različitih gustina (0,45-1,22 g/cm3) u Marineli posudama zapremine V = 500 cm3. Utvrđena je linearna zavisnost efikasnosti brojanja od gustine uzoraka pri čemu su određeni parametri linearne regresije za niz energija iz intervala od 60-2000 keV. Efekt promene gustina na efikasnost brojanja germanijumskih detektora dominantan je u intervalu nižih energija (60-600 keV) i smanjuje se sa porastom energije u intervalu viših energija

Concentrations of natural radionuclides in imported zirconium minerals

The natural radioactivity in imported zircon samples used as glaze for ceramic tiles in the ceramics industry has been presented in this paper. The measurements were made by gamma spectrometry with a high purity germanium detector. The average activity concentrations of 238U and 232Th determined in the measured samples (3250 Bq/kg, and 556 Bq/kg, respectively) are much higher than the concentrations found in the Earth’s crust. The activity concentration of 226Ra is also high in all analyzed samples, while 40K was not detected. The gamma index, I, the external hazard index, Hex, the internal hazard index, Hin, and the radium equivalent activity, Raeq, were calculated. Due to relatively high activity concentration level of uranium in imported zircon samples, specific regulations are necessary for zircon compound used in ceramic industry. It can be concluded that the investigated samples can be used as the component of ceramic glaze in the concentrations not above 3%

Transfer of Cs-134 and Cs-137 from soils to plants in cultivated and uncultivated soils in different regions of Yugoslavia

10th international congress of the International Radiation Protection Association; May 14-19, 2000; Hiroshima, Japa

Migration of depleted uranium contamination through the soil

Military use of ammunition with depleted uranium at South Serbia, caused contamination of the environment. Surface soil and soil profile around projectile with depleted uranium were analyzed three years later by high resolution alpha/gamma spectrometry. It was found that activity levels in the soil layer next to the penetrator changes to 1% of initial value at 15 cm distance. This value is about double background uranium level of the soil at the Bratoselce location.Physical chemistry 2004 : 7th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 21-23 September 200

Trace Elements and Radionuclides in Urban Air Monitored by Moss and Tree Leaves

In urban areas, air quality is strongly influenced by numerous anthropogenic activities. High population density, heavy traffic and domestic heating in winters in the centre, and various industrial activities at the outskirts, influence atmospheric concentrations of trace elements and radionuclides. Consequently, large population is exposed to possible adverse effects arising from the altered urban air composition. Therefore, air quality monitoring has become one of the standard quality control procedures in urban areas

Prirodni i proizvedeni radionuklidi u zemljištu planinskih regiona Republike Srbije i parametri radijacionog rizika

This review paper discusses the content of natural ( 40K, 238U, 226Ra, and 232Th) and artificial (137Cs) radionuclides in the soil of the mountains of Maljen, Tara and Kopaonik in the Republic of Serbia over 2002-2015. In addition, the paper gives radiation hazard parameters, i.e., radium equivalent activity, absorbed dose rate, annual effective dose equivalent, external hazard index, annual gonadal dose equivalent, and excess lifetime cancer risk outdoors that we calculated from the obtained content of the natural radionuclides in the soil samples. We compared the parameters to previously published results for different parts of the country and looked into the radioecological status of the investigated areas.U radu su prikazani rezultati gamaspektrometrijskog određivanja sadržaja prirodnih (40K, 238U, 226Ra i 232Th) i proizvedenog (137Cs) radionuklida u zemljištu sa područja planina Maljen, Tara i Kopaonik. Uzorci zemljišta prikupljeni su u periodu od 2002. do 2015. godine na različitim nadmorskim visinama. Na osnovu sadržaja radionuklida u zemljištu odredili smo parametre radijacionog rizika: radijum ekvivalentnu aktivnost, jačinu doze, godišnju efektivnu dozu spoljašnjeg zračenja, indeks spoljašnjeg hazarda, godišnju gonadnu dozu i faktor rizika pojave kancera na području planinskih regiona Republike Srbije, i potom ih uporedili sa ranije objavljenim rezultatima za pojedine regione Republike Srbije

Detecting scaling in phase transitions on the truncated Heisenberg algebra

We construct and analyze a phase diagram of a self-interacting matrix field coupled to curvature of the non-commutative truncated Heisenberg space. The model reduces to the renormalizable Grosse-Wulkenhaar model in an infinite matrix size limit and exhibits a purely non-commutative non-uniformly ordered phase. Particular attention is given to scaling of model’s parameters. We additionally provide the infinite matrix size limit for the disordered to ordered phase transition line

Some problems in radionuclide activity determination in environmental samples

U radii se razmatraju problemi odredivanja aktivnosti radionuklida 11 uzorcima iz zivolne sredine obzirom na metode sakupljanja uzoraka. metode za odredivanje aktivnosti radionuklida, tehnicke karakteristike i kalibraciju merila i opste usiove merenja. Ukazano je na prednost metode reprezentativnog uzorka i bioindikatora za odredene radionuklide u odnosu na metodu slucajnog uzorka. U opstem slucaju. radiohemijske metode imaju veci procenat gubitaka radionuklida u toku pripremc uzorka i samog merenja ali su cesto osetijivije. dok se kod spektromctrijc gama zracenja isti stepen osetljivosti postize produzenjem merenja i povecanjem mase uzorka. Ovo s druge strane moze predstavijati znacajan svega prirodnih vremena izvor greske, posebno kod merenja niskih aktivnosti, pre r radionuklida zbog varijacija nivoa prirodnog zracenja u toku merenja. Znacajni izvori gresaka mogu poticati i od nehomogenosti uzorka i geometrije merenja, jei su neke geometrije merenja pogodnije u datim uslovima merenja, obzirom na specificnu guslinu matriksa (nosaca radionuklida) i nivo aktivnosti radionuklida. Hemijski sastav i geometrija referentnih standardnih materijala u odnosu na sastav i geometriju merenja uzorka mogu predstavijati dodatni izvor greske. Minimizacija Likupne greske merenja postize se standardizacijom merila i metoda merenja u okviru postupaka interkalibracije i interkomparacije.The paper reviews some of the basic problems in radionuclide activity determination in environmental samples. Problems arise from procedures ' sampling and sample preparation, technical characteristics and calibration or measuring instruments, data processing and presentation. Advantages of the representative sample method and bioindicators over the random sample method accentuated with regard to certain radionuclides. Significant errors in radiochemical methods occur due to losses during sample preparation and measurement. In general, radiochemical methods are more sensitive than gamma radiation spectrometry methods. The same level of sensitivity is achieved by prolonging the measurement period and/or by increasing the sample mass which can be a significant source of error particularly in low activity measurements of natural radionuclides because of natural radiation level variations during measurements. Significant error sources can also stem from non-homogeneity of the sample and measurement geometry. Some measurement geometries are more suitable than others which depends on the specific density of their matrix (radionuclide carrier) and the activity level of radionuclides. Differences in the chemical composition and the geometry betw'een reference materials and the sample can additionally generate errors. Total measurement error is minimized by the standardization of instruments and measurement methods resulting from intercalibration and intercomparison procedures. The importance of Quality Control and Quality Assurance program implementation is emphasized. ar

Radioactivity Concentrations in Spa Waters - Dose Assessment

In this study 6 different spa water samples from Serbia, Hungary and Czech Republic were investigated in order to determine their radioactivity concentrations. These waters have been used on a large scale for medical and bathing purposes; for therapy, rehabilitation and recreation and also used for drinking, which is the most important. The obtained results showed that natural activity concentrations of alpha emitting radionuclides was within World Health Organization recommended levels and Serbian applicable regulations, but the gross beta activity exceed 1 Bq L-1 for some of the samples. Considering the fact that gross beta activity in four samples was higher than recommended levels, gamma spectrometric measurements were performed, in order to identify radionuclides which caused increase of the gross beta activity. It was found that K-40 was responsible for the elevated gross beta activity. Based on the obtained results the annual effective dose was calculated.3rd International Conference on Radiation and Applications in Various Fields of Research (RAD), Jun 08-12, 2015, Budva, Montenegr