1,720,988 research outputs found
The impact of the microenvironment on the survival and migration of melanoma cells with different metastatic potential
Get PDFEffects of metformin and 2-deoxy-D-glucose on MDA-MB-231 cells and model T lymphocytes in vitro
No full textPresnovne spremembe in izogibanje imunskemu sistemu so temeljne lastnosti raka. Metformin in 2-deoksi-D-glukoza (2DG) sta presnovni učinkovini z različnimi obetavnimi protirakavimi in imunomodulatornimi učinki. Njuna kombinacija povzroči odlepljanje živih celic raka dojke MDA-MB-231 z ohranjeno sposobnostjo proliferacije in vitro. Od podlage neodvisna rast rakavih celic in vitro korelira z metastaziranjem in vivo. Obenem zahteva mitohondrijsko biogenezo, vendar presnovne spremembe pri odlepljanju, ter učinek metformina in 2DG na mitohondrije niso znani. Z metabolomiko smo identificirali presnovne spremembe v celicah MDA-MB-231, tretiranih z metforminom in 2DG. Visoka 2DG in kombinacija metformina in nizke 2DG (metformin+2DG) sta spremenili presnovni profil podobno kot metformin. To ne razloži odlepljanja, ki je posledica zmanjšanja N-glikozilacije proteinov z 2DG in njegovega potenciranja z metforminom. Odlepljene celice so bile mehkejše in presenetljivo presnovno bližje kontroli kot pritrjenim tretiranim celicam. Imele so spremenjen nivo NADPH, glutamina in presnove maščobnih kislin, kar je značilno za rast v odlepljenem stanju. Metformin+2DG in visoka koncentracija 2DG sta povečala mitohondrijsko maso celic raka dojke preko aktivacije mitohondrijske biogeneze in povečane velikosti, ne pa tudi števila mitohondrijev. 2DG in metformin+2DG sta inducirala stres endoplazmatskega retikuluma, ki je bil potencialni sprožilec mitohondrijske biogeneze skupaj z energijsim stresom. Aktivacija z adenozin monofosfatom aktivirane proteinske kinaze je pri tem igrala vlogo, a ni bila zadostna za sprožitev mitohondrijske biogeneze. Metformin in 2DG tako povzročita presnovni stres in mitohondrijske prilagoditve, kar omogoča preživetje rakavih celic ob odlepljanju in energijskem stresu. Vzporedno sta 2DG in metformin+2DG zmanjšala izražanje liganda 1 za receptor programirane smrti 1 (PD-L1) na celicah MDA-MB-231 preko zavrte N-glikozilacije in zmanjšala izražanje receptorja programirane celične smrti 1 (PD-1) na celicah Jurkat. Metformin, visoka koncetracija 2DG in metformin+2DG so zavrli proliferacijo, aktivacijo in izločanje interlevkina 2 preko zmanjšanja proizvodnje adenozin trifosfata, nizka 2DG pa je ohranila izločanje interlevkina 2 in povečala izločanje interferona ?. Nizka koncetracija glukoze je okrepila učinek metformina, medtem kot supra-fiziološka koncentracija glukoze ali eksogeni piruvat nista imela učinka. Presnovne učinkovine delno zavrejo funkcijo celic Jurkat, specifične kombinacije pa bi lahko izboljšale protitumorsko imunost preko osi PD-1/PD-L1.Metabolic alterations and immune evasion are emerging hallmarks of cancer. Metformin and 2-deoxy-D-glucose (2DG) are metabolic drugs with several promising anti-cancer and immunomodulatory effects. Their combination induces detachment of viable MDA-MB-231 breast cancer cells retaining proliferation capacity in vitro. Anchorage-independent growth of cancer cells in vitro is correlated to metastasis formation in vivo and requires mitochondrial biogenesis, but the metabolic changes involved in detachment and the effect of metformin and 2DG on mitochondria are unknown. We used liquid chromatography-mass spectrometry metabolomics to identify alterations in metformin and 2DG treated MDA-MB-231 cells. High concentration of 2DG and the combination of metformin and low concentration of 2DG (metformin+2DG) altered the metabolic profile similarly to metformin. These alterations could not explain detachment, which was actually induced by suppressed protein N-glycosylation by 2DG and its potentiation by metformin. The detached cells were softer and, surprisingly, metabolically closer to control than their attached counterparts. They exhibited altered NADPH, glutamine and fatty acid metabolism characteristic for anchorage-independent growth. Metformin+2DG and high 2DG increased mitochondrial mass in breast cancer cells by activating mitochondrial biogenesis and increasing mitochondrial size, but not their number. 2DG and metformin+2DG induced endoplasmic reticulum stress which could trigger mitochondrial biogenesis together with energy stress. Adenosine monophosphate activated protein kinase activation was also involved but not sufficient for mitochondrial biogenesis. Overall, metformin and 2DG induce metabolic and mitochondrial adaptations enabling breast cancer cell survival in detachment and energy stress. In parallel, 2DG and metformin+2DG reduced programmed death ligand 1 (PD-L1) expression in MDA-MB-231 cells by suppressing N-glycosylation and reduced programmed death 1 (PD-1) expression in Jurkat cells. Metformin, high 2DG and metformin+2DG inhibited Jurkat cell proliferation, activation and interleukin 2 secretion by reducing adenosine triphosphate production, but low 2DG preserved interleukin 2 and boosted interferon γ secretion. Low glucose concentration potentiated the effect of metformin, while supra-physiological glucose levels or exogenous pyruvate had no effect. While metabolic drugs partially inhibit Jurkat function, specific combinations could improve anti-tumor immunity via PD-1/PD-L1 axis inhibition
Effect of different nanoparticles on viability, stress response and differentitation of cell line Caco-2
No full textV našem delu smo analizirali vpliv 48-urne izpostavitve nanodelcev (ND) food grade (FG) nano TiO2, nano SiO2 in nano srebra, v zmernih (2 in 10 µg/mL) in višjih koncentracijah (50 in 100 µg/mL) na celično linijo Caco-2. Z metodo diferencialnega barvanja po Hoechstu in s propidijevim jodidom (PI) smo prikazali koncentracijsko odvisen vpliv izbranih ND na preživetje celic. S pomočjo fluorometričnih metod smo analizirali nastanek reaktivnih kisikovih spojin (ROS) v tretiranih nediferenciranih celicah Caco-2 z reagentom CM-H2DCFDA ter analizirali aktivnost alkalne fosfataze (ALP) v diferenciranih celicah Caco-2 preko zaznavanja signala od MUP (metilumbeliferil fosfat) odcepljenih fosfatnih skupin. Delež ROS je bil povečan v primeru celic tretiranih s FG TiO2 in SiO2 pri koncentracijah > 50 µg/mL, vendar nikjer ni prišlo do statistično značilnih razlik v primerjavi s kontrolo. Rezultati ne nakazujejo na vpliv izbranih ND na diferenciacijo celic, kaže pa se od koncentracije odvisen vpliv preučevanih nanodelcev na aktivnost membranske ALP, ki se sintetizira v diferenciranih celicah Caco-2. Prikazali smo vpliv izbranih ND na preživetje celic in vpliv višjih koncentracij izbranih ND na nastanek ROS v tretiranih nediferenciranih celicah Caco-2. Za določitev vpliva izbranih ND na aktivnost ALP v diferenciranih celicah Caco-2 bi morali poskus izvesti v večih bioloških ponovitvah.In our thesis we have analysed the effect of acute treatment of Caco-2 with three nanoparticles (NP) – food grade (FG) nano TiO2, nano SiO2 and nano silver NP with moderate (2 and 10 µg/mL) and high (50 in 100 µg/mL) concentrations. With colouring by Hoechst and propidium iodide (PI) we observed concentration dependent effect of selected NPs on cell viability. With spectrophotometric methods we have analysed the quantity of reactive oxygen species (ROS) in treated undifferentiated cells Caco-2 with reagent CM-H2DCFDA and also analysed the activity of alkaline phosphatase (ALP) in treated differentiated cells by detecting from methylumbelliferyl phosphate derived phosphate groups. Albeit ROS was elevated in with high concentrations FG TiO2 and SiO2 (> 50 µg/mL) treated undifferentitated cells, no statistically significant differences were observed. Although results do not indicate concentration dependent effect of selected NPs on cell differentiation, there could be an effect on alkaline phosphatase activity in treated differentiated cells Caco-2. We have shown an effect of selected NPs on cell viability and effect of high concentrations FG TiO2 and SiO2 NPs on ROS generation in treated undifferentiated cells Caco-2. The effect of selected NPs on ALP activity in treated differentiated cells Caco-2 could be established with additional biological repetitions
NUMERICAL MODELLING OF INDUCTIVE SYSTEM FOR WIRELESS POWER TRANSFER
Get PDFInduktivni sistem za brezžicni prenos elektricne energije predstavlja tehnicno
in tržno zelo zanimiv nacin prenosa elektricne energije. Tudi v podjetju
Kolektor Sikom, PE Magma razvijamo induktivne sisteme za brezžicni prenos
elektricne energije za polnjenje prenosnih naprav v avtomobilski industriji, medicini
in ostalih tržno zanimivih podrocjih.
Doktorska disertacija opisuje numericno modeliranje induktivnega sistema za
brezžicni prenos elektricne energije, ki je sestavljen iz oddajne in sprejemne tuljave z
dodanima feritnima jedroma. Induktivni prenos se loci na resonancni in neresonancni
prenos. Podrobno je obravnavan induktivni neresonancni prenos, saj je podjetje
Kolektor Sikom, PE Magma usmerjeno v izdelavo tuljav z dodanimi feritnimi jedri
in ne v izdelavo elektricnih vezij, ki omogocajo tudi resonancni prenos. Poleg tega
vecina tržno zanimivih aplikacij za induktivni prenos uporablja polnjenje prenosnih
naprav na majhnih razdaljah nekaj milimetrov, kjer je neresonancni prenos dovolj
dobro primerljiv z resonancnim.
V literaturi so predstavljeni vecinoma induktivni sistemi, sestavljeni iz oddajne
in sprejemne tuljave brez feritnih jeder, ki se lahko opisujejo z analiticnimi ali
empiricnimi enacbami. Dodana feritna jedra bistveno izboljšajo brezžicni prenos in
služijo tudi kot magnetna zašcita pred magnetnimi polji iz strani oddajne in
sprejemne tuljave. Vendar pa v literaturi ni predstavljenih enacb za opis induktivnega
sistema z dodanimi feritnimi jedri, saj zaradi kompleksne geometrije feritnih jeder in
nelinearnih lastnosti feritnega materiala analiticen pristop ni vec mogoc. Zato je
nujno potrebno uporabiti programska okolja za numericno modeliranje induktivnega
sistema z dodanimi feritnimi jedri. Tudi obstojeci numericni modeli v literaturi ne
opisujejo vpliva vseh parametrov, ki vplivajo na induktivni sistem.
Namen tega doktorskega dela je z numericnimi modeli: opisati, ovrednotiti in
analizirati vpliv položaja oddajne in sprejemne tuljave z dodanimi feritnimi jedri,
navesti možnosti izbire feritnih materialov iz stališca relativne permeabilnosti in
magnetne zašcite, preuciti vpliv bakrene folije na magnetno zašcito, poiskati
optimalno obliko feritnih jeder, izracunati induktivnosti tuljav z dodanim feritnim
jedrom, preuciti vpliv zlaganja feritnih plošc, dolociti izgube v pletenicah razlicnih
tuljav, ovrednotiti izgube v feritnih jedrih in na koncu še analizirati segrevanje tuljav
s feritnimi jedri. Numericni modeli so tudi primerjani z izmerjenimi vrednostmi.
V uvodnih poglavjih doktorske disertacije je predstavljen induktivni sistem za
brezžicni prenos elektricne energije, sestavljen iz oddajne in sprejemne tuljave.
Induktivni sistem je predstavljen preko razlicnih enacb in kljucnih parametrov: faktor
sklopitve, faktor kvalitete in izkoristek prenosa. Razložena je tudi primerjava med
induktivnim resonancnim in neresonancnim prenosom za induktivni sistem za
brezžicni prenos elektricne energije. Nadalje sta predstavljena parametra tuljav
induktivnost in ohmska upornost. Induktivnost je predstavljena iz izracuna preko
teoreticnih in empiricnih metod, kjer je tudi naveden pregled literature izracuna
induktivnosti zracnih tuljav razlicnih avtorjev. Ohmska upornost pa je sestavljena iz
ciste ohmske upornosti, upornosti zaradi kožnega in sosedstvenega pojava.
V nadaljevanju doktorske disertacije so opisani uporabljeni materiali in
metode. Izracuni numericnih modelov so bili izvedeni v programskih okoljih Comsol
Multiphysics in Ansoft Maxwell. Lastnosti uporabljenih feritnih materialov v
modelih so izbrani na podlagi realnih materialov, ki jih industrijsko uporabljamo za
tovrstne aplikacije. Nazadnje so razložene tudi metode merjenja in navedeni
uporabljeni merilni instrumenti s katerimi so bile verificirane simulacije v
programskih okoljih.
V poglavju 5. Rezultati in razprava so z numericnimi modeli analizirani vplivi
razlicnih geometrij in parametrov: faktor sklopitve k, induktivnost L,
faktor kvalitete Q in magnetne zašcite, ki imajo vpliv na delovanje in lastnosti
induktivnega sistema za brezžicni prenos elektricne energije. Vpliv spreminjanja
položaja na faktor sklopitve je bil narejen na primeru geometrije oddajne in
sprejemne tuljave z dodanima feritnima jedroma v vodoravni smeri, navpicni smeri
in kotu med tuljavama. Ugotovljeno je bilo, da se z vecanjem razdalj v navpicni,
vodoravni smeri in povecevanju kota med tuljavama faktor sklopitve k zmanjšuje.
Dodatno so bile še primerjane med seboj vrednosti lastnih in medsebojnih
induktivnosti tuljav z dodanima feritnima jedroma in razložen pojav negativnega
faktorja sklopitve k.
Iz stališca faktorja sklopitve k in magnetne zašcite je bila izvedena
parametrizacija izbire razlicnih feritnih materialov preko vecanja relativne
permeabilnosti na doloceni geometriji induktivnega sistema. Ugotovljeno je bilo, da
ni smiselno višati relativne permeabilnosti preko dolocene vrednosti, saj s tem ne
izboljšamo bistveno faktorja sklopitve k in magnetne zašcite. Nadalje je bila za
izboljšanje magnetne zašcite na feritnih jedrih dodana tudi bakrena folija, ki še
dodatno izboljša magnetno zašcito.
Feritna jedra, ki se uporabljajo v induktivnem sistemu so razlicnih oblik kot so:
feritni loncki, feritne plošce, E-jedra in U-jedra. V serijski proizvodnji je pri
nacrtovanju induktivnih komponent pomemben kriterij poraba feritnega materiala.
Zato je bila izvedena optimizacija induktivnega sistema sestavljenega iz tuljav z
dodanimi feritnimi jedri iz feritnih palck. Ugotovljeno je bilo, da je za dosego
visokega faktorja sklopitve k potrebno izbrati vecje število feritnih palck. S tem se
doseže manjša poraba materiala in tudi manjša teža feritnega jedra. Poleg tega
predstavlja vecje število feritnih palck dovolj dobro magnetno zašcito. Dodatno je
bilo ugotovljeno, da je vpliv zamika kota na skupno razliko faktorja sklopitve k med
feritnimi palckami na oddajni in sprejemni strani manjši v primeru vecjega števila
feritnih palck.
Iz stališca izracuna induktivnosti tuljav z dodanimi jedri, je bilo ugotovljeno,
da so v literaturi predstavljene predvsem analiticne in empiricne enacbe za tuljave
brez feritnih jeder. Zato je bil uveden nov faktor induktivnosti, ki omogoca hitrejši
poenostavljeni izracun induktivnosti za tuljave z dodanimi feritnimi jedri v
numericnih modelih.
Zaradi omejitev pri izdelavi vecjih feritnih plošc v serijski proizvodnji je bila
razložena tudi možnost izdelave preko tehnike zlaganja. Pri tem se sestavi vecjo
feritno plošco iz vec majhnih feritnih plošc, kjer je potrebno izbrati kompromis med
velikostjo zracne reže in številom majhnih feritnih plošc. Zlaganje feritnih plošc ne
poslabša bistveno faktorja sklopitve k in magnetne zašcite.
V induktivnem sistemu je zelo pomembno tudi dolociti izgube v tuljavah in
feritnih jedrih. Tuljava, ki deluje v visokofrekvencnem obmocju nad 100 kHz je
narejena iz pletenice, ki je sestavljena iz vec manjših vlaken. Iz stališca dolocitve
izgub v pletenicah razlicnih tuljav je bilo narejenih vec analiz zracnih tuljav z
razlicnim številom vlaken in številom ovojev. Izkaže se, da tuljava sestavljena iz
pletenice predstavlja zelo kompleksno geometrijo za numericne modele, saj je le-ta
sestavljena iz velikega števila med seboj prepletenih vlaken. Poleg tega geometrija
pletenice ni enolicno dolocena in poznana, saj je zelo odvisna od izdelave
proizvajalca. Ugotovljeno je bilo, da se je zaradi same kompleksnosti pletenice pri
visokih frekvencah bolje odlociti za izdelavo konkretne tuljave in izvesti meritve
upornosti ali pa uporabiti izracune upornosti in s tem izgub iz omenjene literature.
Nadalje je bil pri doloceni geometriji izveden tudi izracun faktorja kvalitete Q obeh
tuljav z dodanimi feritnimi jedri. Izgube v feritnih jedrih so bile dolocene preko
numericnih modelov in kataloških podatkov feritnega proizvajalca. Iz primerjave
velikosti prevladujocih izgub v induktivnem sistemu je bilo ugotovljeno, da se
prevladujoce izgube nahajajo v tuljavah in ne v feritnih jedrih. Izracunane izgube v
tuljavi in feritnih jedrih so bili nato vnesene še v termicni model. Ugotovljeno je bilo,
da natancno poznavanje izgub v feritnih jedrih, ki najveckrat izhajajo iz kataloških
podatkov materiala, ne prispeva pomembno k izboljšanju natancnosti modelov.
Vse analize in izracuni razlicnih vplivov in parametrov na induktivni sistem so
bili izvedeni s simulacijami v razlicnih numericnih modelih v programskih okoljih,
ki so osnovani na metodi koncnih elementov. Rezultati specificnih numericnih
modelov so bili primerjani z eksperimentalno dobljenimi vrednostmi. Razvoj
numericnih modelov je omogocil natancen vpogled v delovanje sklopa oddajne in
sprejemne tuljave z dodanima feritnima jedroma iz stališca elektromagnetnih in
termicnih pojavov. Razviti numericni modeli bodo pripomogli k hitrejšemu in
boljšemu nacrtovanju induktivnega sistema za brezžicni prenos elektricne energije.An inductive system for wireless power transfer is technically and
commercially very interesting way of transmitting electrical energy. Also in
company Kolektor Sikom, PE Magma we develop systems for inductive wireless
power transfer to charge portable devices in the automotive industry, medicine and
other market interesting areas.
Doctoral dissertation describes the numerical modeling of the inductive system
for wireless power transfer, which consists of the transmitter and the receiver coil
with ferrite cores. Inductive wireless power transfer can be resonant or non-resonant.
Since the company Kolektor Sikom, PE Magma has been focused on production of
coils with ferrite cores we analyze in detail non-resonant transfer while for
applications in power electronics resonant transfer is also relevant. Also, most
interesting market applications for charging portable devices use small distances in
the range of a few millimeters, where non-resonant transfer is comparable with the
resonant transfer.
In the literature, inductive systems mainly consist of a transmitter and receiver
coils without ferrite cores. Such simple systems, can be analyzed by analytical or
empirical equations. In order to improve inductive wireless power transfer, ferrite
cores are also used that in parallel also serve as a magnetic shield against magnetic
fields from the transmitter and receiver coils. However, due to the complex geometry
of the ferrite cores and nonlinear properties of the ferrite material the analytical
approach is no longer possible. It is therefore essential to use finite element software
for numerical modeling of the inductive system with ferrite cores. Studies, which
describe the inductive system with numerical modeling also use simplified models
which do not describe the influence of all parameters.
The aim of this work was to build numerical models: which describe, evaluate
and analyze the impact of position between the transmitter and receiver coils with
ferrite cores, to specify ferrite materials from the relative permeability and magnetic
shield, to consider the impact of copper foil on the magnetic shield, to find the
optimal shape of the ferrite cores, to calculate inductance of coils with ferrite cores,
to examine the effect of assembled ferrite plates, to determine the losses in different
coils made from litz wires, to evaluate the losses in ferrite cores, and finally to
analyze the impact of the heating on transmitter and receiver coils with ferrite cores.
Numerical models are also compared with the measurements.
In the introductory chapters an inductive system for wireless power transfer is
presented, which consists of transmitter and receiver coils. Inductive system is
presented through various equations and parameters: the coupling coefficient, quality
factor and efficiency. A comparison between inductive resonant and non-resonant
wireless power transfer is also presented. Furthermore, the parameters inductance
and ohmic resistance are defined. Inductance is presented from theoretical and
empirical methods, where also an overview of the literature for inductance
calculations of different authors is presented. The ohmic resistance consists of pure
ohmic resistance, resistance due to skin and proximity effect.
Further, the materials and methods are explained. The calculations of
numerical models were made in the programming environments Comsol
Multiphysics and Ansoft Maxwell. Characteristics of ferrite materials in the models
were selected on the basis of realistic materials that can be used or are used for such
industrial applications. Finally, the measuring methods and measuring instruments
which were used for verification of simulations in programming environments are
also discussed.
In the 5. Results and discussion chapter results of numerical models which
analyzed the effects of different geometries and parameters are presented: the
coupling coefficient k, the inductance L, the quality factor Q and magnetic shielding.
All these parameters have an impact on the performance and characteristics of an
inductive system for wireless power transfer. The impact of varying position on
coupling coefficient is presented in example of geometry with transmitter and
receiver coil with additional ferrite cores in horizontal direction, vertical direction
and angle of rotation between coils. It has been found that by increasing the distances
in the vertical and horizontal direction and by increasing the angle between coils the
coupling coefficient k decreases. Additionally, values of self and mutual inductances
of coils with ferrite cores are compared between each other and also the effect of
negative coupling coefficient k is explained.
From the view of the coupling coefficient k and magnetic shielding the
parameterization of various ferrite materials with increasing the relative permeability
was also made for the specific geometry of the inductive system. It has been found
that using materials with higher relative permeability does not significantly improve
the value of coupling coefficient k and magnetic shielding. Futhermore, the copper
foil added on ferrite core significantly improves magnetic shielding.
Furthermore, ferrite cores, which are used in inductive system are of different
shapes: ferrite pots, ferrite plates, the E-core and the U-core. In a serial production of
inductive components consumption of ferrite material is of great importance.
Therefore, optimization of the inductive system made of coils with ferrite cores
which were made from ferrite bars was analyzed. We obtained that to reach high
value of coupling coefficient k it is important to select a higher number of ferrite
bars. This results in less material used and also less weight of a ferrite core. In
addition, higher number of ferrite bars provide sufficient magnetic shielding. Further,
it has been found that the effect of the angle between ferrite bars on the transmitter
and receiver side on the overall coupling coefficient is smaller in the case of higher
number of ferrite bars.
The inductance of coils with ferrite cores as presented in the literature, is
primarily based on analytical and empirical equations for coils without ferrite cores.
Therefore, a new inductance factor was defined which allows faster and simplified
calculation of inductance of coils with ferrite cores in numerical models.
Due to the limitations in manufacturing larger ferrite plates in serial production
also the possibility of making through stacking was analyzed. The larger ferrite plate
is therefore made from small ferrite plates where it is necessary to choose some
compromise between the size of an air gap and the number of ferrite plates. Stacking
of ferrite plates does not deteriorate significantly the coupling coefficient k and
magnetic shielding.
Moreover, it is very important to determine the losses in the coils and in ferrite
cores. The coil, which is used in high frequency range above 100 kHz, is made of
litz wire which consists of number of smaller strands. For the determination of losses
in coils, which are made of litz wire, more air coils with the different number of turns
and strands were analyzed. It was concluded that coil made of litz wire represents
very complex structure in numerical models, since it is made of the large number of
twisted strands. In addition, the geometry of litz wire is not uniquely determined and
known as it is very dependent on the manufacturing process. It has been found that
due to the complex structure of litz wire in high frequencies, it is better to make a
real coil and to make measurements of resistivity or to use resistivity formulas and
thus losses from the literature. Further, there was performed at certain geometry also
the calculation of the quality factor Q of the two coils with the addition of ferrite
cores. The losses in ferrite cores were determined through numerical models and
catalogue data of ferrite manufacturer. In the analysis of losses in the inductive
system, it has been found that the dominant losses are in the coils and not in the
ferrite cores. Both calculated losses in coils and ferrite cores were then inserted also
in a thermal model. It was found that the accurate knowledge of the losses in ferrite
cores, which are usually derived from catalogue data of material, does not
significantly contribute to improve the accuracy of the models.
All analyzes and calculations of different impacts and parameters on inductive
system were made through simulations in different numerical models in the
programming environments which are based on finite element method. Results of
specific numerical models were compared to experimentally obtained values. The
development of numerical models provides a detailed insight into the functioning of
the inductive system made of transmitter and receiver coils with ferrite cores from
view of electromagnetic and thermal phenomena. Developed numerical models will
contribute to a faster and better design of an inductive system for wireless power
transfer
Protein corona analysis of selected nanoparticles, exposed to human serum in vitro.
No full textProteinska korona, ki nastane okoli nanodelcev v fizioloških medijih, ima pomembno vlogo pri biokompatibilnosti nanodelcev. Cilj naše raziskave je bil določanje sestave proteinske korone izbranih nanodelcev izpostavljenih krvnemu serumu zdravih posameznikov. Nanodelce smo inkubirali s humanim serumom, da se je formirala proteinska korona. Proteine korone smo ločili na NaDS-PAGE elektroforeznem gelu in jih identificirali s pomočjo masne spektrometrije. Ugotovili smo, kateri izmed nanodelcev nase vežejo največ proteinov in kako se sestava proteinske korone med njimi razlikuje. Z identifikacijo proteinov, ki se vežejo na izbrane nanodelce v krvnem serumu, smo poglobili razumevanje možnih vplivov različnih nanodelcev na fiziološko ravnovesje po vstopu v organizem. Zanimala nas je sestava proteinske korone, razlike med različnimi nanodelci ter specifično interakcije s proteini, ki bi potencialno lahko povzročili morebitne neželene učinke nanodelcev na procese, kot so strjevanje krvi in aktivacija komplementa ter trombocitov. Potrdili smo hipotezo, da se sestava proteinske korone razlikuje med izbranimi nanodelci ter predvideli vpletenost identificiranih proteinov v procesih hemostaze in imunskega odziva. Glede na rezultate naše raziskave lahko sklepamo, da so izbrani nanodelci vpleteni v nepričakovane interakcije s proteini krvi, kar bi potencialno lahko vplivalo na uspešnost biomedicinskih postopkov, pri katerih se uporabljajo nanodelci. Prav tako bi lahko omenjene interakcije vodile do nezaželenih imunskih odzivov in drugih učinkov. Posledično bi lahko nanodelci predstavljali dejavnik tveganja za zdravje človeka zaradi vse večje izpostavljenosti nanodelcem.Protein corona that forms around nanoparticles in physiological media plays an important role in the biocompatibility of nanoparticles. The aim of our research was to determine the composition of the protein corona of selected nanoparticles in the blood serum of healthy individuals. We incubated nanoparticles with human serum to form the protein corona. We separated the corona proteins on a SDS-PAGE electrophoresis gel and identified them by mass spectrometry. We determined which nanoparticles bind the highest number of proteins and how the composition of the protein corona differs between nanoparticles. By identifying the proteins that bind to selected nanoparticles in blood serum, we deepened our understanding of the potential effects of different nanoparticles on physiological balance after their entry into the body. We were interested in the composition of the protein corona, the differences between different nanoparticles, and in the specific interactions with proteins that could potentially cause adverse effects of nanoparticles on processes such as blood coagulation, complement and platelet activation. We have confirmed the hypothesis that the composition of the protein corona differs between the selected nanoparticles and demonstrated the involvement of the identified proteins in the processes of hemostasis and immune response. Based on the results of our research, we can conclude that the selected nanoparticles are involved in unexpected interactions with blood proteins, which could potentially impact the success of biomedical procedures involving nanoparticles. Additionally, these interactions could lead to undesirable immune responses and other effects. Consequently, nanoparticles could represent a risk factor for human health due to increasing exposure to nanoparticles
Proteomic characterization of nanoparticles for evaluation of their cytotoxicity, immunotoxicity and development of new types of nanoparticles
Get PDFNanodelci so delci zelo majhnih, nanometrskih dimenzij. Človek je lahko izpostavljen nanodelcem preko hrane, kozmetike in tekstila. Možna je tudi izpostavitev ob zdravljenju nekaterih specifičnih bolezni. Mehanizmi delovanja nanodelcev v organizmu še niso povsem jasni. Preden nanodelci pridejo v stik s celicami oziroma tkivi organizma so izpostavljeni medijem, ki vsebujejo makromolekule (proteine, lipide, nukleinske kisline). Odvisno od lastnosti makromolekul, nanodelcev in medija, med makromolekulami in površino nanodelcev potečejo interakcije, ki vodijo do nastanka t.i. biokorone. Biokorona je plast makromolekul, ki tvorijo interakcije s površino nanodelca, kadar pa govorimo o interakcijah med proteini in površino nanodelca, govorimo o proteinski koroni. Količine in tipe proteinov, ki so vezani na površino nanodelca, določajo fizikalno-kemijske lastnosti nanodelcev, lastnosti proteinov in lastnosti okoliškega medija. Osredotočili smo se na dva tipa magnetnih nanodelcev, relevantnih za biomedicinske aplikacije, ter na industrijsko proizvedene nanodelce, ki so prisotni v produktih za vsakdanjo rabo.
V prvem delu disertacije smo pokazali, da je za interakcije med proteini in nanodelci bistvena predpriprava nanodelcev. Silicijeve nanodelce in kobalt feritne nanodelce, oplaščene s poliakrilno kislino, smo pred izpostavitvijo proteinom redčili v štirih različnih medijih ter dokazali, da izbira medija za predpripravo nanodelcev pomembno določa kvalitativno in kvantitativno sestavo proteinske korone. Nadalje smo preverili, če je spremenjena proteinska korona povezana z nastankom citokinov IL-6 in TNF-αv celični liniji THP-1. Povezave med spremenjeno proteinsko korono in izražanjem citokinov nismo dokazali, vendar pa lahko nanodelci vplivajo tudi na druge dele imunskega sistema.
Citotoksičnost kobalt feritnih nanodelcev oplaščenih s polietileniminom smo želeli zmanjšati z dodatnim oplaščenjem z glutationom. Na celični liniji CHO smo pokazali, da lahko z glutationskim oplaščenjem dosežemo najmanj 30% višjo viabilnost v primerjavi z neoplaščeno formulacijo in zmanjšanje nastanka reaktivnih kisikovih zvrsti. Ključen korak je bil dodatek glutationa ob sintezi, saj z dodatkom prostega glutationa v celični medij ob hkratni izpostavitvi nanodelcem nismo dosegli želenega učinka. Primerjali smo tudi pot internalizacije neoplaščene in oplaščene formulacije, kjer nismo opazili razlik. Nanodelce smo našli izključno v znotrajceličnih veziklih, kar je v nasprotju s hipotezo lizosomalnega pobega. Dokazali smo, da so nanodelci kljub dodatnemu oplaščenju še vedno uporabni za transfekcijo, ki je glavna aplikacija omenjenih nanodelcev.
Na celičnih modelih zdravega in rakastega urotelija smo dokazali selektivno endocitozo kobalt feritnih nanodelcev, oplaščenih s poliakrilno kislino, v rakaste celice urotelija. Na podlagi predpostavke o selektivni endocitozi in razumevanja citotoksičnosti kobalt feritnih nanodelcev oplaščenih s polietileniminom smo preverili potencialno obliko zdravljenja urotelijske papilarne neoplazme. Z dodatnim oplaščenjem citotoksičnih nanodelcev z govejim serumskim albuminom smo želeli zmanjšati poškodbe celične membrane, a hkrati ohraniti toksičnost, ki se izrazi po internalizaciji. Na tak način bi, ob predpostavki selektivne endocitoze, dosegli selektivno citotoksičnost proti rakastim celicam. Kratkotrajni učinek (merjenje viabilnosti po treh urah) je delno potrdil našo hipotezo, medtem ko dolgotrajni učinek (merjenje viabilnosti po štiriindvajsetih urah) ni bil v skladu s pričakovanimi rezultati.
V predzadnjem delu disertacije je predstavljena kvantitativna analiza objavljene literature, ki združuje podatke o fizikalno-kemijskih lastnostih nanodelcev, sestavi proteinske korone in učinke na imunski sistem in vitro. Prva ugotovitev analize je bila, da je študij, ki združujejo vse tri kategorije podatkov, izredno malo, razlikovali so se tudi pogoji pod katerimi so bili posamezni eksperimenti izvedeni. Na podlagi 21 študij, ki so ustrezale našim kriterijem, smo naredili kvantitativno analizo. Primerjali smo dve skupini nanodelcev in sicer tiste, ki so sprožili povečan nastanek citokinov, proti ostalim. Pomembne razlike so bile med tipi nanodelcev v obeh skupinah, medtem ko razlik v hidrodinamskem premeru in zeta potencialu med skupinama nismo odkrili. Na podlagi našega vzorca smo sklenili, da sta sestava proteinske korone in sproščanje citokinov neodvisni spremenljivki. Ob koncu je predstavljena študija, s katero smo povezanost med lastnostmi nanodelcev, sestavo proteinske korone in sproščanjem citokinov preverili z lastnimi eksperimenti. Kljub temu, da smo lahko bistveno bolje kontrolirali pogoje posameznih meritev, nismo mogli podati trdnih zaključkov.Nanoparticles are particles of small, nano metric dimensions. Humans are exposed to nanoparticles through food, cosmetics and textile. Moreover, nanoparticles are also increasingly used in healthcare, so there is a possibility of exposure when treating specific diseases. Still, the mechanisms of their action in humans are not clear. Once in the organism, nanoparticles are immediately exposed to physiological fluids containing macromolecules. Based on nanoparticle, macromolecule and medium properties interactions between nanoparticle surface and macromolecules lead to the formation of biocorona. When describing only interactions between nanoparticle surface and proteins this layer of macromolecules, i.e. proteins, is called protein corona. Physicochemical properties of nanoparticles, properties of proteins and properties of surrounding media determine types and quantities of protein bound to nanoparticle surface. We have focused on two types of magnetic nanoparticles relevant for biomedical applications and different industrially engineered nanoparticles present in consumer products.
In the first part of this dissertation we have shown that the selection of media for nanoparticle dilution is a crucial parameter of protein corona composition. Silica nanoparticles and polyacrylic acid coated cobalt ferrite nanoparticles were diluted in four different media prior to corona formation. We have shown that selection of media determined qualitative and quantitative composition of protein corona. Additionally, we tested if differences in corona composition influenced secretion of cytokines IL-6 and TNF-αin the cell line THP-1. There was no connection between differences in protein corona composition and cytokine secretion, but nanoparticles could also affect other parts of immune system.
Next, we tried to reduce cytotoxicity of cobalt ferrite nanoparticles coated with polyethyleneimine by additional coating with glutathione. Using CHO cell line we have shown that additional glutathione coating results in 30% higher viability compared to non-coated formulation and reduction of reactive oxygen species formation. The key was to add glutathione during nanoparticle synthesiswhen added directly to the cell culture media together with nanoparticles, it did not induce the same effect. There were no differences in internalization pathways between nanoparticles. Furthermore, nanoparticles were found exclusively in intracellular vesicles, which is not in accordance with lysosomal escape hypothesis. Moreover, the additional layer of glutathione did not reduce applicability of nanoparticles as a transfection vector.
Cell models of healthy and cancerous urothelium were used to prove selective endocytosis of cobalt ferrite nanoparticles coated with polyacrylic acid into cancerous urothelial cells. Based on this finding and our understanding of cytotoxicity of polyethyleneimine coated nanoparticles, we tested potential bladder papillary neoplasm treatment. With additional layer of bovine serum albumin we tried to reduce direct membrane damage while retaining intracellular toxicity. In this way we would have achieved, based on selective endocytosis, selective cytotoxicity towards cancerous cells. We proved the short-term effect (viability after three hours) but were unable to demonstrate long-term effect (viability after twenty-four hours).
In the next part of this dissertation we are presenting quantitative analysis of published literature, which combines data on physicochemical properties of nanoparticles, composition of protein corona and in vitro immune system effects. Our first conclusion was that the studies combining all three topics are relatively scarcethere were also differences in experimental protocols between the studies. Nonetheless, we performed a quantitative analysis of results collected from the 21 studies that matched our selection criteria. We compared nanoparticles that triggered cytokine secretion with those that did not. We found no differences between hydrodynamic diameter and zeta potential of the two groups, but showed connection between nanoparticle type and cytokine secretion. Based on our analysis we concluded that cytokine secretion and corona composition were independent variables.
In the last part of dissertation we are showing results of our own study, which was designed to analyse connections between nanoparticle characteristics, protein corona composition and cytokine secretion. Despite the fact that we had exactly the same experimental conditions for all experiments, we have not come to a firm conclusion
Effects of metformin on cancer cells in vitro as a function of the available nutrients
Get PDFMetformin se uporablja za zdravljenje sladkorne bolezni in nedavne raziskave so nakazale, da ima morda protirakave učinke. Cilj doktorske disertacije je bil proučiti delovanje metformina na rakave celice v odvisnosti od razpoložljivih hranil v gojišču. Pri tem smo primerjali učinke metformina na klasični enoslojni kulturi z učinki na tumorskih sferoidih. Z uporabo različnih metod za določanje števila, proliferacije, živosti celic in deleža mrtvih celic smo določili, da pomanjkanje piruvata, neesencialnih aminokislin in glukoze poveča učinek metformina na celice MDA-MB-231. Pri pomanjkanju piruvata in/ali glukoze je pri celicah MDA-MB-231 izpostavljenih metforminu nastopila energijska kriza, ki je spodbudila aktivacijo AMPK, kar smo določili s prenosom western. Z uporabo različnih protokolov menjave gojišča in meritvami porabe glukoze smo pojasnili nasprotujoče si rezultate nekaterih raziskav, ki so proučevale učinek nižjih koncentracij glukoze (5–5,6 mM) na delovanje metformina na celice MDA-MB-231. Poleg tega smo povečali učinek metformina na celice MDA-MB-231, MCF-7 in PC-3 z uporabo inhibitorja glikolize, 2-deoksi-D-glukoze (2-DG). Nepričakovano smo opazili, da kombinacija 2-DG in metformina pri 5,6 mM glukozi poveča delež živih odluščenih celic MDA-MB-231 in MCF-7, kar bi bilo lahko pomembno pri razumevanju vpliva presnovnih sprememb na proces metastaziranja rakavih celic.Here we show that depletion of pyruvate, non-essential amino acid and glucose increases the effects of metformin on MDA-MB-231 cells. The effects of metformin differ also between monolayer culture and tumour spheroids. Our results indicate that in glucose-depleted media metformin supressed MDA-MB-231 cell proliferation and reduced their survival due to inhibition of oxidative phosphorylation. In the absence of glucose, MDA-MB-231 cells were unable to adapt to energy crises induced by metformin via upregulation of glycolysis. Thus, metformin probably supressed cellular proliferation in an AMPK-independent manner. Since the absence of glucose increases the effects of metformin on MDA-MB-231 cells, metformin could target cancer cells in a poorly perfused core of the tumour. Medium renewal blocked the anti-proliferative effects of metformin in the presence of 5,6 mM of glucose, which might explain inconsistent results in previous studies. Metformin reduces the number of MDA-MB-231 cells synergistically with 2-DG, which is a competitive inhibitor of glycolysis. Finally, we have observed that combined treatment with metformin and 2-DG induces detachment of viable MDA-MB-231 and MCF-7 cells from the bottom of cell culture wells, which might be important to better understand the effects of changes in metabolic pathways on the process of cancer cell metastazation
Optimization of liposome preparation and their pharmaceutical applicability
No full textLiposomi so majhni vezikli sferične oblike, ki so sestavljeni iz lipidov. Zaradi iste sestave kot celična stena, so biorazgradljivi. Liposomi omogočajo pasivno targetirane terapije, če pa na njihovo steno vežemo še določene ligande, pa jih lahko uporabimo za tarčno dostavo učinkovin. Zaradi njihove široke uporabnosti, je na trgu že veliko liposomalnih formulacij zdravil za različna zdravljenja, tudi proti rakavim obolenjem. Z namenom priprave nove formulacije liposomov za dostavo učinkovin, smo se odločili najprej za postavitev primernega protokola. Ker natančni protokoli za določeno formulacijo niso na voljo, smo najprej izbrali in nato optimizirali protokol priprave ustreznih liposomov, ki bi omogočal zadostno kapsulacijsko učinkovitost vodotopnih molekul. Optimizirali smo parametre nastanka lipidnega filma, temperaturo segrevanja hidracijske raztopine ter tehnik hidracije, optimizirali sestavo hidracijske raztopine in jo prilagodili biološkim pogojem, ter optimizirali dializo. Tako smo iz začetnih približno 0,1 % kapsulacijske učinkovitosti le-to povečali na 10 % za modelno spojino fluorescein. Kot modelno vodotopno učinkovino smo kapsuirali vitamin C, nato pa smo še testirali protokol za kapsulacijo lipofilne molekule digoksina. Vpliv obeh formulacij na preživetje smo preverili na rakavi liniji MDA-MD-231. Pri liposomalnem vitaminu C nam ni uspelo doseči zmanjšanja preživetja in rasti celic, pri liposomalnem digoksinu pa je bil njegov vpliv na viabilnost celic zelo močan, saj je preživelo manj kot 10 % celic.Liposomes are small spherical vesicles which are composed of lipids. Due to containing the same composition as cell walls, they are biodegradable. They can provide the opportunity for developing passively targeted therapies, and if certain ligands are bound to their wall, they are also capable of active targeting. Due to their usefulness and advantages, there are already many liposomal formulations on the market for various treatments, including cancer. With the aim of preparing the liposomes for delivering novel drugs, we have developed our own protocol to do so. Since precise protocols for a particular formulation are not available, we first chose and then optimized the protocol for the preparation of the appropriate liposomes, which would allow sufficient encapsulation efficiency of the water-soluble molecules. For the optimisation we had to vary the lipid film formation parameters, the temperature of the hydration solution and hydration techniques, optimize the composition of the hydration solution and adapt it to biological conditions and optimize the dialysis. Thus, from the initial approximately 0.1 % encapsulation, we improved the efficiency to as much as 10 % encapsulation of the model fluorescein. Vitamin C was encapsulated as a model water-soluble substance and then we tested the protocol for encapsulation of the lipophilic digoxin. The effect of both formulations on survival was verified on the MDA-MD-231 cancer line. In liposomal vitamin C, we failed to achieve an affect on cell viability and cell growth, and in liposomal digoxin its effect on cell viability was very strong, with less than 10 % of cells surviving
The influence of different formulations of TiO2 nanoparticles on survival, differentiation and neurodegenerative changes on human neural cells in vitro
Get PDFNamen magistrskega dela je bil določiti ali izbrani TiO2 nanodelci (ND) (ANATAZ, P25, FG) vplivajo na celice - preživetje, diferenciacijo, nastanek reaktivnih kisikovih zvrsti (ROS), proteine, ki so povezani z nevrodegenerativnimi spremembami, na modelu človeških nevralnih celic SH-SY5Y. Po vzpostavitvi in optimizaciji protokola diferenciacije celic SH-SY5Y, smo diferenciacijo potrdili z določitvijo sprememb v izražanju markerjev diferenciacije (MAP-2, Lamin B, GAP-43) s SDS-PAGE ter prenosom western, kjer smo opazili statistično značilno povečanje vseh diferenciacijskih markerjev v primerjavi z nediferenciranimi celicami. Z uporabo fluorescentnih barvil Hoechst 33342 in PI ter fluorescenčne mikroskopije nismo opazili statistično značilnega vpliva TiO2 ND koncentracij 2, 10 in 25 µg/mL na preživetje diferenciranih celic SH-SY5Y po njihovi 1-dnevni in 5-dnevni izpostavljenosti ND. Prav tako s pomočjo SDS-PAGE ter prenosa western nismo opazili statistično značilnega vpliva TiO2 ND koncentracije 10 in 25 µg/mL na potek diferenciacije celic SH-SY5Y. S pomočjo spektrofluorometrične meritve smo opazili statistično značilno povečanje ROS pri najvišji dodani koncentraciji ND 25 μg/mL, tako pri 5-dnevni izpostavljenosti P25 in ANATAZ ND ter 1-dnevni izpostavljenosti P25 in FG ND. Z uporabo SDS-PAGE ter prenosa western smo opazili, da prihaja do manjše razlike v količini amiloidnega prekurzorskega proteina (APP) ter beta-amiloida (Aβ) po 5-dnevni in 1-dnevni izpostavljenosti celic ND koncentracije 25 µg/mL, ne moremo pa identificirati nastalih fragmentov APP, zato tudi ne moremo določiti pomena teh sprememb. V sklopu magistrskega dela smo uspešno vzpostavili protokol diferenciacije celic SH-SY5Y, pokazali vpliv izbranih TiO2 ND na nastanek ROS ter na količino znotrajceličnih proteinov APP in Aβ. Nismo pa opazili vpliva izbranih ND na preživetje ter diferenciacijo celic SH-SY5Y.The purpose of this master\u27s thesis was to determine whether selected TiO2 nanoparticles (NP) (ANATASE, P25, FG) affect cells - survival, differentiation, formation of reactive oxygen species (ROS), proteins associated with neurodegenerative changes, in the model of human neural cells SH-SY5Y. After establishing and optimising the SH-SY5Y cell differentiation protocol, the differentiation was confirmed by determining changes in the expression of differentiation markers (MAP-2, Lamin B, GAP-43) by SDS-PAGE and western blot, where we observed a statistically significant increase in all differentiation markers compared with undifferentiated cells. Using fluorescent dyes Hoechst 33342 and PI and fluorescence microscopy, no statistically significant effect of TiO2 NP concentrations of 2, 10, 25 µg/mL on the survival of differentiated SH-SY5Y cells was observed after their 1-day and 5-days exposure. Also, no statistically significant effect of TiO2 NP concentrations of 10 and 25 µg/mL on the course of SH-SY5Y cell differentiation was observed by SDS-PAGE and western blot. By means of spectrofluorometric measurement, a statistically significant increase in ROS was observed at the highest added NP concentration of 25 μg/mL, both at 5-days exposure to P25 and ANATASE NP and at 1-day exposure to P25 and FG NP. Using SDS-PAGE and western blot, we observed a small difference in the amount of amyloid precursor protein (APP) and beta-amyloid (Aβ) after 5-days and 1-day of cell exposure to NP at 25 µg/mL concentration, but we could not identify the resulting APP fragments, so nor can we determine the significance of these changes. As part of the master\u27s thesis, we successfully established the SH-SY5Y cell differentiation protocol, showed the influence of selected TiO2 NP on ROS formation and the amount of intracellular proteins APP and Aβ. We did not observe any effects of selected NP on cell survival and differentiation
Translation and critical assessment of the farmacognostic part of Ehrmann\u27s textbook from the year 1834 eith the help of Hager database
Get PDFDiplomsko delo podaja primerjavo in kritično ovrednotenje znanja, ki nam ga v svojem delu iz leta 1834 podaja prof. Ehrmann. Farmakognostični del njegovega učbenika smo v dodatku k diplomski nalogi tudi prevedli. Pri kritičnem ovrednotenju materije medike prve polovice 19. stoletja smo si pomagali s Hagerjevo zbirko monografij učinkovin in drog. Poleg tega smo vsebino Ehrmannovega učbenika primerjali tudi z zdravili, ki jih je pri svojem delu uporabljal njegov sodobnik, drugi mestni zdravnik Viljem Lipič. Lipičev pristop k terapiji je kombinacija humoralne teorije (avtor govori o misteriju ţivljenja, vitalnih sokovih, meteoroloških vplivih) in novoveških vplivov, opravlja obdukcije, uporablja stetoskop. Značaj 19. stoletja se veliko bolj kaţe v Ehrmannovem delu, ki ga zanima izvor rastlin, sodeluje z znanstveniki iz različnih delov sveta, opisuje razvoj trgovine na svetovnem nivoju (trţenje rabarbare), večkrat opozori na etično delovanje človeka, ki se ukvarja s farmacevtsko znanostjo, poskuša prepoznavati ponaredke drog in poziva k previdnosti tudi ostale, zanima ga kemijska sestava drog, njihovo delovanje, priprava pripravkov, pridobivanje drog, kultura pitja čaja idr. Veliko njegovih ugotovitev lahko potrdimo tudi z vidika sodobne znanosti. Njegova sodobnost (empirizem) se kaţe v metodah raziskovanja snovi, njegova povezava s preteklostjo pa v snovi, ki jih raziskuje.
V diplomski nalogi smo se omejili na farmakognostični del učbenika, v katerem so povzeta najnovejša dognanja farmacevtske znanosti v prvi polovici 19. stoletje po izboru prof. Ehrmanna. Profesor je deloval na dunajski univerzi in v svojem delu raziskoval rastlinske droge (korenine, les, liste, cvetove, skorje, plodove in semena), rastlinske produkte (gumije, mlečke, snovi, ki vsebujejo škrob), produkte vrenja (etanol, ocetno kislino, vinski kamen) in dve ţivalski drogi (spuţvo, pijavke). Sintezna kemija je uporabo drog, ki jih navaja Ehrmann, močno skrčila. Ugotovili smo, da se nekatere v farmaciji sploh ne uporabljajo več (korenina melone), druge se uporabljajo le še v ljudski medicini (korenika kainke, korenina ciklame), posamezne znova pridobivajo na pomenu (pijavke, skorja borovca), nekatere so svojo vlogo v farmaciji ohranile do danes (cvet kamilice, list sene, korenina sleza), posamezne predstavljajo izhodišče sintezni kemiji ali izolaciji spojin (opij, skorja kininovca, seme kave, list čaja), nekatere pa so svoj pomen v farmaciji izgubile, a so ga ohranile na drugem mestu (skorja cimetovca, cvet ţafrana, skorja rabarbare, les sandalovine).The diploma focuses on the comparison and critical assessment of the knowledge that is given by professor Ehrmann in his work from the year 1834. The pharmacognostic part of his book was translated in the appendix of the diploma. Hager’s collection of monographs of active ingredients and drugs was used to help to critically assess the Materia Medica from the 19th century. Moreover we compared the contents of Ehrmann’s book with the medication that Viljem Lipič, another contemporary city doctor, used in his work.
Lipič’s approach to therapy is a combination of the humoral theorythe author writes about the mystery of life, vital fluids, weather influences and the influences of the modern era, autopsies, the use of a stethoscope. The character of the 19th century is more visible in Ehrmann’s work, since he’s interested in the origin of plants, cooperates with scientists from all across the globe, describes the rise of the global market (rhubarb market), draws attention several times to the ethical human behaviour in pharmacy, tries to recognise counterfeit drugs and also calls caution upon the others, he is interested in the chemical structure of drugs, their effects, the preparations, drug production, tea culture etc. His research methods are modern (empirical), however, the substances he is researching are keeping his connection with the past. The diploma is limited to the pharmacognostical part of the book where all the newest discoveries in pharmacy from the first half of the 19th century, chosen by Ehrmann, are summarised. The professor was working at the University of Vienna and was researching vegetable drugs (roots, wood, leaves, blossoms, bark, fruits and seeds), vegetable products (rubber, euphorbia, starch substances), fermentation products (ethanol, acetic acid, potassium bitartrate) and two animal drugs (sponge, leech). The usage of the drugs, described by Ehrmann, was reduced by chemical synthesis. We came to the conclusion that some of them are no longer in use (melon root), some are used only in folk medicine (kainka roots, cyclamen rhizome etc.), some are regaining their importance (leeches, pine crust), some have kept their role in pharmacy till the present day (camomile blossoms, senna leaves, mallow roots), some represent the origin of chemical synthesis and substance isolation (opium, cinchona bark, coffee beans, tea leaves), some have lost their importance in pharmacy, but have kept it in another field (cinnamon bark, crocus blossoms, rhubarb bark, sandalwood)
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