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Evaluation of the influence of various parameters on the elemental content of tea infusions by total reflection X-ray fluorescence spectrometry
No full textPripravci čajnih mješavina su nakon vode jedno od najčešće konzumiranih pića na svijetu. Čajne
mješavine uz makronutrijente predstavljaju i bogat izvor različitih mikronutrijenata poput Ca, K, Cu,
Zn, Mn, Fe i Ni te stoga redovita konzumacija čajnih mješavina može pridonijeti pri unosu
preporučenih dnevnih doza elemenata u organizmu. Čajne mješavine osim što su osvježavajući
napitci koji uz to djeluju blago stimulirajuće posjeduju i brojne pozitivne učinke na ljudsko zdravlje
poput snižavanja koncentracije kolesterola u serumu i prevencije različitih kardiovaskularnih
oboljenja te mnoge druge. Količina ekstrahiranih elemenata može među ostalim ovisiti i o
karakteristikama vode korištene za pripremu čajnih mješavina. Cilj ovog diplomskog rada bio je
ispitati utjecaj određenih parametara pri pripravi čajnih mješavina na količinu ekstrahiranih
minerala. Ispitivao se utjecaj različitog tipa voda na samu ekstrakciju (vodovodna, mineralna i
ultračista) te različite temperature vode (90℃ i 4 ℃ ). Dobiveni rezultati su pokazali da na sadržaj
elemenata najveći utjecaj ima primjena vodovodne vode za ekstrakciju te temperatura vode od 90
℃. U svrhu analize korištena je rendgenska fluorescencijska spektrometrija s totalnom refleksijom
(eng. Total Reflection X-Ray Fluorescence Spectrometry, TXRF) kao brza i osjetljiva analitička
tehnika koja vodi brigu o načelima „zelene kemije“.Tea mixtures are among the most consumed beverages in the world, after water. In addition to
macronutrients, teas are also a rich source of various micronutrients such as calcium (Ca), potassium
(K), copper (Cu), zinc (Zn), manganese (Mn), iron (Fe) and nickel (Ni), which is why regular
consumption of teas can contribute to the intake of the recommended daily allowance of elements in
the body. Apart from being refreshing drinks that are also midly stimulating, teas have numerous
beneficial effects on human health, such as lowering serum cholesterol levels and preventing various
cardiovascular diseases, among others. The amount of extracted elements may depend, among other
things, on the properties of the water used for the preparation of tea mixtures. The aim of this work
was to study the influence of certain parameters in the preparation of tea mixtures on the extracted
minerals. The influence of different types of water (tap water, mineral water and ultrapure water) and
different water temperatures (90 ̊C and 4 ̊C) on the extraction itself was tested. The obtained results
showed that the use of tap water for extraction and a water temperature of 90 ̊C had the greatest
influence on the content of elements. Total reflection X-ray fluorescence, TXRF, was used for the
analysis, which is a fast and sensitive analytical technique that takes into account the principles of
„green chemistry“
Preparation and characterization of vesicular phospholipid gel
No full textSvrha ovoga rada bila je pripraviti i okarakterizirati polučvrstu formulaciju liposoma iznimno visoke
koncenteracije fosfolipida (vezikularni fosfolipidni gel, VFG). Za pripravu je korišten sojin
fosfatidilkolin i hidrofilna djelatna tvar. Primjenom visokotlačnog homogenizatora pripravljen je
VFG male veličine vezikula i relativno homogene distribucije veličina. Uklapanje hidrofilne djelatne
tvari u unutarnju vodenu fazu bilo je visoko u usporedbi s klasičnim metodama priprave liposoma.
Izmjerena teksturna svojstva VFG-a pokazuju odgovarajuću čvrstoću i razmazivost prikladnu za
dermalnu primjenu.The aim of this study was to prepare and characterize a semi-solid formulation of liposomes with an
extremely high concentration of phospholipids, i.e., vesicular phospholipid gel (VPG). Soybean
phosphatidylcholine and a hydrophilic model drug were used for the preparation of VPG. Using a
high-pressure homogenizer, VPG with a small size of vesicles and a relatively homogeneous size
distribution was prepared. Incorporation of the hydrophilic drug into the internal aqueous phase of
VPG was high compared to classical methods of liposome preparation. Texture analysis of VPG
showed adequate hardness and spreadability suitable for dermal application
The impact of high-protein diet on appetite regulation and body weight
No full textProblem pretilosti predstavlja globalni zdravstveni izazov s ozbiljnim rizicima za razvoj brojnih kroničnih bolesti poput dijabetesa tipa 2, kardiovaskularnih bolesti i metaboličkog sindroma. Prehrana ima ključnu ulogu u prevenciji i liječenju pretilosti, a visokoproteinska prehrana pokazuje značajan potencijal u regulaciji apetita i kontroli tjelesne težine . Ovaj rad daje prikaz dosadašnjih saznanja o utjecaju visokoproteinske prehrane na kontrolu apetita te prevenciju pretilosti. Mehanizmi kojima visokoproteinska prehrana djeluje na smanjenje apetita uključuju stimulaciju hormona sitosti poput kolecistokinina (CCK), glukagonu sličnog peptida-1 (GLP-1) i peptida YY (PYY). Navedeni hormoni sinergistički signaliziraju osjećaj sitosti smanjujući potrebu za unosom hrane. Istovremeno, razina grelina, hormona gladi, opada nakon unosa proteina, što dodatno doprinosi kontroli apetita. Osim anoreksigenog učinka na apetit, visokoproteinska prehrana potiče metaboličke procese poput glukoneogeneze, ketogeneze i termogeneze. Glukoneogeneza, proces sinteze glukoze iz neugljikohidratnih supstrata, zahtijeva značajnu energetsku potrošnju čime se povećava ukupna potrošnja energije organizma. Ketogeneza, koja nastaje pri smanjenom unosu ugljikohidrata, dovodi do stvaranja ketonskih tijela koja mogu poslužiti kao alternativni izvor energije, a također doprinose smanjenju osjećaja gladi. Termogeneza, metabolički odgovor povezan s probavom i metabolizmom hrane, dodatno doprinosi povećanju energetske potrošnje, osobito nakon konzumacije proteina zbog njihovog visokog termičkog učinka. Iako visokoproteinska prehrana donosi brojne koristi, uključujući povećanje osjećaja sitosti i energetske potrošnje, ona iskazuje i određene negativne učinke, poput povećanog opterećenja bubrega te potencijalnog gubitka kalcija i posljedičnog rizika za zdravlje kostiju, što zahtijeva daljnja istraživanja i opreznu primjenu.The problem of obesity represents a global health challenge, posing serious risks for the development of numerous chronic diseases, including type 2 diabetes, cardiovascular diseases, and metabolic syndrome. Nutrition plays a key role in both the prevention and treatment of obesity, and high-protein diets have shown significant potential in appetite regulation and weight control. This paper provides an overview of current knowledge on the effects of high-protein diets on appetite control and obesity prevention. The mechanisms by which high-protein diets contribute to appetite suppression include the stimulation of satiety hormones such as cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). These hormones work synergistically to signal satiety, reducing the need for food intake. At the same time, levels of ghrelin, the hunger hormone, decrease following protein consumption, further aiding appetite regulation. Beyond their anorexigenic effects, high-protein diets stimulate metabolic processes such as gluconeogenesis, ketogenesis, and thermogenesis. Gluconeogenesis, the process of synthesizing glucose from non-carbohydrate substrates, requires significant energy expenditure, thereby increasing the body's overall energy consumption. Ketogenesis, which occurs when carbohydrate intake is reduced, leads to the production of ketone bodies that can serve as an alternative energy source while also contributing to reduced hunger. Thermogenesis, a metabolic response associated with digestion and food metabolism, further enhances energy expenditure, particularly after protein consumption due to its high thermic effect. Although high-protein diets offer numerous benefits, including increased satiety and energy expenditure, they also present certain potential drawbacks, such as increased kidney strain and the possible loss of calcium, which may pose a risk to bone health. These factors warrant further research and cautious implementation
Seasonal change of catalytic activity of catalase in the plasma of subjects from Vinkovci
No full textKatalaza je jedan od najvažnijih enzima prve linije antioksidativnog sustava obrane od reaktivnih kisikovih vrsta (ROS) i posljedičnog oksidacijskog stresa. Kako bi se utvrdio učinak zagađivača iz zraka na razinu oksidacijskog stresa, u ovom istraživanju praćena je katalitička aktivnost katalaze u plazmi zdravih osoba iz Vinkovaca u dvije sezone, toplijoj i hladnijoj. U prvom dijelu istraživanja optimizirana je spektrofotometrijska metoda određivanja katalitičke aktivnosti katalaze praćenjem razgradnje vodikovog peroksida kako bi se omogućilo pouzdano mjerenje katalitičke aktivnosti katalaze u većem broju uzoraka ljudske plazme uz korištenje čitača pločica. Optimizirana je metoda zatim primijenjena na uzorcima plazme dobrovoljaca iz Vinkovaca (n=55) sakupljenim tijekom toplijeg i hladnijeg dijela godine u sklopu HUMNap projekta (HRZZ), te je uspoređena katalitička aktivnost katalaze između sezona, ali i ovisno o spolu.
Ispitivanja su pokazala da je metoda pouzdana te da se može koristiti za određivanje katalitičke aktivnosti katalaze u većem broju uzoraka ljudske plazme. Izmjerene vrijednosti katalitičke aktivnosti katalaze u ljudskoj plazmi bile su veće u hladnijem dijelu (173,66 ± 58,39 U/mL) nego toplijem dijelu (113,05 ± 69,83 U/mL; p = 2,99*10-6) godine što se može povezati sa sezonom grijanja koja pridonosi povećanoj razini onečišćenja zraka u odnosu na topliji dio godine. Veće onečišćenje zraka i veća potreba organizma za borbom protiv ROS-ova rezultirala je većom sintezom katalaze, čiju su proizvodnju, između ostalog, potaknuli upravo zagađivači iz zraka. Primijećena veća katalitička aktivnost katalaze u uzorcima plazme muških osoba (n=24) u hladnijem (181,89 ± 58,54 U/mL) i u toplijem (122,89 ± 91,59 U/mL) dijelu godine u odnosu na aktivnost katalaze u plazmi osoba ženskog spola (n=31) sakupljenih u hladnijem (167,28 ± 58,42 U/mL) i toplijem (105,43 ± 46,98 U/mL) dijelu godine pokazuje da su muškarci izloženi i nekim drugim vanjskim čimbenicima koji potiču sintezu katalaze.Catalase is one of the most important enzymes of the first line of antioxidant defense against reactive oxygen species (ROS) and consequent oxidative stress. In order to determine the impact of air pollutants on the level of oxidative stress, the catalytical activity of catalase in the plasma of healthy subjects from Vinkovci in two seasons, colder and warmer was determined. In the first part of the study, a reliable spectrophotometric method for assessment of the catalytic activity of catalase in a larger number of human plasma samples based on monitoring the decomposition of hydrogen peroxide using a plate reader was developed. Afterwards, the optimized method was applied to plasma samples of healthy subjects collected in Vinkovci (n=55) during the warmer and colder parts of the year as part of the HUMNap project (HRZZ), and the catalytic activity of catalase was compared between seasons, but also depending on gender.
The results of the study demonstrated that the method is reliable and can be used for monitoring the catalytical activity of catalase in a large number of plasma samples. The level of catalytical activity of catalase in human plasma was higher in the colder period (173.66 ±58.39 U/mL) than in the warmer period (113.05 ± 69.83 U/mL; p = 2.99*10-6) of the year, which can be associated with the heating season that contributes to the increased level of air pollution compared to warmer period of the year. Higher air pollution and higher bodies’ need to fight ROS, results in higher synthesis of catalase, the production of which is, among other things, stimulated by air pollutants. The observed higher catalytic activity of catalase in plasma samples from male subjects (n=24) in the colder (181.89 ± 58.54 U/mL) and warmer (122.89 ± 91.59 U/mL) periods of the year compared to the catalase activity in plasma from female subjects (n=31) collected in the colder (167.28 ± 58.42 U/mL) and warmer (105.43 ± 46.98 U/mL) periods of the year indicates that men are also exposed to some other external factors that promote the synthesis of catalase
The influence of changes in hormonal status on the condition of the skin and adnexa
No full textPromjene u hormonalnom statusu imaju učinak na više organa i organskih sustava, pa tako i na kožu. Koža je naš najveći organ i na se najprije primijećuju promjene. Neke promjene su specifične za pojedine poremećaje te se njihovim primjećivanjem pacijenta može uputiti na daljnju obradu hormonalnog statusa. Hormonalni poremećaji obrađeni u ovom diplomskom radu, kao i njihovi utjecaji na kožu i adnekse kože, su poremećaji hormona štitnjače, poremećaji hormona nadbubrežne žlijezde, sindrom policističnih jajnika, inzulinska rezistencija i dijabetes. Poremećaji štitnjače uzrokuje promjene na razini epidermisa, dermisa, kose, noktiju i žlijezda znojnica. Pacijenti s alopecijom areatom, kroničnom urtikarijom i vitiligom trebaju biti na oprezu s autoimunim bolestima štitnjače te se preporučaju redovite pretrage i praćenje hormona štitnjače hormona. Hiperpigmentacije sluznica, petrifikacija ušne školjke te uzdužna melanonihija ukazuju na smanjenu razinu hormona nadbubrežne žlijezde, dok akne, hirzutizam, ljubičaste široke strije, stanjivanje kože, edem i ženska ćelavost ukazuju na prekomjernu proizvodnju kortizola. Akne su najčešća manifestacija PCOS-a kao rezultat viška androgenih hormona, a uz njih mogu se javiti hirzutizam, seboroični dermatitis i androgena alopecija. Crna akantoza, akne, psorijaza i akrohordon mogu se povezati s inzulinskom rezistencijom i pretilošću, dok dijabetes prate čirevi na stopalima, dijabetička dermopatija, necrobiosis lipoidica diabeticorum i scleredema adultorum.
Pravovremenim uočavanjem kožnih promjena i upućivanjem pacijenta na detaljnije pretrage moguće je otkrivanje ozbiljnih bolesti.Changes in hormonal status have an effect on several organs and organ systems, including the skin. The skin is our largest organ and it is here that we will first notice changes. Some changes are specific to certain disorders, and their observation may refer the patient to further testing of hormonal status. The hormonal disorders discussed in this thesis, as well as their effects on the skin and skin adnexa, are thyroid hormone disorders, adrenal hormone disorders, polycystic ovary syndrome, insulin resistance and diabetes. Thyroid disorders cause changes at the level of the epidermis, dermis, hair, nails and sweat glands. Patients with alopecia areata, chronic urticaria and vitiligo should be on the lookout for autoimmune thyroid diseases and regular examinations and monitoring of thyroid hormones are recommended. Hyperpigmentation of the mucous membranes, petrification of the auricle, and longitudinal melanonychia indicate reduced levels of adrenal hormones, while acne, hirsutism, purple wide stretch marks, thinning of the skin, edema, and female pattern baldness indicate excessive cortisol production. Acne is the most common manifestation of PCOS as a result of excess androgen hormones, and hirsutism, seborrheic dermatitis, and androgenic alopecia may occur with them. Acanthosis nigricans, acne, psoriasis, and acrochordon may be associated with insulin resistance and obesity, while diabetes is accompanied by foot ulcers, diabetic dermopathy, necrobiosis lipoidica diabeticorum, and scleredema adultorum.
Timely detection of skin changes and referral of the patient to more detailed examinations can detect serious diseases
Examination of biological activity of glycerol-hydroxypropyl-Beta-cyclodextrin extracts of winter savory (Satureja montana L.) rich in phenolic compounds for use in cosmetics and phytopharmacy
No full textIzgledu i zdravlju ljudske kože oduvijek se obraćala velika pozornost. Oksidativni stres, upalne reakcije i kožne bolesti uzrokuju neželjene promjene na koži koje se djelomično mogu regulirati kozmetičkim pripravcima. Ipak, postojeće sastavnice kozmetičkih proizvoda i dalje nisu u mogućnosti eliminirati nedostatke u izgledu kože, pa postoji potreba za otkrivanjem novih terapijskih mogućnosti iz prirodnih izvora. Cilj rada bio je ispitati potencijalni kozmetički učinak ekstrakata primorskog vriska bogatih ukupnim polifenolima i ružmarinskom kiselinom koju su dobiveni ekstrakcijom s glicerolom i hidroksipropil-β-ciklodekstrinom . U ispitivanjima biološke aktivnosti ekstrakti su pokazali izvrsnu antioksidativnu aktivnost, ispitanu pomoću DPPH i redukcijske snage i dobro protuupalno djelovanje određeno ispitivanjem inhibicije enzima lipooksigenaze i denaturacije ovalbumina. Ispitivanje inhibitorne aktivnosti ekstrakata prema enzimima elastazi, tirozinazi i hijaluronidazi pokazalo je da ekstrakti nisu ostvarili značajan stupanj inhibicije elastaze i tirozinaze, no uspješno su inhibirali enzim hijaluronidazu. Zahvaljujući tome ekstrakti biljne vrste S. montana mogu se razmotriti kao potencijalni sastojci u budućim kozmetičkim pripravcima namijenjenima poboljšanju izgleda i zdravlja kože.Great attention has always been given to the appearance and health of human skin. Oxidative stress, inflammatory reactions and skin disorders cause adverse effects on the skin that can be partially regulated with cosmetic products. However, current components of cosmetic products are still not able to entirely eliminate skin imperfections, so there is a need for discovering new therapeutic possibilities from natural sources. The goal of this research was investigation of potential cosmetic effects of winter savory extracts, rich in total polyphenols rosmarinic acid, obtained by extraction with glycerol and hydroxypropyl-β-cyclodextrin. In biological activity tests, the extracts had excellent antioxidant activity, tested using DPPH and reducing power methods and good anti-inflammatory activity determined by inhibition of lipoxygenase enzyme and ovalbumin denaturation tests. The inhibitory activity of the extracts was tested on the enzymes elastase, tyrosinase and hyaluronidase. The extracts did not achieve a significant degree of inhibition of elastase and tyrosinase, but they successfully inhibited the enzyme hyaluronidase. Thanks to this, extracts of the plant species S. montana can be considered as potential ingredients in future cosmetic products for the appearance and health of the skin
Phytochemical composition and iological effects of selected Salvia species from the Croatian flora
No full textU okviru ovog doktorskog rada po prvi put su usporedno istraženi fitokemijski sastav i biološki učinci sedam
odabranih biljnih vrsta roda Salvia L. koje samoniklo rastu na području Republike Hrvatske: S. fruticosa
Mill., S. glutinosa L., S. nemorosa L., S. officinalis L., S. pratensis L., S. sclarea L. i S. verticillata L.
Ekstrakcija biološki aktivnih sastavnica iz listova odabranih biljnih vrsta roda Salvia provedena je različitim
organskim otapalima s i bez primjene ultrazvuka, niskotemperaturnim eutektičkim otapalima, ugljikovim(IV)
oksidom u superkritičnom obliku te destilacijom pomoću vodene pare. Kvalitativna i kvantitativna analiza
terpenskih i polifenolnih sastavnica provedena je primjenom spektrofotometrijskih metoda te različitih
kromatografskih tehnika kao što su HPTLC, HPLC-DAD i GC-MS. Ružmarinska kiselina bila je
najzastupljenija fenolna kiselina u svim ispitanim vrstama, dok su glikozidni derivati luteolina i apigenina
otkriveni kao najzastupljeniji flavonoidi. Vrste S. fruticosa i S. officinalis istaknule su se kao vrste izrazito
bogate eteričnim uljem, dok je sadržaj eteričnog ulja u ostalih ispitanih vrsta bio značajno manji. U sastavu
eteričnog ulja vrste S. fruticosa najzastupljenija terpenska sastavnica bio je 1,8-cineol, dok je kariofilen-oksid
prevladavao u eteričnom ulju vrste S. sclarea. Značajni udjeli α- i β-tujona određeni su u eteričnom ulju vrste
S. officinalis, a germakren D bio je glavna sastavnica eteričnih ulja vrsta S. glutinosa i S. verticillata.
Antioksidacijski učinci etanolnih ekstrakata, eteričnih ulja i odabranih terpenskih i polifenolnih sastavnica te
njihova sposobnost inhibicije odabranih enzima koji se smatraju važnim terapijskim metama ispitani su
spektrofotometrijskim metodama u prikladnim eksperimentalnim sustavima. Etanolni ekstrakti ispitanih
biljnih vrsta pokazali su snažna antioksidacijska svojstva na temelju sposobnosti hvatanja slobodnih radikala,
keliranja i redukcije iona željeza te inhibicije lipidne peroksidacije. Ispitani ekstrakti su također imali
sposobnost inhibicije enzima elastaze i tirozinaze, a neki su ekstrakti inhibirali aktivnost enzima
acetilkolinesteraze i α-glukozidaze. Rezultati provedenih fitokemijskih i bioloških ispitivanja odabranih vrsta
roda Salvia L. iz hrvatske flore ukazali su na njihov biomedicinski potencijal i mogućnosti primjene u
sprječavanju i liječenju kroničnih bolesti vezanih uz starenje.
Rad je pohranjen u Središnjoj knjižnici Sveučilišta u Zagrebu Farmaceutsko-biokFor the first time, a comprehensive comparative study of the phytochemical composition and biological
effects of seven insufficiently investigated Salvia species growing wild in Croatia (S. fruticosa Mill., S.
glutinosa L., S. nemorosa L., S. officinalis L., S. pratensis L., S. sclarea L., S. verticillata L.) was conducted
in this thesis. Bioactive natural compounds from the leaves of selected Salvia species were extracted using
various organic solvents, with and without sonication, as well as deep eutectic solvents, supercritical carbon
(IV) oxide and hydrodistillation. The contents of terpenoid and polyphenolic compounds were determined
using spectrophotometric and chromatographic techniques such as HPTLC, HPLC-DAD and GC-MS.
Rosmarinic acid was the predominant phenolic acid, while glycosidic derivatives of apigenin and luteolin
were the most abundant flavonoids. S. fruticosa and S. officinalis were highlighted as species rich in essential
oil, while other tested Salvia species contained significantly smaller amounts of essential oil. The most
abundant terpenoid compound in the essential oil of S. fruticosa was 1,8-cineole and caryophyllene oxide was
the predominant compound in the essential oil of S. sclarea. Furthermore, significant contents of α- and βthujone were present in the essential oil of S. officinalis, whereas germacrene D was the most abundant in the
essential oils of S. glutinosa and S. verticillata. The antioxidant activities of ethanolic extracts, essential oils
and selected terpenoid and polyphenolic compounds, as well as their abilities to inhibit enzymes representing
important therapeutic targets, were determined spectrophotometrically. The ethanolic extracts of selected
Salvia species demonstrated strong antiradical properties, reducing power and metal chelating ability, as well
as lipid peroxidation inhibitory activity. All ethanolic extracts showed anti-elastase and anti-tyrosinase
activity. Moreover, some of them possessed inhibitory activity against acetylcholinesterase and αglucosidase. The results of conducted phytochemical and biological assays point out the biomedical potential
of selected Salvia species from the Croatian flora and the possibilities of their application in the prevention
and treatment of age-related chronic diseases
Analitičke tehnike u terapijskom praćenju lijekova u liječenju raka dojke
No full textCilj istraživanja: Cilj ovog rada je napraviti pregled dosadašnjih uspjeha u razvoju metoda u
terapijskom praćenju lijekova (engl. Therapeutic Drug Monitoring, TDM) kod raka dojke. Komentirat
će se i izazovi koji preostaju kako bi upotreba TDM-a postala standardni pristup u liječenju raka
dojke.
Materijal i metode: Istraživanje se provelo pregledom znanstvene literature i uvidom u trenutnu
kliničku praksu pretraživanjem baza podataka “Scopus”, “Web of Science”, “PubMed”,
“ScienceDirect” i “Directory of Open Access Journals” s ključnim riječima therapeutic drug
monitoring, TDM, breast cancer treatment, analytical methods, chemotherapy individualization, genetic
polymorphism in chemotherapy, bioanalytical methods, recommendations for therapeutic drug monitoring i njihovim
kombinacijama.
Rezultati: Kod velikog broja lijekova proračunavanje doza na temelju površine tijela nije
primjereno. Jedan od problema uvođenja TDM-a u terapiju raka dojke u tim slučajevima je i
nedostatak prikladnih analitičkih metoda. Isto tako, za starije lijekove i lijekove namijenjene za veći
broj indikacija je uspostavljen veći broj metoda i više se zna o njihovoj farmakokinetici pa se za
njih češće provodi TDM, za razliku od novijih lijekova i lijekova koji se koriste u ograničenom
broju indikacija.
Zaključak: TDM je i dalje slabo istraženo i iskorišteno područje te postoji puno prostora za
napredak. Potrebno je razviti brze, jednostavne, robusne i jeftine metode da se osigura racionalna
i učinkovitija terapija, ali i ovdje ima prostora za daljnji razvoj. Međutim, može se očekivati da će
uz razvoj sve većeg broj dostupnih metoda i poboljšanja njihovih performansi, rasti i njihova
popularnost, a samim time će porasti i njihova dostupnost.Objectives: The objective of this thesis is to provide an overview of the previous successes in the
method development for therapeutic drug monitoring (TDM) in breast cancer treatment. The
remaining challenges to make TDM a standard approach in breast cancer treatment will also be
discussed.
Materials and Methods: The research was conducted by reviewing scientific literature and
examining current clinical practice by searching databases "Scopus", "Web of Science", "PubMed",
"ScienceDirect", and "Directory of Open Access Journals" using keywords therapeutic drug
monitoring, TDM, breast cancer treatment, analytical methods, chemotherapy individualization, genetic
polymorphism in chemotherapy, bioanalytical methods, recommendations for therapeutic drug monitoring and their
combinations.
Results: For many drugs, body surface area-based dose calculation is not appropriate. One
problem with introducing TDM into breast cancer therapy in these cases is the lack of suitable
analytical methods. Additionally, for older drugs and drugs with more indications, more methods
have been established and more is known about their pharmacokinetics, so TDM is more
frequently performed, unlike newer drugs and drugs used in a limited number of indications.
Conclusion: TDM is still poorly researched and underutilized, and there is plenty of room for
improvement. It is necessary to develop fast, simple, robust, and inexpensive methods to ensure
rational and more effective therapy, but there is still room for improvement. However, with the
increased number of available methods and improvements in their performance, it can be expected
that their popularity will grow, as their availability
Optimization of pre-analytical processing of a biological sample for the determination of anastrozole and palbociclib by liquid chromatography coupled to mass spectrometry
No full textCilj ovog rada je odabir optimalne predanalitičke obrade uzorka plazme te razvoj nove metode za
istovremenu kvantifikaciju anastrozola (ANA) i palbocikliba (PAL) tekućinskom kromatografijom visoke
djelotvornosti spregnute sa spektrometrom masa (LC-MS). Uspoređene su metode taloženja proteina,
ekstrakcije čvrstom fazom (SPE), uklanjanja fosfolipida i disperzivne mikroekstrakcije tekuće-tekuće
(DLLME). Kako bi se odredili optimalni uvjeti ekstrakcije čvrstom fazom uspoređene su vrijednosti
ekstrakcijskih učinkovitosti i utjecaja matrice šest različitih sorbensa u kombinaciji s različitim eluensima.
Najbolji rezultati su primjećeni kod ekstrakcije na kolonici sa C18 sorbensom, a eluens je acetonitril (ACN)
potom 5 %-tni (v/v) amonijak u MeOH. Kako bi se odredili optimalni uvjeti disperzivne mikroekstrakcije
uspoređene su vrijednosti ekstrakcijskih učinkovitosti i utjecaja matrice pet DLLME varijanti. Najbolji
rezultati su primjećeni kod DLLME vodenog uzorka gdje je ekstrakcijsko sredstvo kloroform, disperzijsko
sredstvo izopropanol, a ionska jakost otapala je povećana dodatkom citratne soli. Uzorci su analizirani i
kvantificirani novom LC-MS metodom. Provedena je reverzno fazna kromatografija na bifenilnoj
kromatografskoj koloni uz binarnu gradijentnu eluciju. Mobilna faza sastoji se od 0,1 % mravlje kiseline u
vodi i 0,1 % mravlje kiseline u ACN. MS analiza provedena je uz elektrosprej ionizaciju u pozitivnom
načinu snimanja uz praćenje ionskih tranzicija m/z 448,2→380,0 i m/z 448,2→319,5 za PAL, te m/z
294,1→225,1 i m/z 294,1→210,0 za ANA. Analiti su identificirani na temelju spektara masa i vremena
zadržavanja. Kvantitativna analiza provodila se integriranjem kromatografskih pikova.The aim of this work is to select the optimal pre-analytical processing of the plasma samples and the
development of a novel method for the simultaneous quantification of anastrozole (ANA) and palbociclib
(PAL) by high performance liquid chromatography coupled to a mass spectrometer (LC-MS). The methods
of protein precipitation, solid phase extraction (SPE), phospholipid removal and liquid-liquid dispersive
microextraction (DLLME) were compared. In order to determine the optimal conditions for solid phase
extraction, the values of extraction efficiency and matrix influence of six different sorbents in combination
with different eluents were compared. The best results were observed during extraction on a column with
C18 sorbent, the eluent in the extraction was acetonitril (ACN), then 5% (v/v) ammonia in methanol. In
order to determine the optimal conditions of DLLME, the values of extraction efficiency and matrix
influence of five DLLME variants were compared. The best results were observed with the DLLME of the
water sample, where the extraction agent is clorophorm, the dispersion agent is isopropanol, and the ionic
strength of the solvent is increased by the addition of citrate salt. The samples have been analyzed and
quantified by a novel LC-MS method. Reverse phase chromatography was performed on a biphenyl column
with binary gradient elution in which the mobile phase consists of 0.1% formic acid disolved in water and
0.1% formic acid disolved in ACN. MS analysis was performed with electrospray ionization in positive
imaging mode by monitoring of ion transitions m/z 448,2→380,0 and m/z 448,2→319,5 for PAL, and m/z
294,1→225,1 and m/z 294,1→210,0 for ANA. Analytes were identified based on their mass spectra and
retention times. Quantitative analysis was carried out by integrating the chromatogram spikes
Patients’ willingness to pay for consultation on inhalation therapy in community pharmacies
No full textKronične respiratorne bolesti, od kojih su najčešće astma i KOPB, jedan su od vodećih uzroka smrtnosti u RH.
Preopterećenost zdravstvenih sustava uzrokuje financijsko poskupljenje zdravstvenih usluga te manjak individualnog
pristupa pacijentu. Spremnost na plaćanje (engl. willingness to pay, WTP) pojam je koji podrazumijeva spremnost
kupca, odnosno pacijenta za plaćanjem pojedine usluge. Cilj je ovog istraživanja bio utvrditi čimbenike koji utječu na
WTP pacijenata za uslugu savjetovanja o njihovoj respiratornoj bolesti, koja im je pružena tijekom posjeta ljekarni.
Istražena je povezanost WTP-a sa sociodemografskim podacima pacijenata, osobnim dojmom pacijenata o ozbiljnosti
respiratorne bolesti, adherencijom te ispravnosti inhalacijske tehnike. Istraživanje je osmišljeno kao intervencijsko, a
uključivalo je savjetovanje pacijenata o njihovoj respiratornoj bolesti i ispravnoj primjeni inhalatora. U istraživanju je
sudjelovalo 100 ispitanika koji boluju od astme ili KOPB-a, te u svojoj terapiji imaju barem jedan inhalator.
Istraživanje je provedeno u ljekarnama u Slavoniji i Dalmaciji te se sastojalo od ispunjavanja upitnika i pacijentove
demonstracije korištenja inhalatora. Na kraju savjetovanja, ispitanici su ispunjavali upitnik o zadovoljstvu
savjetovanjem te pitanja vezana za WTP. Prosječna dob ispitanika bila je 52,11 godina (SD =19,07), uz nešto veći
udio žena (55%). Utvrđeno je da većina ispitanika (93%) pruženo savjetovanje smatra korisnim te da bi takvo
savjetovanje trebalo biti plaćeno iz njihovog zdravstvenog osiguranja (68%). Iznos koji su ispitanici smatrali
prikladnim za plaćanje usluge farmaceuta pri pružanju takvog savjetovanja iznosio je u prosjeku 7,18 € (SD =5,37).
Osim navedenog, istraživanje je pokazalo da je velik udio pacijenata s astmom i KOPB-om nedovoljno kontroliran
(32%), slabo adherentan te ima neispravnu inhalacijsku tehniku (35%). Utvrđeno je da su sljedeći čimbenici bili
povezani s WTP-om ispitanika: regija iz koje dolaze (p =0,019), stupanj završene stručne spreme (p =0,042), stupanj
kontrole respiratorne bolesti (p =0,025) te razina sporadične adherencije (p =0,034). Ispitanici koji smatraju da bi
savjetovanje trebalo biti plaćeno većinom su iz Dalmacije, imaju viši stupanj obrazovanja, bolju kontrolu bolesti te su
sporadično manje adherentni. Za bolje ishode liječenja, potreban je individualiziran pristup pacijentu s ciljem
podučavanja o inhalacijskoj terapiji i njenoj koristi za zdravlje s obzirom da je ona ključna u liječenju kroničnih
respiratornih bolesti.Chronic respiratory diseases, including asthma and COPD, are among the leading causes of mortality in Croatia. The
burden on healthcare systems leads to increased financial costs of healthcare services and a lack of individualized
patient care. Willingness to Pay (WTP) indicates the readiness of a buyer or patient to pay for a particular service. The
aim of this research was to identify factors influencing patients' WTP for services provided to them during counseling
on therapy for asthma and COPD, in community pharmacy. The association between WTP and patients'
sociodemographic data, patients' perception of the seriousness of respiratory disease, adherence, and correctness of
inhalation technique was investigated. The research was designed as an interventional study, involving counseling for
patients about their respiratory disease and correct inhaler use. The study involved 100 respondents with asthma or
COPD, with prescription on at least one inhaler in the therapy. The research was conducted in community pharmacies
in Slavonia and Dalmatia and included questionnaire completion and patient demonstration of inhaler use. At the end
of counseling, respondents completed a questionnaire on satisfaction with the service and WTP for the service.
Average age of the participants was 52,11 (SD =19,07), and slightly more women (55%) were included. Majority of
respondents (93%) considered the counseling helpful and believed that such counseling should be covered by their
health insurance (68%). The average amount respondents believed pharmacists should be paid for providing such
counseling was €7.18 (SD =5.37). Additionally, the study showed that a large proportion of asthma and COPD
patients were insufficiently controlled (32%), poorly adherent, and had incorrect inhalation techniques (35%). The
following factors were associated with respondents' WTP: the region they come from (p =0.019), level of completed
education (p =0.042), level of disease control (p =0.025), and sporadic adherence level (p =0.034). Respondents who
believed counseling should be paid for mostly came from Dalmatia, had higher levels of education, better disease
control, and were sporadically less adherent. For better treatment outcomes, an individualized approach to patient care
is necessary, aiming to educate patients about inhalation therapy and its health benefits, as it is crucial in the treatment
of chronic respiratory diseases