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Utjecaj sunčeva zračenja na kožu i fotoprotekcija
No full textCilj istraživanja
Cilj ovog rada je prikazati utjecaj sunčeva zračenja na kožu te ukazati na moguće negativne
posljedice prekomjernog izlaganja sunčevu zračenju. S obzirom da sve tri vrste sunčeva
zračenja - ultraljubičasto, infracrveno i vidljivi spektar uzrokuju fotooštećenja kože, cilj je
prikazati strategiju fotoprotekcije koja uključuje zaštitu od sva tri dijela spektra sunčeva
zračenja.
Materijali i metode
U izradi teorijskog specijalističkog rada korišteni su razni preglednici stručne znanstvene
literature, znanstvene i stručne knjige, časopisi te mrežne stranice. Specijalistički rad temelji
se na radovima objavljenim u stručnim znanstvenim časopisima i stručnim knjigama. Metode
rada bile su pretraživanje stručne znanstvene literature prema ključnim riječima.
Rezultati
Učinak sunca na kožu rezultat je interakcije ultraljubičastog, infracrvenog i vidljivog zračenja.
UV zračenje biološki je najaktivniji dio spektra i prekomjernim izlaganjem kože dovodi do
nastanka akutnih (eritem, fototoksične i fotoalergijske reakcije) i kroničnih negativnih učinaka
(fotostarenje, fotoimunosupresija, fotokarcinogeneza). Infracrveno zračenje izaziva kutanu
angiogenezu, infiltraciju upalnih stanica, remećenje dermalnog izvanstaničnog matriksa
indukcijom matriksnih metaloproteinaza i mijenjanje dermalne strukture proteina što dovodi
do preranog starenja kože. Vidljivi spektar zračenja inducira pigmentaciju i eritem, uz dodatni
sinergistički učinak u kombinaciji s UVA zračenjem.
Zaključak
S obzirom da sve tri vrste sunčeva zračenja uzrokuju fotooštećenja kože, produkciju
slobodnih kisikovih radikala te fotostarenje nužno je primjenjivati mjere fotoprotekcije. Kako
bi se izbjegle negativne posljedice na kožu primarno je izbjegavati prekomjerno izlaganje
suncu, ne boraviti vani za vrijeme najintenzivnijeg sunčeva zračenja, skloniti se u sjenu,
zaštitit se odjećom, pokrivalom za glavu i sunčanim naočalama te na kožu nanositi
fotozaštitni pripravak. Fotoprotektivni proizvod za kožu mora sadržavati zaštitu širokog
spektra, odnosno zaštitu od UVB i UVA zračenja, a primijeniti ga treba u odgovarajućoj
količini te ga redovito ponovno nanositi. Od trenutno dostupnih filtera niti jedan ne pruža
zaštitu od infracrvenog i/ili vidljivog dijela sunčeva zračenja. Primjenom antioksidansa
smanjuju se štetni učinci slobodnih kisikovih radikala te se na taj način ostvaruje preventivni
učinak protiv oštećenja kože izazvanih sunčevim zračenjem.Objectives
The aim of this study is to show the influence of solar radiation on the skin and to point out
the possible negative consequences of excessive exposure to solar radiation. Given that all
three types of solar radiation - ultraviolet, infrared and visible spectrum cause skin
photodamage, the goal is to present a photoprotection strategy that includes protection from
all three parts of the solar radiation spectrum.
Material and Methods
Various browsers of professional scientific literature, scientific and professional books,
magazines and websites were used in the preparation of this theoretical study. The study is
based on different studies published in professional scientific journals and professional books.
The working methods used in this study were mainly search of professional scientific
literature according to key words.
Results
The effect of the sun on the skin is the result of the interaction of ultraviolet, infrared and
visible radiation. UV radiation is the most biologically active part of the spectrum and
excessive exposure of the skin leads to acute (erythema, phototoxic and photoallergic
reactions) and chronic negative effects (photoaging, photoimmunosuppression,
photocarcinogenesis). Infrared radiation causes cutaneous angiogenesis, infiltration of
inflammatory cells, disruption of the dermal extracellular matrix by induction of matrix
metalloproteinases and changes in the dermal protein structure, which leads to premature
aging of the skin. The visible spectrum of radiation induces pigmentation and erythema, with
an additional synergistic effect in combination with UVA radiation.
Conclusion
Given that all three types of solar radiation cause skin photodamage, the production of free
oxygen radicals and photoaging, it is necessary to apply photoprotection measures. In order to
avoid negative consequences on the skin, the primary thing is to avoid excessive sun
exposure, do not stay outside during the most intense solar radiation, take shelter in the shade,
protect yourself with clothing, headgear and sunglasses, and apply a skin photoprotective
preparations. A photoprotective product for the skin must contain broad-spectrum protection,
protection against UVB and UVA radiation, and it should be applied in the appropriate
amount and reapplied regularly. Of the currently available filters, none provides protection
against the infrared and/or visible part of the sun's radiation. The use of antioxidants reduces
the harmful effects of free oxygen radicals, thus achieving a preventive effect against skin
damage caused by solar radiation
Utjecaj nuspojava antipsihotika na zadovoljstvo liječenjem u pacijentica sa shizofrenijom
No full textCilj istraživanja: Cilj ovog istraživanja je istražiti tip i učestalost nuspojava uzrokovanih
antipsihoticima, koje utječu na negativan stav o farmakoterapiji u pacijenata. Nadalje, specifični
cilj je istražiti učestalost prijavljivanja sumnji na nuspojave lijekova u ove skupine pacijenata.
Ispitanici i metode: Istraživanje je odobreno od strane Etičkog povjerenstva Klinike za
psihijatriju Vrapče, a ustrojeno je kao presječno istraživanje. Ispitanici uključeni u istraživanje
su anketirani u prostorijama Klinike za psihijatriju Vrapče, Zavod za ženske psihotične
poremećaje u razdoblju od svibnja do listopada 2022. godine. Uključni kriterij za ispitanike je
ženski spol, ambulantno liječenje pacijenata, punoljetna dob te potvrđena dijagnoza
shizofrenije.
Rezultati: U istraživanju je sudjelovalo ukupno 109 pacijentica koje su u ispitivanom razdoblju
posjetile Zavod za ženske psihotične poremećaje Klinike za psihijatriju Vrapče te dale svoj
informirani pristanak za sudjelovanje u istraživanju. Najveći udio ispitanica imao je između 50
i 60 godina, nisu imali partnera te nisu bile zaposlene. Čak 43,1% ispitanica je iskusio
nuspojavu antipsihotika, ali je samo jedna pacijentica sumnju na nuspojavu prijavila nadležnom
tijelu.
Zaključak: Rezultati ovog istraživanja pokazuju blago negativniji stav o farmakoterapiji
antipsihoticima u ispitivanoj populaciji koja je iskusila nuspojave, ali pokazuju značajno
neznanje i nedostatak prakse prijavljivanja sumnji na nuspojave antipsihotika. Zbog navedenog
se može zaključiti da je potrebna edukacija i pacijenata i zdravstvenih djelatnika o
farmakovigilanciji.Objective: The aim of this research was to investigate the type and frequency of side effects
caused by antipsychotics, which influence the attitude towards pharmacotherapy in
schizophrenic patients. Furthermore, the specific aim was to investigate the frequency of
reporting suspected adverse drug reactions in these groups of patients.
Subjects and methods: The research was approved by the Ethics Committee of the Vrapče
Psychiatry Clinic, and it was organized as a cross-sectional study. Respondents included in the
research were surveyed in the premises of the Vrapče Psychiatry Clinic, Institute for Female
Psychotic Disorders in the period from May to October 2022. Inclusive criteria for respondents
are female sex, outpatient treatment of patients, legal age and a confirmed diagnosis of
schizophrenia.
Results: A total of 109 patients who visited the Department for Female Psychotic Disorders of
the Vrapče Psychiatry Clinic during the period under investigation participated in the study and
gave their informed consent to participate in the study. The majority of respondents were
between 50 and 60 years old, did not have a partner and were not employed. As many as 43.1%
of respondents experienced a side effect of antipsychotics, but only one patient reported the
suspected side effect to the competent authority.
Conclusion: The results of this study show a slightly more negative attitude towards
antipsychotic pharmacotherapy in the population which experienced side effect, but show
significant ignorance and a lack of practice in reporting suspected side effects of antipsychotics.
Because of the above, it can be concluded that there is a need for education of both patients and
healthcare professionals about pharmacovigilance
Synthesis and characterization of amide type hybrid compounds composed of 6-, 7- and 9-substituted beta-carboline and ferrocene derivates
No full textU ovom radu sintetizirana su tri nova hibridna derivata β-karbolina i ferocena (7, 11, 15), kao i prekursori za njihovu sintezu (1-4, 8, 9, 10, 12-14). Broj reakcijskih koraka za pojedini derivat razlikuje se ovisno o položaju supstitucije β-karbolina. Sinteza 6-supstituiranog derivata 7 odvija se u sedam koraka. Pictet-Spenglerovom reakcijom dolazi do zatvaranja šesteročlanog prstena te nakon oksidacije nastaje derivat s β-karbolinskim prstenom (2). Slijedi kisela hidroliza metilnog etera čime nastaje fenol 3, kojemu je u četvrtom koraku vezana Boc-zaštićena amino skupina preko etilenske poveznice (4).
Ishodišna molekula u sintezi derivata β-karbolina na položaju 7 i 9 je harmin. Derivat na položaju 7 (11) sintetiziran je u pet, a derivat na položaju 9 (15) u četiri reakcijska koraka. U prvom koraku sinteze 7-supstituiranog derivata, kiselom hidrolizom metilnog etera nastaje harmol. Boc-zaštićena aminoetilna skupina povezana je u slučaju harmola preko fenolne skupine (8) a u slučaju harmina preko amino skupine (12). Reagens za navedene sinteze je u oba slučaja 2(tert-butoksikarbonilamino)etil bromidom te se reakcije provode uz cezijev karbonat.
Sljedeći koraci jednaki su za sve produkte. Nakon hidrolize zaštitne Boc-skupine sa spojeva 4, 8 i 12 uz klorovodičnu kiselinu, nastali amini 5, 9 i 13 se oksidiraju u odgovarajuće azide 6, 10 i 14. U zadnjem koraku sinteze dobiveni azidi 6, 10 i 14 reagiraju s etinil ferocenom u reakciji bakrom (I) katalizirane azid-alkin cikloadicije u kojoj dolazi do zatvaranja triazolskog prstena između dva farmakofora te nastaju konačni produkti 7, 11 i 15.
Pripravljenim spojevima potvrđene su strukture korištenjem standardnih analitičkih i spektroskopskih metoda (IR, MS, 1H i 13C NMR) te su im određena tališta. Njihov biološki učinak bit će ispitan u daljnjim istraživanjima koji prelaze okvire ovog rada.In this paper three new β-carboline derivatives (7, 11, 15) have been synthesized, as well as their precursors (1-4, 8, 9, 10, 12-14). The number of reaction steps differs depending on the β-carboline derivatization position. 6-substituted derivative 7 was synthesized in a seven step procedure. Firstly, the six-membered ring was closed using the Pictet-Spengler reaction and, after oxidation, a β-carboline ring was formed (2). This was followed by acidic hydrolysis of the methyl ether, yielding phenol 3, which was then linked to a Boc-protected amino group using ethylene as a spacer (4).
In the synthesis of 7- and 9-substituted derivatives of β-carboline, harmine was used as a starting compound. Derivatives at position 7 (11) and 9 (15) were synthesized in a five and four step procedure. In the first step of the synthesis of harmol was performed by acidic hydrolysis of methyl ether. The Boc-protected aminoethyl group was linked via phenol group in harmol (8) and via amino group in harmine (12). The reagent for both reactions was 2(tert-butoxycarbonylamino)ethyl bromide and the reactions were carried out in the presence of cesium carbonate.
The following steps were equal to all three derivatives. After hydrolysis of the Boc-protecting group from compounds 4, 8 and 12 with hydrochloric acid, the resulting amines 5, 9 and 13 were then oxidized to azides 6, 10 and 14. Finally, azides 6, 10 and 14 reacted with ethinyl ferrocene in a copper (I) catalyzed azide-alkyne cycloaddition reaction, and a triazole ring connecting the two pharmacophores was formed (7, 11 and 15).
Structures of the newly prepared compounds were confirmed using conventional analytical and spectroscopic methods (IR, MS, 1H and 13C NMR) and melting points of the compounds were determined. The biological activity of the compounds will be investigated
Validation of HPLC-DAD method for analysis of leachables originating from rubber stoppers in infusion solutions
No full textInfuzijske otopine spadaju u jedne su od najprimjenjivanijih farmaceutskih oblika kod liječenja
akutno oboljelih pacijenata. Uzevši u obzir činjenice da se primjenjuju parenteralno te da spadaju u
farmaceutske oblike koji imaju visok rizik stupanja u interakcije s ambalažom, potencijalno prisutna
onečišćenja mogu predstavljati ugrozu za zdravlje krajnjih korisnika. Jedan od načina na koji
onečišćenja iz ambalaže mogu dospjeti u infuzijske otopine je prelaskom iz gumenih čepova u
formulaciju pri uvjetima skladištenja. Kako bi se mogla odrediti konačna sigurnost primjene
farmaceutskog pripravka, takva onečišćenja trebala bi se identificirati i kvantificirati. U svrhu ovog
rada validirana je i provedena HPLC-DAD metoda za kvantifikaciju jednog onečišćenja koje potječe
iz gumene ambalaže. Metoda je validirana sukladno sa smjernicama Međunarodnog vijeća za
harmonizaciju (ICH Q2(R2)) te je potom analizirano 37 uzoraka infuzijskih otopina. Od 37 uzoraka,
3 su sadržavala ispitivano onečišćenje u koncentraciji većoj od granice dokazivanja (LOD), a 1 je
uzorak sadržavao onečišćenje u koncentraciji većoj od granice određivanja (LOQ).Infusion solutions are one of the most widely used pharmaceutical forms in the treatment of acutely
ill patients. Taking into consideration the fact that infusion solutions are administered parenterally
and that they belong to a group of pharmaceutical forms that pose a high risk of interacting with the
packaging, the potentially present impurities can pose a threat to the health of end users. One of the
ways in which impurities from packaging can get into infusion solutions is by leaching from rubber
stoppers to the formulation under storage conditions. In order to be able to determine the final safety
of use of the pharmaceutical, such impurities should be identified and quantified. For this thesis, a
HPLC-DAD method was validated and conducted for the quantification of one impurity that is
originating from rubber packaging. The method was validated in accordance with the guidelines
published by the International Council for Harmonization (ICH Q2(R2)) and then 37 samples of
infusion solutions were analyzed. Out of 37 samples, 3 contained the tested impurity in a
concentration higher than the limit of detection (LOD), and 1 sample contained the impurity in a
concentration higher than the limit of quantification (LOQ)
The influence of clinical and histological features on treatment options for patients with Luminal A breast cancer
No full textKarcinom dojke najčešće je dijagnosticirani maligni tumor današnjice. Mortalitet karcinoma dojke u razvijenim
zemljama značajno je smanjen, zahvaljujući razvoju dijagnostike, citostatske terapije i provođenju nacionalnih
programa ranog otkrivanja. Luminalni A podtip najčešći je imunohistokemijski podtip karcinoma dojke. U radu je
ispitan patohistološki nalaz pacijentica oboljelih od luminalnog A karcinoma dojke te pristupi u liječenju. Obuhvaćene
su 72 pacijentice kojima je dijagnoza postavljena tijekom 2020. u KBC Zagreb te su ondje liječene i praćene. Od toga
su 22 pacijentice bile premenopauzalne, a 50 pacijentica postmenopauzalno. Gotovo 60% pacijentica jest u 6. i 7.
desetljeću života. Ni u jedne pacijentice nije utvrđen tumor gradusa 3. Najveća je učestalost karcinoma dojke
nespecifičnog tipa (NST), dok je učestalost lobularnog karcinoma i specijalnih tipova puno manja. Više od polovine
premenopauzalnih pacijentica imalo je bolest stadija II ili III. Većina postmenopauzalnih pacijentica imala je bolest
stadija I. Svega 2 pacijentice imale su bolest stadija IV. Od 72 pacijentice, svega 6 pacijentica nije bilo liječeno
kirurški. Poštedni zahvat nije praćen radioterapijom samo u iznimnim slučajevima, dok se nakon mastektomije
radioterapija većinom izostavlja. Pozitivan nalaz aksilarnih limfnih čvorova imalo je 12 pacijentica. Od 22
premenopauzalne pacijentice, 14 pacijentica inicijalno je propisan tamoksifen, a 8 pacijentica goserelin u kombinaciji
s inhibitorom aromataze ili tamoksifenom. Od 50 postmenopauzalnih pacijentica, 47 pacijentica propisan je inhibitor
aromataze, a 3 pacijenticama tamoksifen. Adjuvantna kemoterapija propisana je 6 pacijentica, dok se 11 pacijentica
liječilo neoadjuvantno. Adjuvantna kemoterapija i neoadjuvantno liječenje primjenjuju se kod stadija II, III i IV. Do
danas 63 pacijentice redovito dolaze na kontrolu i ne pokazuje znakove bolesti, dok je 9 pacijentica izgubljeno iz
praćenja.Breast cancer is the most frequently diagnosed cancer today. Breast cancer mortality in high-income countries
significantly dropped, due to advances in diagnostic methods and cancer therapy, as well as implementation of national
breast cancer screening programs. Luminal A subtype is the most common immunohistochemical subtype of breast
cancer. This study examines histopathological features and treatment approaches in patients with luminal A breast
cancer. Study included 72 patients who were diagnostically evaluated in 2020, and subsequently treated in University
Hospital Centre Zagreb. Of all patients, 22 patients were premenopausal and 50 patients were postmenopausal. Patients
in the sixth and seventh decade represented almost 60% of all patients. All tumors were histologically graded as GI and
GII, with no GIII tumors. The frequency of invasive breast carcinoma of no special type (NST) was the highest, while
the frequency of lobular cancer and special types was much lower. More than half of premenopausal patients had stage
II or III disease. Most postmenopausal patients had stage I disease. Only 2 patients had stage IV disease. Of all patients,
only 6 patients were not treated surgically. Omission of radiotherapy after breast conserving surgery was appropriate
only in exceptional cases, while omitting radiotherapy after mastectomy was common. The presence of positive axillary
lymph nodes was found in 12 patients. Of 22 premenopausal patients, 14 patients were prescribed tamoxifen as initial
treatment option, while 8 patients were prescribed goserelin in combination with aromatase inhibitor or tamoxifen. Of
50 postmenopausal patients, 47 patients were prescribed aromatase inhibitors and 3 patients were prescribed tamoxifen.
Adjuvant chemotherapy was prescribed to 6 patients, while 11 patients received neoadjuvant treatment. Adjuvant
chemotherapy and neoadjuvant treatment were appropriate treatment options for stages II, III and IV. In 3-year followup, 63 patients from the analysed group are alive with no signs of relapse, while 9 patients were lost to follow-up
Pharmacotherapy treatment of non-alcoholic fatty liver disease
No full textNASH i NAFLD vodeći su uzroci transplantacije jetre današnjice. Nezdrava prehrana i kronični stres dovode
do neravnoteže u metabolizmu masti što dovodi do povećanog nakupljanja lipida u hepatocitima. Današnji
pristup liječenju bolesti je promjena životnog stila uvođenjem redovite fizičke aktivnosti te kalorijskog
manjka uz dodatke prehrani. Često taj cilj nije lako ostvariv pa se mora posegnuti za farmakoterapijom.
Današnji lijekovi još uvijek se primjenjuju off-label. Od trenutno korištenih lijekova, najviše su u primjeni
pioglitazon i GLP-1 agonisti, a od novijih lijekova, najviše potencijala ima obetikolična kiselina, iako se i uz
nju vežu neke nuspojave, poput svrbeža i povećanja LDL-a. Iz perspektive farmaceuta, pacijente je bitno
savjetovati o dodacima prehrani koji mogu pomoći kao pomoćna terapija. Najviše se koriste antioksidansi,
vitamin E, no njegovo doziranje je upitno i silimarin. Sve češće se naglašava i važnost primjene probiotika.
Zaključno, radi se o vrlo zahtjevnom terapijskom području koje se sve više istražuje i predstavlja veliki interes
s obzirom na stalan rast oboljelih.NASH and NAFLD are the leading causes of liver transplantation today. Unhealthy diet and chronic
stress lead to an imbalance in fat metabolism, which leads to increased accumulation of lipids in
hepatocytes. Today's approach to the treatment of the disease is to change the lifestyle by introducing
regular physical activity and a caloric deficit with nutritional supplements. Often this goal is not easily
achievable, so pharmacotherapy must be resorted to. Today's drugs are still administered off-label.
Of the currently used drugs, pioglitazone and GLP-1 agonists are the most used, and of the newer
drugs, obeticholic acid has the most potential, although it also has some side effects, such as itching
and an increase in LDL. From a pharmacist's perspective, it is important to advise patients about
nutritional supplements that can help as adjunctive therapy. Antioxidants, silymarin and vitamin E
are mostly used, but its dosage is questionable. The importance of the use of probiotics is increasingly
emphasized. In conclusion, it is a very demanding therapeutic area that is increasingly being
researched and is of great interest considering the constant growth of patients
Synthesis and characterization of N-9-tethered harmicines, harmine-cinnamic acid derivate hybrids
No full textMultiformni glioblastom (GBM) je najčešći primarni maligni tumor mozga s medijanom preživljenja nakon dijagnoze
od samo 15 mjeseci. Liječenje ove bolesti je zahtjevno zbog pojave rezistencije tumorskih stanica na zračenje i
kemoterapiju, što dovodi do progresije i recidiva bolesti. Osim toga, postoji svega nekoliko lijekova za terapiju
multiformnog glioblastoma zbog čega je potrebno razvijati nove djelatne tvari koje bi bile učinkovitije i otpornije prema
razvoju rezistencije.
Cilj ovog diplomskog rada bila je priprava novih molekula s anti-GBM djelovanjem korištenjem principa molekulske
hibridizacije. Harmin, -karbolinski alkaloid s raznolikim biološkim djelovanjem, i derivati cimetne kiseline (DCK-i)
povezani su u jedinstvene molekule (harmicine) korištenjem bakrom(I) katalizirane azid-alkin cikloadicije (klikreakcije) uz generiranje triazolskog tipa poveznice. S obzirom da harmin i DCK-i ispoljavaju anti-GBM svojstva,
očekuje se da će pripravljeni hibridi posjedovati snažno anti-GBM djelovanje. U svrhu priprave hibrida bilo je potrebno
sintetizirati odgovarajuće prekursore: azide DCK-a 3a-c i alkin harmina 4. Alkin je sintetiziran u jednom reakcijskom
koraku, reakcijom harmina i propargil-bromida uz Cs2CO3, dok su azidi pripravljeni u četiri sintetska koraka. U prvom
koraku DCK-i su u reakciji s SOCl2, uz katalitičku količinu DMF-a, prevedeni u kiselinske kloride koji su potom
esterificirani korištenjem EtOH i TEA. Etilni esteri 1a-c reducirani su pomoću LiAlH4, a dobiveni alkoholi 2a-c
prevedeni su u azide 3a-c uz ADMP i DBU. Željeni hibridi 5a-c pripravljeni su klik-reakcijom odgovarajućih prekursora
u MeOH uz katalitičku količinu Cu(II)-acetata.
Novosintetizirani harmicini karakterizirani su uobičajenim spektroskopskim i analitičkim metodama (1H i 13C NMR,
MS i IR) te su procijenjena njihova farmakokinetička svojstva in silico. Svim harmicinima predviđa se dobra oralna
bioraspoloživost, dok se hibridima 5a-b predviđa sposobnost prolaska krvno-moždane barijere. U nastavku istraživanja
ispitat će se antiproliferativno djelovanje harmicina in vitro na humanu staničnu liniju GBM-a.Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor with a median survival time of
only 15 months. The main concern in GBM treatment is the development of resistance, which leads to disease
progression and relapse. In addition, few drugs are available for GBM chemotherapy, highlighting the need for the
development of novel and effective anti-GBM agents.
The aim of this work was to synthesize novel molecules with anti-GBM properties using the molecular hybridization
approach. Harmine, the β-carboline alkaloid with multiple biological effects, and cinnamic acid derivatives (CADs)
were linked via a triazole-type linker using a copper(I)-catalyzed azide-alkyne cycloaddition (“click” reaction) to form
a hybrid molecule. Considering that both harmine and CADs exhibit anti-GBM properties, the proposed hybrids are
expected to have a strong effect on GBM.
To prepare the target hybrids, CAD-based azides 3a-c and harmine-based alkyne 4 were synthesized. The alkyne 4 was
synthesized in one reaction step by reacting harmine with propargyl bromide in the presence of Cs2CO3, whereas the
preparation of azides 3a-c required four-step procedure. In the first step, the CADs were converted to acyl chlorides
with SOCl2 in the presence of DMF. The acyl chlorides were then esterified with ethanol and TEA, and the obtained
ethyl esters 1a-c were reduced to alcohols 2a-c with LiAlH4. Finally, the alcohols were efficiently converted to azides
3a-c with ADMP and DBU. The “click” reaction of the prepared precursors proceeded smoothly in methanol with a
catalytic amount of Cu(II) acetate and gave the desired hybrids 5a-c.
The structures of the harmicines were confirmed by standard analytical and spectroscopic methods (1H and 13C NMR,
IR and MS). The pharmacokinetic properties of harmicines were calculated in silico. Good oral bioavailability was
predicted for all harmicines. Additionally, compounds 5a-b are expected to cross the blood-brain barrier. Further studies
will investigate the antiproliferative activity of the harmicines in vitro against human GBM cell line
Implementation of risk minimization measures for the use of fluoropyrimidines in the Republic of Croatia
No full textFluoropirimidini su skupina kemoterapeutika koji se koriste u liječenju više vrsta raka, a uključuju 5-fluorouracil te njegove oralne prolijekove kapecitabin i tegafur.
U metabolizmu fluoropirimidina glavnu ulogu igra enzim dihidropirimidin-dehidrogenaza (DPD) koju kodira gen DPYD. Polimorfizmi i varijante gena DPYD povezuju se s nedostatkom aktivnosti enzima DPD te povećanim rizikom za razvoj teških nuspojava fluoropirimidina. Stoga je objavljeno je više smjernica koje daju preporuke za farmakogenetičko testiranje ovog gena. Cilj testiranja je otkriti moguće varijante gena DPYD prije terapije fluoropirimidinima te smanjiti rizik od nuspojava. Ovaj rad sadrži pregled metoda genotipizacije i fenotipizacije te sažetak najvažnijih nacionalnih smjernica država Europe i Europske agencije za lijekove (EMA).
U sklopu ovog diplomskog rada, obrađeni su podaci farmakogenetičkog testiranja DPYD u pacijenata Republike Hrvatske u periodu od srpnja 2009. do lipnja 2023. godine. Prikazane su statistike o spolu i dobi pacijenata te broju testova provedenih svake godine. Obradom rezultata genotipizacije izračunate su frekvencije pojedinih varijanti u ispitivanoj populaciji te je prikazano podrijetlo preporuka za testiranje na razini primarne, sekundarne i tercijarne zdravstvene zaštite.Fluoropyrimidines are a group of chemotherapeutic drugs used to treat a spectrum of carcinoma. The group includes 5-fluorouracil and its oral prodrugs capecitabine and tegafur.
The enzyme dihydropyrimidine dehydrogenase, coded by the DPYD gene, has a major role in the metabolism of fluoropyrimidines. DPYD polymorphisms and variants are associated with lack of DPD enzyme activity and increased risk for development of fluoropirimidine severe adverse reactions. Therefore, several guidelines for DPYD testing have been published. The goal of these tests is to detect possible variants of the DPYD gene pre-treatment and to minimise the risk of side effects. This paper includes an overview of different genotyping and phenotyping methods, as well as an overview of the most important national guidelines of European countries and the European Medicines Agency (EMA).
In this master's thesis, the results of more than a decade's worth of pharmacogenetic testing of DPYD in patients from the Republic of Croatia are presented. This paper shows the analysis of patients' sex and age and the number of tests performed each year. Included is the calculated frequency of each of the gene variant and the origin of testing recommendations at the primary, secondary and tertiary health care levels
Determination of total polyphenol content and antioxidant activity of soy-based dietary supplements
No full textBroj dodataka prehrani koji sadrže soju na tržištu i njihova uporaba u stalnom su porastu. Ova skupina dodataka prehrani postala je iznimno zanimljiva zbog preventivnog i terapijskog djelovanja na ljudsko zdravlje. Cilj ovog rada bio je procijeniti kvalitetu ispitivanih dodataka prehrani koji sadrže soju obzirom na ukupni sadržaj polifenola te odrediti antioksidativnu aktivnost istih. Analizirani dodaci prehrani koji sadrže soju mogu se smatrati dobrim izvorom polifenolnih sastavnica. Antioksidativna aktivnost ispitivanih dodataka prehrani u skladu je sa sadržajem ovih biološki aktivnih sastavnica. Korelacija između ukupnog sadržaja polifenola i antioksidativnog učinka snažno je statistički značajna, pa se može zaključiti da je antioksidativno djelovanje proporcionalno sadržaju ovih sekundarnih metabolita. HPLC-DPPH korištena metoda je brza i ponovljiva te prikladna za rutinsku analizu uzoraka. Rezultati ove studije doprinose boljem razumijevanju sadržaja ukupnih polifenola i antioksidativne aktivnosti dodataka prehrani koji sadrže soju.The number of soy-based dietary supplements and their use is constantly increasing. This group of dietary supplements has become extremely interesting due to its preventive and therapeutic effects on human health. This study aimed to evaluate the quality of the tested soy-based dietary supplements concerning the total polyphenol content and their antioxidant activity. The analyzed soy-based dietary supplements could be considered a good source of polyphenolic constituents. The antioxidant activity of the tested dietary supplements is in accordance with the content of these biologically active compositions. The correlation between total polyphenol content and antioxidant activity is strongly statistically significant, so it could be concluded that antioxidant activity is proportionally contained in these secondary metabolisms. This HPLC-DPPH method is fast and reproducible, and suitable for use in routine analysis. The results of this study contribute to a better understanding of the content of total polyphenols and the antioxidant activities of soy-based dietary supplements
Curcumin nanoformulations with antimicrobial activity
No full textKurkumin, polifenol izoliran iz biljke Curcuma longa, potencijalni je kandidat za terapiju različitih bolesti zahvaljujući svojem antimikrobnom, antikancerogenom i antioksidativnom učinku. Međutim, loša fizikalno-kemijska svojstva poput slabe topljivosti u vodi, lipofilnosti, kemijske nestabilnosti i loše bioraspoloživosti ograničavaju njegovu kliničku primjenu. Uklapanjem u nanoformulacije poput liposoma, nanočestica, micela, hidrogelova, nanokristala moguće je unaprijediti farmakokinetička i farmakodinamička svojstva kurkumina te time uvelike unaprijediti terapiju. Brojna istraživanja pokazala su da se uklapanjem kurkumina u nanoformulacije postiže bolja distribucija polifenola u organizmu, poboljšani terapijski učinak s ciljanom dostavom, ravnomjerno i kontrolirano oslobađanje na mjestu djelovanja, produljeno vrijeme eliminacije, povećanje bioraspoloživosti te smanjenje neželjenih učinaka i toksičnosti na zdravo tkivo. Provedena najvažnija ex vivo, in vivo i klinička istraživanja objedinjena ovim radom sistematizirano su opisana s obzirom na vrstu/tip nanoformulacija i svojstva materijala korištenih za njihovu pripravu.Curcumin, a polyphenol isolated from the plant Curcuma longa, is a potential candidate for the treatment of various diseases due to its antimicrobial, anticancer and antioxidant effects. However, physicochemical properties of curcumin, such as poor water solubility, lipophilicity, chemical instability, and poor bioavailability limit its clinical application. Incorporation of curcumin into various nanoformulations (lipid and polymeric), can significantly improve its pharmacokinetic and pharmacodynamic properties, and thus significantly enhance the efficacy of therapy. Numerous studies have shown that curcumin nanoformulations allow better distribution of the polyphenol in the body, increased bioavailability, and therapeutic efficacy by enabling targeted and localized delivery, prolonged and/or controlled release at the site of action, decreased elimination time as well as reduced side effects and toxicity to the healthy tissue. The most important ex vivo, in vivo, and clinical studies included in this paper are systematically described with regard to the type of nanoformulations and the properties of the materials used for their preparation