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Evaluation of the LightCycler PRO System for genotyping FV Leiden, MTHFR and PAI-1 polymorphisms
No full textTrombofilija je skup poremećaja koji povećavaju sklonost organizma stvaranju krvnih ugrušaka (tromba), što
može dovesti do ozbiljnih zdravstvenih komplikacija kao što su duboka venska tromboza i plućna embolija.
Nasljedni rizični čimbenici uključuju genske polimorfizme faktor V Leiden (FV G1691A), PAI-1 5G/4G i
MTHFR C677T. U Kliničkom zavodu za kemiju Kliničkog bolničkog centra Sestre milosrdnice instaliran je
novi analitički sustav LightCycler® PRO (Roche Diagnostics GmbH, Basel, Švicarska) koji bi se koristio za
genotipizaciju navedenih polimorfizama. Cilj ovog rada bio je vrednovati analitički sustav LightCycler® PRO
validacijom analitičkih karakteristika mjernih postupaka genotipizacije FV G1619A, PAI-1 5G/4G i MTHFR
C677T metodom lančane reakcije polimeraze uz analizu krivulje taljenja prije korištenja u rutinskom radu.
Ispitani su analitička nepreciznost, analitička osjetljivost, analitička specifičnost, analitička netočnost,
usporedivost drugom metodom i granica detekcije. Svi ispitani parametri u potpunosti su zadovoljili unaprijed
definirane analitičke kriterije kvalitete i stoga se ispitani mjerni postupci mogu prihvatiti za rutinski rad.Thrombophilia is a collection of disorders which increase an organism's tendency to form blood clots, which can
lead to serious health complications like deep venous thrombosis and pulmonary embolism. Hereditary risk
factors include gene polymorphisms for factor V Leiden (FV G1691A), PAI 5G/4G, and MTHFR C677T. New
analytical system for genotyping aforementioned polymorphisms, LightCycler® PRO (Roche Diagnostics
GmbH, Basel, Švicarska), was installed in the Clinical Department of Chemistry University Hospital Center
Sestre milosrdnice. This study aimed to evaluate new analytical system LightCycler® PRO by validating
analytical characteristics of genotyping polymorphisms FV G1691A, PAI-1 5G/4G, and MTHFR C677T using
real-time polymerase chain reaction with melting curve analysis. Analytical imprecision, analytical sensitivity,
analytical specificity, analytical inaccuracy, repeatability using another method, and limit of detection were
examined. All parameters fully met the pre-defined analytical quality criteria and therefore the evaluated methods
can be accepted for routine work
Metabolism of selected antimicrobial drugs
No full textBroj infektivnih oboljenja, bilo da je riječ o bakterijskim, gljivičnim, virusnim ili parazitarnim
infekcijama, svakodnevno raste i predstavlja nove izazove u liječenju. Osim potrebe za razvojem
novih antimikrobnih lijekova, važno je poznavati farmakokinetske karakteristike već postojećih
lijekova kako bi maksimizirali njihov učinak i smanjili pojavnost rezistencije.
Cilj diplomskog rada bio je istražiti metabolizam određenih antimikrobnih lijekova, s naglaskom na
reakcije biotransformacije, pregled metabolita i njihovih svojstava. U okviru ovog istraživanja,
analizirane su farmakokinetičke karakteristike lijekova, uključujući njihovu apsorpciju, distribuciju,
metabolizam i eliminaciju. Istražene su i specifične interakcije između lijekova i enzima koji
sudjeluju u njihovom metabolizmu, poput citokroma P450, koji može značajno utjecati na
učinkovitost i sigurnost terapije. Također, razmotreni su faktori koji utječu na varijabilnost u
farmakokinetici, uključujući genetske polimorfizme, dob, spol i prisutnost drugih bolesti.
Ova saznanja ističu važnost razumijevanja metabolizma antimikrobnih lijekova za optimizaciju
terapije i smanjenje rizika od nuspojava i otpornosti na lijekove.The prevalence of infectious diseases, whether caused by bacteria, fungi, viruses, or parasites, is
escalating daily, posing new and complex challenges for effective treatment. Alongside the urgent
need for the development of novel antimicrobial agents, it is crucial to gain a comprehensive
understanding of the pharmacokinetic characteristics of existing medications to maximize their
therapeutic efficacy and minimize the incidence of drug resistance. The aim of this thesis is to
investigate the metabolism of select antimicrobial drugs, with a particular focus on
biotransformation reactions, a thorough review of metabolites, and their corresponding properties.
This research encompasses an analysis of the pharmacokinetic characteristics of these drugs,
including their absorption, distribution, metabolism, and elimination. Moreover, the study delves
into specific interactions between these drugs and the enzymes involved in their metabolism, notably
cytochrome P450, which can profoundly influence both the efficacy and safety of therapeutic
interventions. Furthermore, the thesis considers various factors that contribute to variability in
pharmacokinetics, such as genetic polymorphisms, age, sex, and the presence of comorbid
conditions. Overall, this knowledge underscores the critical importance of understanding the
metabolism of antimicrobial drugs in order to optimize therapy and mitigate the risks of adverse
effects and the development of drug resistance
Učinak kemferola na zacjeljivanje rana
No full textCilj istraživanja
Na tržištu raste interes za pripravcima biljnog porijekla za liječenje različitih oboljenja,
uključujući i dermatološke probleme. Kemferol je dobro poznati flavonoid prisutan u brojnim
biljnim vrstama koje se tradicionalno koriste u cijeljenju rana. Cilj ovog rada bio je napraviti
pregled istraživanja kemferola kao aktivne biljne sastavnice ekstrakata koji se primjenjuju kao
pomoć u cijeljenju rana te istražiti njihove mehanizme djelovanja i potencijalnu učinkovitost.
Materijal i metode
U izradi specijalističkog rada korištena je elektronička baza podataka PubMed. Radom
su obuhvaćene znanstvene studije koje su ispitivale učinak kemferola i njegovih derivata na
cijeljenje rana, uključujući i učinak ekstrakata biljnih vrsta koji ih sadržavaju. U pretraživanju
su korištene ključne riječi: zacjeljivanje rana (engl. wound healing) i kemferol. Pretragom baze
PubMed 3. srpnja 2024. godine dobivena su 94 rada od kojih je 45 odgovaralo temi rada.
Rezultati
Kemferol i biljni ekstrakti koji ga sadrže pospješili su cijeljenje rana i smanjili stvaranje
ožiljaka. Učinak kemferola temeljio se na regulaciji upalnih čimbenika, pojačanoj migraciji
stanica, inhibiciji metaloproteinaza i povećanoj sintezi kolagena. Usporedbe sa standardnom
terapijom pokazale su da biljni ekstrakti s kemferolom djeluju jednako dobro ili bolje od
konvencionalnih terapija poput Madecassol®-a, fusidatne kiseline, indometacina ili
hidrokortizona. Također pokazuju bakteriostatski učinak na mikroorganizme poput Bacillus
cereus i Staphylococcus vrste, te antifungalni učinak na Candida vrste. Inovativne obloge za
rane s kemferolom i biljnim ekstraktima pokazale su dobru biokompatibilnost, povećale su
proliferaciju fibroblasta, te pokazale protuupalni i antioksidacijski učinak. Ispitani pripravci
pokazali su i značajnu učinkovitost u zacjeljivanju dijabetičkih rana. S obzirom na to da biljni
ekstrakti sadržavaju brojne sastavnice, opaženi učinak je vjerojatno posljedica sinergizma
među sastavnicama. No studije provedene s čistim kemferolom ukazuju na važnu ulogu koju
taj flavonoid ima u ukupnom učinku ispitanih ekstrakata.
Zaključak
Kemferol i biljni ekstrakti koji ga sadrže pozitivno su utjecali na cijeljenje rana u
provedenim studijama. Unatoč tome, potrebna su daljnja istraživanja kako bi se dobio bolji
uvid u učinkovitost, mehanizam djelovanja i sigurnost primjene.Objectives
There is an increasing interest in preparations of plant origin in the market. Kaempferol
is a well-known flavonoid present in plants traditionally used in wound healing. The aim of
this work was to review the research on the topic of kaempferol and the plants containing it,
and to investigate their mechanisms of action and potential efficacy in wound healing.
Material and Methods
In the research, the electronic database PubMed was utilized. The work included
scientific studies that examined the effect of kaempferol on wound healing including the effects
of the plant extracts containing this flavonoid or its derivatives. The keywords used in the
search were: wound healing, kaempferol. The PubMed database search on 3th of July 2024
resulted in 94 papers, out of which 45 met the selected criteria.
Results
Kaempferol and plant extracts containing it promoted wound healing and reduced scar
formation. The effect of kaempferol was based on the regulation of inflammatory factors,
enhanced cell migration, inhibition of metalloproteinases, and increased collagen synthesis.
Comparisons with standard therapy indicated that the investigated samples performed equally
or better than the conventional treatments such as Madecassol®, fusidic acid, indomethacin or
hydrocortisone. They also exhibited bacteriostatic effects against microorganisms such as
Bacillus cereus and Staphylococcus species, as well as antifungal effects against Candida
species. Innovative wound dressings containing kaempferol and plant extracts demonstrated
good biocompatibility, increased fibroblast proliferation, reduced inflammation, and displayed
antioxidant effects. The investigated samples also showed significant efficacy in healing
diabetic wounds. Given that plant extracts contain numerous constituents, the observed effect
is probably due to the synergism between the extracts' components. However, studies
conducted with pure kaempferol indicate the important role that this flavonoid plays in the
overall effect of the tested extracts.
Conclusions
Kaempferol and plant extracts containing it improved wound healing in the performed
studies. Despite this, further research is needed to gain a better understanding of their efficacy,
mechanism of action and safety of use
Medicinska konoplja - regulatorni status i kontrola kakvoće
No full textCilj istraživanja
Cilj ovog specijalističkog rada je dati sveobuhvatan pregled recentnih podataka o regulativi i
metodama ispitivanja kakvoće biljne droge i ljekovitih pripravaka na bazi medicinske konoplje
te tako doprinijeti boljem razumijevanju važećih zakonskih propisa za stavljanje na tržište i
osiguranje njihove kakvoće.
Materijal i metode
Istraživanje u okviru ovog rada je teorijskog karaktera i uključuje pregled dostupne znanstvene
i stručne literature o predloženoj temi te odgovarajući zakonodavni akti i smjernice dostupne
na stranicama nadležnih regulatornih tijela. Dostupni podaci su kritički razmotreni i
sistematično prikazani u obliku preglednog rada.
Rezultati
Intenzivno se razvijaju različite analitičke metode pogodne za analizu sastava različitih
pripravaka na bazi medicinske konoplje. Osnove za ujednačenu kontrolu kakvoće biljnih tvari,
pripravaka i lijekova na bazi medicinske konoplje na razini EU postavljene su u farmakopejskoj
monografiji Cannabis flos u Europskoj Farmakopeji koja je uspostavljena u srpnju 2024.
godine. S regulatornog aspekta, svi lijekovi na bazi medicinske konoplje i kanabinoida moraju
imati dozvolu za primjenu u liječenju, odnosno proći registracijski postupak pri nadležnim
Europskim ili nacionalnim regulatornim tijelima. Svi trenutačno dostupni lijekovi na bazi
kanabinoida u Europi odobreni su putem ocjene cjelovite dokumentacije u standardnom
registracijskom postupku.
Zaključci
Zbog povijesnih okolnosti, dinamika odobravanja medicinske upotrebe konoplje značajno je
različita u pojedinim državama Europe. U Republici Hrvatskoj dozvoljena je medicinska
upotreba i uzgoj medicinske konoplje, uz poštivanje važećeg regulatornog okvira. Uvrštavanje
monografije biljne droge konopljin cvijet (Cannabis flos) u Europsku farmakopeju predstavlja
značajan iskorak u osiguranju kakvoće lijekova i pripravaka od medicinske konoplje.Objectives
The aim of this work was to provide a comprehensive overview of recent data on regulations
and analytical methods for the quality control of herbal drug and medicinal products based
on medical cannabis and to contribute to a better understanding of the current legal
framework for placing them on the market and ensuring their quality.
Material and methods
The research conducted for this work is theoretical in nature and includes a review of the
available scientific and professional literature on the proposed topic, as well as the relevant
legislation and guidance on the websites of the relevant regulatory authorities. The data was
critically reviewed and systematically presented in the form of a review paper.
Results
There has been intensive development of analytical methods specifically designed to analyze
the composition of various medical cannabis-based preparations. The basis for uniform quality
control of plant substances, preparations and medicinal products based on medical cannabis
at EU level was created with the pharmacopoeial monograph Cannabis flos, published in July
2024. From a regulatory perspective, all cannabis-based medicinal products must be approved
by the competent European or national regulatory authorities. All cannabinoid-based
medicinal products currently available in Europe have been authorized through full
documentation under the standard registration procedure.
Conclusion
Due to historical circumstances, the dynamics of authorizing the medicinal use of cannabis
vary widely across different European countries. In the Republic of Croatia, the medicinal use
and cultivation of medical cannabis are permitted in accordance with the applicable
regulatory framework. The inclusion of the monograph Cannabis flos in the European
Pharmacopoeia represents a significant step forward in ensuring the quality of medicinal
products and preparations based on medical cannabi
Potencijali i izazovi u razvoju multivezikularnih liposoma
No full textCILJ ISTRAŽIVANJA
Cilj ovog rada bio je pružiti sistematizirani pregled objavljene znanstvene i stručne literature vezane za
razvoj i proizvodnju formulacija lijekova temeljenih na tehnologiji multivezikularnih liposoma. Opisana
su specifična strukturna svojstva multivezikularnih liposoma i definirani kritični elementi u proizvodnji
stabilnih formulacija lijekova. Prikazane su prednosti i ograničenja formulacija lijekova
multivezikularnih liposoma u odnosu na konvencionalne oblike liječenja te u odnosu na druge tipove
liposoma.
MATERIJALI/ISPITANICI I METODE
Istraživanje je provedeno pretraživanjem akreditiranih baza podataka prema tematici relevantnoj za
izradu specijalističkog rada. Među općim i specijaliziranim znanstvenim i stručnim člancima odabrani
su relevantni članci s obzirom na postavljene ciljeve te su detaljno proučeni kako bi se napravio
sistematizirani i kritički osvrt na zadanu temu.
REZULTATI
Formulacije multivezikularnih liposoma razvijaju se kako bi se premostila ograničenja konvencionalnih
formulacija lijekova i osigurala dostatna stabilnost lijekova peptidnog karaktera. Zahvaljujući veličini
multivezikularnih liposoma od nekoliko desetaka mikrometara te unutarnjoj strukturi koja podsjeća na
pjenu, nakon primjene formulacije lijeka, moguće je formiranje depoa i produljeno oslobađanje
djelatne tvari kroz dulji vremenski period.
Utvrđeno je da je, uz uobičajene sastavnice liposoma, za formiranje multivezikularnih liposoma
potreban dodatak neutralnih lipida. Korištena metoda pripreme dvostruke emulzije uspješno je
prenesena iz laboratorijskog u industrijsko mjerilo.
Dosad su odobrenje za stavljanje u promet dobile tri formulacije lijekova temeljenih na tehnologiji
multivezikularnih liposoma. Jedna formulacija je dobila odobrenje za kliničko ispitivanje, dok je za
drugu upućen zahtjev za kliničko ispitivanje. Brojne formulacije lijekova u fazi su pretkliničkih
ispitivanja. Dvije odobrene formulacije lijekova povučene su zbog poteškoća u proizvodnji.
ZAKLJUČAK
Lijekovi temeljeni na formulacijama multivezikularnih liposoma pružaju potencijalnu platformu za
premošćivanje brojnih zdravstvenih izazova poput dostave peptidnih lijekova ili dostave lijekova čije
djelovanje ovisi o specifičnoj fazi staničnog ciklusa. Njihova primjena bi mogla pridonijeti poboljšanoj
adherenciji bolesnika zbog smanjene učestalosti doziranja parenteralnih lijekova. Zbog nedostatka
prikladnijih metoda sterilizacije, specifičnog regulatornog okvira i standardiziranih analitičkih metoda,
komercijalizacija ovih lijekova je otežana.OBJECTIVES
The goal of this thesis was to present a systematic review of the published literature on the
development and manufacture of drug formulations based on multivesicular liposome technology.
Specific structural properties of multivesicular liposomes were described as well as critical parameters
in their manufacturing process. The potentials and limitations of drug-loaded multivesicular liposomes
compared to conventional therapy and other types of liposomes were highlighted.
MATERIAL/PATIENTS AND METHODS
The research was conducted by searching accredited databases with regard to the topic of this thesis.
Relevant articles were selected based on the set objectives and studied in detail in order to create a
systematic and critical review of the given topic.
RESULTS
The formulations of multivesicular liposomes are being developed to overcome the limitations of
conventional drug formulations and to ensure adequate stability of peptide-based drugs. Formation of
a depot and prolonged drug release over extended period of time, following administration of drugloaded multivesicular liposomes, are enabled by their size and internal foam-like structure.
The addition of neutral lipids was found to be crucial in formation of multivesicular liposomes. The
implemented double-emulsion method was successfully commercialized.
Until now, three medicinal products based on multivesicular liposome technology were granted
marketing authorisation. One formulation received approval for clinical testing, while a request for
clinical testing has been initiated for another formulation. Numerous drug product formulations are in
the phase of preclinical trials. Two marketed medicinal products have been withdrawn due to
difficulties in the manufacturing process.
CONCLUSION
Drug product formulations based on multivesicular liposome technology provide a potential platform
for overcoming numerous therapeutic challenges like the delivery of peptide drugs or drugs whose
action depends on a specific cell-cycle phase. Utilization of this technology could contribute to
enhanced patient adherence due to the reduction of parenteral administration frequency.
Commercialization of these drug products is difficult due to the lack of adequate sterilization methods,
a specific regulatory framework and standardized analytical methods
D-mannose in the prevention of uncomplicated recurrent outhospital cystitis in women of reproductive age - level of evidence
No full textU suvremenoj medicini, infekcije mokraćnog sustava i dalje predstavljaju iznimno velik ekonomski i socijalni teret na zdravstveni sustav, a nerazumnim propisivanjem antibiotika pridonosi se povećanju antibiotske rezistencije kao i smanjenju njihove učinkovitosti, što također predstavlja jedan od najvećih problema suvremene medicine. Uzimajući u obzir sve te podatke, možemo zaključiti da budućnost liječenja i profilakse infekcija mokraćnog sustava kod osoba ženskog spola, koje od istih i puno češće obolijevaju, moramo potražiti u učinkovitim alternativnim metodama, odnosno zamjenama za antibiotike. Nadalje, u smjernicama Europskog urološkog društva, najmanje je riječi i dokaza o učinku D-manoze što je ujedno i obraloženje odabira navedene teme. Pretragom literaturnih podataka i studija o učinkovitosti D-manoze kao monoterapije u liječenju i prevenciji rekurentnih IMS kod žena reproduktivne dobi, može se zaključiti da je D-manoza učinkovita kako u liječenju, tako i u prevenciji od ponovnih epizoda infekcija mokraćnog sustava, odnosno nekompliciranih cistitisa. Obzirom da je, za daljnje zaključke i potvrde s visokim razinama dokaza, potrebno provesti više preciznijih studija s većim brojem ispitanica, D-manoza se još uvijek vodi kao dodatak prehrani i za sada nema registriranih lijekova na bazi D-manoze, što je upitno sa strane kakvoće same tvari. Za temu ovog diplomskog rada pretražene su baze WoSCC i Scopus prema prilagođenim PRISMA smjernicama te su nakon probira studija koje obuhvaćaju temu ovog rada, studije opisane kroz PICO kriterije. Prema radnoj grupi GRADE, sve probrane studije korištene u evaluaciji dokaza D-manoze za ciljanu skupinu ispitanica isključivo su mala randomizirana ispitivanja s nižom metodološkom kvalitetom, stoga bi se razina dokaza D-manoze svrstala u skupinu II popisanih razina dokaza radne skupine GRADE. Zaključno, pacijente je potrebno educirati o upotrebi učinkovitih alternativnih metoda liječenja kojima bi se smanjila nerazumna potrošnja antibiotika i povećala svijest pacijenata o problemu antibiotske rezistencije. Upravo u tome svemu najveću ulogu može imati ljekarnik kao najdostupniji zdravstveni djelatnik koji bi na temelju znanstveno točnih i utvrđenih podataka, educirao građanke i građane o pravilnoj upotrebi terapije i razumnom pristupu liječenju.In modern medicine, urinary tract infections (UTIs) continue to represent an extremely large economic and social burden on the health system, and the unreasonable prescription of antibiotics contributes to the increase of antibiotic resistance as well as to the reduction of their effectiveness, which is also one of the biggest problems of modern medicine. Considering all these data, we can conclude that the future of treatment and prophylaxis of urinary tract infections in women, who suffer from them much more often, must be found in effective alternative methods, i.e., substitutes for antibiotics. Furthermore, in the guidelines of the European Urological Society, there are only few words or evidence about the effect of D-mannose, which is also the main reason of choosing this topic. By searching literature data and studies on the effectiveness of D-mannose as monotherapy in the treatment and prevention of recurrent UTIs in women of reproductive age, it can be concluded that D-mannose is effective both in the treatment and in the prevention of repeated episodes of urinary tract infections, i.e., uncomplicated cystitis. Considering that, for further conclusions and confirmations with high levels of evidence, it is necessary to conduct more precise studies with a larger number of subjects, D-mannose is still used as a dietary supplement and for now there are no registered medicines based on D-mannose, which presents the questionable side of the quality of the substance itself. For the topic of this thesis, the WoSCC and Scopus databases were searched according to the adjusted PRISMA guidelines, and after selecting the studies that cover the topic of this thesis, the studies were described using the PICO criteria. According to the GRADE working group, all the selected studies used in the evaluation of the evidence of D-mannose for the target group of subjects are exclusively small, randomized trials with lower methodological quality, therefore the level of evidence of D-mannose would be classified in group II of the listed levels of evidence of the GRADE working group. In conclusion, patients need to be educated about the use of effective alternative treatment methods that would reduce the unreasonable consumption of antibiotics and increase patients' awareness of the problem of antibiotic resistance. In solving all the mentioned problems, the greatest role can be played by the pharmacist as the most accessible healthcare worker who, based on scientifically accurate and established data, would educate citizens about the correct use of therapy and a reasonable approach to treatment
Formativna procjena potreba, mogućnosti i prepreka u provedbi depreskripcije terapije u primarnoj zdravstvenoj zaštiti
No full textDeprescribing is the planned and supervised process of dose reduction or tapering, and stopping of medication,
which might be causing harm, or is no longer of benefit to the patient, with the goal of managing polypharmacy
and improving outcomes. This research aimed to explore the need for, and the barriers and facilitators of
deprescribing in primary care in a healthcare system where it has not been researched, implemented, or provided.
Four phases of research were carried out. The systematic review performed in the first phase of this research shows
community-based pharmacists can successfully lead deprescribing interventions and are valuable partners in
deprescribing. Second phase of research unveils the finding that the majority of adults 40 years and older (84%)
would be willing to deprescribe one or more medications, with older adults (65 years and older) being more willing
to have medications deprescribed than younger adults (χ2 (1) = 4.06; p = 0.044). Furthermore, majority of
participating adults (71%) would feel comfortable with pharmacist’s involvement in deprescribing, and 69%
believes pharmacists have competencies to suggest deprescribing to physicians. Positive opinion on pharmacists'
involvement was assessed as a predictive factor for positive attitude towards deprescribing (aOR = 2.351, 95% CI
= 1.176 – 4.699; p = 0.016). Comprehensive Healthcare providers’ OPinions, Preferences, and attitudEs towards
Deprescribing (CHOPPED) questionnaire was developed in the third phase of research, to aid in exploration of
healthcare providers’ determinants important for implementing and providing deprescribing regardless of their
familiarization with deprescribing. Using the CHOPPED questionnaire, it was found that the majority of healthcare
providers (87%) would suggest deprescribing to a patient if appropriate. For pharmacists, the most important
facilitators were extrinsic factors (collaboration facilitators and healthcare facilitators factors), while for physicians
intrinsic (knowledge and awareness) and patient-related factors were more prominent. Moreover, a case vignette
study elucidated pharmacists can identify potential deprescribing targets and suggest deprescribing rationales
which physicians would accept. Collaborative deprescribing targets should be medicines both healthcare providers
share most agreement on, such as nonsteroidal anti-inflammatories (NSAID), opioids (OPI) or diuretics. In a crosssectional
stud conducted in community pharmacies across Croatia, which enrolled 388 patients older than 65 years,
55.2% of participants were identified as potential candidates for deprescribing of one or more medications; 31.1%
of proton pump inhibitors (PPI) users, 74.8% of NSAID, 75.0% of OPI, and 96.1% of benzodiazepine (BZN) users
met at least one deprescribing criterion. Several predictive factors were identified for increased need for
deprescribing, including identifying as a woman (aOR = 2.58; 95% CI =1.59 - 4.18; p < 0.001), poor self-reported
health (aOR = 5.14; 95% CI = 1.73-15.25; p < 0.001), and polypharmacy (aOR = 1.29; 95% CI = 1.17 - 1.44; p <
0.001). Formative evaluation, as a result of this doctoral research, can lead to an implementation strategy facilitated
by CHOPPED questionnaire and interventional protocol (Collaborating for Older aduLts to Deprescribe in
primarY care” (COLDY)), proposed in this doctoral thesis, which can help engage healthcare providers in
collaborative patient care with the goal of promoting deprescribing to enhance patient safety and optimise
pharmacotherapy.Depreskripcija terapije je planirani proces smanjivanja doze ili potpunog ukidanja lijeka iz farmakoterapije, za
koji je rizik korištenja veći od potencijalne koristi ili za kojim više nema potrebe odnosno dokazane učinkovitosti.
Ovo istraživanje za cilj je imalo istražiti potrebe, prepreke i poticatelje depreskripcije u primarnoj zdravstvenoj
zaštiti u zdravstvenom sustavu u kojem dosada nije istraživana, implementirana ili provođena. Istraživanje je
provedeno u četiri faze. Sustavni pregled proveden u prvoj prvi fazi istraživanja pokazuje da javni ljekarnici mogu
uspješno predvoditi depreskripcijske intervencije te da su vrijedni suučesnici u depreskripciji. Druga faza
istraživanja otkriva da bi većina osoba 40 godina i starijih (84%) pristala na depreskripciju jednog ili više lijekova.
Osobe starije životne dobi (starije od 65 godina života) sklonije su prihvatiti depreskripciju terapije u usporedbi s
mlađim odraslim osobama (χ2 (1) = 4.06; p = 0.044). Nadalje, većina ispitanika (71%) osjećala bi se ugodno ako
bi ljekarnik bio uključen u proces depreskripcije, a 69% njih dodatno smatra da ljekarnik ima dovoljno
kompetencija predložiti depreskripciju. Pozitivno mišljenje o uključenosti ljekarnika u proces depreskripcije
terapije utvrđeno je kao prediktivni čimbenik spremnosti na depreskripciju (aOR = 2,351, 95% CI = 1,176 – 4,699;
p = 0,016). Sveobuhvatni CHOPPED upitnik (engl. Comprehensive Healthcare providers’ OPinions, Preferences,
and attitudEs towards Deprescribing) razvijen u trećoj fazi istraživanja omogućuje ispitivanje čimbenika
depreskripcije među zdravstvenim radnicima koji su važni za implementaciju i provođenje depreskripcije. Većina
zdravstvenih radnika (87%) predložila bi depreskripciju terapije pacijentu. Za ljekarnike najvažniji poticatelji
depreskripcije su ekstrinzični čimbenici (čimbenik poticatelja suradnje i čimbenik poticatelja zdravstvenog
sustava), dok su za liječnike primarne zdravstvene zaštite najvažniji intrinzični čimbenici (znanje, osviještenost)
te čimbenici povezani s pacijentom. Rezultati studije prikaza slučaja pokazuju da ljekarnici imaju potrebne
kompetencije prepoznati potencijalno neprikladne lijekova a liječnici su spremni prihvatiti ljekarnikov
depreskripcijski prijedlog (diuretici, nesteroidni protuupalni lijekovi, opioidni analgetici i benzodiazepini). U
posljednjoj fazi istraživanja, koje je uključila 388 osoba starije životne dobi, otkriveno je da je više od polovice
ispitanika (55,2%) kandidat za depreskripciju jednog ili više lijekova, od toga 31,1% korisnika inhibitora protonske
crpke, 74,8% korisnika nesteroidnih protuupalnih lijekova, 75% korisnika opioidnih analgetika, te 96% korisnika
benzodiazepina. Ženski spol (aOR = 2,58; 95% CI =1,59 – 4,18; p < 0,001), politerapija (aOR = 1,29; 95% CI =
1,17 – 1,44; p < 0,001) i loša samoprocjena zdravlja (aOR = 5,14; 95% CI = 1,73-15,25; p < 0,001) prediktivni su
čimbenici za povećanu potrebu za depreskripcijom terapije. Formativna procjena, kao rezultat četiriju faza ovog
doktorskog istraživanja, omogućuje kreiranje implementacijske strategije potpomognute CHOPPED upitnikom,
kao i intervencijskog protokola za kolaborativni pristup depreskripciji terapije osoba starije životne dobi u
primarnoj zdravstvenoj zaštiti (engl. Collaborating for Older aduLts to Deprescribe in primarY care (COLDY))
koje će omogućiti će provođenje depreskripcijske s ciljem optimizacije farmakoterapije i poboljšanja ishoda
The influence of gender and age on C3 N-glycome
No full textGlikozilacija je ko- i posttranslacijska modifikacija koja utječe na smatanje, topljivost, strukturu te samu funkciju proteina. N-glikozilacijom nastaju kompleksni i hibridni podtipovi N-glikana koji su prisutni na većini glikoproteina, dok je visokomanozni podtip rjeđe prisutan. Istraživanja su pokazala da promjene u glikozilaciji proteina prate patološka stanja poput karcinoma, šećerne bolesti, starenja i drugih, što im daje potencijal dijagnostičkih biljega.
C3 komponenta komplementa je glikoprotein koji sadrži dva glikozilacijska mjesta s visokomanoznim glikanima. Nepobitna je uloga ovog proteina u imunološkim procesima koji su podloga za razvoj mnogih bolesti. Prethodna istraživanja utvrdila su razlike u zastupljenosti pojedinih visokomanoznih glikoformi u bolesnih ispitanika. U ovom istraživanju, po prvi puta, analizirane su interindividualne razlike glikozilacije C3 proteina kod zdravih ispitanika kako bi se postavila podloga za daljnja istraživanja njegovog dijagnostičkog potencijala. Pretpostavka istraživanja je da je glikozilacija C3 glikoproteina ovisna o dobi i spolu ispitanika, kao što je pokazano za neke druge ispitivane proteine.
Provedena je LC-ESI-MS analiza obogaćenih glikopeptida kako bi se utvrdila zastupljenost 9 visoko-manoznih glikoformi u 162 ispitanika oba spola u rasponu godina od 20 do 85. Rezultati analize pokazali su statistički značajne, iako ne izražene, interindividualne razlike u 5 glikoformi s obzirom na spol ispitanika. Dob gotovo da i nije imala utjecaj na glikozilaciju C3 glikoproteina kod ispitivane populacije, iako nakon podjele ispitanika po spolu taj utjecaj je malo povećan. Iako ga ne treba zanemariti kod evaluacije dijagnostičkog potencijala, prilično nizak utjecaj dobi i spola na glikozilaciju C3 glikoproteina čine ga robusnijim potencijalnim dijagnostičkim biljegom od drugih, do sada ispitanih, glikoproteina.Glycosylation is a co- and post-translational modification that affects the folding, solubility, structure, and function of proteins. N-glycosylation produces complex and hybrid subtypes of N- glycans that are present on most glycoproteins, while the high-mannose subtype is less common. Research has shown that changes in protein glycosylation accompany pathological conditions such as cancer, diabetes, aging, and others, giving them potential as diagnostic markers.
The C3 component of complement is a glycoprotein that contains two glycosylation sites with high- mannose glycans. The role of this protein in immune processes, which underlie the development of many diseases, is indisputable. Previous studies have identified differences in the prevalence of certain high-mannose glycoforms in diseased subjects. In this study, for the first time, interindividual differences in the glycosylation of the C3 protein in healthy subjects were analyzed to establish a basis for further research into its diagnostic potential. The hypothesis of the study is that the glycosylation of the C3 glycoprotein depends on the age and sex of the subjects, as has been shown for some other proteins studied.
An LC-ESI-MS analysis of enriched glycopeptides was conducted to determine the prevalence of 9 high-mannose glycoforms in 162 subjects of both sexes, ranging in age from 20 to 85. The results of the analysis showed statistically significant, though not pronounced, interindividual differences in 5 glycoforms with respect to the sex of the subjects. Age had almost no influence on the glycosylation of the C3 glycoprotein in the studied population, although this influence slightly increased when the subjects were divided by sex. Although it should not be overlooked in the evaluation of diagnostic potential, the relatively low influence of age and sex on the glycosylation of the C3 glycoprotein makes it a more robust potential diagnostic marker compared to other glycoproteins studied so far
Medications in the treatment of gastric acid hypersecretion
No full textŽelučana kiselina ključna je za normalnu probavu i apsorpciju hranjivih tvar te ima važnu ulogu u zaštiti probavnog sustava od patogena. Međutim, hipersekrecija želučane kiseline može uzrokovati značajne zdravstvene probleme, uključujući gastroezofagealnu refluksnu bolest (GERB), peptički ulkus i Zollinger-Ellisonov sindrom. Ove bolesti imaju kronični tijek, praćene su neugodnim simptomima te značajno narušavaju kvalitetu života oboljelih.
Ovim preglednim radom prikazane su farmakološke karakteristike lijekova koji se koriste za kontrolu hipersekrecije želučane kiseline, uključujući antacide, antagoniste histaminskih H2-receptora i inhibitore protonske pumpe. Svaka od ovih skupina lijekova ima specifične mehanizme djelovanja, farmakokinetske posebnosti, prednosti i nedostake, koje je potrebno poznavati i razumjeti kako bi se za svakog pacijenta odabrao optimalni lijek. Inhibitori protonske pumpe su najučinkovitija terapija te se danas koriste kao glavna terapijska opcija kod poremećaja hiperaciditeta. Međutim, njihova dugotrajna primjena zahtijeva pažljivo praćenje zbog potencijalnih nuspojava, uključujući malapsorpciju vitamina i minerala, povećan rizik od prijeloma i infekcija.
Ključnu ulogu u ispravnoj primjeni lijekova imaju ljekarnici. Kao stručnjaci za lijekove, trebaju osigurati da pacijenti razumiju zašto koriste određene lijekove i kako ih pravilno primjenjivati. Edukacija pacijenata o pravilnoj upotrebi lijekova, mogućim interakcijama i nuspojavama može značajno doprinijeti uspjehu terapije i smanjenju rizika od neželjenih posljedica.Gastric acid is crucial for normal digestion and absorption of nutrients and plays an important role in protecting the
digestive system from pathogens. However, hypersecretion of gastric acid can lead to significant health problems,
including gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger-Ellison syndrome. These conditions
have a chronic course, are accompanied by unpleasant symptoms, and significantly impair the quality of life of affected
individuals.
This review presents the pharmacological characteristics of drugs used to control gastric acid hypersecretion, including
antacids, histamine H2-receptor antagonists, and proton pump inhibitors. Each of these drug classes has specific
mechanisms of action, pharmacokinetic properties, advantages, and disadvantages that need to be understood to select
the optimal medication for each patient. Proton pump inhibitors are the most effective therapy and are currently used as
the main therapeutic option for hyperacidity disorders. However, their long-term use requires careful monitoring due to
potential side effects, including malabsorption of vitamins and minerals, increased risk of fractures, and infections.
Pharmacists play a key role in the correct application of these medications. As medication experts, they should ensure
that patients understand why they are using certain drugs and how to use them properly. Educating patients on the correct
use of medications, possible interactions, and side effects can significantly contribute to the success of therapy and
reduce the risk of adverse outcomes