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Circulating free DNA in osteoarthritis
Osteoartritis (OA), kronična i degenerativna bolest zglobova, najčešći je oblik artritisa. Često se zanemaruje ozbiljnost ove raširene i kronične bolesti. Razvoj lijeka za modificiranje OA otežan je nedostatkom topivih biomarkera za rano otkrivanje OA. Cilj istraživanja OA biomarkera je identificirati rani OA prije pojave radiografskih znakova i razvoja boli. Slobodna cirkulirajuća DNA (cfDNA) mogla bi poslužiti kao neivazivni biomarker OA. Uspoređene su dvije različite metode izolacije cfDNA i cilj je bio potvrditi koju je od njih bolje koristiti u budućoj genomskoj analizi s obzirom na bolji prinos ili čistoću. Istraživanje izvanstaničnog genomskog materijala također može otkriti više o temeljnoj patofiziologiji OA, stoga postoji potreba za definiranjem biomarkera za otkrivanje i praćenje napredovanja OA bolesti. Minimalno invazivne metode tekuće biopsije kao što su uzorkovanje sinovijalne tekućine i krvi za uzimanje genomskog materijala mogu biti osjetljivije od radiografije u otkrivanju, dijagnozi i praćenju OA u budućnosti.Osteoarthritis (OA), a chronic, debilitating and degenerative disease of the joints, is the most common form of arthritis. The seriousness of this prevalent and chronic disease is often overlooked. Disease modifying OA drug development is hindered by the lack of soluble biomarkers to detect OA early. The objective of OA biomarker research is to identify early OA prior to the appearance of radiographic signs and the development of pain. So, the aim of work was extracellular genomic material that could serve as biomarkers of OA, cell-free DNA (cfDNA). Two different cfDNA isolation methods were compared and the aim was to confirm which one is better to use in future genomic analysis considering better yield or purity. There is an unmet need for soluble biomarkers for detecting and then monitoring OA disease progression. Extracellular genomic material research may also reveal more about the underlying pathophysiology of OA. Minimally invasive liquid biopsies such as synovial fluid and blood sampling of genomic material may be more sensitive over radiography in the detection, diagnosis and monitoring of OA in the future
The efficiency of supplementation with alpha-lipoic acid in patients with precancerous cervical lesions
Premaligne lezije vrata maternice etiološki su vezane uz infekciju humanim papiloma virusom
(HPV) i posljedičan razvoj upale i oksidativnog stresa zbog čega bi se antioksidansi mogli
smatrati učinkovitim protiv progresije skvamozne intraepitelne lezije niskog stupnja (engl. low
grade SIL, LSIL). Recentna istraživanja pokazuju da je α-lipoična kiselina (ALA) jedan od
najpotentnijih prirodnih antioksidanasa s još uvijek ograničenom terapijskom primjenom u
liječenju bolesti povezanih s upalom i oksidativnim stresom. Cilj ove randomizirane, dvostruko
slijepe placebom kontrolirane studije je istražiti učinkovitost suplementacije ALA-om (600
mg/dne) na regresiju LSIL-a na uzorku od 100 pacijentica te dobiti širi uvid u terapijski
potencijal i mehanizme djelovanja ALA-e na oksidativni stres, upalne biljege i parametre
lipidnog statusa. Prisutnost LSIL-a utvrđena je nakon citološkog probira, kolposkopskog
pregleda i ciljane biopsije te histološke potvrde citološko-kolposkopske dijagnoze. Parametri
oksidativnog stresa, upale, lipidnog statusa i prisustvo HPV-a su utvrđeni standardnim
laboratorijskim metodama. Prehrambene i životne navike istražene su korištenjem
standardiziranog i validiranog semikvantitativnog upitnika o konzumiranju hrane i pića (engl.
Food Frequency Questionnaire, FFQ). Dobiveni rezultati pokazali su da je suplementacija
ALA-om znatno reducirala broj pacijentica s citološkim abnormalnostima niskog stupnja u
odnosu na pacijentice koje su uzimale placebo. Uzimajući u obzir dobivenu razinu značajnosti
(p < 0,001), prezentirani rezultati upućuju da kratkoročna suplementacija ALA-om pokazuje
klinički značajan učinak na cervikalnu citologiju. Intervencija nije imala značajan utjecaj na
parametre antioksidativnog statusa iako je antioksidativni kapacitet seruma (Trolox
ekvivalentni antioksidativni učinak (engl. Trolox equivalent antioxidant capacity, TEAC),
kapacitet vezanja kisikovih radikala (engl. Oxygen Radical Absorbance Capacity, ORAC) i
Folin-Ciocalteu redukcijski potencijal (engl. Folin-Ciocalteu, FC)) bio povećan nakon
suplementacije kod određenih podskupina pacijentica u ovisnosti o njihovom unosu
antioksidanasa hranom. Utjecaj suplementacije ALA-om na lipemiju ovisio je o inicijalnom
lipidnom statusu pacijentica. Buduće studije bi trebale biti usmjerene na istraživanje
učinkovitosti dugoročnije terapije ALA-om (duže od 3 mjeseca) te uključiti i pacijentice s
visokim stupnjem SIL-a. Također bi se trebale usmjeriti na istraživanje inovativnih formulacija
ALA-e s povećanom bioraspoloživošću, te na istraživanje sinergističkih učinaka modificiranog
životnog stila i suplementacije ALA-om.Precancerous lesions of the cervix are etiologically related to human papilloma virus (HPV)
infection and consequential development of inflammation and oxidative stress, which is why
antioxidants might be considered effective against progression of low-grade squamous
intraepithelial lesion (LSIL). Recent investigations show that α-lipoic acid (ALA) is one of the
most potent natural antioxidants with (still) limited therapeutic application in treatment of
diseases related to inflammation and oxidative stress. This randomized, double-blind, placebocontrolled
study aimed to investigate the effectiveness of ALA supplementation (600 mg/day)
on the regression of LSIL in a sample of 100 patients and to gain a broader insight into
therapeutic potential and mechanisms of action of ALA on oxidative stress, inflammatory
markers and lipid status parameters. The presence of LSIL was determined after the cytological
screening, colposcopic examination and targeted biopsy, as well as histological confirmation
of cytological-colposcopic diagnosis. Parameters of oxidative stress, inflammation, lipid status
and the presence of HPV were determined by standard laboratory methods. Dietary and lifestyle
habits were investigated using a standardized and validated semi-quantitative food
questionnaire (FFQ). Obtained results showed that ALA supplementation significantly reduced
the proportion of patients with low-grade cytological abnormalities, in comparison to placebo.
Given the obtained level of significance (p < 0.001), the presented results indicate that shortterm
ALA supplementation shows a clinically significant effect on cervical cytology.
Intervention did not have a significant influence on oxidative stress parameters although certain
indicators of antioxidant status were increased after supplementation in particular subgroups of
patients, depending on their dietary antioxidant intake. Influence of ALA supplementation on
lipemia depended on initial lipid status of patients. Future studies should focus on the
investigation of effectiveness of long-term therapies (> 3 months) and also include patients with
high-grade SIL; investigation of innovative formulations of ALA that might induce
bioavailability and the investigation of synergistic effects of lifestyle modifications and ALA
supplementation
Pharmacological properties of insulin and abuse in sports
Inzulin je fiziološki hormon nezamjenjive uloge u metabolizmu ugljikohidrata. Njegov nedostatak
zbog djelomičnog ili potpunog izostanka lučenja iz pankreasa predstavlja rastući zdravstveni
problem koji je karakteriziran hiperglikemijom i smanjenom osjetljivošću receptora na perifernim
tkivima na inzulin tkiva. U nadomještanju inzulina u u zadnjih 100 godina koriste se inzulinski
pripravci. Nakon inzulina životinjskog porijekla, danas su u primjeni inzulinski analozi dobiveni
DNA rekombinantnom tehnologijom i modificirani kako bi djelovali brzo i kratko ili dugotrajno.
Razvoj inzulina kao lijeka i dalje traje. Razvijaju se nove i bolje formulacije već postojećih
inzulinskih analoga, primjena se pojednostavljuje te se i dalje ulaže u pronalazak alternativa
supkutanoj injekciji koja većini pacijenata predstavlja najveći nedostatak i izvor neugodnosti.
Zbog svojih poznatih anaboličkih svojstava inzulin se zlorabi i kao doping sredstvo. Takva je praksa
najčešća u bodybuildingu, najčešće u kombinaciji s drugim sredstvima za poboljšanje mišićne mase,
izgleda i ukupne sportske izvedbe.Međutim, pritom se zanemaruju zdravstveni rizici te dugoročne
posljedice primjene inzulina u nemedicinske svrhe i bez kontrole zdravstvenih djelatnika.Insulin is a physiological hormone with an indispensable role in carbohydrate metabolism. Its
deficiency, due to partial or complete lack of secretion from the pancreas, represents a growing
health problem characterized by hyperglycemia and reduced sensitivity of receptors in peripheral
tissues to insulin. Insulin preparations have been used for insulin replacement over the past 100
years. Following animal-derived insulin, today, insulin analogs obtained through recombinant DNA
technology and modified to act quickly and short-term or long-term are in use.
The development of insulin as a drug continues. New and improved formulations of existing insulin
analogs are being developed, administration is being simplified, and efforts are ongoing to find
alternatives to subcutaneous injection, which is the biggest drawback and source of discomfort for
most patients.
Due to its well-known anabolic properties, insulin is also abused as a doping agent. This practice is
most common in bodybuilding, often in combination with other agents to enhance muscle mass,
appearance, and overall athletic performance. However, this neglects the health risks and long-term
consequences of using insulin for non-medical purposes and without medical supervision
Quality of life in patient who suffered from hypothiroidism
Hipotireoza je stanje smanjene funkcije štitnjače koje dovodi do niskih razina hormona štitnjače u stanicama.
Prevalencija varira od 0,1% do 2,0%, dok je subklinička hipotireoza prisutna u 4-10% odraslih, posebno starijih žena.
Bolest se češće javlja kod žena, i to 5 do 20 puta više nego kod muškaraca. Najčešći uzrok je Hashimotov tireoiditis,
autoimuna bolest koja uzrokuje oštećenje štitnjače. Simptomi uključuju umor, porast tjelesne mase, hladnu kožu i
poremećaje pamćenja. Dijagnoza se postavlja laboratorijskim analizama, a liječenje se provodi nadomjesnom
terapijom, najčešće levotiroksinom. Cilj ovog diplomskog rada bio je procijeniti kvalitetu života osoba oboljelih od
hipotireoze. Istraživanje se provodilo u ZU Ljekarna Nives Miloš od kolovoza do studenog 2023. Ispitano je 237
punoljetnih pacijenata, s dijagnozom hipotireoze minimalno šest mjeseci od kojih je većina bila ženskog spola i
prosječne dobi 40,5 godina. Ispitanici su ispunili anonimni upitnik ThyPro 39, koji je korišten za procjenu njihove
kvalitete života, uz dodatna pitanja o komorbiditetima, lijekovima, prehrambenim dodacima i sociodemografskim
podacima. Upitnik mjeri fizičke, psihološke i socijalne simptome te pokazuje utjecaj bolesti na pacijentov svakodnevni
život.. Najčešći komorbiditeti uključuju inzulinsku rezistenciju, hipertenziju i sindrom policističnih jajnika (PCOS).
Liječenje se većinom provodi monoterpaijom levotiroksinom, a 80% ispitanika koristi dodatke prehrani. Istraživanje je
također pokazalo visoku adherenciju (90%) u uzimanju terapije, bez pada adherencije s duljim trajanjem bolesti.
Istraživanje je pokazalo značajne probleme sa umorom, anksioznošću, emocionalnom osjetljivošću te ukupnom
kvalitetom života koja je narušena. Terapija levotiroksinom dobro kontrolira tjelesne simptome, dok psihički simptomi
ostaju izazov. Ovo istraživanje među prvima je koji koriste ThyPro-39 upitnik u Hrvatskoj te onima koji se bave
kvalitetom života osoba oboljelih od hipotireoze, a prvo je koje je u ispitivanje uključilo i utjecaj drugih komorbiditeta
i utjecaj korištenja dodataka prehrani. Rezultati ukazuju na činjenicu da unatoč dobroj kontroli bolesti, pacijenti
prijavljuju poteškoće vezane uz umor, anksioznost, emocionalnu osjetljivost i seksualni život, što ukazuje na značajan
utjecaj bolesti na kvalitetu života koja je znatno narušena u odnosu na zdravu populaciju.Hypothyroidism is a condition characterized by reduced thyroid function, leading to low levels of thyroid hormones in
cells. Its prevalence ranges from 0.1% to 2.0%, while subclinical hypothyroidism affects 4-10% of adults, particularly
older women. The disease is more common in women, occurring 5 to 20 times more frequently than in men. The most
common cause is Hashimoto's thyroiditis, an autoimmune disorder that damages the thyroid gland. Symptoms include
fatigue, weight gain, cold skin, and memory disturbances. Diagnosis is made through laboratory tests, and treatment is
typically administered through hormone replacement therapy, most commonly with levothyroxine. The aim of this
thesis was to assess the quality of life of individuals with hypothyroidism. The study was conducted at ZU Ljekarna
Nives Miloš from August to November 2023. It examined 237 adult patients with a diagnosis of hypothyroidism for at
least six months, most of whom were female with an average age of 40.5 years. Participants completed an anonymous
ThyPRO-39 questionnaire, used to evaluate their quality of life, along with additional questions about comorbidities,
medications, dietary supplements, and sociodemographic data. The questionnaire measures physical, psychological,
and social symptoms and assesses the impact of the disease on the patient’s daily life. The most common
comorbidities include insulin resistance, hypertension, and polycystic ovary syndrome (PCOS). Treatment is
predominantly through monotherapy with levothyroxine, and 80% of participants use dietary supplements. The study
also found high adherence (90%) to therapy, with no decrease in adherence with the duration of the disease.
Significant issues with fatigue, anxiety, emotional sensitivity, and overall diminished quality of life were reported.
While levothyroxine therapy effectively manages physical symptoms, psychological symptoms remain challenging.
This study is among the first in Croatia to use the ThyPRO-39 questionnaire for assessing the quality of life in
individuals with hypothyroidism and is the first to include the impact of other comorbidities and the use of dietary
supplements. The results indicate that despite good disease control, patients report difficulties related to fatigue,
anxiety, emotional sensitivity, and sexual life, which suggests a significant impact of the disease on quality of life,
substantially diminished compared to the healthy population
The provision of pharmaceutical care and its impact on clinical outcomes in patients with chronic diseases in a nursing home
Cilj rada je procijeniti učinak usluge upravljanja farmakoterapijom (CMM) na kliničke ishode pacijenata s kroničnim
bolestima u domu za starije osobe te prikazati provedene intervencije za poboljšanje terapijskih ishoda i njihovu
prihvaćenosti od strane liječnika obiteljske medicine (LOM) i pacijenata. Prospektivno, intervencijsko istraživanje
provedeno je od listopada 2023. do srpnja 2024. u Domu za starije osobe Centar u koje su uključeni korisnici Doma koji
uzimaju barem jedan lijek ili dodatak prehrani i imaju barem jednu kroničnu bolest. CMM usluga pružana je od strane
farmaceuta koji su zajedno s LOM-om i pacijentom postavili specifične terapijske ciljeve (TC) za svakog korisnika.
Sudjelovalo je 56 pacijenata, (87,5 % žena), s medijanom od 11 (1-20) korištenih lijekova i 9 (1-24) komorbiditeta.
Identificirano je 289 terapijskih problema (TP), prosječno 5,5 po pacijentu. Najučestaliji TP bili su „Nepotrebna terapija“
(22,15 %) i „Preniska doza“ (19,72 %). Predloženo je 289 intervencija, od kojih su pacijenti prihvatili 90 %, a LOM 88,04
%. Najčešće intervencije bile su „Prekid terapije“ (27,68 %) i „Povećanje doze lijeka“ (13,49 %). Pokazana je statistički
značajna razlika u broju korištenih lijekova između prve i zadnje konzultacije; kod stacionarnih korisnika uočena je
povećana depreskripcija (p=0,0019), a kod stambenih povećanje broja lijekova (p=0,0014). Najčešći lijekovi koji su
isključeni iz terapije bili su tramadol/paracetamol, diazepam i pantoprazol. Kod pacijenata s dijagnozom primarne
hipertenzije uočen je trend povećanja broja onih koji su postigli terapijski cilj za arterijski krvni tlak na zadnjoj konzultaciji
(33,33 %) u odnosu na prvu konzultaciju (26,67 %). Rezultati ovog istraživanja pokazuju da pružanje usluge CMM i
uključivanje farmaceuta u multidisciplinarni tim s LOM-om i medicinskom sestrom u domu za starije osobe može imati
značajan utjecaj na poboljšanje kliničkih ishoda i optimizaciju terapije korisnika DZS što upućuje na potrebu za širenjem
CMM usluge i u druge domove za starije osobe s ciljem unaprjeđenja zdravstvene skrbi osoba starije životne dobi.The aim of this study is to assess the impact of comprehensive medication management (CMM) services on clinical
outcomes in older patients with chronic conditions in a nursing home, and to present the interventions aimed at improving
therapeutic outcomes, as well as their acceptance by general practitioners (GPs) and patients. A prospective, interventional
study was conducted from October 2023 to July 2024 at the Nursing Home Center. Participants included residents taking
at least one medication or dietary supplement and having at least one chronic disease. The CMM services were provided
by pharmacists, who, together with the GP and patient, established specific goals of therapy for each resident. A total of
56 patients participated, 87.5% of whom were women, with a median of 11 (1–20) medications used and 9 (1–24)
comorbidities. 289 drug therapy problems (DTP) were identified, averaging 5.5 per patient. The most frequent DTPs were
"Unnecessary drug therapy" (22.15%) and "Dosage too low" (19.72%). Overall 289 interventions were proposed, of which
90% were accepted by patients and 88.04% by GPs. The most common interventions were "Discontinue drug therapy"
(27.68%) and "Increase dose" (13.49%). A statistically significant difference in the number of medications used between
the first and final consultations was observed, with increased deprescribing in inpatient care residents (p=0.0019) and
increased medication use in residential users (p=0.0014). The most frequently deprescribed drugs were
tramadol/paracetamol, diazepam, and pantoprazole. For patients diagnosed with primary hypertension, there was an
observed increase in the number of those who achieved the therapeutic goal for the blood pressure at the last consultation
(33.33%) compared to the first consultation (26.67%). The results of this study indicate that providing CMM services and
integrating a pharmacist into a multidisciplinary team with a general practitioner and a nurse in a nursing home can
significantly impact clinical outcomes improvement and optimization of therapy for nursing home residents. This suggests
the need to expand CMM services to other nursing homes to improve healthcare for the elderly
Cerebrospinal fluid leak: comparison of two qualitative methods determining asialo-transferrin
Likvoreja je stanje u kojem cerebrospinalna tekućina istječe kroz oštećenje u duri mater, vanjskoj
ovojnici koja štiti središnji živčani sustav. Likvoreja može imati ozbiljne posljedice, uključujući
infekcije poput meningitisa, te utječe na funkciju mozga zbog gubitka potpore. Glavni cilj rada bio
je usporediti dvije metode za kvalitativno određivanje asijalotransferina, biokemijskog biljega
likvora, u uzorcima sekreta. Asijalotransferin je specifičan za cerebrospinalnu tekućinu, a njegovo
kvalitativno određivanje pomaže u dijagnosticiranju likvoreje. U istraživanju su korištene in-house
metoda i komercijalni test proizvođača Sebia. In-house metoda pokazala se specifičnijom i točnijom,
ali Sebia metoda je brža i praktičnija. Obje metode pokazale su visoku osjetljivost (100%), dok je
in-house metoda imala bolju specifičnost i točnost. Istraživanje je također ukazalo na mogućnost
lažno pozitivnih rezultata zbog prisutnosti bakterija koje mogu interferirati s testom.
Zaključeno je da nema značajne razlike u osjetljivosti između dvije metode, ali je in-house metoda
preciznija. Autori naglašavaju važnost korištenja kliničke slike pacijenta za točnu interpretaciju
rezultata, kao i potrebu za slikovnim tehnikama kako bi se lokaliziralo mjesto istjecanja te omogućilo
pravovremeno liječenje.Cerebrospinal fluid (CSF) leakage represents a condition where cerebrospinal fluid escapes through
a tear in the dura mater, the outer membrane that protects the central nervous system. CSF leakage
can have serious consequences, including infections like meningitis, and it can affect brain function
due to the loss of support. The main aim of the thesis was to compare two methods for the qualitative
determination of asialotransferrin, a biochemical marker of CSF, in fluid samples. Asialotransferrin
is specific to cerebrospinal fluid, and its detection aids in diagnosing CSF leakage. The study utilized
an in-house method and a commercial test from the manufacturer Sebia. The in-house method proved
to be more specific and accurate, while the Sebia method was faster and more practical. Both
methods demonstrated high sensitivity (100%), but the in-house method had better specificity and
accuracy. The research also highlighted the potential for false-positive results due to the presence of
bacteria that can interfere with the test.
It was concluded that there is no significant difference in sensitivity between the two methods,
though the in-house method is more precise. The authors emphasize the importance of using the
patient's clinical picture for accurate interpretation of results, as well as the need for imaging
techniques to localize the site of leakage and enable timely treatment
Samoliječenje boli bezreceptnim analgeticima: opservacijsko istraživanje
CILJ ISTRAŽIVANJA
Cilj ovog istraživanja bio je ispitati stavove i znanja pacijenata o bezreceptnim lijekovima protiv
bolova te utvrditi najčešće medikacijske pogreške proizašle iz samoliječenja boli.
ISPITANICI I METODE
Opservacijsko istraživanje provedeno je u ZU Ljekarna Križevci. U istraživanje su uključena 62
pacijenta koji su prilikom podizanja svoje terapije propisane od strane liječnika, za sebe kupili i
bezreceptni lijek protiv bolova. Podatci za istraživanje dobiveni su iz anketnog upitnika sastavljenog
od 19 pitanja. Preostali podatci odnose se na medikacijsku terapiju svakog pojedinog ispitanika, a
preuzeti su iz zdravstvene kartice pacijenta. Pomoću programa UpToDate Lexidrug zatim su se
ispitivale interakcije korištenih OTC analgetika te analizirale eventualne medikacijske pogreške.
REZULTATI
Najkorišteniji OTC analgetik u samoliječenju boli je ibuprofen, a najčešće prijavljene nuspojave
vezane su uz gastrointestinalni sustav. Jedna trećina ispitanika smatra kako su analgetici koji se
kupuju bez recepta sigurniji za primjenu od onih propisanih od strane liječnika te da su sigurni za
kombiniranje s ostalim lijekovima. Potencijalne interakcije OTC analgetika pronađene su kod 37,11 %
ispitanika.
ZAKLJUČAK
Provedeno istraživanje ukazuje na potrebu za educiranjem pacijenata o odgovornom samoliječenju
boli. Također, naglašava se važnost savjetovanja od strane ljekarnika prilikom izbora lijeka i načina
njegova uzimanja.OBJECTIVES
The aim of this research was to examine the attitudes and knowledge of patients about nonprescription painkillers and to determine the most common medication errors resulting from selftreatment of pain.
PATIENTS AND METHODS
The observational research was carried out in ZU Ljekarna Križevci. The study included 62 patients
who, when taking up their therapy prescribed by the doctor, bought an over-the-counter pain
reliever for themselves. The data for the research was obtained from a survey questionnaire
composed of 19 questions. The remaining data refer to medication therapy of each individual
subject, and were taken from the patient's medical record. Using the UpToDate Lexidrug program,
the interactions of the used OTC analgesics were then examined and possible medication errors were
analyzed.
RESULTS
The most used OTC analgesic in self-medication is ibuprofen, and the most frequently reported side
effects are related to the gastrointestinal system. One third of respondents believe that analgesics
purchased without a prescription are safer to use than those prescribed by a doctor and that they are
safe to combine with other medications. Potential interactions of OTC analgesics were found in
37,11 % of respondents.
CONCLUSION
The conducted research points the need to educate patients about responsible self-treatment of
pain. Also, it highlights the importance of advice from pharmacist when selecting the medication and
learning how to take it
Prikladnost uporabe niskih doza acetilsalicilatne kiseline u osoba starije životne dobi
Cilj istraživanja: Cilj ovog istraživanja je procijeniti prikladnost primjene niskih doza acetilsalicilatne kiseline (ASK) na uzorku nehospitaliziranih bolesnika starije životne dobi, tj. ustanoviti terapijske probleme vezane za ASK. Specifični ciljevi su: 1. Utvrditi udio bolesnika koji imaju prikladno propisanu ASK u terapiji i analizirati prikladne indikacije, 2. Utvrditi udio bolesnika koji imaju neprikladno propisanu ASK i razloge neprikladnog propisivanja ASK, 3. Utvrditi udio bolesnika koji imaju indikaciju za ASK, ali im nije propisana.
Ispitanici i metode: Istraživanje je provedeno na uzorku 391 bolesnika starije životne dobi u okviru EuroAgeism Horizon 2020 projekta. Podaci su prikupljeni u javnim ljekarnama pomoću upitnika razvijenog za potrebe ovog istraživanja. Na temelju smjernica za primarnu i sekundarnu prevenciju kardiovaskularnih događaja vodećih kardioloških društava sastavljeni su kriteriji prema kojima se odlučivalo o prikladnosti propisivanja i problemima u terapiji ASK kod bolesnika koji ju koriste.
Rezultati: U ispitivanju je sudjelovao ukupno 391 ispitanik (143 muškaraca i 248 žena). Prosječna dob ispitanika je bila 74,33 (SD=10,65) godine, a u terapiji su imali prosječno šest lijekova. ASK je koristilo 73 (18,67%) ispitanika. Prema sastavljenim kriterijima, 41 (56,16%) je imao indikaciju za primjenu, a 32 (43,84%) nisu imala indikaciju za prikladno propisivanje ASK. 38 (52,05%) je bilo u povećanom riziku od krvarenja, od kojih 22 (57,89%) nisu imali propisan inhibitor protonske pumpe (IPP). 23 ispitanika (22,33%) s kardiovaskularnom bolesti (KVB) i indikacijom za antiagregacijsku terapiju, ASK nije bila propisana (niti drugi antiagregacijski lijek ili antikoagulans).
Zaključak: Rezultati istraživanja upućuju na značajan udio ispitanika u kojih propisivanje i korištenje ASK nije u skladu s važećim smjernicama kardioloških društava te na potrebu za racionalnijim korištenjem ASK u osoba starije životne dobi budući su one u povećanom riziku od nuspojava povezanih s krvarenjem, a istovremeno i najčešći korisnici ovog lijeka.Objectives: The aim of this research was to assess the appropriateness of low-dose acetylsalicylic acid (ASA) use in a sample of non-hospitalized elderly patients, i.e. to establish therapeutic problems related to low-dose ASA. The specific objectives were: 1. To determine the proportion of patients who had appropriately prescribed ASA in therapy and to analyze the appropriate indications, 2. To determine the proportion of patients who had inappropriately prescribed ASA and the reasons for inappropriate ASA prescribing, 3. To determine the proportion of patients who had an indication for ASA, but was not prescribed.
Patients and methods: The research was conducted on a sample of 391 elderly patients as part of the EuroAgeism Horizon 2020 project. Data were collected in community pharmacies using a questionnaire developed for the purposes of this research. Based on the guidelines for the primary and secondary prevention of cardiovascular events of the leading cardiology societies, criteria were drawn up according to which decisions were made on the appropriateness of prescribing and problems in ASA therapy in patients who use it.
Results: A total of 391 patients (143 men and 248 women) participated in the study. The average age was 74.33 (SD=10.65) years, and they had an average of six drugs in their therapy. ASK was used by 73 (18.67%) patients. According to the compiled criteria, 41 (56.16%) had an indication for use, and 32 (43.84%) did not have an indication for the appropriate prescription of ASA. 38 (52.05%) were at increased risk of bleeding, of which 22 (57.89%) did not have a proton pump inhibitor (PPI). 23 patients (22.33%) with cardiovascular disease (CVD) were not prescribed ASA (nor other antiplatelet drugs or anticoagulants).
Conclusion: The research results point to a significant proportion of patients in whom the prescription and use of ASA is not in accordance with the current guidelines of cardiology societies and the need for more rational use and administration of ASA to elderly patients, since they are at increased risk of side effects related to bleeding, and at the same time, they are the most frequent users of this drug
Pharmacological treatment options for eating disorders
Poremećaji prehrane su kompleksne psihijatrijske bolesti s visokim stopama mortaliteta i morbiditeta.
Karakteriziraju ih abnormalne prehrambene navike i ponašanja, što posljedično ugrožava fizičko
zdravlje i psihosocijalno funkcioniranje oboljelih. Osobe koje pate od ovih poremećaja često imaju
iskrivljenu percepciju vlastitog tijela i tjelesne težine. Iako etiologija poremećaja prehrane nije u
potpunosti razjašnjena, smatra se da su njihovi uzroci složeni i da uključuju biološke, psihološke i
socijalne čimbenike. Liječenje ovih poremećaja zahtijeva sveobuhvatan i multidisciplinaran pristup. U
odraslih pacijenata, trenutna se terapija fokusira na različite bihevioralno orijentirane psihoterapije koje
imaju za cilj poboljšanje simptoma i postizanje zdrave tjelesne težine. Psihoterapija ostaje ključni dio
tretmana, no farmakoterapija predstavlja značajnu alternativu za pacijente koji ne pokazuju dovoljno
napretka s psihoterapijskim metodama. Psihoaktivni lijekovi, iako nemaju primarnu ulogu u liječenju
poremećaja prehrane, značajno doprinose kliničkoj praksi, osobito kod pacijenata s teškim
simptomima. Trenutno su odobreni antidepresiv fluoksetin za bulimiju nervozu i psihostimulans
lisdeksamfetamin za poremećaj prejedanja. Unatoč određenim ograničenjima u studijama provedenima
tijekom posljednjih nekoliko desetljeća, istraživanja u području farmakoterapije kod ovih poremećaja
pokazala su značajan napredak. U budućnosti, fokus će biti usmjeren na nove farmakološke mogućnosti
te biološki utemeljene tretmane, kako bi se dodatno unaprijedila učinkovitost liječenja.Eating disorders are complex psychiatric illnesses with high rates of mortality and morbidity. They are
characterized by abnormal eating habits and behaviors, which consequently jeopardize the physical
health and psychosocial functioning of those affected. Individuals suffering from these disorders often
have a distorted perception of their own body and weight. Although the etiology of eating disorders is
not fully understood, it is believed that their causes are complex and involve biological, psychological,
and social factors. Treatment of these disorders requires a comprehensive and multidisciplinary
approach. In adult patients, current therapy focuses on various behavioral-oriented psychotherapies
aimed at improving symptoms and achieving a healthy body weight.Psychotherapy remains a key
component of treatment, while pharmacotherapy represents a significant alternative for patients who do
not show sufficient progress with psychotherapeutic methods. Psychoactive medications, although not
primary used in the treatment of eating disorders, significantly contribute to clinical practice, especially
in patients with severe symptoms. Currently, the antidepressant fluoxetine is approved for bulimia
nervosa, and the psychostimulant lisdexamfetamine is approved for binge eating disorder. Despite
certain limitations in studies conducted over the past few decades, research in the field of
pharmacotherapy for these disorders has shown significant progress. In the future, the focus will be
directed toward new pharmacological options and biologically based treatments to further enhance the
effectiveness of treatment
Syntheses and mechanisms of solvolysis of benzyl-bromides in methanol
Sintetizirani su različiti benzil-bromidi uporabom odgovarajućih benzilnih alkohola i reagensa za
bromiranje, fosforovog tribromida ili acetil-bromida. Identitet dobivenih spojeva je zatim potvrđen TLC-om
i NMR-om.
Pretpostavljeno je da različiti supstituenti na aromatskom prstenu benzil-bromida različito utječu na
njihovu reaktivnost u metanolu, tj. utječu na mehanizam i brzinu reakcije nukleofilne supstitucije. Ideja ovog
rada bila je odrediti kojim mehanizmom reakcije se odvija solvoliza pojedinih benzil-bromida pomoću
Hammett-Brownove korelacijske analize u 100 % metanolu. Prvo su konduktometrijski određene konstante
brzine reakcije pri 25° C. Konstruiran je graf ovisnosti σ + o logaritmu konstanti brzine i rezultati su potvrdili
početnu pretpostavku – dobivena su dva pravca različitih nagiba (ρ + vrijednosti), čime je potvrđeno da se
solvoliza različito supstituiranih benzil-bromida u metanolu odvija različitim mehanizmom (u eksperimentu
su jedino mijenjani supstituenti na benzenskom prstenu benzil-bromida). Za oba pravca vrijednosti ρ +
su negativne i upućuju da se na reakcijskom centru formira naboj suprotan onome u referentnoj reakciji, u kojoj nastaje negativni benzoatni anion. Dakle, dokazano je da se na reakcijskom centru tijekom provođenja solvoliza različito supstituiranih benzilnih bromida formirao pozitivan naboj. Prvom pravcu pripadaju spojevi 4-metoksibenzil-bromid, 4-(metiltio)benzil-bromid i 4-fenoksibenzilbromid, čije se reakcije metanolize odvijaju SN1 mehanizmom, a nagib pravca iznosi -6,22. Može se zaključiti
da se na reakcijskom centru u prijelaznom stanju ovih spojeva generira značajno jači pozitivan naboj koji je
stabiliziran elektron-donorskom prirodom supstituenata koji zbog toga povećavaju elektronsku gustoću
reakcijskog centra, u odnosu na spojeve koji pripadaju drugom pravcu. SN2 mehanizmom se odvijaju reakcije
spojeva 3,4-dimetilbenzil-bromid, 4-metilbenzil-bromid, 4-tert-butilbenzil-bromid, 4-fenilbenzil-bromid i
3,5-dimetilbenzil-bromid, smještenih na drugi pravac nagiba -2,11. Supstituenti ovih benzil-bromida također
utječu na konstante brzina reakcija solvoliza, međutim, slabiji su elektron-donori te je stoga favoriziran SN2
mehanizam reakcije.Various benzyl-bromides were synthesized using homologous benzyl alcohols and brominating
reagents, phosphorus tribromide or acetyl bromide. The identity of the obtained compounds was confirmed
by TLC and NMR.
It was assumed that different substituents on the aromatic ring differently affect their reactivity,
meaning they affect the mechanism and rate of the nucleophilic substitution reaction. The goal was to
determine the mechanism of solvolysis for each benzyl bromide using Hammett-Brown correlation analysis
in 100 % methanol. Reaction rate constants were first determined conductometrically at 25°C. A plot of σ
+ versus the logarithm of the rate constants was constructed, and the results confirmed the initial hypothesis –
two lines with different slopes (ρ + values) were obtained, confirming that the solvolysis of differently
substituted benzyl bromides in methanol occurs via different mechanisms (the only variable in the experiment
was the substituent on the benzyl bromides). For both lines, the ρ + values are negative, indicating that a charge opposite to that in the reference reaction, where a negative benzoate anion forms, develops at the reaction center. It was proven that a positive charge forms at the reaction center during solvolysis of differently substituted benzyl bromides. The first line
includes 4-methoxybenzyl bromide, 4-(methylthio)benzyl bromide and 4-phenoxybenzyl bromide, whose
solvolysis reactions take place by the SN1 mechanism, with a slope of -6.22. This suggests a significantly
stronger positive charge is generated at the reaction center due to their electron-donating nature, stabilizing
the carbocation intermediate. Reactions of 3,4-dimethylbenzyl bromide, 4-methylbenzyl bromide, 4-tertbutylbenzyl bromide, 4-phenylbenzyl bromide and 3,5-dimethylbenzyl bromide follow the SN2 mechanism, represented by the second line with a slope of -2.11. The substituents of these benzyl bromides also affect the reaction rate constants of solvolysis, however, they are weaker electron donors, and therefore the SN2
reaction mechanism is favored