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Beliefs on pharmacotherapy in patients who suffered from hormone dependent breast cancer
No full textGotovo tri četvrtine malignih karcinoma dojke čine upravo ER+ tumori koji primarno pogađaju postmenopauzalne žene.
Po završetku lokalne terapije i kemoterapije - adjuvantno, indicirana je primjena ciljane endokrine (antihormonske)
terapije. AET obuhvaća aromatazne inhibitore (anastrozol, letrozol i ekesemestan) te SERM (tamoksifen) koji se
uzimaju oralno u trajanju od najmanje pet godina što dokazano smanjuje rizik od recidiva i produljuje trajanje života. S
obzirom na svjesnost velike učinkovitosti AET i činjenice da niska razina adherencije može značajno sniziti njeno
blagotvorno djelovanje, od izrazite je važnosti prepoznati čimbenike neadherencije, osobito one na koje se može utjecati.
Proučavanje psihosocijalnih faktora, poput uvjerenja o lijekovima, potencijalno bi moglo identificirati pacijente s većim
rizikom nepridržavanja ili ranijeg odustajanja od AET. Stjecanje istinskog razumijevanja važnih elemenata koji
doprinose uvjerenju pacijentica o korištenju AET, ali i lijekova općenito, omogućit će uvid u to kako na najbolji mogući
način podržati žene da ustraju u uzimanju svoje dugotrajne AET. Cilj ovog diplomskog rada bio je ispitati uvjerenja i
stavove pacijentica koje su bolovale od hormonski ovisnog karcinoma dojke o njihovoj farmakoterapiji te uvidjeti postoji
li opravdani strah od primjene AET ili je on pak posljedica neinformiranosti. Sudionice ovog istraživanja bile su
isključivo žene koje su bolovale od hormonski ovisnog karcinoma dojke stadija I-III te koje su započele AEL barem tri
mjeseca prije ispunjavanja upitnika. Uključeno je 319 pacijentica prosječne životne dobi 57 godina. Rezultati BMQ
upitnika pokazali su da većina pacijentica zauzima pozitivan stav o AET, smatrajući da im endokrina terapija pomaže i
štiti od ponovnog povratka bolesti. Unatoč blagoj zabrinutosti zbog uzimanja endokrine terapije, potrebe pacijentica za
AET i prisutni strah od povratka bolesti nadilaze njihov strah od uzimanja endokrine terapije i potencijalnih nuspojava.
Ispitanice su također pokazale pozitivna uvjerenja o lijekovima općenito, prevladava mišljenje kako su lijekovi
djelotvorni, sigurni i omogućuju bolji život te da korist njihova uzimanja nadvladava moguće rizike. Istraživanje ovog
tipa prvi je puta provedeno na populaciji pacijenata oboljelih od hormonski ovisnog karcinoma dojke u Hrvatskoj te
doprinosi boljem razumijevanju utjecaja promjenjivih čimbenika, kao što su uvjerenja o lijekovima, na adherenciju.
Sukladno tome, buduća bi se istraživanja trebala usredotočiti na razvoj strategija za poboljšanje kvalitete života i
adherencije kod pacijenata/ica na AET, uzimajući u obzir njihove psihosocijalne karakteristike.Almost three quarters of malignant breast cancers are ER+ tumors that primarly affect postmenopausal women. After
completion of local therapy and chemotherapy the adjuvant use of targeted endocrine (antihormonal) therapy is
indicated. AET comprises aromatase inhibitors (anastrazole, letrozole and exemestane) and SERM (tamoxifen) taken
orally for at least five years which has been shown to reduce the risk of recurrence and prolong life expectancy. Given
the awareness of the high effectiveness of AET and the fact that low levels of adherence can significantly reduce its
beneficial effects, it is extremely important to identify factors of non – adherence, especially modifiable ones. Studying
psyhosocial factors, such as beliefs about medicines may potentially identify patients at greater risk of poor adherence
or premature discontinuation from AET. Acquiring a genuine understanding of important elements that contribute to
patients' beliefs on AET, but also medications in general, would provide insight into how in best way support women to
persevere in taking their long – term AET. The aim of this thesis was to examine beliefs and attitudes of patients who
suffered from hormone - dependent breast cancer on their pharmacotherapy and to evaluate whether fear of taking AET
is justified or exists due to lack of information. Participants in this study were women who suffered from stage I – III
hormone - dependent cancer and who started AET at least three months before completing the questionnaire. This
research included 319 patients whose average age was 57. Results of BMQ questionnaire have shown that majority of
patients have positive attitude on AET, believing that endocrine therapy helps and protects them from disease recurrence.
Despite mild concerns about taking endocrine therapy, patients' needs for AET and the present fear of disease recurrence
outweigh their fear of taking endocrine therapy and potential side effects. Respondents also expressed positive beliefs
about medications in general, there is a prevailing opinion that medications are effective, safe and that enable a better
life, as well as the benefit of taking them outweighs possible risks. This type of study was conducted for the first time
on population of patients with hormone - dependent breast cancer in Croatia and contributes towards better
understanding the impact of modifiable factors, such as beliefs about medicines, on adherence. Accordingly, future
resarch should focus on developing strategies to improve quality of life and adherence in patients taking AET,
considering their psychosocial characteristics
Uloga dugodjelujućih antipsihotika u terapiji shizofrenije
No full textCilj ispitivanja: Cilj ovog rada je pregledno prikazati ulogu dugodjelujućih antipsihotika u terapiji shizofrenije, opisati njihove prednosti i nedostatke u odnosu na oralne oblike antipsihotika, prikazati njihov značaj kod problema neadherencije shizofrenih bolesnika, te se osvrnuti na pitanje politerapije u liječenju shizofrenije. Očekivani doprinos ovog rada je u brizi i pružanju podrške pacijentima sa shizofrenijom i sličnim poremećajima, s kojima se ljekarnici u radu svakodnevno susreću.
Materijal i metode: Pretražena je relevantna znanstvena i stručna literatura, psihijatrijski dijagnostički priručnici, suvremene i važeće terapijske smjernice, publikacije stručnih institucija, baza lijekova Agencije za lijekove i medicinske proizvode, te drugi raspoloživi izvori. Ključne riječi za pretraživanje baze podataka uključivale su sljedeće pojmove: antipsychotics, long-acting antipsychotics, nonadherence, polytherapy, schizophrenia.
Rezultati: Iako je napredak u liječenju shizofrenije značajno smanjio teret bolesti, loša adherencija jedna je od glavnih prepreka u postizanju zadanih terapijskih ciljeva, pa je kontinuitet u liječenju shizofrenije ključan. Na adherenciju u shizofreniji utječe više čimbenika (uvid u bolest, kognitivna oštećenja, politerapija, nuspojave lijekova i mnogi drugi). Dugodjelujući antipsihotici za intramuskularnu primjenu razvijeni su s primarnim ciljem djelovanja na lošu adherenciju. Brojna ispitivanja pokazala su određene prednosti dugodjelujućih antipsihotika u usporedbi s oralnim formulacijama: bolju adherenciju, smanjen rizik za recidiv, smanjen rizik ponovne hospitalizacije i posljedično manje troškove liječenja.
Zaključak: Dugodjelujući antipsihotici se zbog različitih razloga propisuju još uvijek u maloj mjeri. S obzirom na dokazane određene prednosti koje posjeduju, postoji potencijal za njihovu veću primjenu.Objectives: The aim of this paper is to do a review of the role of long-acting injectable antipsychotics in the treatment of schizophrenia, to describe their advantages and disadvantages over oral forms of antipsychotics, to show their importance in the problem of nonadherence in schizophrenia treatment, and to address polytherapy in schizophrenia. The expected contribution of this work is in the care and support of patients with schizophrenia and similar disorders, which pharmacists encounter on a daily basis.
Materials and Methods: Relevant scientific and professional literature, psychiatric diagnostic manuals, contemporary and currently relevant therapeutic guidelines, publications of professional institutions, drug database of the Agency for Medicinal Products and Medical Devices, and other available sources were searched. Database search keywords include the following terms: antipsychotics, long-term antipsychotics, nonadherence, polytherapy, schizophrenia.
Results: Although advances in the treatment of schizophrenia have significantly reduced the burden of disease, poor adherence is one of the main obstacles to achieving the set therapeutic goals, and continuity in the treatment of schizophrenia is crucial. Adherence in schizophrenia is affected by several factors (insight, cognitive impairment, polytherapy, side effects, and many others). Long-acting injectable antipsychotics for intramuscular use have been developed with the primary goal of acting on poor adherence. Numerous studies have shown certain advantages of long-acting antipsychotics compared to oral formulations: better adherence, reduced risk of recidive, reduced risk of rehospitalization, and consequently lower treatment costs.
Conclusion: Long-acting injectable antipsychotics are still prescribed to a small extent for a variety of reasons. Considering their proven advantages, there is potential for larger use
Terapijsko praćenje lijekova kao način poboljšanja ishoda onkološke terapije
No full textCancer is currently one of the leading causes of death in the
world, and different classes of antitumor drugs are used for the
treatment. Traditional cytostatics act not only on tumor cells but also on some
healthy cells and thus show a toxic effect. Despite the development of new, targeted
drugs, the problem of ineffectiveness and toxicity of therapy is still present.
Due to large differences in efficacy and toxicity both in different patients and in
each individual patient, it is desirable to introduce therapeutic drug monitoring
(TDM). Already in early clinical trials, the therapeutic and toxic doses of a drug
is determined by pharmacokinetic and pharmacodynamic studies. However,
depending on the stage and type of the disease, as well as the characteristics of
the patient, it is possible that the effective doses will be significantly lower than
the maximum tolerated dose, or that even the doses above which significant
toxicity occurs will not lead to an adequate effect. Despite the fact that in most
cases the determination of the concentration of drugs in the body ends with
their registration, for some drugs patients could benefit from therapeutic monitoring.
Drugs that are good candidates for TDM must meet a number of pharmacokinetic
and pharmacodynamic conditions, and it is necessary to select an
optimal sample for analysis, which is currently plasma in most cases. The benefit
of therapeutic monitoring of a drug must also be proven by a randomised prospective
study. Therapeutic monitoring of antitumor drugs appears to be an
excellent way of individualising therapy in order to prolong and improve the
quality of life of oncology patients, but its introduction into clinical everyday life
is faced with numerous obstacles. Many see the future of antineoplastic TDM in
the development of simpler monitoring methods, with the relief of the health
system by developing sampling techniques that the patient can carry out at
home, or through different biosensors that would even enable continuous monitoring
of drug concentrations. Finally, the opening of medicine to new technologies
and the involvement of clinical pharmacists, as well as public pharmacists
in the multidisciplinary oncology team will surely ease the implementation of
therapeutic drug monitoring in the clinical practice, thereby improving the therapeutic
outcomes and increasing the therapeutic efficacy, while reducing the
number of adverse events related to antitumor therapy
Reliability of platelet verification by digital morphology on Sysmex DI-60 analyzer
No full textTrombociti ili krvne pločice nastaju u koštanoj srži te čine sastavni dio kompletne krvne slike uz eritrocite i leukocite. Kako bi se izbjeglo izdavanje nepouzdanih i netočnih rezultata zbog predanalitičkih pogrešaka (npr. pseudotrombocitopenije) provodi se mikroskopski pregled razmaza periferne krvi. Mikroskopski pregled daje uvid u stvarno stanje broja trombocita, tj. postoje li stvarno niske vrijednosti trombocita u organizmu ili se radi o in vitro nastalim nakupina trombocita. Zlatni standard određivanja prisutnosti nakupina trombocita je svjetlosna mikroskopija koja je vrlo zamorna i dugotrajna. No zahvaljujući razvoju tehnologije razvijena je digitalna mikroskopija kojom je omogućen brži pregled razmaza periferne krvi. Cilj ovog diplomskog rada je provjerena pouzdanost provjere trombocita uređajem za digitalnu morfologiju Sysmex DI-60 (Sysmex, Kobe, Japan). Uspoređena je prisutnosti nakupina u podizbornicima (WBC, RBC, PLT) Sysmex DI-60 analizatora sa prisutnošću nakupina trombocita svjetlosnom mikroskopijom. Dodatno, uspoređen je broj trombocita dobiven metodom po Fonio-u na uređaju Sysmex DI-60 s brojem trombocita s hematološkog analizatora Sysmex XN-3100. Provjera prisutnosti nakupina pregledom svih podizbornika Sysmex DI-60 analizatora pokazala je zadovoljavajuće slaganje i jednaku procjenu. Razlike između određivanja broja trombocita Fonio i Sysmex XN-3100 metodom su bila male i očekivane jer je Fonio samo aproksimativna metoda određivanja broja trombocita. Shodno tome zaključeno je da se analizator može uvesti u rutinski rad hematološkog laboratorija za provjeru broja trombocita i prisutnosti nakupina trombocita. U dvojbenim slučajevima uputna je dodatna provjera nakupina trombocita svjetlosnom mikroskopijom.Platelets are produced in the bone marrow, and along with erythrocytes and leukocytes, are the essential part of the complete blood count. In order to avoid unreliable and inaccurate results due to preanalytical errors (eg. pseudothrombocytopenia), microscopic examination of peripheral blood smears is performed. Microscopic examination of blood smears provides information whether the patient has really low platelet counts or is it a consequence of platelet aggregation. The gold standard for determining the presence of platelet aggregates is light microscopy which is very tedious and time consuming. With technological advancements, digital microscopy has been developed, which enables faster examination of peripheral blood smears. The aim of this thesis was to verify the reliability of platelet count evaluation using digital morphology analyzer Sysmex DI-60 (Sysmex, Kobe, Japan). The presence of platelet clumps in the submenus (WBC, RBC, PLT) of the Sysmex DI-60 analyzer was compared with the presence of platelet aggregates by light microscopy. Also, platelet count obtained by the Fonio method on Sysmex DI-60 was compared to the platelet count obtained on the hematology analyzer Sysmex XN-3100 analyzer. Assessment of the presence of platelet clumps by reviewing all submenus of the Sysmex DI-60 analyzer showed satisfactory agreement and comparable performance. The differences between the Fonio platelet count and the Sysmex XN-3100 method were irrelevant and expected because Fonio is only an approximate platelet count method. Accordingly, it was concluded that Sysmex DI- 60 can be introduced into the routine work of the hematology laboratory for assessment of the presence of platelet clumps and platelet count estimation. However, any doubtful case requires examination of the peripheral blood smear by light microscopy
Metabolic side-effects of drugs
No full textMetabolički sindrom je definiran kroz prisutnost barem tri od pet poremećaja: pretilost centralnog tipa,
hipertrigliceridemija, nizak HDL-C, hipertenzija i hiperglikemija natašte.
Mehanizmi koji dovode do nastanka metaboličkog sindroma nisu potpuno jasni. Vjerojatno je riječ o složenom
međudjelovanju Različitih endogenih i egzogenih promjenjivih i nepromjenjivih čimbenika rizika, a određene skupine
lijekova su jedan od njih. Metaboličke nuspojave lijekova značajno doprinose razvoju metaboličkog sindroma,
stvarajući tako nove zdravstvene poteškoće, što neposredno utječe na adherenciju i učinkovitost propisane terapije.
Među lijekovima koji izazivaju metaboličke nuspojave najzastupljeniji su lijekovi iz skupine antipsihotika, a značajan
utjecaj na metabolički profil pacijenta ostvarili su i određeni lijekovi iz skupina antiepileptika, kortikosteroida
(glukokortikoida), inhibitora proteaze te antihipertenziva (tiazidni diuretici i beta-blokatori). Učestalost i intenzitet
metaboličkih nuspojava varira između pojedinih skupina lijekova, kao i između lijekova unutar svake od rizičnih
skupina. Kada god je moguće, preporuča se odabir lijeka s povoljnijim utjecajem na metabolički status, posebice kod
visokorizičnih pacijenata koji imaju i druge predispozicije za razvoj metaboličkog sindroma. U nedostatku
učinkovitijih terapijskih opcija, odnosno kada je terapija određenim lijekom nužna, a omjer koristi i rizika prihvatljiv,
metaboličke nuspojave nastoje se maksimalno ublažiti kombinacijom redovitog praćenja ključnih metaboličkih
parametara i prilagodbom doze lijeka, promjenom životnih navika te u konačnici uvođenjem terapije za smanjenje
negativnih posljedica farmakoterapije na pacijentovo zdravlje.The metabolic syndrome is defined by the presence of at least three of five disorders: central obesity,
hypertriglyceridemia, low HDL-C, hypertension, and fasting hyperglycemia.
The mechanisms leading to the development of the metabolic syndrome are not completely understood. The metabolic
syndrome is probably a consequence of complex interactions of the primary disease, the pharmacological properties of
the drug (s) and a number of other variable and invariant risk factors. Metabolic side effects of drugs significantly
contribute to the development of metabolic syndrome, thus creating new health problems, which directly affects the
adherence and effectiveness of prescribed therapy. Among the drugs that cause metabolic side effects, the most
significant metabolic influence is attributed to the drugs from the group of antipsychotics, but a less prominent, yet
significant impact on the metabolic profile of the patient can also be found in certain drugs from the groups of
antiepileptics, corticosteroids (glucocorticoids), protease inhibitors and antihypertensives (thiazide diuretics and betablockers).
The frequency and intensity of metabolic side effects varies between groups of drugs, as well as between
drugs within each of the risk groups. Whenever possible, it is recommended to choose a drug with a more favorable
effect on metabolic status, especially in high-risk patients who have other drug-related predispositions which
additionally increase the risk of developing the metabolic syndrome. In the absence of more effective treatment
options, ie. when therapy with a particular drug is necessary and the benefit-risk ratio is acceptable, metabolic side
effects are minimized by combining continuous monitoring of key metabolic parameters, adjusting drug dosage,
changing lifestyle habits and ultimately introducing therapy to reduce the negative effects of pharmacotherapy on the
patients metabolism and to prevent potential complications to the patient's health
Treatment of postpartum depression
No full textPospartalna depresija jedan je od najčešćih psihijatrijskih poremećaja koji se javlja unutar prvih par tjedana do prvih 12 mjeseci nakon poroda. Klinička slika jednaka je onoj velike depresivne epizode, a prilikom dijagnoze važno je razlikovati od postpartalne tuge i psihoze. Etiologija je multifaktorijalna, pri čemu se smatra da, za sada, najveći utjecaj imaju fluktuacija hormona u kombinaciji sa stresom ili anamnezom mentalnih bolesti u obitelji. Za probir se koristi Edinburška ocjenska ljestvica za postnatalnu depresiju koja je dovoljno osjetljiva i specifična, a predlaže se njeno korištenje barem jednom tijekom trudnoće i barem jednom u postpartalnom razdoblju. Liječenje postporođajne depresije ovisi o čimbenicima rizika koji su doveli do njezinog razvoja, težini simptoma i preferencijama bolesnika. Kod blage postpartalne depresije preporučaju se psihosocijalne intervencije, od kojih se „peer support“ pokazala najučinkovitijom. Kod umjerene postporođajne depresije kod koje ne pomažu psihosocijalne metode, koristi se psihoterapija u obliku kognitivno-bihevioralne (i online oblik), interpersonalne i psihodinamske terapije. Kod teških oblika postpartalne depresije indicirana je farmakološka terapija, unutar koje su prvi izbor selektivni inhibitori ponovne pohrane serotonina. Danas je na tržištu dostupan i breksanolon, specifičan lijek za postpartalnu depresiju koji se sastoji od endogenog neurosteroida alopregnanolona i sulfobutileter-β-ciklodekstrina. Glavni su mu nedostatak način i vrijeme primjene te REMS protokol kojeg se treba pridržavati zbog ozbiljnih nuspojava. Zbog toga, u fazama istraživanja nalaze se novi potencijalni lijekovi čija je najveća prednost pred breksanolonom, barem za sada, oralna primjena. Za posebno teške slučajeve postporođajne depresije može se razmotriti primjena elektrokonvulzivne terapije. Na kraju, u učinkovitom liječenju postporođajne depresije važnu ulogu imaju probir, profilaksa, dijagnostika i odabir prave terapije te proces destigmatizacije u kojem ljekarnici imaju značajan doprinos.Postpartum depression is one of the most common psychiatric disorders occurring within the first few weeks to the first 12 months after delivery. The clinical picture is the same as that of a major depressive episode, and when stating a diagnosis it is important to distinguish between baby blues and psychosis. The etiology is multifactorial, and it is believed that hormone fluctuations in combination with stress or a history of mental illness in the family have the greatest impact. The screening uses the Edinburgh Rating Scale for Postnatal Depression, which is sufficiently sensitive and specific, and its use is suggested at least once during pregnancy and at least once in the postpartum period. Treatment of postpartum depression depends on the risk factors that led to its development, the severity of symptoms and patient preferences. In mild postpartum depression, psychosocial interventions are recommended, of which "peer support" has proven to be the most effective. In case of moderate postpartum depression when psychosocial methods do not work, psychotherapy in the form of cognitive-behavioral (online as well), interpersonal and psychodynamic therapy is used. In severe forms of postpartum depression, pharmacological therapy is indicated, within which selective serotonin reuptake inhibitors are the first choice. Brexanolone, a specific drug for postpartum depression consisting of the endogenous neurosteroid allopregnanolone and sulfobutylether-β-cyclodextrin, is also available on the market today. Its main disadvantages are the method and time of application and the REMS protocol that should be followed due to serious side effects. Therefore, new potential drugs are emerging in the research phases whose greatest advantage over brexanolone, at least for now, is oral administration. For particularly severe cases of postpartum depression, electroconvulsive therapy may be considered. Finally, screening, prophylaxis, diagnosis and selection of the right therapy as well as the destigmatization process, in which pharmacists make a significant contribution, play an important role in the effective treatment of postpartum depression
Interactions of dietary fiber with polyphenols from plant extracts: influence on bioavailability
No full textNova saznanja o ulozi hrane u prevenciji i liječenju bolesti dovela su do razvoja nove/funkcionalne hrane koja, osim esencijalnih nutrijenata nužnih za zadovoljavanje fizioloških potreba organizma, sadrži i sastavnice za koje je dokazano da imaju važnu ulogu u prevenciji i liječenju kroničnih oboljenja. Prehrambena vlakna i biljni ekstrakti koji obiluju antioksidansima, prvenstveno polifenolima, često se kao funkcionalne sastavnice dodaju u konačni proizvod. Međutim, u uvjetima probavnog trakta polifenoli se mogu vezati za frakciju prehrambenih vlakana što na kraju može rezultirati smanjenom oralnom biodostupnosti. Navedene interakcije su vrlo specifične i njihov intenzitet značajno varira u ovisnosti o fizikalno – kemijskim svojstvima vlakana i fenolnog spoja. U ovom radu istražene su interakcije različitih mješavina probavnih vlakana i polifenola iz ekstrakata sjemenki grožđa te ekstrakata biljke Polygonum cuspidatum u in vitro simuliranim uvjetima probavnog trakta. Biodostupnost polifenola nakon provedene digestije mjerena je Folin-Ciocalteu metodom. Ekstrakti biljke Polygonum cuspidatum, koji obiluju resveratrolom, pogodniji su za kombiniranje s prehrambenim vlaknima od ekstrakata sjemenki grožđa. Značajna razlika u afinitetu vezanja za vlakna utvrđena je za ekstrakte sjemenki grožđa od dva različita proizvođača što ukazuje na njihov različiti kemijski sastav.New knowledge about the role of food in the prevention and treatment of diseases has led to the development of new/functional food, which, in addition to the essential nutrients necessary to meet the physiological needs of the body, also contains components that have been proven to play an important role in the prevention and treatment of chronic illnesses. Dietary fiber and plant extracts that are rich in antioxidants, primarily polyphenols, are often added as functional components to the final product. However, under the conditions of the digestive tract, polyphenols can bind to the dietary fiber fraction, which can ultimately result in reduced oral bioavailability. Mentioned interactions are very specific and their intensity varies significantly depending on the physico-chemical properties of the fiber and the phenolic compound. In this paper, the interactions of different mixtures of digestive fiber and polyphenols from grape seed extracts and Polygonum cuspidatum plant extracts were investigated in in vitro simulated conditions of the digestive tract. Bioavailability of polyphenols after digestion was measured by the Folin-Ciocalteu method. Polygonum cuspidatum plant extracts, which are rich in resveratrol, are more suitable for combining with dietary fiber than grape seed extracts. A significant difference in fiber binding affinity was found for grape seed extracts from two different manufacturers, indicating their different chemical composition
Kinetic isotope effects in reactions of phenolic acids and DPPH• radicals
No full textFenolni spojevi se sve više istražuju radi mnogobrojnih bioloških učinaka među kojima se ističe antioksidativni učinak. Za praćenje antioksidativnog učinka često se koristi metoda s DPPH• radikalom. U ovom diplomskom radu određene su konstante brzine reakcija fenolnih kiselina: p-kumarinske kiseline, ferulične kiseline, vanilinske kiseline, vanilina i flavonoida kvercetina s DPPH• u dioksanu te smjesi otapala dioksan-voda (0,99:0,01 v/v i 0,95:0,05 v/v). Određeni su kinetički izotopni efekti reakcija navedenih fenolnih spojeva i DPPH• u smjesi otapala dioksan-voda (0,99:0,01 v/v i 0,95:0,05 v/v). Dobiveni kinetički izotopni efekti, za sve spojeve osim vanilina, upućuje na reakcijski mehanizam HAT (hydrogen atom transfer) ili PCET (proton-coupled electron transfer), što podrazumijeva da u stupnju koji određuje brzinu reakcije dolazi i do prijelaza protona i do prijelaza elektrona. U slučaju vanilina dobiven je inverzni KIE koji upućuje na drugačiji i složeniji mehanizam reakcije. U literaturi nisu pronađeni podatci o kinetičkim izotopnim efektima navedenih reakcija. Dobiveni rezultati doprinose razumijevanju kinetike i mehanizma reakcija fenolnih spojeva i radikala, s čime je povezan jedan dio antioksidativne aktivnosti ovih spojeva.Phenolic compounds are increasingly being researched for their numerous biological effects, among which the antioxidant effect stands out. To monitor the antioxidant potential, the DPPH• free radical scavenging method is often used. In this thesis, the reaction rate constants of phenolic acids: p-coumaric acid, ferulic acid, vanillic acid, vanillin and the flavonoid quercetin with DPPH• in dioxane and solvent mixture dioxane-water (0,99:0,01 v/v and 0,95:0,05 v/v) were examined. The kinetic isotopic effects for the mentioned phenolic compounds and DPPH• reaction in the solvent mixture dioxane-water (0,99:0,01 v/v and 0,95:0,05 v/v) were determined. The obtained kinetic isotope effects, for all compounds except vanillin, refer to the reaction mechanism HAT (hydrogen atom transfer) or PCET (proton-coupled electron transfer), which implies that in the rate-determining step of the reaction, both proton and electron transitions occur. In the case of vanillin, an inverse KIE was obtained, which points to a different and more complex reaction mechanism. No data on the kinetic isotope effects for the mentioned reactions were found in the literature. The obtained results contribute to the understanding of the kinetics and mechanism of reactions of phenolic compounds with radicals, with which a part of the antioxidant activity of these compounds is associated
Validation of reference interval for bile acids for the population of pregnant women from 28th to 42nd week of pregnancy
No full textUsporedba laboratorijskih nalaza pacijenata s referentnim intervalima jedan su od najprimjenjivijih alata za interpretaciju nalaza, postavljanje dijagnoze i praćenje tijeka bolesti. Cilj ovog rada bio je uvesti metodu za određivanje žučnih kiselina u analitički sustav i verificirati njene parametre, te izraditi referentni interval za žučne kiseline za populaciju trudnica od 28. do 42. tjedna trudnoće. U populaciji trudnica žučne kiseline kao specifični biomarker služe za postavljanje dijagnoze intrahepatičke kolestaze u trudnoći, bolesti koja se javlja u trećem tromjesečju i ispoljava kao pruritus, a može biti fatalna za dijete.
Verifikacijom metode je utvrđeno da su žučne kiseline stabilne 2 dana pri 20 ℃, 14 dana pri 4-8 ℃ i 22 dana pri -20 ℃. Verificirana je preciznost metode, a ukupna precitnost je iznosila 2,2%, odnosno 1,7% za koncentraciju žučnih kiselina unutar i iznad gornje granice referentnog intervala. Linearnost je verificirana u koncentracijskom području od 3,5-172,1 μmol/l, a verifikacija referentnog intervala za odrasle je zadovoljila kriterije. Ispitivanje interferencije lipemije pokazalo je blagi pozitivan bias (%) koncentracije žučnih kiselina porastom koncentracije triglicerida u serumu. Lipemija uzrokuje nepouzdane rezultate pri koncentraciji SMOFlipid® 20% emulzije 10 g/L, odnosno pri koncentraciji triglicerida iznad 12,4 mmol/L u uzorcima niske inicijalne koncentracije ŽK.
Izrada referentnog intervala za žučne kiseline provodila se a priori pristupom. Određene su koncentracije žučnih kiselina u 116 uzoraka seruma referentnih ispitanica koje su odabrane temeljem prethodno postavljenih kriterija isključenja i uključenja. Statistička obrada rezultata je provedena prema CLSI smjernicama. Referentni interval za populaciju trudnica od 28. do 42. tjedna trudnoće izrađen je neparametrijskom metodom i iznosi od 1,0 do 7,3 μmol/L.Comparison of the patient's laboratory results with reference intervals is one of the most fundamental tools for interpreting laboratory results, making a clinical decision and monitoring the course of the disease. The aim of this study was to introduce a method for determining bile acids into the analytical system, to verify its parameters, and to establish a reference interval for bile acids for the population of pregnant women from the 28th to the 42nd week of pregnancy. Bile acids as a specific biomarker are used to diagnose intrahepatic cholestasis of pregnancy, a disease that usually occurs in the third trimester and manifests itself as pruritus while being potentially fatal for the child.
Verification of the method showed that bile acids are stable in serum samples for 2 days at 20 ℃, 14 days at 4-8 ℃, and 22 days at -20 ℃. The precision study met the criteria. Within-laboratory precision was 2.2% and 1.7% for the concentration of bile acids within the reference range and above the upper limit, respectively. Linearity was verified for the concentration range of 3.5-172.1 μmol/l, and the verification of the reference interval for adults met the criteria. The lipemia interference test showed a positive bias (%) of bile acid concentration with an increase in serum triglyceride concentration. Lipemia causes unreliable results at a SMOFlipid® 20% emulsion concentration of 10 g/L, i.e. at a triglycerides concentration above 12.4 mmol/L in samples with a low initial concentration of bile acids.
Reference interval for bile acids was determined a priori. Total bile acids concentration was determined in 116 serum samples of the reference pregnant women who were selected based on the previously set exclusion and inclusion criteria. Statistical analysis of the results was carried out according to CLSI guidelines. The reference interval of 1.0 to 7.3 μmol/L for the population of pregnant women from the 28th to the 42nd week of pregnancy was determined using the non-parametric method
Biochemical markers of systemic inflammatory response, stress and cardiac necrosis in patients undergoing cardiac surgery
No full textCiljevi istraživanja bili su ispitati promjenu sistemskog upalnog odgovora,
biokemijskih i hematoloških parametara te biljega stresa i srčane nekroze u periodu do 5 dana
nakon operativnog zahvata aortokoronarnog premoštenja sa i bez izvantjelesnog krvotoka
(ITK) i zamjene aortalnog zaliska; povezanost biljega sistemskog upalnog odgovora sa
biljezima stresa i srčane nekroze; te može li koncentracija ili intenzitet promjene pojedinih
biljega tijekom perioperativnog perioda predvidjeti ishod bolesnika i nastanak komplikacija.
U istraživanje je uključeno 90 ispitanika, podijeljenih u 3 skupine po 30 ispitanika -
revaskularizacija miokarda sa i bez upotrebe ITK te zamjena aortalnog zaliska. Svim
ispitanicima su određivani biokemijski, hematološki biljezi te biljezi upale, stresa i srčane
nekroze u 5 točaka.
Kardiokirurški postupci uzrokovali su porast aktivnosti CK i izoezima CK-MB, koncentracije
CRP-a, kortizola, hsTnT, IL-6, IL-10, rezistina, MCP-1, broja leukocita i postotka
granulocita, te pad koncentracije albumina, mokraćne kiseline, broja eritrocita, koncentracije
hemoglobina, vrijednosti MCV-a i pH u sve tri ispitivane skupine. Pronađena je slaba
korelacija između IL-6 s hsTnT. Razlika u koncentraciji leptina i rezistina prije i nakon
operativnog zahvata te razlika rezistina na kraju i 24 sata nakon operacije pokazao značajnu
ulogu u predviđanju potreba za transfuzijom. Razlika u koncentracijama rezistina prije i
nakon operativnog zahvata te i kortizola neposredno nakon i 24 sata poslije operacije mogu
doprinijeti u predviđanju postoperativne količine izgubljene krvi. Od biokemijskih biljega
aktivnost CK, broj leukocita, pH vrijednost i koncentracije ioniziranog kalcija u pojedinim
točkama mjerenjasu ukazivale na duljinu hospitalizacije, boravka u jedinici intenzivne skrbi i
mehaničke ventilacije te gubitak krvi.
Kardiokirurški zahvati uzrokuju snažnu reakciju organizma te oslobađanje upalnih biljega te
biljega stresa i srčane nekroze u cirkulaciju. Od upalnih biljega samo je IL-6 korelirao s
jačinom srčane nekroze. Koncentracije pojedinih biokemijskih biljega te promjene u
koncentracijama leptina, rezistina i kortizola mogu predvidjeti ishode bolesnika podvrgnutih
kardiokirurškom zahvatu.The aims of the study were to examine the change in the systemic inflammatory
response, biochemical, hematological parameters, stress and cardiac markers in the period up
to 5 days after coronary artery bypass graft surgery using on-pump and off-pump technique
and aortic valve replacement surgery; the association of inflammatory markers with markers
of stress and cardiac necrosis; and whether concentration or the change in concentration
certain markers during the perioperative period can predict patient outcome and occurrence
of complications.
The study included 90 subjects, divided into 3 groups, 30 participants each – on-pump and
off-pump coronary bypass surgery and aortic valve replacement. The following parameters
were measured: complete blood count, CRP, CK, CK-MB, albumin, glucose, lactate, uric
acid, acid-base status, ionized calcium, IL-6, IL-10, leptin, resistin, monocyte chemotactic
protein - 1 (MCP-1), cortisol and troponin T (hsTnT) at 5 points.
Cardiac surgery caused an increase in CK and CK-MB izoenzyme activity, CRP, cortisol and
hsTnT, IL-6, IL-10, resistin and MCP-1 concentration, and leukocytes and granulocytes
count. On the other hand, surgery caused a decrease in albumin, uric acid, hemoglobin
concentration erythrocyte count, MCV and pH values in all three study groups. A weak
correlation was found between IL-6 with hsTnT. The difference in leptin and resistin
concentrations before and after surgery and the difference in resistin at the end and 24 hours
after surgery significantly predicted transfusion needs. The difference between resistin before
and after surgery, together with the difference in cortisol at the end and 24 hours after surgery
predicted the amount of blood loss. CK activity, leukocyte count, pH and ionized calcium
concentration in different time points significantly predicted hospitalization, intensive care
and mechanical ventilation duration as well as blood loss.
Cardiac surgery causes a strong response and a consequential release of inflammatory, stress
and cardiac necrosis markers into the circulation. Interleukin 6 correlated weakly with
cardiac necrosis. Concentration of certain biochemical markers as well as changes in leptin,
resistin and cortisol concentrations predicted patients’ outcome