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    Inhibitors of various protein kinases

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    U ovom radu obrađeni su inhibitori receptora za epidermalni faktor rasta (EGFR) kao i inhibitori Bcr-Abl kinaze, fosfoinozitid-3-kinaze i Janus kinaze te inhibitori Hedgehog signalnog puta. U općem pregledu navedenih protein-kinaza istaknuti su bitni elementi svake skupine. Dan je uvid u signalni put svake navedene kinaze te pregled nekoliko odobrenih inhibitora na tržištu. Zatim je na konkretnim primjerima objašnjena struktura lijeka, važnost određenih dijelova strukture za djelovanje te je opisan sintetski put. Lijekovi obrađeni u ovom radu su: 1) inhibitori EGFR: neratinib i osimertinib, 2) Bcr-Abl inhibtori: nilotinib i ponatinib, 3) PI3K inhibitori: alpelisib i idelalisib, 4) JAK inhibitori: ruksolitinib i fedratinib, 5) Hedgehog inhibitori: sonidegib i vismodegib.In this diploma thesis, epidermal growth factor receptor (EGFR) inhibitors, as well as BCR-Ab1 kinase, phosphoinositide-3-kinase, Janus kinase, and Hedgehog signaling pathway inhibitors, are discussed. The most important facts are highlighted for each protein kinase. An insight into the protein kinase signaling pathways and an overview of approved inhibitors are given. Furthermore, drug structures, structure-activity relationships, and synthetic routes are explained in specific examples. The following drugs are described in detail in this thesis: 1) EGFR inhibitors: neratinib and osimertinib, 2) Bcr-Abl inhibitors: nilotinib and ponatinib, 3) PI3K inhibitors: alpelisib and idelalisib, 4) JAK inhibitors: ruxolitinib and fedratinib, 5) Hedgehog inhibitors: sonidegib and vismodegib

    Oxidation mechanism of nitrogen atoms by hypochlorous acid in structures of chosen psychofarmaceuticals

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    Psihofarmaci su široko korišteni lijekovi zbog velike prevalencije mentalnih bolesti među stanovništvom. Upotreba ovih lijekova najčešće je kronična, a simptomi bolesti se javljaju relativno rano, što znači da je većina pacijenata na terapiji od mlađe odrasle dobi Zbog relativno široke upotrebe, ovi lijekovi mogu se naći otpadnim vodama gdje dolaze u doticaj s hipokloritnom kiselinom, glavnim agensom za pročišćavanje otpadnih voda metodom kloriranja. Također, hipokloritna kiselina stvara se i u organizmu utjecajem enzima iz porodice hemperoksidaza, poglavito mijeloperoksidaze, najčešće pri određenim patološkim stanjima. U organizmu sudjeluje u tvorbi slobodnih radikala reakcijama s različitim endomolekulama te posljedično uzrokovanju oksidativnog stresa. Pažnja je usmjerena na supstituirani i nesupstituirani piperazinski i piperidinski prsten kao dijelove strukture odabranih psihofarmaka: aripiprazola i haloperidola. Računato je koji su produkti vjerojatniji s obzirom da energetske barijere procesa. Rezultati dobiveni u ovome radu pokazali su da se hipokloritna kiselina u reakcijama s navedenim strukturama u okolišu bez otapala ponaša kao donor kloridne, ali i hidroksilne skupine, stvarajući N-okside, N-kloride, N-hidrokside, C-kloride i C-hidrokside. Mehanizmi ovih reakcija proučavani su kvantno-kemijskim modelima kojima su se računale energije produkata, prijelaznih stanja te reaktanata, dok su se strukture optimizirale na B3LYP funkcionalu u kombinaciji s 6-31/G(d) baznim skupom.Due to the high prevalence of mental illness among the population, psychopharmaceutical drugs are widely used. These drugs are most often used to treat chronic illnesses, with the symptoms appearing relatively early. This results in most patients starting treatment as young adults. As a result of the wide usage, these drugs can be found in wastewater where they could potentially react with hypochlorous acid, a commonly used agent for disinfecting wastewater by chlorination. Hypochlorous acid is also formed in the body by enzymes from the hemperoxidase family, especially myeloperoxidase, most often in certain pathological conditions. It participates in the formation of free radicals by reactions with various endomolecules and consequently causes oxidative stress. This paper focused on the substituted and unsubstituted piperazine and piperidine ring as parts of the structure of selected psychopharmaceuticals: aripiprazole and haloperidol. It was calculated which products are more likely given the kinetic and thermodynamic properties of the reactions. The results obtained in this work showed that hypochlorous acid in reactions with these structures in a solvent-free environment acts as a donor of chloride and hydroxyl groups, forming N-oxides, N-chlorides, N-hydroxides, C-chlorides, and C-hydroxides. The mechanisms of these reactions were studied by quantum chemical models that calculated the energies of the reactants, transition states, and products. Structures were optimized with the B3LYP functional in combination with the 6-31/G(d) basis set

    Identifikacija onečišćenja daptomicina primjenom dvodimenzionalne tekućinske kromatografije spregnute s masenim spektrometrom

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    Cilj istraživanja U ovom radu dan je pregled tehnike dvodimenzionalna tekućinska kromatografija. Opisana je primjena dvodimenzionalne tekućinske kromatografije u identifikaciji onečišćenja u ljekovitim oblicima. Cilj rada bio je razviti metodu primjenom navedene tehnike za identifikaciju onečišćenja daptomicina u ljekovitim oblicima, a ista može biti primijenjena i za identifikaciju onečišćenja u aktivnoj farmaceutskoj tvari. Materijali/metode Za identifikaciju onečišćenja daptomicina korišten je dvodimenzionalni tekućinski kromatograf visoke djelotvornosti s analizatorom masa Agilent 1290 Infinity II povezanim s detektorom masa Q-TOF MS, model 6545 (Agilent Technologies, Santa Clara, CA, SAD). Analitička metoda korištena u prvoj dimenziji modificirana je prema literaturno dostupnim podacima kako bi se postiglo bolje razdvajanje kromatografskih pikova daptomicina i prisutnih onečišćenja. U drugoj dimenziji dužina i vrsta kolone, protok i gradijentni program su mijenjani sa svrhom poboljšanja selektivnosti metode. Parametri masenog spektrometra su optimirani direktnim unošenjem radnog standarda daptomicina koncentracije 0,2 mg/mL u instrument. Teorijska pozadina s naglaskom na aktivnu modulaciju i obrnutofaznu kromatografiju istražena je koristeći znanstvene izvore: PubMed, Science Direct. Rezultati 2D-LC/MS metoda razvijena je za identifikaciju onečišćenja daptomicina: lakton daptomicina, β-izomer daptomicina i anhidro-daptomicina. Kako bi se postigla prikladna selektivnost metode razvoj je započeo modifikacijom poznate metode koja je korištena u prvoj dimenziji. Razdvajanje analita provedeno je primjenom obrnutofazne kromatografske kolone (C8). Kromatografskim postupkom u prvoj dimenziji postignuto je zadovoljavajuće razdvajanje ispitanih onečišćenja te je druga dimenzija primijenjena za provjeru čistoće pikova onečišćenja. Za optimizaciju kromatografskog postupka u drugoj dimenziji korištene su također obrnutofazne kromatografske kolone (C18). Za „povezivanje“ dviju dimenzija korišten je prvo engl. multi heart cutting način rada. Međutim, utvrđeno je kako su svi „rezovi“ iz prve dimenzije bili „čisti“ odnosno nije došlo do preklapanja kromatografskih pikova osim u uzorku XEL540/02-17/032. Kako bi se utvrdila čistoća navedenog kromatografskog pika primijenjeno je uzorkovanje u visokoj rezoluciji (engl. High Resolution Sampling) odnosno engl. selective comprehensive 2D-LC način rada. Primjenom ovog načina rada potvrđeno je preklapanje pikova onečišćenja β-izomera daptomicina i drugih strukturno sličnih onečišćenja u uzorku XEL540/02-17/032. Masenom spektrometrijom potvrđen je identitet onečišćenja daptomicina: lakton daptomicina, β-izomer daptomicina i anhidro-daptomicin u tri ispitana ljekovita oblika. Zaključak Dvodimenzionalna tekućinska kromatografija je napredna instrumentalna tehnika kojom je moguće razdvojiti sastavnice složenih uzoraka, pogotovo kada je moguće u potpunosti primijeniti ortogonalnost u separacijskim koracima i spregnuti je s masenim detektorom kako bi dodatno identificirali analit ili dobili više informacija o strukturi same molekule.Objectives The objective of the research was to give the overview of two-dimensional liquid chromatography. This paper will present application of the two-dimensional liquid chromatography in identification of impurities in final dosage form containing daptomycin as active ingredient. The aim of the study was to develop a method using the above technique to identify daptomycin impurities in final dosage form, the same can be applied for the identification of impurities in active pharmaceutical ingredient. Material and methods For experimental work two-dimensional liquid chromatograph Agilent, 1290 Infinity II hyphenated with mass spectrometer Q-TOF MS, model 6545 was used. Instrumental conditions for separation in first dimension was taken over from literature and optimized additionally with change of flow and gradient program introduction for better peak separation. In second dimension column length, flow and gradient program were investigated with the optimization purpose. Mass spectrometer instrumental parameters were optimized by injecting directly daptomycin working standard in concentration 0,2 mg/mL. Theoretical background with accent on active modulation and reverse phase chromatography was studied using scientific sources: PubMed, Science Direct. Results 2D-LC/MS method was developed for identification of daptomycin impurities: lactone daptomycin, β-isomer of daptomycin and anhydro-daptomycin. For development of first dimension chromatographic method previously published method was modified. Separation of selected analytes was performed using reversed phase column (C8). Satisfactory separation of all analytes was obtained using developed method. Therefore, the peak purity was evaluated using second dimensional chromatography. For optimization of chromatographic procedure reversed phase chromatography was (C18) used. Firstly, the multi heart cutting mode was used for connection of two dimensions. It was found that all cuts from first dimension were pure except those found in the sample XEL540/02-17/032. Therefore, High Resolution Sampling or selective comprehensive 2D-LC mode was applied. Using this approach, co-elution of impurity daptomycin β-isomer and other daptomycin related impurities in the sample XEL540/02-17/032 was detected. Mass spectrometry was used for daptomycin impurity identification (lactone daptomycin, daptomycin β-isomer and anhydro-daptomycin) in investigated samples. Conclusion Two-dimensional liquid chromatography is a powerful technique for separation of components of interest, especially when it is possible to apply completely orthogonal approach in separation steps and hyphenated 2D-LC with mass spectrometer for further identification of analyte and for gathering the knowledge and more information about the molecule structure

    Mikrobiološka onečišćenja u (tradicionalnim) biljnim lijekovima

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    Herbal substances, herbal preparations and herbal medicinal products, as well as traditional herbal medicinal products are of natural origin and have a higher risk of microbial contamination compared to chemical drugs. This review addresses microbial contaminants and chemical contaminants as products of microbial presence, referring mainly to mycotoxins. An overview is given on how to ensure suitable microbial quality, considering the importance of preventative measures, manufacturing processes and by applying decontamination processes in the frame of current regulatory aspects. Satisfactory quality regarding microbiological and mycotoxin contamination should be a result of mainly preventive measures, rather than interventions for decreasing the contamination. Evaluation should be based on a case-by-case risk assessment and usually includes tests and limits given in Ph. Eur. (for example TAMC, TYMC, absence of certain specified micro-organisms, testing on mycotoxins) in order to ensure a safe final product for the consumer or patient

    Beta-karbolini - u potrazi za novim terapijskim mogućnostima

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    Beta-carboline alkaloids, natural products ubiquitously distributed in various plants and animals represent a pharmacologically very attractive scaffold due to its convenient synthesis and structural diversity. Their pharmacological potential has been known for centuries and a large number of publications is focused on exploring the possibilities for their application. To name a few, these compounds have exerted antimalarial, antineoplastic, anticonvulsant and anxiolytic activity. In addition, several beta-carboline drugs are already used in therapy or are currently in clinical trials

    Antibakterijski učinak tvari prirodnog podrijetla u kombinaciji s antibioticima

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    Antibiotic resistance is a well-recognised global health problem. One way to address it is to rationally prescribe medications to reduce the frequency of resistance and side effects or toxic effects. In recent times the subject of research is also the combination of different drugs and/or drugs with natural bioactive substances. This paper summarizes several studies of the antibacterial effect of bioactive substances of plant, animal or fungal origin applied alone or in combination with antibiotics used in therapy. The results of these studies show mostly positive synergistic effects. lt can be concluded that, given the promising positive results, with further research, this type of medication could be applied in therapy

    Determining antioxidant activity of itaconic acid derivatives

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    Stanice tumora obilježava disbalans osnovnih staničnih regulacijskih mehanizama, a posljedica toga je njihova nenormalna proliferacija, nekontrolirani rast i dioba. Disbalans oksidacijskih i antioksidacijskih mehanizama, u korist oksidacije nazivamo oksidacijskim stresom. Tim procesom nastaju slobodni radikali. Prisutnost slobodnih radikala može uzrokovati lipidnu peroksidaciju, oštećenje DNA i proteina, može potaknuti citotoksično djelovanje, inducirati mutacije, kromosomske aberacije i naposlijetku dovesti do razvoja tumora. U ovom je radu ispitivana antioksidacijska aktivnost 10 novosintetiziranih spojeva. Sintetizirani spojevi derivati su itakonske kiseline i antimalarika primakina, klorokina i meflokina, kao i konjugati itakonske kiseline i fluoroanilina, piridina i indola. Sintetizirani su kao potencijalni antitumorski i antivirusni agensi. Odabrana je DPPH metoda kojom se brzo i jednostavno procjenjuje antioksidacijska aktivnost u složenijim biološkim uzorcima. DPPH metoda uspostavljena je korištenjem dva poznata spoja s antioksidacijskom aktivnošću, vitaminom C i Troloxom. Potom su standardi i ispitivani spojevi otopljeni u DMSO otapalu do koncentracije od 50 mM, te su radne otopine pripremljene u etanolu u seriji razrjeđenja (1 mM - 0,5 nM). Izmjerena im je apsorbancija i izračunata vrijednost antioksidacijske aktivnosti u odnosu na pozitivnu kontrolu. Ispitivani konjugati itakonske kiseline u DPPH testu nisu pokazali antioksidacijsku aktivnost. Njihove IC50 vrijednosti bile su veće od 1000 μM.Tumor cells are characterized by the imbalance of basic cellular regulation mechanisms, and the result is abnormal proliferation, uncontrolled growth, and division. The disbalance between oxidative and antioxidative mechanisms in favor of oxidation is called oxidation stress. This process creates free radicals. The presence of free radicals can cause lipid peroxidation, damage to DNA and proteins, stimulation of cytotoxic actions, induction of mutations, chromosomal aberrations, which will eventually lead to tumor development. In this paper, the antioxidant activity of 10 newly synthetic compounds were examined. Synthesized compounds are derivatives of itaconic acid and anti-malarial drugs: primaquine, chloroquine and mefloquine, as well as conjugates of itaconic acid and fluoroaniline, pyridine and indole. They are synthesized as potential anticancer and antiviral agents. A DPPH method was chosen to assess antioxidant activity quickly and easily in more complex biological samples. The DPPH method was established using two known compounds with antioxidant activity, vitamin C and Trolox. The standards and test compounds were dissolved in the DMSO solvent to a concentration of 50 mM. The stock solutions were then prepared in ethanol in a dilute series (1 mM - 0.5 nM). They were measured for absorbance and the value of antioxidant activity was calculated in relation to positive control. The examined itaconic acid conjugates in the DPPH test showed no antioxidant activity. Their IC50 values were greater than 1000 μM

    Evaluacija novopropisane antibakterijske terapije pacijentima obrađenim na objedinjenom hitnom bolničkom prijemu KBC-a Zagreb

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    Cilj ovoga istraživanja bio je dobiti uvid u najčešće infekcije zbog kojih pacijenti dolaze u objedinjeni hitni bolnički prijem. Na temelju dobivenih podataka iz nalaza bolesnika te kratkog razgovora procijenjeno je propisuje li se hitna antibakterijska terapija prema aktualnim nacionalnim i međunarodnim smjernicama za liječenje konkretnog infektivnog stanja. Iz podataka o medicinskom stanju i ostaloj terapiji koju pacijenti koriste, procijenjeno je postoji li rizik od interakcija propisane hitne terapije s kroničkom terapijom pacijenata. Opservacijsko istraživanje u ovom radu provedeno je na 57 pacijenata iz jedne ljekarničke jedinice koji su u vrijeme uključivanja u istraživanje trebali započeti antibakterijsku terapiju po izlasku s hitnog prijema KBC-a Zagreb. Dobiveni podaci obrađeni su metodama opisne statistike. U istraživanju je sudjelovalo 30 žena i 27 muškaraca. Najčešća indikacija za korištenje antibakterijske terapije bile su bolesti genitalno-urinarnog sustava (28 %), zatim bolesti dišnog sustava (19 %), bolesti kože i potkožnog tkiva (16 %). Slijedi skupina simptomi, znakovi i abnormalni klinički i laboratorijski nalazi, neklasificirani drugdje (14 %), bolesti oka i adneksa (12 %), skupina ozljede, trovanja i određene druge posljedice s vanjskim uzrokom (9 %) te bolesti krvožilnog sustava i bolesti mišićno-koštanog sustava i vezivnog tkiva. Većina propisane antibakterijske terapije bila je u skladu s nekim od postojećih smjernica u svijetu, budući da za brojne indikacije Hrvatska nema svoje nacionalne smjernice. Nisu pronađene značajnije interakcije između propisane akutne antibakterijske terapije i ostalih lijekova koje pacijenti koriste. To je dijelom i zbog toga što je većinom riječ o mlađim, radno aktivnim ljudima, prosječne dobi 42,1 godina. Potreban je povećan oprez prilikom propisivanja antibiotika za koje je poznato da često i lako ulaze u interakcije, kao što je ciprofloksacin. Analizom nalaza uočeno je da liječnici često ne odrede duljinu trajanja antibakterijskog liječenja (22,8 % ukupnih obrađenih slučajeva). Ovim istraživanjem pokazana je potreba za postojanjem redovito ažuriranih smjernica za liječenje najčešćih infekcija uzrokovanih bakterijskim uzročnicima, te su uočeni određeni propusti u propisivanju akutne antibakterijske terapije iz kojih je vidljivo da bi veće uključivanje farmaceuta (bolničkog ili javnog) moglo značajno unaprijediti liječenje i doprinjeti racionalnijoj, sigurnijoj primjeni antibiotika, s ciljem postizanja željenih ishoda liječenja.The aim of this study was to gain insight into the most common infections due to which patients come to the emergency unit of a hospital. Based on the obtained data from the doctors and a short interview with patients, it was assessed whether emergency antibacterial therapy is prescribed according to current national and international guidelines for the treatment of a specific infectious condition. From the data on the medical condition and other therapy used by the patients, it was assessed whether there is a risk of interactions of the prescribed emergency therapy with the chronic therapy of the patients. This observational study was conducted in one pharmacy, on 57 patients who were required to start antibacterial therapy upon discharge from the emergency department of University Hospital Centre Zagreb at the time of inclusion in the study. The obtained data were processed by methods of descriptive statistics. The study involved 30 women and 27 men. The most common indications for the use of antibacterial therapy were diseases of the genitourinary system (28 %), diseases of the respiratory system (19 %), skin and subcutaneous tissue diseases (16 %), then ICD group R - symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (14 %), eye and adnexal diseases (12 %), ICD group S - injuries, poisoning and certain other consequences with an external cause (9 %) and diseases of the vascular system and diseases of the musculoskeletal system and connective tissue. Most of the prescribed antibacterial therapy complies with some of the existing guidelines in the world, since Croatia does not have its own national guidelines for many indications. No significant interactions were found between prescribed acute antibacterial therapy and other medications used by patients. This is partly because they are mostly younger, working people, with an average age of 42.1 years. Caution should be exercised when prescribing antibiotics that are known to interact frequently and easily, such as ciprofloxacin. The analysis found that emergency department physicians often did not determine the duration of antibacterial treatment (22.8 % of total treated cases). This research showed the need for regularly updated guidelines for the treatment of the most common bacterial infections, and identified some shortcomings in prescribing acute antibacterial therapy, which shows that greater involvement of pharmacists (hospital or public) could significantly improve treatment and contribute to more rational and safer use of antibiotics, with the aim of achieving the desired treatment outcomes

    Uloga ljekarnika u liječenju kožnih bolesti: pogledi i iskustva iz ljekarničke prakse

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    Kronične kožne dermatoze i razni problemi s kožom su značajan zdravstveno socijalni problem i mogu narušiti kvalitetu života pacijenata. Terapija je dugotrajna, s čestim relapsima, a očekivanja pacijenata visoka. Pružanjem ljekarničke skrbi kroz sveobuhvatnu edukaciju, kroz savjetovanje o njezi kože i dermatokozmetičkim proizvodima, te kroz stručno savjetovanje o pravilnoj primjeni propisane farmakološke terapije od strane liječnika, osigurava se postizanje maksimalnog terapijskog uspjeha što dovodi do poboljšanja kvalitete pacijentova života. Ljekarnici u okviru svojih kompetencija i pozicije u primarnoj zdravstvenoj zaštiti imaju značajnu ulogu u liječenju kožnih bolesti, ali je malo dostupnih literaturnih podataka o utjecaju ljekarničke intervencije na prevenciju i liječenje istih. Cilj istraživanja: Cilj ovog istraživanja je bio prikupiti i analizirati poglede i iskustva ljekarnika o njihovoj ulozi u liječenju kožnih bolesti i pružanju ljekarničke skrbi u području dermatofarmakologije te time pridonijeti unapređenju pružanja ljekarničke skrbi u tom području. Metode istraživanja: Pri pretraživanju literature i prikupljanju relevantnih podataka za izradu ovog rada korištena je literatura dostupna putem certificiranih i akreditiranih baza podataka (Pubmed, Cochrane Library, Elsevier, Medscape, Wiley) te udžbenici i ostala dostupna relevantna literatura. Radovi su proučavani analitički, pri čemu su se izdvojili oni najrelevantniji za problematiku ovog specijalističkog rada. Za dobivanje mišljenja ljekarnika osmišljen je on-line anketni upitnik. Kao alat za izradu i obradu podataka upitnika korišten je Google Forms. Poveznica za pristup upitniku poslana je ispitanicima putem elektroničke pošte. U ispitivanje su se uključili ljekarnici zaposleni u javnim ljekarnama u Republici Hrvatskoj. Anketno ispitivanje je bilo anonimno, a prikupljeni podaci koristili su se isključivo za izradu specijalističkog rada, što je i jasno navedeno u upitniku. U obzir su se uzeli samo ispravno i u cijelosti popunjeni upitnici. Upitnik se sastojao od 20 pitanja od kojih su se prva četiri pitanja odnosila na sociodemografske karakteristike ispitanika (spol, godine ljekarničkog staža, tip i vlasništvo ljekarne, raspodjela prema županija). Sljedećih 16 pitanja se odnosilo na stavove i iskustva ljekarnika u Hrvatskoj na temu uloge ljekarnika u liječenju kožnih bolesti. Ukupno je anketirano 157 ljekarnika, a kako su svi ispitanici u cijelosti popunili upitnik, svih 157 popunjenih upitnika se uzelo u obzir kod obrade podataka. Rezultati: Pružanje ljekarničke skrbi iz područja dermatofarmakologije u javnim ljekarnama u Hrvatskoj je često zastupljeno u svakodnevnom radu ljekarnika, a odnosi se na informiranje o pravilnoj njezi kože i upotrebi dermatokozmetičkih proizvoda, na stručno savjetovanje u svrhu samoliječenja te na stručno savjetovanje o pravilnoj primjeni propisane farmakološke terapije od strane liječnika. Ljekarnici, također, uz propisanu farmakološku terapiju preporučuju dostupnu nefarmakološku terapiju, tj. dermatokozmetiku, educiraju pacijente o nefarmakološkim mjerama, kao što su uzroci koji doprinose nastanku bolesti ili ju mogu pogoršati te sudjeluju u javnozdravstvenim akcijama u ljekarni, u svrhu promicanja zdravlja kože. Ljekarnici u Hrvatskoj se najčešće susreću s atopijskim dermatitisom i problematikom akni, te su od dermatokozmetičkih proizvoda najčešće u prilici preporučiti: emolijense i syndete za njegu atopične kože te dermatokozmetičke proizvode za akne koji djeluju na kontroliranje sebuma, antimikrobno, protuupalno, antioksidacijski i/ili keratolitički te hidrirajući. Zaključak: Uloga ljekarnika u liječenju kožnih bolesti nije dovoljno prepoznata u društvu, a organizacija dermatokozmetičkih savjetovališta kao dodatne usluge unutar ljekarne smatra se najboljim načinom za unaprjeđenjem pružanja ljekarničke skrbi iz područja dermatofarmakologije. Ljekarnici, kao najdostupniji zdravstveni djelatnici, često su prvi i zadnji kontakt pacijentima s kožnim problemom. Većina ljekarnika smatra da je potrebno u programu formalne izobrazbe farmaceuta i u stručnom osposobljavanju staviti veći naglasak na stjecanje kompetencija ljekarnika u području dermatofarmacije, a u programu stručnog usavršavanja članova Hrvatske ljekarničke komore organizirati više bodovanih edukacija iz područja kozmetologije i dermatofarmacije.Chronic skin dermatoses and various skin problems are a significant health and social problem and can limit patients' quality of life. Treatment is lengthy, with frequent relapses, and patient expectations are high. Pharmaceutical care through comprehensive education, skin care and dermatocosmetic advice, and support and guidance in adherence to dermatologistrecommended treatment ensures maximum treatment success, resulting in an improvement in the patient's quality of life. As part of their competencies and position within primary health care, pharmacists play a significant role in the management of skin disease, but there is limited data on the impact of pharmaceutical interventions on the prevention and treatment of skin disease. Aim: The aim of this study was to confirm the important and indispensable role of pharmacists in the management of skin diseases and in the provision of dermatopharmacology-related pharmaceutical care, as well as to let pharmacists' opinions and attitudes expressed in the questionnaire contribute to the improvement of dermatopharmacology-related pharmaceutical care. Methods: Source search and collection of relevant research data was done using papers available through certified and accredited databases (Pubmed, Cochrane Library, Elsevier, Medscape, Wiley), textbooks and other available relevant papers. An online questionnaire was created to obtain pharmacists' opinions. Google Forms was used to generate and analyze the data obtained. An access link was emailed to participants. Pharmacists working in Croatian public pharmacies were surveyed. A link to the questionnaire was emailed to participants. Pharmacists working in Croatian public pharmacies were surveyed. The survey was anonymous and the data were used only for the purpose of the work, which was clearly stated in the questionnaire. Only correctly and completely filled questionnaires were analyzed. The questionnaire consisted of 20 questions, the first four of which asked for the socio-demographic data of the participants (gender, professional experience as a pharmacist, type and ownership of pharmacy, county). The following 16 questions were related to the attitudes and experiences of Croatian pharmacists when it comes to the pharmacist's role in the treatment of skin diseases. A total of 157 pharmacists were interviewed, and since all 157 participants completed the entire questionnaire, all 157 questionnaires were used for data analysis. Results: Providing dermatopharmacology-related pharmaceutical care is often part of the daily work of pharmacists in Croatian public pharmacies, and it consists of providing information on proper skin care and the use of dermatocosmetic products, professional advice for the purpose of self-treatment, and professional advice on proper adherence. In addition to prescribed pharmacological treatment, i.e. dermatocosmetics, pharmacists also educate patients about nonpharmacological measures, such as the causes that contribute to the development or exacerbation of the disease, and they participate in public health actions in pharmacies with the aim of promoting skin health. Croatian pharmacists most often deal with problems of atopic dermatitis (eczema) and acne, and most often recommend: emollients and syndets for the treatment of skin affected by eczema, and the following acne products: sebum-controlling products, antimicrobial, antiinflammatory, antioxidant and/or keratolytic and moisturizing products. Conclusion: As part of their competencies and position within primary care, the role of the pharmacist in the management of skin disease is significant but under-recognized in society. Organizing dermatocosmetic consultation as an additional service of a pharmacy is considered the best way to improve dermatopharmacological pharmaceutical care. Pharmacists, as the most available health care workers, are often the first and last contact of a patient with a skin problem. Most pharmacists believe that more emphasis should be placed on pharmacist competencies in dermatopharmacy during formal education and on-the-job training, and that more accredited (points-awarding) courses in cosmetology and dermatopharmacy should be organized as part of pharmacist training offered by Croatian Chamber of Pharmacists

    Method optimization for determination of iron in honey by atomic absorption spectrophotometry

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    Željezo je jedan od najvažnijih elemenata za ljudski organizam. Njegove biološke uloge u tijelu čovjeka su mnogobrojne. Sastavni je dio velikog broja proteina, prostetskih skupina i kofaktor mnogim enzimima. Deficit željeza je najčešći deficit minerala u globalnoj populaciji, a pogađa posebno osjetljive skupine poput djece, adolescenata i mladih žena. Med je namirnica prirodnog porijekla bogatih nutritivnih svojstva i poznata po terapeutskim svojstvima. Kompleksni matriks oligosaharida čini ga zahtjevnim uzorkom za analizu vitamina i minerala. U ovom radu je pomoću Box-Behnkenovog dizajna optimizirana metoda pripreme uzorka za analizu sadržaja željeza u medu atomskom apsorpcijskom spektrometrijom. Višestrukom regresijskom analizom dobivena je kvadratna polinomna jednadžba koja opisuje utjecaj triju odabranih parametra (temperatura, udio kiseline i vrijeme) na sadržaj željeza u medu. Utvrđeni su optimalni parametri te je provedena analiza ukupno 21 različitih uzoraka meda. Ispitivanjem validacijskih parametara utvrđeno je da primijenjena metoda ima zadovoljavajuću linearnost, preciznost i točnost. Nakon analize uzoraka meda utvrđeno je da su koncentracije željeza u medu u korelaciji s rezultatima iz prethodnih istraživanja te da nema statistički značajne razlike između meda različitog geografskog porijekla.Iron is one of the most important elements for the human body. Its biological roles in the human body are numerous. Iron is an integral part of many proteins, prosthetic groups, and a cofactor for many enzymes. Iron deficiency is the most common mineral deficiency in the global population, and particularly affects vulnerable groups such as children, adolescents, and young women. Honey is a food of natural origin with rich nutritional value and known for its therapeutic properties. The complex matrix of oligosaccharides makes it a challenging sample for vitamin and mineral analysis. In this work, the method of sample preparation was optimized for the analysis of iron content in honey by atomic absorption spectrophotometry using Box-Behnken design. Multiple regression analysis yielded a quadratic polynomial equation describing the influence of three selected parameters (temperature, acid content and time) on the iron content in honey. Optimal parameters were determined and a total of 21 different honey samples were analyzed. Validation of the analytical method showed that the method has satisfactory linearity, precision, and accuracy. After the analysis of honey samples, it was found that the iron concentrations in honey correlated with the results of previous studies and there was no statistically significant difference between honeys of different geographical origin

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