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The calculation and the simulation of EPR parameters for the nitrogen-centered radicals
No full textDušikovi slobodni radikali i reaktivne dušikove specije posjeduju različite funkcije u živim organizmima. Radikalne specije su zbog svojih svojstava kratkoživuće i niske stabilnosti, što zahtjeva primjenu različitih kemijskih metoda u istraživanju i opisivanju funkcije radikala.
U ovom radu, opisana su fundamentalna načela elektronske paramagnetske rezonancije, njene primjene u biološkim ispitivanjima. Također, opisane i primijenjene su metode računalne kemije u svrhu dobivanja parametara karakterističnih za elektronsku paramagnetsku rezonanciju, jednu od esencijalnih metoda u analizi anorganskih i organskih slobodnih radikala.
Dušikovi radikali analizirani u ovom radu podijeljeni su u šest skupina ovisno o prirodi supstituenata na dušikovom radikalnom središtu, s tablično prikazanim EPR vrijednostima za pojedini radikal te vrijednostima energije disocijacije veze.
Odabrani spektri za pojedine radikale vizualizirani su u VisualEPR programu i uspoređeni s eksperimentalno dostupnim EPR spektrima, te se pokazalo značajno poklapanje između spektara.Nitrogen-centered radicals, as well as reactive nitrogen species possess a variety of important roles in living organisms. A short longevity and a low stability, as key features of free radicals prompt the implementation of different methods in chemistry as tools in the research of free radicals.
This paper describes the fundamentals of electron paramagnetic resonance and its application in biological research. Furthermore, the methods of computational chemistry are described and utilized in order to yield the characteristic parameters of electron paramagnetic resonance – one of the essential methods in the analysis of inorganic and organic free radicals.
Nitrogen-centered radicals analyzed in this paper are divided in six groups according to the characteristics of the substituents. The results are presented in six tables with EPR parameters and bond dissociation energies given for each radical.
The calculated spectra were visualized with VisualEPR programme and supplemented with a database comparison to their experimental counterparts for a number of nitrogen-centered free radicals. A good agreement between experimental and simulated spectra were observed
Ultrasonic extraction of polyphenolic compounds from species Helichrysum italicum (Roth) G. Don. using (2-hydroxypropyl)-B-cyclodextrins
No full textSmilje (Helichrysum italicum, (Roth), G. Don) je izvor visokovrijednih polifenola, prirodnih antioksidansa. Raznolikost tih kemijskih spojeva, koji pojedinačno ili u sinergiji pridonose farmakološkoj aktivnosti, nudi brojne mogućnosti praktične primjene ekstrakata biljke. U cilju učinkovitog izdvajanja navedenih spojeva iz biljnog materijala provedena je optimizacija ekstrakcijskih uvjeta. U radu je korištena metoda inkapsulacije (2-hidroksipropil)-β-ciklodekstrinom, te ultrazvukom potpomognuta ekstrakcija, u svrhu boljeg iskorištenja i skraćenog vremena ekstrakcije. U usporedbi sa konvencionalnom metodom ekstrakcije etanolom ili drugim organskim otapalima, ova metoda je ekološki prihvatljiva. Provedena je spektrofotometrijska analiza sadržaja ukupnih polifenola i podskupina polifenola, fenolnih kiselina i flavonoida u ekstraktima, te kvantifikacija sadržaja klorogenske kiseline korištenjem tekućinske kromatografije visoke djelotvornosti (engl. HPLC). Najboljim uvjetima ekstrakcije pokazali su se neosporno: snaga ultrazvuka 720 W, temperatura 70 °C, masa droge 0,6 g te voda kao otapalo. Parametri s najvećim utjecajem na ekstrakcijski kapacitet su temperatura i masa droge. Snaga ultrazvuka indirektno utječe na prinos dok glicerol gotovo nema utjecaja. Udio mliječne kiseline pozitivno utječe na ekstrakciju fenolnih kiselina pri nižim temperaturama, dok na koncentraciju flavonoida ima negativan utjecaj.Immortelle (Helichrysum italicum, (Roth), G. Don) is a source of high-value polyphenols, natural antioxidants. The diversity of these chemical compounds, which individually or synergistically contribute to pharmacological activity, offers many possibilities in practical use of plant extracts. In order to efficiently extract mentioned compounds from plant material, extraction conditions were optimised. In this paper, methods that were used were (2-hydroxypropyl)-β-cyclodextrin encapsulation and ultrasound-assisted extraction for the purpose of better extraction efficiency and shortened extraction time. In comparison to conventional extraction method with ethanol or other organic solvents, this method is environmentally friendly. Spectrophotometric analysis of total polyphenols, phenolic subclasses, phenolic acids and flavonoids in the extracts was conducted, as well as quantification of chlorogenic acid content using high performance liquid chromatography (HPLC). The best extraction conditions indisputably proved to be: ultrasound power 720 W, temperature 70 °C, drug weight 0,6 g and water as a solvent. Parameters with the greatest impact on the extraction capacity are temperature and drug mass. Ultrasound power affects the yield indirectly, while glycerol had almost no effect. The proportion of lactic acid has a positive effect on phenolic acids’ extraction at lower temperatures, while it has a negative effect on the flavonoid concentration
Influence of depressive symptoms on adherence in patients with advanced breast cancer
No full textSvaka osma žena u svijetu oboljet će od raka dojke. Kao dostupna terapija sve su češći oralni antitumorski lijekovi koji pospješuju kvalitetu
života pacijentica na adjuvantnoj terapiji. Navedena terapija zahtijeva od pacijenata preuzimanje odgovornosti za uzimanje lijekova i
aktivno sudjelovanje u procesu liječenja. Upravo je zato u ovom kontekstu postao važan pojam adherencije. Literaturni podatci ukazuju
da je adherencija na oralne antitumorske lijekove često suboptimalna. Cilj ovog istraživanja bio je utvrditi stopu adherencije kod pacijentica
s uznapredovalim rakom dojke. Ispitivana je i učestalost depresivnih simptoma te utjecaj depresivnih simptoma na adherenciju kod takvih
pacijentica. Obzirom da smanjena adherencija može dovesti do recidiva bolesti i povećanja smrtnosti, bilo je važno utvrditi čimbenike koji
utječu na nju te potencijalnu prevenciju istih. Provedeno je opažajno, presječno ispitivanje. U istraživanje su bile uključene žene starije od
18 godina koje boluju od uznapredovalog raka dojke (stadij IV), a primaju oralnu terapiju. Adherencija je mjerena validiranim MARS-5
upitnikom, a prisutnost depresivnih simptoma Beckovim inventarom depresije – drugo izdanje. Adherencija pacijentica s uznapredovalim
rakom dojke u ovom istraživanju pokazala se visokom, a iznosila je 24,04 (±1,653) od maksimalno mogućih 25 bodova. Kod pacijentica
s rakom dojke, osobito onih s metastatskim rakom dojke prevalencija depresivnih simptoma je viša nego u općoj populaciji. Smatra se da
depresivni simptomi mogu utjecati na smanjenje adherencije i tako prouzrokovati lošije terapijske ishode. Iako je gotovo 45% pacijentica
imalo neki oblik depresivnih simptoma, statistički značajna povezanost depresivnih simptoma i smanjene adherencije nije nađena
(p=0,455). Na pacijentice s depresivnim simptomima svejedno treba obratiti pažnju jer kronični odgovor na stres koji može doprinijeti
razvoju depresije kod oboljelih od raka, može također pridonijeti povećanju invazivnosti raka.Every eighth woman in the world will be diagnosed with breast cancer. Available oral antitumor drugs are becoming more
common and can improve quality of life in patients that are receiving adjuvant therapy. Previously mentioned therapy requires
patients to take responsibility for taking the medication and to actively participate in the treatment process. That is why term
adherence has become important in this context. Body of literature shows that adherence to oral antitumor drugs is often
suboptimal. The purpose of this research was to determine the rate of adherence in patients with advanced breast cancer. The
prevalence of depressive symptoms and influence of depressive symptoms on adherence was also questioned. Because lower
adherence can lead to disease recurrence and higher mortality rates, it was important to determine the factors that can influence
adherence and how to prevent them. Conducted research was observational and cross-sectional. Women over 18 years with
advanced breast cancer (stage IV) that are on oral therapy were included in the study. Adherence was measured with validated
MARS-5 questioner and the presence of depressive symptoms was measured with Beck’s depression inventory – second edition.
Patients with advanced breast cancer included in the research had a high adherence rate, specifically their score was 24,04
(±1,653) out of maximal possible 25. The prevalence of depressive symptoms in patients with breast cancer, especially those
with metastatic breast cancer is higher than in the general population. It is considered that depressive symptoms can lead to
lower adherence and therefore cause worse therapeutic outcomes. Although almost 45% of patients had some form of depressive
symptoms, the statistically important relationship between depressive symptoms and lower adherence was not found (p=0,455).
Still, it is important to pay attention to patients with depressive symptoms because the chronic stress response which can
contribute to depression in patients with cancer, can also lead to increased cancer invasiveness
Stavovi i iskustva trudnica o uporabi biljnih lijekova i dodataka prehrani
No full textCilj istraživanja: Današnji sveopći trend rasta potrošnje biljnih lijekova i dodataka prehrani,
kao dio samoliječenja, nije zaobišao ni trudnice. Iako prevladava mišljenje da su takvi
pripravci sigurni i neškodljivi, njihova nepravilna primjena bez stručnog nadzora nosi
određeni rizik za majku i dijete. Stoga je cilj ovog rada ispitati stavove trudnica u Hrvatskoj o
uporabi biljnih lijekova i dodataka prehrani te njihova iskustva vezana uz primjenu takvih
pripravaka tijekom trudnoće.
Ispitanici i metode: U ovom je radu pomoću anonimnog upitnika provedeno istraživanje na
uzorku od 110 punoljetnih trudnica. Na početku anketnog upitnika prikupljeni su
sociodemografski podaci o trudnicama. Zatim su prikupljeni podaci o trudnoći, prehrambenim
i životnim navikama tijekom trudnoće te kroničnim bolestima i drugim zdravstvenim
tegobama. Preostalim su pitanjima ispitani stavovi i iskustva trudnica o upotrebi biljnih
lijekova i dodataka prehrani u trudnoći. Istraživanje je provedeno u javnim ljekarnama na
području Hrvatske i jednoj ginekološkoj poliklinici u Zagrebu u razdoblju od rujna 2020. do
veljače 2021. godine.
Rezultati: Gotovo dvije trećine ispitanica (73 %) koristilo je neki biljni lijek ili dodatak
prehrani tijekom trudnoće te se njihova uporaba povećala u odnosu na vrijeme prije trudnoće.
Najviše trudnica uzimalo je vitaminsko-mineralne pripravke (89 %) te fitopreparate (56 %).
Gotovo sve trudnice korištene pripravke kupile su u ljekarni, ali zabrinjava činjenica da je
samo polovica (53 %) dobila stručne informacije vezane uz njihovu primjenu. Svaka četvrta
trudnica koristi biljne lijekove i/ili dodatke prehrani zbog neke zdravstvene tegobe, dok 79 %
njih upotrebljava takve pripravke kako bi ojačale svoje zdravlje. Trudnice su ove pripravke
najčešće uzimale prema preporuci ginekologa (56 %) ili ljekarnika (40 %). Više od 75 %
ispitanica smatra da bi svaka trudnica trebala neovisno o prehrani uzimati folnu kiselinu,
vitamine, minerale i omega 3-masne kiseline. Po pitanju učinkovite i sigurne primjene
fitopreparata kao i kvalitete biljnih lijekova i dodataka prehrani trudnice su pokazale određenu
nesigurnost. Ohrabrujuće je da 76 % trudnica smatra da bi se biljni lijekovi i dodaci prehrani
trebali izdavati isključivo u ljekarnama, ali oko 25 % smatra da ginekolozi i ljekarnici nemaju
dovoljno znanja za kvalitetno savjetovanje o primjeni takvih pripravka u trudnoći. Dvije
trećine ispitanica izrazilo je potrebu za stručnim edukacijama trudnica iz ovog područja.
Zaključak: Utvrđena je visoka stopa korištenja biljnih lijekova i dodataka prehrani u
trudnoći. Upotrebom takvih pripravaka trudnice najčešće žele dodatno obogatiti svoju
uobičajenu prehranu i/ili utjecati na poboljšanje simptoma kod raznih zdravstvenih tegoba
izazvanih promjenama u trudnoći. Kako bi se osigurala učinkovita primjena biljnih lijekova i
dodataka prehrani te prevenirale moguće neželjene posljedice uslijed samoliječenja, potrebna
je uključenost educiranih zdravstvenih djelatnika, posebice liječnika i ljekarnika.Objectives: Today's general trend of growing consumption of herbal drugs and dietary
supplements, as part of self-medication, has not bypassed even pregnant women. Although the
prevailing opinion is that such preparations are safe and harmless, their improper use without
professional supervision carries a certain risk for mother and child. Therefore, the aim of this
research is to examine the attitudes of pregnant women in Croatia regarding the use of herbal
drugs and dietary supplements and their experiences related to the use of such preparations
during pregnancy.
Respondents and Methods: In this work, a survey was conducted using an anonymous
questionnaire on a sample of 110 adult pregnant women. At the beginning of the
questionnaire, sociodemographic data on pregnant women were collected. Data were then
collected on pregnancy, dietary and lifestyle habits during pregnancy, and chronic diseases
and other health problems. The remaining questions examined the attitudes and experiences of
pregnant women regarding the use of herbal drugs and dietary supplements during pregnancy.
The research was conducted in public pharmacies in Croatia and one gynecological polyclinic
in Zagreb in the period from September 2020. to February 2021.
Results: Almost two-thirds of the respondents (73 %) used some herbal drug or dietary
supplement during pregnancy, and their use increased compared to before pregnancy. Most
pregnant women took vitamin-mineral preparations (89 %) and phytopreparations (56 %).
Almost all pregnant women bought the used preparations in a pharmacy, but the fact that only
half (53 %) received professional information related to their use is worrying. Every fourth
pregnant woman uses herbal drugs and/or dietary supplements for some health problem, while
79 % of them use such preparations to strengthen their health. Pregnant women most often
took these preparations as recommended by gynecologists (56 %) or pharmacists (40 %).
More than 75 % of respondents believe that every pregnant woman should take folic acid,
vitamins, minerals and omega 3 fatty acids independently of her diet. Regarding the effective
and safe use of phytomedicines, as well as the quality of herbal drugs and dietary
supplements, pregnant women showed some uncertainty. It is encouraging that 76 % of
pregnant women believe that herbal medicines and nutritional supplements should be
dispensed exclusively in pharmacies, but about 25 % believe that gynecologists and
pharmacists do not have enough knowledge to provide quality advice on the use of such
preparations during pregnancy. Two thirds of the respondents expressed the need for
professional training for pregnant women in this area.
Conclusion: A high rate of use of herbal drugs and dietary supplements during pregnancy
was found. By using such preparations, pregnant women most often want to additionally
enrich their usual diet and/or influence the improvement of symptoms of various health
problems caused by changes during pregnancy. In order to ensure the effective use of herbal
drugs and dietary supplements and to prevent possible unwanted consequences due to selfmedication,
the involvement of educated health professionals, especially doctors and
pharmacists, is necessary
Association between the use of the Pandemrix vaccine and the incidence of narcolepsy type 1 with regard to the HLA-DQB1*06:02 allele frequency
No full textNarkolepsija tipa 1 (NT1) je poremećaj spavanja koji nastaje zbog kronične deficijencije oreksina do koje dolazi zbog selektivnog imunoposredovanog uništenja oreksinskih neurona u hipotalamusu. Osim disregulacije ciklusa spavanje - budnost, bolest se prezentira raznim motoričkim, kognitivnim, psihijatrijskim, metaboličkim i autonomnim simptomima, a najspecifičniji simptom je katapleksija. Etiologija je multifaktorijalna, a uključuje genske, epigenske i okolišne čimbenike. Rizični faktori su pozitivnost na HLA-DQB1*06:02 alelnu varijantu, prethodna infekcija virusom influence H1N1 ili Streptococcus-om te primjena cjepiva protiv influence A H1N1/pdm09 s AS03 adjuvansom (Pandemrix). Patofiziologija bolesti još uvijek je tema istraživanja, no do sad utvrđeni genetički, epidemiološki i eksperimentalni podatci podržavaju hipotezu da je NT1 autoimuna bolest posredovana T-limfocitima usmjerena na oreksinske neurone. Razumijevanje imunopatogeneze NT1 važno je iz javnozdravstvene perspektive jer može usmjeriti daljnja istraživanja u smjeru novih terapijskih mogućnosti narkolepsije i drugih autoimunih bolesti te pomoći uspostaviti globalno koordiniranu mrežu ispitivanja sigurnosti cjepiva kao ključnog čimbenika u borbi protiv budućih pandemija.Narcolepsy type 1 (NT1) is a sleep disorder caused by chronic orexin deficiency that occurs due to selective immune-mediated destruction of orexin neurons in the hypothalamus. In addition to dysregulation of the sleep-wake cycle, the disease presents itself with various motor, cognitive, psychiatric, metabolic, and autonomic symptoms, the most specific symptom being cataplexy. The etiology is multifactorial and includes genetic, epigenetic, and environmental factors. Risk factors include HLA-DQB1*06:02-positivity, previous H1N1 influenza virus or Streptococcus infection, and administration of the AS03-adjuvanted influenza A H1N1/pdm09 vaccine (Pandemrix). The pathophysiology of the disease is still an object of ongoing research, but the genetic, epidemiological, and experimental data established so far support the hypothesis that NT1 is a T-lymphocyte-mediated autoimmune disease targeting orexin-producing neurons. Understanding the immunopathogenesis of NT1 is important from the perspective of public health because it can guide further research toward modern therapeutic approaches to narcolepsy and other autoimmune diseases and also help establish a globally coordinated vaccine safety infrastructure as a crucial factor in the fight against future pandemics
Applicability of the modified QuEChERS method for the detection of the mycotoxin sterigmatocystin in the blood plasma of healthy blood donors
No full textPodaci o izravnoj izloženosti ljudi mikotoksinu sterigmatocistinu (STC) su ograničeni, iako je STC vrlo prisutan u zatvorenim prostorima. Stoga smo odlučili provesti analizu krvne plazme dobrovoljnih darivatelja krvi kako bismo procijenili izloženost zdravih osoba ovom mikotoksinu. Metoda za ekstrakciju STC-a iz uzoraka krvne plazme (N = 94) slijedila je modificiranu QuEChERS metodu, u kojoj je ekstrakcija zakiseljenim acetonitrilom kombinirana s dodatkom soli i pročišćavanjem putem SPE kolona. Pripremljeni ekstrakti analizirani su metodom LC-MS/MS. Analiza je potvrdila prisutnost STC-a u 21/94 uzoraka, ali samo u tragovima, iz čega se može zaključiti da izloženost STC-u ne predstavlja zdravstveni rizik u populaciji obuhvaćenoj istraživanjem. U budućnosti bi se ova metoda mogla koristiti za procjenu izloženosti ljudi i životinja STC-u i evaluaciju njegove toksikokinetike. To bi bilo osobito važno za osobe koje borave u područjima gdje su otkrivene povećane koncentracije STC-a ili za procjenu utjecaja STC-a na kronične upalne ili maligne bolesti.The data on direct human exposure to the mycotoxin sterigmatocystin (STC) is limited, even though STC is highly prevalent in indoor environments. Thus, we decided to conduct an analysis of blood plasma from voluntary blood donors to assess the exposure of healthy individuals to this mycotoxin. The method for extracting STC from blood plasma samples (N = 94) followed the modified QuEChERS method, in which acidic acetonitrile extraction was combined with the addition of salts and purification through SPE columns. The prepared extracts were analyzed using the LC-MS/MS method. The analysis confirmed the presence of STC in 21 out of 94 samples, but only in trace amounts, allowing us to conclude that STC exposure does not pose a health risk to the studied population. In the future, this method could be used in assessing human and animal exposure to STC and evaluating its toxicokinetics. This would be particularly important for individuals residing in areas where increased concentrations of STC have been detected, or to evaluate implication of STC in chronic inflammatory or malignant diseases
Analitičke metode za detekciju krivotvorenih antibiotika
No full textCilj istraživanja
Cilj ovog istraživanja je dati pregled dosad razvijenih i korištenih analitičkih metoda za detekciju krivotvorenih antibiotika. Zatim, istaknuti negativne zdravstvene učinke koji se pojavljuju kao posljedica krivotvorenih lijekova i opisati radnje koje ljekarnici mogu poduzeti u sprječavanju upotrebe krivotvorenih lijekova. Nadalje, objasniti razloge zašto korištenje antibiotika loše kvalitete dovodi do povećanog rizika od razvoja sojeva otpornih na mikroorganizme, neuspjeha liječenja, gubitka povjerenja u zdravstvene sustave i povezanih socio-ekonomskih učinaka.
Materijali i metode
Istraživanja u ovom specijalističkom radu teorijskog su karaktera. Literatura je pretraživana prema temi i predmetu istraživanja, a pretraga je obuhvaćala stručne i znanstvene članke, relevantne farmakopeje (Internacionalna farmakopeja, Europska farmakopeja, Američka farmakopeja USP/NF i Britanska farmakopeja), smjernice i izvještaje regulatornih tijela, Svjetske zdravstvene organizacije i drugih institucija, kao i razne elektroničke izvore. Na temelju proučavanja navedene literature izvedena su vlastita razmatranja na navedenu temu rada.
Pri pretraživanju literature korištene su baze podataka: PubMed, Science Direct, ResearchGate, Scopus, Web of Science, Medline, Embase.
Rezultati
Niti jedna analitička metoda nije dovoljna sama po sebi za identifikaciju svih vrsta krivotvorenih antibiotika zbog velike varijacije u krivotvorinama. Među korištenim analitičkim tehnikama su tekućinska kromatografija visoke djelotvornosti (HPLC) i plinska kromatografija (GC), uz detekcijske sustave poput ultraljubičaste spektroskopije (UV), spektrometrije mase (MS), fluorescencije i kemiluminiscencije. U zemljama s niskim i srednjim dohotkom, zbog ograničenih resursa, prednost imaju brže i jeftinije metode poput kolorimetrije i tankoslojne kromatografije (TLC), iako su one manje selektivne i osjetljive. U zemljama s visokim dohotkom, napredne tehnike poput HPLC-MS pružaju precizne informacije o vrstama prisutnih sastojaka i njihovim količinama, dok su vibracijske spektroskopske tehnike poput Ramanove i spektrometrije apsorpcije bliskog infracrvenog zračenja (NIR) pogodne za primjenu na terenu.
Zaključak
Antimikrobni lijekovi predstavljaju temeljni stup u liječenju infektivnih bolesti. Međutim, s rastućom prijetnjom antimikrobne rezistencije i problematikom krivotvorenih lijekova, jasno je da je potrebna koordinirana globalna akcija. Iako je vizualna inspekcija korisna prva linija obrane, sofisticirane tehnike krivotvorenja zahtijevaju daljnju analizu. Uvođenje naprednih tehnika označavanja i pakiranja, kao što su hologrami, sigurnosne naljepnice i bar kodovi, pomaže u detekciji krivotvorina. Primjena sofisticiranih analitičkih tehnika, uključujući spektrometriju (Ramanovu i NIR) i kromatografiju (tekućinsku i plinsku), ključna je za točnu identifikaciju krivotvorenih antibiotika. Samo kroz kombiniranje regulatornih mjera, naprednih tehnologija i analitičkih metoda, edukacije i globalne suradnje može se efikasno boriti protiv problema krivotvorenih antibiotika i zaštititi javno zdravlje.Objectives
The aim of this research is to provide an overview of the analytical methods developed and used so far for the detection of counterfeit antibiotics. Next, highlight the negative health effects that occur as a result of counterfeit drugs and describe actions that pharmacists can take to prevent the use of counterfeit drugs. Furthermore, to explain the reasons why the use of low-quality antibiotics leads to an increased risk of the development of resistant strains of microorganisms, treatment failure, loss of trust in health systems and related socio-economic effects.
Material and Methods
The research in this specialist work is of a theoretical nature. The literature was searched according to the topic and subject of the research, and the search included professional and scientific articles, relevant pharmacopoeias (International Pharmacopoeia, European Pharmacopoeia, American Pharmacopoeia USP/NF and British Pharmacopoeia), guidelines and reports of regulatory bodies, the World Health Organization and other institutions, as well as various electronic sources. Based on the study of the mentioned literature, their own considerations were made on the mentioned topic of the work. The following databases were used for the literature search: PubMed, Science Direct, ResearchGate, Scopus, Web of Science, Medline, Embase.
Results
No single analytical method is sufficient by itself to identify all types of counterfeit antibiotics due to the wide variation in counterfeits. Among the techniques used are high performance liquid chromatography (HPLC) and gas chromatography (GC), along with detection systems such as ultraviolet spectroscopy (UV), mass spectrometry (MS), fluorescence and chemiluminescence. In low- and middle-income countries, due to limited resources, faster and more economical methods such as colorimetry and thin-layer chromatography (TLC) are preferred, even though they are less sensitive. In high-income countries, advanced techniques such as HPLC-MS provide precise information on the types of constituents present and their amounts, while vibrational spectroscopic techniques such as Raman and NIR are suitable for field applications.
Conclusion
Antimicrobial drugs represent a fundamental pillar in the treatment of infectious diseases, with a revolutionary impact on public health since their introduction in the 20th century. However, with the growing threat of antimicrobial resistance and the problem of counterfeit medicines, it is clear that coordinated global action is needed. While visual inspection is a useful first line of defense, sophisticated counterfeiting techniques require further analysis. The introduction of advanced labeling and packaging techniques, such as holograms, security labels and bar codes, helps in the detection of counterfeits. Application of standard analytical techniques, including spectroscopy (Raman, infrared) and chromatography (liquid and gas), is essential for accurate identification of counterfeit antibiotics. Only by combining regulatory measures, advanced technologies and analytical methods, education and global cooperation can we effectively fight the problem of counterfeit antibiotics and protect public health
Applicability of the modified QuEChERS method for the detection of the mycotoxin sterigmatocystin in urine of healthy blood donors
No full textSterigmatocistin (STC) je kancerogeni i genotoksični mikotoksin kojeg u najvećoj mjeri proizvode ubikvitarne plijesni roda Aspergillus. Mikotoksin je detektiran u brojnim prehrambenim namirnicama, ali i u unutarnjim prostorima sa visokom stopom vlažnosti i poviješću prethodnih poplava. Zabilježeni su brojni mehanizmi kojima ispoljava štetne učinke na organizam, a s obzirom da dijeli biosintetski put i strukturnu sličnost s kancerogenim aflatoksinom B1, potrebna je učinkovita, osjetljiva i dovoljno jednostavna metoda detekcije u biološkim uzorcima. Obradom 94 uzoraka urina zdravih dobrovoljnih darivatelja krvi nastojala se procijeniti izloženost mikotoksinu STC-u. Pritom je korištena optimizirana QuEChERS metoda ekstrakcije i pročišćavanja uzorka. STC je u tragovima detektiran u 18 % uzoraka pri čemu je 61/94 uzoraka obrađen pojednostavljenom QuEChERS metodom, a 38/94 uzoraka je dodatno pročišćeno ekstrakcijom na čvrstoj fazi (SPE). Nije utvrđena statistički značajna razlika u detekciji STC-a s obzirom na metodu pripreme uzoraka. Također nije utvrđen utjecaj dobi i spola ispitanika na prisustvo STC-a u urinu. Dobiveni rezultati pokazali su da u odabranoj zdravoj populaciji dobrovoljnih darivatelja krvi nije utvrđen rizik izloženosti mikotoksinu STC-u. Rezultati također upućuju na prikladnost opisane metode za primjenu u daljnjim istraživanjima usmjerenim na detekciju STC-a u biološkim uzorcima.Sterigmatocystin (STC) is a carcinogenic and genotoxic mycotoxin predominantly produced by ubiquitous molds of the genus Aspergillus. The mycotoxin has been detected in numerous foodstuffs as well as in indoor environments with high humidity and a history of previous flooding. Numerous mechanisms by which it exerts harmful effects on the organism have been documented. Given that it shares a biosynthetic pathway and structural similarity with the carcinogenic aflatoxin B1, there is a need for an effective, sensitive, and sufficiently simple method for its detection in biological samples. By analyzing 94 urine samples from healthy blood donor volunteers, we aimed to assess exposure to the mycotoxin STC. An optimized QuEChERS method for extraction and sample purification was employed. STC was detected in trace amounts in 18 % of samples, with 61/94 samples processed using the simplified QuEChERS method, and 38/94 samples further purified using solid-phase extraction (SPE). No statistically significant difference was found in the detection of STC with respect to the sample preparation method. Additionally, the influence of age and gender on the presence of STC in urine was not statistically significant. The obtained results indicated that there was no risk of STC exposure in the selected healthy population of blood donor volunteers. The results also indicate the suitability of the described method for application in further research aimed at detecting STC in biological samples
Stochastic search of Au4, Au6 and Au8 configurational isomers
No full textU ovom radu provedeno je stohastičko pretraživanje struktura malih klastera zlata Aun (n = 2 – 8), s ciljem identifikacije i karakterizacije osnovnih strukturnih jedinica koje su prikladne za opis formiranja nanočestica zlata. Odabrani klasteri predstavljaju osnovne građevne blokove na kojima se temelje složenije strukture. Korištena procedura „Kick" pokazala se kao vrlo učinkovit i pouzdan alat, posebno u pogledu brzine i preciznosti u pretraživanju plohe potencijalne energije tetramera, heksamera i oktamera zlata. Osim toga, važnu ulogu ima i primijenjena teorijska razina DFT u kvantno-kemijskim izračunima, o kojoj ovise rezultati prirode struktura (minimumi ili stacionarne točke).
Kako se broj atoma zlata u oligomerima povećavao, zabilježen je rast broja mogućih konfiguracijskih i konformacijskih izomera, čime se znatno povećava složenost sustava. Za čestice Au4 locirana su 3 stabilna izomera, za Au6 je locirano 9 struktura te je za Au8 locirano 19 struktura koje su pravi minimumi. Istovremeno, s povećanjem broja atoma zlata u klasterima, zabilježeno je i povećanje raspona relativnih energetskih razlika između različitih klastera (za Au4 raspon oko 42 kJ/mol, za Au6 170 kJ/mol te za Au8 oko 140 kJ/mol), što dodatno otežava identifikaciju najstabilnijih struktura.
Prikazana metoda stohastičkog pretraživanja, u kombinaciji s DFT izračunima, pokazala se izuzetno korisnom ne samo za razumijevanje strukturne raznolikosti malih zlatnih klastera, već i za
širu primjenu u proučavanju većih molekulskih sustava. Ova metodologija može se učinkovito koristiti i za proučavanje interakcija između lociranih izomera i biološki važnih spojeva, otvarajući mogućnosti za daljnja istraživanja na granici nanotehnologije i biokemije.In this work, a stochastic search of the structures of small Aun gold clusters (n = 2 – 8) was carried out, with the aim of identifying and characterizing the basic structural units that are suitable for describing the formation of gold nanoparticles. The selected clusters represent the basic building blocks on which more complex structures are based. The used "Kick" procedure proved to be a very effective and reliable tool, especially in terms of speed and precision in the search of the surface potential energy of tetramers, hexamers and octamers of gold. In addition, the applied theoretical level of DFT plays an important role in quantum chemical calculations, on which the results of the nature of the structures (minima or stationary points) depend.
As the number of gold atoms in the oligomers increased, an increase in the number of possible configurational and conformational isomers was recorded, which significantly increases the complexity of the system. 3 stable isomers were located for Au4 particles, 9 structures were located for Au6, and 19 structures were located for Au8, which were true minima. At the same time, with the increase in the number of gold atoms in the clusters, an increase in the range of relative energy differences between different clusters was recorded (for Au4 the range is about 42 kJ/mol, for Au6 170 kJ/mol and for Au8 about 140 kJ/mol), which further complicates identification of the most stable structures.
The presented stochastic search method, in combination with DFT calculations, proved to be extremely useful not only for understanding the structural diversity of small gold clusters, but also for wider application in the study of larger molecular systems. This methodology can also be effectively used to study interactions between localized isomers and biologically important compounds, opening possibilities for further research at the border of nanotechnology and biochemistry
Farmaceutski oblici i klinički aspekti antimigrenika
No full textCilj istraživanja
Cilj specijalističkog rada je analizirati farmaceutske oblike antimigrenika i njihove kliničke
aspekte. Od kliničkih aspekata navedene su terapijske indikacije, doziranje i način primjene,
kontraindikacije, interakcije, nuspojave, farmakodinamička i farmakokinetička svojstva
antimigrenika. U radu su prikazani farmaceutski oblici antimigrenika odobrenih na području
Europe i SAD-a te oblici koji su u fazi istraživanja i razvoja. Osim upotrebe farmakoterapije u
liječenju migrene ističe se primjena nefarmakoloških metoda kako u akutnoj tako i u
preventivnoj terapiji. Istaknuta je važnost kolaborativne prakse te uloge farmaceuta u
upravljanju migrenom kao najdostupnijeg dionika zdravstvenog sustava.
Materijal i metode
Za izradu ovog specijalističkog rada koristili su se relevantni stručni i znanstveni članci s
najnovijim saznanjima o suvremenim farmaceutskim oblicima antimigrenika. Relevantni članci
pretraživani su prema temi istraživanja od općih prema specijaliziranim te su proučavani na
analitički i kritički način. Izdvojeni su najvažniji rezultati, rasprave i zaključci koji su prikazani
ovim specijalističkim radom. Na temelju proučavanih članaka izvedena su vlastita razmatranja
proučavane problematike koja su dio rasprave. U svrhu pisanja specijalističkog rada, literatura
je pretraživana putem baze podataka PubMed, Hrčak, ScieceDirect, Frontiers te na mrežnim
stranicama regulatornih tijela (HALMED, HZZO, EMA, FDA).
Rezultati
Prema trećem izdanju Međunarodne klasifikacije glavobolja (ICHD-3) migrena se razvrstava u
skupinu primarnih glavobolja, a dijeli se na migrenu bez aure i migrenu s aurom. Migrena
pripada u jednu od najčešćih neuroloških bolesti. Migrena može biti epizodna ili kronična
prema učestalosti pojavljivanja.
Farmakoterapija migrene dijeli se na akutnu i preventivnu. U liječenju migrene koriste se
nespecifični i specifični lijekovi. Specifični lijekovi za liječenje migrene oblikovani su u razne
farmaceutske oblike i doze te pokazuju različita farmakološka svojstva. Odabir terapije za
liječenje migrene treba biti individualan.
Specifični lijekovi za akutno liječenje migrene su triptani i ditani (selektivni antagonisti
serotoninskih (5-hidroksitriptamin) receptora), gepanti (antagonisti receptora peptida
povezanog s kalcitoninskim genom (engl. calcitonin gene-related peptide, CGRP)) te alkaloidi
ražene glavice. Najčešće se primjenjuju oralnim putem (tableta, raspadljiva tableta za usta,
oralni liofilizat, raspadljivi film za usta) te u manjoj mjeri intranazalno (sprej za nos - otopina,
suspenzija, prašak) i supkutano (injekcija).
Specifično preventivno liječenje epizodne i kronične migrene provodi se monoklonskim
protutijelima na CGRP i CGRP receptor, koji se primjenjuju supkutano ili intravenski te
antagonistima CGRP-a, gepantima, koji se primjenjuju oralnim putem (tableta, oralni liofilizat).
Korištenje nefarmakoloških metoda liječenja migrene dovodi do smanjenja pojavnosti
migrene, povećanog učinka preventivne i akutne terapije te do izbjegavanja ili smanjenja
nuspojava primijenjenih lijekova.
Provođenjem kolaborativne prakse u koju je uključen javni ljekarnik, kao najdostupniji
zdravstveni djelatnik, povećava se adherencija bolesnika prema terapiji te postiže bolja
kvaliteta života bolesnika s migrenom. Uloga javnog ljekarnika je edukacija i savjetovanje
bolesnika o farmakološkim i nefarmakološkim metodama liječenja migrene. Provođenjem
ljekarničke skrbi, ljekarnici mogu pomoći u poboljšanju ishoda liječenja migrene.
Zaključak
Za uspjeh liječenja migrene potrebna je individualizacija terapije. Odabir antimigrenika treba
biti prema kliničkoj slici migrene bolesnika, kompetenciji za administraciju antimigrenika te
komorbiditetima.
Upravljanje migrenom je učinkovitije upotrebom antimigrenika s pouzdanom učinkovitošću, u
prikladnom farmaceutskom obliku i s odgovarajućim farmakološkim svojstvima.
Primjenom nefarmakoloških metoda te promjenom nepodržavajućeg načina života mogu se
poboljšati ishodi liječenja migrene te povećati aktivna uloga bolesnika u samom liječenju.
Nefarmakološke metode mogu se primijeniti samostalno te u kombinaciji s akutnom ili
preventivnom terapijom migrene.
Migrena predstavlja javnozdravstveni i socioekonomski problem. Za uspjeh terapije migrene
važna je kolaborativna praksa specijalista neurologa, liječnika opće medicine, javnog ljekarnika
te aktivno sudjelovanje bolesnika u upravljanju migrenom. Cilj je postizanje boljeg terapijskog
ishoda liječenja migrene te posredno smanjenje javnozdravstvenog i socioekonomskog
opterećenja. Ljekarničkim savjetovanjem bolesnika o pravilnoj i pravodobnoj primjeni
antimigrenika može se izbjeći glavobolja uzrokovana prekomjernom upotrebom lijekova te
posljedice koje nosi takav način samoliječenja.
Mogućnost izbora prikladnog farmaceutskom oblika antimigerenika s odgovarajućim kliničkim
aspektima unaprjeđuje zdravstvenu skrb za bolesnika s migrenom, racionalnu upotrebu
lijekova te postizanje boljih farmakoterapijskih učinaka antimigrenika.Objectives
The goal of the expert thesis is to analyze the pharmaceutical forms of antimigraine drugs and
their clinical aspects. Among the clinical aspects, therapeutic indications, dosage and method
of administration, contraindications, interactions, side effects, pharmacodynamic and
pharmacokinetic properties of antimigraine drugs are listed. The paper presents the
pharmaceutical forms of antimigraines approved in Europe and the USA, as well as the forms
that are in the research and development phase. In addition to the use of pharmacotherapy
in the treatment of migraine, the use of non-pharmacological methods in both acute and
preventive therapy stands out. The importance of collaborative practice and the role of
pharmacists in the management of migraine as the most accessible stakeholder in the health
care system were emphasized.
Materials and methods
Relevant professional and scientific articles with the latest knowledge about modern
pharmaceutical forms of antimigraine were used for the preparation of this specialist work.
Relevant articles were searched according to the research topic from general to specialized
and were studied in an analytical and critical way. The most important results, discussions and
conclusions presented in this specialist work have been highlighted. On the basis of the
studied articles, their own considerations of the studied issue were performed, which are part
of the discussion. For the purpose of writing a specialist paper, the literature was searched
through the databases PubMed, Hrčak, ScieceDirect, Frontiers and on the websites of
regulatory bodies (HALMED, HZZO, EMA, FDA).
Results
According to the third edition of the International Classification of Headache Disorders (ICHD3), migraine is classified in the group of primary headaches, divided into migraine without aura
and migraine with aura. Migraine belongs to one of the most common neurological diseases.
Migraine can be episodic or chronic according to the frequency of occurrence.
Pharmacotherapy of migraine is divided into acute and preventive. In the treatment of
migraine, non-specific and specific drugs are used. Specific drugs for the treatment of migraine
are formulated in various pharmaceutical forms and dosages and show different
pharmacological properties. The choice of therapy for the treatment of migraine should be
individual.
Specific drugs for the acute treatment of migraine are triptans and ditans (selective serotonin
(5-hydroxytryptamine) receptor antagonists), gepants (calcitonin gene-related peptide (CGRP)
receptor antagonists) and ryegrass alkaloids. They are most often administered orally (tablet,
disintegrating oral tablet, oral lyophilizate, disintegrating oral film) and to a lesser extent
intranasally (nasal spray – solution, suspension, powder) and subcutaneously (injection).
Specific preventive treatment of episodic and chronic migraine is carried out with monoclonal
antibodies to CGRP and CGRP receptor, which are administered subcutaneously or
intravenously, and CGRP antagonists, gepants, which are administered orally (tablet, oral
lyophilisate).
The use of non-pharmacological methods of migraine treatment leads to a reduction in the
incidence of migraine, an increased effect of preventive and acute therapy, and the avoidance
or reduction of side effects of the drugs used.
By implementing a collaborative practice in which the public pharmacist is involved, as the
most accessible healthcare professional, the patient's adherence to therapy increases and the
quality of life of migraine patients is improved. The role of the public pharmacist is to educate
and advise patients on pharmacological and non-pharmacological methods of migraine
treatment. By implementing pharmacy care, pharmacists can help improve migraine
treatment outcomes.
Conclusion
The success of migraine treatment requires individualization of therapy. The choice of
antimigraine should be based on the clinical picture of the patient's migraine, the competence
for antimigraine administration and comorbidities.
Migraine management is more effective by using antimigraine drugs with reliable efficacy, in
a suitable pharmaceutical form and with appropriate pharmacological properties.
By applying non-pharmacological methods and changing an unsupportive lifestyle, the
outcomes of migraine treatment can be improved and the patient's active role in the
treatment itself can be increased. Non-pharmacological methods can be applied
independently and in combination with acute or preventive migraine therapy.
Migraine represents a public health and socioeconomic problem. For the success of migraine
therapy, the collaborative practice of specialist neurologists, general practitioners, public
pharmacists and the active participation of patients in migraine management is important.
The goal is to achieve a better therapeutic outcome of migraine treatment and indirectly
reduce the public health and socioeconomic burden. By advising patients at the pharmacy on
the correct and timely use of antimigraine drugs, headaches caused by overuse of drugs and
the consequences of such self-medication can be avoided.
The possibility of choosing a suitable pharmaceutical form of antimigraine drug with
appropriate clinical aspects improves health care for patients with migraine, the rational use
of drugs and the achievement of better pharmacotherapeutic effects of antimigraine drugs