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Pharmacotherapeutic approach to the treatment of irritable bowel syndrome
No full textSindrom iritabilnog crijeva je kompleksna gastrointestinalna bolest i najčešći funkcionalni poremećaj crijeva. Bolest se manifestira različitim simptomima uključujući promjenu u broju i obliku stolica, bolovima u trbuhu, nadutosti i ponekada simptomima izvan gastrointestinalnog sustava. Etiopatogeneza bolesti je multifaktorijalna i uključuje različite genetske, mikrobiološke, imunološke, hormonalne i psihološke čimbenike. Dijagnoza SIC-a se postavlja isključivanjem drugih organskih bolesti i praćenjem Rimskih kriterija IV. Upravljanje SIC-om uključuje različite terapijske pristupe, farmakološke i nefarmakološke. Farmakološki pristupi obuhvaćaju laksative, antidijaroike, spazmolitike, antidepresive i ponekad antibiotike. Nefarmakološki pristupi podrazumijevaju prilagodbu prehrambenih navika, korištenje određenih dodataka prehrani i probiotika, redovitu tjelovježbu i psihoterapiju. Važno je istaknuti individualizirani pristup liječenju koji je ključan kod SIC-a, jer se simptomi bolesti i odgovor na terapiju razlikuju između pacijenata. Potrebna su daljnja istraživanja kako bi se bolje razumjeli mehanizmi ove bolesti i razvili učinkovitiji terapijski pristupi i podigla kvaliteta života bolesnika koji pate od sindroma iritabilnog crijeva.Irritable bowel syndrome (IBS) is a complex gastrointestinal disorder and the most common functional bowel disorder. The disease manifests with various symptoms including changes in bowel habits, abdominal pain, bloating, and sometimes extra-intestinal symptoms. The etiopathogenesis of the disease is multifactorial and includes various genetic, microbiological, immunological, hormonal, and psychological factors. The diagnosis of IBS is established by excluding other organic diseases and following the Rome IV criteria. Management of IBS involves various therapeutic approaches, both pharmacological and non-pharmacological. Pharmacological approaches include laxatives, anti-diarrheal agents, spasmolytics, antidepressants, and sometimes antibiotics. Non- pharmacological approaches include dietary modifications, the use of specific dietary supplements and probiotics, regular exercise, and psychotherapy. It is important to emphasize the individualized approach to treatment, which is crucial in IBS, as symptoms and response to therapy vary among patients. Further research is needed to better understand the mechanisms of this disease and to develop more effective therapeutic approaches to improve the quality of life of patients suffering from irritable bowel syndrome
Hyaluronate/mannitol microspheres for nasal prednisolone delivery
No full textNazalna primjena kortikosteroida uobičajena je u ublažavanju simptoma upalnih bolesti nosne sluznice poput rinitisa, rinosinuitisa i nosnih polipa. Lokalnom primjenom kortikosteroida smanjuje se rizik od nuspojava, osigurava se brži nastup djelovanja i precizno doziranje. Trenutno registrirani oblici nazalnih kortikosteroida su otopine i suspenzije koje se nakon primjene kratko zadržavaju na mjestu djelovanja. Razvojem praškastih farmaceutskih oblika osigurava se dulje zadržavanje i veća koncentracija lijeka na mjestu primjene.
Cilj ovog diplomskog rada bio je pripraviti manitolsko-hijaluronske mikrosfere s uklopljenim prednizolonfosfatom. Mikrosfere su pripravljene metodom sušenja raspršivanjem. Određivanjem fizičko-kemijskih svojstava mikrosfera ispitan je utjecaj masenog udjela prednizolonfosfata na svojstva mikrosfera. Ispitana su reološka svojstva otopina koje su sadržavale različiti udio natrijevog hijaluronata (0,05 %-0,5 %, m/m) i konstantan udio prednizolona (0,1 %, m/m) i manitola (6 %, m/m).
Iz početnih otopine koje su sadržavale konstantan udio natrijevog hijaluronata (0,05 %, m/m) i manitola (6 %, m/m) te udio prednizolona od 0,05 % do 0,15 % (m/m) uspješno su pripravljene mikrosfere metodom sušenja raspršivanjem. Iskorištenje procesa smanjivalo se povećanjem udjela prednizolona u mikrosferama od 54,96 % do 42,65 %. Uspješnost uklapanja prednizolona iznosila je od 84,68 % do 98,79 %, dok je sadržaj prednizolona u ukupnoj masi mikrosfera iznosio od 0,69 % do 2,37 %. Udio čestica manjih od 10 μm,iznosio je od 4,2 ± 0,3 % do 19,7 ± 0,2 %. Udio vlage u praškastim uzorcima povećavao se s povećanjem udjela prednizolona od 1,64 % do 2,55 % (m/m). Vrijednosti zeta potencijala iznosile su se od -9,3 ± 0,6 do -15,1 ± 1,4 mV. Hausnerov omjer određivan je za usporedbu svojstva tečenja mikrosfera te je uočeno da se povećanjem udjela prednizolona Hausnerov omjer smanjuje. Iznosio je od 1,553 ± 0,129 do 1,889 ± 0,192. U procesu bubrenja u SNF-u mikrosfere s većim udjelom prednizolona pokazuju smanjeni kapacitet bubrenja. Reološkom karakterizacijom otopina natrijevog hijaluronata, manitola i prednizolona utvrđeno je da se uzorci ponašaju kao pseudoplastični sustavi. Dodatak 0,1 % (m/m) prednizolona u otopinu s 0,5 % (m/m) natrijevog hijaluronata i 6 % (m/m) manitola smanjuje viskoznost otopine.Nasal administration of corticosteroids is common in reducing symptoms of inflammatory diseases of the nasal mucosa like rhinitis, rhinosinusitis and nasal polyps. Local application of corticosteroids reduces the risk of side effects, ensures faster onset of action and precise dosing. Currently registered forms of nasal corticosteroids are solutions and suspensions that exhibit short retention time at the site of action. The development of powder pharmaceutical forms ensures longer retention and a higher concentration of the drug at the site of application.
The aim of this study was to prepare hyaluronate and mannitol-based microspheres with incorporated prednisolone phosphate. The microspheres were prepared using the spray drying method. The influence of the prednisolone phosphate content on the characteristics of the microspheres was examined by determining their physicochemical properties. The rheological properties were also examined for solutions containing a variable concentration of sodium hyaluronate (0.05 %-0.05 %, w/w) along with a constant prednisolone (0.1 %, w/w) and mannitol (6 %, w/w) concentration.
Microspheres were successfully prepared by the spray drying method from the feed solutions containing a sodium hyaluronate (0.05 %, w/w), mannitol (6 %, w/w), and prednisolone (0.05 to 0.15 %, w/w). The process yield decreased with increasing prednisolone content from 54.96 % to 42.65 %. Drug entrapment efficiency ranged from 84.68 % to 98.79 %, while the microspheres drug loading varied from 0.69 % to 2.37 %. The fraction of particles smaller than 10 μm was ranging from 4.2 ± 0.3 % to 19.7 ± 0.2 %. The moisture content in the powdered samples slightly increased from 1.64 % to 2.55 % (w/w) with the increase in prednisolone content. Zeta potential values ranged from
-9.3 ± 0.6 mV to -15.1 ± 1.4 mV. The Hausner ratio was determined to compare the flow properties of the microspheres and it was observed that the Hausner ratio decreased with increasing prednisolone content. It ranged from 1.553 ± 0.129 to 1.889 ± 0.192. In the swelling process in SNF, microspheres with higher prednisolone content showed reduced swelling capacity. Rheological characterization of sodium hyaluronate, mannitol, and prednisolone solutions showed that the samples behave as pseudoplastic systems. The addition of 0.1 % (w/w) prednisolone to a solution with 0.5 % (w/w) sodium hyaluronate and 6 % (w/w) mannitol reduces the viscosity of the solution
Utjecaj umjetne inteligencije na kontrolu kakvoće lijekova u farmaceutskoj industriji
No full textCilj istraživanja
U posljednjem desetljeću, umjetna inteligencija (engl. Artificial Intelligence, AI) unaprijedila
je mnoge industrije, a farmaceutska industrija nije iznimka. Primjena umjetne inteligencije u
kontroli kakvoće lijekova otvara nove horizonte u učinkovitosti, preciznosti i smanjenju
troškova. Ovaj tehnološki napredak omogućava bržu i točniju analizu podataka o kvaliteti
lijekova koja je važna za sigurnost pacijenta. Cilj ovog istraživanja, temeljen na pregledu
dostupne literature, je dublje razumijevanje kako umjetna inteligencija može unaprijediti
procese u kontroli kakvoće lijekova. Umjetna inteligencija, primjerice, može automatski
prepoznati i klasificirati nepravilnosti u sastavu lijeka, što značajno smanjuje rizik od ljudske
pogreške. Međutim, unatoč brojnim prednostima, postoje i izazovi u integraciji tih tehnologija
u postojeće sustave, uključujući pitanja kompatibilnosti, potrebe za specijaliziranim znanjima i
etičke dileme. Nadalje, s razvojem tehnologija umjetne inteligencije mijenjaju se i regulatorni
zahtjevi, postavljajući nove standarde za sukladnost u farmaceutskoj industriji. U tom kontekstu,
daljnje istraživanje i razvoj tehnologija umjetne inteligencije bit će ključni za ostvarivanje
punog potencijala u poboljšanju kontrole kakvoće lijekova.
Materijal i metode
Istraživanja provedena u okviru ovog specijalističkog rada teorijski su usmjerena. Tijekom
izrade, literatura je odabrana i analizirana s obzirom na njezinu relevantnost za temu i predmet
istraživanja, uzimajući u obzir autore i publikacije u časopisima i knjigama. Pretraživanje je
obuhvatilo širok spektar literature, od općih članaka do specijaliziranih radova i aktualnih
smjernica regulatornih tijela. Za potrebe istraživanja literature korištene su baze podataka kao
što su PubMed, Science Direct, ResearchGate, Scopus i Web of Science.
Rezultati
Rezultati provedenog teorijskog istraživanja i analiza stručne literature ukazuju na to da
umjetna inteligencija pruža značajna unapređenja u procesima analize kvalitete lijekova,
osobito kroz povećanje učinkovitosti, preciznosti i smanjenje operativnih troškova. Međutim,
unatoč evidentnim prednostima, integracija umjetne inteligencije u postojeće sustave u
farmaceutskoj industriji donosi određene izazove. Ti izazovi uključuju problematiku
kompatibilnosti nove tehnologije s već postojećim sustavima, potrebu za specijaliziranim
tehničkim znanjem te utječu na promjene u regulatornim zahtjevima. Nadalje, istraživanje
ukazuje na potrebu kontinuiranog istraživanja i razvoja u području umjetne inteligencije, kako
bi se u potpunosti iskoristili njeni potencijali u unapređenju procesa kontrole kvalitete lijekova.
Zaključak
Integracija umjetne inteligencije u farmaceutsku industriju otvara nove mogućnosti za
optimizaciju procesa kontrole kvalitete lijekova, otkrivanje nedostataka, odstupanja, toksičnosti,
krivotvorina te unaprjeđenje farmakovigilancije. Kroz ovo istraživanje, pokazano je da umjetna
inteligencija može značajno unaprijediti preciznost i učinkovitost u analizi kvalitete lijekova,
smanjujući rizik od ljudskih pogrešaka i poboljšavajući sigurnost pacijenata. Unatoč trenutnih
izazova integracije umjetne inteligencije u farmaceutsku industriju te nedostatku regulatornih
okvira, kontinuiranim istraživanjem i prilagodbom, ona ima potencijal unaprijediti industriju,
poboljšavajući ne samo proizvodne procese već i dajući sigurnija i učinkovitija zdravstvena
rješenja.Objectives
In the last decade, artificial intelligence (AI) has advanced many industries, and the
pharmaceutical industry is no exception. The application of artificial intelligence in drug quality
control opens new horizons in efficiency, precision, and cost reduction. This technological
advancement enables faster and more accurate analysis of drug quality data, which is important
for patient safety. The goal of this research, based on a review of available literature, is to gain
a deeper understanding of how artificial intelligence can improve processes in drug quality
control. Artificial intelligence, for instance, can automatically recognize and classify
irregularities in drug composition, significantly reducing the risk of human error. However,
despite numerous advantages, there are also challenges in integrating these technologies into
existing systems, including issues of compatibility, the need for specialized knowledge, and
ethical dilemmas. Furthermore, with the development of artificial intelligence technologies,
regulatory requirements are also changing, setting new standards for compliance in the
pharmaceutical industry. In this context, through the review of available literature, further
research and development of artificial intelligence technologies will be key to realizing the full
potential in improving drug quality control.
VI
Material and Methods
The research conducted within the framework of this specialist work is theoretically oriented.
During its development, literature was selected and analyzed based on its relevance to the theme
and subject of the research, taking into account authors and publications in journals and books.
The search covered a wide range of literature, from general articles to specialized works and
current guidelines from regulatory bodies. Databases such as PubMed, Science Direct,
ResearchGate, Scopus, and Web of Science were used for the purpose of researching literature.
Results
The results of the conducted theoretical research and analysis of the professional literature
indicate that artificial intelligence provides significant improvements in the processes of drug
quality analysis, especially through increasing efficiency, precision, and reducing operational
costs. However, despite the evident advantages, the integration of artificial intelligence into
existing systems in the pharmaceutical industry presents certain challenges. These challenges
include issues of compatibility of the new technology with existing systems, the need for
specialized technical knowledge, and the impact on changes in regulatory requirements.
Furthermore, the research points to the need for continuous research and development in the
field of artificial intelligence in order to fully utilize its potentials in improving the processes
of drug quality control.
Conclusion
The integration of artificial intelligence into the pharmaceutical industry opens new
opportunities for optimizing drug quality control processes, detecting defects, deviations,
toxicity, counterfeits, and improving pharmacovigilance. Through this theoretical research, it
has been shown that artificial intelligence can significantly enhance precision and efficiency in
drug quality analysis, reducing the risk of human errors and improving patient safety. Despite
the current challenges of integrating artificial intelligence into the pharmaceutical industry and
the lack of regulatory frameworks, with continuous research and adaptation, it has the potential
to enhance the industry, improving not only production processes but also providing safer and
more effective healthcare solutions
Voltammetric methods for the analysis of beta blockers
No full textBeta blokatori su skupina lijekova koji se propisuju kod različitih kardiovaskularnih bolesti, no često se koriste i kao doping sredstva u raznim sportovima pa je iz tog razlogavrlo važno razviti jednostavne, precizne i osjetljive metode za njihovo određivanje. Elektroanalitičke metode imaju značajnu ulogu i često su korištene metode u svrhu određivanja ove vrste lijekova.
U ovom radu dan je pregled radova odabranih različitih voltametrijskih metoda i razvijenih elektrokemijskih senzora dobivenih modifikacijom ugljikovih elektroda za određivanje beta blokatora. Pritom su u ispitivanjima najčešće korištene diferencijalna pulsna voltametrija te pravokutnovalna voltametrija, a od elektroda upotrebljavaju se ugljikova staklasta elektroda, elektroda od ugljikove paste, elektroda od grafitne mine te dijamantna elektroda s primjesama bora. Za modifikaciju površina elektroda najčešće se koriste raznovrsni nanomaterijali, koji se nanose zasebno ili u kombinacijama, s ciljem poboljšanja svojstava elektroaktivnih površina i izvedbenih značajki razvijenih elektroanalitičkih metoda za određivanje beta blokatora. Nanocjevčice ugljika često se koriste kao modifikatori površina ugljikovih elektroda, a njihova upotreba omogućuje nižu granicu detekcije odnosno veću osjetljivost zbog povećanja elektroaktivne površine i njihove elektrokatalitičke aktivnosti. Najčešće upotrijebljena elektroda u analizama beta blokatora jest ugljikova staklasta elektroda čija se površina često modificira s ciljem poboljšanja parametra poput osjetljivosti, selektivnosti i reproducibilnosti.Beta blockers are a group of drugs that are prescribed for various cardiovascular diseases, but they are also often used as doping agents in some sports, so for this reason
it is very important to develop a simple, precise and sensitive method for their determination. Electroanalytical methods play a significant role and are often used for determining this type of drugs.
This paper provides an overview of selected different voltammetric methods and developed electrochemical sensors obtained by modifying carbon electrodes for the determination of beta blockers. Differential pulse voltammetry and square wave voltammetry were mostly used in the tests, and the electrodes used were glassy carbon electrode, carbon paste electrode, pencil graphite electrode and boron-doped diamond electrode. Various nanomaterials are most often used to modify electrode surfaces, which are applied separately or in combinations, with the aim of improving the properties of electroactive surfaces and the performance characteristics of developed electroanalytical methods for determining beta blockers. Carbon nanotubes are often used as surface modifiers of carbon electrodes, their use enables a lower detection limit and greater sensitivity due to the increase of the electroactive surface and their electrocatalytic activity. The most commonly used electrode in beta blocker analyzes is glassy carbon electrode whose surface is often modified in order to improve parameters such as sensitivity, selectivity and reproducibility
Optimization of superoxide radical measurement by fluorescence microscopy
No full textSuperoksidni radikal (O2∙−) primarni je kisikov radikal, koji u glavnini nastaje tijekom procesa
oksidativne fosforilacije u mitohondrijima i pokreće kaskadu stvaranja drugih reaktivnih kisikovih
vrsta (ROS) u stanici. Neravnoteža između stvaranja ROS-ova i mogućnosti biološkog sustava da ih
detoksificira i da popravlja štetu koja je u nastanku, dovodi do oksidacijskog stresa (OS), koji je
povezan s razvojem mnogih bolesti. Zbog pretpostavke da je O2∙− potencijalno koristan u procjeni
razine OS-a i činjenice da bi mjerenje O2∙− moglo imati dijagnostičku svrhu, cilj ovog rada bio je
optimizirati metodu za mjerenje O2∙− u stanicama na fluorescentnom mikroskopu. Za detekciju O2∙−
korištena je fluorescentna proba dihidroetidij (DHE), a pokus je proveden na bukalnim stanicama.
U prvom je koraku istraživanja optimizirana metoda mjerenja O2∙− u stanicama, u smislu
koncentracije DHE i vremena inkubacije stanica s DHE. Rezultati su pokazali da su optimalni uvjeti
za mjerenje O2∙− u stanicama 10-minutna inkubacija stanica na sobnoj temperaturi (25ºC) s otopinom
DHE u koncentraciji od 20 μM zbog najoptimalnijeg obojenja citoplazme. Nakon toga je
optimizirana metoda primijenjena za mjerenje O2∙− u stanicama koje su tretirane s H2O2 da bi se
inducirao OS. Potvrđeno je da je H2O2 uspješan induktor OS-a, odnosno da uspješno potencira
stvaranje O2∙− u stanicama. Do indukcije povišene razine O2∙− u bukalnim stanicama došlo je nakon
10-minutne inkubacije stanica s 30 mM otopinom H2O2. Razvijenu je metodu moguće primijeniti za
praćenje razine O2∙−, a time i OS-a, u stanicama.The superoxide radical (O2∙−) is the primary oxygen radical, predominantly formed during the process of
oxidative phosphorylation in mitochondria, and it initiates a cascade of other reactive oxygen species
(ROS) production in the cell. An imbalance between ROS production and the biological system's ability
to detoxify them and repair the resulting damage leads to oxidative stress (OS), which is associated with
the development of many diseases. Due to the assumption that O2∙− could be potentially useful in
assessing OS levels and the fact that measuring O2∙− could have diagnostic purposes, the aim of this
study was to optimize a method for measuring O2∙− in cells using a fluorescent microscope. The
fluorescent probe dihydroethidium (DHE) was used for detecting O2∙−, and as experimental model,
buccal cells were used. In the first step of the research, the method for measuring O2∙− in cells was
optimized in terms of DHE concentration and cell incubation time with DHE. Results indicate that the
optimal conditions for measuring O2∙− in cells are 10 minutes incubation of cells at room temperature
(25ºC) with a DHE solution at a concentration of 20 μM for the most optimal cytoplasmic staining.
Subsequently, the optimized method was applied to measure O2∙− in cells treated with H2O2 to induce
OS. It was confirmed that H2O2 is a successful inducer of OS, meaning that it effectively enhances the
production of O2∙− in cells. Elevated levels of O2∙− in buccal cells were induced after 10 minutes
incubation of the cells with a 30 mM H2O2 solution. The developed method can be applied to monitor
O2∙− levels and, consequently, OS in cells
Endocrine disrupting effects of mixtures containing plastic nanoparticles and selected pharmaceuticals in vitro
No full textPretjerano korištenje i loše gospodarenje plastikom, doveli su do onečišćenja okoliša nanočesticama plastike (engl. plastic nanoparticles, PNP). Iako broj istraživanja o štetnim učincima PNP raste, nedostaju pouzdane informacije o učincima PNP na ljudsko zdravlje, posebice interakcijama s endokrinim sustavom. Osim PNP, okoliš je onečišćen i brojnim lijekovima. Paracetamol, ibuprofen, karbamazepin i fluoksetin svrstavaju su među lijekove koji su u okolišu kvantificirani u znatnim količinama. PNP mogu adsorbirati lijekove te činiti složene smjese čije djelovanje još nije istraženo. Unatoč tome, prisutnost okolišnih onečišćivala u složenim smjesama zanemaruje se te se primarno ispituje učinak pojedinačnih tvari. Cilj istraživanja bio je utvrditi endokrino disruptivne učinke složenih smjesa PNP i lijekova. Istraživanje se temelji na ispitivanju učinaka na aktivnost estrogenskog receptora (ER) i proces steroidogeneze. Složene smjese pripremljene su miješanjem lijekova i/ili nanočestica polistirena, polipropilena i polietilena. PNP su karakterizirane obzirom na oblik, veličinu, raspodjelu veličina i ζ potencijal. Učinci pojedinih tvari i njihovih smjesa na preživljenje stanica ispitani su pomoću MTS testa i protočnom citometrijom. Unos PNP u stanice određen je metodom protočne citometrije. Učinci na ER aktivaciju ispitani su luciferaznim testom prema OECD smjernici 455, a utjecaj na proces steroidogeneze qPCR-om i LC-MS/MS metodom prema OECD smjernici 456. Dobiveni rezultati pokazali su da se učinci pojedinačnih tvari značajno razlikuju u odnosu na učinke složenih smjesa. Smjese PNP i lijekova pokazale su znatno jače toksične i endokrino disruptivne učinke. Binarne i tercijarne smjese lijekova pokazuju složeni odnos doze i biološkog odgovora koji ovisi o sastavu smjese.Excessive use and inadequate management of plastic have led to environmental pollution with plastic nanoparticles (PNP). Although the number of studies on the adverse effects of PNP is increasing, there is a lack of reliable information on the effects of PNP on human health, especially their interactions with the endocrine system. In addition to PNP, the environment is also polluted with numerous drugs. Paracetamol, ibuprofen, carbamazepine and fluoxetine are among the drugs that are quantified in the environment in significant quantities. PNP can adsorb drugs and form complex mixtures whose action has not been investigated. Despite this, the presence of environmental pollutants in complex mixtures is neglected and the primary focus is on the effect of individual substances. The aim of the research was to determine endocrine disrupting effects of complex mixtures of PNP and drugs. Research is based on the examination of the effects on the estrogen receptor (ER) acitivity and the process of steroidogenesis. Complex mixtures were prepared by mixing drugs and/or nanoparticles of polystyrene, polypropylene and polyethylene. PNPs are characterized by means of shape, size, size distribution and ζ potential. The effects of individual substances and their mixtures on cell survival were tested using the MTS assay and flow cytometry. PNP uptake into cells was determined by flow cytometry. The effects on ER activation were tested with the luciferase assay and OECD Guideline No. 455, and the influence on the steroidogenesis with qPCR and the LC-MS/MS method and OECD Guideline No. 456. The obtained results showed that the effects of individual substances differ significantly compared to the effects of complex mixtures. Mixtures of PNP and drugs showed significantly stronger toxic and endocrine disrupting effects. Binary and ternary mixtures of drugs show a complex dose-biological response relationship that depends on the composition of the mixture
Calmodulin based identification of airborne fungi from the genera Aspergillus, Penicillium and Talaromyces in a damp-damaged living environment
No full textPlijesni rodova Aspergillus, Penicillium i Talaromyces su jedni od najčešćih gljivičnih zagađivača stambenih prostora oštećenih vlagom koji predstavljaju značajan rizik za zdravlje ukućana s obzirom da mogu uzrokovati brojne akutne, ali i kronične zdravstvene posljedice. Da bi se procijenio obujam zagađenja prikupljeni su uzorci zraka u stanu s vidljivim porastom plijesni, kao i u neposrednoj blizini u svrhu kontrole. Od plijesni izoliranih iz uzoraka izdvojene su one rodova Penicillium, Aspergillus i Talaromyces u svrhu daljnje analize. Identificirane su do razine vrste sekvenciranjem dijela gena za kalmodulin (CaM) i usporedbom dobivenih nukleotidnih slijedova s podacima NCBI baze podataka. Među aspergilima (13/35) je dominirao A. jensenii (9/13), a identificirani su i A. creber (1/13), A. puulaauensis (1/13), A. welwitschiae (1/13) te A. aureolatus (1/13). P. chrysogenum/rubens je bila najzastupljenija vrsta roda Penicillium (8/24) od kojih su 2 uzorka identificirana iz vanjskog zraka. Preostale penicilije uključuju P. expansum (3/24), P. polonicum (2/24), P. speluncae (2/24), P. allii (1/24), P. commune (1/24) i P. digitatum (1/24). Po jedan od svakog izolata P. biourgeianum, P. brevicompactum te P. kongii su identificirani samo iz uzoraka vanjskog zraka. Jedini izolat roda Talaromyces je identificiran kao T. wortmannii. Iako CaM pruža precizniju identifikaciju od ITS molekularnog markera, ne može se primijeniti u razlučivanju vrsta P. commune od P. palitans i P. camemberti, kao i P. chrysogenum i P. rubens. Prema dostupnoj literaturi, identificirane vrste ukazuju na značajan zdravstveni rizik izloženim stanarima primarno zbog zabrinjavajućeg profila sekundarnih metabolita. Rezultati naglašavaju povezan dugoročni zdravstveni rizik asociran s boravkom u vlažnim stambenim prostorima s vidljivom porastom plijesni, a ukazuju i na potrebu za daljnjim istraživanjima s obzirom na prevalentnost tog problema.Fungi from the genera Aspergillus, Penicillium, and Talaromyces are among the most prevalent fungal contaminants found in damp-damaged living environment, posing significant health risks to inhabitants. These fungi can trigger various acute and chronic health issues. To assess the extent of contamination, indoor air samples were collected from an apartment with visible mould growth and outdoor air samples were collected as a control Among all the isolated fungi, those affiliated with the genera Aspergillus, Penicillium, and Talaromyces were specifically selected for further analysis. Identification was carried out at the species level utilizing partial calmodulin (CaM) gene sequencing, with obtained nucleotide sequences compared against the NCBI database. Among Aspergilli (13/35 isolates) A. jensenii was the most dominating species (9/13) while there was only one isolate each of A. creber, A. puulaauensis, A. aureolatus and A. welwitschiae. P. chrysogenum/rubens was the most frequent Penicillium species (8/24), two of which were from outdoor air samples. Other Penicillia included P. expansum (3/24), P. polonicum (2/24), P. speluncae (2/24), P. allii (1/24), P. commune (1/24) and P. digitatum (1/24). One of each isolates of P. biourgeianum, P. brevicompactum and P. kongii were only only identified among outdoor air isolates. The single isolate assigned to the Talaromyces sp. was identified as T. wortmannii. Although CaM provided more precise species identification compared to the the ITS molecular marker, it showed a limitation in distingishing P. commune from P. palitans and P. camemberti as well as P. chrysogenum and P. rubens. Based on the available literature, the identified species pose a significant health threat to occupants exposed to them, primarily due to their concerning array of secondary metabolites. This underscores a related long-term health risk associated with residing in damp and mouldy housing. Moreover, it highlights the necessity for additional research, given the prevalence of this issue
Mechanical property analysis of dietary supplements containing phytoestrogens
No full textUporaba dodataka prehrani sve je zastupljenija kao dio zdravog života, zbog čega se javlja sve veći
broj dostupnih pripravaka na tržištu. Važno je imati na umu da se kvaliteta različitih dodataka
prehrani može bitno razlikovati, što znači da njihova učinkovitost neće biti jednaka. Kako bi se
osigurala učinkovitost, ali i sigurnost primjene dodataka prehrani potrebno je poznavati o kojim
svojstvima ovisi njihova kvaliteta te redovito provoditi ispitivanja tih svojstava. Mehanička svojstva
gotovih pripravaka i sirovina korištenih u njihovoj proizvodnji vrlo su bitna svojstva o kojima ovisi
funkcionalnost pripravaka.
Cilj ovog ispitivanja bio je ispitati mehanička svojstva skupine dodataka prehrani i sirovina koje
sadrže fitoestrogene. Ispitani su gotovi pripravci u obliku tableta i kapsula, kojima su određene
varijabilnost masa, rastrošljivost te raspadljivost, kao i prašci koji se koriste kao sirovine u
proizvodnji dodataka prehrani, kojima je ispitana nasipna gustoća i gustoća nakon potresanja te su
izračunati Hausnerov omjer i indeks kompresibilnosti.
U ispitivanju varijabilnosti mase sve ispitane kapsule imale su odstupanje od prosječne mase uzorka
unutar dozvoljenih granica od 10 %. Ispitane tablete također su imale odstupanje od prosječne mase
unutar dozvoljenih granica od 5 %. U ispitivanju rastrošljivosti kod ispitivanih tableta zabilježeno
je smanjenje mase tableta koje je bilo unutar dozvoljenih granica od 1 %. U ispitivanju raspadljivosti
svi uzorci u obliku kapsula raspali su se unutar propisanog vremena od 30 minuta. Kod uzorka u
obliku tableta 5 ispitanih tableta nije se u potpunosti raspalo unutar propisanog vremenskog
intervala. Jedan od ispitanih prašaka imao je svojstva tečenja klasificirana kao prolazna, dok su
preostala dva praška imala svojstva tečenja klasificirana kao vrlo loša.The use of dietary supplements is more and more prevalent as a part of a healthy lifestyle, which
causes and increase of the number of products available on the market. It’s important to keep in
mind that that the quality of different dietary supplements can vary greatly, which means their
efficacy won’t be equal. To ensure efficacy, but also safety of dietary supplement use it’s necessary
to know which properties affect their quality and regularly perform tests of those properties.
Mechanical properties of end products and raw materials used in their manufacture are very
important properties that affect performance of dietary supplements.
The aim of this study was to test the mechanical properties of a group of dietary supplements and
raw materials containing phytoestrogens. End products in the form of tablets and capsules were
tested, determining their mass variability, friability, and disintegration, as well as powders that can
be used in manufacture of dietary supplements, which had their bulk density and tapped density
tested, based on which their Hausner ratio and compressibility index were calculated.
In mass variability testing all tested capsules deviated from the corresponding average mass within
the allowed limit of 10%. The tested tablets also deviated from the average mass within the allowed
limit of 5%. In friability testing the tested tablets showed the loss of mass within the allowed limit
of 1%. In disintegration testing all samples in the form of hard capsules disintegrated within the
prescribed time frame of 30 minutes. For the sample in the form of tablets, 5 tested tablets failed to
fully disintegrate within the prescribed time frame of 30 minutes. One of the tested powder samples
had passable flow properties, while the other two samples very poor flow properties
Kinetics and mechanism of the reaction of L-ascorbic acid and p-benzoquinone
No full textL-askorbinska kiselina (vitamin C) je poznati antioksidans prisutan u voću i povrću. Svoj terapijski potencijal ostvaruje ne-enzimskom redukcijom slobodnih radikala. Moguća je njena primjena u organskim redoks reakcijama, npr. redukcija p-benzokinona. p-Benzokinon pripada skupini kinona, koji su poznati zbog svog antitumorskog, antibiotskog i fungicidnog djelovanja. Kombinacija askorbinske kiseline i kinona se razmatra zbog svoje potencijalne primjene u antitumorskoj terapiji. U ovom je diplomskom radu ispitana kinetika i mehanizam reakcije L-askorbinske kiseline i p-benzokinona radi boljeg razumijevanja reakcijskog mehanizma, ali i dodatnog opisivanja ova 2 reaktanta. Istraživanje kinetike i mehanizma ove reakcije provedeno je u čistoj vodi. Konstanta brzine reakcije L-askorbinske kiseline i p-benzokinona u vodi pri 25⁰C iznosi 415,7 ± 4,1 dm3 mol-1 s-1. Isto tako su izmjerene konstante brzine za ovu reakciju pri različitim temperaturama, u rasponu 15-40⁰C. Na temelju dobivenih rezultata prikazane su Arrheniusove i Eyringove ovisnosti konstante brzine o temperaturi iz kojih su određeni aktivacijski parametri. Arrheniusovi aktivacijski parametri iznose: Ea = 31,49 ± 1,89 kJ mol-1 i A= 1,368 ∙ 108. Eyringovi aktivacijski parametri iznose: ΔH‡ = 29,00 ± 1,89 kJ mol-1, ΔS‡= -97,53 ± 6,27 J K-1 mol-1 i ΔG‡ = 58,08 ± 2,66 kJ mol-1 pri 25⁰C. Određen je i kinetički izotopni efekt (KIE) za reakciju pri 25⁰C te iznosi 2,65 ± 0,10 i potvrđuje da u stupnju koji određuje brzinu reakcije dolazi do prijelaza protona. U konačnici je provedena termokemijska analiza reakcije te su stupnjeviti reakcijski mehanizmi (PT/ET i ET/PT) odbačeni kao mogući mehanizmi prijelaza protona i elektrona. Predloženi mehanizam je CPET.L-ascorbic acid (vitamin C) is a well-known antioxidant present in fruits and vegetables. It achieves its therapeutic potential by non-enzymatic reduction of free radicals. It can be used in organic redox reactions, e.g. reduction of p-benzoquinone. p-Benzoquinone is a part of the group quinones, which are known for their antitumor, antibiotic and fungicidal activity. Combination of ascorbic acid and quinones is considered for its potential use in antitumor therapy. In this thesis, the kinetics and mechanism of the reaction of L-ascorbic acid and p-benzoquinone were examined for a better understanding of the reaction mechanism, but also for an additional description of these 2 reactants. Research of the kinetics and mechanism of this reaction was performed in pure water. The reaction rate constant of L-ascorbic acid and p-benzoquinone in water at 25⁰C is 415.7 ± 4.1 dm3 mol-1 s-1. The rate constants for this reaction were also measured at different temperatures, in the range 15-40⁰C. Based on the obtained results, the Arrhenius and Eyring plots of the rate constants against temperatures are presented, from which the activation parameters were determined. Arrhenius activation parameters are: Ea = 31.49 ± 1.89 kJ mol-1 and A= 1.368 ∙ 108. Eyring's activation parameters are: ΔH‡ = 29.00 ± 1.89 kJ mol-1, ΔS‡= -97.53 ± 6.27 J K-1 mol-1 and ΔG‡ = 58.08 ± 2.66 kJ mol-1 at 25⁰C. The kinetic isotope effect (KIE) for the reaction at 25⁰C was also determined: 2.65 ± 0.10, confirming that the proton transition occurs in the step that determines the rate of the reaction. In the end, a thermochemical analysis of the reaction was performed and stepwise reaction mechanisms (PT/ET and ET/PT) were rejected as possible mechanisms of proton and electron transition. The proposed mechanism is CPET
Botanička obilježja, kemijski sastav i primjena tonkovca – Dipteryx odorata (Aubl.) Forsyth f
No full textDipteryx odorata (Aubl.) Forsyth f. is a neotropical plant species belonging to the Fabaceae family. This species is characterized by a round high crown, gray bark and pink flowers. It is best known for its black wrinkled seeds, which are used in cooking and production of alcoholic beverages and perfume. The seeds contain a high percentage of coumarins. Coumarin chemistry remains one of the primary areas of study for phytochemists, owing to their structural diversity and therapeutic effects. These chemical compounds have diverse bioactivity such as analgesic, anticoagulant, anti-HIV, antiinflammatory, antibacterial, antineoplastic, antioxidant, and immunomodulatory. However, coumarin is hazardous in high amounts, thus it must be used with caution; the use of these seeds is regulated by law in many countries. Despite success in the extraction, separation, structure elucidation, and bioactivity testing of natural coumarins, only minor progress in the study of their production has been reported. Natural sources of coumarins, such as tonka beans, are important for the pharmaceutical industry for the reasons stated above