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Cases of suspected off-label use in children reported to the Agency for Medicinal Products and Medical Devices
No full textCilj ovog diplomskog rada je opisati slučajeve sumnji na off-label primjenu lijeka spontano prijavljene Hrvatskoj agenciji za lijekove i medicinske proizvode u pedijatrijskoj populaciji u razdoblju do 31.12.2021. godine. Identificirani su slučajevi u kojima je prijavljena sumnja na off-label primjenu lijeka u osoba mlađih od 18 godina, zaprimljeni zaključno s 31.12.2021. godine. Primarno su analizirane prijave sumnji na nuspojave koje pripadaju High Level Term: Off-label use prema MedDRA. Prijave su analizirane prema dobu i spolu pacijenta, vrsti prijavitelja, djelatnoj tvari, ATK klasifikaciji lijekova, PT klasifikaciji MedDRA i prema ozbiljnosti nuspojava. Ukupno je zaprimljeno 36 prijava sumnji na off-label primjenu lijekova za pacijente mlađe od 18 godina. Najviše prijava je zaprimljeno za djecu starosti od 2 do 11 godina. Najmanje prijava je zaprimljeno za novorođenčad, od 0 do 27 dana starosti. Prema ATK klasifikaciji lijekova, najčešće su bili uključeni lijekovi s djelovanjem na živčani sustav, lijekovi s djelovanjem na sustavne infekcije, lijekovi s djelovanjem na respiratorni sustav i lijekovi s djelovanjem na osjetila. Najzastupljenije djelatne tvari pod sumnjom bile su paliperidon, diklofenak, pantoprazol i mikafungin. Od ukupno 36 zaprimljenih prijava, u tri slučaja se nisu razvile nuspojave na primijenjen lijek, u 21 slučaju su se javile nuspojave koje ubrajamo u neozbiljne, a u 12 slučajeva došlo je do razvoja ozbiljnih nuspojava od čega je u tri slučaja došlo do smrti. Ovim radom uočena je potreba za unapređenjem farmakovigilancijskog sustava te potreba za edukacijom zdravstvenih djelatnika i pacijenata o prijavljivanju korištenja lijekova izvan odobrenih uvjeta te nuspojava koje nastaju primjenom istih.This thesis aims to describe cases of suspected off-label use of drugs spontaneously reported to the Croatian Agency for Medicinal Products and Medical Devices in the pediatric population in the period until the end of 2021 (December 31st). By the end of the same year, there have been identified cases of reporting the suspicion of off-label use of the drug by patients younger than 18 years old. Primary analyses were made for the reports of suspected adverse reactions belonging to High-Level Term: Off-label uses according to MedDRA. Reports were investigated according to the age and sex of the patient, the reporter qualification, the active ingredients, the ATK classification of drugs, the PT classification of MedDRA, and the severity of side effects. A total of 36 reports of suspected off-label use of drugs by patients younger than 18 years old were received. Most applications were received for children between 2 and 11 years old. The lowest number of applications was received for newborns, from 0 to 27 days of age. According to the ATK classification of drugs, drugs with effects on the nervous system, drugs with effects on systemic infections, drugs with effects on the respiratory system, and drugs with effects on the senses were the ones that were the most often included. The most commonly suspected active ingredients were paliperidone, diclofenac, pantoprazole, and micafungin. Out of a total of 36 received reports, there were 3 cases with no side effects developed, 21 cases with side effects we consider to be frivolous, and 12 cases with severe side effects developed (including 3 cases in which death occurred). This thesis identified the need for improvements in the pharmacovigilance system and the need to educate healthcare professionals and patients about reporting the off-label drug use and the side effects that arise from using them
Medication errors in paediatric population
No full textMedikacijske pogreške su nenamjerne pogreške u medikacijskom ciklusu (propisivanje, distribucija, priprema i primjena lijekova) koje se mogu spriječiti. Ukoliko se ne spriječe uzrokuju štetu ili imaju tendenciju stvaranja štete u organizmu pacijenta. Posebno ranjiva skupina pacijenata koja je osjetljiva na medikacijske pogreške jest pedijatrijska populacija, koja zahtjeva prilagodbu farmakoterapije (prilagodba doziranja, načina primjene, učestalosti doziranja i dr.). Svaka prilagodba je mogući rizik od pogreške. Medikacijske pogreške predstavljaju veliki teret za javno zdravlje. Postoji potreba za minimiziranjem rizika i prevencijom pogrešaka kroz postojeća regulatorna tijela (EMA, HALMED).
Cilj ovog istraživanja je bio opisati razloge osjetljivosti pedijatrijskih pacijenata, vrste medikacijske pogreške koje se događaju i predstaviti načine minimizacije pogrešaka u medikacijskom ciklusu u pedijatrijskoj populaciji.
U izradu rada korišteni su znanstveni radovi utemeljeni na dokazima koji su objavljeni u znanstvenim časopisima, dostupnima u bazama podataka Medline, Pub Med, Science Direct, Scopus i Google Scholar.
Rezultati su pokazali kako je pedijatrijska populacija osjetljiva zbog nezrelosti organizma te razlika u apsorpciji, distribuciji, metabolizmu i eliminaciji u odnosu na odraslu osobu. Pogreške se događaju u bolnicama, u ambulantama i privatnim domovima gdje su roditelji/skrbnici odgovorni za pravilnu primjenu farmakoterapije. Najčešće medikacijske pogreške bile su: primjena pogrešne doze lijekova i primjena krivoga lijeka. Većinom nisu bile životno ugrožavajuće. Prevencija je moguća ukoliko se medikacijske pogreške budu prijavljivale, ako se zdravstvenim djelatnicima omoguće stimulativni uvjeti rada i ako se roditeljima/skrbnicima precizno objasni primjena terapije.Medication errors are unintentional mistakes in the medication cycle (prescription, distribution, preparation and administration) that can be prevented. If they are not prevented, they cause damage or have a tendency to cause damage in the patient's body. A particularly vulnerable group of patients who are sensitive to medication errors is the pediatric population, which requires adjustment of pharmacotherapy (adjustment of dosage, method of administration, frequency of dosing, etc.). Any adjustment is a possible risk of error. Medication errors represent a major burden on public health. There is a need to minimize risks and prevent errors through existing regulatory bodies (EMA, HALMED).
The aim of this research was to describe the reasons for the sensitivity of pediatric patients, the types of medication errors that occur, and to present ways of minimizing errors in the medication cycle in the pediatric population.
Scientific papers based on evidence published in scientific journals, available in Medline, Pub Med, Science Direct, Scopus and Google Scholar databases were used in the preparation of the paper.
The results showed that the pediatric population is sensitive due to the immaturity of the organism and differences in absorption, distribution, metabolism and elimination compared to adults. Errors occur in hospitals, clinics and private homes where parents/caregivers are responsible for the correct use of pharmacotherapy. The most common medication errors were: administration of the wrong dose of medication and administration of the wrong medication. Most of them were not life-threatening. Prevention is possible if medication errors are reported, if health professionals are provided with stimulating working conditions and if the application of therapy is explained precisely to parents/caregivers
Supportive care in breast cancer
No full textLijekovi koji se koriste u liječenju karcinoma dojke imaju raznovrsne načine djelovanja te ne djeluju samo na tumorsko tkivo nego i na ostale dijelove tijela, rezultirajući nuspojavama. Jedne od najčešćih nuspojava uključuju mučninu, povraćanje, bol, proljev, konstipaciju, umor, gubitak kose, anemiju itd. te iste mogu smanjiti kvalitetu života, otežati ili prekinuti liječenje ili ugroziti sam život pacijenta.
Srećom, većina nuspojava može se kupirati odgovarajućim nefarmakološkim mjerama, dodacima prehani i lijekovima, a tu važnu ulogu ima i ljekarnik koji svojim znanjem pravovremeno reagira i predlaže pacijentu odgovarajuću terapiju. Time se poboljšava kvaliteta života pacijenta, omogućava se nastavak liječenja i smanjuju troškovi u zdravstvu.Medicines used in treatment have various modes of action and do not only affect tumor tissue, but also other parts of the body, resulting in side effects. One of the most common are nausea, vomiting, pain, diarrhea, constipation, fatigue, hair loss, anemia etc., which can reduce the quality of life, complicate or interrupt the treatment, and endanger the life of the patient.
Fortunately, most of the side effects can be controlled with appropriate non-pharmacological measures, dietary supplements and medicines, where the pharmacist plays an important role using his knowledge to respond in a timely manner and suggesting the appropriate therapy to the patient. This improves the patient's quality of life, enables the continuation of treatment and reduces healthcare costs
Overview of Dioscorides’ recipes in Croatian books of folk recipes
No full textThe aim of this paper is to present an overview of Dioscorides’ recipes from his work De materia medica which
are found in Croatian folk medicine preserved in books of folk recipes called ljekaruše. The particularities of five
published and analysed Croatian books of folk recipes from the 17th and 18th century are examined. Recipes
with drugs of herbal and animal origin, which are most often mentioned in Croatian books of folk recipes, and
which were available in folk medicine at the time, are compared with those from Dioscorides’ work. Many herbal
drugs described in books of folk recipes are today used in contemporary phytotherapy, and modern biomedical
research reveals new bioactive substances and confirms new and potential biological activities in medicinal
plants used in folk medicine, which is the basis for further study of De materia medica by Dioscorides and
ethnomedicinal collections. Croatian books of folk recipes are a valuable resource for multidisciplinary study,
including for medicinal and pharmaceutical historians, philologists and ethnologists
Contribution of complete sequence analysis of von Willebrand factor and coagulation factor VIII genes in the diagnosis of von Willebrand disease and distinction from mild haemophilia A
No full textVišestruka uloga von Willebrandova faktora (VWF) u hemostazi, složenost njegove strukture i veliki broj mutacija u različitim dijelovima gena za VWF čine von Willebrandovu bolest (VWB) klinički izrazito heterogenim poremećajem, a njegovu pravilnu dijagnostiku i razlikovanje od blage hemofilije A otežanima. Cilj ovog istraživanja bio je primijeniti cjeloviti pristup dijagnostici VWB-a u Republici Hrvatskoj koji uključuje globalne i visokodiferentne koagulacijske pretrage kojima su ispitana funkcionalna i strukturna svojstva VWF-a te molekularnu analizu svih sljednih varijanti u genima za VWF i faktor zgrušavanja VIII (FVIII) sekvenciranjem sljedeće generacije (NGS) i dodatnim pretraživanjem velikih delecija i duplikacija metodom višestrukog umnažanja vezanih sondi. Istraživanje je obuhvatilo 83 ispitanika, a mutacije u genu za VWF nađene su kod njih 48. Na temelju rezultata koagulacijskih pretraga i genetičke analize, 19 ispitanika klasificirano je kao tip 1 VWB-a, šest kao tip 3, dok je među 23 ispitanika s tipom 2 VWB-a 15 imalo tip 2A, sedam tip 2B, a tip 2N potvrđen je u jednom slučaju. Heterozigotni genotip utvrđen je kod 38 ispitanika, sedam su bili složeni heterozigoti i tri homozigoti. Ukupno je utvrđeno 36 različitih mutacija u genu za VWF, od kojih su 13 novootkrivene. Mutacije u genu za FVIII nađene su kod petero ispitanika, pri čemu je u dva muška homozigota postavljena dijagnoza blage hemofilije A, dok su tri ženske ispitanice heterozigoti i smatraju se nositeljicama hemofilije A. Kod jedne je ispitanice uz mutaciju u genu za FVIII nađena i mutacija u genu za VWF. Dvije su mutacije u genu za FVIII novootkrivene. Kod 30 (36 %) ispitanika nisu nađene mutacije u genima za VWF i FVIII, pri čemu je devet ispitanika zbog aktivnosti VWF-a ispod 50 % svrstano u kategoriju tzv. ꓹꓹniskog VWF-a“. Ovo istraživanje upozorilo je na znatnu heterogenost genetičke osnove VWB-a u hrvatskoj populaciji, a istodobno sekvenciranje gena za VWF i FVIII tehnologijom NGS omogućilo je jednoznačno postavljanje dijagnoze VWB-a te diferencijalno dijagnostičko razlučivanje od blage hemofilije A. Time je osigurana osnova za pravilno liječenje i skrb za bolesnike te su razjašnjeni molekulsko-patofizološki mehanizmi koji su u podlozi poremećaja krvarenja kod obrađenih bolesnika.Multiple functions of von Willebrand factor (VWF), its structural complexity and numerous mutations throughout the whole VWF gene impact the clinical heterogeneity of von Willebrand disease (VWD) and make its accurate diagnosis and distinction from mild haemophilia A challenging. The aim of the present study was to introduce a comprehensive laboratory diagnostic approach that included screening and specific coagulation assays, as well as molecular analysis of VWF and coagulation factor VIII (FVIII) genes by means of next-generation sequencing (NGS) and additional targeted screening for deletions and duplications using the multiplex ligation-dependent probe amplification method. Of the 83 study participants, 48 were identified with disease-associated mutations in the VWF gene, of whom 19 were classified as type 1 VWD, six as type 3 VWD, while among the 23 patients with type 2 VWD, 15 were assigned as type 2A, seven as type 2B, and in one case type 2N VWD was confirmed. Heterozygous genotype was present in 38 patients, compound heterozygosity in seven patients while three patients were homozygous for mutations within the VWF gene. In total, 36 distinct disease-associated mutations were found within the VWF gene, of which 13 were novel. Four study participants were identified with mutations within the FVIII gene only, while one female participant had mutations both in VWF and FVIII genes. The two siblings who were homozygous for a mutation in the FVIII gene were diagnosed with mild haemophilia A, while the three heterozygous females were classified as carriers of mild haemophilia A. Two mutations within the FVIII gene were novel. Of the remaining 30 (36 %) study participants without mutations within the VWF and FVIII genes, nine had VWF activity below 50 % and were classified as “low VWF“. The present study revealed considerable genetic heterogeneity among patients with VWD in Croatia. The application of simultaneous sequencing of whole VWF and FVIII genes by means of NGS was proven as a valid approach for differential diagnosis of VWD subtypes, as well as for unambiguous distinction of VWD from mild haemophilia A. This study provided basis for appropriate patient treatment and care, as well as enhanced the understanding of the underlying molecular pathophysiology of the bleeding phenotype in the evaluated patients
Utvrđivanje terapijskih problema primjenom "najbolje moguće medikacijske povijesti" u starijih pacijenata kod prijema u bolnicu
No full textCilj istraživanja: Cilj ovog istraživanja je procijeniti učestalost politerapije, potencijalno neprikladnih lijekova (PNL-ova), interakcija lijekova i rizičnih lijekova s obzirom na oštećenu bubrežnu funkciju primjenom “najbolje moguće medikacijske povijesti” (engl. Best Possible Medication History - BPMH) u starijih osoba zaprimljenih u bolnicu. Također, cilj je utvrditi korelacije između pojedinih farmakoterapijskih problema te njihovu povezanost s određenim značajkama pacijenata.
Pacijenti i metode: Provedeno je prospektivno opservacijsko istraživanje u Klinici za unutarnje bolesti, Kliničke bolnice Dubrava, u populaciji bolesnika starije životne dobi kod prijema. Klinički farmaceut uzeo je BPMH za svakog pacijenta unutar 24 sata od prijema. Politerapija je definirana kao istovremena primjena 5-9 lijekova, a prekomjerna politerapija kao primjena ≥10 lijekova. Analiza PNL-ova provedena je pomoću EU(7)-PIM kriterija. Potencijalno klinički značajne interakcije lijekova su utvrđivane pomoću programa Lexicomp® Lexi-Interact TM. Kriterij za utvrđivanje pacijenata s oštećenjem bubrežne funkcije bio je eGFR < 60 ml/min/1,73 m2; KDIGO stadiji 3a, 3b, 4 i 5, dok su se rizični lijekovi za primjenu u ovoj subpopulaciji bolesnika utvrđivali prema važećim sažetcima opisa svojstava lijekova (HALMED). Primjenom Spearmanovog korelacijskog koeficijenta određivana je povezanost između pojedinih farmakoterapijskih problema. Također, provedena je logistička regresijska analiza kako bi se utvrdila povezanost farmakoterapijskih problema s određenim značajkama pacijenata.
Rezultati: Istraživanje je uključilo 383 pacijenta starije životne dobi, prosječne dobi od 76 godina (70-80), od kojih su 52% bile žene. Kod 49,9% pacijenata zabilježena je politerapija, a 31,8% pacijenata koristilo je 10 ili više lijekova. Ukupno je 80,7% (n=309) ispitanika bilo izloženo PNL-ovima. Kod 90,6% pacijenata utvrđena je jedna ili više potencijalno klinički značajnih interakcija lijekova.
Ukupno 43,6% ispitanika imalo je oslabljenu bubrežnu funkciju, od kojih je 64,7% imalo jedan ili više propisanih rizičnih lijekova s obzirom na oštećenu bubrežnu funkciju s neprilagođenom dozom ili su bili kontraindicirani. Utvrđene su pozitivne korelacije između pojedinih farmakoterapijskih problema.
Zaključak: Primjenom BPMH klinički farmaceut utvrdio je visoku učestalost različitih farmakoterapijskih problema u starijih osoba zaprimljenih u bolnici. Ovo istraživanje ukazuje na važnost primjene BPMH kao odgovarajućeg alata za otkrivanje farmakoterapijskih problema kod bolesnika starije životne dobi, prilikom transfera skrbi, posebno zbog utvrđenih pozitivnih korelacija između farmakoterapijskih problema, što ukazuje da oni nisu neovisni, te se može očekivati njihovo istovremeno pojavljivanje.Objectives: The aim of the study was to expand the use of Best Possible Medication History (BPMH) and to evaluate polypharmacy, potentially inappropriate medications (PIMs), drug-drug interactions (DDIs) and inappropriately prescribed renal risk drugs (RRDs) on hospital admission as well as to determine their mutual relationship and association with certain patients’ characteristics.
Patients and methods: An observational prospective study was conducted at the Internal Medicine Clinic of University Hospital Dubrava in elderly population. The hospital clinical pharmacist obtained the BPMH for each patient within 24 hours of admission. The presence of polypharmacy (5-9 medications) and excessive polypharmacy (>10 medications) was determined. The EU(7)-PIM criteria were applied for PIMs detection. The pharmacotherapy data were analysed for potential clinically significant DDIs by using Lexicomp® Lexi-Interact TM software. The estimated glomerular filtration rate (eGFR) was applied to identify patients with renal impairment (eGFR < 60 ml/min/1,73 m2; KDIGO stages 3a, 3b, 4 and 5).
In this subpopulation of patients, RRDs were determined by checking their Summary of Product Characteristics (HALMED) available at the time of the study. The Spearman correlation coefficient was used to analyse the relationship between polypharmacy, PIMs, DDIs and inappropriately prescribed RRDs, and logistic regression was also performed to determine their association with certain patients’ characteristics.
Results: The study included 383 elderly patients; 52% of them were female, with a median age of 76 (70-80). The median number of prescription medications in BPMH was 8 (5-11). Overall, 49,9% of patients used 5-9 prescription medications and 31,8% used 10 or more medications. PIMs based on EU(7)-PIM criteria occurred in 80,7% (n=309) of the participants. The most common PIM was pantoprazole. In total, 90,6 % of patients had at least one potential clinically significant DDI. In total, 43,6% of patients were found to have eGFR < 60 ml/min/1,73 m2, of which 64,7% of patients had one or more inappropriately prescribed RRDs. Analysis determined positive correlations between certain pharmacotherapy problems.
Conclusion: The clinical pharmacist detected high incidence of polypharmacy, PIMs, DDIs and inappropriately prescribed RRDs by using BPMH on hospital admission in the elderly. This study highlights the importance of using the BPMH as a suitable tool for detection of pharmacotherapy problems in elderly patients, during the transfer of care. The positive correlations between pharmacotherapy problems indicate that they are not independent and that there is a greater probability than the random one they will occur simultaneously
Electrochemical and computational determination of redox properties of ferrocenolated purine deriviates
No full textVažno svojstvo ferocenskih nukleobaza predstavlja redoks potencijal kojim se može predvidjeti njihov antitumorski učinak. Osim što se može dobiti eksperimentalno, korištenjem voltametrije, može se dobiti i teorijski primjenom kvantne kemije. To jest DFT-a. Kako bi se dobili rezultati visoke točnosti i preciznosti važan je izbor DFT metode. Stoga je često korištena B3LYP metoda. U ovom radu dokazan je lakši način teorijskog računanja redoks potencijala primjenom DFT metode B3LYP na ferocenoiliranim purinskim derivatima s različitim baznim skupovima za željezo (SDD i LanL2TZf). Umjesto računanja promjene slobodne Gibbsove energije za svaki oksidirani i reducirani oblik spoja u plinovitom i solvatiranom stanju, dovoljni je izračunati energiju HOMO orbitala reduciranog oblika. Do korelacije između energija HOMO orbitala reduciranih oblika analita i njihovih eksperimentalno dobivenih redoks potencijala došlo se na temelju prethodno dokazane korelacije između teorijski izračunatih energija HOMO orbitala reduciranih oblika ferocenoliranih derivata, uz bazni skup LanL2TZf za željezo, i njihovih eksperimentalno dobivenih energija ionizacije. Što je viša energija HOMO orbitale to je niža energija ionizacije spoja. Spojevi s nižom energijom ionizacije lakše se oksidiraju. U radu je dobivena slična korelacija. Što je viša energija HOMO orbitale to je niži redoks potencijal spoja te se lakše oksidira. Za što bolju linearnu korelaciju važan je i bazni skup željeza što je još jednom potvrdilo korištenje LanL2TZf (R2= 0,9842).Također prilikom mjerenja redoks potencijala cikličkom i pravokutnovalnom voltametrijom potvrđeno je da N7-regiozomeri imaju viši redoks potencijal u usporedbi s odgovarajućim N9-regioizomerima. Voltamometrija bi se mogla koristiti kao jednostavna i brza metoda razlikovanja N7- i N9-ferocenoil nukleobaza.An important property of ferrocene nucleobases is the redox potential that can predict their antitumor effect. In addition to being obtained experimentally, using voltammetry, it can also be obtained theoretically by applying quantum chemistry. That is DFT. In order to obtain results of high accuracy and precision, the choice of the DFT method is important. Therefore, the B3LYP method is often used. In this paper, an easier way of theoretical calculation of redox potential was proved by applying the DFT method B3LYP on ferrocenolated purine derivatives with different base sets for iron (SDD and LanL2TZf). Instead of calculating the change in free Gibbs energy for each oxidized and reduced form of the compound in the gaseous and solvated state, its HOMO energy of the reduced form orbit is sufficient. The correlation between HOMO orbital energies of reduced analyte forms and their experimentally obtained redox potentials was based on the previously proven correlation between theoretically calculated HOMO orbital energies of reduced forms of ferrocenolated derivatives, with the base set LanL2TZf for iron, and their experimentally obtained energies. The higher the energy of the HOMO orbital the lower the ionization energy of the compound. Compounds with lower ionization energy are more easily oxidized. A similar correlation was obtained in the paper. The higher the energy of the HOMO orbital, the lower the redox potential of the compound and the easier it oxidizes. The basis set of iron is also important for better linear correlation, which was once again confirmed by the use of LanL2TZf (R2 = 0.9842). Also when measuring redox potentials by cyclic and squarevawe voltammetry, it was confirmed that N7-regioisomers have a higher redox potential compared to the corresponding N9-regioisomers. Voltammetry could be used as a simple and fast method of distinguishing N7- and N9-ferrocenoyl nucleobases
Harmine derivatives as potential biofilm inhibitors
No full textBiofilm je zajednica različitih vrsta mikroorganizama koji su uklopljeni u matriks. Matriks predstavlja fizičku
barijeru koja otežava penetraciju antibiotika do ciljnih stanica, a s druge strane, zbog viskoelastičnosti otežano je
mehaničko uklanjanje. Navedeno čini biofilm kako zdravstvenim, tako i industrijskim problemom s obzirom da se
može formirati na bilo kojoj metalnoj ili plastičnoj površini. U ovom radu sintetizirana su tri potencijalna inhibitora
biofilma (6-8). Sinteza se odvijala u četiri koraka, a kao početni spoj uzet je harmin. U prvom koraku sinteze
Michaelovom adicijom dobiven je ester 1. U idućem koraku u reakciji hidrolize dobivena je kiselina 2. U trećem
koraku sinteze reakcijom couplinga između kiseline 2 i odgovarajućeg amina (4-amino-1-Boc-piperidina, 4-(NBoc-
amino)piperidina ili N-Bocetilendiamina), uz HATU/DIEA dobiveni su N-Boc zaštićeni amidi (3-5). Boc
zaštitna skupina uklonjena je u kiselim uvjetima, uz TFA, te su dobiveni odgovarajući amidi (6-8). Spojevima su
određena su tališta, a njihove strukture potvrđene su standardnim spektroskopskim i spektrometrijskim tehnikama
(IR, 1H i 13C NMR, MS). U daljnjim istraživanjima, bit će ispitano njihovo inhibitorno djelovanje na bakterijski
biofilm.Biofilm is a community consisting of various types of microorganisms embedded in extracellular matrix, which
represents a physical barrier that complicates antibiotic penetration to target bacteria. Furthermore, mechanical
removal is complicated due to viscoelastic properties of biofilm. Aforementioned makes biofilm a major
healthcare, as well as industrial problem, due to the fact that it can be formed on any metal or plastic surface. Three
potential biofilm inhibitors have been synthetized (6-8). Synthesis was done in a four step procedure using harmine
as a starting compound. The first step included Michael reaction resulting in esther 1, which was subsequently
hydrolised to give acid 2. The third step included coupling reaction between acid 2 and corresponding amine (4-
amino-1-Boc-piperidine, 4-(N-Boc-amino)piperidine or N-Boc-ethylenediamine), in the presence of
HATU/DIEA, resulting in N-Boc protected amides (3-5). Boc protective group was removed under acid conditions,
(TFA), to yield final compounds, amides (6-8). Melting points of new compounds were determined and their
structures were confirmed using standard spectroscopic and spectrometric techniques (IR, 1H and 13C NMR, MS).
Their inhibitory activity on bacterial biofilm will be tested in further studies
Načela oblikovanja kozmetičkih proizvoda za osjetljivu kožu
No full textCILJ ISTRAŽIVANJA
Zbog životnog stila sve veći broj ljudi ima subjektivne i/ili objektivne simptome osjetljive kože. Cilj predloženog specijalističkog rada je pregledno prikazati i sistematizirati relevantne dokaze vezane uz pozitivne ili negativne učinke sastojaka i/ili kozmetičkih oblika na izazivanje osjetljivosti kože, a koji su važni u razvoju kozmetičkih proizvoda za osjetljivu kožu.
MATERIJALI I METODE
Pri izradi specijalističkog rada pretražene baze su podataka PubMed/Medline, Elsevier, Scopus i ResearchGate. Za pretraživanje su korištene ključne riječi “sensitive skin”, “reactive skin”, “skin sensitization”, “contact sensitivity”, “skin senzitizers”, “dermocosmetic”, “cosmetic science”, “cosmetic technology”, “skin irritation”, “formulating”, “ingredients”, “humectants”, “preservatives”, “surfactants”, “cleanser”, “emulsifier”, “solubilizers”, “UV filters” zasebno i u kombinacijama. Pregledane su sve publikacije iz rezultata pretrage s dostupnim cjelovitim tekstovima ili s dostupnim sažetcima. Odabir znanstvenih radova ograničen je na izvorne znanstvene radove na engleskom jeziku. Radovi koji odgovaraju odabranim kriterijima odabrani su neovisno o datumu njihove objave. Literatura je pretraživana od općih prema specijaliziranim člancima pri čemu su odabrani članci relevantni za problematiku specijalističkog rada.
REZULTATI
Oblikovanje kozmetičkog proizvoda za osjetljivu kožu zahtjeva posebnu pažnju. Dok za neke skupine sastojaka postoje konkretni podaci o iritacijskom potencijalu, neki ih sastojci nemaju ili su oskudni. Korištenje sastojaka koji su dugo u primjeni s poznatim i dobro ispitanim učinkom na kožu, dodavanje minimalni potrebni broj sastojaka, testiranje proizvoda prije lansiranja na tržište i praćenje povratnih informacija kupaca o neželjenim reakcijama može osigurati siguran i neškodljiv proizvod za osjetljivu kožu.
ZAKLJUČAK
Kozmetički proizvodi su dio svakodnevne higijene ljudi, a zbog velikog broja ljudi koji imaju ili smatraju da imaju osjetljivu kožu važno je razvijati kozmetičke oblike koji su sigurni, obavljaju svoju funkciju, a ne sadrže sastojke koji imaju velik iritacijski potencijal. Prilikom oblikovanja takvog proizvoda potrebno je eliminirati nepotrebne sastojke iz proizvoda, ukloniti sve alergene i poznate iritanse ili smanjiti njihov udio, koristiti prikladne antioksidanse i izbjegavati tvari koje povećavaju penetraciju drugih sastojaka u kožu.
Konzervansi i parfemi su najčešći alergeni u kozmetici. Pravilan odabir konzervansa i izostavljanje parfema kod razvoja kozmetičkog proizvoda za osjetljivu kožu ključni koraci koji umanjuju mogućnost nastanka iritacije nakon korištenja proizvoda.
Korištenje blagih neionskih i/ili amfoternih površinski aktivnih tvari i njegujućih sastojaka u pH mediju sličnom koži osigurava se blagost i smanjuje iritacijski potencijal sredstava za pranje. Nakon pranja kože slijedi nanošenje hidratantne kreme koju treba oblikovati tako da sadrži adekvatan omjerom lipida, okluziva i humektansa (ovisno kojem tipu kože je namijenjena), sastojke niskog iritacijskog potencijala i otapala koja ne povećavaju penetraciju drugih sastojaka. Ako se radi o kremi sa zaštitnim faktorom, najbolji izbor su fizički filteri jer, za razliku od kemijskih, nemaju zabilježene negativne reakcije na koži. Uz funkcionalne sastojke kozmetički proizvodi mogu sadržavati i kozmeceutike čiji izbor i korišteni udjeli trebaju biti pažljivo odabrani.
Nakon razvoja kozmetičkog oblika poželjno je ispitati njegov iritacijski potencijal, a nakon izlaska na tržište pratiti pojave neželjenih događaja kod normalne ili razumno predvidljive uporabe.OBJECTIVES
Due to lifestyle, an increasing number of people have subjective an/or objective symptoms of sensitive skin. Thea aim of proposed thesis is to cleary present and systematize the relevant evidence related to the positive or negative effects of ingredients and/or cosmetics formulations on causing skin sensitivity, which are important in the development of cosmetic products for sensitive skin.
MATERIAL AND METHODS
PubMed / Medline, Elsevier, Scopus and ResearchGate are used to create a thesis database. The keywords “sensitive skin”, “reactive skin”, “skin sensitization”, “contact sensitivity”, “skin sensitizers”, “dermocosmetic”, “cosmetic science”, “cosmetic technology”, “skin irritation”, “Formulating”, “ingredients”, “humectants”, “preservatives”, “surfactants”, “cleanser”, “emulsifier”, “solubilizers”, “UV filters” were used for the search separately and in combinations. All publications from search results with available full texts or with available abstracts were reviewed. The selection of scientific papers is limited to original scientific papers in English. Papers that meet the selected criteria were selected regardless of the date of their publication. The literature was searched from general to specialized articles, with selected articles relevant to the issue of specialist work.
RESULTS
Designing a cosmetic product for sensitive skin requires special attention. While specific irritant potential data are available for some groups of ingredients, some ingredients do not have them or are scarce. Using ingredients that have been used for a long time with a known and well-tested effect on the skin, adding the minimum required number of ingredients, testing the product before launch and monitoring customer feedback on side effects can ensure a safe and harmless product for sensitive skin.
CONCLUSION
Cosmetic products are part of people's daily hygiene, and due to the large number of people who have or consider to have sensitive skin, it is important to develop cosmetic products that are safe, perform their function, and do not contain ingredients that have irritating potential. When designing such a product, it is necessary to eliminate unnecessary ingredients from the product, remove all allergens and known irritants (or reduce their content), use appropriate antioxidants and avoid substances that increase the penetration of other ingredients into the skin.
Preservatives and perfumes are the most common allergens in cosmetics. Proper selection of preservatives and omission of perfumes in the development of a cosmetic product for sensitive skin are key steps that reduce the possibility of irritation after using the product.
The use of mild non-ionic and/or amphoteric surfactants and nourishing ingredients in a skin-like pH medium ensures gentleness and reduces the irritating potential of washes. After washing the skin, apply a moisturizer that should be formulated to contain an adequate ratio of lipids, occlusions and humectants (depending on the skin type), ingredients with low irritation potential and solvents that do not increase the penetration of other ingredients. If it is a cream with a sun protecting factor, the best choice are physical filters because, unlike chemical ones, they do not have any negative reactions on the skin. In addition to functional ingredients, cosmetic products may also contain active ingredients whose selection and the proportions used should be carefully selected.
After the development of the cosmetic product, it is desirable to examine its irritating potential, and after entering the market to monitor the occurrence of adverse events in normal or reasonably predictable use
The concept of developing vaccines based on nucleic acids
No full textZanimanje za razvojem cjepiva temeljenih na nukleinskim kiselinama pojavio se prije trideset godina, no zadnjih deset godina intenzivno se istražuju mogućnosti primjene takvih cjepiva za prevenciju infektivnih bolesti, terapiju tumora i genetičkih poremećaja. Razlog tolikoga interesa za njihovim razvojem jest velik potencijal ovih cjepiva. Osim što uzrokuju humoralni i stanični imunosni odgovor aktivacijom i T i B limfocita proces njihove proizvodnje je jednostavan te, nakon primjene, ne postoji opasnost od razvoja burne reakcije, pa čak i bolesti. Glavni nedostatak ovih cjepiva jest nedovoljna imunogenost odnosno stimulacija imunosnoga sustava. Smatra se da je nedovoljna imunogenost takvih cjepiva povezana s njihovom nestabilnošću i nedostatnom dostavom nukleinskih kiselina u stanice. Istraživanja su dovela do brojnih rješenja navedenih problema. Inkorporacijom nukleinskih kiselina u sustave koji su djelotvorni u njihovoj dostavi u stanice, povećava se sinteza antigena, a time i stimulacija imunosnoga sustava. Posebnim dizajniranjem i modifikacijom molekula nukleinskih kiselina, kao što je optimizacija kodona i modifikacija baza kod mRNA ili te dodatak adjuvanasa kod DNA, povećava se njihova stabilnost i imunogenost. Zahvaljujući ovim metodama danas je u tijeku velik broj kliničkih istraživanja koja bi vrlo brzo mogla dovesti do svakodnevne primjene ovih cjepiva u prevenciji i terapiji bolesti.Interest in the development of vaccines based on nucleic acids appeared thirty years ago, but in the last ten years their application has been intensive for the prevention of infectious diseases and therapy of cancer and genetic disorders. The reason for so much interest in their development is the great potential of these vaccines. In addition to causing a humoral and cellular immune response by activating both T and B lymphocytes, the process of their production is simple and, after application, there is no danger of developing a violent reaction or even disease. The main drawback of these vaccines is insufficient immunogenicity, i.e. stimulation of the immune system, which is due to instability and insufficient delivery of nucleic acids to cells due to a large amount of negative charge. To date, many solutions have been discovered that could solve this problem. By incorporating nucleic acids into systems that are effective in delivering them to cells, the synthesis of antigens increases, and thus the stimulation of the immune system. Special design and modification of nucleic acid molecules, such as codon optimization and base modification in mRNA, and the addition of adjuvants to DNA increase their stability and, also, immunogenicity. Thanks to these methods, a large number of clinical researches are in circulation today, which could very soon lead to the daily use of these vaccines in the prevention and treatment of diseases