University of Zagreb
Repository of Faculty of Pharmacy and Biochemistry University of ZgrebNot a member yet
2946 research outputs found
Sort by
Nanoemulzije unaprijeđene biofarmaceutske vrijednosti za liječenje bolesti suhoga oka/Biopharmaceutically improved nanoemulsions for the treatment of dry eye disease IP-2019-04-2174 (BeatDED)
No full textUsporedba vrijednosti LDL kolesterola procijenjenih Friedewaldovomm, Martin/Hopkinsovom i Sampsonovom jednadžbom
No full textKorištenje Friedewaldove jednadžbe za procjenu vrijednosti LDL kolesterola (LDL-K)
ne zahtjeva dodatni financijski trošak zbog čega se u laboratorijima diljem svijeta, pa
tako i u Republici Hrvatskoj, ona koristi više nego direktne metode za određivanje
vrijednosti LDL-K. Zbog svojih ograničenja, a i sukladno preporukama Europskog
društva za kardiologiju (ESC) iz 2021. godine potrebno ju je zamijeniti
Martin/Hopkinsovom ili Sampsonovom jednadžbom. Obzirom na razlike u procjeni
LDL-K korištenjem različitih jednadžbi i sukladno dobroj laboratorijskoj praksi
potrebno je provesti usporedbu metoda, što do sada još nije provedeno u Hrvatskoj.
Cilj istraživanja:
Ovim istraživanjem provesti će se usporedba vrijednosti LDL-K procijenjenih
Friedewaldovom, Martin/Hopkinsovom i Sampsonovom jednadžbom. Prema
dobivenim vrijednostima LDL-K utvrditi će se stupanj slaganja klasifikacije
bolesnika u skupine kardiovaskularnog rizika.
Ispitanici i metode:
Provedeno je retrospektivno istraživanje u Odjelu laboratorijske dijagnostike
Specijalne bolnice za medicinsku rehabilitaciju Varaždinske Toplice. Za potrebe ovog
istraživanja koristili su se isključivo rezultati ukupnog kolesterola, triglicerida, HDL-K i
LDL-K koji su zatraženi i dobiveni tijekom rutinske laboratorijske obrade bolesnika u
razdoblju od 01.01.2021. do 30.11.2023. i koji su dostupni u laboratorijskom
informacijskom sustavu (LIS). Ispitanici kojima je koncentracija triglicerida veća od
4,5 mmol/L isključeni su iz daljnjeg istraživanja (N=21). U ispitivanje je uključeno 655
ispitanika oba spola (291 muškaraca i 364 žena). Vrijednost LDL-K se procijenila
korištenjem Friedewaldove, Martin/Hopkinsove i Sampsonove jednadžbe.
Rezultati:
Usporedbom vrijednosti LDL-K određenog sa sve tri jednadžbe korištenjem BlandAltman metode i Passing-Bablok regresijske analize na sljedeći način: u cijelom
rasponu vrijednosti LDL-K, te unutar skupina podijeljenih prema terapijskim ciljnim
vrijednostima LDL-K (LDL-F) (≤ 1,3 mmol/L, 1,4 - 1,7 mmol/L, 1,8 - 2,5 mmol/L, 2,6
- 2,9 mmol/L, ≥ 3 mmol/L) definirane preporukama ECA/ESC utvrđena su statistički
značajna odstupanja pri čemu Friedewaldova jednadžba mjeri niže vrijednosti od
Martin/Hopkinsove i Sampsonove jednadžbe. Stupanj slaganja klasifikacije
ispitanika u pojedine skupine ovisno o vrijednosti LDL-K procijenjenog
Friedewaldovom i Martin/Hopkinsovom jednadžbom iznosi 0,94 (95%CI 0,92 –
0,95), odnosno 0,96 (95%CI 0,94 -0,97) kada se ispitanici klasificiraju ovisno o
vrijednosti LDL-K procijenjenog Friedewaldovom i Sampsonovom jednadžbom.
Zaključak:
Ovim ispitivanjem utvrđeno je da su prisutna statistički značajna odstupanja između
vrijednosti LDL-K procijenjenih s tri različite jednadžbe pri čemu Friedewaldova
jednadžba mjeri niže vrijednosti od Martin/Hopkinsove i Sampsonove jednadžbe.
Srednja vrijednost razlike raste s snižavanjem vrijednosti LDL-K i najveća odstupanja
su prisutna upravo kod vrijednosti LDL-K koje su važni terapijski ciljevi kod osoba s
velikim i vrlo velikim kardiovaskularnim rizikom. Procjena vrijednosti LDL-K
Friedewaldovom jednadžbom u tih osoba može dovesti do pogrešnog terapijskog
pristupa i posljedično do lošijeg kardiovaskularnog ishoda te ju je uputno zamijeniti
Martin/Hopkinsovom ili Sampsonovom jednadžbom.The estimation of LDL cholesterol (LDL-C) using the Friedewald equation does not
require additional financial costs, therefore laboratories around the world, including
those in the Republic of Croatia, use it more than direct methods for determining the
value of LDL-C. Due to its limitations, and in accordance with the recommendations
of the European Society of Cardiology (ESC) from 2021, it should be replaced by the
Martin/Hopkins or Sampson equation. Considering the differences in the estimation
of LDL-C using different equations and in accordance with good laboratory practice,
it is necessary to perform method comparison, which has not yet been done in
Croatia.
Objectives:
This research will compare LDL-C values estimated by the Friedewald,
Martin/Hopkins and Sampson equations. According to the obtained LDL-C values,
the degree of agreement in the classification of patients into cardiovascular risk
groups will be determined.
Patients and Methods:
A retrospective study was conducted in the Department of Laboratory Diagnostics
of the Special Hospital for Medical Rehabilitation Varaždinske Toplice. For the
purposes of this study, only the results of total cholesterol, triglycerides, HDL-C and
LDL-C were used, which were requested and obtained during the routine laboratory
analysis in the period from 01/01/2021 until 30/11/2023 and which were available
within the laboratory information system (LIS). Subjects whose triglyceride
concentration was higher than 4.5 mmol/L were excluded from further research
(N=21). A total of 655 subjects (291 men and 364 women) were included in the
study. The concentration of LDL-C was estimated using the Friedewald,
Martin/Hopkins and Sampson equations.
Results:
By comparing the value of LDL-C estimated by all three equations using the BlandAltman method and Passing-Bablok regression analysis as follows: in the entire
range of LDL-C values, and within groups divided according to the therapeutic
target values of LDL-C (LDL-F) ( ≤ 1.3 mmol/L, 1.4 – 1.7 mmol/L, 1.8 – 2.5 mmol/L,
2.6 – 2.9 mmol/L, ≥ 3 mmol/L) defined by ECA/ESC recommendations statistically
significant differences were found, whereby the Friedewald equation measures
lower values than the Martin/Hopkins and Sampson equations. The degree of
agreement in the classification of subjects into individual groups depending on the
value of LDL-C estimated by Friedewald and Martin/Hopkins equation was 0.94
(95%CI 0.92 – 0.95) and 0.96 (95%CI 0.94 -0.97) when subjects are classified
depending on the value of LDL-C estimated by the Friedewald and Sampson
equation.
Conclusion:
This study determined that there were statistically significant differences between
LDL-C values estimated with three different equations, with the Friedewald equation
measuring lower values than the Martin/Hopkins and Sampson equations. The mean
value of the difference increases with lowering of LDL-C values, and the largest
deviations are present for LDL-C values, which are important therapeutic goals in
people with high and very high cardiovascular risk. The assessment of LDL-C values
by the Friedewald equation in these individuals may lead to a wrong therapeutic
approach and consequently to a worse cardiovascular outcome thus this equation
should be replaced by the Martin/Hopkins or Sampson equation
Clinical use of bacteriophages
No full textTerapija bakteriofagom, koja koristi viruse za liječenje bakterijskih infekcija, ima dugu povijest, ali je izgubila popularnost s
razvojem antibiotika. S obzirom na krizu otpornosti na antimikrobne lijekove, ponovno je zainteresirala mnoge zemlje. Dok je
Zapadni svijet tek nedavno počeo istraživati ovu terapiju, u Istočnoj Europi se ona već duže vrijeme prakticira. Cilj ovog
diplomskog rada bio je pružiti pregled slučajeva rezistentnih bakterijskih infekcija tretiranih terapijom bakteriofaga. Posebna
pažnja posvećena je grupiranju najčešćih vrsta infekcija kako bi se razumjeli obrasci i trendovi u primjeni. Rad također detaljno
opisuje kliničke profile pacijenata, uključujući demografske podatke, povijest bolesti i karakteristike infekcija. Analiziran je
način primjene terapije, uključujući doziranje i trajanje liječenja, te moguće kombinacije s drugim pristupima. Na kraju,
provedena je evaluacija uspješnosti terapije, uzimajući u obzir ishode liječenja i nuspojave, kako bi se procijenila učinkovitost
ovog pristupa u borbi protiv otpornijih bakterijskih infekcija. Ovaj diplomski rad ukazuje na to da bakteriofagi predstavljaju
obećavajuću alternativu za liječenje rezistentnih bakterijskih infekcija, nudeći inovativan pristup u borbi protiv otpornosti na
antibiotike. Također, u ovom radu naglašavamo veliku potrebu za uspostavljanjem jasno definirane regulative i smjernica za
primjenu terapije bakteriofagima, kako bi se osigurala dosljednost i relevantnost dobivenih podataka.Phage therapy, which uses viruses to treat bacterial infections, has a long history but lost popularity with the development of
antibiotics. However, the current crisis of antimicrobial resistance has reignited interest in this therapy in many countries.
Although the Western world has only recently begun exploring this therapy, it has been practiced for a longer time in Eastern
Europe. The aim of this thesis was to provide an overview of cases of resistant bacterial infections treated with phage therapy.
Special attention was given to categorizing the most common types of infections to understand patterns and trends in
application. The paper also details the clinical profiles of patients, including demographic data, medical history, and
characteristics of infections. The method of therapy application was analyzed, including dosage, duration of treatment, and
potential combinations with other approaches. Finally, an evaluation of the therapy's success was conducted, considering
treatment outcomes and side effects to assess the effectiveness of this approach in combating resistant bacterial infections. This
thesis highlights that phages represent a promising alternative for treating resistant bacterial infections, offering an innovative
approach in the fight against antibiotic resistance. Additionally, we emphasize the urgent need for establishing clearly defined
regulations and guidelines for the application of phage therapy to ensure the consistency and relevance of the obtained data
Hijaluronska kiselina i cijeljenje rana
No full textCilj: Cilj ovog rada bio je sustavni pregled literature o ulozi hijaluronske kiseline (HA)
i njezinih obloga i terapijskih sustava u zacjeljivanju rana, s naglaskom na njezine
biološke funkcije, molekularne mehanizme djelovanja i potencijalne kliničke
primjene.
Metode: Provedena je sveobuhvatna analiza dostupne literature, uključujući
znanstvene članke, pregledne radove i kliničke studije koje se bave ulogom HA-e u
procesu zacjeljivanja rana. Poseban naglasak stavljen je na formulacije koje
uključuju HA-u te usporedba s drugim biopolimerima poput kitozana i alginata.
Rezultati: Rezultati pokazuju da HA igra ključnu ulogu u regulaciji upalnog
odgovora, stimulaciji angiogeneze i reorganizaciji ekstracelularnog matriksa, čime se
ubrzava proces zacjeljivanja rana. Komercijalni pripravci s HA-om pokazali su se
učinkovitim u različitim kliničkim studijama, dok kombinacija HA-e s drugim
biopolimerima nudi dodatne prednosti, uključujući dugotrajnu hidrataciju i poticanje
regeneracije tkiva.
Zaključak: Hijaluronska kiselina je središnja komponenta u modernim terapijskim
pristupima za liječenje rana. Njezina primjena u kombinaciji s drugim bioaktivnim
tvarima i naprednim tehnologijama, poput 3D bioprintanja, pruţa nove mogućnosti za
poboljšanje ishoda liječenja. Daljnja istraţivanja trebaju biti usmjerena na
optimizaciju formulacija i primjenu HA-e u personaliziranoj medicini.Objective: The aim of this work was to provide a systematic review of the literature
on the role of hyaluronic acid (HA) and its dressings and delivery systems in wound
healing, with a focus on its biological functions, molecular mechanisms of action, and
potential clinical applications.
Methods: A comprehensive analysis of the available literature was conducted,
including scientific articles, review papers, and clinical studies that address the role
of HA in the wound healing process. Special emphasis was placed on formulations
containing HA and comparisons with other biopolymers such as chitosan and
alginate.
Results: The results indicate that HA plays a crucial role in regulating inflammatory
response, stimulating angiogenesis, and reorganizing the extracellular matrix,
thereby accelerating the wound healing process. Commercial HA-based
preparations have proven effective in various clinical studies, while the combination
of HA with other biopolymers offers additional benefits, including sustained hydration
and enhanced tissue regeneration.
Conclusion: Hyaluronic acid is a central component in modern therapeutic
approaches for wound treatment. Its application in combination with other bioactive
substances and advanced technologies, such as 3D bioprinting, provides new
opportunities for improving treatment outcomes. Further research should focus on
optimizing formulations and applying HA in personalized medicine
Development of a new electroanalytical method for determination of pimavanserin
No full textParkinsonova bolest je kronična neurodegenerativna bolest, a liječenje bolesti usmjereno je na kontrolu motoričkih i nemotoričkih simptoma. Pimavanserin je prvi antipsihotik s indikacijom za liječenje halucinacija i deluzija u psihozama povezanih s Parkinsonovom bolešću.
Svrha ovoga rada bila je pronalaženje osnove za razvoj nove elektroanalitičke metode za određivanje pimavanserina utvrđivanjem elektroanalitičkih svojstava lijeka cikličkom i pravokutnovalnom voltametrijom.
Snimanjem cikličkih voltamograma dokazana je ireverzibilna oksidacija pimavanserina, a
najbolji voltametrijski odgovor dobiven je analizom otopine pimavanserina na elektrodi od staklastog ugljika (GCE) u 0,1 M H2SO4 kao osnovnom elektrolitu.
Modifikacijom GCE nanomaterijalima u 0,3%-tnoj etanolnoj otopini Nafiona dobiveni su još bolji voltametrijski odgovori zbog povećanja aktivne površine elektrode i elektrokatalitičkog utjecaja nanomaterijala na oksidaciju lijeka. Kombinacija nanomaterijala grafitizranih ugljikovih nanocjevčica i grafenovih nanopločica (1:1) u 0,3%-tnoj etanolnoj otopini Nafiona dala je najbolje voltametrijske odgovore. Također, Nafion kao polimer pridonosi boljoj adheziji nanomaterijala na površinu GCE, a kao kationsko izmjenjivačka smola ostvaruje elektrostatske interakcije s pozitivno nabijenim skupinama pimavanserina u kiselom mediju. Potencijal oksidacije pimavanserina na tako modificiranoj GCE iznosi 1,21 V u 0,1 M H2SO4 kao osnovnom elektrolitu pri definiranim optimalnim uvjetima pravokutnovalne voltametrije (frekvencija 75 Hz, amplituda 20 mV te porast potencijala 4 mV).
Postoji mogućnost razvoja nove elektroanalitičke metode za istovremeno određivanje pimavanserina i levodope jer njihovi potencijali oksidacije ne interferiraju, no kombinacija pimavanserina i ropinorola nije dobar kandidat za istovremenu analizu zbog preklapanja oksidacijskih pikova lijekova.Parkinson's disease is a chronic neurodegenerative disease and its treatment is aimed at controlling motor and nonmotor symptoms. Pimavanserin is the first antipsychotic with an indication for treatment of hallucinations and delusions in psychoses associated with Parkinson's disease.
The aim of this paper was to determine the basis for the development of a new electroanalytical method for the determination of pimavanserin by determining the electroanalytical properties of the drug by cyclic and square-wave voltammetry.
Irreversible oxidation of pimavanserin was demonstrated by scanning cyclic voltammograms. The best voltammetric response was obtained by analysing pimavanserin solution on a glassy carbon electrode (GCE) in 0.1 M H2SO4 as the background electrolyte.
Modification of GCE by nanomaterials in 0.3% Nafion ethanolic solution yielded even better voltammetric responses due to the increase in the active surface of the electrode, and the electrocatalytic effect of the nanomaterials on drug oxidation. The combination of nanomaterials of graphitized carbon nanotubes and graphene nanoplatelets (1:1) in 0.3% Nafion ethanolic solution gave the best voltammetric responses. Nafion as polymer contributes to better adhesion of nanomaterials to the GCE surface. Also, as cation exchange membrane, it achieves electrostatic interactions with protonated groups of pimavanserin in an acidic medium. The oxidation potential of pimavanserin at such a modified GCE is 1.21 V in 0.1 M H2SO4 under defined optimal conditions of square-wave voltammetry (75 Hz frequency, 20 mV amplitude and 4 mV potential step).
There is a possibility of developing a new electroanalytical method for the simultaneous determination of pimavanserin and levodopa as their oxidation potentials do not interfere. However, the combination of pimavanserin and ropinorol is not a good candidate for simultaneous analysis due to overlapping drug oxidation peaks
Development and validation of a method for determining paracetamol in tablets using Raman spectroscopy
No full textParacetamol (acetaminofen) je danas u svijetu jedan od najčešće korištenih OTC lijekova. Koristi se za liječenje blage do umjerene boli i povišene tjelesne temperature, a nalazi se i u kombiniranim pripravcima za liječenje simptoma prehlade i gripe. Iako poznat kao jako siguran lijek, zbog visoke dostupnosti i široke primjene, postao je jedan od vodećih uzroka smrti među lijekovima zbog slučajnog ili namjernog predoziranja. Paracetamol je radi svog hepatotoksičnog djelovanja vodeći uzrok akutnog zatajenja jetre u SAD-u. Cilj rada bio je razviti i validirati metodu za određivanje paracetamola u tabletama primjenom Ramanove spektroskopije te primjenom validirane metode odrediti udio paracetamola u uzorcima tableta. Prije validacije metode, bilo je potrebno provesti preliminarna ispitivanja, kojima se odabralo najbolje punilo te najbolji laser za ispitivanje validacijskih parametara. Preliminarnim ispitivanjima, kao najbolje punilo, odabrana je laktoza. Kod validacije analitičke metode ispitivani su parametri: linearnost, homogenost, preciznost (ponovljivost i intermedijarna preciznost) te granica određivanja i dokazivanja. Rezultati provedenih validacijskih mjerenja za sve parametre uglavnom su se nalazili unutar postavljenih granica. Određena odstupanja mogu se objasniti pogreškom analitičara prilikom priprave uzorka. Primjenom validirane metode na realne uzorke, dobivene su vrijednosti udjela paracetamola u uzorcima tableta i uspoređene s deklariranim. U daljnjim istraživanjima primijenit će se kemometrijski pristup analizi podataka radi bolje kvantifikacije paracetamola u uzorcima.Paracetamol (acetaminophen) is one of the most widely used OTC drugs in the world today. It is used to treat mild to moderate pain and fever, and it is also found in combined preparations to treat cold and flu symptoms. Although known as a very safe drug, highly available and widely applicable, it has become one of the leading causes of death when drugs are concerned, due to accidental or intentional overdose. Paracetamol is the leading cause of acute liver failure in the United States because of its hepatotoxic effects. The aim of this study was to develop and validate a method for determination of paracetamol in tablets, using Raman spectroscopy and to use this validated method to determine the proportion of paracetamol in tablet samples. Prior to the validation of the method, it was necessary to conduct preliminary tests to select the best filler and the best laser for testing validation parameters. Preliminary test showed that lactose was the best filler. During the validation of the analytical method, following parameters were examined: linearity, homogeneity, precision (repeatability and intermediate precision) and the limit of determination and quantification. The results of the validation measurements, performed for all parameters, were generally within the set limits. Certain deviations can be explained by the analyst's error in preparing the sample. By applying the validated method to real samples, paracetamol content in tablet samples was obtained and compared to the theoretical ones. In further research, a chemometric approach to dana analysis will be applied in order to improve quantification of paracetamol in the samples
Use of herbal preparations in pregnancy
No full textS obzirom na moguće štetne učinke primjene pojedinih biljnih vrsta u trudnoći, upoznatost s učestalošću i navikama korištenja biljnih lijekova i pripravaka tijekom trudnoće važna je za sve zdravstvene djelatnike koji skrbe o trudnicama. Cilj ovog ispitivanja bio je utvrditi sklonost trudnica korištenju biljnih pripravaka za vanjsku i unutarnju primjenu i prikupiti njihove stavove i uvjerenja o sigurnosti, učinkovitosti i dostupnosti biljnih pripravaka u usporedbi s konvencionalnim lijekovima, te utvrditi načine informiranja o biljnim pripravcima. Kod trudnica koje su tijekom trudnoće koristile biljne pripravke, cilj je bio prikupiti podatke o tome u kojem su ih tromjesečju i koliko često u prosjeku koristile, prema čijoj preporuci, jesu li s time upoznale svog ginekologa te gdje su bili kupljeni i za koje smetnje i/ili namjene su bili korišteni koji biljni pripravci. U tu svrhu korišten je anketni upitnik koji su prije trudničkog pregleda na Odjelu za ginekologiju i porodništvo Opće bolnice Zabok i bolnice hrvatskih veterana u Zaboku ispunile ukupno 102 trudnice. Dobiveni rezultati ukazali su na to da je 56 % ispitanica, od kojih je većina bila s područja Krapinsko-zagorske županije, koristilo biljne pripravke tijekom trudnoće. Mnoge od njih koristile su ih svakodnevno (27 %) ili više od dva puta tjedno (20 %), najčešće bez preporuke (55 %), a često i bez znanja svog ginekologa (48 %). Iako se većina ispitanica nije smatrala dovoljno informiranima o biljnim pripravcima koji se smiju koristiti u trudnoći, 60 % svih trudnica vjerovalo je da su biljni pripravci sigurni za korištenje u trudnoći te sigurniji od konvencionalnih lijekova. Ispitanice su biljne pripravke najčešće koristile kod suhog i nadražajnog kašlja, problema sa suhom kožom, infekcija mokraćnog sustava, grlobolje te mučnine i povraćanja. Najčešće korištena biljna vrsta bio je badem, a navelo ga je 50 % trudnica koje su koristile biljne pripravke i to isključivo za vanjsku primjenu, dok su manje zastupljeni đumbir (27 %), brusnica (25 %), kamilica (23 %) i bijeli sljez (12,5 %) bili u pravilu korišteni za unutarnju primjenu. Kao najpouzdaniji izvor informacija o biljnim pripravcima trudnice su u najvećoj mjeri navodile liječnika (55 %) i ljekarnika (47 %), a najveći udio ispitanica naveo je i da biljne pripravke kupuju upravo u ljekarnama (52 %). Zato je na liječnicima i ljekarnicima odgovornost pripadnicama ove posebno osjetljive populacije pružati pravovremene i potpune informacije o biljnim lijekovima i biljnim pripravcima, a kako bi se izbjegli mogući rizici te osigurala njihova sigurna i učinkovita primjena.In view of potential adverse effects of the use of certain plant species during pregnancy, knowledge about the frequency and habits of using herbal medicines and preparations during pregnancy is important for all healthcare professionals who provide care to pregnant women. The aim of this study was to determine the tendencies of pregnant women to use herbal preparations for external and internal use and to collect their views and beliefs on the safety, efficacy and availability of herbal preparations in comparison to conventional drugs, as well as to determine their ways of informing about herbal preparations. The aim was to collect data on the trimester in which pregnant women had been using herbal preparations and how often on average, according to whose recommendation, whether their gynecologist had been informed about it or not, where the herbal preparations were bought and for which disturbances and/or for what purpose was each of them used. For this purpose, a questionnaire was used, which was filled out before the medical examination at the Department of Gynecology and Obstetrics of the General Hospital Zabok and the Hospital of Croatian Veterans in Zabok by a total of 102 pregnant women. The obtained results indicated that 56% of the respondents, most of whom were from Krapina-Zagorje County, had been using herbal preparations during pregnancy. Many of them used them on a daily basis (27%) or more than twice per week (20%), usually without recommendation (55%), and often without the knowledge of their gynecologist (48%). Although most respondents did not think of themselves as being sufficiently informed about herbal preparations that may be used during pregnancy, 60% of all pregnant women believed that herbal preparations were safe to use during pregnancy and safer than conventional drugs. The respondents most often used herbal preparations for dry and irritating cough, dry skin problems, urinary tract infections, sore throat as well as nausea and vomiting. The most commonly used plant species was almond, which was mentioned by 50% of pregnant women that had been using herbal preparations, exclusively for external use, while less represented ginger (27%), cranberry (25%), chamomile (23%) and marsh mallow (12,5%) were mainly used internally. Physicians (55%) and pharmacists (47%) were cited by pregnant women as the most reliable providers of information on herbal preparations, and the largest share of respondents also stated that they were buying herbal preparations in pharmacies (52%). It is therefore the responsibility of physicians and pharmacists to provide members of this particularly sensitive population with timely and complete information on herbal medicines and herbal preparations in order to avoid possible risks and to ensure their safe and effective use
Cleaved SNAP-25 as a marker of central site of Botulinum toxin Type A action on pain
No full textIsprva samo smrtonosni toksin koji uzrokuje botulizam, BT-A se već više od 30 godina uspješno koristi u liječenju
različitih bolesti, od čega je kronična bol indikacija koja se i dalje istražuje.
Iako se smatra jednim od najpotentnijih bioloških toksina, pročišćeni farmakološki pripravak BT-A u nanomolarnim
dozama koristi se u liječenju različitih kliničkih stanja praćenih povećanom kontraktilnošću mišića. U pogledu liječenja
boli, velika mu je prednost što nakon jednokratne primjene njegovo djelovanje traje do nekoliko mjeseci, te tu dobiva
prednost nad poznatim analgeticima, naročito za liječenje kronične boli.
Dosadašnja istraživanja na modelima visceralne i bilateralne boli, u kojima je uočen bilateralni analgetski učinak BT-A
nakon unilateralne periferne i intratekalne, ali ne i središnje intracerebroventrikularne i intracisternalne primjene,
poslužili su kao temelj hipoteze o središnjemu segmentalnom analgetskom djelovanju BT-A na spinalnoj razini.
Imunohistokemijski detektiran pocijepani SNAP-25 u dorzalnome rogu kralješnične moždine
upućuje na retrogradni aksonalni transport s periferije do leđne moždine gdje onda ispoljava svoj antinociceptivni učinak
tako što modulira prijenos bolnog impulsa senzornim vlaknima na razini prve sinapse u leđnoj moždini.
Ovim radom se imunohistokemijski detektirao pocijepani SNAP-25 u dorzalnome rogu leđne moždine nakon periferne
primjene BT-A u desnu šapu štakora na karagenanskom modelu upalne boli. Nadalje, u skupini u kojoj je primijenjen
antitoksin (i.t.) uočena je statistički manja količina pocijepanog SNAP-25 proteina, što sugerira mogući transsinaptički
prelazak BT-A na razini leđne moždine. Ta saznanja svakako otvaraju prostor daljnjim istraživanjima o samome
mehanizmu transinaptičkog transporta BT-A.At first merely a lethal toxin which causes botulism, BT-A has been successfully used for more than 30 years in the
treatment of various ailments, of which chronic pain is an indication that continues to be researched. Though considered
to be one of the most potent biological toxins, its purified pharmacological preparation BT-A in nanomolar doses is used
in treating various clinical conditions accompanied by augmented muscular contractility. With regard to pain treatment,
it offers a significant advantage – after a single administration, its effects persist for several months, which gives it an
edge over popular analgesics, especially for chronic pain treatment.
Previous research on visceral and bilateral pain models, which have shown a bilateral analgesic effect of BT-A after
unilateral peripheral and intrathecal, but not central intracerebroventricular and intracisternal administration, has served
as the foundation of the hypothesis on the central segmental analgesic effect of BT-A at the spinal level.
Immunohistochemically detected cleaved SNAP-25 in the dorsal horn of the spinal cord indicates a retrograde axonal
transport from the periphery to the spinal cord where it exhibits
its antinociceptive effect by modulating pain impulse transmission via sensory fibers at the level of the first synapse in
the spinal cord.
This paper has immunohistochemically detected cleaved SNAP-25 in the dorsal horn of the spinal cord after the
peripheral administration of BT-A in the right footpad of rats in the carrageenan-induced inflammation model.
Furthermore, the group in which the antitoxin was administered showed a statistically reduced amount of the cleaved
SNAP-25 protein, which suggests the possibility of the transsynaptic transfer of BT-A at the level of the spinal cord.
These observations invite further research into the transsynaptic transfer mechanism of BT-A
Synthesis and characterization of artezunate β-carboline hybrid
No full textOtkriće artemizina označilo je prekretnicu u terapiji malarije, čemu svjedoči preporuka SZO da se ACT koristi kao prva linija u liječenju ove bolesti. Međutim, pojava rezistentnih sojeva plazmodija ugrožava učinkovitost terapije, zbog čega je potrebno kontinuirano razvijati nove antimalarike. Jedan od pristupa u dizajniranju i razvoju novih lijekova je molekulska hibridizacija koja podrazumijeva povezivanje dvije biološki aktivne molekule u jedinstveni kemijski entitet, odnosno hibridnu molekulu. Racionalnim odabirom roditeljskih molekula moguće je pripraviti hibrid koji djeluje na različite mete zbog čega ostvaruje snažnije djelovanje te neće doći do razvoja rezistencije. U okviru ovog diplomskog rada pripravljen je hibrid artezunata, polusintetskog derivata artemizinina i harmina, β-karbolinskog alkaloida s izraženim antimalarijskim djelovanjem korištenjem reakcije povezivanja uz coupling reagens HATU i bazu DIEA (spoj 6). Za potrebe sinteze hibrida, sintetiziran je i amin 5, u pet reakcijskih koraka. Struktura konačnog spoja potvrđena je uobičajnim analitičkim i spektroskopskim metodama (IR, MS, 1H i 13C NMR). U nastavku istraživanja pripravljenom hibridu bit će ispitano antimalarijsko i protutumorsko djelovanje.The discovery of artemisinin was a breakthrough in the treatment of malaria leading to the recommendation of the WHO to use ACT as the first-line therapy against malaria. Nevertheless, the occurrence of drug-resistant Plasmodium strains challenges its efficency and urges the need for constant development of new antimalarials. One of the approaches in the discovery of new bioactive agents is molecular hybridization, which represents synthesis of novel chemical entities (hybrid molecule) by forming covalent bond between two biologically active molecules. Rational selection of parent molecules enables the preparation of a hybrid with improved properties. Within this Master Thesis, hybrid (6) comprising artesunate, semisynthetic derivative of artemizinin and harmine, β-carboline alkaloid with pronounced antimalarial activity, was prepared by coupling reaction using HATU and DIEA. For the purpose of the hybrid synthesis, amine 5 was synthesized as well, through five reaction steps. The structure of novel compound was confirmed using standard analytical and spectroscopic methods (IR, MS, 1H i 13C NMR). Antimalarial and antiproliferative activity of the synthesized hybrid 6 will be evaluated in the future studies
Topical appliacation of rosemary (Salvia rosmarinus Spenn.)
No full textProblemi s kožom vrlo su česti te zahvaćaju ljude svih dobnih skupina. Stavljaju velik psihološki teret na pojedince i smanjuju kvalitetu života, a bolesti kože predstavljaju velik ekonomski teret za liječenje i prevenciju. Topikalna primjena lijekova najbolji je izbor za tretiranje ovakvih simptoma zbog svog brzog nastupa djelovanja te smanjenja mogućnosti sistemskih nuspojava, a biljni pripravci postaju sve popularniji izbor pacijenata prilikom liječenja benignijih stanja. Cilj ovog diplomskog rada bio je pregledati dostupnu literaturu o topikalnoj primjeni i učincima ružmarina (Salvia rosmarinus Spenn.) te utvrditi klinički značaj tih učinaka na kožne bolesti te potencijal uporabe u kozmetičkim pripravcima. Ružmarin je biljka s područja Mediterana, bogat je polifenolnim sastavnicama i triterpenima, a eterično ulje bogato mu je oksigeniranim monoterpenima. Poznat je po svojem antioksidativnom, antimikrobnom i protuupalnom djelovanju. Ovi učinci imaju velik potencijal u liječenju i prevenciji kožnih bolesti i stanja posebice nakon topikalne primjene pripravaka. U dostupnoj literaturi najviše se ističu studije koje su ispitivale učinak na alopeciju, upalne bolesti kože, dermatitise, uključujući i atopijski dermatitis, cijeljenje rana i starenje kože. Iako je provedeno čak i nekoliko kliničkih istraživanja koji potvrđuju dobar učinak pripravaka ružmarina u ovim indikacijama, daljnja opsežna istraživanja su potrebna kako bi se dodatno razjasnili mehanizmi djelovanja i sastavnice odgovorne za učinke.Dermal problems are very common, and they affect people of all ages. They place a great psychological burden on the individual and reduce the quality of life, and skin diseases represent a great economic burden for treatment and prevention. Topical application of drugs is the best choice for the treatment of such symptoms due to its rapid onset of action and reduction of the possibility of systemic side effects, and herbal preparations are becoming an increasingly popular choice for patients when treating more benign conditions. The aim of this work was to review the literature on the topical application and effects of the rosemary (Salvia rosmarinus Spenn.) and determine the clinical significance of these effects on skin diseases and the potential for use in cosmetic preparations. Rosemary is a plant from the Mediterranean area, it is rich in polyphenolic components and triterpenes, and its essential oil is rich in oxygenated monoterpenes. It is known for its antioxidant, antimicrobial and anti-inflammatory effects. These effects have great potential in the treatment and prevention of skin diseases and conditions, especially after topical application of the preparations. In the available literature, the most prominent are studies that examined the effect on alopecia, inflammatory skin diseases, dermatitis, including atopic dermatitis, wound healing and skin aging. Although even a few clinical studies have been conducted that confirm positive effect of rosemary in these indications, further extensive research is needed to additionally clarify the mechanisms of action and the compounds responsible for the effects