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Preparation and characterisation of in situ gelling donepezil solutions for nasal administration
No full textUslijed porasta broja oboljelih od Alzheimerove bolesti (AB) te nedostataka oralne primjene donepezila
kao glavnog lijeka u liječenju simptoma AB-a, javlja se potreba za razvojem inovativnih farmaceutskih oblika
donepezila za druge putove primjene. Nazalna primjena lijeka smanjuje rizik od nuspojava te omogućuje
zaobilazak krvno-moždane barijere i izravnu dostavu lijeka u mozak. In situ gelirajući sustavi inovativni su
farmaceutski oblici za nazalnu primjenu lijekova, s potencijalom povećane bioraspoloživosti, smanjene doze
i olakšane primjene u odnosu na oralnu primjenu, koja može biti otežana u Alzheimerovoj bolesti zbog
problema s gutanjem.
Cilj ovog rada bio je pripraviti i karakterizirati in situ gelirajuće sustave za nazalnu primjenu donepezila,
temeljene na kitozanu kao gelirajućem polimeru. U okviru istraživanja uspješno su pripravljene in situ
gelirajuće otopine donepezila (0,4 – 0,5 mg mL-1, m/V), s kitozanom (6,15 i 9,23 mg mL-1, m/V) i β-GP-om
(188,46 mg mL-1, m/V) kao pomoćnim tvarima. Pripravljene in situ gelirajuće otopine prikladnog su pH za
nazalnu primjenu (pH u rasponu od 7,36 do 7,46). Variranjem formulacijskih parametara postignuto je
prikladno vrijeme geliranja u odnosu na očekivani mukocilijarni klirens (formulacije s trenutnim geliranjem
te geliranjem u vremenskom intervalu od 4,2 ± 0,0 do 4,9 ± 0,1 min). Temperatura geliranja in situ gelirajućih
otopina donepezila bila je u rasponu od 33,0 ± 0,6 do 36,5 ± 0,1 °C. Pripravljene otopine bile su
pseudoplastičnog karaktera. Viskoznost u mirovanju otopina bila je u rasponu od 22,3 ± 0,4 do 113,6 ± 0,8
mPa s te je rasla s povećanjem koncentracije kitozana. Provedena ispitivanja pokazala su potencijal in situ
gelirajuće otopine donepezila, kitozana i β-GP-a kao prikladne tehnološke platforme za nazalnu primjenu
donepezila.Due to the increasing incidence of Alzheimer's disease (AD) and the lack of oral administration of
donepezil as first-line treatment of AD symptoms, there is a need to develop innovative donepezil
pharmaceutical forms for other routes of administration. Nasal drug delivery decreases a side effect risk,
enables a bypass of the blood-brain barrier and a direct transport of the drug to the brain. In situ gelling
systems are innovative pharmaceutical forms for nasal drug delivery with the potential to enhance
bioavailability, decrease the dose, and simplify administration compared to oral delivery, which can be
difficult for Alzheimer's disease patients due to swallowing problems.
The aim of this study was to prepare and characterize in situ gelling systems for nasal administration of
donepezil, based on chitosan as a gelling polymer. Within this study, in situ gelling donepezil solutions (0.4
– 0.5 mg mL-1, w/v) were successfully prepared with chitosan (6.15 – 9.23 mg mL-1, w/v) and β-GP (188.46
mg mL-1, w/v) used as excipients. Prepared in situ gelling solutions were characterised by adequate pH value
for nasal administration (pH interval 7.36 – 7.46). Appropriate gelation time considering mucocilliary
clearance was obtained by varying formulation parameters (formulations with instant gelation and gelation
within the interval of 4.2 ± 0.0 to 4.9 ± 0.1 min). Gelation temperature of in situ gelling donepezil solutions
was in the range of 33.0 ± 0.6 to 36.5 ± 0.1 °C. Prepared solutions showed pseudoplastic behavior. The zeroshear
viscosity of solutions was in the range of 22.3 ± 0.4 to 113.6 ± 0.8 mPa s, and it increased with the
increase in chitosan concentration. This study has shown the potential of in situ gelling solution of donepezil,
chitosan, and β-GP as an appropriate technological platform for nasal delivery of donepezil
Optimisation of polypropylene gycol extraction of bioactive compounds from olive leaves (Olea europaea L)
No full textListovi masline smatraju se jeftinim biljnim materijalom koji se može koristiti kao
izvor visokovrijednih polifenolnih spojeva. U ovom radu su razvijene dvije ekološki prihvatljive
metode za ekstrakciju bioaktivnih spojeva iz lista masline, koristeći netoksičnu smjesu vode,
polipropilen glikola i mliječne kiseline kao otapalo. Za ekstrakciju polifeno la iz lista masline
korištene su ultrazvukom potpomognuta ekstrakcija i ekstrakcija magnetnom miješalicom.
Ispitan je učinak dvaju ekstrakcijskih parametara: omjer sastavnica otapala i omjer čvrstog
prema tekućem (0,1-0,8 g/10 mL) na fenolni profil. Sadržaj oleuropeina, glavne bioaktivne
komponente u listu masline, je određen pomoću RP-HPLC-DAD-a. Sadržaj ukupnih polifenola,
flavonoida i fenolnih kiselina je određen spektrofotometrijskim metodama. Povećanje
organskog otapala i biljnog materijala u ultrazvučnoj ekstrakciji rezultiralo je višim
vrijednostima ukupnih polifenola i oleuropeina. Analizom fenolnih sadržaja dobivenih
ekstrakata utvrđeno je da je konvencionalna metoda ekstrakcije uz magnetnu miješalicu
učinkovitija u odnosu na ultrazvučnu ekstrakciju. Određeni su sadržaji polifenola uz magnetnu
mješalicu pri 25 °C i 20´: ukupni polifenoli 21,45 mg OLE/mL, ukupni flavonoidi 0,24 mg
QE/mL, ukupne fenolne kiseline 0,94 mg CAE/mL i oleuropein 6,47 mg/mL.Olive leaves are considered to be a cheap herbal material that can be used as
a source of phenolic compounds with high added value. In this work, two environmentally
friendly methods for the extraction of bioactive components from olive leaves were developed
using non-toxic mixtures of water, polypropylene glycol, and lactic acid as a solvent. Ultrasoundassisted
extraction and extraction with a magnetic stirrer of polyphenols from olive leaves were
investigated and the phenolic contents of obtained extracts were compared. In this thesis, two
extraction parameters were examined: ratio of solvent components and the ratio of solid to solvent
(0,1-0,8 g/10 mL) on the phenolic profile. The content of oleuropein, the main bioactive
compound in the extracts was determined using RP-HPLC-DAD. Total phenol, flavonoid, and
phenolic acid content were determined by spectrophotometric methods. The increase of organic
solvent and plant material in the ultrasound-assisted extraction resulted in increased total phenol
content and oleuropein. The analysis of phenolic content of obtained extracts suggested that
conventional extraction with a magnetic stirrer was more effective compared to an ultrasoundassisted
extraction. Obtained contents of phenolics using magnetic stirrer at 25 °C and 20´ were:
total phenol content 21,45 mg OLE/mL, total flavonoid content 0,24 mg QE/mL,total phemolic
acid content 0,94 mg CAE/mL and oleuropein content 6,47 mg/mL
Verification of latex anti-TNF-alpha nephelometric assay
No full textFaktor tumorske nekroze alfa prepoznat je kao glavni regulator upalnog odgovora, ali i kao pro-upalni citokin uključen u patogenezu nekih autoimunih bolesti. Iz tog razloga stvoreni su antagonisti TNF-α. Farmakokinetička varijabilnost, nuspojave vezane uz koncentraciju lijeka i uski terapijski raspon čine terapijsko praćenje koncentracije ovih lijekova korisnim u kliničkoj praksi.
U ovome radu opisan je postupak verifikacije kvantitativne imunonefelometrijske metode N Latex aTNFα (Siemens Healthineers) za određivanje lijekova adalimumaba i infliksimaba na potpuno automatiziranom analizatoru Atellica® NEPH 360 (Siemens Healthineers) u uzorku seruma. Verifikacija je obuhvatila ispitivanje preciznosti koristeći kontrolne uzorke proizvođača, usporedbu s enzimskim imunokemijskim testom RIDASCREEN ADA/IFX Monitoring (R-Biopharm AG) te provjeru granice kvantifikacije. Verifikacija je provedena u Zavodu za kliničku kemiju, KBC Sestre milosrdnice u Zagrebu.
Postupak je obuhvatio 66 uzorka seruma pacijenata u kojima je zatražena kvantifikacija ADA (N = 33) ili INF (N = 33). Ponovljivost i unutarlaboratorijska nepreciznost za određivanje ADA iznosi 5,0 % i 5,4 % za visoku razinu te 4,6 % i 4,7 % za nisku razinu kontrola, dok za određivanje INF iznosi 7,2 % i 6,1 % za visoku razinu te 4,5 % i 4,0 % na nisku razinu kontrole. Usporedba metoda je potvrdila da ne postoji proporcionalno ni konstanto odstupanje između metoda. Regresijskom analizom dobivena je jednadžba y = -0,095 (95%CI -0,148– 0, 092) + 0,995 (95%CI 0,881– 1,053) za ADA, dok za INF y = -0,062 (95%CI -0,381 – 0,439) + 0,958 (95%CI 0,834 – 1,107). Bland-Altman analiza potvrdila da je da ne postoji statistički značajno konstantno niti proporcionalno odstupanje. Provjerom LoQ potvrđeni su deklarirane vrijednosti proizvođača pri određivanju ADA (0,37 mg/L) i INF (0,39 mg/L). Rezultati verifikacije su potvrdili prikladnost ispitivane metode pri kvantitativnom određivanju ADA i INF.Tumor necrosis factor alpha is recognized as the main regulator of the inflammatory response, but also as a pro-inflammatory cytokine involved in the pathogenesis of some autoimmune diseases. For this reason, TNF-α antagonists were designed. Pharmacokinetic variability, drug concentration-related side effects and a narrow therapeutic range make therapeutic concentration monitoring of these drugs useful in clinical practice.
This thesis describes the verification procedure of the quantitative immunonephelometric method N Latex aTNFα (Siemens Healthineers) for the measurement of the drugs adalimumab and infliximab on the automated analyzer Atellica® NEPH 360 (Siemens Healthineers) in a serum sample. The verification included teh study of precision using quality control samples, comparison with the enzyme immunochemical test RIDASCREEN® ADA/IFX Monitoring (R-Biopharm AG) and a study of the limit of quantification. The verification was carried out at the Department of Clinical Chemistry, Sestre milosrdnice University Hospital Center, Zagreb.
The procedure included 66 serum samples from patients in whom ADA (N = 33) or INF (N = 33) quantification was requested. Repeatability and within-laboratory imprecision for the determination of ADA was 5.0% and 5.4% for the high level QC and 4.6% and 4.7% for the low level QC, while for the determination of INF was 7.2% and 6.1% for the high level QC and 4.5% and 4.0% to a low level QC. The comparison of the methods confirmed that there is no proportional or constant deviation between the methods. Regression analysis yielded the equation y = -0.095 (95%CI -0.148– 0. 092) + 0.995 (95%CI 0.881– 1.053) for ADA, while for INF y = -0.062 (95%CI -0.381 – 0.439) + 0.958 (95%CI 0.834 – 1.107). Bland-Altman analysis confirmed there is no statistically significant constant nor proportional deviation. The LoQ study confirmed the manufacturer declared values for ADA (0.37 mg/L) and INF (0.39 mg/L). The verification results confirmed the suitability of the tested method for the quantitative determination of ADA and INF
NMR study of gold nanoparticles preparation in presence of citric acid
No full textSve češća upotreba nanočestica u biomedicinske svrhe potaknula je izradu ovog istraživačkog
rada kako bi se obogatilo znanje i razumjeli mehanizmi tijekom priprave istih. Literaturnim
pregledom stvoren je katalog oksidacijskih reakcija limunske kiseline koje mogu dati
potencijalne produkte u sintezi nanočestica. Eksperimentalni dio priprave nanočestica zlata
u prisutnosti limunske kiseline (Turkevicheva metoda) proveden je u sintetskom laboratoriju
Instituta za medicinska istraživanja i medicinu rada u Zagrebu. Snimanje NMR spektara
reakcijskih alikvota provedeno je u Zavadu za organsku kemiju Farmaceutsko –
biokemijskog fakulteta. Proučavanjem NMR spektara reakcijskih smjesa prošireno je
razumijevanje mehanizama oksidacije limunske kiseline i razjašnjena je stabilnost suspenzije
nanočestica zlata u vodi. Najizraženiji signal nusprodukta u svakom snimljenom spektru
odgovara kemijskom pomaku acetona koji nastaje katalitičkom dehidracijom limunske
kiseline. Prisutnost acetona eksperimentalno je dokazana dodavanjem poznatog spoja u
uzorak, čime se pojačao postojeći signal. U spektru osim acetona, u području nižeg
magnetskog polja pojavljuje se prošireni signal koji odgovara limunskoj kiselini u interakciji
s formiranim nanočesticama, odnosno predstavlja „coating agent“ kao što je opisano u radu.
Uz proširenje signala, vidljivi su i signali koji upućuju na oksidacijske međuprodukte opisane
u uvodnom dijelu, a njihovi kemijski pomaci odgovaraju očekivanim 1H signalima. Radi se
o dikarboksiacetonu i acetooctenoj kiselini, koji su dobiveni podešavanjem reakcijskih
uvjeta. Na taj način dokazano je postojanje onečišćenja tijekom sinteze nanočestica.Increased usage of nanoparicles in biomedicine has inspired the making of this research. It's
goal is to enrich the knowledge and improve the understanding of mechanisms during the
shyntesis of nanoparticles. The potencial products of nanoparticles synthesis were chosen
from a list of oxidation reactions of citric acid, compiled by studying the literature. The
experiment consists of two parts. The first part is Turkevich's method of making nanoparticles
in labaratory of Medical research institute in Zagreb, followed by NMR spectroscopy at
Institute for organic chemistry on Faculty of Pharmacy and Biochemistry. The understanding
of oxidation mechanisms of citric acid was expanded and the stability of nanoparticle water
suspension was clarified by analizing the NMR spectrum of reaction mixtures. The most
expressed signal in almost every spectrum corresponds to the chemical shift of acetone, which
is created in catalytic dehydration of citric acid. Presence of acetone was experimentaly
proven by adding the known substance in the sample, which amplified the existing signal.
Except acetone, in lower magnetic field region, the expanding signal appeared which
represents the citric acid in interaction with formed gold nanoparticles, that is „coating agent“
as described in the paper. Besides the expanding signal, there are some discreet signals which
indicate that there are oxidation intermidiate products as described in introductory part and
their chemical shifts correlate with predicted. The molecules in question are
dicarboxyacetone and acetoacetate which are created by modulating the reaction conditions.
All these evidance shows that there are impurities in shyntesis mixture of nanoparticles
Oštećenje bubrežne funkcije i terapijski problemi u bolesnika starije životne dobi kod prijema u bolnicu
No full textCilj istraživanja: Cilj ovog istraživanja bio je procijeniti vrstu i učestalost rizičnih lijekova s obzirom na bubrežnu funkciju i ostalih farmakoterapijskih problema (politerapije, potencijalno neprikladnih lijekova i potencijalno klinički značajnih interakcija lijekova) primjenom najbolje moguće medikacijske povijesti (engl. Best Possible Medication History-BPMH) kod osoba starije životne dobi s oštećenom bubrežnom funkcijom koje su bile zaprimljene u bolnicu. Cilj je bio utvrditi i korelaciju između navedenih farmakoterapijskih problema.
Ispitanici i metode: U Službi internističkih djelatnosti Nacionalne memorijalne bolnice “Dr. Juraj Njavro” Vukovar provedeno je prospektivno opservacijsko istraživanje među pacijentima starije životne dobi kojima je vrijednost procijenjene GFR na prijemu u bolnicu bila manja od 60 ml/min/1,73m2, odnosno koji se svrstavaju u kategorije bubrežne funkcije G3a, G3b, G4 i G5. Procijenjeni stupanj glomerularne filtracije (eGFR) računao se za svakog pacijenta korištenjem CKD-EPI formule. Klinički farmaceut je za svakog od ovih pacijenata izradio BPMH unutar 24h od prijema u bolnicu. Za analizu rizičnih lijekova s obzirom na bubrežnu funkciju koristili su se važeći sažetci opisa svojstava lijeka (HALMED). Politerapija je definirana kao istodobna primjena od 5 do 9 lijekova, a prekomjerna politerapija kao primjena ≥10 lijekova. Analiza PNL-ova provedena je pomoću EU(7)-PIM kriterija. Potencijalno kliniĉki znaĉajne interakcije lijekova su utvrđivane pomoću programa Lexicomp® Lexi-Interact TM. 2. Povezanosti između terapijskih problema u BPMH utvrđena je računanjem Pearsonovog koeficijenta korelacije pomoću programa Microsoft Excel.
Rezultati: Istraživanje je uključilo 67 ispitanika starije životne dobi s oštećenom bubrežnom funkcijom, prosječne dobi 76 (72-85). 64% ispitanika su bile žene (n=43). Kod 89,6% pacijenata utvrđen je 171 rizičan lijek s obzirom na stupanj oštećenja bubrežne funkcije.
49,1% rizičnih lijekova s obzirom na bubrežnu funkciju imali su ili neprilagođenu dozu ili su bili kontraindicirani s obzirom na oslabljenu bubrežnu funkciju. Ukupno je 65,7% ispitanika u BPMH koristilo najmanje jedan neprikladno propisan rizični lijek (neprilagođena doza i kontraindiciran) s obzirom na bubrežnu funkciju; 35,8% ispitanika imali su jedan ili više kontraindiciranih lijekova s obzirom na bubrežnu funkciju; 38,8% pacijenata imalo je najmanje jedan lijek kojem je bila neprilagođena doza s obzirom na bubrežnu funkciju.
Politerapiju je primjenjivalo 28,4% ispitanika (između 5 i 9 lijekova), dok je prekomjernu politerapiju (10 i više lijekova) primjenjivalo 64,2% ispitanika. Ukupno je 98,5% ispitanika imalo najmanje 1 PNL prema EU(7)-PIM listi. Kod 98,5% (n=66) je zabilježena barem jedna klinički značajna interakcija. Utvrđene su pozitivne korelacije između analiziranih farmakoterapijskih problema.
Zaključak: Klinički farmaceut je primjenom BPMH utvrdio veliku zastupljenost svih farmakoterapijskih problema u osoba starije životne dobi s oslabljenom bubrežnom funkcijom koje su bile zaprimljene u bolnicu tijekom provođenja istraživanja. Istraživanje ukazuje na značaj izrade BPMH za utvrđivanje različitih farmakoterapijskih problema kod bolesnika starije životne dobi s oslabljenom bubrežnom funkcijom prilikom transfera skrbi, tj. odmah na prijemu pacijenata u bolnicu. Utvrđene pozitivne korelacije između farmakoterapijskih problema ukazuje na njihovu međusobnu ovisnost tj. na očekivano istovremeno pojavljivanje.Objectives: The aim of the study was to assess the type and frequency of renal risk drugs and other pharmacotherapeutic problems (polypharmacy, potentially inappropriate medication and
drug-drug interactions) by using the Best Possible Medication History, BPMH) in elderly with impaired kidney function who were admitted to the hospital. Also, the goal was to determine the correlation between these pharmacotherapeutic problems.
Patients and methods: An observational prospective study was conducted at the Department of Internal Medicine of the National Memorial Hospital "Dr. Juraj Njavro" Vukovar, among elderly patients whose estimated GFR at admission to the hospital was less than 60 ml/min/1.73m2, i.e. who are classified as renal function categories G3a, G3b, G4 and G5. Estimated glomerular filtration rate (eGFR) was calculated for each patient by using the CKD-EPI formula. The clinical pharmacist created a BPMH for each of these patients within 24 hours since admission to the hospital. Summaries of product characteristics (HALMED) available at the time of the study were used for the analysis of renal risk drugs. Polytherapy is defined as the simultaneous use of 5 to 9 drugs, and excessive polytherapy as the use of ≥10 drugs. The analysis of potentially inappropriate medication was performed using the EU(7)-PIM criteria. Potentially clinical significant drug-drug interactions were detected by using the Lexicomp® Lexi-Interact TM program. 2. Connections between therapeutic problems in BPMH were determined by calculating the Pearson correlation coefficient using the Microsoft Excel program.
Results: The study included 67 elderly subjects with impaired renal function, average age 76 (72-85). 64% of them were women (n=43). In 89.6% of patients, 171 renal risk drugs were found. 49.1% of renal risk drugs had either an unadjusted dose or were contraindicated due to impaired renal function. In total, 65.7% of patients used at least one inappropriately prescribed renal risk drug (unadjusted dose and contraindicated); 35.8% of patients had at least one contraindicated renal risk drug; 38.8% of patients had at least one drug whose dose was unadjusted due to renal function. Polypharmacy was used by 28.4% of patients (between 5 and
9 drugs), while excessive polypharmacy (at least 10 drugs) was used by 64.2% of patients. In total, 98.5% of patients had at least 1 PNL according to the EU(7)-PIM list. 98.5% (n=66) patients were found to have at least one potentially significant drug-drug interaction. Analysis determined positive correlations between certain pharmacotherapy problems.
Conclusion: The clinical pharmacist detected high incidence of all pharmacotherapeutic problems in elderly people with impaired renal function who were admitted to the hospital during the research. The study highlights the importance of using a BPMH for determining various pharmacotherapeutic problems in elderly patients with impaired renal function during the transfer of care, immediately upon admission to the hospital. The positive correlations between pharmacotherapeutic problems indicate that they are dependent and their simultaneous occurrence is expected
The effect of Satureja montana L. essential oil and thymol on pyocyanin synthesis of Pseudomonas aeruginosa
No full textPseudomonas aeruginosa ubikvitaran je oportunistički patogen te jedan od najznačajnijih uzročnika bolničkih infekcija. Posjeduje velik broj faktora virulencije između kojih se ističe plavo-zeleni pigment piocijanin koji djeluje proupalno, dovodi do stvaranja slobodnih radikala i oksidativnog stresa te potiče stvaranje biofilma i apoptozu neutrofila. Zbog velike stope morbiditeta i mortaliteta te sve veće antibičke rezistencije uključen je u kategoriju kritičnih bakterijskih patogena za koju je nužno potrebno istraživanje i razvoj novih oblika terapije. Eterična ulja su još iz davnina poznata za svoja antimikrobna svojstva, a eterično ulje biljne vrste Satureja montana L. pokazalo je iznimno antibakterijsko djelovanje te je stoga u ovom radu ispitivan utjecaj eteričnog ulja satureje i njezine glavne monoterpenske sastavnice timola u koncentracijama 0,5 mg/mL, zasebno i u kombinaciji s aminoglikozidnim antibiotikom tobramicinom u koncentraciji 0,5 mg/L , na rast i stvaranje piocijanina bakterijskog soja P. aeruginosa PAO1. Ispitivanje utjecaja na rast bakterijske kulture provedeno je mjerenjem optičke gustoće na 600 nm dok je učinak na proizvodnju piocijanina određen mjerenjem apsorbancije ekstrahiranog piocijanina na 520 nm te normaliziranjem vrijednosti na broj bakterijskih stanica. Rezultati su pokazali da eterično ulje satureje i timol pokazuju inhibitorni učinak na rast bakterijskih stanica P. aeruginosa te sinergistički djeluju na smanjenje rasta u kombinaciji s tobramicinom. S druge strane, timol nije pokazao značajan utjecaj na stvaranje pigmenta piocijanina dok je u prisustvu eteričnog ulja satureje došlo do povećanog stvaranja pigmenta u odnosu na netretiranu bakterijsku kulturu. U kombinaciji s tobramicinom, eterično ulje i timol pokazali su antagonističko djelovanje te doveli do povećanog stvaranja pigmenta. Rezultati ovog rada doprinose boljem razumijevanju kompleksnih interakcija između eteričnih ulja i njezinih sastavnica na P. aeruginosa s ciljem unaprjeđenja terapije infekcija uzrokovanih P. aeruginosa.Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen and one of the most significant causes of healthcare-associated infections. It possesses a variety of virulence factors, namely the blue-green pigment pyocyanin, which acts proinflammatory, leads to the production of free radicals and oxidative stress as well as induces biofilm formation and neutrophil apoptosis. Due to the huge morbidity and mortality and the increasing antibiotic resistance, it is considered a critical pathogen for which research and new therapy are urgently needed. Essential oils have been recognised for their antimicrobial properties, and the essential oil from Satureja montana L. has shown exceptional antibacterial properties. This research examined the effect of Satureja essential oil and its main monoterpene component thymol, both in concentrations 0,5 mg/mL, alone and in the combination with the aminoglycoside antibiotic tobramycin, on the growth and pyocyanin production of the bacterial cells of P. aeruginosa PAO1.
The effect on bacterial growth was examined by measuring the optical density at 600 nm while the effect on pyocyanin production was determined by measuring the absorption of the extracted pyocyanin at 520 nm and normalised on the number of bacterial cells. The results showed that Satureja essential oil and thymol both showed inhibitory effects on P. aeruginosa growth and they both acted synergistically with tobramycin. On the other hand, thymol showed no significant effect on pyocyanin production, while pyocyanin production was increased in the presence of Satureja essential oil. In combination with tobramycin, the essential oil and thymol showed antagonistic action that led to increased pigment production. The results of this study contribute to a better understanding of the complex interaction between essential oils and their components on P. aeruginosa with the goal of improving the therapy of infections caused by P. aeruginosa
Use of herbal preparations in infants, early and preschool
No full textBiljke i biljni pripravci čine moguću alternativu kod raznih smetnji i stanja u dječjoj dobi. Cilj ovog istraživanja bio je utvrditi sklonost i navike roditelja korištenju biljnih pripravaka kod djece u dobi od mjesec dana do šest godina, stavove o sigurnosti, učinkovitosti i dostupnosti biljnih pripravaka te učestalost korištenja istih. U tu svrhu korišten je anketni upitnik kojeg je ispunilo ukupno 106 ispitanika u prostoru Specijalističke pedijatrijske ordinacije Metka Regan, dr. med. u Zagrebu prilikom dolaska djece na sistematske preglede. Čak 51,96 % roditelja potvrdilo je da koristi biljne pripravke kod djece, a od njih 81,13 % odgovorilo je da radije koristi biljne pripravke nego konvencionalne lijekove kod djece. Učestalost korištenja biljnih pripravaka kod djece raste s njihovom dobi, što se može povezati s povećanom osjetljivošću dojenčadi. Gotovo polovica ispitanika u potpunosti se slagala s tvrdnjom da su biljni pripravci sigurni za korištenje kod djece. Roditelji su naveli da najčešće koriste biljne pripravke kod djece prema preporuci liječnika i ljekarnika, a velika većina roditelja koji koriste biljne pripravke kod svoje djece tvrdila je da je djetetov liječnik upoznat s time da djetetu daju biljne pripravke. Roditelji su najčešće koristili biljne pripravke kod suhog i nadražajnog te produktivnog kašlja, ogrebotina, manjih rana i uboda insekata, a najčešće navedena biljna vrsta bila je kamilica, koju je koristilo čak 16,98 % roditelja.Herbs and herbal preparations are a possible alternative for various medical disturbances and conditions during childhood. The aim of this study was to determine the preferences and habits of parents that use herbal preparations in children aged one month to six years, their attitudes about the safety, effectiveness and availability of herbal preparations, and the frequency of their usage. For this purpose, a questionnaire was distributed and filled out by a total of 106 respondents in the Pediatric Specialty Clinic Metka Regan, MD. in Zagreb at the time of children’s regular physical exams. As many as 51.96% of parents confirmed that they use herbal preparations in children, and 81.13% of them answered that they prefer using herbal preparations rather than conventional medicines in children. The frequency of usage of herbal preparations in children increased with their age, which may be associated with increased sensitivity of infants. Almost half of the respondents fully agreed with the statement that herbal preparations were safe for children. Parents stated that they most often use herbal preparations in children as recommended by doctors and pharmacists, and the vast majority of parents who use herbal preparations in their children claimed that the child's doctor was aware that they were giving herbal preparations to the child. Parents most often used herbal preparations for dry and irritating or productive cough, minor wounds, scratches, and insect bites. The most common plant species was chamomile, which was used by 16.98% of parents
A molecular docking study of synthetic peptide inhibitor derivatives as potential human fibroblast collagenase inhibitors
No full textUzimajući u obzir čovjekov sve duži životni vijek, javlja se sve veća potreba za održavanjem optimalne razine kolagena tijekom još
duljeg perioda života. Padom razine kolagena nakon 25. godine za otprilike 2% godišnje osoba se tijekom procesa starenja susreće s
mnogim oslabljenim funkcijama organizma. Promjene su najprije vidljive u obliku boranja kože te njezine smanjene elastičnosti, a
kasnije se mogu razviti i razne bolesti zglobova (artritisi) s oticanjem i smanjenom pokretljivošću te poremećaji mineralizacije i
gustoće kostiju, što sve zajedno dovodi do smanjene kvalitete života. U ovom trenutku, najistraživanija mogućnost povećanja razine
kolagena u organizmu je pomoću dodataka prehrani temeljenih na kolagenu. Tržište je trenutno zasićeno mnogim farmaceutskim
oblicima kolagena, koji se dobivaju iz različitih životinjskih, posebice ribljih, izvora. Cilj ovog istraživanja je skrenuti pažnju na malo
drugačiji pristup održavanja koncentracija kolagena u organizmu, koji bi mogao biti puno učinkovitiji u praksi. Budući da je glavni
razlog smanjenja razine kolagena u organizmu njegova povećana razgradnja posredovana enzimima matriksnih metaloproteinaza
(MMP), smatra se da bi inhibicija upravo tih enzima dovela do sprječavanja razgradnje kolagena u organizmu te bi se na taj način
očuvala razina endogenog kolagena tijekom puno duljeg životnog razdoblja. Postojećim istraživanjem Borkakoti i sur. (1994)
pronađena je sintetski inhibitor koji se veže u katalitičko mjesto enzima humane kolagenaze fibroblasta te posljedično sprječava
razgradnju kolagena. Ovaj inhibitor je pokazao dobra i strukturna i ADMET svojstva, koja su poželjna kod razvoja novih lijekova.
Vodeći se navedenim saznanjima, cilj ovog istraživanja bio je poboljšati vezanje inhibitora u aktivno mjesto enzima te tako postići
jači inhibitorni učinak. Metodom molekulskog sidrenja ispitivao se inhibitorni učinak ukupno 765 molekula dizajniranih po uzoru na
prethodno nađeni sintetski inhibitor, pri čemu je njihova struktura prilagođena prirodi aminokiselinskih ostataka u aktivnom mjestu
enzima. Rezultati istraživanja pokazuju da ligandi 157 i 303 posjeduju najbolji inhibitorni učinak na ispitivani enzim s energijom
vezanja od ΔG = –9,2 kcal mol-1, što je za 2,8 kcal mol-1 niže od energije vezanja početne molekule sintetskog inhibitora. Međutim,
navedene dvije molekule imaju ponešto lošija farmakokinetička svojstva od početne molekule, a ono što se istaknulo posebno lošim
je njihov toksikološki profil. Dobivene molekule vrijedne su daljnjeg razmatranja s obzirom na izrazito povoljnu energiju vezanja u
aktivno vezno mjesto enzima, međutim da bi bile primjenjive u praksi, moraju proći daljnju optimizaciju prvenstveno toksikoloških,
a potom i farmakokinetičkih svojstava.Given the current trend of longer life expectancy, there is an increasing need to maintain an optimal collagen levels during an even
more extended lifespan. Due to a decrease in collagen levels after the age of 25 by approximately 2% per year, a person encounters
many weakened body functions during the process of aging. Firstly, changes are visible in the form of skin wrinkles and its reduced
elasticity, but later on various joint diseases (like arthritis), as well as mineralization and bone density disorders can develop.
Currently, the most used method to increase collagen levels in the body is through collagen-based dietary supplements. The market
offers a wide range of pharmaceutical collagen products derived from various animal (especially fish) sources. The aim of this
research was to draw attention to a slightly different approach to maintaining collagen concentrations in the body, which could be
much more effective in practice. Particularly, since the main reason for the decrease in the collagen level in the body is the increased
collagen breakdown mediated by matrix metalloproteinases (MMP) enzymes, it is believed that inhibition of these enzymes would
lead to a prevention of collagen breakdown in the body, thus preserving the level of endogenous collagen much during a much longer
life expectancy. The existing research by Borkakoti et al. (1994) found a synthetic inhibitor that binds to the catalytic site of the
human fibroblast collagenase enzyme and consequently prevents collagen degradation. This molecule showed good structural and
ADMET properties, desirable in new drug development. Based on these findings, the goal of this research was to improve the binding
of the inhibitor to the enzyme active site and thus to achieve a stronger inhibitory effect. Using molecular docking, the inhibitory
effect of a total of 765 new molecules was predicted. The molecules were designed based on the model of the previously found
synthetic inhibitor and adapted to the nature of amino acid residues in the active site of the enzyme. The research results show that
ligands 157 and 303 have the best inhibitory effect on the tested enzyme with a binding energy of ΔG = –9.2 kcal mol-1, which is 2.8
kcal mol-1 lower than the binding energy of the initial synthetic inhibitor. However, the aforementioned two molecules exhibit slightly
inferior pharmacokinetic properties than the initial synthetic inhibitor, with their toxicological profile being particularly concerning.
The resulting molecules are worthy of further consideration due to the very favorable binding energy in the enzyme active site
however, in order to be applicable in practice, they must undergo further optimization primarily of toxicological and then
pharmacokinetic properties
Total polyphenol content and antioxidant activity of dietary supplements used by women in menopause
No full textU posljednje vrijeme provode se mnoga istraživanja radi procjene antioksidativnog djelovanja polifenolnih sastavnica u hrani i dodacima prehrani. Ove biološki aktivne tvari su iznimno cijenjene zbog preventivnog i terapijskog djelovanja na ljudsko zdravlje. Cilj ovog rada bio je procijeniti kvalitetu dodataka prehrani koji sadrže lan, crvenu djetelinu, hmelj i konopljiku obzirom na ukupni sadržaj polifenola te odrediti antioksidativnu aktivnost istih. Sadržaj ukupnih polifenola u analiziranim dodacima prehrani određen je Folin-Ciocalteu metodom, dok je antioksidativna aktivnost istih procijenjena HPLC-DPPH metodom. Ova kromatografska metoda se pokazala brza i ponovljiva te prikladna za rutinsku analizu uzoraka. Ispitivani dodaci prehrani koji sadrže ekstrakte navedenih biljaka dobar su izvor polifenolnih spojeva. Antioksidativna aktivnost analiziranih dodataka prehrani u skladu je sa sadržajem ovih sekundarnih metabolita. Korelacija između ukupnog sadržaja polifenola i antioksidativne aktivnosti je statistički značajna, iz čega je vidljivo da je antioksidativno djelovanje proporcionalno koncentraciji ovih bioaktivnih sastavnica. Rezultati ovog istraživanja doprinose boljem razumijevanju sadržaja ukupnih polifenola i antioksidativne aktivnosti dodataka prehrani koji sadrže lan, crvenu djetelinu, hmelj i konopljiku.Recently, many studies have been conducted to evaluate the antioxidant activity of polyphenolic components in foods and dietary supplements. These biologically active substances are highly valued phytochemicals due to their preventive and therapeutic effects on human health. This study aimed to evaluate the quality of the flax-based, red clover-based, hop-based and chasteberry-based dietary supplements concerning the total polyphenol content and their antioxidant activity. The total polyphenol content in the analyzed dietary supplements was determined by Folin-Ciocalteu method, while the antioxidant activity was estimated by HPLC-DPPH method. This chromatography method has been shown to be fast and reproducible, and suitable for use in routine analysis. The tested dietary supplements containing extracts of these plants are a good source of polyphenolic compounds. The antioxidant activity of the analyzed dietary supplements is in accordance with the content of these secondary metabolites. The correlation between the total polyphenol content and antioxidant activity is statistically significant, and the antioxidant activity is proportional to the concentration of these bioactive compounds. The results of this study contribute to a better understanding of the content of total polyphenols and the antioxidant activity of flax-based, red clover-based, hop-based and chasteberry-based dietary supplements
Važnost razumijevanja farmakokinetičko-farmakodinamičkih odnosa antibiotika u individualiziranom pristupu liječenju pneumonije kod mehanički ventiliranih bolesnika
No full textCilj istraživanja: Cilj je ovoga rada prikazati važnost razumijevanja i poznavanja farmakokinetičko-farmakodinamičkih odnosa antibiotika u individualiziranom doziranju lijeka i postizanju učinkovitog liječenja pneumonije kod mehanički ventiliranih bolesnika.
Materijali i metode: Napravljen je sustavni i retrospektivni pregled stručne i znanstvene literature. Pretražene su trenutno važeće smjernice, publikacije stručnih institucija, terapijski priručnici te drugi raspoloživi izvori relevantni za temu rada. Ključne riječi za pretraživanje baza podataka (Medline/Pubmed, Cochraine, ScienceDirect i Up to date) uključivale su sljedeće pojmove: engl. antibiotics, dosage, pharmacokinetic-pharmacodynamic relationships, ventilator-associated pneumonia – etiology, pathogenesis, clinical manifestations, patient characteristics, pharmacotherapy.
Rezultati: U radu je sistematično prikazana pneumonija kod mehanički ventiliranih bolesnika, uključujući etiologiju, patogenezu, kliničku sliku, prognozu i farmakoterapiju bolesti. Prisutnost uzročnika sa smanjenom osjetljivošću i patofiziološke promjene u organizmu mehanički ventiliranih bolesnika utječu na farmakokinetiku antibiotika i povećavaju rizik od suboptimalnog doziranja lijeka. Suboptimalno doziranje smanjuje vjerojatnost postizanja farmakokinetičko-farmakodinamičkih odnosa antibiotika potrebnih za postizanje učinkovite koncentracije lijeka na mjestu infekcije i povezano je s lošim terapijskim ishodom. Individualizacijom doziranja mogu se postići optimalne koncentracije antibiotika u intervalu doziranja kako bi se osigurala učinkovita terapija i smanjio rizik od pojave toksičnosti i razvoja antimikrobne rezistencije.
Zaključak: Odabir antibiotika i doziranje potrebno je individualizirati za svakog bolesnika u skladu s njegovim specifičnim karakteristikama, a poznavanje povezanosti ishoda liječenja s farmakokinetičko-farmakodinamičkim odnosima lijeka može koristiti u osiguravanju optimalne terapije.Objectives: The aim of this paper is to show the importance of understanding and knowing the pharmacokinetic-pharmacodynamic relationships of antibiotics in individualized drug dosing and achieving effective treatment of Ventilator-associated pneumonia.
Subjects and methods: A systematic and retrospective review of professional and scientific literature was made. Currently valid guidelines, professional institutions publications, therapeutic manuals and other available sources relevant to the topic of the work were searched. Keywords for searching the databases (Medline/Pubmed, Cochraine, ScienceDirect and Up to date) included the following terms: antibiotics, dosage, pharmacokinetic-pharmacodynamic relationships, ventilator-associated pneumonia – etiology, pathogenesis, clinical manifestations, patient characteristics, pharmacotherapy.
Results: The paper systematically presents ventilator-assosiated pneumonia, including etiology, pathogenesis, clinical manifestations, prognosis and pharmacotherapy of the disease. The presence of pathogens with reduced sensitivity and physiological changes in the organism of mechanically ventilated patients affect the pharmacokinetics of antibiotics and increase the risk of suboptimal drug dosing. Suboptimal dosing reduces the likelihood of achieving the pharmacokinetic-pharmacodynamic relationships of antibiotics necessary to achieve effective drug concentrations at the site of infection and is associated with poor therapeutic outcomes. By individualizing the dosage, optimal antibiotic concentrations can be achieved in the dosing interval to ensure effective therapy and reduce the risk of toxicity and the development of antimicrobial resistance.
Conclusion: The choice of antibiotics and dosing must be individualized for each patient in accordance with his specific characteristics, and knowledge of the relations between treatment outcomes and the pharmacokinetic-pharmacodynamic relationship of the drug in ensuring optimal therapy