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Development and validation of the RP-HPLC method for the determination of triiodthyronine and thyroxins in biological sample
No full textHipotireoza je patološko stanje koje se javlja zbog smanjenja stvaranja i lučenja hormona štitnjače. Terapija hipotireoze oslanja se na primjenu levotiroksina, no identificirana je subgrupa pacijenata s ostatnim simptomima unatoč toj terapiji. Zbog toga u zadnja dva desetljeća sve veći broj pacijenata poseže za tiroidnim pripravcima koji osim tiroksina sadrže i trijodtironin. Prirodni tiroidni pripravci su po sastavu suhi prah štitne žlijezde. Problem njihovog korištenja su neriješena pitanja sadržaja koji se razlikuje između proizvođača, ali i između pojedinih serija istog proizvođača. Do sada mali se broj istraživanja bavio utvrđivanja u tiroidnim pripravcima i stabilnosti T3 i T4 u njima. Stoga je cilj ovog rada razviti i validirati brzu, specifičnu i pouzdanu metodu tekućinske kromatografije visoke djelotvornosti na reverznoj fazi s UV-Vis detekcijom za istovremeno kvantificiranje T3 i T4 u takvom biološkom uzorku. Antrakinon je korišten kao unutarnji standard za kvantifikaciju T3 i T4. Metoda je validirana ispitivanjem točnosti, preciznosti, specifičnosti, linearnosti te granice detekcije i granice kvantifikacije. Razvijena metoda je visoko specifična (RSD 0,41170 % za T3 i 0,35716 % za T4) i točna (analitički prinos 103,29 % – 116,81 %). Metoda je linearna u ispitivanom koncentracijskom području (0,125 – 2,5 μg/mL). Intra i inter-testna preciznost je visoka (RSD za T3 i T4 te unutarnjeg standarda bio niži od 5 %). Limit detekcije i limit kvantifikacije niski su za oba analita (LOD 80 ng/mL, LOQ 243 ng/mL). Metoda je primijenjena za kvantitativnu analizu T3 i T4 u komercijalnom tiroidnom pripravku unutar i izvan roka trajanja. Rezultati kvantitativne analize tiroidnog pripravka koji je bio unutar roka valjanosti slažu se s deklariranim vrijednostima sadržaja dok je analiza uzorka izvan roka trajanja pokazala smanjenu količinu T3 i T4.Hypothyroidism is a pathological condition that occurs due to a decrease in the formation and secretion of thyroid hormones. Hypothyroidism therapy relies on the use of levothyroxine, but a subgroup of patients with residual symptoms has been identified despite this therapy. That is why in the last two decades an increasing number of patients are resorting to thyroid preparations that contain triiodothyronine in addition to thyroxine. Natural thyroid preparations are by composition dry powder of the thyroid gland. The problem of their use is unresolved issues of content that differs between manufacturers but also between individual series of the same manufacturer. A small number of studies have been done so far with the aim of solving this issue, so the aim of this paper is to develop and validate a fast, specific and reliable method of High-performance liquid chromatography on the reverse phase with UV-Vis detection for simultaneous quantification of T3 and T4 in such biological sample. Anthraquinone was used as an internal standard for quantifying T3 and T4. The method is validated by examining the accuracy, precision, specificity, linearity and limit of detection limit of quantification. The developed method is highly specific (RSD 0.41170 % for T3 and 0.35716 % for T4) and accurate (analytical yield 103.29 % - 116.81 %). The method is linear in the concentration area studied (0.125-2.5 μg/mL). Intra and inter-test accuracy is high (RSD for T3 and T4 and internal standard was lower than 5%). Limit of detection and limit od quatification are low for both analytes (LOD 80 ng/mL, LOQ 243 ng/mL). The method was applied for quantitative analysis of T3 and T4 in a commercial thyroid preparation inside and outside the shelf life. The results of quantitative analysis of the thyroid preparation that was within the shelf life correspond to the declared content values, while the sample analysis outside the shelf life showed a decreased amount of T3 and T4
Synthesis and characterization of novel harmine and mefloquine hybrid ureas
No full textOvaj rad dio je istraživanja provedenog na Zavodu za farmaceutsku kemiju Farmaceutsko-biokemijskog fakulteta Sveučilišta u Zagrebu. Istraživanje obuhvaća dizajn, sintezu i biološku evaluaciju derivata harmina s potencijalnim antimalarijskim djelovanjem. Cilj ovog rada bila je sinteza i karakterizacija novih hibridnih urea harmina i meflokina. Sinteza je započeta prevođenjem derivata meflokina do odgovarajućeg amina 1. Harmol 2 je dobiven iz harmina, dok je fenol 7 dobiven iz 5-metoksitriptamina. Harmin, harmol i fenol 7 su pomoću 2-(Boc-amino)etil bromida i klorovodične kiseline prevedeni u odgovarajuće amine 3, 5 i 10. Nukleofilnom supstitucijom uz CDI iz amina 3, 5 i 10 te amina 1 sintetizirani su konačni produkti – uree 12a-c.
Strukture svih novosintetiziranih spojeva potvrđene su uobičajenim analitičkim i spektroskopskim metodama (IR, 1H i 13C NMR, MS) te im je određena temperatura tališta. Sva tri konačna spoja djelomično zadovoljavaju Lipinskijeva i Veberova pravila koja se koriste za predviđanje oralne bioraspoloživosti lijekova. Također, web alat SwissADME predviđa slabu oralnu bioraspoloživost urea 12a-c. Antimalarijsko i citostatsko djelovanje novosintetiziranih derivata bit će ispitano u daljnjim istraživanjima koja prelaze okvire ovog rada.This paper is part of ongoing research at the Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb. The research includes the design, synthesis and biological evaluation of novel harmine derivatives as potential antimalarial drugs. The aim of this diploma thesis was the synthesis and characterization of novel harmine urea derivatives comprising mefloquine moiety in their structure. The synthesis began with the transformation of the mefloquine derivative to amine 1. Harmol 2 was generated from harmine, while phenol 7 was generated from 5-methoxytryptamine. Then, harmine, harmol and phenol 7 were converted into amines 3, 5 and 10 using 2-(Boc-amino)ethyl bromide and subsequently, hydrochloric acid. The final products, ureas 12a-c, were synthesized by nucleophilic substitution from amines 3, 5, 10 and amine 1. CDI was used as a coupling reagent.
The structures of newly synthesized compounds were confirmed using analytical and spectroscopic methods (IR, 1H and 13C NMR, MS). In addition, melting points were determined for solid compounds. Novel derivatives fulfil some of Lipinski’s and Veber’s criteria for good oral bioavailability of potential drugs. SwissADME web tool predicts poor oral bioavailability as well. The antimalarial and cytostatic activity of the newly synthesized compounds will be examined in further studies
Side effects and therapeutic options for treating side effects of radiation in patients who have recovered from hormone-dependent breast cancer
No full textKarcinom dojke najčešća je maligna bolest u žena i vodeći uzročnik smrtnosti. Liječenje uključuje
operativni zahvat, radioterapiju, kemoterapiju, endokrinu terapiju, imunoterapiju odnosno
kombinaciju pojedinih navedenih terapija, sukladno propisanim smjernicama. Odluka o vrsti
terapije temeljena je na nalazu stadija karcinoma, općem stanju pacijenta, dobi i komorbiditetima.
Radioterapija se primjenjuje nakon poštednog operativnog zahvata ili mastektomije, s ciljem
povećanja ukupnog i specifičnog preživljenja te smanjenja rizika relapsa bolesti. Suvremene
radiološke tehnike apliciraju dozu zračenja na ciljano područje, uz značajnu poštedu izloženih
organa. Preporučuje se provesti terapiju zračenjem 4 tjedna po operaciji, odnosno 4 tjedna od
primijenjene kemoterapije. Nuspojave radioterapije mogu izazvati akutnu toksičnost ozračenog
područja, ali i kronične komplikacije, koje se javljaju i nekoliko godina po završenoj terapiji
zračenjem. Iste se tretiraju farmakološki i simptomatsko-suportivnim mjerama, a liječenje provodi
multidisciplinarni tim.Breast cancer is the most common malignant disease in women and the leading cause of death.
Treatment includes surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy, or a
combination of the above-mentioned therapies, in accordance with the prescribed guidelines. The
decision on the type of therapy is based on the finding of the cancer stage, patient's general condition,
age and comorbidities. Radiotherapy is applied following sparing surgery or mastectomy, with the
aim of increasing overall and specific survival and reducing the risk of disease relapse. Modern
radiological techniques apply a dose of radiation to the target area, with significant sparing of the
exposed organs. It is recommended to carry out radiation therapy 4 weeks after the surgery, i.e. 4
weeks after chemotherapy. The side effects of radiotherapy can cause acute toxicity of the irradiated
area, but also chronic complications, which occur several years after the end of radiation therapy.
They are treated with pharmacological and symptomatic-supportive measures, and the treatment is
carried out by a multidisciplinary team
Longevity and IgG glycosylation: A study of N-glycan stability over a decade
No full textGlikan je kompleksan spoj sastavljen od velikog broja monosaharida povezanih glikozidnim vezama, a koji biomolekule
dobivaju procesom glikozilacije. Termin se glikan često koristi za opisivanje ugljikohidratnog dijela glikokonjugata. Najčešći
monosaharidi u glikokonjugatima su Glc, Gal, GlcNAc, GalNAc, Man, Fuc, Xyl i Sia. Glikom se odnosi na cjelokupan repertoar
glikanskih struktura unutar organizma, stanice ili tkiva u određenom vremenu i uvjetima. Stoga, N-glikom IgG podrazumijeva
cijeloukupni spektar glikana koji se mogu pronaći na IgG. Glikani su specifično vezani za pojedinca te nisu zapisani u genomu i
podliježu utjecaju epigenetike, prehrane i trenutnog stanja pojedinca. Analiza glikoma može pružiti uvid u trenutno zdravstveno
stanje i personalizirati terapiju zbog čega su glikani vrijedni prediktivni biomarkeri. Kako bi mogli poslužiti za takvo što moramo
biti sigurni da je N-glikom IgG stabilan u određenom vremenskom periodu, a pošto su strukture glikana jako osjetljive na male
promjene korisno je i praktično stvoriti automatizirani pristup prilikom izolacije glikana, što su i ciljevi ovog istraživačkog rada.
U ispitivanju su prisustvovali dvojica zdravih muškaraca kojima su uzimani uzorci krvi u periodu od pet, odnosno, deset
godina. Uzorci u razdoblju od pet godina uzimani su svaka tri mjeseca, dok su uzroci u razdoblju od deset godina uzimani svaka
tri tjedna. Krv je uzeta na antikoagulans (EDTA) i centrifugirana čime je odvojena plazma iz koje je, uz pomoć pločice monolita s
proteinom G automatiziranom metodom koristeći Tecan Freedom EVO sustav i robotiku, izoliran IgG. N-glikani oslobođeni su
PNGaza F i fluorescentno obilježeni APTS nakon čega su analizirani xCGE-LIF metodom. Izračunata su četiri derivirana svojstva
(S, G1, G2 i G0) jer je pokazano kako upravo ona igraju ključnu ulogu u starenju. Također, izračunata su i dva derivirana svojstva
F i B koja doprinose uvidu u stabilnost glikana tijekom godina.
Analizom je podataka uočeno kako N-glikom IgG pokazuje vrlo dobru stabilnost u vremenskom periodu od deset godina što
znači da se uzorci plazme stari do deset godina pouzdano mogu koristiti za daljnja biološka istraživanja. Trend starenja prati
smanjenje sijalinizacije (S) i povećanje degalaktozilacije (G0), uz nepromijenjenu sržnu fukozilaciju (F) i monogalaktozilaciju
(G1), a odstupanja ukazuju na trenutna stanja i promjene u organizmu i oko njega.A glycan is a complex compound consisting of a large number of monosaccharides linked by glycosidic bonds that biomolecules obtain through the process of glycosylation. The term "glycan" is often used to describe the carbohydrate portion of glycoconjugates. The most common monosaccharides in glycoconjugates include Glc, Gal, GlcNAc, GalNAc, Man, Fuc, Xyl, and Sia. Glycome refers to the total repertoire of glycan structures in an organism, cell, or tissue at a particular time and under particular conditions. Therefore, the N-glycome of IgG refers to the entire spectrum of glycans that can be found in IgG. Glycans are individually specific, not encoded in the genome, and are subject to the influence of
epigenetics, diet, and the current state of the individual. Analysis of glycans can provide information about current health status and personalize therapy, making glycans valuable predictive biomarkers. To fulfill this purpose, it is essential to ensure that the N-glycome of IgG remains stable over a specific time period and understand how it changes with aging. Due to the sensitivity of glycan structures to minor changes, it is useful and practical to develop an automated approach for glycan isolation, which is the objective of this research study. The study involved two healthy male participants from whom blood samples were collected over a period of five and ten years. During the fiveyear period, samples were collected every three months, while during the ten-year period, samples were collected every three weeks. Blood was
collected using an anticoagulant (EDTA) and centrifuged to separate plasma. IgG was then isolated from the plasma using an automated method with a protein G monolith plate, utilizing the Tecan Freedom EVO system and robotics. N-glycans were released by PNGase F and fluorescently labeled with APTS before being analyzed using the xCGE-LIF method. Four derived traits (S, G1, G2, and G0) were calculated as they have been shown to play a crucial role in aging. Additionally, two derived traits, F and B, were calculated to provide insights into the stability of glycans over the years. Data analysis revealed that the N-glycome of IgG exhibits excellent stability over a ten-year period, indicating that plasma samples aged up to ten years can reliably be used for further biological research. The aging trend is characterized by decreased sialylation (S) and increa sed degalactosylation (G0), with unchanged core fucosylation (F) and monogalactosylation (G1). At the same time, deviations indicate current states and changes in the organism and its environment
Predictive survival value of preoperative calculated hematological parameters in patients with ovarian cancer
No full textOvim radom se željela ispitati prediktivna vrijednost predoperativnih izvedenih hematoloških parametara
(NLR, PLR i SII) kod pacijentica s rakom jajnika operiranih na Klinici za tumore KBC Sestre milosrdnice u
Zagrebu. Prikupljeni podaci 32 pacijentice su statistički obrađeni i prikazani Kaplan – Meier krivuljama
sveukupnog preživljenja. Pacijentice su raspoređene u dvije skupine; prva skupina je imala vrijednosti
računskih hematoloških parametara ispod (NLR 2,36; PLR 150,2; SII 612), a druga iznad odabranih
graničnih vrijednosti (NLR > 2,36; PLR > 150,2; SII > 612). Dobiveni rezultati su pokazali veću
vjerojatnost preživljenja za prvu skupinu pacijentica 12 mjeseci nakon operacije, a 60 mjeseci nakon
operacije, veću vjerojatnost preživljenja imale su pacijentice iz druge skupine. Zbog malog broja
pacijentica uvrštenih u ovaj rad, na temelju dobivenih rezultata ne možemo donositi konačne zaključke ni
potvrditi predoperativnu prediktivnu vrijednost ispitivanih računski dobivenih hematoloških parametara
(NLR, PLR, SII), već samo podržati daljnja istraživanja u ovom području.In this study, we wanted to examine the predictive value of preoperatively derived hematological
parameters (NLR, PLR and SII) in patients with ovarian cancer operated at the Tumor Clinic KBC
Sestre milosrdnice in Zagreb. The collected data of 32 patients were statistically processed and
presented with Kaplan-Meier curves of overall survival. The patients were divided into two
groups; the first group had values of calculated hematological parameters below (NLR 2,36;
PLR 150,2; SII 612), and the second group above the selected limit values (NLR > 2.36; PLR
> 150.2; SII > 612). The obtained results indicated a higher probability of survival for the first
group of patients 12 months after the operation, and 60 months after the operation, a higher
probability of survival for the patients from the second group. Based on the obtained results and a
small sample size of patients included in this study, one cannot draw a final conclusion or
confirmation of the preoperative predictive value of the calculated hematological parameters
(NLR, PLR, SII) but can support further investigations in this therapeutic area
Effects of epidurally administered dexmedetomidine and dexamethasone on postoperative pain, analgesic requirements, inflammation, and oxidative stress in thoracic surgery
No full textThe aim of this study was to compare the effects of dexmedetomidine and dexamethasone as adjuvants to pre-operative epidural administration of local anesthetic (ropivacaine) in thoracic surgery on the post-operative level of pain, use of analgesics, inflammation, and oxidative stress. The study enrolled 42 patients who underwent elective thoracic surgery in a one-year period at the University Hospital Dubrava (Zagreb, Croatia). Based on a computer-generated randomization list the patients were assigned to the dexmedetomidine (n = 18) or dexamethasone (n = 24) group. Post-operatively, patients of dexmedetomidine group reported lower pain (VAS value 1 h post-surgery, 3.4 ± 2.7 vs. 5.4 ± 1.8, dexmedetomidine vs. dexamethasone, p < 0.01) and had lower analgesic requirements in comparison with dexamethasone group. Thus, dexmedetomidine in comparison with dexamethasone was more efficient in lowering pain and analgesia requirements 24 h after the surgery. On the contrary, dexamethasone had better anti-inflammatory properties (CRP level 24 h post-surgery, 131.9 ± 90.7 vs. 26.0 ± 55.2 mg L–1, dexmedetomidine vs. dexamethasone, p < 0.01). Both dexmedetomidine and dexamethasone exhibited antioxidant effects, however, their antioxidant properties should be further explored. The results of this study improve current knowledge of pain control in thoracic surgery
Prikladnost farmakoterapije hiperuricemije u bolesnika hospitaliziranih u Specijalnoj bolnici za medicinsku rehabilitaciju Varaždinske toplice
No full textPosljednjih dvadeset godina u razvijenim zemljama prati se rast broja bolesnika s
asimptomatskom hiperuricemijom i rast broja bolesnika kojima su uvedeni lijekovi za
snižavanje urata kod asimptomatske hiperuricemije. Trenutno važeće smjernice European
League Against Rheumatism (EULAR) iz 2016. godine i američke smjernice 2020 American
College of Rheumatology Guideline for the Management of Gout (ACR) također ne preporučuju
uvođenje lijekova za snižavanje urata kod asimptomatske hiperuricemije. Kod bolesnika starije
životne dobi, koji imaju velik broj komorbiditeta i uzimaju velik broj lijekova to predstavlja
dodatan problem jer se povećava rizik interakcija lijekova i nuspojava.
Ciljevi istraživanja: Utvrditi udio bolesnika s asimptomatskom hiperuricemijom u
ukupnom broju bolesnika uključenih u istraživanje, utvrditi jesu li propisanom
farmakoterapijom za snižavanje urata postignute koncentracije mokraćne kiseline u serumu
unutar referentnih vrijednosti i utvrditi potencijalno klinički značajne interakcije lijekova (X,
D i C) koji se koriste u liječenju hiperuricemije s drugom propisanom farmakoterapijom.
Ispitanici i metode: Provedeno je prospektivno istraživanje u periodu od 1. svibnja 2022.
do 31. prosinca 2022. godine u Specijalnoj bolnici za medicinsku rehabilitaciju Varaždinske
Toplice, na odjelu za rehabilitaciju ortopedsko traumatoloških bolesnika. U istraživanje su
uključeni bolesnici stariji od 18 godina s dijagnozom hiperuricemije, gihta i/ili uratne
nefrolitijaze koji u farmakoterapiji imaju, pored lijekova za snižavanje urata, još barem jedan
lijek. Iz medicinske dokumentacije bolesnika uzeti su opći podaci koji uključuju dob i spol,
postavljene dijagnoze, propisanu farmakoterapiju i koncentraciju mokraćne kiseline u serumu.
Unutar 24 sata od zaprimanja bolesnika, uz potpisani informirani pristanak, proveden je
razgovor i uzeta najbolja moguća medikacijska povijest. Za utvrđivanje potencijalnih klinički
značajnih interakcija lijekova korištena je baza podataka Lexi-Comp®Online.
Rezultati: U istraživanje je uključeno 58 bolesnika prosječne starosti 75 godine, od čega
53,4 % muškaraca. Bolesnicima su ukupno propisana 623 lijeka što je 10,7 lijekova po
bolesniku. Ukupno 41,4 % bolesnika je imalo asimptomatsku hiperuricemiju koja je liječena
alopurinolom. Manje od polovice bolesnika (48,3 %) je imalo koncentraciju mokraćne kiseline
u serumu unutar referentnih vrijednosti. Utvrđeno je 95 potencijalno klinički značajnih
interakcija alopurinola stupnja D i C kliničke značajnosti s drugim propisanim lijekovima, što
iznosi 1,8 potencijalno klinički značajnih interakcija alopurinola po bolesniku. Udio interakcija
lijekova stupnja značajnosti D iznosio je 12,6 %, a stupnja značajnosti C 87,4 %. Kod bolesnika
koji su u farmakoterapiji imali propisan febuksostat nisu utvrđene potencijalne klinički
značajne interakcije lijekova.
Zaključak: Uvođenje farmakoterapije za snižavanje urata kod bolesnika s
asimptomatskom hiperuricemijom povećava se rizik od nuspojava i klinički značajnih
interakcija lijekova čime se može ugroziti sigurnost bolesnika. Više od polovice bolesnika koji
su primali farmakoterapiju za snižavanje urata nije imalo koncentraciju mokraćne kiseline u
serumu unutar referentnih vrijednosti. Rezultati ukazuju na važnost optimizacije
farmakoterapije kod bolesnika s hiperuricemijom.In the last twenty years, in developed countries, there has been an increase in the number of
patients with asymptomatic hyperuricemia and an increase in the number of patients who were
introduced to urate-lowering drugs for asymptomatic hyperuricemia. The currently valid
guidelines of the European League Against Rheumatism (EULAR) from 2016 and the 2020
American College of Rheumatology Guideline for the Management of Gout (ACR) also do not
recommend the introduction of urate-lowering drugs in asymptomatic hyperuricemia. In elderly
patients, who have a large number of comorbidities and take a large number of medications,
this represents an additional problem because the risk of drug interactions and side effects
increases.
Research Objectives: To determine the proportion of patients with asymptomatic
hyperuricemia in the total number of patients included in the research, to determine whether the
prescribed pharmacotherapy for lowering urate achieved serum uric acid concentrations within
the reference values, and to determine potentially clinically significant drug interactions (X, D
and C) used in treatment hyperuricemia with other prescribed pharmacotherapy.
Patients and methods: A prospective study was conducted in the period from 1 May 2022
until 31 December 2022, in the Special Hospital for Medical Rehabilitation in Varaždinske
Toplica at the Department for Rehabilitation of Orthopedic Trauma Patients. The study
included patients over 18 years of age with a diagnosis of hyperuricemia, gout and/or urate
nephrolithiasis who, in addition to urate-lowering drugs, have at least one other drug in their
pharmacotherapy. General data including age and sex, established diagnoses, prescribed
pharmacotherapy and serum uric acid concentration were taken from the patients medical
records. Within 24 hours of receiving the patient, with signed informed consent, an interview
was conducted and the best possible medication history was taken. The Lexi-Comp®Online
database was used to identify potential clinically significant drug interactions.
Results: 58 patients with a median age of 75 years were included in the study, of which
53,4 % were men. A total of 623 drugs were prescribed to the patients, which is 10,7 drugs per
patient. A total of 41,4 % of patients had asymptomatic hyperuricemia that was treated with
allopurinol. Less than half of the patients (48,3 %) had serum uric acid concentration within the
reference values. A total of 95 potentially clinically significant interactions of grade D and C
of allopurinol with other prescribed drugs were identified, which means 1,8 potentially
clinically significant interactions of allopurinol per patient. The share of drug interactions of
significance level D was 12,6 %, and of significance level C 87,4 %. In patients who were
prescribed febuxostat in pharmacotherapy, no potential clinically significant drug interactions
were identified.
Conclusion: The introduction of pharmacotherapy to lower urate in patients with
asymptomatic hyperuricemia increases the risk of side effects and clinically significant drug
interactions, which may endanger patient safety. More than half of the patients receiving uratelowering pharmacotherapy did not have a serum uric acid concentration within reference
values. The results indicate the importance of optimizing pharmacotherapy in patients with
hyperuricemia
Utjecaj savjetovanja kliničkog farmaceuta kod otpusta iz bolnice na adherenciju bolesnika pri uzimanju peroralnih antibiotika
No full textCilj istraživanja: Cilj istraživanja je utvrditi utječe li savjetovanje kliničkog farmaceuta pri otpustu iz bolnice pozitivno na adherenciju bolesnika pri uzimanju peroralnih antibiotika propisanih u bolnici.
Ispitanici i metode: Istraživanje je obuhvatilo 60 ispitanika hospitaliziranih na Odjelu nefrologije i endokrinologije Opće bolnice „dr. Tomislav Bardek“ Koprivnica. Prije otpusta iz bolnice prikupljali su se socio-demografski podaci te klinički podaci pomoću upitnika, razgovora s ispitanikom te pregleda medicinske dokumentacije u Bolničkom informacijskom sustavu (BIS). Osim ovih podataka mjerila se i adherencija kod uzimanja kronične terapije pomoću Medication Adherence Report Scale (MARS-5). Nakon otpusta iz bolnice i nakon završene antibiotske terapije koja im je propisana u bolnici ispitanici su kontaktirani telefonski te su ispitani o adherenciji. Statistička obrada rađena je pomoću IBM SPSS software®.
Rezultati: Istraživanje je pokazalo da je 19,6 % ispitanika bilo neadherentno prilikom korištenja antibiotika. Svi neadherentni ispitanici su se nalazili u neintervencijskoj skupini. Statistička obrada pokazala je kako savjetovanje kliničkog farmaceuta statistički značajno (p = 0,001) pozitivno utječe na adherenciju ispitanika pri uzimanju antibiotika nakon otpusta iz bolnice.
Zaključak: Implementacija preventivnih mjera kao što je savjetovanje bolesnika mogla bi imati pozitivan utjecaj na adherenciju bolesnika čime bi se potencijalno smanjili troškovi u zdravstvenom sustavu te poboljšala kvaliteta života samih bolesnika.Objectives: The aim of the study was to determine whether counseling by a clinical pharmacist has a positive effect on patient adherence to prescribed antibiotic therapy.
Patients and Methods: This study included 60 patients who were hospitalised on Nephrology and endocrinolgy ward in General hospital „dr. Tomislav Bardek“ Koprivnica. Sociodemographic and clinical characteristics of patients were obtained from hospitals informational system and through interviews with the patients. The Medication Adherence Report Scale (MARS-5) was used to collect information about adherence to long-term treatment. To gather information on adherence to prescribed antibiotic therapy patients were contacted by phone. IBM SPSS software® was utilized for statistical analysis.
Results: 19.6 % patients in the study were non-adherent during antibiotic use. All non-adherent patients were in non-interventional group. Statistical analysis showed that counseling provided by a clinical pharmacist has a statistically significant positive effect on patients' adherence to antibiotics after hospital discharge.
Conclusion: The implementation of preventive measures such as patient counseling could have positive impact on patient adherence. This, in turn, has the potential to reduce healthcare costs and improve patients' quality of life
Heterocyclic hybrid compounds, aminoquinoline and anthranilic acid derivatives, as potentional inhibitors of bacterial biofilm synthesis
No full textse od antranilne kiseline I njezinih halogeniranih derivate te derivate 4-amino-7-klorokinolina. Kao poveznica
između dva farmakofora izabran je 1,3,4-oksadiazol, peteročlani heterociklički prsten stabilan na enzimsku i kemijsku
razgradnju.
Sinteza je započeta amidacijom derivata metilnih estera antranilne kiseline u odgovarajuće hidrazide (2a-e) u
reakciji s vodenom otopinom hidrazina. Metilni esteri 1a i 1b prethodno su priređeni iz odgovarajućih kiselinskih
derivata korištenjem tionil-klorida i metanola, dok su preostali esteri bili komercijalno dostupni. Hidrazidi su zatim
prevedeni u odgovarajuće 3-H-1,3,4-oksadiazol-2-onske derivate (3a-e) reakcijom s CDI. Drugi građevni element,
aminokinolinski derivat 4 priređen je reakcijom 4,7-diklorokinolina i etilendiamina. 1,4-Disupstituirani semikarbazidi
5a-e dobiveni su u reakciji kinolinskog derivata 4 i oksadiazola 3a-e. U zadnjem reakcijskom koraku, u reakciji
ciklizacije zatvoren je 1,3,4-oksadiazolni prsten te su dobiveni konačni produkti 6a-e.
Dobiveni spojevi karakterizirani su uobičajenim analitičkim i spektroskopskim tehnikama: 1H i 13C NMR i
MS. Čistoća im je utvrđena UPLC analizom te je kod svih sintetiziranih spojeva iznosila preko 95 %. Tališta
sintetiziranih spojeva određivana su diferencijalnom pretražnom kalorimetrijom.
Izračun fizičko-kemijskih deskriptora spojeva te njihovih farmakokinetičkih parametara napravljen je pomoću
besplatne web aplikacije SwissADME. Na temelju rezultata može se zaključiti da bi spojevi trebali imati
zadovoljavajuća svojstva topljivosti i permeabilnosti što ukazuje na dobru oralnu bioraspoloživost.
Ispitivanja biološkog djelovanja sintetiziranih spojeva izlaze iz okvira ovog rada te će biti provedena naknadno.In the course of this paper, five novel hybrid compounds were synthesized and structurally characterized. Their
structures consisted of anthranilic acid and its halogenated derivatives, along with 7-chloro-4-aminoquinoline. 1,3,4-
oxadiazole, a five-membered heterocyclic ring resistant to chemical and enzymatic degradation, was used as a linker
between the two pharmacophores.
The synthesis began with the amidation of anthranilic acid methyl ester derivatives into their corresponding
hydrazides (2a-e), in a reaction with an aqueous solution of hydrazine. Methyl ester derivatives 1a and 1b were
previously obtained from the corresponding acid derivatives, using thionyl chloride and methanol, while the remaining
ester derivatives were comercially available. The hydrazides were then converted to the corresponding 3-H-1,3,4-
oxadiazol-2-one derivatives (3a-e) in a reaction with CDI. Another building block, the aminoquinoline derivative 4 was
obtained in the reaction between 4,7-dichloroquinoline and ethylenediamine. 1,4-disubstituted semicarbazides 5a-e were
obtained in the reaction between the aminoquinoline derivative 4 and the 3-H-1,3,4-oxadiazol-2-one derivatives 3a-e.
During the final reaction step, a 1,3,4-oxadiazole ring was enclosed in a cyclization reaction and the final products 6a-e
were obtained.
The synthesized compounds were characterized using standard analytical and spectroscopic techniques: 1H and
13C NMR and MS. Their purity was determined by UPLC analysis, all of which exceeded 95 %. Melting points of the
synthesized compounds were determined by differential scanning calorimetry.
The calculation of the compounds' physicochemical descriptors, along with their pharmacokinetical parameters
was performed using a free web tool called SwissADME. Based on the results, it can be concluded that the compounds
show satisfactory properties in terms of solubility and permeability, which indicates high oral bioavailability.
Biological screening of the synthesized compounds is beyond the scope of this paper, and will be performed in
the future
Ekstrakcija bioaktivnih sastavnica iz cvatova industrijske konoplje superkritičnim CO2
No full textCiljevi istraživanja: Definirati optimalne uvjete izolacije kanabinoida i terpena iz cvata industrijske konoplje primjenom “zelene” ekstrakcije ugljikovim dioksidom u superkritičnom stanju (sCO2); kvantificirati dobivene ekstrakte na udio kanabinoida i terpena; te odrediti antioksidacijske i antimikrobne učinke sCO2 ekstrakata.
Materijal i metode: Za istraživanje su korišteni osušeni cvatući vršni dijelovi industrijske konoplje (Cannabis sativa L.) sorte Futura 75 s hrvatskog tržišta. Ekstrakcija ciljanih bioaktivnih sastavnica provedena je primjenom sCO2. Eksperimentalna matrica napravljena je prema dizajnu centralnog kompozitnog plana pokusa, a analizom varijance procjenjen je stupanj točnosti primijenjene metodologije. Identifikacija i kvantifikacija isparljivih sastavnica sCO2 ekstrakata provedena je u vezanom sustavu plinske kromatografije i spektrometrije masa (GC-MS), dok su kanabinoidi određeni metodom tekućinske kromatografije visoke djelotvornosti (HPLC-DAD). Antioksidacijska svojstva dobivenih ekstrakata određena su primjenom DPPH testa, dok je antibakterijska aktivnost ispitana mikrodilucijskom metodom za određivanje minimalnih inhibitornih koncentracija.
Rezultati: Analiza plinskom kromatografijom i spektrometrijom masa (GC-MS) pokazala je β-mircenski kemotip sCO2 ekstrakata, s visokim udjelom α-pinena i β-pinena te nizom drugih monoterpena s manjim udjelima, dok je najzastupljeniji seskviterpen bio β-kariofilen. Glavni kanabinoidi sCO2 ekstrakata bili su CBDA i CBD, praćeni manje zastupljenim CBCA, CBC, THCA-A, THC, CBGA, CBG, CBDVA, dok CBN i THCVA nisu detektirani. sCO2 ekstrakt dobiven pri tlaku 320 bara i temperaturi 40 °C, s najvećim sadržajem CBDA, imao je najbolja antioksidacijska svojstva. Svi ekstrakti su pokazali dobro antibakterijsko djelovanje na vrste E. coli, P. aeruginosa, B. subtilis i S. aureus. sCO2 ekstrakt s najvećim udjelom CBD-a, koji sadrži i visok udio α-pinena, β-pinena, β-mircena i limonena, pokazao je najbolje antibakterijsko djelovanje. Uspostavljeni su optimalni uvjeti za sCO2 ekstrakciju kanabinoida i terpena iz industrijske konoplje. Temperatura od 60 °C pokazala se optimalnom za sve ispitivane odzive, dok je tlak pokazao različit učinak ovisno o ciljanim spojevima. Za monoterpene optimalan je bio niži tlak, dok je viši tlak bio pogodan za ekstrakciju seskviterpena. Primjena viših tlakova bila je poželjna i za ekstrakciju CBD-a. Postupkom dekarboksilacije kao predtretmana biljnog materijala prije sCO2 ekstrakcije dobiveni su ekstrakti s visokim prinosom CBD-a kao dominantnom sastavnicom.
Zaključak: Optimiran je proces sCO2 ekstrakcije za dobivanje ekstrakata industrijske konoplje s antioksidacijskim i antibakterijskim svojstvima te potencijalom topikalne primjene u medicinske i kozmetičke svrhe. Istraživanje je potvrdilo selektivnost primijenjene tehnike za ekstrakciju ciljanih terpena i kanabinoida iz cvatova industrijske konoplje.The objective of the research: To define the optimal conditions for isolation of cannabinoids and terpenes from industrial hemp inflorescences by applying "green" supercritical carbon dioxide extraction (sCO2); to quantify the obtained extracts on the content of cannabinoids and terpenes; and to determine the antioxidant and antimicrobial activities of sCO2 extracts.
Material and methods: Dried inflorescences of industrial hemp (Cannabis sativa L.) of Croatia-grown Futura 75 variety were used for the research. Extraction of target bioactive compounds using sCO2 was carried out. The experimental matrix was made according to the central composite design, and the analysis of variance was used to assess the degree of accuracy of the applied methodology. Identification and quantification of volatile compounds of sCO2 extracts was determined by gas chromatography-mass spectrometry combined system (GC-MS), while cannabinoids were determined by high-performance liquid chromatography (HPLC-DAD). The antioxidant properties of the obtained extracts were determined by a DPPH scavenging assay, while antibacterial activity was tested by a microdilution method for the determination of minimal inhibitory concentrations.
Results: Analysis with gas chromatography and mass spectrometry (GC-MS) showed β-myrcene chemotype in sCO2 extracts, with a high content of α-pinene and β-pinene and a number of other monoterpenes in smaller proportions, while the most dominant sesquiterpene was β-caryophyllene. The main cannabinoids of sCO2 extracts were CBDA and CBD, followed by less common CBCA, CBC, THCA, THC, CBGA, CBG, and CBDVA, while CBN and THCVA were not detected. sCO2 extract obtained at a pressure of 320 bar and a temperature of 40 °C, with the highest CBDA content, exhibited the best antioxidant properties. All extracts exhibited good antibacterial effect against E. coli, P. aeruginosa, B. subtilis and S. aureus. sCO2 extract with the highest content of CBD, which also contains a high content of α-pinene, β-pinene, β-myrcene and limonene, showed the best antibacterial activity. Optimal conditions have been established for the sCO2 extraction of cannabinoids and terpenes from industrial hemp. The temperature of 60 °C proved to be optimal for all studied responses, while pressure had a different effect depending on the compounds targeted. For monoterpenes, lower pressure was optimal, while higher pressure was suitable for the extraction of sesquiterpenes. The application of higher pressures was also desirable for CBD extraction. By using decarboxylation as a pretreatment of plant material before sCO2 extraction, extracts with a high yield of CBD were obtained.
Conclusion: sCO2 extraction process for obtaining industrial hemp extracts with antioxidant and antibacterial activities and with the potential of topical application for medical and cosmetic purposes has been optimized. The provided research confirmed the selectivity of the applied technique for the extraction of targeted terpenes and cannabinoids from industrial hemp inflorescences