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The effect of cryopreservation on recovery of hematopoetic stem cells and leukocytes subpopulation collected from peripheral blood by leukapheresis
Zbog očekivanog daljnjeg razvitka i primjene pripravaka za staničnu terapiju, potrebno je poznavati čimbenike koji utječu na vijabilnost i preživljenje stanica nakon kriopohrane. Cilj ovog prospektivnog istraživanja bio je u uzorcima autolognih i alogenih pripravaka stanica prikupljenih iz periferne krvi leukaferezom odrediti broj živih krvotvornih matičnih stanica (KMS) i subpopulacija leukocita 7-amino aktinomicin D (7-AAD)/aneksin V metodom i standardnom 7-AAD metodom te ispitati utjecaj kriopohrane i različitih čimbenika na preživljenje odmrznutih stanica, a i vremensko razdoblje od odmrzavanja koje je prihvatljivo za određivanje vijabilnosti stanica u svrhu procjene kvalitete pripravaka stanica. U 30 autolognih i 30 alogenih uzoraka pripravaka stanica „single-platform“ metodom određen je broj živih KMS-a, limfocita T i B, NK stanica i monocita. Stabilnost odmrznutih uzoraka ispitana je u tri točke: odmah po odmrzavanju te sat vremena i tri sata nakon odmrzavanja. Vijabilnosti svih populacija stanica određene 7-AAD/aneksin V metodom bile su statistički značajno niže u odnosu na 7-AAD metodu u svježim i odmrznutim uzorcima autolognih i alogenih pripravaka, no dobivene razlike nemaju utjecaj na laboratorijsku procjenu kvalitete pripravaka KMS. U autolognim pripravcima kriopohrana najmanje utječe na preživljenje CD3+/CD8+ stanica, a u alogenima na limfocite B (CD19+ stanice). U autolognim i alogenim pripravcima kriopohrana najviše utječe na postotak preživljenja CD34+ stanica, a kod subpopulacija leukocita na preživljenje monocita (CD14+ stanica) i u autolognim i alogenim pripravcima. U autolognim pripravcima na preživljenje CD3+ i CD3+/CD4+ stanica negativno je utjecala viša koncentracija trombocita, a na preživljenje CD3+/CD8+ stanica duljina pohrane svježeg pripravka prije kriopohrane. U alogenim pripravcima postotak granulocita negativno je utjecao na preživljenje limfocita T.
Ispitivanjem utjecaja kriozaštitne otopine na vijabilnost stanica nakon odmrzavanja dobiveno je da se apsolutni broj živih KMS-a, limfocita B i monocita statistički značajno smanjuje već sat vremena od odmrzavanja te je pripravke s tim vrstama stanice potrebno transplantirati odmah po odmrzavanju.
U ovom istraživanju zapaženo je različito preživljenje KMS-a i subpopulacija leukocita nakon kriopohrane. Stoga bi svaki transplantacijski centar trebao u svojim uvjetima ispitati kako kriozaštitna otopina i ostali čimbenici utječu na vijabilnost i preživljenje stanica od interesa.Due to the expansion of cell therapy using not only haematopoietic stem cells (HSC) but also other leukocyte subpopulations, the loss of these cells in cryopreserved apheresis products needs to be evaluated. The primary aim of this prospective study was to evaluate the post-thaw recovery of HSC and leukocyte subpopulations using the flow cytometry 7-AAD and 7-AAD/annexin V methods. The secondary aim was to assess how the post-thaw recovery is affected by various parameters, and the third aim was to examine how the time of exposure to cryoprotective solution containing DMSO after thawing affects the sample stability and viability of HCS and leukocyte subpopulations in autologous and allogeneic PBSC samples. In samples of 30 autologous and 30 allogeneic PBSC products, the number of viable HCS, T and B lymphocytes, NK cells and monocytes was determined using the "single-platform" method. The stability of the samples post-thaw was tested at three points: immediately after thawing and one hour and three hours post-thaw. The lowest post-thaw recovery was observed in autologous and allogeneic for CD34+ cells. In leukocyte subpopulation, the lowest post-thaw recovery was observed for CD14+ cells, both autologous and allogeneic. The highest post-thaw recovery was observed for CD3+/CD8+ cells in autologous, and for CD19+ cells in allogeneic samples. The statistically significant difference was observed between autologous and allogeneic PBSC products for CD3+ cell recovery and CD3+/CD8+ cell recovery. The evaluation of factors that could adversely affect the post-thaw recovery in autologous samples showed weak negative correlations between platelet concentration and CD3+ recovery, as well as between storage time and CD3+CD8+ recovery. In allogeneic samples, a strong negative correlation was observed only between the percentage of granulocytes and CD3+, CD3+/CD8+ and CD3+/CD4+ cell recoveries. Analysis of the absolute count of viable cells in thawed samples showed a significant difference between all measurement points for CD34+, CD14+ and CD19+ cells. No significant differences were observed for post-thaw stability of allogeneic samples analysed between products stored before cryopreservation ≥ 24 hours (N=20), and those stored < 24 hours (N=10), except for viable CD3+/CD4+ cells after three hours post-thaw. Since various post-thaw recoveries of leukocyte subpopulations were observed, the cell therapy manufacturing centers should evaluate how their cryopreservation method and other factors affect the recovery of cell population of interest in their settings
Značaj GLP-1 agonista u kliničkoj praksi
Šećerna bolest tip 2 je jedan od vodećih uzroka smrti u suvremenom svijetu. Razina glukoze u
krvi je povezana sa razvojem kardiovaskularnih bolesti, bubrežnih bolesti, pretilosti i ostalih
bolesti koje proizlaze iz makrovaskularnih i mikrovaskularnih komplikacija šećerne bolesti tip
2. Antihiperglikemici su lijekovi izbora u terapiji hiperglikemije koji imaju dokazanu
djelotvornost u smanjenju povišene razine glukoze u krvi. Zbog pojavnosti ne adherencije u
terapiji i loše kontrole glikemije u krvi koristeći neke od antihiperglikemika poboljšanje
kvalitete života pacijenata oboljelih od šećerne bolesti tip 2 je svakodnevni cilj. GLP-1 agonisti
su antihiperglikemici koji svojim načinom i učestalošću primjene uz pozitivnu kliničku
značajnu djelotvornost i na druga tkiva u organizmu povećavaju adherenciju u terapiji i
učinkovito smanjuju povišenu razinu glukoze u krvi. Povećana zainteresiranost među
znanstvenicima za istraživanje GLP-1 agonista postoji zbog njihovog kvalitetnog djelovanja i
dodatnih mogućnosti koje ovi lijekovi posjeduju u liječenju pacijenata.
U radu se prikazuje farmakodinamika, farmakokinetika GLP-1 agonista. Navodi se utjecaj
GLP-1 agonista na: mikrovaskularne posljedice šećerne bolesti tip 2, makrovaskularne
posljedice šećerne bolesti tip 2, tjelesnu težinu, kardiovaskularnu sigurnost, renoprotekciju i
smanjenje razine glukoze u krvi. Komparativnom analizom te prikazom prikupljenih
znanstvenih radova, koji su korišteni u ovom istraživanju, rad propituje potrebu dodatnog
istraživanja GLP-1 agonista. Ovo je pregledni, teorijski rad, a obrađuje lijekove koji se koriste
u liječenju šećerne bolesti tip 2, jedne od najzastupljenijih bolesti u svijetu. Za izradu rada
koristi se sustavno pretraživanje literature prema temi i predmetu istraživanja, autorima i
časopisu. Pretraga literature se provodi putem online baza podataka: PubMed, UpToDate,
Cochrane i Elsevier. Koriste se još i stručni članci, smjernice, priručnici te podaci službenih
web-stranica važnih za temu istraživanja. Ključne riječi za pretraživanje baza podataka
sadržavaju sljedeće pojmove: GLP-1 agonist, type 2 diabetes, clinical, effect, cardiovascular,
importance, glucose. U literaturi su identificirani mogući mehanizmi djelovanja GLP-1
agonista na snižavanje glukoze u krvi te fizikalno-kemijska svojstva GLP-1 agonista zbog kojih
ovi lijekovi imaju velik značaj za kliničku praksu. Proučavaju se tipovi GLP-1 agonista, njihov
kemijski sastav, doze, svojstva i učinci važni za kliničku praksu u liječenju šećerne bolesti tipa
2 uz kritički osvrt.
Učinci GLP-1 agonista na ljudski organizam posljedica su njihovog mehanizma djelovanja u
kojem dolazi do interakcije s GLP-1 receptorom što dovodi do povećanja koncentracije
unutarstaničnog cikličkog adenozinmonofosfata. Lučenje inzulina ovisno je o glukozi i u
slučaju povišene koncentracije glukoze u krvi se luči inzulin iz β stanica Langerhansovih
otočića gušterače. GLP-1 agonisti smanjuju lučenje glukagona. Također djeluju i usporavanjem
želuca, čime se smanjuje apsorpcija glukoze iz hrane nakon obroka. Prikazane znanstveno
utvrđene činjenice govore o tome da su GLP-1 agonisti djelotvorniji od nekih drugih
antihiperglikemika i u smanjenju tjelesne težine, normalizaciji glikemije te zaštiti
kardiovaskularnog sustava, bubrežnog sustava i drugih tkiva u organizmu. Strukturiranim
pregledom ovaj rad omogućava brzo pronalaženje činjenica koje su važne za: pacijente oboljele
od šećerne bolesti tip 2, znanost, struku i kliničku praksu.Type 2 diabetes is one of the leading causes of death in the modern world. The level of glucose
in the blood is associated with the development of cardiovascular diseases, kidney diseases,
obesity and other diseases resulting from macrovascular and microvascular complications of
type 2 diabetes. Antihyperglycemic drugs are the drugs of choice in the treatment of
hyperglycemia, which have proven effectiveness in reducing elevated blood glucose levels. Due
to the occurrence of non-adherence in therapy and poor blood glucose control using some
antihyperglycemic drugs, improving the quality of life of patients with type 2 diabetes is a daily
goal. GLP-1 agonists are antihyperglycemic drugs that, by their method and frequency of
administration, have a positive clinical effect on other tissues in the body and increase
adherence to therapy and effectively reduce elevated blood glucose levels. There is an increased
interest among scientists in the research of GLP-1 agonists because of their high-quality effects
and the additional possibilities that these drugs have in the treatment of patients.
The paper presents the pharmacodynamics, pharmacokinetics of GLP-1 agonists. The influence
of GLP-1 agonists on: microvascular consequences of type 2 diabetes, macrovascular
consequences of type 2 diabetes, body weight, cardiovascular safety, renoprotection and
reduction of blood glucose levels is stated. Through a comparative analysis and presentation of
the collected scientific papers, which were used in this research, the paper questions the need
for additional research on GLP-1 agonists. This is an overview, theoretical paper, and it deals
with the drugs used in the treatment of type 2 diabetes, one of the most prevalent diseases in
the world. A systematic search of the literature according to the topic and subject of the
research, authors and journal is used for the preparation of the paper. Literature search is carried
out through online databases: PubMed, UpToDate, Cochrane and Elsevier. Expert articles,
guidelines, manuals and data from official websites relevant to the research topic will also be
used. Keywords for searching databases include the following terms: GLP-1 agonist, type 2
diabetes, clinical, effect, cardiovascular, importance, glucose. In the literature, the possible
mechanisms of action of GLP-1 agonists on lowering blood glucose and the physicochemical
properties of GLP-1 agonists, which make these drugs of great importance for clinical practice,
have been identified. The types of GLP-1 agonists, their chemical composition, doses,
properties and effects important for clinical practice in the treatment of type 2 diabetes are
studied with a critical review.
The effects of GLP-1 agonists on the human body are a consequence of their mechanism of
action in which there is an interaction with the GLP-1 receptor, which leads to an increase in
the concentration of intracellular cyclic adenosine monophosphate. Secretion of insulin is
dependent on glucose, and in case of elevated blood glucose concentration, insulin is secreted
from the β cells of pancreatic islets of Langerhans. GLP-1 agonists reduce glucagon secretion.
They also act by slowing down the stomach, which reduces the absorption of glucose from food
after a meal. The presented scientifically proven facts show that GLP-1 agonists are more
effective than some other antihyperglycemic drugs in reducing body weight, normalizing
glycemia, and protecting the cardiovascular system, kidney system, and other tissues in the
body. With a structured review, this paper enables quick finding of facts that are important for:
patients with type 2 diabetes, science, profession and clinical practice
Diterpenes and phenolic compounds from Salvia brachyodon Vandas
Salvia brachyodon, the short-tooth sage, is one of the rarest plant species and endemic in the Adriatic area of the Balkan Peninsula. As aside from its essential oil, only limited information on its phytochemical composition is known, a more detailed study of the leaves was undertaken. From its leaves two diterpenes, agastanol (2), and a new natural compound 1, i.e., 3-methyl-4-methylen-11,12,14-trihydroxy-8,11,13-abietatrien-7-one, were isolated and identified by NMR spectroscopy and mass spectrometry. In addition, caffeic acid, isoquercitrin, luteolin 7-O-glucoside and rosmarinic acid were identfied by comparison with reference compounds. The fraction containg the diterpenes as well as the isolated compound 1 showed significant antimycobacterial activity against Mycobacterium smegmatis. The diterpenes of S. brachyodon represent promising antimycobacterial substances for further evaluation. Due to the endangered nature of the plant, the wide use of S. brachyodon and its bioactive compounds could be achieved by growing the plants in culture
Ljekarničko savjetovanje kod reakcije na stres
Cilj istraživanja: Cilj ovog rada je utvrditi koje su stvarne mogućnosti ljekarničkog savjetovanja osoba koje pate od mentalnih tegoba uzrokovanih stresom u Hrvatskoj, izuzev poremećaja usnivanja i spavanja. U radu je prikazano kojim bezreceptnim lijekovima i dodacima prehrani, izuzev homeopatije, za tu namjenu hrvatski ljekarnik trenutno raspolaže u svom radu.
Ispitanici i metode: U ovom specijalističkom radu korištena je znanstvena i stručna literatura iz područja medicine i (fito)farmacije. Prikupljeni znanstveni članci rezultat su pretraživanja baza podataka kao što su Pubmed, ScienceDirect, Google Scholar, a važan izvor informacija bile su i internet stranice poput Europske agencije za lijekove i Hrvatske agencije za lijekove i medicinske proizvode.
Rezultati: Ljekarnik zaposlen u javnim ljekarna u Republici Hrvatskoj u svrhu samoliječenja psihičkih posljedica djelovanja stresa na organizam može savjetovati uzimanje nekog od ukupno samo tri bezreceptna lijeka. Broj dodataka prehrani i aromaterapijskih proizvoda koji mogu biti dobra potpora očuvanju mentalnog zdravlja daleko je veći. Pri samoliječenju određenih skupina pacijenata kao što su djeca, trudnice i dojilje, ljekarnici raspolažu s vrlo malim brojem pripravaka koje mogu ponuditi.
Zaključak: Psihičke posljedice djelovanja stresa na organizam mogu biti razne. Osobe koje odluče potražiti pomoć često se prvo obrate ljekarnicima u javnim ljekarnama, od kojih se očekuje da učinkovitom komunikacijom procijene je li samoliječenje za njih sigurno, te ako je tako mogu savjetovati uzimanje bezreceptnh lijekova ili dodataka prehrani. Aromaterapija, te uzimanje adaptogena i probiotika, često su nedovoljno iskorištene opcije učinkovite borbe sa stresom. Njihova pravodobna, sigurna i učinkovita uporaba velike ovisi o kompetencijama ljekarnika koji mora neprekidno usvajati nova znanja i profesionalne vještine.Purpose of the research: The aim of this work was to determine the real potential of counseling by a pharmacist for people suffering from stress-related mental disorders in the Republic of Croatia, with the exception of falling asleep and sleep-through disorders. This work presents the OTC medicines and food supplements (except of homeopathic products) currently available to a Croatian pharmacist for this purpose.
Subjects and methods: This specialist paper is based on scientific and professional literature from fields of medicine and (phyto)pharmacy. The research articles collected are the result of a search in databases such as Pubmed, ScienceDirect and Google Scholar, while the websites of institutions such as the European Medicines Agency and the Croatian Agency for Medicinal Products and Medical Devices were also used as important sources of information.
Results: A pharmacist in a public pharmacy in the Republic of Croatia could recommend to a patient one of only three OTC available medications for self-treatment of the psychological effects of stress on the organism. The number of food supplements and aromatherapy products that can provide good support for maintaining mental health is far greater. Very few products are available to pharmacists for self-treatment of patient groups such as children or pregnant/ breastfeeding women.
Conclusion: There are a variety of psychological effects of stress on the organism. Individuals who decide to seek help often first consult a community pharmacist, who is expected to determine through effective communication whether or not self-treatment is safe for these patients and, if deemed safe, recommend the use of certain OTC medicines or food supplements. Aromatherapy, adaptogens and probiotics are often underutilized options for effective stress relief. Their timely, safe and effective use depends largely on the competencies of the pharmacist, who must continually acquire new professional knowledge and skills
Ethnobotanical use of Olea L. species
Etnobotanika je znanost o tradicionalnoj uporabi biljaka. Rod Olea L. broji do 50-ak svojta koje se smatraju urođenim istočnom dijelu Sredozemlja. Najpoznatija vrsta roda Olea je Olea europaea koja raste i u Hrvatskoj. Zabilježene su njezine primjene u brojnim etnobotaničkim studijama gdje se najčešće navode primjena kao hipoglikemik i antihipertenziv. S obzirom na rastuću učestalost kardiovaskularnih bolesti u svjetskoj populaciji posljednjih godina, navedene primjene masline zabilježene u etnobotaničkim studijama od potencijalne su važnosti za razvoj novih biljnih lijekova. Ovim diplomskim radom nastojao se dati pregled ljekovitih primjena vrsta roda Olea L. na temelju provedenih etnobotaničkih istraživanja čiji su rezultati objavljeni u periodu od 2017. do 2021. godine, a čime je obuhvaćena primjena u različitim zemljama te se pokušalo utvrditi koje su vrste od najvećeg potencijala za pojedine indikacije. Rezultati su pokazali kako se 94 % zabilježenih primjena odnosilo na vrstu Olea europaea. Dijabetes je spomenut u 32 % radova, a svi su se odnosili na vrstu Olea europaea, čiji se listovi u narodu najčešće pripremaju u obliku dekokta ili infuza.Ethnobotany is a science of traditional use of plants by human beings. The genus Olea L. comprises up to about 50 taxa, which are considered native to the eastern part of the Mediterranean region. The most famous species of the genus Olea is Olea europaea, which is native to Croatia as well. Its uses have been recorded in numerous ethnobotanical studies, where hypoglycaemic and antihypertensive use are most commonly reported. In view of the growing frequency of cardiovascular diseases in the world population in recent years, the uses of olive, recorded in ethnobotanical studies, have potential importance for the development of new herbal medicines. This diploma thesis attempted to provide an overview of the medicinal uses of species from the genus Olea L. based on the conducted ethnobotanical research, of which results have been published in the period from 2017 to 2021, and which covered applications in different countries, and tried to determine which species have the greatest potential for particular indications. The results showed that 94% of the recorded applications referred to Olea europaea. Diabetes was mentioned in 32 % of papers, which all referred to Olea europaea. Traditionally, its leaves are most often prepared in the form of decoction or infusion
Mineral analysis in Kombucha drinks and their function in the organism
Napitak od kombuche predstavlja popularni napitak od fermentiranog čaja, funkcionalnu namirnicu s raznim dobrobitima poput antibakterijskog i antioksidativnog svojstva te podupiranja imunosnog sustava i metabolizma. Dobrobiti kombucha napitka kriju se u bioaktivnim komponenama koje sadrži, a one uključuju aminokiseline, vitamine, polifenole, vlakna i organske kiseline. Među njima, prisutni su i važni biogeni elementi kao što su željezo, mangan i cink. Ti elementi neophodan su dio enzima ključnih u održavanju različitih biokemijskih procesa u organizmu, stoga je njihova dnevna konzumacija važna za optimalno zdravlje čovjeka. Zbog načina proizvodnje i vrste početnih sastojaka korištenih u proizvodnji, kombucha napitci su po svome sastavu raznoliki. U ovome radu prvi su se puta tehnikom masene spektrometrije s induktivno spregnutom plazmom (ICP-MS) analizirali minerali kalcija, željeza, magnezija, cinka i mangana u pet različitih uzoraka kombucha napitka, od kojih je jedan bio kontrolni uzorak. Analiza uzoraka omogućila je praćenje promjena koncentracija minerala u svakome uzorku te uvid u utjecaj različitih dodataka u uzorcima na koncentraciju samih minerala.Kombucha drink is a popular drink made of fermented tea. This functional food has various health benefits including antibacterial and antioxidant properties and a role in supporting the immune system and metabolism. The benefits of the kombucha drink are founded on the bioactive components it contains, which include amino acids, vitamins, polyphenols, fibers, and organic acids. Among them, important biogenic elements such as iron, manganese, and zinc are also present. As a functional part of various enzymes, these elements are crucial in maintaining various biochemical processes in the body, therefore their daily consumption is important for optimal human health. Kombucha drinks are diverse in their composition due to differences in the production method and the type of used ingredients. In this paper, the minerals calcium, iron, magnesium, zinc, and manganese were, for the first time, analyzed with the inductively coupled plasma mass spectrometry method (ICP-MS) in five different samples of a kombucha drink, one of which was used as a control sample. The sample analysis enabled the monitoring of the change in mineral concentrations in each sample and observing the influence of different additives in the samples on the concentration of the minerals themselves
Adherence of patients on adjuvant endocrine therapy who have recovered from breast cancer
Drugi po redu uzročnik smrti u Hrvatskoj predstavljaju novotvorevine. Karcinom koji se najviše dijagnosticira kod žena je karcinom dojke te gotovo 70% pacijentica koje su oboljele od karcinoma dojke imaju hormonski ovisan tip karcinoma. Terapija hormonski ovisnog karcinoma dojke često obuhvaća AET. Adjuvantna endokrina terapija se sastoji od supresije jajnika, SERM-ova (tamoksifen) i AI (anastrozol, letrozol i eksemestan). Unatoč dokazanim koristima koji se postižu primjenom AET adherencija pacijentica nije zadovoljavajuća. Smatra se kako se uzrok tome može pronaći u dugom trajanju terapije, ali i u nuspojavama koje sama terapija uzrokuje. Cilj ovog diplomskog rada bilo je ustanoviti adherenciju pacijentica s HR+ karcinomom dojke koje se liječe adjuvantnom endokrinom terapijom. Istraživanje je dizajnirano kao presječno, opažajno u kojem su podatci prikupljeni u jednoj točci u vremenu. U istraživanju je sudjelovalo 353 ispitanice srednje dobi 54 (± 11,89) godine. Većina ispitanica bila je udana ili je živjelo u izvanbračnoj zajednici, visoko obrazovano te zaposleno na puno radno vrijeme. Postotak ispitanica koje je bilo na terapiji tamoksifenom je 39,1% dok je na terapiji AI bilo 55,0% ispitanica (23,8% anastrozol, letrozol 26,5%, eksemestan 4,7%). Za procjenu adherencije ispitanice su popunjavale validirani upitnik MARS_5. Ispitanice smo, s obzirom na njihove odgovore, bili podijelili na adherentne i neadherentne pacijentice. Rezultati MARS_5 upitnika su pokazali kako je adherentno bilo 53,0% ispitanica dok je neadherentno bilo 40,2% ispitanica (24,1%, nenamjerno neadherentno, 3,1%, namjerno neadherentno, 13,0% namjerno i nenamjerno neadherentno). Postoji značajna razlika u adherenciji između pacijentica koje su bile na terapiji AI (70,8%) u odnosu na one koje su bile na terapiji tamoksifenom (37,2%). Istraživanje ovakvog tipa na ženama koje su preboljele karcinom dojke te su trenutno na AET, prvi put je provedeno u Hrvatskoj. Ovo istraživanje doprinosi boljem razumijevanju adherencije žena koje su na AET te je važno identificirati razloge neadherencije pri AET te donijeti pravilne odluke o daljnjim intervencijama.Second leading cause of death in Croatia is cancer. The most diagnosed carcinoma in women is breast cancer, almost 70% of patients with breast cancer have a hormon dependant breast cancer. Therapy for hormone-dependent breast cancer frequently include AET. Adjuvant endocrine therapy consists of ovarian suppression, SERMs (tamoxifen) and AI (anastrozole, letrozole and exemestane). Despite the proven benefits achieved by using AET, the adherence of patients is not satisfactory. It is believed that the cause of this can be found in the long duration of the therapy, but also in the side effects caused by the therapy itself. The goal of this thesis was to examine the adherence of patients with HR+ breast cancer treated with adjuvant endocrine therapy. The research was designed as a cross-sectional, observational study in which data were collected at one point in time. Research was conducted on 353 respondents with an average age of 54 (± 11,89). Most of the respondents were married or cohabiting, highly educated and were employed full-time. Percentage of subjects who were on tamoxifen therapy is 39,1%, while 55,0% of subjects were on AI therapy (23,8% anastrozole, 26,5% letrozole, 4,7% exemestane). To assess adherence, the subjects filled out the validated questionnaire MARS_5. Based on their answers, we divided the subjects into adherent and non-adherent patients. The results of the MARS_5 questionnaire showed that 53,0% of respondents were adherent, while 40,2% of respondents were non-adherent (24,1%, unintentionally non-adherent, 3,1%, intentionally non-adherent, 13,0% intentionally and unintentionally non-adherent). There was a significant difference in adherence between patients on AI therapy (70,8%) compared to those on tamoxifen therapy (37,2%). Research of this type on women who have survived breast cancer and are currently on AET was conducted for the first time in Croatia. This research contributes to a better understanding of the adherence of women who are on AET. It is important to identify why adherence to AET is so low and to make proper decisions about further interventions
The potential of kratom in the treatment of nociceptive pain
Kratom je biljka s dugom povijesti tradicijskog korištenja kod brojnih stanja pri čemu je
često droga izbora za samoliječenje boli. Cilj ovog diplomskog rada je bio prikupiti relevantne
pretkliničke in vivo i kliničke studije koje su proučavale analgetsko djelovanje ekstrakata
kratoma, njegovih alkaloida (mitragina, 7-hidroksimitraginina) i polusintetskih derivata,
razjasniti mehanizam djelovanja i procijeniti ima li potencijal da postane novi legalni analgetik.
Zbog uočene povezanosti dugotrajne primjene kratoma s razvojem ovisnosti, diplomski rad je
baziran samo na liječenju boli nociceptivnog tipa. Sve studije koje su uključene u diplomski rad
su potvrdile kako ekstrakti, izolirani alkaloidi i njihovi polusintetski derivati kratoma posjeduju
analgetska svojstva. Ovim sustavnim pregledom je ustanovljeno da su analgetski učinci
posredovani uglavnom opioidnim sustavom i da to može postati sigurnosti problem kod primjene.
Unatoč tome, ovaj rad nudi dokaze da postoji potencijal da jedan od alkaloida kratoma ili pak
spoj polusintetiziran iz tih alkaloida postane analgetik koji bi bio učinkovitiji i sigurniji u odnosu
na morfin.Kratom is a plant with a long history of traditional use for numerous conditions, often being
the drug of choice for self-treatment of pain. The aim of this thesis was to collect relevant
preclinical in vivo and clinical studies that investigated the analgesic effect of kratom extracts, its
alkaloids (mitragynine, 7-hydroxymitragynine) and semi-synthetic derivatives, clarify the
mechanism of action and assess whether it has the potential to become a new legal analgesic. Due
to the observed association of long-term use of kratom with the development of addiction, the
thesis is based only on the treatment of pain of the nociceptive type. All studies that are included
in the thesis confirmed that extracts, isolated alkaloids and their semi-synthetic derivatives of
kratom possess analgesic properties. In this systematic review, it was found that the analgesic
effects are mediated mainly by the opioid system and that this may become a safety issue in
administration. Nevertheless, this thesis offers evidence that there is a potential for one of the
kratom alkaloids or a compound semi-synthesized from these alkaloids to become an analgesic
that would be more effective and safer than morphine
Agava - botanički podaci, kemijski sastav i uporaba
Agave is a genus of succulent monocotyledons native to Central
America’s arid and semiarid regions, particularly Mexico, where
up to 119 endemic species have been identified. Physiological features that allow
them to live in such surroundings, such as Crassulacean Acid Metabolism (CAM)
and inulin storage, are also the foundation of these plants’ connection with
Mexicans and their culture. Agaves are utilized for a variety of purposes, including animal feed and horticulture, but the most common is the production of
aguamiel and traditional alcoholic beverages like tequila, pulque, mezcal, bacanora, and raicilla. Aguamiel is classified as a nutraceutical beverage due to its
high concentration of health-promoting ingredients. It has a high content of
fructooligosaccharides, regarded as prebiotics, vital vitamins, and minerals such
as B group vitamins, phosphorus, zinc, iron, and phenolic compounds with
various medical actions (antibiotics, adjuvants, anticholesterolemics, etc.).
Because of their widespread popularity, agave alcoholic beverages are greatly
profitable. Agave genes, linked with adaptations to arid environments, are a
potential resource for the genetic engineering of other agronomically important
crops
Kompatibilnost djelatne i pomoćnih tvari u lijekovima za terapiju upalnih bolesti crijeva – in silico pristup
Cilj istraživanja:
Cilj ovog rada je dati literaturni pregled provedenih predformulacijskih ispitivanja za lijekove koji
se koriste u liječenju upalne bolesti crijeva. U sklopu ovog cilja dati će se uvid u do sada provedena
ispitivanja kompatibilnosti djelatne i pomoćnih tvari. Također evaluirati će se inkompatibilnosti
djelatne s pomoćnim tvarima utvrđene pomoću računalnog programa PharmDE®.
Materijal i metode:
Rad daje pregled provedenih predformulacijskih ispitivanja kompatibilnosti djelatne tvari koje se
koriste u terapiji upalne bolesti crijeva i pomoćnih tvari. Pretražene su dostupne bibliografske baze
podataka i servisi (Medline/PubMed, ScienceDirect, EMBASE i dr.), uz primjenu ključnih riječi:
preformulation study, compatibility, interaction, PharmDE, colon disease... Znanstvena literatura
je pregledana za lijekove koji se koriste u liječenju upalne bolesti crijeva, a korištenjem programa
PharmDE® provedena je analiza rizika i dat je uvid u nekompatibilnosti pomoćnih tvari i djelatne
iz različitih farmakoterapijskih skupina koje se koriste u terapiji upalne bolesti crijeva.
Rezultati:
Navedena istraživanja pokazala su kako korištenjem umjetne inteligencije, u ovom slučaju
programa PharmDE®, je moguće u vrlo kratkome vremenu dobiti uvid u potencijalne interakcije
između pomoćnih tvari i određenih funkcionalnih skupina koje su prisutne u strukturi djelatne tvari.
Dobiveni podaci uspoređeni su s literaturno dostupnim podacima.
Zaključak:
Eksperimentalno ispitivanje kompatibilnosti je dugotrajan i skup proces tijekom kojeg je iznimno
zahtjevno uključiti u istraživanje velik broj pomoćnih tvari kako bi se utvrdilo stupa li u interakciju
s njima djelatna tvar. Posljednjih godina umjetna inteligencija pronalazi svoju primjenu u
farmaceutskoj industriji, a jedan od takvih primjera je korištenje računalnog programa PharmDE®
za provedbu simulacije studije kompatibilnosti djelatne i pomoćnih tvari. Osim što je upotreba
programa PharmDE® prilikom predviđanja nekompatibilnosti ekološki prihvatljiva, program je
vrlo jednostavan za korištenje i u kratkome vremenu generira veliki broj podataka. Ipak, dobivene
podatke potrebno je kritički sagledati kako bi se donijeli valjani zaključci.Objectives:
The aim of this thesis is to provide a literature review of preformulation study for drugs used in the
treatment of inflammatory bowel disease. As part of this goal, an insight will be given into the
compatibility tests of drugs and excipients carried out so far. Drug incompatibilities with excipients
determined using the PharmDE® computer program will also be evaluated.
Material and Methods:
The thesis provides an overview of the conducted preformulation study on the compatibility of the
active substance and excipients. Available bibliographic databases and services (Medline/PubMed,
ScienceDirect, EMBASE, etc.) were searched, using keywords: preformulation study,
compatibility, interaction, PharmDE, colon disease ... Scientific literature was reviewed for drugs
used in treatment inflammatory bowel disease, and using the PharmDE® program, a risk analysis
was performed and an insight into the incompatibility of excipients and drugs for inflammatory
bowel disease was provided.
Results:
These studies showed that using artificial intelligence, in this case the PharmDE®, it is possible in
a very short time to gain insight into potential reactions between excipients and certain functional
groups that are present in the structure of the active substance. The results obtained with in silico
approach were compared with availble literature data.
Conclusion:
Experimental compatibility testing is a time-consuming and expensive process during which it is
not possible to include a large number of excipients to test whether interactions with the active
substance occur or not. The artificial inteligence has been used in pharmaceutical industries for
several decades, and one such example is the PharmDE® program used to simulate the
compatibility and predict the incompatibility of active and auxiliary substances. Besides the use of
the PharmDE® program when predicting incompatibility is environmentally friendly, very easy to
use and generates a large amount of data in a short time, the obtained data must also be viewed
critically