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Primjena ciklodekstrina u razvoju farmaceutskih oblika za primjenu antitumorskih lijekova
No full textCyclodextrins (CDs) are excipients able to form inclusion complexes
with sterically compatible lipophilic endogenous molecules
and drugs, increasing their solubility and chemical stability. Enhanced biocompatibility
and the potential to form nanostructures give CDs an advantage
over other commercially available excipients. CDs appear as attractive carriers
for antitumor drugs, which often show limited aqueous solubility and chemical
stability. Therefore, CD may provide the development of new dosage forms and
delivery systems of antitumor drugs with improved bioavailability, reduced toxicity
and enhanced therapeutical efficiency. In addition, the interactions of CDs
with endogenous molecules may act synergistically with antitumor drugs in
cancer treatment. Further functionalization of CDs by attaching the ligands specific
for receptors typical for tumour cells may provide active tumor targeting of
the included cytostatic drugs, additionally enhancing the effectiveness and safety
of cancer therapy
Evaluation of erythrocytes morphological characteristics using Sysmex DI-60 digital morphology analyzer
No full textPoremećaji eritrocita se odražavaju karakterističnim morfološkim promjenama, stoga je bitno
detektirati i kvantificirati morfološke abnormalnosti. Hematološki analizatori daju pouzdane rezultate
kompletne krvne slike u većini slučajeva, ali u prisutnosti morfoloških promjena eritrocita još uvijek ne
mogu ponuditi cjelovitu kliničku sliku. U tu svrhu izvodi se pregled razmaza periferne krvi koji se
posljednjih godina nastoji automatizirati, a razvojem umjetne inteligencije i algoritama za digitalnu
mikroskopiju to postaje moguće. Cilj ovog rada bio je ispitati pouzdanost automatizirane procjene
morfoloških karakteristika eritrocita digitalnom mikroskopijom na uređaju Sysmex DI-60, kao dio
verifikacije novog uređaja za digitalnu morfologiju u svrhu uvođenja automatizirane procjene
morfoloških karakteristika eritrocita u rutinski laboratorijski rad. Ispitana je korelacija šest morfoloških
karakteristika (polikromazija, hipokromija, anizocitoza, mikrocitoza, makrocitoza, poikilocitoza)
dobivenih na uređaju za digitalnu mikroskopiju, s parametrima dobivenima na hematološkom
analizatoru Sysmex XN-3100 (Rtc, MCH, RDW, MCV). Utvrđena je umjerena korelacija između
hipokromije i MCH, mikrocitoze i MCV, anizocitoze i RDW. Slaba korelacija utvrđena je između
polikromazije i broja retikulocita te između makrocitoze i MCV. Kako bi slaganje između ovih
parametara bilo bolje, potrebno je poboljšati same algoritme digitalne mikroskopije, ali i prilagoditi
kriterije za stupnjevanje pojedinih karakteristika.Erythrocytes' disorders are reflected in characteristic morphological changes, therefore it is
essential to detect and quantify them. Hematology analyzers provide reliable results of a complete
blood count in most cases, but in the presence of erythrocytes' morphological changes they still
cannot offer a complete clinical picture. In this case, inspection of the peripheral blood smear is
performed. In recent years, there have been attempts made to automate this process, and with the
development of artificial intelligence and algorithms for digital microscopy, this became possible.
The aim of this thesis was to test the reliability of the automated assessment of erythrocytes'
morphological characteristics using Sysmex DI-60 digital morphology analyzer. The correlation of
six morphological characteristics (polychromasia, hypochromia, anisocytosis, microcytosis,
macrocytosis, poikilocytosis) obtained on a Sysmex DI-60 with parameters obtained on a
hematology analyzer Sysmex XN-3100 (Rtc, MCH, RDW, MCV) was examined. Moderate
correlation was found between hypochromia and MCH, microcytosis and MCV, anisocytosis and
RDW. Weak correlation was found between polychromasia and reticulocytes' count as well as
between macrocytosis and MCV. In order to obtain better agreement between these parameters, it
is necessary to improve the digital microscopy algorithm, but also to adjust the criteria for grading
individual characteristics
Physicochemical characterization of dietary supplements used in the therapy of inflammatory bowel diseases
No full textUpalne bolesti crijeva skupina su autoimunih bolesti koje karakterizira kronično ili relapsno upalno stanje u
gastrointestinalnom traktu. Zabrinjava rast incidencije i prevalencije ovih bolesti u općoj populaciji jer ozbiljno
narušavaju kvalitetu života pacijenata i predstavljaju brojne izazove za zdravstvo. Zbog izazovnog i
dugotrajnog liječenja, pacijenti s upalnim bolestima crijeva nerijetko posežu za dodacima prehrani. Kako je
broj pacijenata koji koriste dodatke prehrani u porastu, u fokus dolazi pitanje kontrole kvalitete dodataka
prehrani.
Cilj ovoga rada bio je prema USP protokolima provesti fizikalno-kemijsku karakterizaciju biljnih dodataka
prehrani koji se koriste u terapiji upalnih bolesti crijeva.
Ispitivano je 36 uzoraka u različitim dozirnim oblicima: tablete, prašci, tvrde capsule i meke kapsuse.
Provedena su sljedeća ispitivanja: ispitivanje nasipne gustoće i gustoće nakon protresivanja (USP),
varijacije mase dozirnih oblika (USP ), raspadljivosti (USP ), pucanja mekih kapsula (USP
), rastrošljivosti tableta (USP ) i ispitivanje sile loma tableta (USP ). Najbolja svojstva
tečenja prema nasipnoj gustoći nakon protresivanja među ispitivanim uzorcima prašaka imaju sirovine
kurkume, a najlošija uzorci andrografisa. Sve ispitivane tablete i kapsule zadovoljile su kriterij USP-a u
ispitivanju varijacije mase. Samo jedan uzorak nije zadovoljio kriterij raspadljivosti. U ispitivanju pucanja
mekih kapsula i rastrošljivosti tableta svi su uzorci zadovoljili USP kriterije. Sila loma ispitivanih tableta bila
je u rasponu od 27,7 do 248,5N. . Loša svojstva tečenja sirovina mogla bi uzrokovati neujednačenost dozirnih
jedinica, a tableta koja se nije raspala najvjerojatnije neće biti učinkovita in vivo.Text Inflammatory bowel diseases are a group of autoimmune diseases characterized by chronic or relapsing
inflammatory conditions in the gastrointestinal tract. The increasing incidence and prevalence of these
diseases in the general population are concerning because they seriously compromise the quality of life of
patients and present numerous challenges for healthcare Due to the challenging and prolonged treatment,
patients with inflammatory bowel diseases often turn to dietary supplements. As the number of patients using
these supplements is growing, it is important to investigate their effectiveness and safety.
The aim of this work was to conduct a physicochemical characterization of herbal dietary supplements used
in the therapy of inflammatory bowel diseases according to the USP protocols.
36 samples were tested in various dosage forms: tablets, powders, hard capsules and soft capsules. The
following tests were carried out: bulk density and tapped density (USP ), weight variation of dosage
forms (USP ), disintegration (USP ), soft capsule rupture (USP ), tablet friability (USP
) and tablet breaking force (USP ).The raw materials of turmeric have the best flow properties,
according to tapped density testing, among the tested powder samples, while the andrographis samples have
the least desirable flow properties. All tested tablets and capsules passed the USP weight variation test. Only
one sample did not meet the disintegration criteria. In the soft capsule rupture and tablet friability testing, all
samples met the USP criteria. Tablet breaking force was in the range from 27.7 to 248.5N. Poor raw material
flow characteristics can cause unequal dosing units, while a tablet that did not disintegrate is unlikely to be
effective in vivo
Prediktivne jednadžbe za procjenu brzine glomerularne filtracije
No full textKronična bubrežna bolest (KBB) predstavlja rastući javnozdravstveni problem. Bolesnici u ranim
stadijima KBB-a pretežno su bez simptoma, a tijekom vremena bolest postepeno napreduje te u
konačnici može dovesti do potpunog i trajnog zatajenja bubrežne funkcije što značajno narušava
kvalitetu života bolesnika. Zbog toga je važno pravovremeno otkriti kroničnu bubrežnu bolest i usporiti
njezino napredovanje prema završnom stadiju, koji je veliko opterećenje za bolesnika i zdravstveni
sustav. Uloga laboratorijske medicine u dijagnostici i praćenju KBB-a je od velike važnosti jer izračun
brzine glomerularne filtracije (engl. glomerular filtration rate, GFR), uz korištenje odgovarajućih
prediktivnih jednadžbi, omogućuje kliničarima da na relativno jednostavan i lako dostupan način
procijene bubrežnu funkciju ispitanika.
Cilj istraživanja: Cilj ovog specijalističkog rada je kroz analizu stručne literature, dati sustavni pregled
razvoja i karakteristika najčešće korištenih jednadžbi za procjenu brzine glomerularne filtracije (engl.
estimated GFR, eGFR) u općoj populaciji (djeca i odrasli).
Metodologija: Metode rada uključivale su pregled dostupne znanstvene i stručne literature: stručnih
knjiga, mrežnih stranica stručnih društava koja su vezana uz problematiku ovog istraživanja i
elektronskih bibliografskih baza podataka kao što su ScienceDirect, Elsevier i PubMed (Medline). Pri
pretraživanju su korištene ključne riječi vezane uz tematiku ovog specijalističkog rada, kao na primjer:
kronična bubrežna bolest, brzina glomerularne filtracije, kreatinin, djeca, cistatin C, eGFR jednadžbe,
prevalencija, KDIGO.
Rezultati: Identificirane su i na jednom mjestu pregledno prikazane glavne specifičnosti najčešće
korištenih jednadžbi za procjenu brzine glomerularne filtracije u općoj populaciji. Jednadžbe daju
optimalne rezultate kada se primjenjuju na sličnu populaciju ispitanika i koriste metode mjerenja koje
su ekvivalentne onima korištenim u razvoju jednadžbe.
Zaključak: Procijenjena GFR jedan je od glavnih kriterija za definiranje i stupnjevanje KBB-a i zato ju
je ključno točno procijeniti. Različite prediktivne jednadžbe različito procjenjuju GFR i stadije KBB-a,
ovisno o vrsti ispitanika na kojoj su evaluirane i o varijablama koje su uključene u izračun. Poznavanje
karakteristika i odabir odgovarajuće jednadžbe utječe na točnost i pravilnu interpretaciju rezultata
eGFR-aChronic kidney disease (CKD) is a growing public health problem. The early stage of CKD is mostly
asymptomatic, and over time the disease gradually progresses and ultimately can lead to complete and
permanent failure of kidney function when kidney function is irreversible damaged, and the patient's
quality of life is significantly decreased. It is of great interest to timely detect CKD and try to delay its
progression towards the final stage, which is a great burden for both the patient and the healthcare
system. The role of laboratory medicine in the diagnosis and monitoring of CKD using estimation of
glomerular filtration rate (GFR) is very important, because it enables clinicians to assess the renal
function of subjects in a relatively simple and easily accessible way.
Objectives: This specialist thesis will provide a systematic review of the development and characteristics
of frequently used equations for estimating the glomerular filtration rate (eGFR) in the general
population (children and adults).
Methodology: Methods include a review of the available scientific and professional literature:
professional books, websites of professional societies related to the issues of this research and electronic
bibliographic databases such as ScienceDirect, Elsevier and PubMed (Medline). Here are some of the
keywords related to the topic of this specialist theisis: chronic kidney disease, glomerular filtration rate,
creatinine, children, cystatin C, eGFR equations, prevalence, KDIGO.
Results: The main specifics of frequently used equations for estimating glomerular filtration rate in the
general population have been identified and presented in one place. Equations performs best when
applied to a similar patient population and using measurement methods that are equivalent to those used
in the equation´s development.
Conclusion: It is crucial to accurately estimate the GFR, because it is one of the main criteria for defining
and staging of CKD. Different predictive equations estimate GFR and CKD stages differently,
depending on the evaluated patient population and the variables included in the calculation. The
accuracy and correct interpretation of eGFR results deeply depends on knowing the characteristics and
choosing the appropriate equation
Procoagulant and thrombogenic conditions in COVID-19 infection
No full textKrajem 2019. godine u kineskoj pokrajini Wuhan pojavio se novi virus SARS-CoV-2 pa je Svjetska zdravstvena organizacija ubrzo proglasila pandemiju. Bolest uzrokovana ovim korona virusom, COVID-19, može se manifestirati blažim simptomima sličnima gripi ili težim koji mogu dovesti do smrtnoga ishoda. Glavni put ulaska virusa u stanicu domaćina je putem ACE2 receptora koji je eksprimiran na alveolarnim epitelnim stanicama, srcu, bubrezima, plućima, itd. Koagulopatija uzrokovana COVID-19 (CAC) po život je opasno stanje u čiji su mehanizam nastajanja uključeni imunosni sustav, disfunkcija vaskularnog endotela i hiperkoagulabilnost. Parametri koji se koriste za procjenu hemostaze, tijek i progresiju bolesti su PV, fibrinogen, razgradni produtki fibrinogena, broj trombocita, koncentracija proteina C. Kao najpouzdaniji marker pokazala se koncentracija D-dimera. Rizični faktori za nastanak CAC i kardiovaskularnih bolesti su genske predispozicije kao što su polimorfizmi gena ITGB3 PIA1/PIA2 i ꞵ-Fbg, te prisutnost hipertenzije i dijabetes. Komplikacije koje su često prisutne su mikro- i makrotromboza, diseminirana intravaskularna koagulacija, miokarditis, aritmije i zatajenje srca. U antikoagulantnoj terapiji najbolji se pokazao niskomolekularni heparin, dok direktne oralne antikoagulanse i inhibitore agregacije trombocita treba koristiti s oprezom zbog brojnih interakcija, ponajprije s antiviroticima. Također, preporuča se koristiti nafamostat, ako je moguće u kombinaciji s heparinom. Pojavom cjepiva protiv SARS-CoV-2 i njegovom širokom primjenom, uočene su brojne nuspojave kao i nastanak autoimunih bolesti, poput stečene autoimune deficijencije FXIII.At the end of 2019, a new SARS-CoV-2 virus appeared in the Chinese province of Wuhan, and the World Health Organization soon declared it a pandemic. The disease caused by the corona virus, COVID-19, can manifest itself with mild flu-like symptoms or more severe ones that can lead to death. The main way the virus enters the host cell is through the ACE2 receptor, which is expressed on alveolar epithelial cells, the heart, kidneys, lungs, etc. Coagulopathy caused by COVID-19 (CAC) is a life-threatening condition in which the immune system, vascular endothelium dysfunction and hypercoagulability are involved. The parameters used to assess hemostasis and the course and progression of the disease are PV, fibrinogen, fibrinogen degradation products, platelet count, protein C concentration, and D-dimer concentration proved to be the most reliable marker. Risk factors for CAC and cardiovascular diseases are genetic predispositions such as ITGB3 PIA1/PIA2 and ꞵ-Fbg gene polymorphisms, as well as the presence of hypertension and diabetes. Complications that are often present are micro- and macrothrombosis, disseminated intravascular coagulation, myocarditis, arrhythmias and heart failure. In anticoagulant therapy, low-molecular-weight heparin proved to be the best, while direct oral anticoagulants and platelet aggregation inhibitors should be used with caution due to numerous interactions, primarily with antivirals. Also, it is recommended to use nafamostat, if possible in combination with heparin. With the advent of the vaccine against SARS-CoV-2 and its widespread use, numerous side effects and the emergence of autoimmune diseases have been observed, such as autoimmune-acquired factor XIII deficiency
Kliničko značenje ekvola kao bioaktivnog metabolita daidzeina
No full textCilj istraživanja
Danas se na tržištu Republike Hrvatske nalaze biljni pripravci za ublažavanje menopauzalnih tegoba na
bazi soje i crvene djeteline. Nova znanstvena istraživanja upućuju na potrebnu podjelu populacije na
proizvođače i neproizvođače ekvola jer se terapijski učinak izoflavona može očekivati u osoba koje
mogu stvoriti aktivni metabolit ekvol. Stoga je cilj specijalističkog rada dati sustavni pregled
istraživanja o ovoj temi i ukazati na važnost stvaranja ekvola za terapijski učinak biljnih lijekova i
dodataka prehrani na bazi soje i crvene djeteline.
Materijal i metode
Istraživanja u okviru ovoga specijalističkog rada teorijskog su karaktera i uključuju pregled dostupne
literature o dosadašnjim suvremenim znanstvenim istraživanjima ekvola kao bioaktivnog metabolita
daidzeina. U pretraživanju su se koristile dostupne elektronske bibliografske baze podataka kao što
su: PubMed, ScienceDirect, Elsevier, Frontiers media, Plos one, Wolter Kluwer i dr. Upotrijebljene su
tražilice Google i Google Scholar.
Rezultati
U okviru ovog rada prikazani su rezultati istraživanja učinka ekvola na različita područja ljudskog
zdravlja s naglaskom na menopauzalne tegobe, kardiovaskularne bolesti, osteoporozu, demenciju,
PMS, karcinom dojke i prostate te starenje kože. U pregled su uključena i istraživanja o strukturi i
mehanizmu djelovanja ekvola te istraživanja o crijevnim bakterijama koje su uključene u proces
stvaranja ekvola iz daidzeina. Napravljen je osvrt na dodatke prehrane na bazi ekvola i na biotehnološki
pristup proizvodnji funkcionalne hrane s ekvolom.
Zaključak
Ekvol je aktivni metabolit izoflavona nastao isključivo djelovanjem crijevnih bakterija u osoba koji su
„proizvođači ekvola“. Mehanizam djelovanja ekvola još uvijek nije do kraja razjašnjen iako je dokazano
da je selektivni modulator ERβ pa ga svrstavamo u SERM. Sve je više kliničkih dokaza o djelovanju
ekvola, međutim, potrebne su duže, randomizirane kliničke i opservacijske studije biološkog utjecaja
S-ekvola u ljudskom organizmu. Razvijen je standardizirani prirodni dodatak prehrani koji sadrži S-
(−)ekvol, a dobiva se fermentacijom otopine sojinih klica sojem bakterija Lactococcus 20-92 mliječne
kiseline.Objectives
On the market of the Republic of Croatia there are herbal products based on soy and red clover used
for the relief of menopausal symptoms. New scientific research points to the need to divide the
population into equol producers and equol non-producers, since only the individuals who can produce
the active metabolite equol can be expected to have the therapeutic effect of isoflavones. Therefore,
the aim of this work is to provide a systematic overview of the research on this topic and to highlight
the importance of equol formation for the therapeutic effect of herbal drugs and dietary supplements
based on soy and red clover.
Material and methods
Research in this paper is a theoretical one and includes a detailed overview of the available literature
on current modern scientific research on equol as a bioactive metabolite of daidzein. Available
electronic bibliographic databases such as: PubMed, ScienceDirect, Elsevier, Frontiers media, Plos one,
Wolter Kluwer, etc. were used in the research. Google and Google Scholar search engines were used
for the data collection
Results
This paper presents the research results on the effects of equol on various areas of human health,
focusing on menopausal symptoms, cardiovascular disease, osteoporosis, dementia, PMS, breast and
prostate cancer and skin aging. The review also includes research on the structure and mechanism of
action of equol, as well as on colonic bacteria involved in the process of forming equol from daidzein.
An overview of equol-based dietary supplements and the biotechnological approach to the production
of equol-containing functional foods is provided.
Conclusion
Equol is an active isoflavone metabolite formed exclusively by the action of intestinal bacteria in
humans that are equol producers. The effect of equol is not yet fully understood, but it has been
shown to be a selective modulator of ERβ and is classified as a SERM. Clinical evidence of the effects
of equol is growing, but longer randomized clinical trials and observational studies of the biological
effects of S-equol in the human body are still needed. A standardized natural dietary supplement
containing S-(-)equol has been developed and is obtained by fermenting a solution of soybean sprouts
with a strain of Lactococcus 20-92 lactic acid bacteria
Expression of brain-derived neurotrophic factor in Alzheimer's disease
No full textAlzheimerova bolest (AB) je progresivni neurodegenerativni poremećaj, a neurobiološke promjene karakteristične za
AB nastupaju vrlo rano u odnosu na vrijeme ispoljavanja kliničkih simptoma. Blagi kognitivni poremećaj (engl. mild
cognitive impairment, MCI), u nekim slučajevima, može prethoditi AB-u. Ranije postavljanje dijagnoze, prije nastanka
značajnih kognitivnih deficita, te pravovremena terapijska intervencija, uvelike bi promijenili kvalitetu života i ishode
oboljelih. U tu se svrhu intenzivno istražuju novi biljezi i terapijske mete, poput moždanog neurotrofnog čimbenika
(engl. brain-derived neurotrophic factor, BDNF). Cilj ovog istraživanja bio je ispitati može li se razina ekspresije
BDNF-a (na razini gena i proteina) povezati sa stupnjem kognitivnog deficita, te istražiti povezanost dva najčešće
istraživana polimorfizma gena BDNF s dijagnozom AB-a, razinom kognitivnog oštećenja i utvrditi postoji li utjecaj
navedenih polimorfizama na ekspresiju gena BDNF ili na koncentraciju ovog neurotrofina na periferiji. U istraživanje
je bilo uključeno 153 ispitanika, podijeljenih prema dijagozi na ispitanike s AB-om i one s dijagnozom MCI-ja. Za
analizu su korišteni uzoci pune krvi iz koje je izvojena plazma siromašna trombocitima za određivanje koncentracije
BDNF-a, a frakcija s leukocitima korištena je za izolaciju ukupne RNA i DNA, odnosno određivanje ekspresije gena
BDNF i genotipizaciju polimorfizama gena BDNF rs6265 i rs56164415. Rezultati istraživanja upućuju na višu
koncentraciju BDNF-a u plazmi ispitanika oboljelih od AB-a u odnosu na ispitanike s MCI-jem, uz negativnu korelaciju
između koncentracije BDNF-a u plazmi i ostvarenog broja bodova na psihometrijskim testovima. Osim toga, zabilježena
je niža relativna ekspresija gena BDNF u ispitanika oboljelih od AB-a u odnosu na ispitanike s MCI-jem, što upućuje
na moguće kompenzatorne neuroprotektivne mehanizme. Promatranjem polimorfizama gena BDNF, zabilježena je viša
učestalost alela A, s obzirom na polimorfizam rs6265, u skupini ispitanika oboljelih od AB-a. Značajno bolje očuvane
kognitivne funkcije zabilježene su kod homozigota GG s obzirom na polimorfizam rs6265, odnosno kod nositelja alela
T u slučaju polimorfizma rs56164415, što upućuje na postojanje rizičnih alela za navedene polimorfizme i time daje
uvid u nasljednu komponentu bolesti. Dostupni podaci u literaturi su heterogeni i potrebna su daljnja istraživanja, s
naglaskom na uključivanje kontrolne skupine zdravih ispitanika usklađenih po dobi.Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with characteristic neurobiological changes
appearing decades prior to symptom onset. In some cases, mild cognitive impairment (MCI) precedes AD. Earlier
diagnosis, before significant cognitive decline, would allow for earlier intervention and better quality of life for those
affected. Therefore, significant scientific effort is directed at the discovery of new biomarkers and therapeutic targets
for AD, such as brain-derived neurotrophic factor (BDNF). The aim of this study was to analyze whether there is a
connection between BDNF expression and cognitive decline, and whether the two most investigated BDNF
polymorphisms affect AD diagnosis, cognitive decline, BDNF expression or plasma BDNF concentration. A total of
153 participants were included in the study, divided into two subgroups according to diagnosis (AB or MCI). Whole
blood samples were processed in order to obtain platelet-poor plasma, which was used for the determination of BDNF
concentration. Genomic DNA and total RNA were isolated from peripheral blood for determining relative BDNF
expression and genotyping of BDNF polymorphisms rs6265 and rs56164415. Results suggest significantly increased
plasma BDNF concentration in AD patients compared to MCI subjects, while negative correlation was observed between
plasma BDNF concentration and psychometric test scores. Furthermore, lower BDNF gene expression was noticed in
patients with AD compared to MCI subjects. These findings might suggest compensatory neuroprotective mechanisms.
Regarding BDNF polymorphisms, a higher frequency of A allele (rs6265) was detected in AD patients, while rs6265
GG homozygotes and/or carriers of rs56164415 T allele performed better on psychometric tests. Identifying A and C
alleles as risk alleles gives us a better insight into genetic factors possibly affecting disease progression. Current
published data are heterogenous and further studies are needed, with an emphasis on inclusion of healthy age-matched
controls
Potreba za deskripcijom benzodiazepina u osoba starije životne dobi na razini primarne zdravstvene zaštite
No full textCilj je ovog istraživanja bio odrediti udio starijih osoba u primarnoj zdravstvenoj zaštiti koje koriste
benzodiazepine (BZD), analizirati vrstu, dozu, trajanje terapije i način primjene BZD-a te ustanoviti
postoji li potencijal za depreskripciju BDZ-a. Također su analizirane klinički značajne interakcije između
BZD-a i ostalih lijekova te dodataka prehrani.
Istraživanje je provedeno na uzorku od 264 pacijenata starije životne dobi (>65 godina), u javnim
ljekarnama na području Zagreba, Istre i Kvarnera, u periodu od ožujka 2019. do ožujka 2020. godine.
Dio je većeg istraživanja koje se provodi u više europskih zemlja u sklopu projekta EuroAgeism Horizon
2020. Za potrebe istraživanja definirano je četiri kriterija za depreskripciju, koristeći kanadske,
australske i tasmanijske smjernice za depreskripciju BZD-a te podatke navedene u Sažetku opisa
svojstava lijekova, na temelju kojih se odlučivalo o tome koji ispitanici bi mogli imati koristi od
depreskripcije ovih lijekova.
U ispitivanju je sudjelovalo 264 pacijenata, od kojih je 35,2 % muškaraca i 64,8 % žena prosječne dobi
74,49 (SD=6,81) godina. Ispitanici su koristili prosječno 5,97 ± 3,17 lijekova, BZD je koristilo 90 ispitanika
(34,2 %), najčešće diazepam (n=41, 45,6 %) i alprazolam (n=25, 27,8 %). Najčešće indikacije za
korištenje BZD-a bili su problemisa spavanjem (n=36, 40,0 %), anksioznost (n=26, 28,9 %) i kombinacija
anksioznosti i nesanice (n=9, 10,0 %). Najviše ispitanika, njih 70 % (63 ispitanika), zadovoljilo je kriterij
C za depreskripciju BZD-a koji se odnosio na trajanje terapije (duže od 12 tjedana). 30 % ispitanika
imalo je prekoračenu preporučenu maksimalnu dnevnu dozu za starije osobe. Dobiveni rezultati
pokazali su da bi 75 pacijenata (83,3 %) moglo imati koristi od depreskripcije. Osim toga, pokazalo se
da bi se svim ispitanicima koji koriste BZD trebalo pristupiti s ciljem revizije terapije.
Iz dobivenih rezultata dalo bi se zaključiti o potrebi za racionalnijim korištenjem BDZ-a u starijih osoba
na razini primarne zdravstvene zaštite. Potrebno je podići svijest o problemu prekomjernog
propisivanja BZD-a starijima kao rizičnoj skupini te educirati liječnike i ljekarnike o alternativnim
terapijskim mogućnostima. Također valja obratiti pažnju na interakcije između BZD-a i drugih lijekova,
osobito onih koji djeluju na SŽS, iz razloga što mogu povećati rizik nuspojava, padova i lomova.
Smjernice i kriteriji za depreskripciju mogle bi biti koristan alat za racionalniju primjenu BZD-a.The goals of this study were to determine the percentage of older people in Croatian primary health
care who use benzodiazepines (BZD) and to characterize those drugs by type of drug, dose, and duration
of treatment. The study also aimed to estimate the need for deprescribing BZD and analyse clinically
significant interactions between BZD and other medications, including over-the-counter drugs.
A total of 264 older patients (>65 years) from two regions (Zagreb and Istra and Kvarner) were included
in this study. Data were collected from patients in community pharmacies using a standardized
questionnaire between March 2019 and May 2020. This study is part of a larger study conducted in
several European countries as part of the EuroAgeism Horizon 2020 project. To determine which
patients could benefit from deprescribing BZD, four criteria for deprescribing were defined using
Canadian, Australian, and Tasmanian guidelines, as well as the Summary of Product Characteristics of
the drugs analysed.
Of the 264 patients included in the study, 35.2% were male and 64.8% were female, with a mean age
of 74.49 (SD=6.81) years. On average, patients used 5.97 ± 3.17 drugs, with 90 patients (34.2%) using
BZD. Diazepam was the most commonly used BZD (n=41, 45.6%), followed by alprazolam (n=25,
27.8%). The most common indications for BZD use were insomnia (n=36, 40.0%), anxiety (n=26, 28.9%),
and a combination of both (n=9, 10.0%). The majority of patients (n=63, 70%) used BZD for more than
12 weeks, which met the criteria for deprescribing. 30% of the patients exceeded the recommended
maximum daily dosage for older adults. The results indicated that at least 75 patients (83.3%) could
benefit from deprescribing BZD. Furthermore, all patients who participated in this study and used BZD
should have their therapy reviewed and optimized.
The results of this study highlight the need for the rationalization of BZD use in older adults in primary
care settings. There is a necessity to raise awareness about prescribing BZD drugs to older adults and
educate doctors and pharmacists about alternative therapeutic options. Additionally, attention should
be given to interactions between BZD drugs and other medications, especially those with an impact on
the central nervous system, as their combined use can increase the risk of side effects, falls, and
fractures. Guidelines and criteria for deprescribing can serve as useful tools in rationalizing the usage
of BZD drugs among older adults
Liquid biopsy in the diagnosis of malignant diseases
No full textMaligne bolesti predstavljaju glavni uzrok smrtnosti nakon kardiovaskularnih oboljenja. Dijagnoza karcinoma često je u poodmakloj i neoperabilnoj fazi, stoga metastatsko širenje karcinoma predstavlja glavni uzrok smrti pacijenata oboljelih od malignih bolesti. Tekuća biopsija predstavlja inovativni koncept na području onkološke dijagnostike. Neinvazivna je metoda kojom se iz uzorka krvi ili neke druge tjelesne tekućine izoliraju elementi poput cirkulirajuće tumorske stanice (CTC), slobodna cirkulirajuća DNA (cfDNA), cirkulirajući egzosomi ili mikroRNA koji sami služe kao biljezi ili sadrže specifične biljege.Imunocitokemijskim testom je utvrĎeno da su CTC invazivne te da je njihova prisutnost u korelaciji sa smanjenim preživljavanjem osoba oboljelih od malignih bolesti. Egzosomi kao izvanstanične vezikulne strukture takoĎer predstavljaju specifičan biljeg koji pospješuje rast, invaziju, metastaziranje i angiogenezu tumora. Reprezentativniji su u odnosu na ostale biljege, jer sadrže biološki materijal iz roditeljskih stanica. TakoĎer, na površini mogu imati eksprimirane specifične tumorske biljege, poput proteina, koji povećavaju kemorezistenciju.Tekuća biopsija obuhvaća izoliranje CTC-a, egzosoma, cfDNA te njihovu daljnju analizu. Može se primijeniti za dijagnozu, predviĎanje prognoze, molekularno profiliranje tumora, planiranje liječenja, praćenja pacijenta, praćenja evolucije tumora i otkrivanja relapsa.Malignant diseases are the leading cause of death after cardiovascular disease. The diagnosis of cancer is often in an insidious and inoperable phase, so metastatic spread of cancer is the leading cause of death in patients with malignant diseases. Liquid biopsy is an innovative concept in the field of oncology diagnostics. It is a non-invasive method of isolating elements such as circulating tumor cells (CTC), free circulating DNA (cfDNA), circulating exosomes or microRNAs that themselves serve as markers or contain specific markers from a blood sample or some other body fluids. Immunocytochemical test revealed that CTC were invasive and that their presence correlated with reduced survival of persons with malignant diseases. Extracellular vesicles also represent a specific marker that promotes tumor growth, invasion, metastasis, and angiogenesis. They are more representative compared to other markers because they contain biological material from the parent cells. Also, they may have specific tumor markers, such as proteins, expressed on the surface, which increase chemoreresistance. Liquid biopsy involves the isolation of CTCs, exosomes, cfDNA, and their further analysis. It can be used for diagnosis, prognosis prediction, molecular tumor profiling, treatment planning, patient monitoring, tumor evolution monitoring, and relapse detection
ABCG2 and SLCO1B1 gene polymorphisms as risk factors to statin therapy
No full textPrema podatcima WHO-a, koronarna arterijska bolest (CAD) postala je jednom od najvećih „ubojica“ suvremenog
svijeta. Dislipidemija, odnosno povišene razine ukupnog kolesterola, lipoproteina niske gustoće (LDL), triglicerida (TG) ili
snižene razine lipoproteina visoke gustoće (HDL), smatra se jednim od kritičnih čimbenika za razvoj CAD-a. U posljednje
su vrijeme statini najšire propisivani lijekovi u prevenciji i terapiji CAD-a i ishemijskog inzulta. Štoviše, oni dokazano
smanjuju morbiditet i mortalitet snižavanjem razine LDL - kolesterola u krvnoj plazmi. Međutim, statini uzrokuju mnoge
ozbiljne nuspojave, poput miopatije i rabdomiolize. Štoviše, kako se statini koriste u dugotrajnoj terapiji kroničnih bolesti,
velik je i rizik od nuspojava kao posljedice interakcija s drugim lijekovima u politerapiji. Također, utvrđene su velike
interindividualne razlike u smanjenju razina LDL - kolesterola te u incidenciji ADR-a prilikom terapije statinima.
Postoje čvrsti znanstveni dokazi o važnosti membranskih prijenosnika OATP1B1 i BCRP u farmakokinetici statina.
Oba transportera pokazuju značajnu genetičku varijabilnost, a učestalost polimorfizama SLCO1B1 521T>C i ABCG2
421C>A ima veliku i populacijsku i rasnu varijabilnost. Varijantni je alel SLCO1B1 521C najučestaliji u europskoj (16 %),
azijatskoj (12 %) i afričkoj populaciji (1 %). Varijantni alel ABCG2 421A je najučestaliji u Azijata (30 %), zatim u bjelačkoj
populaciji (10-15 %), dok je najrjeđi u afričkoj populaciji (2 %). Rezultati ustanovljeni u populaciji Hrvatske u skladu su s
rezultatima dobivenima za druge europske, bjelačke populacije. Polimorfizmi gena povezuju se s varijabilnom kinetikom, ali
i podložnosti razvoja neželjenih učinaka lijekova supstrata, jer varijabilna aktivnost u prijenosu lijekova preko barijera u
probavnom sustavu, na barijeri jetra-žuč te tubulima bubrega u slučaju BCRP, te unos lijeka u jetra putem OATP1B1 mogu
značajno modulirati apsorpciju, distribuciju i izlučivanje lijekova-supstrata. Stoga analiza polimorfizama SLCO1B1 i
ABCG2 može poslužiti u individualizaciji i optimizaciji liječenja statinima te minimalizaciji rizika razvoja nuspojava,
prvenstveno miotoksičnosti i hepatotoksičnosti.According to the WHO, coronary artery disease (CAD) has become one of the greatest „killers“ of the modern
world. Dyslipidemia, or elevated levels of total cholesterol, low-density lipoprotein (LDL), triglycerides (TG), or decreased
levels of high density lipoprotein (HDL), is considered one of the critical factors for the development of CAD. Recently,
statins have been the most widely prescribed drugs in the prevention and treatment of CAD and of ischemic stroke.
Moreover, it is proved that they reduce morbidity and mortality by lowering LDL cholesterol levels in the blood plasma. On
the other side, statins may cause many serious side effects, such as myopathy and rabdomyolysis. Moreover, as statins are used in the long-term therapy of chronic diseases, there is a high risk of side effects as a consequence of interactions with other drugs in polytherapy. Also, great interindividual differences were found in the reduction of LDL-cholesterol levels and in the incidence of ADR during statin therapy.
There is a strong scientific evidence of the importance of OATP1B1 and BCRP membrane transporters in statin
pharmacokinetics. Both transporters show significant genetic variability, and the frequency of polymorphisms SLCO1B1
521T>C and ABCG2 421C>A has great both population and racial variability. The variant allele SLCO1B1 521C is most
common in the European (16 %), Asian (12 %) and African (1 %) population, while the ABCG2 421A variant allele is most
common in Asians (30 %), followed by the white population (10 – 15 %), while it is the rarest in the African population (2
%). The results established in this study are accordant to the results obtained for other European, white populations. Gene
polymorphisms are associated with variable kinetics, but also the susceptibility to the development of adverse drug reactions
of the substrate, because variable activity in drug transport across barriers in the digestive system, liver-bile barrier, renal
tubules in case of BCRP, and drug intake in the liver via OATP1B1 can significantly modulate the absorption, distribution
and excretion of substrate drugs. Therefore, the analysis of SLCO1B1 and ABCG2 polymorphisms can serve to individualize
and optimize statin treatment and minimize the risk of side effects, primarily myotoxicity and hepatotoxicity