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Reliability of digital microscopy in determination of the reticulocyte count
No full textRetikulociti su mladi eritrociti, stanice bez jezgre i sa ostacima ribonukleinske kiseline u
citoplazmi. Razvijaju se u koštanoj srži iz acidofilnog eritroblasta. Broj retikulocita važan je
laboratorijski parametar u procjeni eritropoetske aktivnosti koštane srži u odgovoru na anemiju,
krvarenja, kemoterapiju i različite toksine. Zlatni standard brojenja retikulocita je svjetlosna
mikroskopija koja je dugotrajna i zamorna, sklona greškama zbog varijabilnosti i subjektivnosti
među promatračima. Razvojem tehnologije razvijaju se i digitalni analizatori za morfologiju
stanica koji omogućuju brži pregled razmaza periferne krvi. Cilj ovog diplomskog rada je
usporediti rezultate brojenja retikulocita ručnom metodom na svjetlosnom mikroskopu, na Sysmex
XN-10 hematološkom analizatoru automatiziranom metodom i brojenjem unutar eritrocitnog
podizbornika na Sysmex DI-60 analizatoru za digitalnu morfologiju stanica i provjeriti je li on
pogodan za određivanje broja retikulocita. Za procjenu usporedivosti metoda korišteni su
Spearmanov koeficijent korelacije ranga (ρ), Passing-Bablok regresija i Bland-Altman analiza.
Utvrđena je vrlo visoka korelacija između Sysmex DI-60 i automatizirane Sysmex XN-10 (ρ =
0,970) metode i ručne metode (ρ = 0,970) što ukazuje na vrlo dobru podudarnost metoda. Utvrđeno
je manje, očekivano odstupanje između Sysmex DI-60 metode i ručne metode, odnosno Sysmex
XN-10 metode. Zaključeno je da se analizator može uvesti u rutinski rad hematološkog laboratorija
za određivanje broja retikulocita unutar eritrocitnog podizbornika.Reticulocytes are young erythrocytes, cells without a nucleus and with remnants of ribonucleic
acid in their cytoplasm. They develop in the bone marrow from acidophilic erythroblasts. The
number of reticulocytes is an important laboratory parameter in assessing the erythropoietic
activity of the bone marrow in response to anemia, bleeding, chemotherapy, and various toxins.
The gold standard for counting reticulocytes is light microscopy, which is time-consuming and
tedious, prone to errors due to variability and subjectivity among observers. With the advancement
of technology, digital analyzers for cell morphology have been developed, enabling faster
examination of peripheral blood smears. The aim of this thesis is to compare the results of
reticulocyte counting using the manual method with light microscopy, the automated method on
the Sysmex XN-10 hematology analyzer, and the counting within the erythrocyte submenu on the
Sysmex DI-60 cell morphology analyzer, and to determine if it is suitable for reticulocyte counting.
To assess the comparability of the methods, Spearman's rank correlation coefficient (ρ), Passing-
Bablok regression, and Bland-Altman analysis were used. A very high correlation was found
between the Sysmex DI-60 and the automated Sysmex XN-10 (ρ = 0,970) method and the manual
method (ρ = 0,970), indicating a very good concordance of the methods. A small, expected
deviation was found between the Sysmex DI-60 method and the manual method, as well as the
Sysmex XN-10 method. It was concluded that the analyzer can be introduced into the routine work
of the hematology laboratory for reticulocyte counting within the erythrocyte submenu
Biological variability of anti-müllerian hormone, inhibin B and androstendion in women of reproductive age
No full textBiološka varijabilnost je prirodna fluktuacija analita oko homeostatske točke koja pridonosi nesigurnosti kod interpretacije dobivenih rezultata. Varijacije analita u određenog pojedinca oko homeostatske točke nazivamo intraindividualna biološka varijabilnosti, a variranje homeostatskih točaka pojedinaca u grupi referentnih osoba oko prosječne vrijednosti istog analita nazivamo interindividualna biološka varijabilnost. Specifikacije sastavnica biološke varijabilnosti pridonose definiranju analitičkih ciljeva kvalitete, odabiru odgovarajućeg uzorka, odgovarajućih jedinica za izražavanje rezultata te najprikladnijeg načina interpretacije nalaza. Cilj ovoga istraživanja bio je odrediti sastavnice biološke varijabilnosti za pretrage AMH, inhibin B i androstendion. U istraživanju je sudjelovalo 40 žena reproduktivne dobi, u rasponu od 19 do 42 godine. Uzorci su uzeti u tri uzastopna menstruacijska ciklusa, na 2. ili 3. dan ciklusa. Utvrđene su vrijednosti ukupne varijabilnosti (CVT), analitičke varijacije (CVA), intraindividualne varijabilnosti (CVI) te interindividualne varijabilnosti (CVG) za svaku pretragu. Za AMH su dobiveni sljedeći rezultati: CVT od 16,0 %, CVA od 4,6 %, CVI od 15,3 % te CVG od 67,7 %. Za androstendion je dobiven CVT od 18,1 %, CVA od 2,1 %, CVI od 17,9 % te CVG od 41,2 %. Za inhibin B dobiven je CVT od 34,5 % , CVA od 26,1 %, CVI od 33,1 % te CVG od 42,4 %. Za pretrage AMH i androstendion utvrđeno je da biološka varijabilnost više doprinosi promjenjivosti rezultata od analitičke varijacije što treba uzeti u obzir pri tumačenju rezultata. Za pretragu inhibina B ukupna analitička varijacija manja je od ukupne intraindividualne varijabilnosti, no kod nekih ispitanica analitička varijacija je nadilazila intraindividualnu sastavnicu, stoga pretraga nije zadovoljila minimalne specifikacije kvalitete za nepreciznost.Biological variability is the natural fluctuation of the analyte around the homeostatic point which contributes to uncertainty in the interpretation of the obtained results. Variations of an analyte in a certain individual around the homeostatic point is called intraindividual biological variability, and variation of homeostatic points of individuals in a group of reference population around the average value of the same analyte is called interindividual biological variability. The specifications of the components of biological variability contribute to the definition of analytical quality goals, the selection of the appropriate sample, the appropriate units for expressing the results, and the most appropriate way of interpreting the findings. The aim of this research was to determine the components of biological variability for AMH, inhibin B and androstenedione tests. Forty women of reproductive age, ranging from 19 to 42 years, participated in the research. Samples were taken in three consecutive menstrual cycles, on the 2nd or 3rd day of the cycle. The values of total variability (CVT), analytical variation (CVA), intraindividual variability (CVI) and interindividual variability (CVG) were determined for each analyte. The following results were obtained for AMH: CVT of 16.0%, CVA of 4.6%, CVI of 15.3% and CVG of 67.7%. CVT of 18.1%, CVA of 2.1%, CVI of 17.9% and CVG of 41.2% were obtained for androstenedione. CVT of 34.5%, CVA of 26.1%, CVI of 33.1% and CVG of 42.4% were obtained for inhibin B. For AMH and androstenedione tests, it was determined that biological variability contributes more to the variability of results than analytical variation, which should be taken into account when interpreting results. For inhibin B test, the total analytical variation is less than the total intraindividual variability, but in some subjects the analytical variation exceeded the intraindividual component, therefore the test did not meet the minimum quality specifications for imprecision
Znanja, stavovi i iskustva ljekarnika o primjeni biljnih lijekova i dodataka prehrani u trudnoći
No full textCilj istraživanja: Primjena biljnih lijekova i dodataka prehrani među trudnicama je u porastu
jer im pruža osjećaj neštetnosti i sigurnosti, što može dovesti do neracionalne upotrebe takvih
pripravaka i povećati rizik od nepovoljnog ishoda trudnoće. Kako bi se osigurala učinkovita i
sigurna upotreba pripravaka za samoliječenje u trudnoći, vrlo je važna uloga javnih ljekarnika
kao najdostupnijih zdravstvenih djelatnika. Stoga je cilj ovog istraživanja ispitati znanja,
stavove i iskustva ljekarnika u Republici Hrvatskoj o primjeni biljnih lijekova i dodataka
prehrani u trudnoći.
Ispitanici i metode: U ovom radu provedeno je istraživanje na uzorku od 98 javnih ljekarnika.
U istraživanju su sudjelovali magistri farmacije s najmanje jednom godinom staža u javnoj
ljekarni. Istraživanje je provedeno putem anonimnog upitnika koji je kreiran za potrebe rada.
Na početku anketnog upitnika prikupljeni su sociodemografski podaci o ispitanicima (dob,
spol, godine rada u ljekarni, veličina mjesta u kojem se nalazi ljekarna i dodatno školovanje),
a preostala pitanja bila su vezana uz njihova znanja, iskustva i stavove o primjeni biljnih
lijekova i dodataka prehrani u trudnoći. Istraživanje je provedeno u javnim ljekarnama na
području Hrvatske u razdoblju od svibnja do srpnja 2020. godine.
Rezultati: Najviše ljekarnika (60 %) savjetuje trudnice nekoliko puta mjesečno. Trudnice ih
uglavnom traže savjete vezano uz probavne tegobe povezane s trudnoćom i u slučaju simptoma
prehlade/viroze. Upotrebu biljnih lijekova i dodataka prehrani najviše ispitanika (60-79 %)
savjetuje kod mučnine i povraćanja, proljeva, zatvora i hemoroida. Najčešće korišteni pripravci
kontraindicirani u trudnoći bili su oni koji sadrže medvjetku (N = 20) te biljne droge s
antracenskim derivatima (N = 7). Uočene nuspojave uglavnom su bile probavne tegobe (N =
11) povezane s primjenom pripravaka koji sadrže željezo (pojedinačno ili multivitaminsko
mineralne formule), omega-3 masne kiseline ili đumbir. Ljekarnici su kod tri trudnice uočili
klinički značajnu interakciju između željeza i levotiroksina. Nezadovoljstvo dostupnošću
stručnih informacija o primjeni biljnih lijekova i dodataka prehrani u trudnoći izrazilo je nešto
više od polovice ispitanika. Za savjetovanje trudnica većina ljekarnika koristi brzo i lako
dostupne izvore informacija, pisanu uputu o biljnom lijeku odnosno deklaraciju dodatka
prehrani i/ili stručnu literaturu. Gotovo svi ljekarnici smatraju da se biljni lijekovi i dodaci
prehrani trebaju izdavati uz savjet ljekarnika, te je polovica zabrinuta zbog sigurnosti primjene
dodataka prehrani u trudnoći. Iako se veliki dio ispitanika smatra kompetentnim savjetovati
trudnice o primjeni biljnih lijekova i dodataka prehrani, čak 98 % iskazalo je potrebu za
dodatnim stručnim edukacijama iz ovog područja.
Zaključci: Zahvaljujući svojim znanjima i vještinama, kao i dostupnosti pacijentu, javni
ljekarnici su u prilici savjetovati trudnice o racionalnoj upotrebi biljnih lijekova i/ili dodataka
prehrani kod bolesti prikladnih za samoliječenje, a također mogu prepoznati kada je neki
pripravak kontraindiciran, izaziva nuspojave ili stupa u interakcije. S obzirom na iskazanu
nesigurnost u donošenju terapijskih odluka kod samoliječenja trudnica, ljekarnicima su
potrebne dodatne edukacije kako bi poboljšali svoje stručne kompetencije vezane uz ovu temu
i tako trudnicama pružili adekvatnu ljekarničku skrb.Objectives: Increased use of herbal drugs and dietary supplements among pregnant women,
because of their feeling of harmlessness and safety, may lead to unreasonable use of such
products and enhance the risk of unfavorable pregnancy outcome. To ensure efficient and safe
use of products for self-medication during pregnancy, the role of public pharmacists as the
most accessible healthcare professionals is outstandingly important. The goal of this research
is to examine knowledge, attitude and experience of pharmacists in the Republic of Croatia
with regard to usage of herbal drugs and dietary supplements during pregnancy.
Respondents and Methods: In this work research has been carried out on a sample of 98
public pharmacists. The participants in the research were masters of pharmacy with at least one
year of internship in public pharmacy. The research was carried out by means of an anonymous
questionnaire created for this purpose. At the beginning of the survey questionnaire
sociodemographic data of respondents (age, sex, years of working experience in pharmacy,
size of city where pharmacy is located, further education) were collected. Remaining questions
were about their knowledge, experience and attitude in application of herbal drugs and dietary
supplements during pregnancy. Research was carried out in public pharmacies on the territory
of Croatia in the period from May to July 2020.
Results: Majority of pharmacists (60 %) advise pregnant women several times a month.
Pregnant women mostly seek counsel related to digestive problems linked to pregnancy and
related to symptoms of cold/viruses. The majority of respondents (60-79 %) advise the use of
herbal drugs and dietary supplements in a case of nausea, vomiting, diarrhea, constipation or
hemorrhoids. Most commonly used products contraindicated during pregnancy were those
containing bearberry (N = 20) and herbal drugs with anthracene derivatives (N = 7). Observed
side effects were mostly digestive problems (N = 11) linked to use of products containing iron
(in isolation or within multivitamin formulae), omega 3 fatty acids or ginger. In three
pregnancies pharmacists reported clinically relevant interaction between iron and
levothyroxine. Slightly more than half of respondents have stated their dissatisfaction related
to the availability of official information on usage of herbal drugs and dietary supplements
during pregnancy. To advise pregnant women, the majority of pharmacists use easily
obtainable sources of information, written instruction and declaration on dietary supplements
and/or professional literature. Almost all pharmacists believe that herbal drugs and dietary
supplements should be handed out after professional counsel. Half of them are concerned about
the safety of use of dietary supplements during pregnancy. Despite the fact that the vast
majority of respondents consider themselves competent in advising pregnant women about the
application of herbal drugs and dietary supplements, 98 % still expressed the need for further
professional education in this domain.
Conclusions: Public pharmacists, thanks to their knowledge and skill as well as their
accessibility to the patients, have the opportunity to counsel pregnant women on rational use
of herbal drugs and/or dietary supplements related to diseases appropriate for self- medication.
They are able to recognize if some product is contraindicated, causes side effects or enters into
interactions. Taking into account the uncertainty in therapy decision making, stated by
pharmacists, with regard to self-medication of pregnant women, pharmacists are in need of
further education to improve their professional competence linked to this topic. Only then will
they be able to offer adequate pharmaceutical care to pregnant women
Pharmacological activity and application of isatin and isatin derivatives
No full textIzatin je prirodni alkaloid narančaste boje izoliran iz biljaka roda Isatis prisutnih po cijelom svijetu. O.L. Erdman i A. Laurent prvi su puta 1841. godine sinetizirali izatin oksidacijom indiga smjesom dušične i kromne kiseline, a do danas je otkriven velik broj izatinskih derivata od kojih su neki pokazali značajna antitumorska, antibakterijska, antikonvulzivna, protuupalna i brojna druga djelovanja. Iako izatinski derivati imaju širok spektar djelovanja, do sada se antitumorsko djelovanje pokazalo najznačanijim. Sunitinib je derivat izatina koji je 2006. godine registrirala EMA u liječenju GIST-a, a kasnije i za liječenje neoperabilnih ili metastatski dobro diferenciranih tumora gušterače (pNET) i metastatskog karcinoma bubrežnih stanica (MRCC). Osim što je registriran kao lijek u navedenim indikacijama, sunitinib prolazi kroz klinička ispitivanja kao dvojna terapija s docetakselom, kapecitabinom i paklitakselom. Inhibitor je više tirozin kinaza te tako sprječava rast tumora, proliferaciju stanica i angiogenezu, a značajno inhibitorno djelovanje pokazao je prema VEGFR i PDGFR. Indirubin je poznat izatinski derivat s protuupalnim, antiproliferativnim, hepatoprotektivnim i protuleukemijskim djelovanjem. Iako njegova sigurnost i učinkovitost nije dokazana, u tradicionalnoj se kineskoj medicini koristi u terapiji psorijaze, prevenciji mastitisa uzrokovanog LPS-om E. Coli i S. aureus te kao dodatna terapija CML-a. Hibridi izatinskih derivata s fluorokinolonima ispituju se kao antibakterijska terapija u liječenju infekcija uzrokovanih H. influenzae, K. pneumonia, P.aeruginosa. U najnovijim istraživanjima pronađeno je da djelovanjem bakterijskih enzima u crijevima dolazi do sinteze izatina iz triptofana što uzrokuje povećane koncentracije izatina u tjelesnim tekućinama i mozgu. Do navedene promjene dolazi tijekom izloženosti akutnom stresu, tijekom Parkinsonove bolesti zbog povećanog broja bakterija roda Enterococcaceae te se često javlja kod pacijenata oboljelih od bulimije. Ovim diplomskim radom prikazana su najistaknutija farmakološka djelovanja izatina i izatinskih derivata i učinak bakterijske mikroflore na rad i funkciju mozga.Isatin is natural alkaloid, isolated as orange solid from plants of Isatis genus. First synthesis of isatin dates back to 1841. when O.L. Erdman and A. Laurent obtained it by oxidation of indigo with mixture of nitric and chromic acid. Up to now, large number of isatin derivatives with various pharmacological activities, some of which are antibacterial, antitumor, anticonvulsant, anti-inflammatory etc., have been reported. Isatin derivatives as antitumor agents have been mostly studied and Sunitinib is the one of isatin derivatives which EMA registrated in 2006. for treatment of GIST, pNet's and MRCC. At the moment, Sunitinib is in the clinical trial in combination with capecitabine, paclitaxel and docetaxel in treatment for the different types of tumours. It is multi-tyrosine receptor kinase inhibitor and therefore it prevents growth and proliferation of tumors cells and angiogenesis. Significant inhibitory activity has been reported with VEGFR and PDGFR. Indirubin is isatin derivative with anti-inflammatory, antiproliferative, hepatoprotective and antileukemic activity. Although it's safety and efficiency are not proven, in Chinese traditional medicine it is used in treatment of psoriasis, mastitis caused by E. Coli and S. aureus prevention and as additional therapy of the CML. Isatin hybrids of fluoroquinolones show antibacterial activity to H. influenze, K. pneumonie, P. aerugionosa and many others. Recent studies reported that isatin can be synthesized from triptofan by gastrointestinal bacterial enzymes which leads to high isatin concentarion in body fluids and brain. This is often caused by acute stress, large number of Enterococcaceae in patient with Parkinson disease and bulimia. This review shows the most prominent pharmacological effect of isatin and isatin derivatives and the effect of bacterial microflora on activity and function of brain
Hrvoje Iveković, sveučilišni profesor kemije, rektor Sveučilišta u Zagrebu i predsjednik Matice hrvatske
No full textOvaj diplomski rad pruža sveobuhvatan pregled života i djelovanja Hrvoja Ivekovića (1901. – 1991.). Svoje akademsko obrazovanje stekao je u području kemije, studirajući na Visokim tehničkim školama u Brnu te Zagrebu gdje je i diplomirao (1924.). Iveković je bio redoviti profesor opće i anorganske kemije sa stehiometrijom na Farmaceutskom fakultetu (kasnije Farmaceutsko-biokemijski fakultet) i predstojnik Zavoda za anorgansku, analitičku i fizikalnu kemiju (kasnije Zavod za opću i anorgansku kemiju) od 1945. pa sve do umirovljenja (1971.). Zaslužan je za obnavljanje rada Farmaceutskog fakulteta (1945.) gdje je u nekoliko mandata obnašao dužnost dekana. Bio je rektor Sveučilišta u Zagrebu (1954. – 1956.). Njegov značajan doprinos znanosti ogleda se u njegovim istraživanjima u području kemije, posebice u tehnologiji dobivanja i iskorištavanja boksita te kemiji pitkih, podzemnih, termalnih i mineralnih voda. Razvio je originalan postupak ekstrakcije aluminija i nekih rijetkih metala iz boksita koristeći acetilaceton. Dobitnik je Nagrade za životno djelo (1976.). Sudjelovao je aktivno u kulturnom i javnom životu promovirajući hrvatsku kulturu i jezik. Bio je predsjednik Matice hrvatske od 1968. do 1970. godine.This master's thesis provides a comprehensive overview of the life and work of Hrvoje Iveković (1901 - 1991). He obtained his academic education in the field of chemistry, studying at the High Technical Schools in Brno and Zagreb, where he graduated in 1924. Iveković was a full time professor of general and inorganic chemistry with stoichiometry at the Faculty of Pharmacy (later the Faculty of Pharmacy and Biochemistry) and the head of the Department of Inorganic, Analytical, and Physical Chemistry (later the Department of General and Inorganic Chemistry) from 1945 until his retirement in 1971. He played a significant role in revitalizing the Faculty of Pharmacy in 1945 and served as dean for several terms. He also served as the Rector of the University of Zagreb from 1954 to 1956. His notable contributions to science include his research in the field of chemistry, particularly in the technology of obtaining and utilizing bauxite and the chemistry of potable, underground, thermal, and mineral waters. He developed an original method for extracting aluminum and some rare metals from bauxite using acetylacetone. He was awarded a Lifetime Achievement Award in 1976. Iveković was actively involved in cultural and public life, promoting Croatian culture and language. He served as the president of the Matrix Croatica (Matica hrvatska) from 1968 to 1970
Biopharmaceutical characterization of carbopol gel for the dermal application of melatonin
No full textMelatonin je neurohormon koji se istražuje za liječenje raznih bolesti i stanja. Broj istraživanja dermalnih formulacija melatonina raste zbog njegovog potencijala u liječenju upalnih bolesti kože, sprječavanju znakova starenja, zaštiti kože od UV zračenja i zacjeljivanju rana. Dermalni put primjene lijeka omogućuje jednostavnost korištenja i postizanje visoke koncentracije lijeka izravno na mjestu primjene. Gelovi za dermalnu primjenu omogućuju dulje zadržavanje djelatne tvari na mjestu primjene te produljeno oslobađanje uklopljenog lijeka. Cilj ovog rada bio je odrediti biofarmaceutska svojstva karbopolskog gela s melatoninom za dermalnu primjenu. Pripravljen je gel karbopola (0,1 %, m/m) i polietilenglikola (PEG-a; 5 %, m/m) s uklopljenim melatoninom (0,1 %, m/m; formulacija CPM). Termodinamička topljivost melatonina u fiziološkoj otopini puferiranoj fosfatnim puferom (pH 7,4) iznosila je 1,34 ± 0,08 mg/ml, a u fosfatnom puferu (pH 5,5) 1,60 ± 0,22 mg/ml. Ispitivanjem in vitro oslobađanja melatonina, CPM formulacija je, u usporedbi s kontrolnom otopinom, karakterizirana produljenim oslobađanjem lijeka. Zabilježeno je nešto brže oslobađanje melatonina iz CPM-a pri pH 7,4 u usporedbi s medijem pH vrijednosti 5,5, no razlika nije pokazana statistički značajnom (f2 = 52,86). Usporedba dobivenih profila oslobađanja melatonina iz CPM-a u oba medija s poznatim matematičkim modelima pokazala je najbolju podudarnost s Korsmeyer-Peppasovim modelom. Difuzija melatonina iz formulacije pratila je Fickov mehanizam. Vijabilnost od 82,5 ± 4,3 % određena MTT testom potvrdila je biokompatibilnost formulacije CPM. Biofarmaceutska karakterizacija provedena u ovom radu ukazuje na potencijal formulacije CPM kao farmaceutskog oblika za dermalnu primjenu melatonina.Melatonin is a neurohormone currently under investigation for the treatment of various diseases and conditions. The number of studies on dermal melatonin formulations is increasing, due to its potential in treating inflammatory skin diseases, preventing signs of aging, protecting the skin from UV radiation, and promoting wound healing. The dermal drug administration route enables the simplicity of application and high drug concentration at the site of application. Dermal gels enable prolonged retention of the active substance at the application site and its prolonged release. The aim of this study was to determine the biopharmaceutical properties of a carbopol gel with melatonin for dermal administration. The gel was prepared using carbopol (0.1%, w/w) and polyethylene glycol (PEG; 5%, w/w) with the addition of melatonin (0.1%, w/w; CPM formulation). The thermodynamic solubility of melatonin in phosphate buffered saline (pH 7.4) was 1.34 ± 0.8 mg/mL, and 1.60 ± 0.22 mg/mL in phosphate buffer (pH 5.5). In vitro release study showed the prolonged melatonin release from CPM formulation compared to the control solution. A slightly more rapid release of melatonin from CPM was observed at pH 7.4 compared to the medium with a pH value of 5.5, but the difference was not statistically significant (f2 = 52.86). Comparison of the melatonin release profiles from CPM in both media with known mathematical models showed the best fit with the Korsmeyer-Peppas model. The diffusion of melatonin from the formulation followed Fickian mechanism. The viability of 82.5 ± 4.3% determined by the MTT assay confirmed the biocompatibility of the CPM formulation. Biopharmaceutical characterization performed in this study indicates the potential of the CPM formulation as a pharmaceutical form for dermal application of melatonin
Use of direct oral anticoagulants in the pediatric population
No full textIncidencija venske tromboembolije (VTE) u pedijatrijskoj populaciji značajno je porasla u posljednjih dvadeset godina, posebno među hospitaliziranom djecom. Ovaj porast se može pripisati boljoj dijagnostici, ali i povećanju rizičnih čimbenika od kojih je najčešći korištenje centralnog venskog katetera. Terapija VTE-e kod djece može se podijeliti na standardnu terapiju, koja uključuje primjenu nefrakcioniranog heparina (UFH), niskomolekularnog heparina (LMWH) i antagonista vitamina K (VKA). Ovi lijekovi imaju brojne nedostatke, heparini (UFH, LMWH) se primjenjuju parenteralno, a njihov antikoagulacijski učinak je nepredvidiv jer je ovisan o antitrombinu (AT), koji je kod novorođenčadi i bolesne djece često smanjen. Donedavno jedina oralna opcija su bili VKA, koji imaju spor početak i završetak djelovanja, brojne interakcije s hranom i lijekovima, što zahtjeva često praćenje i prilagodbu doze. Odobrenje direktnih oralnih antikoagulansa (DOAK) predstavlja značajan korak naprijed u liječenju VTE-e kod pedijatrijske populacije. Ovi lijekovi u odnosu na standardnu terapiju imaju brojne prednosti, poput jednostavnije primjene, manje potrebe za redovitim praćenjem te potencijalno niži rizik od interakcija i nuspojava. No unatoč prednostima, primjena DOAK-a kod djece nosi sa sobom ograničenja i izazove. Iako kliničke studije pokazuju sličnu djelotvornost i sigurnost kao standardna terapija, primjena kod djece mlađe od 1 godine, onkoloških pacijenata te osoba s oštećenjem funkcije jetre i bubrega je ograničena. Glavni nedostatak DOAK-a je nemogućnost primjene antidota kod djece, budući da nema dovoljno podataka o njihovoj sigurnosti i djelotvornosti.The incidence of venous thromboembolism (VTE) in the pediatric population has increased significantly over the past twenty years, especially among hospitalized children. This increase can be attributed to improved diagnostics, but also to an increase in risk factors, the most common being use of a central venous catheter. Treatment of VTE in children can be divided into standard therapy, which includes use of unfractionated heparin (UFH), low molecular weight heparin (LMWH) and vitamin K antagonists (VKA). These drugs have numerous disadvantages: heparins are administered parenterally, and their anticoagulation effect is unpredictable because it depends on antithrombin (AT), which is often reduced in neonates and sick children. Until recently, the only oral option was VKA, which have a slow onset and end of action, numerous interactions with food and drugs, which requires frequent monitoring and dose adjustment. The approval of direct oral anticoagulants (DOACs) represents a significant step forward in pediatric VTE treatment. Compared to standard therapy, these drugs have several advantages, easier application, less need for regular monitoring, and a potentially lower risk of interactions and side effects. Despite the advantages, the use of DOACs in children comes with limitations and challenges. Although clinical studies show similar efficacy and safety as standard therapy, their use in children under 1 year of age, oncology patients, and those with impaired liver and kidney function is limited. The main disadvantage of DOACs is the lack of an antidote in children, as there is insufficient dana on their safety and efficacy
Pharmacological treatment options for Alzheimer disease
No full textCilj ovoga preglednog rada je prikazati terapijske mogućnosti liječenja Alzheimerove bolesti, kako simptomatske, tako i nove generacije lijekova koji utječu na tijek bolesti, zatim lijekove koji su procesu istraživanja, s naglaskom na kliničku fazu 3 te ostale dobro poznate lijekove koji su potencijalni kandidati za prenamjenu.
Alzheimerova bolest progresivna je neurodegenerativna bolest koja pogađa milijune ljudi diljem svijeta. Svojim napredovanjem dovodi do gubitka pamćenja, kognitivnog propadanja i promjena u ponašanju rezultirajući potpunom ovisnošću oboljele osobe o pružatelju skrbi. Ključne patofiziološke značajke ove bolesti su izvanstanično nakupljanje amiloidnih plakova i unutarstanično nakupljanje tau spletova, praćeno neuroupalom, neurodegeneracijom i atrofijom mozga.
Farmakološke mogućnosti liječenja Alzheimerove bolesti su ograničene. Usmjerene su većinom na ublažavanje postojećih simptoma bolesti i uključuju antagonist NMDA receptora memantin i inhibitore acetilkolinesteraze: donepezil, rivastigmin i galantamin. Međutim, brojnim kliničkim istraživanjima nastoji se pronaći odgovarajuća terapija koja će utjecati na osnovne patolfiziološke procese koji uzrokuju ili dovode do pogoršanja bolesti. Takvom terapijom mogla bi se zaustaviti ili usporiti progresija bolesti.
Američka Agencija za hranu i lijekove je odobrila tri biološka lijeka usmjerena na amiloidnu patologiju - adukanumab, lekanemab i donanemab. Ova tri monoklonska protutijela, iako su izazvala podijeljena mišljenja znanstvene zajednice, neosporivo su prekretnica u liječenju Alzheimerove bolesti.
Osim toga, jedan od pristupa u pronalaženju nove terapije uključuje prenamjenu postojećih lijekova, što može rezultirati značajnim financijskim i vremenskim uštedama.This review summarizes fundamental information on Alzheimer's disease and aims to present currently available symptomatic treatment, disease-modifying therapy, potential targets for new drug development, potential future disease-modifying therapy with an emphasis on phase 3 of clinical trials, and drug repurposing candidates.
Alzheimer's disease is a progressive neurodegenerative disorder affecting millions of people worldwide. As it progresses, it leads to memory loss, cognitive decline, and behavioral changes, resulting in complete dependence of affected individuals on caregivers. Key pathophysiological features include extracellular accumulation of amyloid plaques and intracellular accumulation of tau tangles, accompanied by neuroinflammation, neurodegeneration, and brain atrophy.
Pharmacological treatment options for Alzheimer's disease are limited. They are mainly focused on alleviating existing symptoms and include NMDA receptor antagonist memantine and acetylcholinesterase inhibitors: donepezil, rivastigmine, and galantamine. However, numerous clinical studies aim to find the appropriate therapy that will impact the underlying biological processes that are causing or contributing to the worsening of the disease.
The US FDA has approved three new therapies targeting amyloid pathology: aducanumab, lecanemab and donanemab. Despite divided opinions within the scientific community, these three monoclonal antibodies present undeniably a breakthrough in the treatment of Alzheimer's disease.
There is also one additional approach in seeking new therapies and it involves repurposing existing drugs, which could lead to significant financial and time savings
Važnost dodatnih hematoloških parametara u dijagnozi infekcije COVID-19 i sepse
No full textCilj istraživanja: Suvremeni hematološki analizatori imaju mogućnost precizne
klasifikacije i kvantifikacije stanica koje se javljaju uslijed upalnih stanja, pri čemu se
mjere brojni dodatni hematološki parametri. Cilj istraživanja bio je utvrditi utječe li
imunološki odgovor na koronavirusnu infekciju uzrokovanu SARS-CoV-2 (COVID-19)
i sepsu na dostupne hematološke parametre te mogu li oni imati dodanu vrijednost u
ranoj dijagnostici tih stanja.
Ispitanici i metode: U istraživanje je uključeno 200 bolesnika podijeljenih u tri
skupine; kontrolna skupina, bolesnici s COVID-19 i sepsom. Parametri koji su
predmet ovog istraživanja su broj leukocita, neutrofilnih granulocita (NEUT), limfocita
(LYMPH), monocita (MONO) i nezrelih granulocita (IG), parametri aktivacije neutrofila
(NEUT-RI, NEUT-GI), reaktivni limfociti (RE-LYMP), limfociti koji sintetiziraju antitijela
(AS-LYMP), reaktivni monociti (RE-MONO) te računski omjeri navedenog (NLR, MLR
i IGLR). Ispitano je postoji li statistički značajna razlika u navedenim parametrima
između različitih skupina te su izračunate mjere dijagnostičke točnosti.
Rezultati: Postoji statistički značajna razlika u NEUT %, LYMPH, RE-LYMP, CRP-u
te računskim omjerima između COVID-19 bolesnika i kontrolne skupine (P<0,001) uz
dobru dijagnostičku točnost za navedene parametre (AUC>0,7). U ranoj dijagnostici
bolesnika sa sepsom korisni pokazatelji su NEUT>78,1 %, LYMPH0,6
%, NEUT-RI>52,7 FI, NLR>4,13, IGLR>0,06 i CRP>120 mg/L te postoji statistički
značajna razlika u ovim parametrima između kontrolne skupine i bolesnika sa
sepsom (P<0,001). Pojava RE-MONO pokazuje visoku specifičnost u ovoj skupini
bolesnika.
Zaključak: COVID-19 dovodi do neutrofilije i limfopenije te porasta računskih omjera.
Sepsa dovodi do značajne promjene gotovo svih parametara leukocitnih
subpopulacija uz porast NEUT-RI i pojavu RE-MONO kao ranih dijagnostičkih
pokazatelja aktivacije imunološkog sustava.Objectives: Modern hematology analyzers offer a series of clinical parameters that
provide precise classification and quantification of cells found in inflammatory
conditions. The aim of this study was to determine whether the immune response to
coronavirus infection caused by SARS-CoV-2 virus (COVID-19) and sepsis affects
these hematological parameters and if they have added value in the early diagnosis
of these conditions.
Patients and Methods: Two hundred patients divided into three groups; the control
group, patients with COVID-19 and those with sepsis were included in this study. The
following parameters of interest were evaluated: the number of leukocytes, neutrophil
granulocytes (NEUT), lymphocytes (LYMPH), monocytes (MONO) and immature
granulocytes (IG), parameters of neutrophil activation (NEUT-RI, NEUT-GI), reactive
(RE-LYMP), antibody synthesizing lymphocytes (AS-LYMP), reactive monocytes
(RE-MONO) and calculated ratios (NLR, MLR, IGLR). The difference in the evaluated
parameters between different groups and their diagnostic accuracy has been
assessed.
Results: There is statistically significant difference in NEUT %, LYMPH, RE-LYMP,
CRP and calculated ratios between COVID-19 and control group (P<0.001) with good
diagnostic accuracy for these parameters (AUC>0.7). In early diagnosis of sepsis,
useful indicators are NEUT>78.1 %, LYMPH0.6 %, NEUT-RI>52.7 FI,
NLR>4.13, IGLR>0.06 and CRP>120 mg/L with significant difference in these
parameters between control group and sepsis (P<0.001). The appearance of REMONO
indicates high specificity in this group of patients.
Conclusion: COVID-19 is characterised with neutrophilia, lymphopenia and
increased calculated ratios. Sepsis leads to a significant change of almost all tested
parameters with an increase of NEUT-RI and RE-MONO as early indicators of
immune system activation
Laboratory diagnostics of direct oral anticoagulants
No full textU svijetu je vidljiv trend porasta incidencije tromboembolijskih bolesti, a glavni alat u kontroli ovih
bolesti predstavljaju antikoagulansi. Sa sve većom upotrebom direktnih oralnih antikoagulansa u
liječenju ovih bolesti, javljaju se novi izazovi za kliničke laboratorije. Iako su DOAK-i lijekovi za
koje nije potrebno rutinsko praćenje, postaje jasno da određene situacije ipak zahtijevaju njihovo
određivanje. Ovaj rad donosi pregled recentnih znanstvenih spoznaja o laboratorijskim pretragama
koje se mogu koristiti za određivanje koncentracije DOAK-a te objašnjava utjecaj DOAK-a na
tradicionalne probirne pretrage hemostaze. Jasno je da rutinski testovi poput PV, APTV ili TV nisu
dovoljno osjetljivi za procjenu antikoagulacijskog učinka ili čak detekciju DOAK-a u pacijenata, ali
je važno da su laboratoriji upoznati s utjecajem DOAK-a na ove pretrage. Za određivanje
koncentracije DOAK-a u plazmi mogu se koristiti specifične kromogene i koagulometrijske metode;
za izravne inhibitore trombina diluirano trombinsko vrijeme, ekarinska kromogena metoda,
ekarinski koagulometrijski test i anti-FIIa test, a za izravne inhibitore FXa anti-FXa test.There is a prominent global trend of increasing incidence of thromboembolic diseases, and
the main tool for controlling these conditions is anticoagulant therapy. With the growing use
of direct oral anticoagulants (DOACs) in the treatment of these diseases, new challenges are
emerging for clinical laboratories. Although DOACs do not require routine monitoring, it is
becoming clear that certain situations do require their measurement. This paper provides an
overview of recent scientific findings on laboratory tests that can be used to determine DOAC
concentrations and explains the impact of DOACs on traditional hemostasis screening tests.
It is evident that routine tests such as PT, aPTT, or TT are not sensitive enough to assess the
anticoagulant effect or even detect DOACs in patients, but it is important that laboratories
are aware of the impact of DOACs on these tests. Specific chromogenic and coagulometric
methods can be used to determine DOAC concentrations in plasma; for direct thrombin
inhibitors, diluted thrombin time, ecarin chromogenic method, ecarin clotting test, and antiFIIa test can be used, while for direct factor Xa inhibitors, the anti-FXa test is appropriate