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Examination of the interference of ascorbic acid and glucose in the detection of analytes in urine
No full textAnaliza mokraće jedan je od najčešće korištenih dijagnostičkih postupaka, a osim u dijagnostici koristi se kao uzorak
izbora za probir različitih bolesti te u praćenju tijeka bolesti i uspješnosti terapije.
Interferencije su glavni izvor predanalitičkih pogrešaka u laboratorijskoj medicini. Prisutnost različitih egzogenih ili
endogenih tvari može ometati mjerenje i dovesti do lažno povišenih ili lažno sniženih rezultata kemijske analize zbog čega
je potrebno za svaku pretragu poznavati moguće interferencije kako bi se izbjeglo izdavanje neispravnih nalaza i
usmjeravanje dijagnostike u krivom smjeru.
Askorbinska je kiselina snažan redukcijski i antioksidativni agens te najčešće korišteni vitaminski dodatak prehrani. To je
kemijski aktivna molekula koja se lako apsorbira iz probavnog trakta i brzo raspoređuje u tjelesna tkiva. Budući da vitamin
C pripada skupini vitamina topljivih u vodi, ako se unese u suvišku brzo se nepromijenjen eliminira iz organizma putem
mokraće. Posljedično, mokraća takvih pacijenata sadržava veću koncentraciju ovog vitamina od uobičajene. Zbog svoje
reduktivne sposobnosti askorbinska je kiselina poznati interferirajući spoj u biokemijskim testovima koji uključuju
indikatorske sustave s oksidazama i peroksidazama. Ovi se testovi koriste pri mjerenju glukoze, ukupnog kolesterola,
triglicerida i mokraćne kiseline, a askorbinska kiselina također može interferirati u određivanju bilirubina, fosfata, ureje,
kreatinina i različitih enzima.
S druge strane, šećerna je bolest najbrže rastuća kronična bolest u svijetu. Kod nekontrolirane šećerne bolesti, koncentracija
glukoze u krvi kontinuirano je visoka, što rezultira pojačanim izlučivanjem glukoze putem bubrega. Glukoza je
monosaharid za koji je poznato da može imati utjecaj na različite metode kemijske analize. Najpoznatija je interferencija
glukoze u određivanju kreatinina Jaffeovom metodom, ali interferencija je do sad uočena i prilikom određivanja albumina
i pojedinih elektrolita.
Cilj ovog istraživanja bio je utvrditi utječu li povišene koncentracije askorbinske kiseline i glukoze na laboratorijske
pretrage u mokraći. Istraživanje je provedeno u Kliničkom zavodu za kemiju, KBC Sestre milosrdnice. Za istraživanje je
korišten nasumično odabrani uzorak 24 satne mokraće, a parametri koje smo određivali su ukupni proteini, albumin,
amilaza, natrij, kalij, kloridi, kalcij, anorganski fosfati, magnezij, kreatinin, ureja i mokraćna kiselina. Pripremljeno je 7
uzoraka različite koncentracije dodanog interferenta. Askorbinska je kiselina pripremljena u koncentracijama 0, 0,2, 0,4,
0,5, 1, 2 i 5 g/L, a glukoza u koncentracijama 0, 10, 20, 30, 40, 50 i 60 mmol/L. Sva mjerenja rađena su u duplikatu, za
statističku analizu korišten je program Microsoft Excel.
Rezultati istraživanja nisu pokazali statistički značajno odstupanje prema definiranim kriterijima prihvatljivosti za
određivanje koncentracije albumina, amilaze, natrija, kalija i fosfata. Međutim, askorbinska je kiselina interferirala u
određivanju kloridnih, kalcijevih i magnezijevih iona. S druge strane, povišena koncentracija glukoze interferirala je s
određivanjem proteina, kalcija, magnezija, kreatinina, ureje i mokraćne kiseline.
Na temelju dobivenih rezultata zaključujemo da rezultate analize određenih parametara kod pacijenata koji imaju povišene
koncentracije glukoze i/ili askorbinske kiseline u mokraći treba tumačiti s oprezom.Urine analysis is one of the most used diagnostic procedures, and in addition to being diagnostic tool, it is used as the
sample of choice for screening various diseases, in monitoring the course of the disease and treatment progress.
Interferences are a major source of preanalytical errors in laboratory medicine. The presence of various exogenous or
endogenous substances can interfere with the measurement and lead to falsely elevated or falsely reduced results of
chemical analysis, which is why it is necessary to know possible interferences for each test to avoid issuing incorrect
laboratory reports and directing diagnostics in the wrong direction.
Ascorbic acid is a powerful reducing and antioxidant agent and the most commonly used vitamin food supplement. It is a
chemically active molecule that is easily absorbed from the digestive tract and rapidly distributed to body tissues. Since
vitamin C belongs to the group of water-soluble vitamins, if taken in excess, it is quickly eliminated unchanged from the
body through the urine. Consequently, the urine of such patients contains a higher concentration of this vitamin than usual.
Due to its reductive ability, ascorbic acid is a known interfering compound in biochemical tests that include indicator
systems with oxidases and peroxidases. These tests are used to measure glucose, total cholesterol, triglycerides and urate,
while ascorbic acid can also interfere with the determination of bilirubin, phosphate, urea, creatinine and various enzymes.
On the other hand, diabetes is the fastest growing chronic disease in the world. In poorly controlled diabetes, the
concentration of glucose in the blood is continuously high, which results in increased excretion of glucose through the
kidneys. Glucose is a monosaccharide that is known to affect various methods of chemical analysis. The most well-known
is the interference of glucose in the determination of creatinine by the Jaffe method, but the interference has so far also
been observed in the determination of albumin and certain electrolytes.
The aim of this research was to determine whether elevated concentrations of ascorbic acid and glucose affect laboratory
tests in urine. The research was conducted at the Clinical Institute of Chemistry, KBC Sestre milosrdnice. A randomly
selected 24-hour urine sample was used for the research, and the parameters we determined were total proteins, albumin,
amylase, sodium, potassium, chlorides, calcium, inorganic phosphates, magnesium, creatinine, urea and uric acid. 7
samples of different concentrations of the added interferent were prepared. Ascorbic acid was prepared in concentrations
of 0, 0.2, 0.4, 0.5, 1, 2 and 5 g/L, and glucose in concentrations of 0, 10, 20, 30, 40, 50 and 60 mmol/L. All measurements
were made in duplicate, while the Microsoft Excel program was used for statistical analysis.
The results of the research showed no statistically significant deviation according to the defined acceptance criteria for
determining the concentration of albumin, amylase, sodium, potassium and phosphate. However, ascorbic acid interfered
in the determination of chloride, calcium and magnesium ions. On the other hand, elevated glucose concentration interfered
with the determination of protein, calcium, magnesium, creatinine, urea and uric acid.
Based on the obtained results, we conclude that the results of the analysis of certain parameters in patients with elevated
concentrations of glucose and/or ascorbic acid in the urine should be interpreted with caution
Virulence factors of the bacteria enterococcus faecium from different isolation sources
No full textBakterija Enterococcus faecium je komenzalni organizmi u mikrobioti probavnog sustava čovjeka, ali ih
nalazimo i u okolišu, tlu, vodama, hrani, biljkama i životinjama. Ovi koki smatraju se i oportunističkim
patogenima jer mogu uzorkovati razne infekcije u čovjeka. Cilj ovog rada je ispitati osjetljivost prikupljenih
bakterijskih sojeva E. faecium na antimikrobni lijek vankomicin te ispitati slijedeće virulentne čimbenike;
stvaranje biofilma, β-hemolitičku aktivnost te hidrofobnost stanične površine. Prikupljeno je 90 sojeva
bakterije Enterococcus faecium iz tri različita izvora; klinički uzorci iz bolničke sredine, hrana te otpadne
vode. Iz svakog izvora uzeto je 30 sojeva. Ispitivanjem osjetljivosti sojeva na antibiotik vankomicin utvrđeno
je da je najveći broj rezistentnih sojeva prikupljeno iz bolničke sredine, a ispitivanjem sposobnosti stvaranja
biofilma pokazalo se da su sojevi izolirani iz bolnice i hrane značajno bolji produktori biofilma od sojeva
izoliranih iz otpadnih voda. Također, utvrđeno je da izolati iz hrane imaju najveću hidrofobnost stanične
površine, a ispitivanjem β-hemolitičke aktivnosti 90 sojeva utvrđeno je da su svega šest soja β-hemolitički
aktivna; tri izolata iz hrane, dva iz bolnice te jedan iz otpadnih voda. U ispitivanih sojeva rezistentnih na
vankomicin (VRE) nije uočena korelacija virulentnih čimbenika hidrofobnosti stanične površine i stvaranja
biofilma u uvjetima in vitro. Međutim, ispitivanje je provedeno na malom uzorku sojeva VRE te se ne može
izvući opći zaključak moguće korelacije. Iz dobivenih se podataka može zaključiti da postoji razlika u
virulentnim čimbenicima između izoliranih sojeva bakterije E. faecium, stoga se početna hipoteza pokazala
točnom.The bacterium Enterococcus faecium is a commensal organism in the microbiota of the human digestive
system, but we also find it in the environment, soil, water, food, plants and animals. These cocci are also
considered opportunistic pathogens because they can sample various infections in humans. The aim of this
study is to test the sensitivity of the collected bacterial strains of E. faecium to the antimicrobial drug
vancomycin and to test the following virulence factors; biofilm formation, β-hemolytic activity and
hydrophobicity of the cell surface. 90 strains of Enterococcus faecium bacteria were collected from three
different sources; clinical samples from the hospital environment, food and waste water. 30 strains were taken
from each source. Testing the sensitivity of the strains to the antibiotic vancomycin showed that the largest
number of resistant strains were collected from the hospital environment and testing the ability to form
biofilms showed that strains isolated from hospitals and food are significantly better biofilm producers than
strains isolated from wastewater. Also, it was determined that isolates from food have the highest
hydrophobicity of the cell surface and testing the β-hemolytic activity of 90 strains revealed that only six
strains are β-hemolytically active; three isolates from food, two from the hospital and one from waste water.
From the examined vancomycin-resistant (VRE) strains, no correlation was observed between the virulence
factors of cell surface hydrophobicity and biofilm formation under in vitro conditions. However, the test was
conducted on a small sample of VRE strains and a general conclusion of a possible correlation cannot be
drawn. From the obtained data, it can be concluded that there is a difference in virulence factors between the
isolated strains of E. faecium bacteria, therefore the initial hypothesis proved to be correct
Preparation and charachterization nanosuspension of loteprednol etabonate
No full textU ovom eksperimentalnom diplomskom radu izrađene su nanosuspenzije loteprednol etabonata uz
dodatak površinski aktivne tvari SoluPlusa® metodom vlažnog mljevenja. Vlažno mljevenje je
provedeno u ampulama uz dodatak kuglica itrij stabiliziranog cirkonijevog oksida i magnetskih
mješača na višekanalnom mješaču pri sobnoj temperaturi brzinom od 350 okretaja u minuti.
Ispitivan je i utjecaj vremena vlažnog mljevenja na veličinu čestica nanosuspenzije loteprednol
etabonata kao bitnog procesnog parametra. Karakterizacija nanosuspenzija provedena je metodom
fotonske korelacijske spektroskopije i transmisijskom elektronskom mikroskopijom. Izrađivane su
micele SoluPlusa® u pročišćenoj vodi i u fosfatnom puferu s ciljem ispitivanja utjecaja pH na
veličinu micela. Ishodne mikrosuspenzije loteprednol etabonata prosječne su veličine čestica više
od 3000 nm, dok su nanokristali izrađeni vlažnim mljevenjem prosječne veličine čestica oko 180
nm, a indeks polidisperznosti nanosuspenzija iznosila je u prosjeku oko 0,4. Nanosuspenzijama je
ispitivana stabilnost u vremenskom razdoblju od 7 dana. Izrađene nanosuspenzije su pokazale
nestabilnost kroz taloženje i agregiranje čestica nanokristala te su bile mliječno bijele boje.In this experimental thesis, nanosuspensions of loteprednol etabonate were prepared with the addition
of the surfactant SoluPlus® using the wet milling method. Wet millin was performed in ampoules
with the addition of a ball of yttrium stabilized zirconium oxide and magnetic stirrers on a multichannel mixer at room temperature at a speed of 350 revolutions per minute. The influence of wet
milling time on the particle size of loteprednol etabonate nanosuspension was also examined as an
important process parameter. The characterization of the nanosuspension was carried out by the
method of photon correlation spectroscopy and transmission electron microscopy. SoluPlus®
micelles were made in purified water and in phosphate buffer in order to test the effect of pH on the
micelle size. The resulting loteprednol etabonate microsuspensions have an average particle size of
more than 3000 nm, while the nanocrystals produced by wet milling have an average particle size of
about 180 nm, and the polydispersity index of the nanosuspension was on average about 0.4.
Nanosuspensions were tested for stability over a period of 7 days. The prepared nanosuspensions
showed instability through precipitation and aggregation of nanocrystal particles and were milky
white in color
Breast cancer - new method of treatment
No full textRak dojke je najčešća vrsta raka kod žena u svijetu. Svake godine brojka novih dijagnosticiranih slučajeva raka dojke veća je od 1 700 000, a oko 500 000 oboljelih žena umre od ove zloćudne bolesti. Pojavnost raka dojke se povećava s dobi, iako se tempo porasta usporava nakon menopauze. Ovaj rad opisuje glavne vrste i podtipove raka dojke, njihove simptome kao i metode dijagnostike. Također su opisane i glavne metode liječenja raka dojke: radioterapija, kemoterapija, hormonska terapija, imunoterapija i kirurško liječenje. U glavnom dijelu su posrednije opisane imunoterapijske metode, a spominju se i određena istraživanja staničnih puteva koji bi mogli biti ključni u budućoj terapiji raka dojke.Breast cancer is the most common female type of cancer in the world. Every year the number of newly – diagnosed cases is more than 1 700 000 and about 500 000 of them ends with a deadly outcome. Rate of breast cancer increases with age, alhtough the increase rate slows down after menopause. This paper describes main types and subtypes of breast cancer, as well as its symptoms and dignostic methods. Main treatment methods, such as radiotherapy, chemotherapy, hormonal therapy, immunotherapy and surgical treatment are also described. The main part of the paper contains immunotherapy methods and there is also a mention of researches of certain cellular pathways that could be crucial for the breast cancer therapy in the future
Liposomal antibiotics
No full textAntimikrobna rezistencija je tijekom zadnja dva desetljeća postala jedan od glavnih problema u učinkovitoj antimikrobnoj terapiji. Znanstvenici predlažu dva smjera u borbi protiv rezistencije: razvoj novih antibiotika ili unaprjeđenje postojećih uklapanjem u različite lipidne i polimerne nanosustave te hibridne sustave s antimikrobnim peptidima.
Uklapanjem antibiotika u liposome poboljšavaju se njegova farmakokinetička svojstva i bioraspoloživost, smanjuje toksičnost, te u većini slučajeva povećava antimikrobna aktivnost. Osim toga, liposomi služe kao zaštita antibiotika od neželjenih učinaka metabolizma, a pritom štite i pacijenta koji uzima lijek od neželjenih nuspojava antibiotika. Liposomski antibiotici mogu biti dizajnirani da ciljaju intracelularne infekcije gdje važnu ulogu imaju konvencionalni liposomi koji bivaju fagocitirani i transportirani do inficiranih stanica. PEG-iliranjem površine liposoma produljuje se vrijeme polueliminacije što doprinosi održavanju konstantne razine antibiotika u serumu. Liposomi koji na svojoj površini imaju imunoglobuline, proteine ili saharide usmjereni su prema specifičnim ciljevima kao što su određena tkiva, patogeni ili bakterijski biofilm.
Brojna istraživanja u ovom području rezultirala su kliničkim ispitivanjima liposomskih antibiotika, a neki od njih su i registrirani, što je sistematizirano prikazano ovim radom.Antimicrobial resistance has become one of the major problem for effective antimicrobial therapy, and the list of antibiotic-resistant bacteria is increasing over the last two decades. To overcome this problem, scientists suggest two options: the development of new antibiotics or the improvement of already existing antibiotics by their incorporation in nanocarriers and synthesis of antimicrobial peptides. Among the various nanosystems investigated, liposomes have the longest clinical use.
Incorporation of antibiotics into liposomes results in: improved pharmacokinetics and bioavailability of the liposomally-incorporated antibiotic, reduced toxicity, increased activity against intracellular and extracellular pathogens and modified drug release. Liposomes serve as a way of protecting antibiotics against early metabolic degradation, as well as protecting patients against drug side effects. Liposomal antibiotics can be ingested by macrophages and transported to the infected cells. By modifying the liposomal surface by polyetileneglycol derivatives, the circulation time increases, thus mantaining adequate levels of the antibiotic in serum. Moreover, to achieve targeted delivery to pathogens and biofilm, the liposomal surface can be modified with immunoglobulins, proteins or saccharides.
This paper provides an overview of selected, the most perspective, liposomal antibiotics aimed for parenteral, pulmonary and dermal delivery, which are currently in preclinical and clinical studies
Study of noncovalent interactions between mycotoxin sterigmatocystin, human serum albumin and cyclodextrin Bridion by isothermal titration calorimetry
No full textSterigmatocistin (STC) je kancerogeni mikotoksin (IARC 2B) čiji su najznačajniji proizvođači plijesni roda
Aspergillus iz serije Versicolores koje su široko rasprostranjene u okolišu. Sugammadex je gama tip
ciklodekstrina koji se primjenjuje za reverziju rokuronijem izazvane anestezije. S obzirom na strukturno
konformacijsku podudarnost molekula STC i rokuronija, ovim radom se htjela provjeriti mogućnost
korištenja Sugammadexa kod intoksikacije sa STC. U tu svrhu korištena je metoda izotermalne titracijske
kalorimetrije (ITC). Iz dobivenih termodinamičkih parametara proizlazi da između STC i HSA prevladavaju
hidrofobne interakcije i vodikove veze. Ispitivanje je također pokazalo da se uklapanje STC toksina u
hidrofobnu unutrašnjost Sugammadexa temelji na hidrofobnim interakcijama te konstanta disocijacije od
3,49×10-6 dokazuje veći afinitet nego prema HSA. Proveden je i kompetitivni eksperiment kojim je potvrđena
mogućnost Sugammadexa da istisne STC iz kompleksa s HSA zahvaljujući većem afinitetu vezanja STC za
Sugammadex. Usporedbom s literaturnim podacima dobivenim istom metodom za rokuronij i Sugammadex,
afinitet vezanja rokuronija za Sugammadex (KD=1,79×10-7 M) usporediv je sa afinitetom STC i
Sugammadexa. Na temelju ovih rezultata, može se zaključiti da postoji mogućnost primjene Sugammadexa
kao antidota kod intoksikacije mikotoksinom STC, a klinički značaj potrebno je dalje istražiti na
odgovarajućim staničnim i/ili in vivo modelima.Sterigmatocystin (STC) is a carcinogenic mycotoxin (IARC 2B) produced mainly by molds from the series
Versicolores of the genus Aspergillus, which are widely distributed in the environment. Sugammadex is a
gamma-cyclodextrin derivative used for the reversal of rocuronium-induced anesthesia. Considering the
structural-conformational similarity between the molecules of STC and rocuronium, this study aimed to
investigate the possibility of using Sugammadex in STC intoxication. The isothermal titration calorimetry
(ITC) method was employed for this purpose. The obtained thermodynamic parameters indicate that
hydrophobic interactions and hydrogen bonds prevail between STC and HSA. The study also demonstrated
that the incorporation of the mycotoxin STC into the hydrophobic cavity of Sugammadex is based on
hydrophobic interactions, while the corresponding dissociation constant of 3.49×10-6 M suggests a higher
affinity compared to HSA. A competitive experiment was conducted, confirming the ability of Sugammadex
to displace STC from the complex with HSA due to a higher binding affinity of STC for Sugammadex.
Comparison with literature data obtained using the same method for rocuronium and Sugammadex showed
that the binding affinity of of rocuronium for Sugammadex (KD=1.79×10-7 M) is comparable to the affinity
of STC and Sugammadex. Based on these results, it can be concluded that Sugammadex has the potential to
be used as an antidote in STC mycotoxin intoxication, but further investigation conducted on appropriate
cellular and/or in vivo models is needed to elucidate the clinical significance of these results
Ethnobotanical use of Sideritis species
No full textRod Sideritis sastoji se od više od 150 zeljastih ili grmastih jednogodišnjica ili trajnica
rasprostranjenih u području Zapadnog Palearktika. Ime je dobio po tome što su se u prošlosti vrste
ovoga roda koristile za liječenje rana uzrokovanih željeznim oružjem, a danas se u narodu koriste
kao lijek protiv mnogih bolesti i stanja na gotovo cijelom području rasprostranjenosti. Cilj ovog
diplomskog rada je prikazati rezultate posljednjih etnobotaničkih istraživanja o tradicionalnoj
upotrebi vrsta roda Sideritis i razmotriti farmakološku pozadinu najčešće zabilježenih bioloških
djelovanja. Najveći broj radova navodi upotrebu navedenih vrsta protiv gripe i/ili prehlade,
respiratornih smetnji te gastrointestinalnih smetnji. Od značajnijih upotreba spominju se još smetnje
živčanog sustava, urinarne smetnje, rane, ulkusi, hemoroidi, afte te dijabetes. Koriste se nadzemni
biljni dijelovi većinom za pripremu infuza. Primjena na ovaj način pripremljenih pripravaka kod
kašlja povezanog s prehladom i kod blagih gastrointestinalnih smetnji odobrena je od strane
Europske agencije za lijekove. Prema broju različitih načina primjene i radova koji ih spominju
najviše su se istaknule sljedeće vrste: S. libanotica, S. perfoliata, S. scardica, S. montana, S. raeseri,
S. trojana, S. syriaca i S. arguta. Uz dokazana biološka djelovanja i potvrđene tradicionalne
primjene važno je naglasiti potrebu za daljnjim istraživanjima kako bi se iskoristio puni terapeutski
potencijal ovih vrsta.The genus Sideritis comprises over 150 herbs and small shrubs, annuals and perennials distributed
in the Western Palearctic zone. Its name isrelated to the use ofthe herbs in the past for curing wounds
caused by iron arms and today they are used by the people as medicines against many diseases and
conditions in almost the entire distribution area. The aim of this diploma thesis is to review the latest
ethnobotanical research on the traditional use of species from the genus Sideritis and to discuss the
pharmacological background of the most frequently recorded biological actions. The greatest
number of papers stated the use of the mentioned species against flu and/or cold, respiratory
disorders and gastrointestinal disorders. Other important uses include disorders of the nervous
system, urinary disorders, wounds, ulcers, hemorrhoids, canker sores, and diabetes. Aerial plant
parts are mostly used for the preparation of infusions. The use of such preparations for cough
associated with cold and for mild gastrointestinal discomfort has been approved by the European
Medicines Agency. According to the number of different applications and the number of papers that
mention them, the following species were the most prominent: S. libanotica, S. perfoliata,
S. scardica, S. montana, S. raeseri, S. trojana, S. syriaca, and S. arguta. Besides proven biological
effects and verified traditional uses, it isimportant to emphasize the need for further research in order
to use the full therapeutic potential of these species
The role of CYP2J2 gene polymorphisms in clinical medicine
No full textEnzimi citokrom P450 (CYP) imaju ključnu ulogu u stvaranju epoksieikozatrienoičnih kiselina (EET), metabolita
arahidonske kiseline koji ostvaruju različite zaštitne i protuupalne učinke, prvenstveno na kardiovaskularni sustav. One potiču
vaskularnu relaksaciju, angiogenezu i fibrinolizu, djeluju protuupalno te moduliraju aktivnost ionskih kanala. CYP2J2 je glavni
enzim odgovoran za epoksidaciju arahidonske kiseline u EET u srcu i koronarnim arterijama. Polimorfizam CYP2J2 *7 u
promotorskoj regiji gena smanjuje njegovu ekspresiju za 48 % što rezultira smanjenom koncentracijom EET, disregulacijom
proupalnih i profibrotičkih čimbenika te promijenjenom aktivnosti ionskih kanala. Kako su upravo ti mehanizmi uključeni u
nastanak fibrilacije atrija, hipoteza ove studije jest kako postoji povezanost polimorfizma CYP2J2 *7 i fibrilacije atrija. Budući
da CYP2J2 nije eksprimiran u venama te ne doprinosi patogenezi venske tromboze, genotipizirano je 179 ispitanika s
fibrilacijom atrija te 102 ispitanika s trombozom. Učestalost alela CYP2J2 *7 u ispitivanoj populaciji bila je 5,51 %. Zbog istih
čimbenika rizika za obje bolesti, nije bilo značajne razlike u učestalosti dislipidemije, hipertenzije i šećerne bolesti, ali su se
ispitanici razlikovali s obzirom na dob i spol. Regresijsko analizom utvrđeno je kako prisutnost barem jednog varijantnog alela
*7 povećava omjer vjerojatnosti za razvoj fibrilacije atrija. Analizirajući podatke prema spolu, nije utvrđena razlika u
učestalosti genotipova kod muškaraca dok je kod žena razlika bila statistički značajna (p = 0,047). Pripadajući omjer
vjerojatnosti za razvoj fibrilacije atrija kod žena iznosio je 4,010 (95 % CI: 1,127 – 19,041). Sveukupno, rezultati ovog
istraživanja upućuju kako polimorfizam CYP2J2 *7 može pridonijeti povećanom riziku za razvoj fibrilacije atrija u hrvatskoj
populaciji, osobito u žena.Cytochrome P450 (CYP) enzymes play a crucial role in the formation of epoxyeicosatrienoic acids (EETs),
metabolites of arachidonic acid which have various protective and anti-inflammatory effects, particularly on the cardiovascular
system. CYP2J2 is the key enzyme responsible for epoxidation of arachidonic acid into EETs in the heart and coronary arteries.
The presence of the CYP2J2 *7 polymorphism in the gene's promoter region reduces its expression by 48% which,
consequently, leads to decreased EET concentrations, dysregulation of proinflammatory and profibrotic factors, and altered ion
channel activity. As these mechanisms are involved in the development of atrial fibrillation, the hypothesis of this study is that
there is an association between CYP2J2 *7 polymorphism and atrial fibrillation. Since CYP2J2 is not expressed in veins and
has no significant contribution to the pathogenesis of venous thrombosis, 179 subjects with atrial fibrillation and 102 subjects
with thrombosis were genotyped. In the studied population the frequency of the CYP2J2 *7 allele was 5.51%. Due to similar
risk factors for both diseases, no significant differences between groups were observed in the frequency of dyslipidemia,
hypertension, and diabetes. However, differences in age and gender were found. Regression analysis revealed that the
occurrence of at least one variant allele *7 increased the odds ratio of atrial fibrillation. The difference in genotype frequency
was not determined in men, but a statistically significant difference (p = 0.047) was observed in women. The corresponding
odds ratio of atrial fibrillation for women was 4.010 (95 % CI: 1.127 – 19.041). Overall, the results imply that the CYP2J2 *7
polymorphism may contribute to an increased risk of atrial fibrillation in the Croatian population, especially in women
Criteria for conducting second-tier tests in newborn screening for homocystinuria and vitamin B12 deficiency
No full textRijetke bolesti imaju nisku prevalenciju u populaciji, javljaju se u manje od pet pojedinaca na 10 000 osoba i većinom
se kasno dijagnosticiraju. Nasljedne metaboličke bolesti su rijetke bolesti koje nastaju kao posljedica smanjene
aktivnosti enzima, prijenosnika ili kofaktora. NBS je postupak kojim se organizirano i sustavno otkrivaju urođene
bolesti u novorođenačkoj populaciji sa svrhom njihovog pravovremenog prepoznavanja. NBS je u RH započeo 1978.,
a danas se izvodi probira na devet nasljednih metaboličkih bolesti. Testovi probira nisu dijagnostički testovi, oni
upućuju na novorođenčad koja bi mogla imati određeni metabolički poremećaj i isključuju one koji te poremećaje
vjerojatno nemaju. Laboratoriji koji provode NBS na klasičnu homocistinuriju i manjak vitamina B12 koriste različite
postupnike. Provođenje proširenog NBS-a metodom LC-MS/MS iz uzorka DBS-a podrazumijeva analizu
aminokiselina i acilkarnitina, kao primarnih biljega, derivatiziranim ili nederivatiziranim metodama. Zbog velikog
broja lažno pozitivnih rezultata nakon analize primarnih biljega C3, C2, Met i Phe na homocistinuriju i manjak
vitamina B12, neophodno je u postupnik uvrstiti i specifičnije drugostupanjske testove (tHcy, MMA). Cilj ovog rada
je priprema proširenja novorođenačkog probira u RH na navedene bolesti. U tu je svrhu napravljena usporedba
šestomjesečnih rezultata mjerenja analita od interesa (C3, C2, Met i Phe) i njihovih međusobnih omjera u NBS-u RH s
vrijednostima istih analita koji se koriste u postupnicima novorođenačkih programa Austrije, Italije, Njemačke i
Španjolske. Procijenjeno je da bi primjenom kriterija iz postupnika navedenih zemalja na rezultate NBS RH, za
šestomjesečno razdoblje, broj uzoraka za mjerenje Hcy u drugostupanjskom testu bio prihvatljiv za provođenje NBS-a
na homocistinuriju i manjak vitamina B12 u RH.Rare diseases have a low prevalence in the population, they occur in less than five individuals per 10 000 people and
are mostly diagnosed late. Inherited metabolic diseases are rare diseases that occur as a result of reduced activity of
enzymes, transporters or cofactors. NBS is a procedure for the organized and systematic detection of congenital
diseases in the newborn population with the purpose of their timely recognition. In the Republic of Croatia NBS
started in 1978, and today screening is performed for nine inherited metabolic diseases. Screening tests are not
diagnostic tests, they indicate newborns who may have a certain metabolic disorder and exclude those who probably
do not have these disorders. Laboratories that perform NBS for classic homocystinuria and vitamin B12 deficiency
use different procedures. Carrying out an extended NBS using the LC-MS/MS method from a DBS sample implies the
analysis of amino acids and acylcarnitine, as primary markers, by derivatized or non-derivatized methods. Due to the
large number of false positive results after the analysis of the primary markers C3, C2, Met and Phe for
homocystinuria and vitamin B12 deficiency, it is necessary to include more specific second-tier tests (tHcy, MMA) in
the procedure. The aim of this paper is to prepare the extension of newborn screening in Croatia for the mentioned
diseases. For this purpose, a comparison was made of the six-month results of measuring the analytes of interest (C3,
C2, Met and Phe) and their mutual ratios in the NBS of the Croatia with the values of the same analytes used in the
procedures of the newborn programs of Austria, Italy, Germany and Spain. It was estimated that by applying the
criteria from the procedures of the mentioned countries to the results of the NBS of the Republic of Croatia, for a
six-month period, the number of samples for measuring Hcy in the second-tier test would be acceptable for conducting
the NBS for homocystinuria and vitamin B12 deficiency in Croatia
Učestalost i osobitosti ljekarničkih intervencija: presječna studija
No full textCilj istraživanja: Cilj ovog rada je definirati osobitosti i učestalost intervencija ljekarničke
skrbi koje pružaju ljekarnici u svojoj rutinskoj praksi u javnim ljekarnama na području
Republike Hrvatske.
Ispitanici i metode: Provedeno je opservacijsko, presječno istraživanje u kojem je dobrovoljno
sudjelovao 71 ljekarnik. Podaci su anonimno prikupljani putem on-line obrasca, osmišljenog
za potrebe ovog istraživanja. Korišteni obrazac sastojao se od dva upitnika; prvi upitnik se
odnosi na općenite podatke o ljekarniku i ljekarni u kojoj radi, a drugi je prikupljao podatke o
ljekarničkim intervencijama, temeljeno na PCNE V9.1 (engl. Pharmaceutical Care Network
Europe) klasifikaciji terapijskih problema. Sudionici su tijekom proizvoljno odabrana
uzastopna tri dana bilježili sve provedene intervencije putem on-line obrasca, a oni koji nisu
imali niti jednu intervenciju bili su zamoljeni da taj odgovor označe u upitniku po isteku tri
dana. Dobiveni podaci su statistički obrađeni.
Rezultati: Ukupno je 71 ljekarnik prijavio 152 provedene intervencije. Prosječni broj
provedenih intervencija u periodu od tri dana iznosio je 2,14 (1,70), a kretao se od 0 do 7.
Većina sudionika (53,5%) imala je 1 do 2 intervencije s medijanom procijenjenog trajanja
intervencije od 6 min. Istraživanjem nije utvrđena statistički značajna povezanost između
obilježja ljekarnika i ljekarni u kojima ljekarnici rade s brojem provedenih intervencija.
Pokazalo se da su intervencije za koje je bila potrebna suradnja s liječnikom trajale duže i bile
uspješnije u potpunom rješavanju terapijskog problema (83,3%) od onih za koje nije bila
potrebna suradnja s liječnikom (52,2%). Intervencije koje su ljekarnici predložili u ovom
istraživanju su u 64,5% slučajeva doprinijele potpunom rješenju terapijskog problema, bile su
u velikoj mjeri prihvaćene (90,8%) i sve osim jedne su ocijenjene kao valjane.
Zaključak: Istraživanje je pokazalo da ljekarnici svakodnevno provode intervencije koje
doprinose rješavanju i prevenciji terapijskih problema te na taj način osiguravaju sigurnu i
učinkovitu farmakoterapiju. Važna je uključenost liječnika u proces rješavanja terapijskog
problema kako bi terapijski problem bio uspješno riješen, stoga postoji potreba za
osiguravanjem učinkovitog kanala komunikacije na relaciji ljekarnik – liječnik. Veliki udio
prihvaćenih ljekarničkih intervencija i njihova procijenjena valjanost govore da ljekarnici
sudionici istraživanja posjeduju potrebne stručne kompetencije za uspješno provođenje
intervencija u svrhu rješavanja i prevencije terapijskih problema i provođenja ljekarničke skrbi.Objectives: This study aimed to explore the prevalence and nature of pharmacists’
interventions conducted in the routine practice in community pharmacies setting in Croatia,
related to the use of medications.
Subjects and methods: The study was conducted as observational, cross-sectional study with
71 volunteer participants. The data was anonymously collected via online survey developed
for the purpose of this research. The survey consisted of two questionnaires, one referring to
general information of pharmacist and community pharmacy he/she is employed in, and the
other questionnaire based of PCNE V9.1 (Pharmaceutical Care Network Europe) classification
of drug-related problems. Participants were documenting all recognized drug related problems
and conducted interventions via online survey during a period of three consecutive days.
Participants who did not have any intervention during the three-day period were asked to report
that in the survey. All collected data was statistically analyzed.
Results: There were in total 152 conducted interventions by 71 pharmacists. Average number
of conducted interventions during a three-day period was 2,14 (1,70), ranging from 0 to 7.
Most participants (53,5%) had 1 or 2 interventions with median of duration of intervention
being 6 minutes. This research did not find statistically significant relationship between
characteristics of pharmacist or community pharmacies and number of conducted
interventions. There are indications that interventions conducted on a prescriber/physician
level were potentially more time-consuming and had higher rates of completely solved drugrelated problems (83,3%), compared to interventions which didn't include intervening on
prescriber/physician level (52,2%). Interventions suggested by participants during this research
had a rate of 64,5% completely solved drug-related problems, 90,8% of interventions were
accepted and all but one were rated as valid.
Conclusion: This research showed that community pharmacists intervene on an every-day
basis. That way they contribute to solving and prevention of drug-related problems, ensuring
safe and efficient drug therapy. In order to successfully solve drug-related problems, it’s
important to include prescriber/physician in solving of drug-related problems, showing a
recognized need to ensure efficient way of communication between pharmacists and
physicians. High percentage of valid and accepted interventions imply that study participants
have necessary skills to successfully conduct interventions in order to solve and prevent drugrelated problems and to provide pharmaceutical care