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Nutritivne intervencije u atopijskom dermatitisu
Cilj istraživanja: Cilj ovog rada je istražiti opravdanost i učinkovitost nutritivne intervencije
(promjene obrazaca prehrane i/ili primjene dodataka prehrani) u prevenciji i
terapiji atopijskog dermatitisa u djece (suplementacije majke u perinatalnom periodu i
tijekom dojenja te nutritivne intervencije u djeteta tijekom najranijeg djetinjstva) i odraslih.
Materijal i metode: Prilikom izrade ovog rada pretraživane su baze podataka:
PubMed/MEDLINE, Elsevier, Scopus, ResearchGate i pretraživač Google Scholar. Tijekom
pretraživanja korištene su ključne riječi „supplement”, „nutrition”, „atopic dermatitis”,
„pregnancy”, „children”, „infants”, „vitamin D”, „fish oil” te „probiotics”. U istraživanje su
uključene metaanalize, smjernice, kliničke studije i pregledni znanstveni radovi objavljeni u
periodu 2011.-2021, s posebnim naglaskom na klinička ispitivanja. U nedostatku novijih
relevantnih studija iznimno su u obzir uzeta i starija istraživanja.
Rezultati: Mogućnosti nutritivne intervencije u atopijskom dermatitisu intenzivno se
istražuju, a uključuju primjenu eliminacijskih dijeta te suplementaciju (mikro)nutrijentima i
probioticima. U prevenciji i terapiji atopijskog dermatitisa najviše se primjenjuju vitamin D,
ω-3 masne kiseline i probiotici te u manjoj mjeri vitamin E, cink i selen. Eliminacijske dijete
opravdane su samo u slučaju utvrđene alergije.
Zaključak: Usprkos brojnim dokazima o učinkovitosti nutritivnih intervencija u prevenciji i
ublažavanju simptoma atopijskog dermatitisa rezultati do sada provedenih kliničkih studija su
nekonzistentni što rezultira niskim razinama dokaza o učinkovitosti i nepostojanjem službenih
smjernica za primjenu. Potrebna su daljnja istraživanja kako bi se optimizirale terapijske
smjernice i dodatno istražila sigurnost primjene dodataka prehrani u prevenciji i liječenju
atopijskog dermatitisa.Objectives: The aim of this paper is to investigate the justification and effectiveness of
nutritional intervention (changes in eating patterns and/or the use of dietary supplements) in
the prevention and therapy of atopic dermatitis in children (supplementation of the mother in
the perinatal period and during breastfeeding, and nutritional intervention in the child during
early childhood) and adults.
Material and methods: During the preparation of this paper, following databases were
searched: PubMed/MEDLINE, Elsevier, Scopus, ResearchGate and the Google Scholar
search engine was also used. During the search, the keywords "supplement", "nutrition",
"atopic dermatitis", "pregnancy", "children", "infants", "vitamin D", "fish oil" and
"probiotics" were used. The research includes meta-analyses, guidelines, clinical studies and
review scientific papers published in the period 2011-2021, with a special emphasis on
clinical trials. In the absence of recent relevant studies, older researches were also taken into
account.
Results: The possibilities of nutritional intervention in atopic dermatitis are intensively
researched, and include the use of elimination diets and supplementation with
(micro)nutrients and probiotics. Vitamin D, ω-3 fatty acids and probiotics are mostly used in
the prevention and treatment of atopic dermatitis, and to a lesser extent vitamin E, zinc and
selenium. Elimination diets are justified only in case of established allergy.
Conclusion: Despite numerous evidences on the effectiveness of nutritional interventions in
the prevention and alleviation of symptoms of atopic dermatitis, the results of clinical studies
conducted so far are inconsistent, resulting in low levels of evidence of effectiveness and the
absence of official guidelines for use. Further research is needed to optimize therapeutic
guidelines and further investigate the safety of dietary supplements in the prevention and
treatment of atopic dermatitis
Procjena zadovoljstva bolesnika načinom liječenja šećerne bolesti tipa 2
Cilj istraživanja: Primaran cilj ovog istraživanja je utvrditi zadovoljstvo bolesnika s
farmakoterapijom koju koriste za liječenje šećerne bolesti tipa 2 i utvrditi antidijabetike koji
su pridonijeli većem zadovoljstvu bolesnika s liječenjem šećerne bolesti tipa 2 prema
rezultatima DTSQ-a. Sekundarni cilj istraživanja je utvrditi kako i ostali parametri (sociodemografski, klinički, antropometrijski i adherencijski) utječu na zadovoljstvo bolesnika s
liječenjem šećerne bolesti tipa 2.
Ispitanici i metode: Ovo presječno istraživanje provelo se na razini primarne zdravstvene
zaštite u Gradskoj ljekarni Zagreb, Šestinska cesta 1, Zagreb u trajanju od prosinca 2022. do
veljače 2023. godine. U istraživanju je bilo uključeno 50 ispitanika. Uključujući kriteriji za
sudjelovanje u istraživanju su bili životna dob od 18 i više godina, dijagnosticirana šećerna
bolest (dijabetes) tipa 2 unazad najmanje 3 mjeseca i potpisani informirani pristanak.
U svrhu prikupljanja podataka, koristio se obrazac koji se sastoji od 2 dijela. Prvi dio obrasca
je kreiran za potrebe rada i u njega se bilježe: socio-demografske karakteristike pacijenata
(dob, spol, razina obrazovanja, radni i bračni status, životne navike), antropometrijske mjere
(visina, tjelesna masa, indeks tjelesne mase), kliničke karakteristike pacijenata (vrijednost
glukoze u krvi natašte, HbA1c, komplikacije dijabetesa, komorbiditeti, trajanje dijabetesa i
terapija za liječenje dijabetesa) i adherencija u uzimanju lijekova. Drugi dio obrasca za
prikupljane podataka je DTSQ koji mjeri zadovoljstvo pacijenata s liječenjem šećerne bolesti.
Deskriptivnom statistikom analiziralo se postojanje povezanosti između zadovoljstva s
liječenjem šećerne bolesti tipa 2 utvrđenog DTSQ-om i socio-demografskih i kliničkih
osobina pacijenata te adherencije utvrđenih u prvom dijelu obrasca. Podaci su analizirani
statističkim programom TIBCO Statistica v.13 (TIBCO Software Inc., Kalifornija, SAD).
Rezultati: Prosječna vrijednost rezultata DTSQ-a je bila 31,16 ± 4,36. S obzirom na veličinu
uzorka i vrstu farmakoterapije, pacijenti su podijeljeni u 4 skupine: prva skupina je koristila
samo oralne antidijabetike, druga skupina je uz oralne antidijabetike koristila i inzuline, treća
skupina je uz oralne antidijabetike koristila i GLP-1 agoniste (supkutana primjena), dok je
četvrta skupina uz oralne antidijabetike koristila inzuline i GLP-1 agoniste (supkutana
primjena). Rezultati po skupinama su bili redom: 1. skupina (31,06 ± 4,64), 2. skupina (30,80
± 4,76), 3. skupina (32,10 ± 3,07), 4. skupina (29,00 ± 7,07). Nije utvrđena statistička
značajnost između ovih skupina što se tiče utjecaja na DTSQ rezultat (ANOVA test ; F=0,32 ;
P=0,810). Od ostalih parametara koji su se ispitivali statistička značajnost je jedino
ustanovljena za duljinu trajanja dijabetesa (ANOVA test ; F=4,21 ; P=0,021), vrijednost
glikiranog hemoglobina (T-test ; t=3,61 ; P<0,001) i percipiranu hipoglikemiju (Pearsonov
koeficijent korelacije ; r= -0,31 ; P=0,026).
Zakljuĉak: Putem DTSQ upitnika nije ustanovljeno da određene vrste farmakoterapije
statistički značajno rezultiraju povećanim zadovoljstvom pacijenata s obzirom na druge.
Ovakvi rezultati idu u prilog individualiziranom liječenju šećerne bolesti tipa 2, a od
parametara za koje je ustanovljena statistička značajnost svakako bi pri odabiru
farmakoterapije trebalo pripaziti na mogućnost izazivanja hipoglikemije koja je kod naših
pacijenata statistički značajno narušavala zadovoljstvo liječenjem. Vrijednost glikiranog
hemoglobina osim pokazatelja kontrole glikemije, može poslužiti kao i parametar koji
sugerira zadovoljstvo farmakoterapijom. S obzirom na duljinu trajanja dijabetesa, trebalo bi se
više posvetiti pacijentima u eventualnoj modifikaciji farmakoterapije ili liječenju popratnih
komorbiditeta kako se s vremenom ne bi narušavalo zadovoljstvo liječenjem.Objectives: The primary goal of this research is to determine patient satisfaction with
pharmacotherapy used for the treatment of type 2 diabetes and to determine the antidiabetic
drugs that contributed to greater patient satisfaction with type 2 diabetes treatment according
to the results of the DTSQ. The secondary goal of the research is to determine how other
parameters (socio-demographic, clinical, anthropometric and adherence) affect the
satisfaction of patients with type 2 diabetes treatment.
Patients and methods: This cross-sectional study was conducted at the level of primary
health care in the Gradska ljekarna Zagreb, Šestinska cesta 1, Zagreb from December 2022 to
February 2023. 50 patients were included in the study. Inclusion criteria for participation in
the study were age of 18 years and older, type 2 diabetes diagnosed at least 3 months ago and
signed informed consent.
For the purpose of data collection, a form consisting of 2 parts was used. The first part of the
form was created for the needs of the work and it records: socio-demographic characteristics
of patients (age, gender, level of education, work and marital status, lifestyle habits),
anthropometric measurements (height, body mass, body mass index), clinical characteristics
of patients (fasting blood glucose value, HbA1c, complications of diabetes, comorbidities,
duration of diabetes and therapy for the treatment of diabetes) and adherence to medication.
The second part of the data collection form is the DTSQ, which measures patient satisfaction
with diabetes treatment.
Descriptive statistics were used to analyze the existence of a connection between satisfaction
with the treatment of type 2 diabetes as determined by the DTSQ and socio-demographic and
clinical characteristics of patients and adherence determined in the first part of the data
collection form. The data were analyzed with the statistical program TIBCO Statistica v.13
(TIBCO Software Inc., California, USA).
Results: The average value of the DTSQ score was 31,16 ± 4,36. Considering the size of the
sample and the type of pharmacotherapy, the patients were divided into 4 groups: the first
group used only oral antidiabetics, the second group used oral antidiabetics as well as insulin,
the third group used oral antidiabetics and GLP-1 agonists (subcutaneous administration),
while the fourth group, in addition to oral antidiabetics, used insulin and GLP-1 agonists
(subcutaneous administration). The results by group were: Group 1 (31,06 ± 4,64), Group 2
(30,80 ± 4,76), Group 3 (32,10 ± 3,07), Group 4 (29,00 ± 7,07). No statistical significance
was determined between these groups regarding the influence on the DTSQ score (ANOVA
test ; F=0,32 ; P=0,810). Of the other parameters that were examined, statistical significance
was only established for the duration of diabetes (ANOVA test ; F=4,21 ; P=0,021), glycated
hemoglobin value (T-test ; t=3,61 ; P<0,001) and perceived hypoglycemia (Pearson's
correlation coefficient ; r=-0,31 ; P=0,026).
Conclusion: Through the DTSQ questionnaire, it was not established that certain types of
pharmacotherapy statistically significantly result in increased patient satisfaction compared to
others. These results are in favor of individualized treatment of type 2 diabetes, and of the
parameters for which statistical significance was established, when choosing
pharmacotherapy, the caution is required due possibility of inducing hypoglycemia, which in
our patients statistically significantly impaired satisfaction with treatment. The glycated
hemoglobin value, in addition to being an indicator of glycemic control, can also serve as a
parameter that suggests satisfaction with pharmacotherapy. Considering the duration of
diabetes, more attention should be paid to patients in the eventual modification of
pharmacotherapy or the treatment of accompanying comorbidities so that the satisfaction with
treatment is not impaired over time
Determination of phenolic content and DPPH radical scavenging activity of functional fruit juices fortified with Thymus serpyllum L. and Salvia officinalis L. extracts
The objective of this study was to spectrophotometric determinate the total phenolic, flavonoid, hydroxycinnamic acid, and flavonol content of orange, pineapple, and apple juices fortified with wild thyme (Thymus serpyllum L.), Dalmatian sage (Salvia officinalis L.), and wild thyme-Dalmatian sage (3 : 1, v / v) extracts, and to evaluate their DPPH radical scavenging activity as a contribution to the development of a new functional beverage. The plant extracts addition increased the amount of phenolic compounds in fruit juices and improved their antioxidant properties. The highest concentrations of bioactive compounds and the greatest DPPH radical activity were obtained by adding Dalmatian sage extract to orange juice. Our study provides the novelty of fortifying fruit juices with wild thyme and Dalmatian sage extracts and offers significant potential for the creation of functional beverages
Učinkovitost mjera minimizacije rizika u sprečavanju medikacijskih pogrešaka primjenom salbutamola u pedijatrijskoj populaciji
Cilj istraživanja
Cilj ovog istraživanja je prikazati i analizirati prijave slučajeva medikacijskih pogrešaka s djelatnom tvari salbutamol u farmaceutskom obliku otopine za atomizator u pedijatrijskoj populaciji te ispitati jesu li mjere minimizacije rizika koje je HALMED dosada proveo u svrhu njihovog sprječavanja bile učinkovite.
Materijal i metode
Pretražena je baza nuspojava Republike Hrvatske za razdoblje od 01. siječnja 2016. godine do 31. prosinca 2022. godine. Slučajevi medikacijskih pogrešaka analizirani su prema dobi bolesnika, spolu bolesnika, zabilježenim reakcijama, osobama koje su počinile medikacijsku pogrešku te prema godini zaprimanja. Napravljena je analiza medikacijskih pogrešaka prema nuspojavama te analiza nuspojava prema ozbiljnosti, očekivanosti, ishodu i tipu nuspojava. Provedena je anketa o dosada provedenim mjerama minimizacije rizika među ljekarnicima zaposlenima u javnim ljekarnama. Poslan je upit regulatornim tijelima drugih država članica Europske unije i Europskog gospodarskog prostora kako bi se podaci usporedili s podacima iz Republike Hrvatske.
Rezultati
U navedenom razdoblju zaprimljeno je 108 slučajeva medikacijskih pogrešaka uzrokovanih primjenom salbutamol otopine za atomizator u pedijatrijskoj populaciji. Svi slučajevi zaprimljeni su od Instituta za medicinska istraživanja i medicinu rada. Najviše slučajeva zabilježeno je u djece u dobi od 1 godine do 7 godina starosti. Najčešće zabilježene medikacijske pogreške bile su slučajno predoziranje djeteta lijekom, slučajna izloženost djeteta lijeku, primjena pogrešnog lijeka te primjena lijeka pogrešnim putem. U slučajevima slučajnog predoziranja djeteta lijekom, u 55,4% slučajeva primijenjena doza lijeka bila je deset puta veća od propisane. U 41,7% slučajeva razvile su se nuspojave, a najčešće su zabilježene tahikardija, tremor i povraćanje. U 86,7% slučajeva nuspojave nisu ocijenjene ozbiljnima, dok su u 13,3% slučajeva nuspojave ocijenjene ozbiljnima.
Zaključak Rezultati ovog istraživanja ukazuju da se medikacijske pogreške uz primjenu salbutamol otopine za atomizator u pedijatrijskoj populaciji i dalje događaju. Kao uzroci medikacijskih pogrešaka identificirani su pogrešno razumijevanje propisane doze lijeka zbog vrlo male količine odnosno volumena lijeka koji je potrebno primijeniti, zamjena lijekova zbog sličnosti u izgledu unutarnjeg pakiranja te dostupnost lijeka djeci. Potrebno je daljnje provođenje mjera minimizacije rizika kako bi se rizik od medikacijskih pogrešaka smanjio ili u potpunosti spriječio. Sprječavanjem medikacijskih pogrešaka spriječit će se i razvoj nuspojava u pedijatrijskoj populaciji, uključujući razvoj teških i ozbiljnih nuspojava, te na taj način doprinijeti zaštiti zdravlja pedijatrijskih bolesnika.Objectives
The aim of this search was to present and analyse medication error reports with salbutamol nebuliser solution in pediatric population and to measure the effectiveness of risk minimisation measures which Agency for Medicinal Products and Medical Devices of Croatia (HALMED) had already performed in order to prevent them.
Material and Methods
A search of national adverse drug reaction (ADR) database was conducted for the period from January 1st 2016 to December 31st 2022. Medication error reports were analysed according to the patient's age, patient's gender, reactions reported, persons who made medication errors and according to the year of the receipt. Analysis of medication errors according to ADRs was performed and ADRs were analysed according to the seriousness, listedness, outcome and type of reactions. A survey was conducted among pharmacists employed in community pharmacies regarding risk minimisation measures which HALMED had already performed. An on-line survey was conducted between regulatory agencies of the European Union and European Economic Area member states in order to compare the data with Croatian data.
Results
A total of 108 medication error reports with salbutamol nebuliser solution in pediatric population were received in the stated period. All of the reports were received from the Institute for Medical Research and Occupational Health. The most of the reports were observed in the children aged from 1 to 7 years. The most commonly reported medication errors were accidental overdose, accidental exposure to product by child, wrong drug administered and drug administered via inappropriate route. In 55.4% of the accidental overdose cases, dose administered was ten times higher than dose prescribed. ADRs occurred in 41.7% of the reports, and the most commonly reported was tachycardia, followed by tremor and vomiting. In 86.7% of the reports ADRs were assessed as non-serious, while in 13.3% of the reports were assessed as serious.
Conclusion
The results of this search indicate that medication errors with the use of salbutamol nebuliser solution in the pediatric population continue to occur. Incorrect understanding of prescribed dose due to very small amount i.e. volume of the medicinal product, switch of medicinal products due to similarity in inner packaging and availability of medicinal product to children were identified as causes of medication errors. Further risk minimisation measures are warranted in order to minimise the risk or to completely prevent the occurrence of medication errors. By preventing medication errors, the occurrence of ADRs in pediatric population would be prevented as well, including those severe and serious, thus contributing to preservation of health in pediatric patients
Therapy of visceral hypersensitivity in irritable bowel syndrome
Visceralna preosjetljivost je važna komponenta sindroma iritabilnog crijeva, a pogađa 30-60% pacijenata, pretežito mlađe dobi i ženskog spola. Patofiziološka podloga visceralne preosjetljivosti nije još do kraja objašnjena, no smatra se da razni periferni i središnji faktori, poput psihološkog stresa i poremećaja crijevne permeabilnosti, mogu uzrokovati promjenu dvosmjerne signalizacije osi crijeva-mozak i povećanu senzitizaciju perifernog (enteričkog) i središnjeg živčanog sustava. Spazmolitici kao periferni neuromodulatori koriste se za smanjenje spazama i abdominalne boli. Antidepresivi se danas najčešće koriste kao središnji neuromodulatori, a istražuju se i atipični antipsihotici. Ovi lijekovi svojim kompleksnim djelovanjem na serotoninski i druge neurotransmitorske sustave djeluju izravno i posredno na neke patofiziološke komponente u podlozi visceralne preosjetljivosti, a posebno su korisni kod pacijenata s psihičkim poremećajima u anamnezi. U raznim studijama, tvari prirodnog porijekla poput berberina i kurkumina, kao i probiotici, pokazuju učinkovitost u smanjenju visceralne preosjetljivosti, što zahtijeva daljnja istraživanja. Istraživanja ukazuju na širok spektar medijatora i receptora uključenih u transmisiju, percepciju i modulaciju bolnih signala porijeklom iz gastrointestinalnog trakta, posebice na razini komunikacije crijeva-mozak, koji se istražuju kao potencijalne nove mete za specifičnije lijekove s neuromodulatornim djelovanjem na visceralnu preosjetljivost.Visceral hypersensitivity is an important component of irritable bowel syndrome, and affects 30-60% of patients, mostly younger and female. The pathophysiological basis of visceral hypersensitivity has not yet been fully explained, but it is believed that various peripheral and central factors, such as psychological stress and disorders of intestinal permeability, can cause a change in the bidirectional signaling of the gut-brain axis and increased sensitization of the peripheral (enteric) and central nervous system. Antispasmodics as peripheral neuromodulators are used to reduce spasms and abdominal pain. Today, antidepressants are most often used as central neuromodulators, and atypical antipsychotics are also being investigated. With their complex action on serotonin and other neurotransmitter systems, these drugs act directly and indirectly on some pathophysiological components underlying visceral hypersensitivity, and are especially useful in patients with a history of mental disorders. In various studies, substances of natural origin such as berberine and curcumin, as well as probiotics, show efficacy in reducing visceral hypersensitivity, which requires further research. Research indicates a wide spectrum of mediators and receptors involved in the transmission, perception and modulation of pain signals originating from the gastrointestinal tract, especially at the level of gut-brain communication, which are being investigated as potential new targets for more specific drugs with neuromodulatory effects on visceral hypersensitivity
The association of Val66Met and C270T polymorphisms in the gene coding for brain derived neurotophic factor (BDNF) and BDNF plasma concentration with depression, severity of symptoms and treatment reponse
Veliki depresivni poremećaj čest je psihijatrijski poremećaj, no njegova kompleksna patofiziologija i velika heterogenost predstavljaju zapreku u utvrđivanju čimbenika rizika i razvoju boljih terapijskih pristupa. Farmakološka terapija depresije zasniva se velikim dijelom na primjeni antidepresiva. Escitalopram djeluje kao inhibitor ponovne pohrane serotonina, dok vortioksetin pripada multimodalnim lijekovima koji uz inhibiciju SERT-a djeluje i na druge mete, poput 5-HT receptora.
Prema neurotrofinskoj teoriji, manjak BDNF-a, koji je bitan za neuralnu plastičnost u pojedinim moždanim regijama, igra ključnu ulogu u nastanku depresije i odražava se također i u uzorcima krvi. U BDNF genu nalazi se više polimorfizama, uključujući Val66Met i C270T polimorfizam, koji se povezuju s promjenama u ekspresiji i procesuiranju BDNF-a, kao i s razvojem različitih psihijatrijskih bolesti, uključujući i depresiju.
Cilj ovog rada bio je istražiti povezanost koncentracije BDNF-a u plazmi, te BDNF Val66Met i C270T polimorfizama s razvojem depresije, težinom depresivnih simptoma i učinkom antidepresivnih lijekova.
Istraživanje je potvrdilo sniženu koncentraciju BDNF-a u plazmi depresivnih bolesnika. Ispitanici s ponavljanim epizodama depresije imali su težu kliničku sliku od ispitanika sa prvom epizodom depresije, no ona se nije značajno razlikovala nakon 4 tjedna antidepresivne terapije. I vortioksetin i escitalopram, pokazali su se kao učinkoviti antidepresivni lijekovi, ali je samo vortioksetin povisio koncentraciju BDNF-a u plazmi. BDNF Val66Met polimorfizam, za razliku od C270T polimorfizma, utjecao je na bazalnu koncentraciju BDNF-a u plazmi, ali niti jedan nije bio povezan sa razvojem depresije, težinom simptoma i odgovorom na terapiju. Potrebna su daljna istraživanja BDNF-a na većem broju ispitanika, kao i nakon dugotrajne antidepresivne terapije.Major depressive disorder is a common psychiatric disorder; however its complex pathophysiology and large heterogeneity, hinder the determination of risk factors and development of better therapeutic approaches. Pharmacological therapy of depression is largely based on the use of antidepressants. Escitalopram functions as a selective serotonin reuptake inhibitor, while vortioxetine belongs to a new group of multimodal drugs, which, besides SERT inhibition, affects other targets, including 5-HT receptors.
According to the neurotrophin theory, lack of BDNF, which is essential for brain neural plasticity, plays a key role in development of depression and is reflected in blood samples. Several BDNF gene polymorphisms, including Val66Met and C270T, are associated with changes in BDNF expression and processing, and development of various psychiatric diseases, including depression.
We aimed to investigate the association of BDNF plasma concentrations, BDNF Val66Met and C270T polymorphisms with the development of depression, severity of depressive symptoms and effect of antidepressant drugs.
Findings confirmed decreased plasma BDNF concentration in depressed patients. Subjects with repeated depression episodes had more severe clinical picture than patients with a first depression episode, but it was not significantly different after 4 weeks of antidepressant therapy. Both vortioxetine and escitalopram proved to be effective antidepressant drugs, but only vortioxetine increased BDNF plasma concentration. BDNF Val66Met polymorphism, in contrast to C270T polymorphism, affected basal plasma BDNF concentration, but none of them was associated with development of depression, severity of symptoms, and therapy response. Further BDNF studies are needed using larger number of participants, as well as long-term antidepressant therapy
Investigation of the presence of 5-methoxysterigmatocystin in beer by thin layer chromatography
5-metoksisterigmatocistin (5-MET) je slabo istraženi mikotoksin za kojeg je zabilježeno da ima citotoksična i genotoksična svojstva. Strukturno je srodan sterigmatocistinu (STC), zajedno s kojim ga mogu proizvoditi plijesni roda Aspergillus serije Versicolores. Te su plijesni često prisutne u zatvorenim vlažnim i prašnjavim prostorima. Takvi prostori mogu biti skladišta i proizvodni pogoni u pivovarama. S obzirom na to da je pivo u Hrvatskoj konzumirano u velikim količinama, prisutnost ovih aspergila i biosinteza mikotoksina predstavljaju javnozdravstveni rizik ako je pivo kao krajnji proizvod kontaminirano 5-MET. Za analizu je skupljeno 58 različitih uzoraka piva s hrvatskog tržišta. Ekstrakcija je provedena korištenjem acetonitrila kao otapala, isoljavanjem i propuštanjem uzorka kroz SPE kolonu. Pripremljeni ekstrakti analizirani su tankoslojnom kromatografijom. Stacionarna faza bio je silikagel 60, a mobilna faza smjesa toluena, etil-acetata i mravlje kiseline (90% v/v) u omjeru 5:4:1. Za pojačanje fluorescencije ploče su sušene, grijane i prskane etanolnom otopinom aluminijeva klorida. Limit detekcije za 5-MET iznosio je 3.2 μg/mL. 5-MET je detektiran u 27 od 58 (46,55%) uzoraka. Njegova prisutnost potvrđena je UV-Vis spektroskopijom nakon ekstrakcije strugotine s TLC ploče. Rezultati ovog istraživanja predstavljaju prvi nalaz 5-MET u pivu. Također, potvrđuju prikladnost primijenjene metode te predstavljaju signal za potencijalnu javnozdravstvenu opasnost, imajući na umu ogromnu potrošnju piva. Istraživanja koja uključuju veći broj uzoraka te primjenjuju sofisticiranije kromatografske tehnike (poput LC/MS) omogućila bi precizniju interpretaciju ovih rezultata i kvantitativnu analizu 5-MET. Uz to, omogućila bi osjetljiviju detekciju (detekciju 5-MET u manjim koncentracijama) i selektivniju detekciju (s većom razinom sigurnosti da je u pitanju 5-MET a ne neki strukturno srodan spoj).5-methoxysterigmatocystin (5-MET) is unsufficiently investigated cytotoxic and genotoxic mycotoxin. It is structurally related to sterigmatocystin (STC) and produced namely by molds from the genus Aspergillus, series Versicolores. These molds are frequently found in damp and dusty indoor environments. In beer production, storage and production spaces fit this description. Given the high consumption of beer in Croatia, presence of these Aspergillus molds amd their production of mycotoxins constitutes a public health risk if beer in its end product state is contaminated with 5-MET. Fifty eight different samples of beer marketed in Croatia were collected for the purposes of this analysis. The extraction was performed by acetonitrile as a solvent, salt-induced precipitation and phase extraction with SPE columns. The prepared extracts were analysed by thin-layer chromatography. Silica gel 60 was used as stationary phase and a 5:4:1 mixture of toluene, ethyl-acetate and formic acid (90% v/v) as mobile phase. To enhance fluorescence, TLC plates were dried, heated and sprayed with an ethanol solution of aluminium chloride. Limit of detection (LOD) for 5-MET was 3.2 μg/mL. 5-MET was detected in 27 of 58 (46,55%) samples. Its presence was confirmed by UV-Vis spectroscopy following the extraction of the spot of interest from the TLC plate. This is the first time 5-MET has been detected in beer. Additionally, this study confirms the suitability of the applied method and serves as a signal for a potential public health risk, considering the high levels of beer consumption. Research that includes a larger number of samples and uses more sophisticated analytic techniques (such as LC/MS) would allow for a more accurate interpretation of these results and enable quantitative analysis. Additionally, it would increase sensitivity (making detection of smaller quantities of 5-MET possible) and selectivity (the likelihood that 5-MET is detected, as opposed to structurally related compounds)
Digital medications
Mentalne bolesti vodeći su globalni uzročnici morbiditeta i mortaliteta. Farmakološka terapija predstavlja temelj liječenja mentalnih bolesti, a adherencija na lijekove u njihovom slučaju izuzetno je važna zbog dugotrajnog liječenja i ozbiljnih posljedica ako se liječenje prijevremeno prekine. Shizofrenija je kompleksna kronična mentalna bolest koja se liječi antipsihoticima. Namjerna i nenamjerna neadherencija na antipsihotike predstavlja glavni problem u liječenju shizofrenije, koja se javlja zbog ozbiljnih nuspojava antipsihotika i zbog toga što bolesnik nije svjestan bolesti. Prvi odobreni digitalni lijek Abilify MyCite sadrži antipsihotik aripiprazol kao djelatnu tvar. Radi se o sustavu digitalne medicine koji uključuje tabletu sa probavljivim senzorom i djelatnom tvari, nosivi flaster, aplikaciju na pametnom telefonu i mrežni portal. Radi na principu prijenosa digitalnog signala sa senzora na nosivi flaster u trenutku kada senzor dođe u kontakt sa želučanom tekućinom. Podatci o primjeni lijeka, ali i drugi podatci o zdravstvenim i životnim navikama na mrežnom portalu dostupni su liječniku i osobama kojima bolesnik odobri pristup. Još jedan digitalni sustav koji se istražuje je ID-Cap sustav sa senzorom ugrađenim u kapsulu. Radi na principu prijenosa radio signala niskog inteziteta na uređaj za očitavanje u trenutku kada kapsula dođe u kontakt sa želučanom tekućinom. AiCure je sustav vizualnog prepoznavanja koji snima video i temelji se na analizi slike lica s ciljem provjere je li bolesnik uzeo propisan lijek. Sustavi digitalne medicine razvijeni su s ciljem poboljšanja adherencije što rezultira boljim zdravstvenim ishodima i smanjenim troškovima zdravstvene skrbi. Međutim, do sada nema kliničkih dokaza da digitalni lijekovi mogu dosljedno pratiti ingestiju u stvarnom vremenu ili poboljšati adherenciju. Zbog toga se postavlja pitanje je li pri odobrenju Abilify MyCite primijenjena evergrin strategija za produljenje roka trajanja lijeka Abilify. Nadalje, digitalne lijekove prate brojni etički problemi kao što su negativni utjecaj na autonomiju i privatnost bolesnika, subjektivni osjećaj prisile i kontrole, narušeno povjerenje u odnosu između liječnika i bolesnika i utjecaj farmaceutskih kompanija na liječnika. Napravljena je usporedba digitalnih lijekova s ostalim konvencionalnim i inovativnim terapijskim sustavima. Dok su digitalni lijekovi osmišljeni primarno s ciljem svakodnevnog praćenja ponašanja prilikom uzimanja lijekova, ostali inovativni terapijski sustavi osmišljeni su s ciljem poboljšanja svojstava i isporuke lijekova što posljedično dovodi do poboljšanja adherencije. Potrebno je provesti klinička istraživanja s naglaskom na procjenu adherencije i kvalitete života bolesnika koji uzimaju digitalne lijekove i educirati liječnike i bolesnike o inovativnim terapijskim sustavima.Mental disorders are the leading global cause of mortality and morbidity. Pharmacological therapy represents the basis for treatment of mental disorders and medication adherence is in their case extremely important due to long-term treatment and serious consequences if the treatment is stopped prematurely. Schizophrenia is a complex chronic mental illness that is treated with antipsychotics. Intentional and unintentional non-adherence to antipsychotics is the main problem in treatment of schizophrenia, which occurs due to the serious side effects of antipsychotics and because the patient is unaware of the illness. The first approved digital medication Abilify MyCite contains the antipsychotic aripiprazole as the active substance. It represents the digital medicine system which contains a tablet with an ingestible sensor and active substance, a wearable patch, an application on a smartphone and a web portal. It works on the principle of transmitting the digital signal from the sensor to the wearable patch in the moment when the sensor comes into contact with gastric fluid. Data on drug ingestion, as well as other data on health and life habits on the web portal are available to the doctor and other individuals, to whom the patient grants access. Another digital system in research is the ID-Cap system, with a sensor built in the capsule. It works on the principle of transmitting a low-intensity radio signal to a reading device when the capsule comes into contact with gastric fluid. AiCure is a visual recognition system which records video and is based on facial image analysis to verify that the patient has taken the prescribed medication. Digital medicine systems have been developed with the explanation for improving adherence which results in better health outcomes and reduced healthcare costs. However, there is no clinical evidence which suggest that digital medications can consistently monitor medication ingestion in real time or improve adherence. Therefore, the question arises as to whether the Abilify MyCite approval has used evergreening to extend the lifetime of the medication Abilify. Furthermore, digital medications are accompanied by several ethical issues such as the negative impact on patient autonomy and privacy, the subjective feeling of coercion and control, the disturbed trust in the relationship between doctor and patient and the impact of pharmaceutical companies on doctor. The comparison of digital medications with other conventional and innovative therapeutic systems was made. While the digital medications are primarily designed to monitor medication-related behaviour on a daily basis, other innovative therapeutic system are designed to improve drug properties and delivery, which in turn can lead to improved adherence. Clinical research should be conducted with an emphasis on assessing the adherence and quality of life of patients who take digital medications, and doctors and patients should be educated about innovative therapeutic systems
Potential clinically significant drug-drug interactions in prescribed pharmacotherapy of non-hospitalized patients and models of pharmacists interventions
Uvod: Interakcije lijekova su važan aspekt u sigurnosti primjene lijeka i velik izazov za zdravstveni sustav. Ljekarnik je u obavezi i mogućnosti utjecati na prevenciju i upravljanje interakcijama lijekova.
Svrha rada: Utvrditi pojavnost potencijalnih klinički značajnih interakcija lijekova u propisanoj farmakoterapiji izvanbolničkih pacijenata u Republici Hrvatskoj (RH). Za iste odrediti modele ljekarničkih intervencija te ispitati stavove ljekarnika o interakcijama lijekova i ljekarničkim intervencijama.
Metode i ispitanici: Provedeno je retrospektivno konsekutivno uzorkovanje propisane farmakoterapije iz 40 randomiziranih javnih ljekarni u RH. Koristeći Lexi-Interact™ Online analizirana je farmakoterapija te su za utvrđene interakcije potom određeni modeli ljekarničkih intervencija. U uključenim ljekarnama je proveden i upitnik koji ispituje stav ljekarnika o interakcijama lijekova i ljekarničkim intervencijama.
Rezultati: Sveukupno je uključeno 4107 pacijenata i utvrđeno 14175 klinički značajnih interakcija. Barem jedna interakcija utvrđena je kod 78,6 % pacijenata, a izloženost pacijenata određenom tipu interakcija iznosila je za interakcije stupnja C 74,1 %, za stupanj D 31,4 % i za stupanj X 4,1 %. Najučestaliji modeli ljekarničkih intervencija bili su modeli kategorije II (intervencije koje ljekarnik provodi u suradnji s liječnikom). Upitnik je ispunilo 97,9 % ljekarnika. Većina se složila da je upravljanje interakcijama lijekova važan segment ljekarničke skrbi te da treba razviti standardiziranu strategiju upravljanja interakcijama lijekova.
Zaključak: Istraživanje pokazuje opću izloženost izvanbolničkih pacijenata u RH potencijalnim klinički značajnim interakcijama lijekova. Istraživanje također daje uvid u zastupljenost i vrstu modela ljekarničkih intervencija kojima bi se unaprijedila ljekarnička skrb i sigurnost pacijenta.Background: Drug-drug interactions (DDIs) are a big challenge for any healthcare system. Pharmacists are obligated to prevent and manage DDIs.
Aims: To determine potential clinically significant DDI incidence in prescribed outpatient pharmacotherapy in Croatia. Furthermore, the aim was to set pharmacists' intervention models and to determine pharmacists' stance on DDIs and pharmacists' interventions.
Patients and methods: This was a retrospective study which consecutively analyzed prescribed outpatient pharmacotherapy from 40 randomly selected community pharmacies in Croatia. DDIs were identified using Lexi-Interact™ Online. Models of pharmacy interventions were determined for the most common identified interactions. Furthermore, a survey was conducted among pharmacists in seleceted pharmacies to evaluate their stance towards DDIs and pharmacist interventions.
Results: Overall, 4107 patients were incluced and 14175 clinically significant DDIs were identified. Atleast one DDI was found in 78.6 % of patients, with patient exposure to C, D and X category of 74.1 %, 31.4 % and 4.1 %, respectively. The most frequent models of pharmacist interventions were category II models (pharmacist intervention in cooperation with physicians). The survey was completed by 97.9 % of pharmacists. The results showed that most pharmacists agree that pharmacist interventions are an important segment of pharmaceutical care and that development of stadardized strategy of pharmacist interventions is needed.
Conclusion: The study found high outpatient exposure to potential clinically significant DDIs. The study gives an insight to possible models of pharmacist interventions which could improve pharmaceutical care and increase patient safety
High-throughput N-glycosylation analysis of complement component C3 as biomarker of type 1 diabetes
Ubrzani razvoj analitičkih tehnika u posljednjih nekoliko desetljeća omogućio je temeljito istraživanje procesa N-glikozilacije u brojnim patofioziološkim stanjima, a uočene promjene u mnogima od njih dovele su do strelovitog rasta interesa za glikobiologiju. Promjene u N-glikozilaciji danas se smatraju vrijednim biljezima raznih bolesti, te se njihova specifičnost pokušava iskoristiti u diferencijalne, dijagnostičke i prognostičke svrhe. Prethodne studije pokazale su da je N-glikanski profil plazmatskih proteina promijenjen u šećernoj bolesti tipa 1 (ŠBT1). Jedna od izraženije uočenih promjena bila je ona u zastupljenosti visoko-manoznih glikanskih struktura u plazmatskom N-glikomu. Ove strukture dominantno bi mogle potjecati s komponente komplementa C3, budući da je to glikoprotein s isključivo visoko-manoznim glikanima vezanima na proteinsku okosnicu za kojeg je poznato da doprinosi razvoju ŠBT1 pojačavanjem autoimunih upalnih procesa. Iz tog je razloga u ovom radu razvijena visokoprotočna metoda za analizu N-glikozilacije pojedinih glikozilacijskih mjesta ljudskog C3 proteina upotrebom tekućinske kromatografije spregnute sa spektrometrom masa (LC-MS) temeljena na njegovu obogaćivanju iz plazme pomoću lektinskog afinitetnog medija visokog afiniteta za manozu. Novorazvijenom metodom zatim je analizirana krvna plazma ispitanika novodijagnosticiranih šećernom bolesti tipa 1 i njihove zdrave braće i sestara te su uočene značajne promjene C3 N-glikoma. ŠBT1 povezana je s porastom manje procesuiranih struktura s više manoznih podjedinica na oba N-glikozilacijska mjesta. Nadalje, C3 N-glikozilacija je analizirana u odrasloj populaciji ispitanika s različitim stupnjem najčešćih komplikacija ŠBT1 – retinopatije i albuminurije. Pokazano je da se C3 N-glikom značajno mijenja u teškoj albuminuriji u ŠBT1, no da je neovisan o trajanju bolesti. Retinopatija je pak dovela do promjene samo jedne glikoforme, dok su svi osim jednog C3 glikopeptida značajno povezani s razinama hemoglobina A1c (HbA1c). Predstavljene spoznaje ukazuju na uključenost N-glikozilacije i C3 komponente komplementa u patofiziologiju šećerne bolesti tipa 1 te upućuju na značaj C3 N-glikoma kao potencijalnog dijagnostičkog i prognostičkog biljega ove bolesti i njoj pridruženih komplikacija.Rapid development of analytical techniques in the last few decades has enabled a thorough investigation of the N-glycosylation process in numerous pathophysiological conditions, and the observed changes in many of them have led to a rapid growth of interest in the field of glycobiology. Changes in N-glycosylation are now considered valuable biomarkers of various diseases, and their specificity is being exploited for differential, diagnostic and prognostic purposes. Previous studies have shown that the N-glycan profile of plasma proteins is altered in type 1 diabetes (T1D). One of the more pronounced changes observed was in he abundance of high-mannose glycans in the plasma N-glycome. These structures could predominantly originate from the complement component C3, a glycoprotein with exclusively high-mannose glycans attached to its protein backbone, which is known to contribute to the development of T1D by enhancing autoimmune inflammatory processes. For this reason, a high-throughput method for the site-specific N-glycosylation analysis of human C3 protein was developed in this study using liquid chromatography coupled to a mass spectrometer (LC-MS), based on its enrichment from plasma using lectin affinity matrix. The newly developed method was then used to analyze blood plasma of subjects newly diagnosed with type 1 diabetes and their healthy siblings, and significant changes in C3 N-glycome were observed. T1D was associated with an increase in less processed structures with more mannose subunits at both C3 N-glycosylation sites. Furthermore, C3 N-glycosylation was analyzed in the adult population of T1D subjects with different degrees of the most common complications of T1D – retinopathy and albuminuria. It was shown that C3 N-glycome significantly changes in severe albuminuria in T1D, but is independent of disease duration. Retinopathy led to a change in only one glycoform, while all but one C3 glycopeptide was significantly associated with levels of hemoglobin A1c (HbA1c). The findings presented indicate the involvement of N-glycosylation and the C3 complement component in the pathophysiology of type 1 diabetes and indicate the importance of C3 N-glycome as a potential diagnostic and prognostic biomarker of this disease and its associated complications