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Immunotherapy of diabetes type 1
No full textDijabetes tipa 1 (DT1) je autoimuna endokrinološka bolest koja nastaje kao posljedica uništenja β stanica gušterače koje proizvode hormon inzulin. Uzrokom razvoja DT1 smatra se kombinacija okolišnih i genetskih čimbenika koji dovode do autoimunosti posredovane u najvećoj mjeri autoreaktivnim T limfocitima. Trenutna terapija DT1 nadomjescima inzulina liječi posljedicu bolesti bez ostvarivanja učinka na očuvanje β stanica. Imunoterapija bi usmjeravanjem prema različitim sastavnicama imunosnog sustava mogla djelovati direktno na uzrok DT1. Najveći potencijal u održavanju remisije DT1 pokazuju teplizumab, alefacept i antitimocitni globulini, a djelovanje sva tri imunoterapijska pristupa usmjereno je prema sprječavanju aktivacije T limfocita. Unatoč pozitivnim rezultatima trenutno ni jedan oblik imunoterapije nije odobren za liječenje DT1.Diabetes type 1 (DT1) is an autoimmune endocrine disease that results from the destruction of insulin producing pancreatic β cells. The cause of DT1 development is considered to be a combination of environmental and genetic factors that lead to autoimmunity mediated mostly by autoreactive T lymphocytes. Current DT1 insulin replacement therapy treats the consequences of the disease without having an effect on β cell preservation. Immunotherapy, by targeting different components of the immune system, could act directly on the cause of DT1. Teplizumab, alefacept and antithymocyte globulins show the greatest potential in maintaining DT1 remission, and the action of all three immunotherapeutic approaches is aimed at preventing T lymphocyte activation. Despite the positive results, currently no form of immunotherapy is approved for the treatment of DT1
Public health aspect of colorectal cancer with an emphasis on the incidence in certain populations, life habits and prevention possibilities
No full textKolorektalni karcinom (CRC) obuhvaća heterogenu skupinu bolesti koja zahvaća debelo crijevo i rektum. Većina CRC-a jesu adenokarcinomi koji nastaju iz premalignih lezija, polipa. Čimbenici koji pridonose razvoju ove vrste malignoma multifaktorijalni su, a uključuju genetske i okolišne čimbenike. Osobe s nasljednim polipoznim sindromom ili Lynchovim sindromom spadaju u visokorizičnu skupinu ljudi za razvoj CRC-a. Visok rizik imaju i osobe s obiteljskom anamnezom ove bolesti ili osobe koje boluju od upalnih bolesti crijeva. Većinu CRC-a čine sporadični slučajevi koji se pojavljuju u starijoj dobi. CRC je bolest modernoga čovjeka što znači da je uvelike uvjetovana vanjskim faktorima i stilom života. Prehrambene navike, sjedilački način života, konzumacija alkohola i duhanskih proizvoda smatraju se rizičnim čimbenicima na koje se može utjecati. Usprkos napretku liječenja ove bolesti, kao ključne strategije pokazali su se preventivni postupci. Primarna prevencija podrazumijeva zdrave prehrambene obrasce, fizičku aktivnost i kemoprevenciju. Za uspjeh primarne prevencije potrebno je razvijati strategije na razini države koje promoviraju zdrav način života. Kemoprevencija je perspektivno područje istraživanja. Dotada, programi probira osiguravaju otkrivanje premalignih promjena i bolesti u ranoj fazi te pravovremeno liječenje.Colorectal cancer (CRC) includes a heterogeneous group of diseases that affect colon and rectum. Most CRC are adenocarcinomas that arise from premalignant lesions, polyps. Factors contributing to the development of this type of malignancy include genetic and environmental factors. People with hereditary polyp syndrome or Lynch syndrome belong to a high-risk group of people for developing CRC. People with a family history of this disease or people suffering from inflammatory bowel disease are at high risk too. Most CRC are sporadic cases that occur in old age. CRC is a disease of modern age which means that it is largely conditioned by external factors and lifestyle. Eating habits, sedentary lifestyle, consumption of alcohol and tobacco products are considered as modifiable risk factors. Despite advances in the treatment of this disease, prevention methods have proven to be key strategies. Primary prevention includes healthy eating patterns, physical activity and chemoprevention. For primary prevention to succeed, it is necessary to develop state-level strategies that promote a healthy lifestyle. Chemoprevention is a promising area of research. Until then, screening programs ensure the detection of premalignant changes and disease at an early stage and timely treatment
Anticancer activity of selenium nanoparticles synthesized with tomato and tangerine pectins as a coating agent
No full textU ovom istraživanju razvijeni su postupci biosinteze nanoselena uz stabilizaciju pektinima rajčice i
mandarine kao sredstava za oblaganje te uz dodatnu funkcionalizaciju ekstraktom komine masline
(EKM) bogatim polifenolima. Nakon provedene sinteze, provedena je fizikalno-kemijska
karakterizacija dobivenih nanosustava te je ispitan njihov učinak na stanične linije HepG2 i Caco-2.
Dodatkom EKM povećan je prinos sinteze, a nanočestice su pokazale unimodalni tip raspodjele s
rasponom veličine srednjeg promjera 110,4 do 235,4 nm. Zeta potencijal novosintetiziranih sustava
kretao se u rasponu od -25, 9 mV do -21,1 mV, gdje su negativnije vrijednosti dobivene u
funkcionaliziranim nanočesticama. IC50 vrijednosti sintetiziranih nanosustava kretale su se 56.4-
245.2 µg/mL. Selen u nanoobliku pokazao je manju toksičnost od selenita, a uzorci funkcionalizirani
EKM uglavnom su pokazali manju toksičnost u odnosu na nefunkcionalizirane uzorke. Primjenom
pektina komine mandarine i rajčice moguće je dobiti nanočestice selena, smanjene toksičnosti (u
odnosu na selenit) i odgovarajućih fizikalno-kemijskih i funkcionalnih svojstava, uključujući i
antikancerogeno djelovnje, koja se dodatno poboljšavaju funkcionalizacijom ekstrakta komine
masline.In this paper, we investigated the possibility of nanoselenium biosynthesis using tomato- and
mandarin pomace derived pectins as coating agents and olive pomace extract (OPE) as the
functionalization agent. The relative yields of the newly propesed synthesis processes were
examined by UV / VIS spectroscopy; the size and stability of the nanoparticles were determined by
using the dynamic light scattering technique and by measuring zeta potential. The anticancer efects
of obtained nanoparticles were investigated in HepG2 and Caco-2 cell lines. using the colorimetric
MTT method, and the IC50 value was calculated for each sample. Using these methods, it was
determined that unimodal particle size distribution was obtained by proposed biosynthesis processes
with average diameters rangin from 110.4 to 235.4 nm. Zeta potential of investigated nanosystems
ranged from -25.9 mV to -21.1 mV and therefore all obtained samples can be considered stable.
Samples fuctionalized with OPE showed lower negative values of zeta potential indicating improved
stability. IC50 values for the HepG2 cell line showed that all nanoselenium samples had significantly
lower toxicity in comparison to the inorganic form of selenium, selenite. Similar was shown on
Caco-2 cell culture with the exception of a sample synthesized with purified tomato pectin and with
the addition of OPE that showed higher toxicity than selenite. In conclusion, with this type of
biosynthesis, it is possible to synthesize stable selenium nanoparticles that show less toxicity in
comparison to selenite.and posses anticancer effects that are aditionally improved by
functionalization by OPE
Učestalost off-label propisivanja i primjene antimikrobnih lijekova u Klinici za infektivne bolesti "Dr. Fran Mihaljević" u Zagrebu
No full textCilj istraživanja: Cilj je ovog istraživanja utvrditi učestalost off-label propisivanja
antimikrobnih lijekova (AML-ova) u Klinici za infektivne bolesti “Dr. Fran Mihaljević” u
Zagrebu, odrediti vrste i usklađenost off-label primjene sa smjernicama Klinike i Europskog
društva kliničke mikrobiologije i infektologije (ESCMID, eng. European Society of Clinical
Microbiology and Infectious Diseases), kako bi se postavili temelji za daljnje analize.
Materijal i metode: Retrospektivnim presječnim istraživanjem obuhvaćena su djeca i odrasli
bolesnici hospitalizirani u Klinici na dan s najvećim brojem hospitalizacija, 17.1.2019.
godine. Off-label primjena AML-a bila je ona koja nije bila u skladu sa Sažetkom opisa
svojstava lijeka (SmPC).
Primjena AML-ova klasificirana je u pet skupina:
1. primjena u skladu sa SmPC-om
2. off-label primjena u skladu sa smjernicama Klinike
3. off-label primjena u skladu s ESCMID smjernicama
4. off-label primjena koja nije u skladu sa smjernicama Klinike
5. off-label primjena koja nije u skladu s ESCMID smjernicama
Rezultati: Istraživanje je obuhvatilo 63 odrasle osobe, od kojih 36 (57,1%) muškaraca, i 92
djece, od kojih 44 (47,8%) dječaka. Najmanje jednim AML-om liječen je 61 (96,8%) odrasli i
60 (65,2%) djece.
Ukupno je zabilježeno 134 preskripcije u odraslih, od toga 42 (31,3%) off-label u odnosu na
SmPC. AML-ovi su propisivani off-label u odnosu na dozu, režim doziranja i indikaciju,
nekad istovremeno prema dva kriterija, ukupno 52 off-label slučaja. Od navedenih off-label
slučajeva: u 22 (42,3%) nisu postojale smjernice Klinike, a 11 (36,7%) je bilo u skladu; u 20
(38,5%) slučajeva nisu postojale ESCMID smjernice, 5 (15,6%) je bilo u skladu, a u 22
(68,8%) usklađenost se nije mogla odrediti.
Najčešće su u odraslih off-label propisani: oseltamivir - 11 puta (8,2%), cefuroksim - 4 (3%)
te vankomicin, meropenem i piperacilin/tazobaktam - po 3 puta (2,2%).
Ukupno je zabilježeno 73 preskripcije u djece, od toga 31 (42,5%) off-label u odnosu na
SmPC. Lijekovi su propisivani off-label u odnosu na dozu, indikaciju i dob, nekad
istovremeno prema dva kriterija, ukupno 33 slučaja. Od navedenih off-label slučajeva za 10
(30,3%) nisu postojale smjernice Klinike, a 4 (17,4%) je bilo u skladu. ESCMID smjernice su
postojale za samo jedan klinički sindrom, s njim nije bilo usklađenosti.
Najčešće su u djece off-label propisani: ceftriakson - 8 (10,9%), oseltamivir - 7 (9,6%) i
azitromicin - 3 (4,1%) puta.
Zaključak: Rezultati ukazuju da je off-label primjena AML-ova u Klinici prisutna. Ovi
rezultati su u skladu s dosadašnjim istraživanjima. Na rezultate je utjecalo nepostojanje
smjernica za mnoge indikacije i heterogenost smjernica. Zabilježeno je i off-label propisivanje
koje nije u skladu sa smjernicama.Objectives: The study aimed to determine the frequency of off-label prescribing of
antimicrobial drugs (AML) at the University Hospital for Infectious Diseases “Dr Fran
Mihaljević ”in Zagreb. Another aim was to determine the types of such prescribing and the
compliance of off-label applied AML with the Clinic guidelines and the European Society of
Clinical Microbiology and Infectious Diseases (ESCMID) guidelines to set foundations for
further analysis in the improvement of patient care.
Material and methods: A retrospective cross-sectional study included pediatric and adult
patients hospitalized at the Clinic on the day with the highest number of hospitalizations in
2019, January 17. Any use of AML that did not comply with the Summary of Product
Characteristics (SmPC) was considered off-label use.
The use of antimicrobial drugs was classified as one of the following:
1. use in accordance with the SmPC
2. the off-label use that follows Clinic guidelines
3. the off-label use that follows ESCMID guidelines
4. the off-label use that does not follow Clinic guidelines
5. the off-label use that does not follow ESCMID guidelines
Results: The study included 63 adults (36 men, 57.1%) and 92 pediatric patients (44 boys,
47.8%). 61 (96.8%) adult and 60 (65.2%) pediatric patients used at least one AML. We
recorded 134 prescriptions in adults, out of which 42 (31,3%) were off-label. Off-label was
prescribed concerning dose, dosing regimen and indication, sometimes simultaneously
concerning two criteria (dose and dosing regimen), so there were 52 off-label cases. Out of
those, in 22 (42,3%) off-label cases, there were no Clinic guidelines, and 11 (36,7%) cases
followed them, while in 20 (38,5%) cases, there were no ESCMID guidelines, 5 (15,6%)
followed them, and in 22 (68,8%) cases we could not establish compliance.
The most commonly off-label prescribed AMLs were: oseltamivir - 11 (8,2%) times,
cefuroxime - 4 (3%) and vancomycin, meropenem and piperacillin/tazobactam - 3 times each
(2,2%).
We recorded 73 prescriptions in children, out of which 31 (42,5%) were off-label. Offlabel
was prescribed concerning dose, indication and population, sometimes simultaneously
concerning two criteria, so there were 33 off-label cases. Out of those 33, in 10 (30,3%) offlabel
cases, there were no Clinic guidelines, and 4 (17,4%) followed them. There was only
one ESCMID guideline, and there was no compliance.
The most commonly off-label prescribed AMLs were: ceftriaxone - 8 (10,9%) times,
oseltamivir - 7 (9,6%) and azitromycin - 3 (4,1%) times.
Conclusion: The data obtained indicate that off-label use of AML in the Clinic is present,
which is consistent with previous research. The non-existence of guidelines for many
indications and the heterogeneity of available ones affected the results. There was also offlabel
prescribing not compliant with the guidelines
Effect of Micromeria thymifolia (Scop.) Fritsch essential oil and pulegone on production of pyocyanin by Pseudomonas aeruginosa PAO1
No full textPseudomonas aeruginosa je oportunistički patogen koji dovodi do infekcija najčešće imunokompromitiranih osoba. Smatra se klinički najznačajnijom vrstom unutar roda Pseudomonas. Sposobnost stvaranja velikog broja strukturnih i sekrecijskih faktora virulencije kao i formiranje biofilma otežava liječenje infekcija P. aeruginosa. Sve veći razvoj bakterijske rezistencije kod P. aeruginosa, zbog neracionalne primjene antibiotika, dovodi do potrebe za istraživanjem alternativnih mogućnosti liječenja. Jedna od takvih mogućnosti je primjena eteričnih ulja. To su aromatične, hlapljive otopine kompleksnog sastava koje posjeduju antimikrobno djelovanje. U ovom radu ispitan je učinak eteričnog ulja vrste Micromeria thymifolia (Scop.) Fritsch i njegove glavne komponente pulegona u koncentracijama od 0,5 mg/mL na rast planktonskih stanica i proizvodnju sekrecijskog faktora virulencije piocijanina kod P. aeruginosa PAO1. Osim njihovog pojedinačnog učinka ispitivan je i potencijalni sinergistički učinak s aminoglikozidnim antibiotikom tobramicinom u subinihibitornoj koncentraciji 0,5 mg/L. Istraživanje učinka na rast planktonskih stanica P. aeruginosa PAO1 provedeno je spektrofotometrijskim mjerenjem optičke gustoće pri 600 nm. Eterično ulje mikromerije i pulegon pokazali su inhibitorni učinak na rast planktonskih stanica. Eterično ulje mikromerije pokazalo je i sinergistički učinak s tobramicinom pojačavajući njegovo djelovanje. Kombinacija pulegona i tobramicina nije dovela do pojave značajnog sinergizma u inhibiciji rasta planktonskih stanica P. aeruginosa PAO1. Ispitivanje učinka na proizvodnju piocijanina provedeno je spektrofotometrijskim mjerenjem ekstrahiranog piocijanina pri 520 nm. Eterično ulje mikromerije pokazalo je inhibitorni učinak, dok sami pulegon nije. Ispitivanja međudjelovanja tobramicina s eteričnim uljem i pulegonom pokazala su njihov antagonistički učinak koji je doveo do smanjenja djelovanja tobramicina. Rezultati ovog rada pridonose boljem razumijevanju kompleksnosti i antimikrobnog potencijala eteričnih ulja.Pseudomonas aeruginosa is an opportunistic pathogen that most commonly leads to infections of immunocompromised individuals. It is considered to be the most clinically significant species within the genus Pseudomonas. The ability to produce a large number of structural and secretory virulence factors and to form biofilm complicates the treatment of P. aeruginosa infections. There is a great need to explore alternative treatment options because of the increase in development of bacterial resistance in P. aeruginosa, due to the irrational use of antibiotics. One of these alternative options is the use of essential oils. These are aromatic, volatile solutions of complex composition that possess antimicrobial activity. This study investigated the effect of Micromeria thymifolia (Scop.) Fritsch essential oil and its component pulegon in concentrations of 0,5 mg/mL on planktonic cell growth and production of virulence factor pyocyanin in P. aeruginosa PAO1. In addition to their individual effect, a potential synergistic effect with the aminoglycoside antibiotic tobramycin in subinhibitory concentration of 0,5 mg/L was also investigated. The effect on the planktonic growth of P. aeruginosa PAO1 cells was measured spectrophotometrically at 600 nm. Micromeria essential oil and pulegon used in concentration of 0,5 mg/mL showed an inhibitory effect on planktonic cell growth. Micromeria essential oil also showed a synergistic effect with tobramycin by enhancing its effect on growth of P. aeruginosa PAO1 plankton cells. The combination of pulegone and tobramycin did not lead to significant synergism. The effect on production of pyocyanin by P. aeruginosa PAO1 was investigated by spectrophotometric measurements of extracted pyocyanin at 520 nm. Micromeria essential oil showed an inhibitory effect, while pulegon did not. Interaction of tobramycin with essential oil and pulegon showed their antagonistic effect leading to a decrease in the activity of tobramycin. The results of this work contribute to a better understanding of the complexity and antimicrobial potential of essential oils
General anesthetics and premedication in general anesthesia
No full textOpća anestezija je stanje potpune neosjetljivosti na vanjske podražaje, a postiže se primjenom općih anestetika, uz odgovarajuću anestetsku premedikaciju. Navedeno stanje mora biti reverzibilne prirode, kako bi pacijent nakon provedenog zahvata ponovno uspostavio sve životno važne funkcije. Sve opisano moguće je provesti zahvaljujući anesteticima različitih povoljnih karakteristika primijenjenih najčešće u međusobnoj kombinaciji, te pomno odabranom i kontroliranom dozirnom režimu od strane nadležnog anesteziologa. Uvriježena podjela općih anestetika temeljena na putu primjene uključuje intravenske i inhalacijske predstavnike. Neizostavna komponenta anestetskog režima su neuromišićni relaksansi. Intravenski opći anestetici imaju izuzetno izuzetno brz početak djelovanja, budući da je izbjegnuta apsorpcijska etapa njihove farmakokinetike. Mete djelovanja su im uglavnom receptori γ-aminomaslačne kiseline, te glutamatni i dopaminski receptori, putem kojih ostvaruju pretežno hipnotski učinak. Među najpoznatije predstavnike intravenske opće anestezije uvrštavaju se tiopental, propofol, etomidat, midazolam i ketamin. Ulazni i izlazni put inhalacijskih anestetika iz organizma pacijenta su pluća, zbog čega oni moraju biti u obliku plinova ili hlapljivih tekućina. Potentnost im se dogovorno određuje i uspoređuje preko njihove liposolubilnosti, izražene preko minimalne alveolarne koncentracije (MAK). Neki od poznatijih predstavnika ove skupine su eter, dušični oksidul, halotan, sevofluran, izofluran, enfluran i desfluran. Neuromišićni relaksansi važna su komponenta opće anestezije za osiguranje dišnog puta i prikladnih intubacijskih uvjeta tijekom operativnog zahvata. Djeluju preko acetilkolinskog neurotransmiterskog sustava, a, ovisno o mehanizmu djelovanja, dijelimo ih na depolarizirajuće (sukcinilkolin) i nedepolarizirajuće (mivakurij, atrakurij, vekuronij, rokuronij i pankuronij). Po potrebi, djelovanje im je moguće poništiti uz pomoć dostupnih antagonista, podijeljenih na antikolinergike (neostigmin, edrofonij i piridostigmin) i ciklodekstrine (Sugamadeks). Anestetska premedikacija uključuje lijekove primijenjene pacijentu prije samog anestetika, a važna je za pripremu i optimiranje uvjeta za odvijanje predviđene operacije, te za prevenciju mogućih postoperativnih komplikacija. Većina takvih lijekova daje se pacijentu oko 60 minuta prije početka zahvata. Kao dio predoperativne pripreme primjenjuju se opioidni analgetici (fentanil), antikolinergici (atropin) i benzodiazepini (midazolam). S druge strane, antiemetici (metoklopramid), antibiotici (cefalosporini/vankomicin, klindamicin) i antikoagulansi (heparin) dio su premedikacije zadužen za prevenciju poslijeoperacijskih komplikacija poput mučnine i povraćanja, infekcija i venske tromboembolije.General anesthesia is a state of complete insensitivity to external stimuli, and is achieved by the use of general anesthetics, supplemented by drugs from the regime of anesthetic premedication. This condition must be reversible in nature, so that the patient can re-establish all vital functions after the procedure. All of the above can be performed thanks to anesthetics of various favorable characteristics, most often used in combination with each other, and carefully selected and controlled dosing regimen by a competent anesthesiologist. The standard classification of general anesthetics based on the route of administration includes intravenous and inhalation agents. Neuromuscular relaxants are also an indispensable component of the anesthetic regime. Intravenous general anesthetics, has extremely fast onset of action, since the absorption stage of their pharmacokinetics is thus avoided. Their targets are mainly γ-aminobutyric acid receptors, and glutamate and dopamine receptors, through which they achieve a predominantly hypnotic effect. The most well-known representatives of intravenous general anesthesia include thiopental, propofol, etomidate, midazolam and ketamine. The entry and exit pathways of inhaled anesthetics from the patient's body are the lungs, which is why they must be in the form of gases or volatile liquids. Their potency is determined and compared by their liposolubility, expressed through the minimum alveolar concentration (MAC). Some of the better known representatives of this group are ether, nitrous oxide, halothane, sevoflurane, isoflurane, enflurane and desflurane. Neuromuscular relaxants are an important component of general anesthesia to provide airway and appropriate intubation conditions during surgery. They act through the acetylcholine neurotransmitter system, and, depending on the mechanism of action, divided into depolarizing (succinylcholine) and non-depolarizing (mivacurium, atracurium, vecuronium, rocuronium, pancuronium) representatives. If necessary, their action can be reversed with the help of available antagonists, divided into anticholinergics (neostigmine, edrophonium and pyridostigmine) and cyclodextrins (Sugamadex). Anesthetic premedication includes drugs administered to the patient before the anesthetic, and is important for the preparation and optimization of conditions for the planned operation, and for the prevention of possible postoperative complications. Most such drugs are given to the patient about 60 minutes before the procedure. Opioid analgesics (fentanyl), anticholinergics (atropine) and benzodiazepines (midazolam) are used as part of preoperative preparation. On the other hand, antiemetics (metoclopramide), antibiotics (cephalosporins/vancomycin, clindamycin) and anticoagulants (heparin) are part of premedication responsible for the prevention of postoperative complications such as nausea and vomiting, infections and venous thromboembolism
Effect of alpha lipoic acid supplementation on plasma reducing capacity and activity of superoxide dismutase
No full textOksidativni stres se javlja zbog povećane količine reaktivnih kisikovih spojeva (ROS) ili
smanjenog kapaciteta enzimatskih i neenzimatskih antioksidativnih sustava. Alfa lipoična kiselina
je moćan antioksidans s trenutnom primjenom u terapiji dijabetičke polineuropatije. Brojna
istraživanja proučavaju utjecaj alfa lipoične kiseline na oksidativni stres i njenu potencijalnu
primjenu u terapiji raznih bolesti povezanih s oksidativnim stresom. Cilj ovog rada bio je ispitati
utjecaj suplementacije alfa lipoičnom kiselinom na ukupan antioksidativni kapacitet seruma, a s
obzirom na neke parametre životnog stila pacijentica (pretilost, pušenje, korištenje dodataka
prehrani i način prehrane). Antioksidativni status pacijentica određen je mjerenjem reduktivnog
potencijala plazme i mjerenjem aktivnosti superoksid dismutaze (SOD). Nije uočen značajni
utjecaj pušenja, korištenja dodataka prehrani, indeksa tjelesne mase niti načina prehrane na
aktivnost SOD. Podskupina pacijentica s najvišim unosom povrća (1.kvartil) imale su značajno
veći reduktivni potencijal plazme od ostalih pacijentica. Suplementacija sa 600mg alfa-lipoične
kiseline/dne kroz 3 mjeseca nije značajno utjecala na reduktivni potencijal plazme niti aktivnost
SOD u krvi ispitanica. Potrebno je provesti dodatna istraživanja s većim brojem ispitanika,
različitim biomarkerima oksidativnog stresa i različitim dozama alfa lipoične kiseline da bi se
utvrdio utjecaj suplementacije alfa lipoične kiseline na antioksidativni kapacitet.Oxidative stress may occur as a result of an increased amount of reactive oxygen species (ROS) or
reduced enzymatic or nonenzymatic antioxidant system capacity. Alpha lipoic acid is a potent
antioxidant, currently used in the treatment of diabetic polyneuropathy. Numerous trials are
examining the effect of alpha lipoic acid on oxidative stress and its potential application in the
treatment of various oxidative stress related diseases. The goal of this paper was to examine the
effect of alpha lipoic acid supplementation on total serum antioxidant capacity, in regard to
lifestyle parameters (obesity, smoking, diet and dietary supplements). Antioxidative status of the
patients was determined using ferric reducing ability of plasma assay and by measuring
superoxide dismutase activity (SOD). There was no significant observed effect of smoking, use of
dietary supplements, body mass index, or diet on SOD activity. The group of patients with the
highest vegetable consumption (1st quartile) showed significantly higher reducing ability of
plasma compared to other patients. 90 day 600mg/day alpha lipoic acid supplementation showed
no significant effect on reducing ability of plasma or SOD activity in the blood of the patients.
Additional research should be conducted using a larger number of participants, different oxidative
stress biomarkers and different doses of alpha lipoic acid to determine the effects of alpha lipoic
acid supplementation on antioxidant capacity
Depression among children and adolescents - challenges and therapeutic possibilities
No full textDepresija je vrlo čest mentalni poremećaj koji pogađa čitavu svjetsku populaciju, javlja se u
približno 5-6% odraslih osoba, a zabrinjavajuća činjenica jest da se javlja i u 2% dječje populacije
te 4-8% adolescenata. Cilj ovog diplomskog rada jest ukazati na ozbiljan društveni problem te na
važnost ranog kognitivno-bihevioralnog psihoterapijskog i farmakoterapijskog pristupa oboljelima.
Prilikom dijagnosticiranja depresije važno je razlikovati kliničko depresivno stanje od normalne
tuge i promjena raspoloženja. Nastanak i razvoj depresije nastoji se objasniti različitim biološkim
hipotezama, kao što su genska predispozicija, smanjena količina ili funkcija monoamina u
središnjem živčanom sustavu, smanjene razine glutamata i neurotrofnog čimbenika moždanog
podrijetla, stanje upale, hormonalni poremećaji, dok s druge strane postoje razne psihosocijalne
teorije poput psihodinamske, bihevioralne, kognitivne te humanističkog pristupa razvoju depresije.
Početno liječenje depresije, posebice blažeg oblika, u djece i adolescenata čini psihoedukacija uz
praćenje stanja pacijenta 6-8 tjedana prije samog liječenja antidepresivima ili psihoterapije. U
slučaju blage depresije, aktivna podrška i praćenje obiteljskih liječnika pokazala se kao važna
terapijska strategija, a između ostalog uključuje zakazivanje čestih kontrolnih posjeta. U slučaju
umjerene do teške depresije, uvodi se farmakoterapija i/ili psihoterapija. Prvu liniju antidepresiva
za primjenu kod djece i adolescenata predstavljaju selektivni inhibitori ponovne pohrane
serotonina, odnosno fluoksetin koji je jedini odobren od strane regulatornih agencija za lijekove,
dok je escitalopram odobren za primjenu u pedijatrijskoj populaciji starijoj od 12 godina.
Farmakokinetika lijekova zbog fizioloških posebnosti u dječjoj dobi je drugačija, što
podrazumijeva prilagodbu doze i intervala doziranja. Liječenje antidepresivima treba nastaviti i
nakon povlačenja simptoma u razdoblju od 6 do 12 mjeseci. Elektrokonvulzivna terapija
primjenjuje se kod teškog oblika depresije sa ili bez psihotičnih simptoma, i to nakon slabog ili
nikakvog odgovora na farmakoterapiju u kombinaciji sa psihoterapijom.
Depresija, čija prevalencija u dječjoj i adolescentskoj dobi kontinuirano raste, predstavlja sve veći
problem, kako oboljelima i njihovim skrbnicima, tako i svim dionicima uključenima u odgoj i
pružanje skrbi toj najosjetljivijom populaciji. Poseban izazov predstavlja terapija, gdje nedostaje
jasnih smjernica, što ukazuje na nužnost dobro dizajniranih kliničkih studija kako bi se osigurala
dugoročno učinnkoviti i sigurni terapijski pristupi temeljeni na dokazima.Depression is a very common mental disorder that affects the entire world population, it occurs in
approximately 5-6% of the adults, and the worrying fact is that it also occurs in 2% of the
children's population and 4-8% of the younger population. The aim of this thesis is to point out a
serious social problem and the importance of an early cognitive-behavioral psychotherapeutic and
pharmacotherapeutic approach. When diagnosing depression, it is important to distinguish a
clinically clear depressive state from normal sadness, and criteria for a depressive episode include
depressed mood, loss of interest and pleasure for at least 2 weeks, and changes from previous
functioning. The origin and development of depression is trying to be explained by different
biological hypotheses, such as genetic predisposition, reduced amount or function of monoamines,
reduced level of glutamate and brain-derived-neurotrophic factor, inflammatory state, hormonal
disorders, while on the other hand there are various psychosocial theories such as psychodynamic,
behavioral, cognitive and humanistic approach to the development of depression. The initial
treatment of depression among children and adolescents consists of psychoeducation, and it is
necessary to monitor the patient's condition for 6-8 weeks using validated scales before treatment
with antidepressants or psychotherapy. In the case of mild depression, active support and
monitoring by family doctors has proven to be an important therapeutic strategy, and among other
things, it includes scheduling frequent control visits. In the case of moderate to severe depression,
family doctors should consult with mental health services and then begin with antidepressant
therapy or psychotherapy. The first line of antidepressants for children and adolescents are
selective serotonin reuptake inhibitors, while tricyclic antidepressants should be removed from
therapy because they do not show sufficient effectiveness, and in addition, they cause serious sideeffects
that are fatal in case of overdose. Fluoxetine is the best choice for the treatment of
depression among children and adolescents because it is the only one approved by the FDA for this
use, while escitalopram is approved for use in the pediatric population older than 12 years. The
metabolism of drugs in children and adolescents differs from that in adults, it is increased in
children and adolescents, therefore withdrawal symptoms may occur and for this reason the dosage
should be adjusted. Treatment with antidepressants should be continued even after the withdrawal
of symptoms for a period of 6 to 12 months. The therapy should not be stopped suddenly, the dose
should be gradually reduced, otherwise a withdrawal syndrome could occur. Electroconvulsive
therapy is used in severe depression with or without psychotic symptoms, i.e. after a weak or no
response to pharmacotherapy in combination with psychotherapy.Depression, whose prevalence in
children and adolescents is continuously increasing, is a growing problem, both for sufferers and
their caregivers, as well as for all stakeholders involved in the education and provision of care to
this most sensitive population. A particular challenge is therapy, where there is a lack of clear
guidelines, which indicates the necessity of well-designed clinical studies to ensure long-term
effective and safe evidence-based therapeutic approaches
Purity and quality assessment of Dalmatian and continental immortelle macerate
No full textSmilje (Helichrysum italicum (Roth) G. Don) je tipična mediteranska biljka iz porodice Asteraceae koja zbog svojih ljekovitih svojstava ima dugogodišnju medicinsku i farmaceutsku primjenu. U ovom diplomskom radu izmjereni su kemijski (kiselinski broj) i fizikalni (relativna gustoća, indeks refrakcije) parametri, pH vrijednost i sadržaj eteričnog ulja macerata dalmatinskog i kontinentalnog smilja u maslinovom ulju (n=6) u svrhu ispitivanja čistoće i kvalitete macerata smilja. Izmjerena vrijednost kiselinskog broja iznosila je između 1,71 i 2,88 mg KOH/g, relativna gustoća iznosila je između 0,905 i 0,988, indeks refrakcije je bio između 1,4691 i 1,4743. Izmjerena pH vrijednost iznosila je između 4,40 i 5,25, a sadržaj eteričnog ulja je bio od <0,08 do 0,51 %. Dobivene vrijednosti uspoređene su s referentnim vrijednostima za eterično ulje smilja i maslinovo ulje budući da referentne vrijednosti za macerat smilja u maslinovom ulju nisu dostupne u literaturi. Dobiveni rezultati pokazuju da nema značajnih razlika između uzoraka macerata dalmatinskog i macerata kontinentalnog smilja. S obzirom na sve veću upotrebu pripravaka smilja u medicinske i kozmetičke svrhe, postoji potreba za definiranjem referentnih vrijednosti kemijskih i fizikalnih parametara za procjenu čistoće i kvalitete macerata smilja.Immortelle (Helichrysum italicum (Roth) G. Don), belonging to the family of Asteraceae, is a typically Mediterranean plant that has a long-lasting medicinal and pharmaceutical use. In this thesis, chemical (acid value) and physical (relative density, refractive indeks) parametres, pH value and essential oil content of Dalmatian and continental immortelle olive oil macerates were measured in order to investigate the purity and the quality of immortelle oil macerates. The measured acid value was between 1,71 i 2,88 mg KOH/g, the relative density was between 0,905 and 0,988, the refractive index was between 1,4691 and 1,4743. The measured pH value was between 4,40 and 5,25 and the essential oil content was from<0,08 to 0,51 %. The obtained values were compared with the reference values for immortelle essential oil and for olive oil because the reference values for immortelle olive oil macerate are not available in the literature. The obtained results showed that there are no significant differences between the samples of Dalmatian immortelle oil macerates and continental immortelle oil macerates. Considering the increasing use of immortelle preparations for medicinal and cosmetic purposes, there is a need to define the reference values of chemical and physical parameters to assess purity and quality of immortelle oil macerates
Klinička istraživanja djelotvornosti matične mliječi
No full textMatična mliječ je bijeložućkasti, viskozni žljezdani sekret pčela radilica (Apis mellifera L.) koji
primarno služi kao hrana za pčelinje ličinke i maticu. U tradicionalnoj medicini spominje se
već stoljećima te se zbog niza navodnih blagotvornih učinaka na ljudsko zdravlje danas
uvelike koristi kao funkcionalna hrana, dodatak prehrani ili kozmetički sastojak. Kao
najcijenjeniji pčelinji proizvod odlikuje se visokom nutritivnom vrijednošću i sadržajem
jedinstvenih bioaktivnih sastavnica, prvenstveno 10-hidroksi-2-decenske kiseline (10-HDA)
koja se zajedno s glavnim proteinima matične mliječi (engl. major royal jelly protein, MRJP)
te rojalizinom i apisinom smatra odgovornom za različite korisne biološke i farmakološke
učinke.
Ciljevi: Cilj ovog specijalističkog rada je dati sveobuhvatan pregled dosadašnjih znanstvenih
spoznaja o kliničkoj učinkovitosti matične mliječi u prevenciji i liječenju bolesti.
Materijali/pacijenti i metode: Istraživanja u okviru ovog specijalističkog rada teorijskog su
karaktera i obuhvaćaju pregled znanstvene literature o dosad provedenim kliničkim studijama
koje su uključivale primjenu matične mliječi. Pretražene su dostupne elektroničke
bibliografske baze podataka, kao što su PubMed (Medline), Embase, Current Contents
Connect, Cochrane Library i Google Scholar te baze registriranih kliničkih studija,
korištenjem ključnih riječi vezanih za temu rada. Prikupljeni relevantni znanstveni radovi
detaljno su proučeni s obzirom na definirani znanstveni problem, protokol istraživanja,
analizu rezultata i izvedene zaključke te su sistematično prikazani i kritički procijenjeni.
Rezultati: Ustanovljeno je postojanje većeg broja kliničkih studija među kojim su najbrojnije
randomizirane placebom kontrolirane studije koje su uključivale zdrave pojedince ili pacijente
s različitim zdravstvenim tegobama. Protutumorsko djelovanje, suzbijanje nuspojava
antitumorske terapije, pozitivan učinak kod osoba s dijabetesom, ali i pozitivni učinci na
metabolički sindrom, ženske tegobe, autoimune bolesti, benignu hiperplaziju prostate, neki
su od dokazanih kliničkih učinaka suplementacije matičnom mliječi.
Zaključak: Rezultati dosadašnjih nekliničkih i kliničkih studija ukazuju na značajan potencijal
primjene matične mliječi u prevenciji i terapiji niza zdravstvenih tegoba. Međutim,
jednoznačnih kliničkih dokaza o učinkovitosti još nema dovoljno, a razlog tome su
malobrojnost kliničkih ispitivanja, mali broj ispitanika i/ili nehomogenost dobivenih rezultata. S
obzirom na rastući globalni trend primjene prirodnih proizvoda u prevenciji i liječenju bolesti,
provedeni sustavni pregled dosadašnjih znanstvenih spoznaja o učinkovitosti matične mliječi
doprinosi usvajanju novih znanja i podizanju stručnih kompetencija nutricionista, farmaceuta,
liječnika i drugih zdravstvenih djelatnika u svrhu boljeg savjetovanja pacijenata te također
može biti koristan za usmjeravanje budućih kliničkih istraživanja.Royal jelly is a whitish-yellow, viscous glandular secretion of worker bees (Apis mellifera L.)
that primarily serves as food for honeybee larvae and queen bees. It has been well known in
traditional medicine for centuries, so owing to a number of alleged beneficial effects on
human health, it is today widely used as a functional food, dietary supplement or cosmetic
ingredient. Being the most valuable bee product, it is characterized by high nutritional value
and content of unique bioactive components, primarily 10-hydroxy-2-decenoic acid (10-HDA),
which together with the major royal jelly proteins (MRJP), royalisin and apisin are considered
to be responsible for various beneficial biological and pharmacological effects.
Objectives: The aim of this work is to provide a comprehensive overview of the current
scientific knowledge on the clinical effectiveness of royal jelly in the prevention and treatment
of diseases.
Material/Patients and Methods: The research within this work is of a theoretical nature and
includes a review of the scientific literature on clinical studies which included the use of royal
jelly. Available electronic bibliographic databases such as PubMed (Medline), Embase,
Current Contents Connect, Cochrane Library and Google Scholar, as well as databases of
registered clinical studies were searched using keywords related to the topic of the thesis.
The collected relevant scientific papers were studied in detail with regard to the defined
scientific problem, research protocol, analysis of results and derived conclusions, and are
systematically presented and critically evaluated.
Results: The existence of a large number of clinical studies was established, among which
the most numerous were randomized, placebo-controlled studies that included healthy
individuals or patients with various health conditions. Antitumor activity, suppression of side
effects of antitumor therapy, positive effect in patients with diabetes, metabolic syndrome,
and autoimmune diseases, but also positive effects on women health and benign prostatic
hyperplasia are some of the proven clinical effects of royal jelly supplementation.
Conclusion: The results of recent non-clinical and clinical studies indicate the significant
potential of using royal jelly in the prevention and therapy of a number of health problems.
However, there is still not enough unambiguous clinical evidence of effectiveness, and the
reason for this is the small number of clinical trials, the small number of participants and/or
the inhomogeneity of the results obtained. Taking into account the global growing trend of
using natural products in disease prevention and treatment, a systematic review of current
scientific knowledge on the effectiveness of royal jelly contributes to the adoption of new
knowledge and the raising of the professional competences of nutritionists, pharmacists,
doctors as well as other health professionals for the purpose of better patient counseling, and
also may be useful for direction of further clinical investigations