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Introduction: Breast cancer resistance protein (BCRP/ABCG2) is an efflux transporter important in pharmacokinetics of a number of drugs. We evaluated effect of a loss-of-function polymorphism ABCG2 c.421C>A on exposure to mycophenolic acid (MPA) in stable adult renal transplant recipients of Croatian origin. Materials and methods: Patients (n=68 ; 43 co-treated with cyclosporine, 25 with tacrolimus) were genotyped for ABCG2 c.421C>A and 11 polymorphisms in genes encoding enzymes and transporters implicated in MPA pharmacokinetics. Donors were genotyped for polymorphisms suggested to affect renal MPA secretion. ABCG2 c.421C>A variant vs. wild-type (wt) patients were matched in respect to demographic, biopharmaceutic and genetic variables (full optimal combined with exact matching) and compared for dose-adjusted steady-state MPA pharmacokinetics (Frequentist and Bayes [skeptical neutral prior] estimates of geometric means ratios, GMR). Results: Raw data (12 variant vs. 56 wt patients) indicated by around 40% higher total exposure (frequentist GMR=1.45, 95%CI 1.10-1.91 ; Bayes = 1.38, 95%CrI 1.07-1.81) and by around 30% lower total body clearance (frequentist GMR=0.66, 0.58-0.90 ; Bayes=0.71, 0.53-0.95) in variant carriers than in wt controls. The estimates were similar in matched data (11 variant vs. 43 wt patients): exposure GMR=1.41 (1.11-1.79) frequentist, 1.39 (1.15-1.81) Bayes, with 85.5% probability of GMR >1.20 ; clearance GMR=0.73 (0.58-0.93) frequentist, 0.71 (0.54-0.95) Bayes. Raw data indicated exposure difference in tacrolimus-treated but not in cyclosporine-treated patients (P for genotype-calcineurin type interaction 0.045 frequentist, 92.7% Bayes). Conclusions: Loss-off-function polymorphism ABCG2 c.421C>A increases steady-state exposure to MPA in stable renal transplant patients. The effect might be conditional on the type of calcineurin inhibitor.

Provedeno je ispitivanje mukoadhezivnog učinka medicinskog proizvoda namjenjenog za peroralnu primjenu klase II

Purpose: Comfrey (Symphytum officinale L) is a medicinal plant with a long tradition in the treatment of painful muscular and joint complaints. Propolis has been used since ancient times for the treatment of various conditions, such as wound healing treatment as one of them. The purpose of this study was to determine the efficacy of ointment containing comfrey and propolis in the treatment of mild acute sports injuries. Methods: This prospective cohort epidemiological study that included 144 participants of both genders, mean age 36.9±15.7 years, was conducted in the general practice setting in Osijek, Croatia, from April till September 2016. Participants were instructed to use tested ointment three times daily during three weeks. A specially designed questionnaire was used to collect demographic data and data concerning their sports injury symptoms and to evaluate the intensity of the latter data according to the scale defined in the research protocol. Results: The study showed statistically significant improvements in the intensity of pain of participants (Wilcoxon signed-rank test ; p

Mikofenolna kiselina (MPA) pokazuje varijabilnu farmakokinetiku (PK). Metabolizira se enzimima UGT u MPA-glukuronid koji podliježe enterohepatičkoj recirkulaciji. U izlučivanje putem žuči i bubrega uključen je i protein multirezistencije 2 (MRP2) kodiran genom ABCC2. Ispitali smo PK MPA u stanju ravnoteže u ispitanika s bubrežnim presatkom u odnosu na genotip ABCC2 donora i primatelja, uz druge kliničke kovarijable uključujući komedikaciju s ciklosporinom ili takrolimusom. Bolesnici (n=68, muškarci=53%, dob 15-72 godine) su dobivali mikofenolat-natrij, (EC-MPS) (n= 45, 2x720 mg/dan) ili mikofenolat mofetil (MMF) (n=23, 2x500 do 2x1000 mg/dan) i svi su dobivali ciklosporin (n=43) ili takrolimus (n= 25) te kortikosteroide. Uzorak krvi se uzimao tijekom jednog intervala doziranja (12 sati) u 0, 0.5, 1, 2, 3, 8, 12 h nakon jutarnje doze. MPA je analizirana metodom HPLC. Genotipizacija ABCC2 -24C>T i 1249G>A je provedena metodom PCR u stvarnom vremenu. PK parametri (ln- transformirani) su analizirani prilagodbom generalnog linearnog modela s neovisnim parametrima za dob, spol, indeks tjelesne mase, liječenje (EC-MPS ili MMF), vrstu kalcineurinskog inhibitora te genotip donora i primatelja (-24C>T i 1249G>A). S obzirom na genotip donora ABCC2: alel -24T je neovisno povezan s nižimom Cmin (omjer geometrijskih sredina, GMR=0.61, 90% CI 0.40-0.92), nižom ostatnom koncentracijom Co (GMR=0.54, 0.35- 0.83), nižom ostatnom koncentracijom C12 (GMR 0.61, 0.37-0.99) i većim oscilacijama koncentracija MPA (GMR=1.88, 1.09-3.23). S obzirom na genotip primatelja ABCC2: alel 1249A je neovisno povezan s nižom Cmin (GMR=0.55, 0.36-0.66), nižom ostatnom koncentracijom C12 (GMR=0.54, 0.32-0.90) i većim oscilacijama koncentracija MPA (GMR=1.85, 1.05- 3.28). Pacijenti liječeni ciklosporinom i koji su bili nositelji alela ABCC2 1249A (niska aktivnost), imali su za 30 % niži AUC MPA u odnosu na pacijenate liječene s takrolimusom, a koji su imali genotip visoke aktivnosti, ABCC2 1249GG. Kombinacija ciklosporina i varijantnih alela ABCC2 (-24T, 1249A) bila je povezana s Cmax/AUC, povišenima za 60%, odnosno 52%. Zaključujemo da je farmakokinetika MPA pod značajnim utjecajem polimorfizama ABCC2 donora i primatelja te ciklosporina u istodobnoj terapiji što može biti klinički značajno.

Matična mliječ je prirodni eliksir koji čuva zdravlje i vitalnost čovjeka. Od njezinih mnogobrojnih sastojaka izdvaja se 10-hidroksi-2-decenska kiselina (10-HDA), u prirodi prisutna samo u matičnoj mliječi. Ona ima važne biološke učinke od kojih se izdvajaju antibakterijsko, protuupalno i imunmodulatorsko djelovanje. Sadržaj 10-HDA određuje kvalitetu matične mliječi, njezinu učinkovitost kao i učinkovitost proizvoda u koji je ugrađena kao sastavna komponenta. Zbog netočnog deklariranja te čestog krivotvorenja, javila se potreba za sustavnom kontrolom proizvoda s matičnom mliječi, posebno dodataka prehrani i kozmetike. Cilj našeg rada bio je optimizirati HPLC metodu za određivanje 10-HDA kako bi se rutinski mogla vršiti kontrola kvalitete matične mliječi, kao sirovine i kao sastavne komponente u gotovim farmaceutskim i kozmetičkim proizvodima. Validirana HPLC metoda s DAD detektorom (Diode Array Detector) za kvantitativno određivanje 10-HDA provodila se na C18 koloni izokratnom eluacijom pri valnoj duljini 210 nm. Mobilna faza sastojala se od jednakih udjela metanola i vode zakiseljenih s ortofosfatnom kiselinom (w = 0, 5 %). Identifikacija se provodila usporedbom vremena zadržavanja i UV spektra uzorka i odgovarajućeg standarda 10-HDA. Uzorci za ispitivanje su otopljeni ili razjeđeni vodom što je posljedično imalo eluiranje komponenti topljivih u vodi i nesimetričnost pika 10-HDA. Dodatnim zakiseljavanjem mobilne faze do 0, 6 % potisnuta je ionizacija karboksilne skupine 10-HDA što je ravnotežu pomaklo prema stacionarnoj fazi čime je postignuto optimalno zadržavanje i dobra simetrija pika 10-HDA. Linearnost je zadržana u koncentracijskom rasponu od 0, 13–100 μg/mL(R > 0, 999) uz granica dokazivanja (LOD) 0, 048 μg/mL te granicu kvantifikacije (LOQ) 0, 145 μg/mL. Preciznost metode ispitana je dodatno kroz ponovljivost mjerenjem tri različite koncentracije unutar jednog dana (RSD < 0, 46 %), a srednja preciznost mjerenjem tri različite koncentracije tijekom tri dana (RSD < 1, 22 %). Točnost metode ispitana je analizom tri različita koncentracijska nivoa (analitički prinosi 98, 8—99, 6 %). Izdržljivost metode ispitana je promjenama valne duljine detekcije i temperature pri čemu su dobiveni zadovoljavajući rezultati. Zaključak: Optimizacija predočene HPLC metode pokazala se vrlo učinkovitom za rutinsko kvantitativno određivanje 10-HDA u matičnoj mliječi i različitim proizvodima koji je sadrže. Analitika je pokazala da neki proizvodi gdje je deklarirana svježa matična mliječ kao i neki kozmetički proizvodi ne sadarže 10-HDA što postavlja pitanje učinkovitosti, stabilnosti ili krive deklaracije proizvoda.

Uvod: Ciklosporin A (CSA) je imunosupresiv, ciklički peptid fungalnog porijekla, inhibitor je kalcineurina koji blokira aktivaciju i proliferaciju T-stanica sprječavajući otpuštanje interleukina-2. Praćenje koncentacije (TDM) ciklosporina u transplantiranih bolesnika važno je zbog njegove uske terapijske širine i značajne biološke varijabilnosti. Preniska koncentracija CSA može dovesti do odbacivanja transplantiranog organa, a previsoka koncentracija do pojave njegove toksičnosti. Cilj: Cilj istraživanja je bio usporediti CMIA (chemiluminescent microparticle immunoassay) i ECLIA (electrochemiluminescence immunoassay) metode dva različita proizvođača. Materijali i metode: Istraživanje je provedeno na 29 uzoraka pune krvi transplantiranih pacijenata na terapiji ciklosporinom. Koncentracije ciklosporina određene su CMIA i ACMIA metodom. Obje metode zahtijevaju ručnu pripremu uzorka. Usporedivost metoda učinjena je Passing- Bablok regresijskom analizom dok su razlike srednjih vrijednosti između ove dvije metode izračunate Bland-Altman analizom. Rezultati: Koeficijent korelacije između ove dvije metode iznosio je 0, 9907 (P0, 10). Passing - Bablok regresijska analiza dala je slijedeće rezultate: y= 14, 3080 + 0, 9481x (95 % CI za odsječak na osi y 8, 0451 do 23, 8713, 95% CI za koeficijent pravca 0, 8523 do 1, 0150). Na Bland- Altman prikazu razlika srednjih vrijednosti je iznosila -4, 9% (95% CI -11, 7034 do 1, 9179). Zaključak Uvidom u rezultate može se zaključiti da CMIA i ECLIA daju usporedive rezultate. Između ove dvije metode postoji konstantna razlika (odsječak na osi y), odnosno rezultati dobiveni CMIA metodom niži su oko -4, 9% od rezultata dobivenih ECLIA metodom.

Background. Mycophenolic acid (MPA) displays variable pharmacokinetics (PK). It is metabolized by UGTs to inactive 7-O-MPA-glucuronide (MPAG). MPA and MPAG are subject to enterohepatic recirculation. Biliary and kidney excretion of MPA/MPAG involves several transporters, including multidrug resistant protein-2 (MRP2) coded by polymorphic gene ABCC2. MRP2 serves as an efflux carrier of drug conjugates and many nonconjugated compounds in organs including intestine, liver and kidney. We assessed steady-state PK of MPA in renal allograft recipients in respect to donor and recipient ABCC2 genotypes. Patients and methods. Patients (n=68, men=36, age 15-72 years) were treated with mycophenolate sodium (MY) (n= 45, 2x720 mg/day) or mycophenolate mofetil (MMF) (n=23, 2x500 to 2x1000 mg/day), and all received cyclosporine (n=43) or tacrolimus (n= 25) and corticosteroids. Blood samples were taken during one dosing-interval (12 hrs) at 0, 0.5, 1, 2, 3, 8, and 12 h after the morning dose. PK parameters (ln- transformed) were analyzed by fitting generalized linear models with independents: age, sex, body mass index, treatment (MY or MMF), calcineurin inhibitor type, donor and recipient genotypes at two polymorphic loci (ABCC2 C-24T, G1249A). Results. Pharmacokinetic parameters for MPA are: Cmax, ss (ng/mL per mg dose) 16.08.7 ; Tmax, ss (hrs) 2 (0.2-12) ; AUC, ss (ng*h/mL per mg dose) 52.327.6 ; Cmin, ss (ng/mL per mg dose) 1.71.5 ; Trough 1 (time 0) (ng/mL per mg dose) 3.62.9 ; Trough 2 (time 12) 2.62.6. Regarding the donor ABCC2 genotypes: T- allele (C-24T) was independently associated with lower Cmin (geometric mean ratio, GMR=0.61, 90% CI 0.40-0.92), lower trough 1 (GMR=0.54, 0.35-0.83), lower trough 2 (GMR 0.61, 0.37-0.99) and greater MPA concentration oscillations (GMR=1.88, 1.09-3.23). Regarding the recipient genotypes: A-allele (G1249A) was independently associated with lower Cmin (GMR=0.55, 0.36-0.66), lower trough 2 (GMR=0.54, 0.32-0.90) and greater % swing (GMR=1.85, 1.05-3.28). Conclusion. The pharmacokinetics of MPA is affected by the donor and recipient ABCC2 polymorphisms.

In the first half of the 20th century, attempts at transplantation of organs were unsuccessful because there were no clear ideas about the processes of immune response. With the advances in immunology, immunosuppressive drugs were developed. Initially, it was thought that successful immunosuppression can be achieved only by achieving complete immunodeficiency. Today we are entering an era in which the aim of a standard combination therapy will be no more to suppress the immune system, but to modulate it. Eff ective, safe and cost-eff ective therapy requires dosage individualization based on therapeutic drug monitoring.

Uvod. Snažna biološka aktivnost propolisa potvrđena kroz njegov antiinflamatorni, antibakterijski, antifungalni, antivirusni i anestezirajući učinak opravdava njegovu upotrebu u različitim farmaceutskim oblicima svrstanim prema zakonskoj regulativi u kozmetiku s posebnom namjenom (1, 2). Isti prije stavljanja u promet podliježu registraciji pri Ministarstvu zdravstva i socijalne skrbi Republike Hrvatske koje izdajući rješenje o stavljanju u promet potvrđuje namjenu proizvoda (2). Cilj. Prikazati provjeru kvalitete propolisa kvantificiranjem aktivnih sastojaka. Potvrditi učinkovitost proizvoda na bazi propolisa (mast za ublažavanje simptoma hemoroida i mast namijenjena njezi kože sklonoj pojavi akna) kod ciljnih skupina korisnika. Materijali i metode. Farmakološki aktivni sastojci propolisa flavonoidi i fenolne kiseline izdvojeni su iz propolisa ekstrakcijom odgovarajućim otapalom. Metodom tekućinske kromatografije visoke djelotvornosti (HPLC) provedena je identifikacija i kvantifikacija kvercetina, naringenina, krizina, pinocembrina, galangina i kavene kiseline. Linearnost metode zadovoljavala je raspon od 6.25 – 100 µg/ml, a koeficijent korelacije za sve flavonoide bio je viši od 0, 9993. Od studenog 2008. do veljače 2009. godine te u razdoblju od prosinca 2010. do svibnja 2011. godine u Osijeku su provedene dvije prospektivne kohortne epidemiološke studije. U prvoj studiji sa 46 ispitanika oba spola, prosječne dobi 53.6±14.3 godina sa hemoroidalnim simptomima: krvarenje, napinjanje, bolnost i svrbež, ispitivana je učinkovitost masti na bazi propolisa u ublažavanju istih tijekom tri mjeseca. U drugoj studiji sa 20 ispitanika oba spola, prosječne dobi 22.0±6.1 (raspon 15-35) godina oboljelih od blagog oblika acne vulgaris, ispitivana je učinkovitost masti na bazi propolisa u njezi kože sklonoj pojavi akna. Svaki ispitanik praćen je mjesec dana. Rezultati mjerenja u ispitivanim ekstraktima propolisa te rezultati ispitivanja učinkovitosti odabranih kozmetičkih proizvoda na bazi propolisa dobiveni u epidemiološkim istraživanjima obrađeni su metodama deskriptivne statistike, a za statističku obradu podataka korišten je statistički softver SPSS za Windows, verzija 13.0 (SPSS Inc., Chicago, IL, USA). Rezultati. Mjerenja provedena u ekstraktima propolisa pokazala su različitu zastupljenost pojedinih flavonoida u rasponu od 0.1-10 mg/ml. To upućuje na veliku varijabilnost propolisa kao sirovine i potrebu određivanja minimalne koncentracije pojedinih flavonoida vezanu za učinkovitost. Istraživanje s ciljem potvrde učinkovitost masti na bazi propolisa za ublažavanje simptoma hemoroida pokazalo je značajno smanjenje ili potpuni nestanak ispitivanih simptoma bez prijave pogoršanja. Istraživanje s ciljem potvrde učinkovitost masti na bazi propolisa u njezi kože sklonoj pojavi akna pokazalo je kako se stanje kože lica u promatranom razdoblju poboljšalo kod 2/3 ispitanika bez prijave pogoršanja. Diskusija. Prema načelima dobre proizvođačke prakse provjerava se udio aktivnih sastojaka propolisa. Za sada nema propisa o minimalnim količinama flavonoida u propolisu. Svoje standarde kvalitete određuje zasebno svaki proizvođač garantirajući time učinkovitost proizvoda (3). Ostaje pitanje potvrde učinkovitosti gotovog proizvoda koji je napravljen s određenim sirovinama. Provedba epidemioloških istraživanja na ciljnim skupinama korisnika mogu osim potvrde učinkovitosti i definiranja namjene ukazati i na potrebu korekcije obzirom na količinu pojedinih djelatnih sastojaka u proizvodu. Zaključci. Propolis je sa svojim aktivnim sastojcima flavonoidima i fenolnim kiselinama najvećim dijelom odgovoran za djelotvornost masti na bazi propolisa svrstanih u kozmetiku s posebnom namjenom stoga je potrebno kontrolirati njegovu kvalitetu kao sirovine. Ispitivane masti su u tradicionalnoj primjeni pokazale učinkovitost u liječenju hemoroida i acne vulgaris, a epidemiološka istraživanja dodatno su potvrdila namjenu ispitivanih proizvoda iz skupine kozmetike s posebnom namjenom.

Since ancient times, propolis has been used as a traditional monastic, folk and natural medicine in many countries. In recent studies, a wide range of pharmacological properties were demonstrated for this substance, including antibacterial, antiviral, antifungal, anti-oxidant, antitumor, ad stringent and anti-inflammatory activity with the latter one been specially emphasized. Flavonoids and phenol acids in propolis represent main compounds responsible for its various curative effects. Acne vulgaris is one of the most common skin diseases. It affects all ages but mainly young people at the sensitive period of puberty. The origin of acne vulgaris is complex and incompletely understood. At least four pathophysiologic events take place within acne-infected hair follicles: androgen-mediated stimulation of sebaceous gland activity, abnormal keratinisation leading to follicular plugging (comedo formation), proliferation of the bacterium Propionibacterium acnes within the follicle, and inflammation. In addition to these four basic mechanisms, genetic factors, stress, and possibly diet may influence the development and severity of acne. Current treatments for acne include topical and oral antibiotics, topical and oral retinoids, topical benzoyl peroxide, topical azelaic acid, topical salicylic acid and hormonal therapy. All acne treatments have potential side effects, some of which may be severe. Therefore, there is a growing demand by patients for a fast, safe, and side-effect-free novel therapy. The aim of this study was to determine the efficiency of ointment that contains propolis tincture and sulfogirodal embedded in the proper grease base as a topical treatment for mild facial acne vulgaris. The prospective cohort epidemiological study will follow the group of patients suffering from mild facial acne vulgaris for one month. The patients will be instructed to use novel topical treatment based on propolis and the evaluation of their skin will be done using the Investigator's Global Assessment (IGA) acne severity scale at the beginning of the treatment, two and four weeks after the continuous treatment with propolis based ointment. Propolis extract embedded in this ointment is very effective with sebaceous gland secretion and with retrieving natural balance with young skin damaged by acne and blackheads. Sulfogirodal is a mild ceratolitic that enables „opening“ of sebaceous glands. Same as propolis, it has an anti-inflammatory effect, which helps with skin softening and faster healing of damaged skin parts. Based on all that the success of such treatment is expected for studied group of patients suffering from mild facial acne vulgaris.

Svrha rada: Propolis se od davnina koristio u tradicionalnoji i narodnoj medicini. Provedena istraživanja ukazala su na širok raspon njegovih farmakoloških učinaka, uključujući antibakterijsku, antivirusnu, antifungalnu, antioksidativnu, antitumorsku, adstringentnu i posebno antiupalnu djelotvornost. Amonij sulfogirodalat (smjesa amonijevih soli sulfonskih kiselina) je antiflogistik s keratolitičkim učinkom koji se prema starim, a i današnjim recepturama uspješno primjenjuje za tretiranje čireva (furunculi). Acne vulgaris predstavlja najčešću kroničnu upalnu bolest kože kod ljudi. To je bolest koja pogađa sve dobne skupine stanovništva, no uglavnom se javlja kod mlađih osoba u osjetljivom razdoblju puberteta. Etiologija acne vulgaris je kompleksna. Današnje liječenje akne može uključivati primjenu lokalnih i oralnih antibiotskih pripravaka, lokalnih i oralnih retinoidnih pripravaka, lokalnu primjenu steroida te liječenje hormonskim pripravcima. Svi ovi oblici liječenja akne imaju potencijalne nuspojave, od kojih neke mogu biti vrlo teške. Stoga postoje stalni i rastući zahtjevi pacijenata i struke za brzim i sigurnim novim načinom liječenja bez štetnih nuspojava. Cilj ovog istraživanja bio je utvrditi učinkovitost masti s ekstraktom propolisa i amonij sulfogirodalatom (Ichthammolum) u liječenju blagog oblika acne vulgaris na koži lica. Materijali i metode: Tijekom 2010. i 2011. godine na Odjelu za dermatovenerologiju Kliničkog bolničkog centra Osijek provedena je prospektivna kohortna epidemiološka studija. Studija je uključila šesnaest bolesnika koji pate od blagog oblika acne vulgaris na koži lica (numerička ocjena 2 prema ljestvici globalne procjene težine akne namijenjenoj za uporabu u kliničkim istraživanjima - IGA), pri čemu je svatko od njih bio praćen mjesec dana. Prosječna dob svih bolesnika bila je 23, 1±6, 5 godina (raspon 15 do 35 godina). Bilo je 31, 3 % (5/16) muškaraca i 68, 7 % (11/16) žena. Svi pacijenti uključeni u istraživanje dobili su detaljne upute za korištenje ovog novog lokalnog pripravka na bazi propolisa, a procjena stanja njihove kože učinjena je pomoću prethodno spomenute ocjenske ljestvice u tri navrata: na početku liječenja te dva i četiri tjedna nakon kontinuiranog liječenja s testiranim pripravkom. Rezultati: Preliminarni rezultati pokazali su kako je nakon četiri tjedna liječenja kod 62, 5 % (10/16) bolesnika došlo do značajnog poboljšanja stanja kože lica. Među njima bilo je 70, 0 % (7/10) bolesnika čiji je IGA rezultat nakon četiri tjedna liječenja bio 0, što znači kako je njihova koža lica bila potpuno normalna, čista bez prisustva akne. Kod niti jednog bolesnika uključenog u istraživanje nije zabilježeno pogoršanje stanja kože lica. Zaključak: Ekstrakt propolisa ugrađen u testirani pripravak svojim antibakterijskim i antiflogističkim učinkom uspješno pomaže u saniranju bakterijskih infekcija koje prate kožu lica zahvaćenu acne vulgaris pospješujući brže zacjeljivanje njezinih oštećenih dijelova. Amonij sulfogirodalat svojim keratolitičkim učinkom smanjuje i sprječava začepljenje dlačnih folikula. Preliminarni rezultati ovog istraživanja pokazali su kako je mast na bazi propolisa s amonij sulfogirodalatom, klasificirana u skupinu kozmetike s posebnom namjenom, uspješna kao oblik lokalnog liječenja kod ispitivane skupine bolesnika s blagim oblikom akne na koži lica.

Introduction: Haemorrhoid disease is a very common health problem. Initial therapy for chronic symptoms of this disease is conservative. This implies topical therapy with one of the commercially available ointments although no rigorous evidence exists to support the use of the topical therapies because of the lack of proper conducted scientific studies. Aim: The aim of this study was to determine the efficiency of propolis based ointment in relief and suppression of the haemorrhoid disease type I and II symptoms which include bleeding, pain, itching and straining of the haemorrhoidal veins and its efficiency in preventing the relapse of these symptoms. Materials and methods: This prospective cohort epidemiological study lasted from November 2008 until February 2009. The study included 46 participants of both genders, mean age 53.6±14.3 (range 23 – 80) years, suffering from the symptoms of the haemorrhoid disease type I or type II for which they had been treated by their chosen general practitioners in Osijek, Croatia. Specially designed questionnaire was used to collect anamnestic data (demographic and data concerning the haemorrhoid disease symptoms) and to evaluate the intensity of the later ones according to the scale defined in the research protocol. Each participant was monitored during three months and the evaluation of his or her symptoms was conducted on the day of his or her enrolment in the study (0 status), and 1, 2 and 3 months after the continuous therapy. Results: During the study period the large decrease in intensity or complete disappearance of analysed symptoms had occurred in all patients and none of the patients had reported the exacerbation or relapse of any of the symptoms. Discussion and conclusion: Ointment with propolis extract efficiently affected all the analysed symptoms of the haemorrhoid disease thus having very significant place within the conservative treatment of haemorrhoids.

Due to its scientifically confirmed biological activity, propolis became a component of numerous medical products. The Croatian legislative regulation still have not given guidelines for the propolis standardisation, but only the recommendations for the synchronization according to the guide that point out to the dry residue. In the EU declaration one can often observe propolis as a component, with its quality been additionally marked with the minimal content of flavonoid galangine. Our Firm concluded that spectrophotometric method with aluminium chloride is quite appropriate for the fast quantification of the flavonoids with the similar structure such as galangine and quercetin. Measurement has been done with the ethanol propolis extract solutions. High-pressure liquid chromatography (HPLC) is much more accurate method for the evaluation of the galangine quantity in the raw material or in the final product. HPLC system with the diode array detector (DAD) can perform accurate determination of several flavonoids simultaneously (galangine, pinocembrine, quercetin etc.). With use of this method one can faster processed the larger number of samples, and there is also a possibility of additional confirmation via characteristic up front recorded UV spectrums of individual flavonoids. In our measurements we have been comparing the dry residue of the various ethanol propolis extract solutions in relation with the galangine and quercetin quantities determined by the use of the spectrophotometric and HPLC analytical methods. The quantity of the dry residue was not in correlation with the values of galangine and quercetin determined by the use of the spectrophotometric and HPLC analytical methods. The values of galangine and quercetin obtained by the use of spectrophotometric analytical method were higher than those obtained by the use of HPLC analytical method which corresponds to a formation of complexes with aluminium chloride with the structurally similar flavones and flavonols. According to our studies, HPLC with DAD is better, more specific and more accurate technique for quantification of individual flavonoids and for the performing of the propolis standardisation towards one of the flavonoids as well.

Uporaba propolisa u humanoj medicini ima dugu tradiciju pri čemu se osobito ističe njegova višestruko dokazana protuupalna aktivnost. Cilj ovog istraživanja bio je utvrditi učinkovitost masti s ekstraktom propolisa (sadrži min.115 mg/kg galangina) u olakšavanju i suzbijanju simptoma hemoroidalne bolesti I i II stupnja (krvarenja, napinjanja, bolnosti i svrbeža) te njezinu učinkovitost u sprječavanju njihova ponovnog pojavljivanja. U istraživanje je bilo uključeno ukupno 46 ispitanika oba spola prosječne dobi 53.6±14.3 godina (raspon 23 do 80 godina). Među ispitanicima je bilo 52.2% (24/46) njih s hemoroidalnom bolesti I. stupnja te 47.8% (22/46) njih s hemoroidalnom bolesti II. stupnja, a svi su se oni liječili u ordinaciji svoga odabranog liječnika obiteljske medicine u Osijeku. Istraživanje je trajalo tri mjeseca (studeni 2008. - veljača 2009. godine). Posebno dizajniranim upitnikom od svakog su ispitanika dobiveni demografski podaci, podaci o vrsti posla kojeg obavlja, načinu prehrane te količini dnevno popijene vode, podaci o režimu pražnjenja crijeva te pridruženim bolestima i lijekovima koje uzima, kao i detaljni anamnestički podaci o dužini trajanja hemoroidalne bolesti, njezinom stupnju, zastupljenosti istih tegoba u krvnih srodnika te jačini svakog od 4 praćena simptoma (krvarenje, bol, svrbež, napinjanje). Opisani simptomi bili su praćeni tijekom 3 mjeseca, a njihova evaluacija kod svakog ispitanika vršena je na dan uključivanja u studiju (0 stanje), te 1, 2 i 3 mjeseca nakon kontinuirane uporabe masti (tj. stanje nakon 1, 2 i 3 mjeseca terapije). Istraživanje je pokazalo kako su se u promatranom razdoblju svi ispitivani simptomi kod svih ispitanika bitno smanjili ili pak potpuno nestali, a niti jedan ispitanik nije prijavio pogoršanje niti jednog od promatranih simptoma. Iz svega se može zaključiti kako je ispitivani pripravak, koji je prema zakonskoj regulativi svrstan u kozmetiku s posebnom namjenom (mast s ekstraktom propolisa), nadasve dobar terapijski izbor u promatranim kategorijama bolesnika s hemoroidalnom bolesti.

Introduction: Imatinib is a 2-phenylaminopyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. It is used in chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. Materials and Methods: The aim of this study was to develop and validate sensitive and specific high-perfomance liquid chromatography (HPLC) method for the determination of imatinib in serum/plasma. Imatinib was extracted from serum with methanol. Clozapine was used as an internal standard. The sample was fractionated on a column MN EC Nucleosil 100-5-C-18 EC 250 x 4.6 mm with a mobile system consisting of ammonium acetate buffer, methanol and acetonitrile (40:40:20). The flow rate was 0.75 ml min-1. Quantitation was performed by measurement of UV detector at the wavelength of 265 nm. Results: Calibration curve was linear in the range of 40 - 5000 ng/ml, limit of detection (LOD) was 13.1 ng/ml and limit of quantitation (LOQ) was 38.6 ng/m. Recovery ranged from 94.1% to 105.7%. Repeatability expressed as a coefficient of variation was 4.90% and 1.95% for 75 and 1500 ng/ml, respectively, and the coefficient of variation for intermediate precision was

Introduction: Haemorrhoids are symptomatic in approximately 4% of the general population and in the 50% of the people aged over 50 years. Initial therapy for chronic symptoms of the haemorrhoidal disease is conservative which implies topical therapy with one of the commercially available unguents. In this respect it should be highlighted that the use of propolis in human medicine has a very long tradition and today there are several proven beneficially activities of this compound on human health, such as its antibacterial, antiviral, antifungal, anticancerogenic, adstringent and anti-inflammatory activity, with the latter one been specially emphasized. The World Health Organization now considers propolis an important part of dietetics and a natural cure. Flavonoids in propolis represent main compounds responsible for its various curative effects. The aim of this study was to determine the efficiency of unguent with propolis extract (which contains minimally 115mg/kg of flavonoid galangin) in relief and suppression of the haemorrhoid disease type I and II symptoms which include bleeding, pain, itching and straining of the haemorrhoidal veins and its efficiency in preventing the relapse of these symptoms. Materials and methods: The prospective cohort epidemiological study lasted from November 1st, 2008 until February 28th, 2009 and included 46 participants of both genders with the mean age 53.6±14.3 (range 23 – 80) years which were suffering from the symptoms of the haemorrhoidal disease type I or type II for which they had been treated by their chosen general practitioners. During the enrolment of the participants in the study (first contact with their physician) they were asked to fill out the questionnaire providing us with the basic anamnestic data such as: age, gender, weight, height, additional illnesses, duration of their symptoms connected with the haemorrhoidal disease, the intensity of their symptoms connected with the haemorrhoidal disease (they have scored those in the scale from 0 to 3 with 0 meaning without symptoms, 1 mild symptoms, 2 moderate symptoms and 3 heavy symptoms), data on their general nutritional habits, data dealing with the features of their bowel movement (frequency of weekly bowel movement including the data on constipation or diarrhoea), presence or absence of family history of haemorrhoidal disease and the type of job that they are working (job during which they are mainly sitting down or standing or job during which they are moving around quite often). Each participant that had been included in the study was monitored during 3 months and the evaluation of his or her symptoms was conducted on the day of his or her enrolment in the study (0 status), and 1, 2 and 3 months after the continuous usage of tested unguent (status after 1, 2 or 3 months of continuous therapy). Results: During the study period the large decrease in intensity or complete disappearance of studied symptoms (bleeding, pain, itching and straining of the haemorrhoidal veins) has occurred in all patients and none of the patients has reported the exacerbation or relapse of any of the mentioned symptoms. In the end of the treatment with tested unguent there were 40 patients or 87.0% (40/46) of them that were completely without any of the four studied symptoms of haemorrhoidal disease. Conclusions: The tested product (unguent with propolis extract) efficiently affected all the studied symptoms of the haemorrhoidal disease thus presenting the highly efficient new approach in the conservative treatment of the haemorrhoids.

Introduction: A large number of antiepileptic’s are used to treat epilepsy. Therapeutic monitoring of this disorder is frequent and necessary due to considerable interindividual differences in drug concentrations and efficacy. Along with clinical and exogenous factors, genetic predispositions have been recognized as an important factor in therapy individualization and they take a prominent place in developing algorithms for the selection of the most appropriate drug and dose for each patient. Among pharmacogenetic markers, polymorphic transport proteins, which are responsible for drug transport across various barriers, offered themselves as significant factors of variability and bioavailability of different antiepileptic’s. Transporter proteins that play important role in pharmacokinetics are located in intestinal, renal and hepatic epithelial membranes. ABC transporters such as P-glycoprotein (ABCB1) affect bioavailability of their substrate drugs. The aims of the study were to evaluate the impact of polymorphisms of ABCB1 (C3435T, C1236T, G2677T/A) on antiepileptic drug disposition. We therefore correlated plasma levels of lamotrigine in mono- and polytherapy (carbamazepine, oxcarbazepine, levetiracetame, phenytoin, phenobarbiton, topiramate, valproate) with gene variants. Patients and Methods: A total of 222 epileptic patients, aged 16-76 years, were stratified into lamotrigine monotherapy group (n=58), a group receiving lamotrigine plus inductors (n=98), inhibitors (n=29) or both (n=37). ABCB1 genotyping (C3435T, C1236T, G2677T/A) was performed by Real-time PCR and PCR-RFLP. Therapeutic drug monitoring was performed by HPLC with diode array detector and immunoassay. Results: A statistically significant correlation was confirmed between lamotrigine concentration and additional drugs (p

Intensive animal production must remain an economically viable business and must also satisfy consumer demands in terms of food quality and safety. In the past, it has relied on antibiotics and other medications to solve many of these problems. Today there are increasing concerns about the development of bacteria resistant to antibiotics, which has led to a ban on their use as growth promoters in animal production within the EU. Nutritional solutions are now required for resolving these issues. Humans have been using propolis for a long time and much is known about its biological activity. Many different characteristics have been shown, such as antimicrobial, anti-inflammatory, antioxidant, immunostimulating and cytostatic. Nevertheless, studies on the nutritional benefits of propolis are still scarce, especially in sense of animal nutrition. It is well known that use of various immunostimulants, as dietary supplements, can improve the innate defence of animals providing resistance to pathogens during periods of high stress and to improve animal’s performance characteristics that are needed in order to obtain high productivity of animal production. Taking into account all of that it is logical to try incorporate propolis as a dietary supplement in modern domestic animals feeding protocols. Pilot studies made on chickens are encouraging because they showed that average weight gain, feed consumption and efficiency were significantly higher for propolis fed birds, which also had reduced mortality rates in comparison to control diet. This opportunity to improve animal production using the natural substances is important for all countries, especially for Croatia who is trying to become a member of EU and to become equal and concurrent in the global European and world market.

Propolis se koristi kao sirovłna za izradu proizvoda koji su zakonskim propisima svrstani u kategoriju dodataka prehrani i u kozmetiku s posebnom namjenom. Sastav propolisa je varijabilan, a ovisi o klimi, zemljopisnom položaju gdje se košnice nalaze, prevladavajućoj vegetaciji, kao i prisutnosti zagađivača okoline. Za farmakološki učinak propolisa odgovoran je sadržaj flavonoida te je njihovo odredivanje nužno kako bi se dobio kvalitetan proizvod. Farmaceutska literatura ne propisuje minimalne količine flavonoida koje bi podržavale očekivani učinak gotovog proizvoda. Tvrtka Apipharma d.o.o. razvila je kolorimetrijsku metodu s aluminijevim kloridom za rutinsko određivanje flavonola galangina i quercetina koji su redovito zastupljeni u propolisu hrvatskog porijekla. Odreden je minimalni postotak udjela ovih dviju komponenata koji opravdava zahtjeve kvalitete gotovog proizvoda prema upotrijebljenoj sirovini. Mjerenje se provodi na etanolnim iscrpinama propolisa i iz dobivenih vrijednosti se izračuna udio flavonoida u sirovini propolisa (min 3-5 % prema galanginu i quercetinu) koja ulazi u proizvodni proces.

A 40-year-old man was admitted to the emergency department after a suicide attempt. The patient was found at home unconscious, with an openbottle of antifreeze near him. The patient was in a coma on admission, but neurological examination excluded intracranial changes. Results of initial urine and serum toxicological screening tests were negative. Laboratory values indicated metabolic acidosis, leukocytosis, urinalysis revealed hematuria and unrecognized crystals. Osmolality and osmol gap were not determined on patient admission. Treatment with ethanol as an antidote and hemodialysis were started because of metabolic acidosis, anamnestic data and clinical status of the patient, and subsequently led to improvement of his condition. Further toxicological analyses of glycolic and oxalic acids in serum and urine samples were performed by ion-chromatography (IC) method and showed high values in spot urine and serum ultrafiltrate at admission, but during therapy the values progressively decreased. Treatment of poisoned patient for 3 weeks resulted in complete recovery. # 2007 Elsevier Ireland Ltd. All rights reserved.

Introduction: Gabapentin (Gabalept_, Katena_, Neurontin_) and vigabatrin (Sabril_) are chemical compounds that represent new-generation antiepileptic drugs. Gabapentin (GBP) has been designed as a structural analogue of GABA, and has been demonstrated to increase GABA concentration. The mechanism of action is related to events modulated through its interaction with a receptor thought to be associated with L-system amino acid carrier protein. Vigabatrin (VGB) is a synthetic GABA derivate. It is an enzyme-activated, irreversible inhibitor of GABA transaminase that resulted from a systematic search into possible ways of increasing GABAergic inhibition through interference with GABA metabolism. GBP and VGA are eliminated renally completely unchanged and the pharmacokinetic varability is more predictable. Material and Method: A simple method was developed for the routine clinical monitoring of the antiepileptic drugs GBP and VGB in the serum of patients with epilepsy using high- performance liqid chromatography (HPLC) with fluorescence detector set at λexc=235 nm and λem=435 nm. After protein precipitation with acetonitril compounds are pre-column derivatized by o-phthaldehyde (OPA). Separations were carried out at 28° C on Nucleodur C18 100-5 column (dp=5_m) from Macherey Nagel. The mobile phase was isocratic, consisting of 0.02 M phosphoric acid and acetonitril (45:55, v/v) with flow-rate 0.6 ml/min. Results: The method was fully validated and linear calibration curves were obtained in the concentration ranges from 21.9 to 146.0 _mol/L for GBP and 57.9 to 386.5 _g/ml for VGB. The limit of detection (LOD) was 0.047 _mol/L for GBP, and 1.724 _mol/L for VGB. The limit of quatitation (LOQ) was 0.123 _mol/L for GBP, and 3.718 _mol/L for VGB. The within-day precision expressed as relative standard deviations (RSD) for two different concentration levels (n = 10) were 10% for both compounds, and day-to-day RSD at two different concentration levels during 3 separate days were 5% for GBA, and 10 % for VGB. Conclusion: The described method was simple, fast, highly sensitive and reproducible, while endogenous compounds did not interfere with the assay. It was used for simultaneous analysis of both antepileptic drugs in therapeutic drug monitoring.

Introduction: Oxcarbazepine (Trileptal) is a keto-derivative of carbamazepine. It was developed by introducing minimal changes in the structure of carbamazepine, which altered the metabolism to avoid the production of epoxide metabolite. Oxcarbazepine is rapidly metabolized to a pharmacologically active monohydroxy metabolite (MDH ; 10-hydroxy-carbazepine, licarbazepine). 10-hydroxy-carbazepine has independent anticonvulsant properties and is mainly responsible for the effect of oxcarbazepine. The aim of this study was to develop and validate a HPLC method for measuring oxcarbazepine and 10-hydroxy-carbazepine simultaneously with other antiepileptics (lamotrigine, carbamazepine, phenobarbitone, phenytoin) which are already in routine use in our laboratory. Materials and Methods: Serum sample (250 _L) pretreatment was based on liquid extraction with ethylacetate/hexane, evaporated and desolved in 200 _L mobile phase. The separation was obtained on reverse-phase column (C18, 250X4, 6 mm I.D. 5_m) using a phosphate buffer/acetonitrile/methanol mixture (pH 6, 8) as a mobile phase, at the flow rate of 1.3 ml/min andDADdetector at 237nm ; total time for chromatographic separation was 13 min. Results: The calibration curves were linear for both analytes (r= 0.9975) in the expected therapeutic range. Intermediate precision (inter-day) expressed as relative standard deviations was less than 3% for 10-hydroxy-carbazepine and oxcarbazepine at two concentration levels. Accuracy, expressed as percent error, ranged from 94.5-103.8% for 10-hydroxycarbazepine and from 88-100% for oxcarbazepine. The limit of quantitation was 2.07 _mol/L for 10-hydroxy-carbazepine and 0.08 _mol/L for oxcarbazepine. Conclusion: Based of analytical parameters (linearity, precision, accuracy, limit of quantitation), the presented method is suitable for pharmacokinetic studies and therapeutic drug monitoring. The method shows good specificity with other prescribed drugs. While less pronounced than for carbamazepine, pharmacokinetic variability for oxcarbazepine was still considerable, and it can be affected by age, pregnancy, concurrent disease and drug-drug interaction. These characteristics suggest that therapeutic drug monitoring may be of value in treatments with oxcarbazepine.

Mycophenolate mofetil (MMF) is an immunosupressive drug used in prophylaxis of rejection of transplanted solid organs in combination with cyclosporine A (CyA) and steroids. It is metabolised in the liver to the active component mycophenolic acid (MPA), an irreversible noncompetitive inhibitor of cell enzime 5'-monophosphate (IMP)dehydrogenase. The aim of the study was...

Sve šira primjena propolisa u medicini, kozmetici i industriji hrane zahtijeva nove pristupe u kontroli kvalitete bilo da se radi o sirovini ili gotovom proizvodu. Propolis je prirodni proizvod koji ima varijabilan sastav ovisan o više faktora među kojima su i ekološki čimbenici. Zahtjevi kvalitete okreću se standardizaciji propolisa u odnosu na određene flavonoide, provjeru onečišćenja i određivanje roka valjanosti. Tekućinska kromatografija visoke djelotvornosti (HPLC) uz photodiode array detector (DAD) omogućuje brzu i jednostavnu kvantifikaciju slijedećih flavonoida: kvercetina, krizina, naringenina, pinocembrina i galangina te identifikaciju onečišćenja, ali i drugih sastavnica propolisa. Metoda omogućuje stabilne i reproducibilne uvjete te korištenje vlastite UV baze podataka ili specijalne HPLC-DAD baze podataka. Identifikacija navedenih flavonoida u analiziranim uzorcima propolisa i gotovim farmaceutskim oblicima koji ga sadrže, provedena je usporedbom s retencijskim vremenom i UV spektrom odgovarajućeg standarda. Za procjenu valjanosti metode određene su granice detekcije i kvantifikacije, a ispitana su reproducibilnost, točnost i linearnost u očekivanom rasponu. Svaki neometani kromatografski pik > 1 ng uz SI (similarity index) > 0, 999 mogao se nakon provedene analize usporediti sa spektrom iz knjižnice i na taj način identificirati pa su izbjegnute greške u nižem području kvantifikacije koje obično donose onečišćenja. Metoda se tako pokazala pouzdanom u probiranju sirovina, ali i praćenju stabilnosti preparata s propolisom. Preklopljeni spektri kvantificiranih flavonoida zapravo su „otisci prstiju“ djelatnih komponenti analiziranog uzorka bilo da se radi o propolisu kao sirovini ili proizvodu koji ga sadrži.

Propolis (pčelinja smola), prirodni je pčelinji proizvod. Od davnina se koristio u narodnoj medicini, a danas ima sve širu primjenu u području funkcionalne prehrane, veterine, kozmetike i medicine. Snažna biološka aktivnost propolisa potvrđuje se kroz njegov antibakterijski, antifungalni, antivirusni, anestezirajući, antiinflamatorni, antioksidativni, citostatički, imunostimulirajući i kroz druge učinake. Antibakterijsko djelovanje opravdava primjenu propolisa kao antiseptika. Flavonoidi i ostale aktivne komponente propolisa (derivati benzojeve i cimetne kiseline te cimetnog alkohola, seskviterpeni i dr.), dobro se ekstrahiraju u alkoholu, a alkoholni ekstrakt propolisa pokazuje snažan učinak na mnoge gram – pozitivne (Staphilococcus, Streptococcus, Bacillus, Corynebacterium), gram – negativne (Proteus, Salmonella, E.coli, Klebsiela, Schigella), neke anaerobne (Clostridium tetani, Clostridium perfringens) kao i neke penicilin rezistentne vrste bakterija. Glavni nosioci antibakterijskog djelovanja propolisa su flavonoidi, posebno pinocembrin i galangin. Antiseptičko djelovanje propolisa koji uz to ima i blagi anestezirajući efekat, opravdano je stoga uporabom njegovih alkoholnih ekstrakata koji su namijenjenji za deznfekciju manjih ozljeda kože i sluznice usne šupljine. Preparati u obliku krema, masti i losiona imaju blaži antiseptički učinak, ali zbog velike biološke aktivnosti propolisa mogu dodatno pomoći u različitim područjima terapijskih indikacija (gljivična oboljenja, upalne promjene).

Background and Purpose: Anticonvulsant drug phenytoin exhibits non linear pharmacokinetics with large interindividual differences. Phenytoin is a substrate of CYP2C9 and CYP2C19, and the P- glycoprotein encoded by the MDR1 gene. We assessed the polymorphisms of CYP2C9, CYP2C19 and MDR1, and their effects on the phenytoin disposition by evaluating the correlation of phenytoin (PHT) and phenytoin metabolic ratio (PMR) with polymo)phisms of CYP2C9, CYP2C19 and C3435T in the MDR1 gene. Materials and Methods: Sixty-four healthy volunteers were included in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were performed for the most frequent alleles: CYP2C9*1, *2, *3, CYP2C19*1*2, *3, and C3435T - MDR1. The 12h-serum concentrations after 300 mg oral dose of phenytoin were used for phenotype analysis. Phenytoin (PHT) and main metabolite (p-HPPH) were analyzed by HPLC. Results: The highest phenytoin serum concentrations (6.52 +/- 0.56 mg/L) were in subjects with CYP2C9*2/*2 plus CYP2C19*2/wt genotype and were significantly different from the lowest concentrations (3.95 +/- 0.83 mg/L) in subjects with wt/wt genotypes (p < 0.01). The highest PMR values (0.48 +/- 0.05) were noted in homozygous subjects for CYP2C9*wt plus CYP2C19*wt and the lowest PMR value (0.08) in homozygous subjects for defective alleles CYP2C9*2 plus CYP2C19*2 whereas heterozygous subjects had intermediate values (0.26 +/- 0.06) with the major role of polymorphic CYP2C9. Phenytoin serum levels and metabolic ratios were significantly different in subjects with MDR1 CC genotype from those in subjects with MDR1 TT genotype: p < 0.05. Conclusion: analysis of CYP2C9, CYP2C19 and MDR1 genotypes could have predictive value for phenytoin disposition in clinical practice.

Patients diagnosed with traumatic shock suffer from severe oxidative stress caused by disordered balance between free radicals and antioxidants. The aim of the study was to establish antioxidative ability (ImAnOx) in patients with traumatic shock, and to determine whether supplementation therapy with vitamins E and C lead to improved antioxidative ability in these patients. The first group of patients (N=20) was supplemented with vitamin E (300 IU i.m.) and vitamin C (1000 mg i.v.) once daily during seven days, whereas the second group (N=28) obtained no supplementation therapy. ImAnOx was determined by colorimetric test, Immuno Diagnostik Company, on admission to hospital and on days 1, 3, 7 and 15 of the hospital stay. There was a statistically significant difference on days 3, 7 and 15 (p < 0.0005) between mean ImAnOx concentration values of the two patient groups during the period of observation. Our findings support the conclusion that supplementation therapy with vitamins E and C resulted in enhanced antioxidative ability in patients with traumatic shock.

Prehlada i gripa su respiratorne virusne bolesti visoke učestalosti među populacijom te uzrokuju velike socijalno-ekonomskih probleme (izostanak s posla). Osim prevencije gripe (aktivnom imunizacijom), za smanjenje simptoma i trajanja prehlada i gripe, osim &#8220 ; klasičnih&#8221 ; lijekova kao npr. analgetika, antipiretika, dekongestiva, ekspektoransa i sl. na tržištu je prisutan veliki broj biljnih pripravaka koji se deklariraju kao imunomodulatori odnosno imunostimulansi. Prema Wagneru i Wiesenaueru (1995) pod biljnim imunomodulatorima smatraju se one biljne vrste odn. sastavnice koje za cilj imaju profilaksu i terapiju kroničnih (i recidivirajućih) miješanih infekcija (bakterijskih i virusnih) ; profilaksu oportunističkih infekcija kod rizičnih pacijenata ; pomoćnu terapiju kod primjene citostatika i antibiotika i posljedične imunosupresije, autoimunih bolesti i profilakse metastaza. U tu svrhu najupotrebljavanije su biljke: vrste roda Echinacea (E. purpurea, E. pallida, E. angustifolia) ; Eleuterococcus senticosus ; Eupatorium perfoliatum i E. cannabinum ; Baptisia tinctoria ; Viscum album ; Thuja officinalis ; Calendula officinalis ; Chamomilla recutita ; Achyrocline saturoioides ; Panax ginseng i dr.). Određene lipofilne i polarne sastavnice izolirane iz nadzemnih i podzemnih dijelova biljnih vrsta roda Echinacea pokazuju imunomodulirajući učinak in vitro i in vivo. Dugostoljetna etnobotanička iskustva uporabe ovih biljnih vrsta nisu ukazala na toksičnost niti na značajne nus-pojave, ali manjkaju znanstveno zabilježeni podaci o bioraspoloživosti, sinergizmu i potentnosti sastavnica s imunomodulatornim učincima kao i podaci o standardizaciji pripravaka i kliničke studije. Njemačka komisija &laquo ; E&raquo ; preporuča primjenu istještenog soka iz svježih (tek ubranih) nadzemnih dijelova vrste Echinacea purpurea (kao i pripravke u učinkovitoj dozi stabilizirane s etanolom) kao pomoćnu terapiju kod prehlade i gripe, kroničnih infekcija gornjih dišnih putova i donjeg urinarnog sustava teško zaraštavajućih rana i kroničnih čireva. Kod gripe se također preporuča korištenje pripravaka iz korijena vrste E. pallida.

Traumatic shock as an acute and general disorder in perfusion of all organ systems is related to oxidant /antioxidant imbalance. Vitamin E is the most effective lipid soluble antioxidant. The aim of this work was to investigate the level in which the use of antioxidative vitamins E and C decreased adverse effects of lipid peroxidation in traumatic shock. For this purpose, two groups of patients with traumatic shock aged 20-45 years were tested: 1) 10 patients administered the substitution of vitamin E (300 mg) and of C (1000 mg ) during the first 7 days after admission ; 2) 10 patients without substitution. The study was performed during four different periods: at admission, on day 3, on day 7, and on day 15 after admission. Vitamin E was determined by HPLC method using fluorescent detector. Vitamin E values were as follows: 1) 5.9, 5.6, 5.8, 8.6 ng/ml in group with substitution, 2) 5.7, 5.2, 4.7, 6.6 ng/ml in group without substitution. Vitamin E concentration was on day 15 increased by 30% in the group administered vitamin E and vitamin C, thus suggesting that vitamin E and vitamin C substitution might be justified in patients with traumatic shock.