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    Biljni ekstrakti i sekundarni metaboliti u tretmanu hiperpigmentacije kože

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    Cilj istraživanja Poremećaji pigmentacije kože sve su češći estetski problem. Zlatni standard terapije je dugo bio hidrokinon, ali se zbog njegovih nuspojava i dugoročne sigurnosti, intenzivno istražuju biljni ekstrakti i sekundarni metaboliti koji se u njima nalaze. Cilj rada je pregled i sistematizacija rezultata istraživanja biljnih ekstrakata i sekundarnih metabolita koji se koriste u pripravcima za terapiju hiperpigmentacije kože te procjena učinkovitosti i opravdanosti njihove primjene. Materijal / Ispitanici i metode Za potrebe pisanja pretražene su relevantne bibliografske baze podataka. Pretragom su obuhvaćeni izvorni znanstveni radovi, prvenstveno kliničke studije, koje su ispitivale terapiju hiperpigmentacije biljnim ekstraktima te biljnim sekundarnim metabolitima, a koje imaju dostupne cjelovite tekstove ili iznimno sažetke. Odabir znanstvenih radova je bio ograničen na one objavljene na engleskom jeziku. Radovi koji su odgovarali kriterijima bili su odabrani neovisno o datumu njihove objave. Rezultati Studije uključene u ovaj rad pokazale su da su biljni ekstrakti učinkoviti u terapiji hiperpigmetacije. U rad su uvrštene kliničke studije koje su ispitivale učinak aloe vere, indijskog ogrozda, sjemenki grožđa, biljne vrste Klasea quinquefolia, orhideje Brassocattleya marcella, peršina, primorskog bora, riže, sladića, štavelja i tratinčice, te sekundarnih metabolita poput aloesina, kojične kiseline, glabridina i β-arbutina. Među navedenim biljnim ekstraktima i sastavnicama najbolje su ispitani arbutin i kojična kiselina. Biljne opcije dovele su do smanjenja veličine i intenziteta hiperpigmentacijskih mrlja, uz djelotvornost koja se može usporediti s hidrokinonom, ali s manje nuspojava. Zaključak Biljni ekstrakti i sekundarni metaboliti obuhvaćeni ovim radom pokazali su značajan učinak u tretmanu hiperpigmentacija. Unatoč tomu, potrebna su dodatna ispitivanja uz dugoročno praćenje pacijenata i nakon prestanka upotrebe terapije, što će pridonijeti boljem uvidu u učinkovitost i sigurnost njihove primjene.Objectives Skin pigmentation disorders are an increasingly common aesthetic problem. The gold standard of therapy has long been hydroquinone, but due to its side effects and long-term safety, plant extracts and secondary metabolites are intensively investigated. The aim of this work is to review and systematize the results of research of plant extracts and secondary metabolites used in products for skin hyperpigmentation and to assess the effectiveness and justification of their application. Material and Methods For preparation of this work relevant bibliographic databases have been searched. The study included original scientific papers, primarily clinical trials, which examined the therapy of hyperpigmentation with herbal extracts and plant secondary metabolites. The studies with available full texts or exceptionally summaries were included. The selection of scientific papers was limited to those published in English. Papers that matched the criteria were selected regardless of the date of their publication. Results Studies included in this work have demonstrated that herbal extracts are effective in therapy of hyperpigmentation. Clinical studies done on Aloe vera, Indian gooseberry, grapevine seed, plant species Klasea quinquefolia, orchid Brassocattleya marcella, parsley, maritime pine, rice, licorice, amla and daisy, as well as secondary metabolites such as aloesin, kojic acid, glabridin and β-arbutin have been included. Among the aforementioned plant extracts and metabolites arbutin and kojic acid were included in the greatest number of studies. Herbal options have led to a decrease in the size and intensity of hyperpigmentation spots, with efficacy comparable to hydroquinon but with fewer side effects. Conclusions Herbal extracts and secondary metabolites have shown a significant effect in the treatment of hyperpigmentation. However, additional trials with long-term monitoring even cessation of therapy, are needed for better insight into their efficacy and safety

    Biological therapy in atopic dermatitis treatment

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    Biološka terapija novi je način liječenja umjerenog do teškog atopijskog dermatitisa. Terapija bi mogla značajno poboljšati kvalitetu života pacijentima kojima dostupna lokalna terapija ne pruža adekvatnu kontrolu bolesti. Također, sistemska terapija koja se koristi u liječenju, nosi značajan rizik nuspojava za bolesnike te se primjenjuje u ograničenom vremenskom razdoblju. Biološka terapija atopijskog dermatitisa tek je u svom usponu te je za sada odobren jedan lijek za tu indikaciju. Mnogi drugi lijekovi u raznim su fazama kliničkih ispitivanja i tek čekaju odobrenje. Ovi lijekovi mogli bi znatno pomoći pacijentima koji se bore s upalnom kožnom bolesti koja predstavlja velik teret njima, njihovim obiteljima te zdravstvenom sustavu i društvu u cjelini. Dodatno proučavanje etiologije bolesti i razvoj novih bioloških lijekova pomoći će u razumijevanju ove i sličnih bolesti. Farmaceut, kao dio zdravstvenog tima, može pomoći u podizanju svijesti o atopijskom dermatitisu te doprinijeti u optimizaciji, sigurnosti i učinkovitosti terapije te edukaciji pacijenata o značenju i ciljevima novog načina liječenja.Biological therapy is a new way of treating moderate-to-severe atopic dermatitis. Therapy could significantly improve the quality of life of patients for whom available local therapy does not provide adequate control of the disease. Furthermore, systemic therapy used in the treatment, brings great risk of side effects for the patients and is applied in limited period of time. Biological therapy of atopic dermatitis is still rising and only one drug has been approved for this indication so far. Many other drugs are at various stages of clinical trials and are still awaiting approval. These drugs could significantly help patients struggling with an inflammatory skin disease that is a major burden to them, their families, health system and the society at large. Further studies of the etiology of the disease and development of new biological agents will help in understanding this and similar diseases. Pharmacist, as the part of the health care team, could help raise awareness about atopic dermatitis, contribute to the optimization, safety and effectiveness of therapy and educate patients about the meaning and goals of the new way of treatment

    Determination of antioxidant activities of selected Salvia species

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    U okviru ovog diplomskog rada istraženi su prisutnost i antioksidacijski učinak fenolnih spojeva u metanolnim i etanolnim ekstraktima listova odabranih vrsta roda Salvia s područja Hrvatske (S. brachyodon, S. fruticosa, S.glutinosa, S. nemorosa, S. officinalis, S. pratensis, S. sclarea i S. verticillata). Primjenom metode tankoslojne kromatografije dokazana je prisutnost ružmarinske kiseline i luteolin-7-O-glukozida u listovima svih uzoraka. Kvercitrin je prisutan samo u vrsti S. verticillata, a rutin u vrstama S. brachyodon, S. fruticosa i S. officinalis. Antioksidacijski učinak etanolnih ekstrakata ispitan je pomoću tri spektrofotometrijske metode u usporedbi s troloksom i EDTA. Utvrđena je sposobnost hvatanja DPPH radikala (IC50: 3,88-7,93 μg/mL), redukcije iona željeza(III) ( IC50: 9,43- 18,36 μg/mL) te keliranja iona željeza(II) ( IC50: 163,55-1592,53μg/mL). Dobiveni rezultati pokazuju da istraživane biljne vrste sadrže flavonoide i fenolne kiseline koji doprinose njihovim antioksidacijskim učincima.The presence of phenolic compounds and their antioxidative effect in methanolic and ethanolic leaf extracts of selected species of the Salvia genus from Croatia (S. brachyodon, S. fruticosa, S.glutinosa, S. nemorosa, S. officinalis, S. pratensis, S. sclarea and S. verticillata) were studied in this diploma thesis. The presence of rosmarinic acid and luteolin-7-O-glucoside was detected by thin-layer chromatography in all leaf samples. Quercitrin was present only in the S. verticillata extract and rutin was detected in leaf extracts of S. brachyodon, S. fruticosa and S. officinalis. The antioxidative effects of ethanolic extracts were determined by using three spectrophotometric methods in comparison to trolox and EDTA. The abilities of scavenging DPPH radical (IC50: 3.88- 7.93 μg/mL), reduce ferric ions (IC50: 9.43-18.36 μg/mL) and chelate ferrous ions were determined. The obtained results have shown that the studied plant species contain flavonoids and phenolic acids which contribute to their antioxidative effects

    Development and nasal deposition optimisation of innovative pharmaceutical forms of corticosteroids

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    Nazalna primjena lijeka uobičajena je u liječenju lokalnih oboljenja nosne sluznice. Istražuje se i kao alternativni put sistemske primjene lijekova, a pruža mogućnost i izravne dostave lijeka u središnji živčani sustav. Ograničenja nazalne primjene lijeka uključuju otežanu dostavu lijeka u ciljno područje te mukocilijarni klirens koji skraćuje vrijeme kontakta lijeka i nosne sluznice. Nazalna primjena kortikosteroida česta je u liječenju bolesti nosne sluznice i paranazalnih sinusa, a u novije vrijeme predlaže se i u liječenju neuroupalnih procesa. U okviru ovog doktorskog rada, primjenjujući načela kakvoće utemeljene kroz dizajn, razvijena su tri inovativna in situ gelirajuća sustava s uklopljenim kortikosteroidom za nazalnu primjenu u obliku spreja: (i) in situ gelirajuća mikrosuspenzija flutikazonpropionata (FP-a), (ii) in situ gelirajuća nanosuspenzija FP-a pripravljena uz vlažno mljevenje te (iii) praškasti sustav mikrosfera s natrijevim deksametazonfosfatom (NDF-om) i inertnog nosača. Provedena je njihova temeljita fizičko-kemijska i biofarmaceutska karakterizacija. Polimerni sastav in situ gelirajućih mikro- i nanosuspenzija FP-a osigurao je pseudoplastično ponašanje, prikladnost za primjenu raspršivanjem (tj. prikladnu veličinu raspršenih kapljica i kut raspršenja) te svojstvo geliranja u kontaktu sa simuliranim nosnim fluidom (SNF). Mikrosfere s NDF-om, pripravljene sušenjem raspršivanjem, karakterizirane su velikom uspješnošću uklapanja lijeka, odgovarajućim sadržajem ostatne vlage te sposobnošću bubrenja u SNF-u pri čemu nastaje gel. Smjese mikrosfera s NDF-om i inertnog nosača bile su homogene te boljih svojstava tečenja i užeg kuta raspršenja od samih mikrosfera. Postignuta je uspješna depozicija sva tri farmaceutska oblika u ciljnoj regiji nosne šupljine, ovisno o željenom učinku. Razvijeni farmaceutski oblici karakterizirani su boljom mukoadhezivnošću u usporedbi s konvencionalnim oblicima. Oslobađanje lijeka iz svih razvijenih oblika bilo je prikladno za nazalnu primjenu. Nanonizacija FP-a rezultirala je većom mukoadhezivnošću formulacije te većom topljivošću i brzinom oslobađanja FP-a iz in situ gela, pružajući mogućnost smanjenja primijenjene doze. Svim sustavima potvrđena je biokompatibilnost in vitro na modelu Calu-3 stanica te fizičko-kemijska stabilnost. Praškasti sustav s NDF-om pokazao je potencijal poboljšanja permeacije lijeka kroz nazalni epitel. Prilagođavanjem procesnih, formulacijskih i/ili parametara primjene korištenjem dizajna eksperimenta razvijeni su inovativni farmaceutski oblici kortikosteroida s potencijalom produljenog zadržavanja na mjestu primjene, povoljnih biofarmaceutskih svojstava i optimirane depozicije u nosnoj šupljini.Nasal drug delivery is well estabilshed in the treatment of local nasal mucosa diseases. It is also being investigated as an alternative route of systemic drug delivery, as well as the possibility of direct drug delivery to the central nervous system. Limitations of nasal drug administration include difficult drug delivery to the target area and mucociliary clearance, which shortens the contact time between the drug and the nasal mucosa. Nasal use of corticosteroids is common in the treatment of diseases of the nasal mucosa and paranasal sinuse. Recently it has been suggested in the treatment of neuroinflammatory processes. Within this doctoral thesis, employing quality by design principles, three innovative in situ gelling pharmaceutical forms of corticosteroid for nasal spray application have been developed: (i) in situ gelling microsuspension of fluticasone propionate (FP), (ii) in situ gelling nanosuspension of FP prepared by wet media milling; and (iii) powder platform consisting of dexamethasone sodium phosphate (DSP)-loaded microspheres blended with an inert carrier. Thorough physicochemical and biopharmaceutical characterization of developed systems was performed. The polymer composition of the in situ gelling micro- and nanosuspensions of FP ensured shear thinning behavior, suitability for administration as a spray (i.e., suitable droplet size and spray angle), and immediate gelling in contact with simulated nasal fluid (SNF). Microspheres with DSP, prepared by spray drying, are characterized by high drug entrapment efficiency, adequate residual moisture content, and good swelling ability in SNF, forming a gel. Blends of microspheres with DSP and inert carrier were homogeneous and had better flow properties and a narrower spray cone angle than the microspheres alone. Successful deposition of all three pharmaceutical forms in the target region of the nasal cavity model was achieved, depending on the desired effect. Developed pharmaceutical forms are characterized by better mucoadhesiveness compared to conventional forms. Drug release from all developed forms was suitable for nasal administration. Nanonization of FP resulted in greater mucoadhesiveness of the formulation and increased solubility and release rate of FP from the in situ gel, providing the possibility of reducing the applied dose. Biocompatibility on the in vitro Calu-3 cell model and the physicochemical stability was confirmed for all developed formulations. The powder system with DSP showed the potential to improve drug permeation through the nasal epithelium. By varying process, formulation and/or administration parameters, employing design of experiments, innovative pharmaceutical forms of corticosteroids with the potential for prolonged retention at the site of administration, favourable biopharmaceutical properties and optimized deposition in the nasal cavity have been successfully developed

    Hepatotoxicity of dietary supplements and herbal extracts

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    Hepatotoksičnost dodataka prehrani je sverastući zdravstveni problem. Zbog manjka regulacije i standardizacije u proizvodnji, uz širokodostupnost pripravaka, zdravstveni radnici moraju biti na oprezu prilikom preporuke ovakvih proizvoda. Jetra je glavni organ metabolizma ksenobiotika te je kao takva sklona oštećenjima različitim mehanizmima stoga je ključno poznavati laboratorijske parametre i kliničke simptome oštećenja jetre kako bi se pacijente znalo pravovremeno upozoriti na mogućnost hepatotoksičnog djelovanja pripravka. Uz nekoliko analiziranih pripravaka koji su dostupni u Republici Hrvatskoj poput suplemenata koji sadrže ekstrakt crvene riže ili zelenog čaja, u radu je anketirano 105 studenata Farmaceutsko-biokemijskog fakulteta Sveučilišta u Zagrebu u vezi procjene njihovih znanja i stavova o hepatotoksičnosti dodataka prehrani i biljnih ekstrakata. Najveći broj studenata nije bio upoznat ili je nedovoljno upoznat s utjecajem biljnih pripravaka na jetru te smatra da se mora dodatno educirati i povećati oprez prilikom preporuke i/ili korištenja istih. Ono što i dalje ostaje problem je slaba dokazivost uzročno-posljedične veze između pripravaka i njihovih utjecaja na jetru zbog prisutnosti politerapije te ostalih rizičnih čimbenika u etiologiji oštećenja jetre. Iako ne postoje direktni i konačni zaključci o kompletnom utjecaju obrađenih pripravaka na jetru, potreban je dodatni oprez kako bi se rizik od štetnog utjecaja na jetru smanjio te odabrao pravi pripravak za pojedinog pacijenta kao temelj personalizirane medicine čemu moderna struka, uključujući i medicinu temeljena na dokazima, teže.Hepatotoxicity of dietary supplements is a growing health problem. Due to the lack of regulation and standardization in production, together with the wide availability of products, health professionals must be careful when recommending such supplements. Liver is the main organ of xenobiotic metabolism and as such is prone to damage by various mechanisms. Therefore, it is crucial to know the laboratory parameters and clinical symptoms of liver damage so that the patients could be warned in time about the possible hepatotoxic side effects. In addition to several analyzed supplements available in the Republic of Croatia, such as ones containing red rice extract or green tea extracts, a total of 105 students of the Faculty of Pharmacy and Biochemistry of the University of Zagreb were interviewed to assess their knowledge and attitudes regarding hepatotoxicity of dietary supplements and plant extracts. Most students were not familiar or were insufficiently familiar with the effect of herbal preparations on the liver and believe that additional education should be provided with increased caution when recommending and / or using these supplements. What remains a problem is the poor provability of a cause-and-effect relationship between preparations and their effects on the liver due to the presence of polytherapy and other risk factors in the etiology of liver damage. Although there are currently no direct and definitive conclusions about the complete impact of treated supplements on the liver, extra caution is needed to reduce the risk of adverse effects on the liver and choose the right product for the right patient as the end goal of evidence-based medicine

    Separation of α-1 glycoprotein forms using low pressure anion exchange chromatography

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    Cilj ovog rada bio je odijeliti frakcije AGP-a različitih izoelektričnih točaka anionsko izmjenjivačkom kromatografijom. AGP je protein plazme čije su različite forme zabilježene kako u peptidnom tako i u glikanskom dijelu. Različite glikoforme i genske varijante AGP-a pokazuju različita fizikalno-kemijska svojstva, a jedno od tih svojstava je i pI molekule što otvara mogućnost analize AGP-a kromatofokusiranjem. Korištena metoda, kromatofokusiranje, bazirana je na stvaranju ionskih veza između nabijenih grupa biomolekula i ionsko-izmjenjivačkog gela/nosača koji nosi suprotan naboj. Promjenom pH otopine dolazi do promjene u naboju biomolekule te u njezinoj eluaciji s kolone. Zbog različitih izoelektričnih točaka formi, različit pH otopine će uzrokovati promjenu naboja u biomolekuli te forme što se očituje različitim retencijskim vremenom. Nativna (sijalinizirana) forma AGP-a je analizirana tri puta anionsko izmjenjivačkom kromatografijom, koristeći jednu, tri i pet kolona dok je AGP koji je prethodno desijaliniziran, analiziran anionsko izmjenjivačkom kromatografijom koristeći pet kolona. Rezultati analize su grafički prikazani koristeći Excel program, prikazujući ovisnost pH otopine i apsorbancije uzroka o volumenu otopine. Iz grafičkog prikaza je vidljivo da su korištenjem metode nepotpuno odijeljene dvije frakcije AGP-a različitih izoelektričnih točaka dok se povećanjem korištenih kolona, povećala razlučivost metode.The goal of this work was to separate fractions of AGP by using anion exchange chromatography. AGP is a plasma protein with different forms in its peptide and glycan portion of molecule. Different glycoforms and genetic variants of AGP have different physico-chemical properties. pI as one of those properties enables separation of AGP forms by using the chromatofocusing technique. Chromatofocusing is based on the formation of ionic bonds between charged groups of the biomolecule and ion-exchange gel/carrier carrying opposite charge. Changing the pH of the solution, causes the change of the molecule charge and its elution of the column. Due to the different isoelectric points of the forms, different values of pH in the solution change charge of the molecule, which leads to forms having different retention times at column. Native (sialylated) form of AGP was analized by using one, three or five columns in a row of anion exchange chromatography while AGP that was previously desialylated was analyzed using anion exchange chromatography only with five columns in a row. Results show the relation between pH or absorbance of the sample and volume of the solution. It can be concluded that two forms of AGP with different isoelectric points were separated, but not completely. Using a higher number of columns increased separation

    Effect of vitamin D on nutritional and functional status in patients with chronic graft versus host disease (cGVHD) after allogeneic stem cell transplantation

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    Kronična reakcija davatelja protiv primatelja (cGVHD) osnovni je uzrok kasnog morbiditeta i mortaliteta nakon alogenične transplantacije krvotvornih matičnih stanica (alo-TKMS). Režim kondicioniranja, imunosupresivna terapija te komplikacije cGVHD-a mogu negativno utjecati na status vitamina D, kao i na nutritivni i funkcionalni status bolesnika. Ovo je prvo prospektivno istraživanje utjecaja nadomjesne terapije vitaminom D na nutritivni i funkcionalni status alo-TKMS ispitanika, kao i na karakteristike cGVHD-a. U istraživanje su bila uključena ukupno 102 alo-TKMS bolesnika (spol: 54 M i 48 Ž; dob 50 (39-59)), od kojih je bilo 65 cGVHD i 37 kontrolnih bolesnika koji nisu razvili cGVHD. Svim ispitanicima je na prvom i kontrolnom pregledu određen nutritivni i funkcionalni status, status vitamina D i ostali laboratorijski parametri te im je, ovisno o inicijalnim serumskim vrijednostima, propisana nadomjesna terapija vitaminom D. Rezultati ovog istraživanja pokazali su da je malnutricija, prema subjektivnoj globalnoj procjeni bolesnika (PG-SGA), prisutna u oko 40 %, narušenost funkcionalnog statusa prema snazi stiska šake (HGS) i PG-SGA procjeni u oko 50 %, a nedostatak (<50 nmol/L) i manjak vitamina D (<75 nmol/L) kod oko 50 i 30 % ispitanika bez obzira na prisutnost cGVHD-a. U istraživanju je nađena snažna povezanost nutritivnog i funkcionalnog statusa (P<0,0005). Niski HGS (30,2 % cGVHD, 10,8 % kontrole) i blagi gubitak mišićne mase kod ispitanika ukazuju na povišen rizik za razvoj sarkopenije. Zahvaćenost probavnog sustava cGVHD-om bio je čimbenik rizika umjerene i teške malnutricije prema PG-SGA-u (B+C), a malnutricija, prisutnost cGVHD-a, zahvaćenost probavnog sustava, jetre i pluća cGVHD-om čimbenici rizika niskog HGS-a. Nije pronađena povezanost serumskih vrijednosti vitamina D s nutritivnim i funkcionalnim statusom, kao ni s njihovom promjenom nakon nadomjesne terapije vitaminom D. Ispitanici koji su primali najvišu dozu nadomjesne terapije vitaminom D (2000 IU) imali su i najveću promjenu njegovih serumskih vrijednosti. Niske vrijednosti vitamina D bile su povezane s cGVHD-om jetre (P<0,05). Čimbenik rizika nedostatka vitamina D kod svih ispitanika bilo je mijeloablativno kondicioniranje, a kod cGVHD bolesnika aktivnost bolesti. Rezultati pokazuju da alo-TKMS bolesnici, neovisno o prisutnosti cGVHD-a, imaju narušen nutritivni i funkcionalni status, kao i nedostatak vitamina D, ne samo u prvim mjesecima nakon alo-TKMS-a nego i godinama nakon toga. Nadomjesna terapija vitaminom D utjecala je na oporavak serumskih vrijednosti, ali ne i na promjenu mišićne mase i snage.Chronic graft versus host disease (cGVHD) is the underlying cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Conditioning regimen, immunosuppressive therapy, and complications of cGVHD may affect vitamin D status as well as the nutritional and functional status of patients. This is the first prospective study of the impact of vitamin D replacement therapy on the nutritional and functional status of allo-TKMS subjects as well as on the characteristics of cGVHD. A total of 102 allo-HSCT patients (gender: 54 M and 48 F; age 50 (39- 59)) were included in the study, of whom 65 were cGVHD and 37 were control patients. In all participants, nutritional and functional status, vitamin D levels and other laboratory parameters were assessed at the first and control examinations, and depending on the initial serum values, they were prescribed vitamin D replacement therapy.The results of this study showed an incidence of malnutrition aassessed with patient generated subjective global assessment (PG-SGA) in about 40%, impaired functional status assessed with hand grip strength (HGS) and PG-SGA in about 50% and vitamin D deficiency (<50nmol / L) in about 50% and insuficiency (<75nmol / L) in about 30% of all subjects regardless of the presence of cGVHD. A strong correlation between nutritional and functional status was found in the study (P <0.0005). Low HGS (30.2% cGVHD, 10.8% control) and mild loss of muscle mass in out participants indicate an increased risk of developing sarcopenia. Gastrointestinal cGVHD was a risk factor for moderate and severe malnutrition as assessed by PG-SGA (B + C) and malnutrition, cGVHD and cGVHD of the digestive system, liver, and lungs risk factors for low muscle strength. were. We did not find an association of serum vitamin D values with nutritional and functional status or with their change after vitamin D supplementation. The most significant change in serum vitamin D values was present in patients receiving the highest dose of vitamin D supplementation (2000IU). In cGVHD patients, low vitamin D levels were associated with liver cGVHD (P <0.05). Risk factors for vitamin D deficiency in all subjects was myeloablative conditioning, and in cGVHD patients, disease activity. Our results showed that allo-HSCT patients, regardless of the presence of cGVHD, have impaired nutritional and functional status as well as vitamin D deficiency not only in the first months but also in the years after allo-HSCT. Vitamin D supplementation affected the recovery of vitamin D serum values, but not the change in muscle mass and strength

    Odabrani nusproizvodi biljnoga podrijetla kao kozmeceutici

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    Cilj istraživanja: Nusproizvodi vinarstva, proizvodnje maslinova ulja i prerade agruma zbog svojega sastava i mogućnosti ekstrakcije posjeduju potencijal za primjenu u kozmetičkoj industriji. Cilj ovog istraživanja je provesti detaljnu pretragu literature o zabilježenim djelovanjima njihovih ekstrakata na kožu samostalno, ili u sklopu kozmetičkih formulacija. Materijali i metode: Za potrebe pisanja specijalističkog rada pretražene su elektroničke baze ScienceDirect i PubMed. Pregledane su sve publikacije koje su se pojavile kao rezultat pretrage s dostupnim cjelovitim tekstovima, ili u iznimnim slučajevima sažecima. Odabir je ograničen na izvorne radove objavljene na engleskom jeziku s istraženim djelovanjem ekstrakata nusproizvoda na kožu i mehanizme povezane s tim učinkom. Rezultati: Radom su obuhvaćene 52 publikacije, od čega 22 za nusproizvode vinarstva, 18 za nusproizvode proizvodnje maslinova ulja te 12 za nusproizvode prerade agruma. Navedena istraživanja sistematično su obrađena na temelju zabilježenih učinaka. Nusproizvodi vinarstva i proizvodnje maslinova ulja pokazali su anti-aging, antimikrobno i protuupalno djelovanje te djelovanje na zacjeljivanje rana, melanogenezu i povećanje učinkovitosti pripravaka UV zaštite. Komina grožđa, uključujući peteljke, najbolje je istražen dio nusproizvoda vinarstva. Ekstrakti lista masline najbolje su istražen dio nusproizvoda proizvodnje maslinova ulja. Nusproizvodi prerade agruma pokazali su anti-aging, antimikrobno i protuupalno djelovanje te djelovanje na zacjeljivanje rana, melanogenezu i aktivaciju TRPA-1. Ekstrakti lišća različitih vrsta agruma najbolje su istražen dio nusproizvoda prerade agruma. Zaključak: Sve tri vrste nusproizvoda pokazuju potencijal za primjenu u kozmetici kao sastavnice proizvoda različitih namjena. Izražena je potreba za optimiranjem ekstrakcijskih postupaka s fokusom na pojedine skupine bioaktivnih molekula uzimajući u obzir i sinergijske učinke, kao i za istraživanjem optimalnih oblika dostave koji bi rezultirali maksimalnim iskorištenjem povoljnih djelovanja. Također, nužan je veći broj kliničkih studija s primjenom formuliranih pripravaka s većim brojem ispitanika budući da su brojna djelovanja potvrđena primjenom samostalnih ekstrakata, te in-vitro.Objective of the research: By-products of winemaking, olive oil production and citrus processing, due to their composition and well researched extraction possibilities, have the potential for use in the cosmetic industry. The aim of this research is to conduct a detailed literature review on the effects of these by-products' extracts on their own or as a part of cosmetic formulations. Materials and methods: For the purposes of writing this research, the electronic databases ScienceDirect and PubMed were searched. All publications that appeared as a result of the search with available full texts, or in exceptional cases abstracts, were reviewed. The selection was limited to original papers published in English with the investigated effect of by-product extracts on skin and skin-related mechanisms. Results: The paper includes 52 publications, 22 of which are for by-products of winemaking, 18 for by-products of olive oil production and 12 for by-products of citrus processing. These studies have been systematically processed based on the recorded effects. By-products of winemaking and olive oil production have shown anti-aging, antimicrobial and anti-inflammatory effects, as well as effects on wound healing, melanogenesis and increasing the effectiveness of UV protection preparations. Grape pomace, including stalks, is the best researched part of winemaking by-products. Olive leaf extracts are the best researched part of the by-products of olive oil production. Citrus by-products have shown anti-aging, antimicrobial and anti-inflammatory effects, as well as effects on wound healing, melanogenesis and TRPA-1 activation. Leaf extracts of different types of citrus fruits are the best researched part of citrus processing by-products. Conclusion: All three types of by-products show the potential for use in cosmetics as ingredients of products with different purposes. There is a need to optimize the extraction procedures focusing on certain groups of bioactive molecules taking into account possible synergistic effects, as well as to explore optimal forms of delivery that would result in maximum utilization of the by-products' beneficial properties. Also, clinical studies with the application of formulated cosmetic preparations on larger number of subjects are necessary, since a number of effects have been confirmed mostly on extracts alone and in-vitro

    Uloga ceramida u održavanju i obnovi epidermalne barijere

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    Koža je najveći ljudski organ i njezina glavna uloga je zaštita organizma od vanjskih utjecaja i sprečavanje gubitka vode i elektrolita. Najgornji sloj kože, stratum corneum, predstavlja prvu crtu barijerne funkcije kože. Ceramidi, masne kiseline i kolesterol tvore ekstracelularni lipidni matriks epidermalne barijere i složeni su u guste ortorombske strukture unutar instersticija stratum corneuma. Ceramidi igraju glavnu ulogu u održavanju tih struktura tako da samo male promjene u sastavu i/ili količini ceramida rezultiraju poremećajem barijerne funkcije kože što dovodi do dehidracije kože, povećane propusnosti te u konačnici može dovesti i do patoloških stanja. Ceramidi osim strukturalne uloge djeluju i kao bioaktivni glasnici te igraju mnoge uloge u imunološkom odgovoru kože. Zbog spoznaje da topikalno primjenjeni egzogeni ceramidi povoljno utječu na funkciju i izgled kože, da nisu toksični te da imaju veliku podnošljivost, kozmetički brandovi počeli su ih koristiti u svojim formulacijama za suhu kožu i obnovu kožne barijere. Cilj ovog rada je dati sustavni pregled znanja o strukturi i funkciji glavnih lipida kožne barijere - ceramidima, o načinu formiranja lipidnih membrana rožnatog sloja i o njihovoj molekularnoj organizaciji te dati pregled dostupnih dermatokozmetičkih pripravaka s ceramidima za održavanje i obnovu kožne barijere.Skin is the largest human organ and its main role is to protect the organism from external factors and to prevent water and electrolyte loss. The uppermost layer of skin, the stratum corneum, represents the first line of the skin's barrier function. Ceramides, fatty acids and cholesterol form the extracellular lipid matrix of the epidermal barrier and are packed into thick orthorhombic structures within the interstitium of the stratum corneum. Ceramides play the main role in maintaining these structures, so even small changes in the composition and/or the amount of ceramides result in the impairment of the skin barrier function, which leads to skin dehydration and increased permeability, which in turn can lead to pathological states. Except their structural role, ceramides also act as bioactive messengers and play many roles in the skin's immune response. Since it has been observed that topically applied exogenous ceramides benefit the function and the appearance of the skin, are not toxic and that they have a great tolerability, cosmetic brands have started using them in their formulations for dry skin and for skin barrier restoration. The aim of this paper is to give a systematic overview of the structure and the function of the main skin barrier lipids- ceramides, the formation of the lipid membranes of the horny layer and their molecular organisation, as well as to give an overview of available dermatocosmetic products containing ceramides for the maintenance and restoration of the skin barrier

    Determination of naphthoquinones in invasive alien plants Impatiens glandulifera Royle and I. balfourii Hook.f. from Croatia

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    The study aimed to develop an HPLC method for a simultaneous determination of 2-hydroxy-1,4-naphthoquinone (2-HNQ) and 2-methoxy-1,4-naphthoquinone (2-MNQ) in plant material. The method was implemented to determine naphthoquinones (NQs) in leaves and flowers of the invasive alien species Impatiens glandulifera and I. balfourii collected in Croatia. Two NQs extraction methods from plant material were compared: decoction and ultrasonic extraction. Validation parameters indicate that the developed method is reliable for the simultaneous determination of 2-HNQ and 2-MNQ in plant material. The decoction extraction obtained a higher NQs yield than ultrasonic extraction. In the leaves and flowers of I. glandulifera and I. balfourii only 2-MNQ was detected. Both, I. glandulifera and I. balfourii, had higher 2-MNQ concentrations in flowers than in leaves. A significantly higher 2-MNQ concentration was found in I. glandulifera compared to I. balfourii. Therefore, I. glandulifera can be considered a rich source of 2-MNQ whose antitumor potential is established

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