Neuroleptic properties of urapidil in condition in vitro and in vivo

Istražena su neuroleptička svojstva urapidila u štakora u uvjetima in vitro i in vivo. Urapidil je antihipertenziv, agonist centralnih 5-HT1a receptora i antagonist perifernih alfa 1 receptora s utjecajem na dopaminergičku transmisiju. Na stanicama PC12 i SH-SY5Y urapidil u dozi od 100 i 200 µM ne djeluje antioksidacijski (za razliku od kvercetina), niti zaustavlja smrt stanica izazvanu metamfetaminom (kao i haloperidol), ali dovodi do zaustavljanja aktivnosti efektorskih kaspaza 3/7 mitohondrijskog puta. In vivo u dozi od 0.25, 0.5 i 1 mg/štakoru intraperitonealno (i.p.), urapidil dovodi do povećanja lokomocije, bez izazivanja abnormalnih kretnji ili stereotipija karakterističnih za metamfetamin. Doze od 15, 20 i 25 mg/štakoru i.p. dovode do progresivne katalepsije, dok doza od 25 mg/štakoru i.p. urapidila u predtretmanu i posttretmanu zaustavlja hiperlokomociju i stereotipije izazvane metamfetaminom. Urapidil blokira aktivnost kaspaza 3/7 nakon primjene metamfetamina i iskazuje jasna neuroleptička svojstva, vjerojatno vežući se za dopaminske (D2) receptore.Neuroleptic properties of urapidil were investigated in vitro and in vivo models in rats. Urapidil is an antihypertensive agent, agonist of central 5-HT1a and antagonist of peripheral alpha 1 receptors, with the effect on dopaminergic transmission. On PC12 and SH-SY5Y cells urapidil at doses of 100 and 200 µM is not acting like antioxidant (like quercetin does), nor stops cell death (like haloperidol) caused by methamphetamine, but blocks the activity of effector caspase 3/7 mitochondrial pathway. In vivo at a dose of 0.25, 0.5 and 1 mg/rat intraperitoneally (i.p.) it increases locomotion, but without causing abnormal movement or stereotypy like metamphetamine does. At doses of 15, 20 and 25 mg/rat i.p. urapidil causes progressive catalepsy. When applied as pretreatment and posttreatment it antagonizes metamphetamine induced hyperlocomotion and stereotypy. Urapidil blocks the activity of caspase 3/7 following administration of methamphetamine and expresses clear neuroleptic properties likely by binding to dopamine (D2) receptors

Two stone medieval heads in the Museum of Slavonia

The Collection of Medieval Stone Monuments of the Museum of Slavonia of Osijek involves, apart from architectonic elements, two stone heads. Although the heads were unclassified and lacked data on their origin and discovery site until recently, the handover record of 1971 suggests that the Regional Institute for Monument Protection rendered, along with other medieval findings from various sites, ’the head of a stone sculpture’ found in a medieval church in Voćin during protection works. The church was the prominent and now again restored Late Gothic Church of the Visitation of the Blessed Virgin Mary. Since other field documentation includes no data on its discovery, the head is likely to have been found during clearance of the church and Franciscan monastery premises. Now there is the problem of determining which head was found in the Voćin church. Katarina and Eufrozina, Nikola Iločki’s daughters and Lovro Iloćki’s sisters, had the church and the Franciscan monastery of Voćin (oppidum Athyna, Attina) built in the last decade of the 15th century. After the Ottoman occupation of Voćin in 1543, the abode in the monastery and church was terminated and the buildings were severely devastated. The fragmentarily preserved and severely damaged head of Christ crowned with thorns was initially considered ’the head of the stone sculpture’ of Voćin because the other head with an ivy wreath was later found in the depot. Analysis of the stone which the heads were made of has catered both for general data on possible places where the sculpture was made and for some specific indicators such as the way of deterioration and emergence of damage or the content of the white protective coating. The attempt of iconographic analysis and search for closer analogies for the second, finely shaped head with a youthful face and curly hair covered with an English ivy wreath have not given any concrete results, just some indications. The position of the head with respect to the fully preserved neck implies that this might be a full figure staring at something above(Christ on the cross, another person) or a head serving as a decorative console table. This issue has entailed different opinions in the paper as well as has its dating. Beside the common standpoint that this is highly valuable late mediaeval stone figural plastics, particularly if the lack of any evidence of the kind from the pre-Turkish period in eastern Croatia is taken into consideration, the head with an ivy wreath has aroused different opinions on its date of manufacture. The estimates range from the end of the 14th or the beginning of the 15th century all the way to the late 19th or the early 20th century. In this view, one should bear in mind that the colleagues could get use of only photo-documentation. The author of the paper is more prone to the latter dates, taking account of the historical data. The views on a possible stylistic and temporal connection with the findings of sculptures from the later reign of Sigismund (the second and third decade of the 15th century) in Buda are also opposing. The same can be said for the stone head which might be found in the Voćin church whereat slight prevalence is given to the head with an ivy wreath. Yet, certain conclusions require more specific data. The fragment of the upper part of the head of Christ crowned with thorns can be, due its fragmentariness, only generally dated to the 14th-15th century period. All the dilemmas and a relatively large range in the dating of the head with an ivy wreath once again point to the importance of keeping precise archaeological museum documentation since otherwise, even the most significant findings can be completely discredited in the professional and scientific sense. Instead of a conclusion one needs to stress the rarity and the artistic and monumental value of the two stone heads for the late medieval period in eastern Croatia and hope that further research of the documentation of other medieval sites in eastern Croatia will ’dig up’ new data on ’the head of the stone sculpture’

Propolis extract and its bioactive compounds - from traditional to modern extraction technologies

Propolis is a honeybee product known for its antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. It is rich in bioactive molecules whose content varies depending on the botanical and geographical origin of propolis. These bioactive molecules have been studied individually and as a part of propolis extracts, as they can be used as representative markers for propolis standardization. Here, we compare the pharmacological effects of representative polyphenols and whole propolis extracts. Based on the literature data, polyphenols and extracts act by suppressing similar targets, from pro-inflammatory TNF/NF-B to the pro- proliferative MAPK/ERK pathway. In addition, they activate similar antioxidant mechanisms of action, like Nrf2-ARE intracellular antioxidant pathway, and they all have antimicrobial activity. These similarities do not imply that we should attribute the action of propolis solely to the most representative compounds. Moreover, its pharmacological effects will depend on the efficacy of these compounds’ extraction. Thus, we also give an overview of different propolis extraction technologies, from traditional to modern ones, which are environmentally friendlier. These technologies belong to an open research area that needs further effective solutions in terms of well-standardized liquid and solid extracts, which would be reliable in their pharmacological effects, environmentally friendly, and sustainable for production

Hereditary haemorrhagic telangiectasia – systematic review and single center experience

Cilj istraživanja: Cilj je ovog rada prikazati klinička iskustva našeg centra s oboljelima od hereditarne hemoragijske teleangiektazije (HHT). Prikazali smo kliničku sliku svojih bolesnika, nove dijagnostičke i terapijske mogućnosti, kao i svjetske smjernice u dijagnostici bolesti. Ispitanici i metode: U ovu retrospektivnu studiju uključeno je 13-ero bolesnika liječenih u Klinici za unutarnje bolesti KB-a Dubrava u razdoblju od 2008. do 2017. godine. Rezultati: Bilo je 9 muškaraca i 4 žene u dobi između 45 i 80 godina (medijan 70 godina). Svih 13-ero bolesnika prezentiralo se sideropeničnom anemijom i rekurentnim epistaksama koje su ujedno bile i najraniji znak bolesti. Dvanaestero bolesnika imalo je mukokutane teleangiektazije, a njih devetero gastrointestinalna krvarenja. U jednog bolesnika dokazana je pulmonalna, a kod još jednoga hepatalna arteriovenska malformacija. Nakon medijana praćenja od 60 mjeseci devetero je bolesnika živo, a njih četvero preminulo je. Zaključci: Prava dijagnoza bolesti u većine naših bolesnika postavljena je tek u starijoj dobi iako su se simptomi javljali i puno prije. U Republici Hrvatskoj ne postoje točni podaci o broju oboljelih, kao ni smjernice za otkrivanje i liječenje komplikacija bolesti. Nužno je formiranje multidisciplinarnih timova radi unaprjeđenja dijagnostike, ranijeg otkrivanja komplikacija bolesti te sveobuhvatnijeg praćenja bolesnika.Aim: The aim of this study is to present our center’s clinical experience with hereditary haemorrhagic telangiectasia (HHT). Herein, we showed clinical presentations of our patients, new diagnostic and therapeutic options, as well as the international guidelines for HHT diagnosis. Patients and methods: In this retrospective study, we identified 13 patients that were treated at the Department of Medicine, Clinical Hospital Dubrava from 2008 to 2017. Results: There were nine men and four women aged between 45 and 80 years (median 70 years). All 13 patients presented with sideropenic anaemia and recurrent epistaxis that was the earliest sign of the disease. Twelve patients had mucocutaneous telangiectasia, and nine patients were presented with gastrointestinal bleeding. One patient was diagnosed with pulmonary arteriovenous malformation, and the other one with hepatic malformation. After a median follow-up of 60 months, nine patients are alive, and four patients died. Conclusion: Most of our patients were diagnosed in older age, although the symptoms appeared much earlier in life. There are no data on the number of patients with HHT in the Republic of Croatia. Also, guidelines for diagnosis and screening for complications are lacking. Therefore, it is necessary to form a multidisciplinary team for diagnostic improvement, early detection of complications, and more intensive monitoring of patients

After 40 Years Gossypiboma Caused Spleen Abscess

We report a case of spleen abscess cased by foreign body (gossypiboma) after 40 years. After physical examination, laboratory, ultrasonography and CT findings with diagnosis of acute abdomen, 73 years old woman had undergone laparatomy. Operation revealed intraabdominal spleen abscess. Capsulotomy and drainage of the collection was performed before splenectomy. Histological examination showed foreign body material surrounded by chronic inflammation, foreign body-type multinucleated giant cells, extravasated red blood cells and fibroblastic proliferation. From anamnesis we found that woman was operated only once during a life with diagnosis of extrauterine pregnancy, 40 years ago. Spleen abscess caused by gossypiboma after 40 years was never described before. However, diagnosis like this is very well known but rarely published because medical-legal implication. Education, professionalism and cooperation of all persons involved in surgical procedure are very important to prevent accidentally mistakes

Nonaqueous Polyethylene Glycol as a Safer Alternative to Ethanolic Propolis Extracts with Comparable Antioxidant and Antimicrobial Activity

We compared the chemical composition, antioxidant and antimicrobial activity of two propolis extracts: one obtained with nonaqueous polyethylene glycol, PEG 400 (PgEP), and the other obtained with ethanol (EEP). We analyzed the total phenolic content (TPC) and the concentrations of ten markers of propolis antioxidant activity with HPLC-UV: caffeic acid, p-coumaric acid, trans-ferulic acid, trans-cinnamic acid, kaempferol, apigenin, pinocembrin, chrysin, CAPE, and galangin. Antioxidant activity was tested using DPPH and FRAP assay, and antimicrobial activity was assessed through minimum inhibitory concentrations (MICs) and minimum biofilm eradication concentration (MBEC) determination. Maceration gave the yield of propolis of 25.2 ± 0.08% in EEP, and 21.5 ± 0.24% in PgEP. All ten markers of antioxidant activity were found in both extracts, with all marker concentrations, except kaempferol, higher in EEP. There was no significant difference between the TPC and antioxidant activity of the PgEP and the EEP extract ; TPC of PgEP was 16.78 ± 0.23 mg/mL, while EEP had TPC of 15.92 ± 0.78 mg/mL. Both extracts had antimicrobial activity against most investigated pathogens and Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli biofilms. EEP was more effective against all tested susceptible pathogens, except E. coli, possibly due to higher content of kaempferol in PgEP relative to other polyphenols. Nonaqueous PEG 400 could be used for propolis extraction. It gives extracts with comparable concentrations of antioxidants and has a good antioxidant and antimicrobial activity. It is a safe excipient, convenient for pediatric and veterinary formulations

Chemical Composition, Antioxidant and Antibacterial Activity of Different Extracts of Poplar Type Propolis

Chemical composition, antioxidant activity and in vitro antibacterial activity of propolis from the central, continental part of Croatia were studied. Propolis hydro-ethanolic extracts (PHEE), prepared using three different methods and two solvent mixtures contained high amounts of flavonoids (20.95–28.11 % TIC), aromatic acids (8.17–15.91 % TIC) and their esters (9.27-11.91 % TIC). The PHEE obtained in this study showed high antioxidant activity (DPPH IC50 values from 9.96–19.95 µg/ml and FRAP 38.0–41.9 mM Fe2+/mg PHEE). Despite differences in composition, the PHEE samples exhibited significant antibacterial activities, affecting tested strains of Staphylococcus aures, Enterococcus faecalis, Escherichia coli and Moraxella catarrhalis. The use of different solvent ratio and extraction procedures selectively increases or decreases the content of specific propolis components in the extract which can have a beneficial effect on the application of propolis extracts. This work is licensed under a Creative Commons Attribution 4.0 International License

Antioksidacijski učinak nove intramamarne formulacije na bazi pčelinjih proizvoda Apimasta® u muznih krava.

The aim of this study was to determine the antioxidant effect of the novel bee-product based intramammary formulation Apimast® on the oxidative status of dairy cows. Apimast® was administered intramammarily three times at 12 h intervals to 10 dairy cows on each of the three dairy farms. The oxidative status markers and some metabolic parameters were determined in the milk (GSH-Px, d-ROM, SOD, BAP, TAS) and in the serum (SOD, GSH-Px, NEFA, BHB, glucose). The results showed that the effect of Apimast® was mostly local, regardless of the concentration used (3% and 1%) as there was an increase in the concentration of GSH-Px and TAS in the milk, but not in the blood. It is also of a short-term nature since the values of these parameters were significantly lower 7 days after application. The expected connection between the increase of ROM in milk samples from the microbiologically positive quarters was not found. The results of this study confirm the local antioxidant effect of Apimast® in the udder, with implications for non-antibiotic subclinical mastitis treatment.Cilj istraživanja bio je odrediti učinak nove intramamarne formulacije na bazi pčelinjih proizvoda, Apimasta®, na oksidacijski status muznih krava. Apimast® je apliciran u tri navrata s razmacima od 12 sati u 10 krava na tri različite farme. Izmjereni su markeri oksidacijskog statusa kao i određeni metabolički pokazatelji u mlijeku (GSH-Px, d-ROM, SOD, BAP, TAS) i serumu (SOD, GSH-Px, NEFA, BHB, glukoza). Učinak Apimasta® bio je uglavnom lokalan, bez obzira na primijenjenu koncentraciju (1 i 3 %), jer porast koncentracija GSH-Px i TAS-a u mlijeku nije pratio porast u serumu. Promjene svih mjerenih pokazatelja bile su kratkotrajne i nakon sedam dana vraćale su se na približne vrijednosti početnih koncentracija. U bakteriološki pozitivnim četvrtima vimena nije zabilježen porast ROM-a. Ovo istraživanje potvrđuje lokalni antioksidacijski učinak Apimasta® u vimenu, što je relevantno s aspekta neantibiotskog liječenja supkliničkog mastitisa

“Intramammary propolis formulation for prevention and treatment of mastitis in dairy ruminants”, the first project of collaboration between the Faculty of Veterinary Medicine and the business sector financed from EU structural funds

Projekt suradnje Veterinarskoga fakulteta i tvrtke Hedera d.o.o. iz Splita „Intramamarna formulacija propolisa za prevenciju i tretman mastitisa kod mliječnih preživača“ sufinanciran je iz strukturnih instrumenata Europskog fonda za regionalni razvoj (EFRR) te iz Državnog proračuna Republike Hrvatske. Ovo je prvi strukturni projekt suradnje s industrijom koji je Veterinarski fakultet ostvario, a ukupan iznos odobrenih sredstava je 3.048.238,43 kuna. Cilj je projekta istraživanje i razvoj inovativne intramamarne formulacije propolisa za prevenciju i tretman mastitisa kod krava i koza. Glavne prednosti ove formulacije u odnosu na standardne intramamarne antibiotike jesu nepostojanje karencije i vrlo vjerojatno nemogućnost razvoja rezistencije, budući da je propolis mješavina nekoliko stotina spojeva sa složenim antimikrobnim i antioksidacijskim učincima. Razvoj ovakvog proizvoda, koji nedostaje nacionalnom i međunarodnom tržištu, dovest će do jačanja gospodarskog sektora, među ostalim i smanjenjem financijskih troškova proizvođača mlijeka te lakšim postizanjem standarda ekološkog stočarstva. Interdisciplinarna suradnja ostvarena tijekom ovog projekta, kao i investicije u opremu i edukaciju, ojačat će kapacitet Veterinarskoga fakulteta za daljnje transfere znanja i tehnologije.The project of collaboration between the Faculty of Veterinary Medicine in Zagreb and the small enterprise Hedera Ltd from Split, entitled: “Intramammary propolis formulation for prevention and treatment of mastitis in dairy ruminants”is co-financed from the structural instruments of the European fund for regional development (EFRD) and the State Budget of Republic of Croatia. This is the first structural project of collaboration between the Faculty of Veterinary Medicine and the business sector. The project’s estimated value is 3,048,238.43 HRK. The main goal of the project is research and development of innovative intramammary propolis formulation, as an alternative to antibiotic treatment of mastitis in dairy cows and goats. The development of this unique and original product may contribute to strengthening the business sector, through reducing the costs of milk production by facilitating meeting organic criteria in dairy farming. Interdisciplinary expert collaboration, along with investments in equipment and education, will strengthen the capacity of the Faculty of Veterinary Medicine for further transfer of knowledge & technology projects

Hearing in children with otitis media with effusion--clinical retrospective study [Oštećenje sluha kod djece sa sekretornim otitisom]

Hearing loss accompanied with middle ear effusion was analyzed according to audiometric frequencies for different age group. Results for left and right ears were compared in/and between study and control group. Pure tone audiometry for bone and air conduction and tympanometry was performed in study group of ninety-eight children with conductive hearing loss and otitis media with effusion. Control group included fifty-seven children with hearing loss, enlarged adenoids, dysfunction of Eustachian tube and no present middle ear effusion served. Means of hearing loss thresholds for 250 Hz-4 kHz were established and compared between groups of right vs. left ears of tested vs. control ears according to age subgroups: 1-3 yr, 4-6 yr, 7-9 yr, 10-12 yr, 13-15 yr. At age 1-3 yr otitis media with effusion children showed no ear side difference in hearing loss. Age groups of 4-6 and 7-9 yr otitis media with effusion children showed left ears with higher threshold of hearing loss across all of the tested frequencies than right ears in study and control ears. Right ears showed smaller hearing loss in study and control group and no age group predicted for hearing impairment. Higher hearing loss threshold for 4 kHz in adolescence in otitis media with effusion ears is early sign of sequels after repetitive episodes of middle ear effusion. Control groups showed no ear side or age group dependent difference of hearing loss threshold. Age group of 4-6 and 7-9 y have faster craniofacial structural change in soft tissue than bone base so ear side differences suggest being developmentally determined