113 research outputs found

    MUSLIMS IN THE PRACTICE OF THE EUROPEAN COURT OF HUMAN RIGHTS THROUGH THE PRISM OF FREEDOM OF RELIGION IN EDUCATION

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    In this paper, the authors presented the characteristic cases from the case law of theEuropean Court of Human Rights in which members of the Islamic community consideredthat their freedom of religion under Article 9 of the European Convention on Human Rightsand Fundamental Freedoms has been violated. At the same time, in those cases, there wasfrequently violation of Article 2 of Protocol No. 1 to the Convention, which provides for theright to education, cumulatively with above mention article. The starting point is the case ofDahlab v. Switzerland, after which the authors specifically addressed several other cases inwhich the European Court of Human Rights considered these rights

    The influence of genes’ polymorphism of CYP3A5, CYP2C8 and CYP1A2 metabolising enzymes on efficacy and safety of carbamazepine therapy in children

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    Primena karbamazepina u terapiji epilepsija praćena je značajnom inter- individualnom varijabilnošću u efikasnosti i bezbednosti, zbog koje je ishod terapije kod jednog dela pacijenata neizvestan. Biotransformacija karbamazepina zavisi od aktivnosti niza CYP enzima, uključujući CYP3A5, CYP2C8 i CYP1A2. Cilj ovog ispitivanja bio je da utvrdi učestalost nekih od funkcionalno značajnih varijacija gena CYP3A5, CYP2C8 i CYP1A2 u srpskoj pedijatrijskoj populaciji, kao i da proceni njihov uticaj na farmakokinetiku, efikasnost i bezbednost karbamazepina. Studija je uključila 40 pacijenata sa epilepsijom lečenih karbamazepinom. Genotipizacija je obuhvatila CYP3A5*2 (g.27289C>A, rs28365083), CYP3A5*3 (g.6986A>G, rs776746), CYP2C8*3 (g.416G>A, rs11572080), CYP2C8*5 (g.475delA, rs72558196), CYP1A2*1F (g.-163C>A, rs762551) i CYP1A2*1C (g.-3860G>A, rs2069514) varijacije, a sprovedena je metodom lančanog umnožavanja DNK (engl. polymerase chain reaction, PCR) i njenim modifikacijama (PCR-RFLP, AS-PCR). Koncentracija karbamazepina u serumu merena je nakon postignutog ravnotežnog stanja metodom tečne hromatografije visokih preformansi (engl. high performance liquid chromatography, HPLC). Efikasnost lečenja procenjivana na osnovu kontrole napada i EEG promena tokom trajanja studije, a bezbednost na osnovu laboratorijskih parametara i pojave neželjenih događaja. Takođe, sprovedena je populaciona farmakokinetička analiza, sa ciljem da dodatno proceni efekat ispitivanih polimorfizama, ali i izabranih demografskih i kliničkih faktora, na srednju vrednost klirensa karbamazepina. Učestalost ispitivanih varijacija CYP3A5, CYP2C8 i CYP1A2 gena iznosila je 97,5% za CYP3A5*3, 17,5% za CYP2C8*3 i 65,0 % za CYP1A2*1F, dok CYP3A5*2, CYP2C8*5 i CYP1A2*1C nisu detektovani. Analiza uticaja CYP3A5*3 na farmakokinetiku karbamazepina pokazala je da kod homozigotnih nosilaca varijantnog alela postoji tendencija ka nižim dozama ( ±σ: 15,06 ± 4,45 mg/kg naspram 18,74 ± 5,55 mg/kg, p= p=0.26), višim postignutim koncentracijama ( ±σ: 0,45 ± 0,13 mg/kg naspram 0,38 ± 0,03 mg/kg, p=0,47). Ispitivanje uticaja CYP2C8*3 pokazalo je da je korelacija između dnevne doze i postignute serumske koncentracije karbamazepina nakon prilagođavanja doze bila je značajna samo u grupi ispitanika bez CYP2C8*3 polimorfizma (r=0,52, p=0,002). Pritom, kod nosilaca ove varijacije uočena je tendencija ka nižim dnevnim dozama ( ±σ: 14,19 ± 5,39 mg/kg naspram 15,46 ± 4,35 mg/kg, p=0,5) i višim dozno normalizovanim koncentracijama leka ( ±σ: 0,54 ± 0,18 mg/ml naspram 0,43 ± 0,11 mg/ml, p=0,04). Populaciona farmakokinetička analiza koja je uključila CYP2C8*3 pokazala je da na klirens karbamazepina utiču pol i dnevna doza leka (CL (L/h)=0.215+0.0696*SEX+0.000183*DD, gde SEX ima vrednost 1 za muški i 0 za ženski pol, a DD odgovara ukupnoj dnevnoj dozi karbamazepina izraženoj u mg), ali ne i ispitivani CYP2C8 polimorfizam. Analiza uticaja CYP1A2*1F na farmakokinetiku karbamazepina pokazala je značajnu korelaciju između dnevne doze i postignute serumske koncentracije leka, ali samo u prisustvu CYP1A2*1F varijacije (r=0,68, p=0,0004). Kod homozigotnih nosilaca CYP1A2*1F varijacije uočena je i tendencija ka višim dozama ( ±σ: 16,23 ± 3,83 mg/kg naspram 14,43 ± 4,92 mg/kg, p=0,21) i nižim dozno- normalizovanim serumskim koncentracijama leka ( ±σ: 0,42 ± 0,12 mg/kg naspram 0,47 ± 0,14 mg/kg, p=0,26). Uticaj CYP1A2 −163A/A genotipa, ali i pola i ukupne dnevne doze leka, na klirens karbamazepina potvrđen je i populacionom farmakokinetičkom analizom, koja je rezultirala jednačinom CL(l/h)=0.176+0.0484*SEX+0.019*CYP1A2+0.000156*DD. Analiza uticaja ispitivanih polimorfizama na efikasnost i bezbednost terapije karbamazepinom nije pokazala statistički značajne razlike u praćenim parametrima među genotipski različitim grupama. U zaključku, učestalost ispitivanih varijacija CYP3A5, CYP2C8 i CYP1A2 gena kod Srba odgovara prethodno publikovanim podacima za belu populaciju. Za sada nema dovoljno kliničkih dokaza u korist uvođenja rutinske genotipizacije ispitivanih CYP3A5 i CYP2C8 polimorfizama kod dece srpske populacije na terapiji karbamazepinom. Međutim, dokazano je da CYP1A2 −163C>A (CYP1A2*1F) polimorfizam značajno utiče na farmakokinetiku leka. S obzirom na pokazanu učestalost ovog polimorfizma u srpskoj populaciji, primena rutinske genotipizacije bi mogla doprineti adekvatnijem izboru doze karbamazepina kada je indikovana njegova primena.Carbamazepine in epilepsy treatment includes significant inter-individual variability in efficacy and safety, which led to the fact that the therapy outcome is unpredictable in some patients. Carbamazepine biotransformation depends on activity of several CYP enzymes including CYP3А5, CYP2C8 and CYP1А2. The aim of the present study was to investigate the frequency of some of functionally important variants of genes: CYP3А5, CYP2C8 and CYP1А2 in Serbian pediatric population, and to assess their influence on pharmacokinetic, efficacy and safety of carbamazepine. The study involved 40 pediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was included CYP3A5*2 (g.27289C>A, rs28365083), CYP3A5*3 (g.6986A>G, rs776746), CYP2C8*3 (g.416G>A, rs11572080), CYP2C8*5 (g.475delA, rs72558196), CYP1A2*1F (g.-163C>A, rs762551) и CYP1A2*1C (g.-3860G>A, rs2069514) variations, and conducted using polymerase chain reaction (PCR) and their modifications (PCRRFLP, AS-PCR). Carbamazepine steady state serum concentrations were determined by high performance liquid chromatography (HPLC). The efficacy was assessed based on the control of attacks and EEG changes during the study, and safety was assessed based on assessments of laboratory parameters and adverse events reported during the study. The population pharmacokinetic analysis was additionally assessed the effect of investigated genes polymorphisms, as well as the effect of chosen demographic and clinical factors on the carbamazepine clearance. Frequencies of investigated CYP3А5, CYP2C8 и CYP1А2 gene variations were 97,5% for CYP3A5*3, 17,5% for CYP2C8*3 and 65,0 % for CYP1A2*1F, while CYP3A5*2, CYP2C8*5 and CYP1A2*1C were not detected. Analysis of CYP3A5* influence on pharmacokinetic of carbamazepine showed that in homozygous carriers of variant allele compared to other subjects there was a tendency observed towards lower dose requirements ( ±σ: 15,06 ± 4,45 mg/kg vs. 18,74 ± 5,55 mg/kg) and higher drug concentrations ( ±σ: 0,45 ± 0,13 mg/kg vs. 0,38 ± 0,03 mg/kg). Analysis of CYP2C8*3 influence showed that correlation of daily doses and serum concentrations after dose adjustments was significant only in the group without CYP2C8*3 polymorphism (r=0,52, p=0,002). In carriers of this variation there was tendency observed towards lower daily doses ( ±σ: 14,19 ± 5,39 mg/kg vs 15,46 ± 4,35 mg/kg, p=0,5) and higher dose normalized concentrations of the drug ( ±σ: 0,54 ± 0,18 mg/ml vs 0,43 ± 0,11 mg/ml, p=0,04). The population pharmacokinetic analysis which included CYP2C8*3 revealed that the sex and daily dose, but not this CYP2C8 polimorphism, affect carbamazepine clearance (CL(L/h)=0.215+0.0696*SEX+0.000183*DD, where SEX has value 1 for male and 0 for female, аnd DD has value of carbamazepine total daily dose in mg). Analysis of CYP1A2*1F on carabamezepine pharmacokinetic revealed the significant correlation of daily doses and concentration only in the group of CYP1A2*1F carriers (r=0,68, p=0,0004). In homozygotes carriers of CYP1A2*1F variation the tendency towards higher doses ( ±σ: 16,23 ± 3,83 mg/kg vs 14,43 ± 4,92 mg/kg, p=0,21) and lower dose normalized serum concentration of the drug ±σ: 0,42 ± 0,12 mg/kg vs 0,47 ± 0,14 mg/kg, p=0,26) was detected. The influence of CYP1A2 −163A/A genotype and sex and total daily dose on the carbamazepine clearance was additionally confirmed by population pharmacokinetic analysis, with the equitation CL(l/h)=0.176+0.0484*SEX+0.019*CYP1A2+0.000156*DD. The analysis of the effect of investigated genes polymorphisms on efficacy and safety of the carbamazepine therapy did not revealed any statistically significant difference among different genotypes’ groups. In conclusion, the frequency of CYP3А5, CYP2C8 и CYP1А2 gene polymorphisms correlated well to previously published data for Caucasians. As for now, there is no significant clinical evidence that could support routine genotyping of investigated CYP3A5 and CYP2C8 polimorphisms in Serbian epileptic children on carbamazepine treatment. However, it has been proven that CYP1A2 −163C>A (CYP1A2*1F) polymorphism significantly affects the drug pharmacokinetic. Considering the observed frequency of this polymorphism in Serbian population, the use of the routine genotyping could contribute to the more adequate carbamazepine dosing when it is indicated as therapy

    Fragments of Wall Painting from Residential Buildings at the Site of Čair (Viminacium)

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    This paper focuses on the remains of wall paintings from residences of the area of antique Viminacium (capital of Roman province of Upper Moesia). The largest number of specimens comes from the residences researched during the reexcavations in 2007 at the site of Čair, while a smaller portion comes from the public bath (thermae) and amphitheater. Detailed analysis of the fragments of wall painting showed that these buildings were once meticulously maintained since the materials show traces of renovation. These fragments revealed an entirely new image of plaster composition, which differs significantly from that found in the funerary painting of Viminacium. Highly polished surfaces of certain specimens, as well as possible figurative representations, indicate luxurious buildings which were in use during the 2nd and 3rd century

    Establishment and in-house validation of stem-loop rt pcr method for microrna398 expression analysis

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    MicroRNAs (miRNAs) belong to the class of small non-coding RNAs which have important roles throughout development as well as in plant response to diverse environmental stresses. Some of plant miRNAs are essential for regulation and maintenance of nutritive homeostasis when nutrients are in excess or shortage comparing to optimal concentration for certain plant species. Better understanding of miRNAs functions implies development of efficient technology for profiling their gene expression. We set out to establish validate the methodology for miRNA gene expression analysis in cucumber grown under suboptimal mineral nutrient regimes, including iron deficiency. Reverse transcription by "stem-loop" primers in combination with Real time PCR method is one of potential approaches for quantification of miRNA gene expression. In this paper we presented a method for "stem loop" primer design specific for miR398, as well as reaction optimization and determination of Real time PCR efficiency. Proving the accuracy of this method was imperative as "stem loop" RT which consider separate transcription of target and endogenous control. The method was verified by comparison of the obtained data with results of miR398 expression achieved using a commercial kit based on simultaneous conversion of all RNAs in cDNAs

    Dr Atanasije Puljo - pionir srpske stomatologije

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    This paper describes the life and work of Dr. Atanasije Puljo (1878-1944). He was a volunteer in the Balkan wars, an active participant in the First World War; he was the first who noted the importance of team-work of a dentist and a surgeon in the care of jaw and facial injuries. He established primacy in this field, as he came up with this brilliant idea three years before other colleagues. His method of treatment of the upper jaw neglected fractures, called the Balkan method, was recognized worldwide. Dr. Puljo is the pioneer of dental radiology in Serbia, founder of the Odontology Clinic of the Medical Faculty and main supporter of the establishment of the School of Dentistry. Merits of Dr. Atanasije Puljo, medical practitioner with a broad knowledge in different fields, remain within the academic institution that was founded by this pioneer of dentistry in Serbia.Dr Atanasije Puljo (1878-1944) bio je dobrovoljac u balkanskim ratovima, aktivni učesnik u Prvom svetskom ratu i prvi koji je uočio značaj zajedničkog rada zubnog lekara i hirurga u zbrinjavanju ranjenika s povredama vilica i lica. Na taj način zauzeo je primat u ovoj oblasti i tri godine pre drugih došao na ovu genijalnu zamisao. Svetski je priznata njegova metoda lečenja zastarelih preloma gornje vilice, nazvana 'balkanska metoda'. Dr Puljo je pionir stomatološke rendgenologije u Srbiji, osnivač Odontostomatološke klinike Medicinskog fakulteta i idejni začetnik Stomatološkog fakulteta u Beogradu. Zasluge dr Atanasija Pulje, sveobuhvatnog medicinara, ostaju utemeljene u instituciji fakulteta koju je pionirski začeo ovaj rodonačelnik stomatologije u Srbiji

    Uloga opeke u hidrauličnosti maltera Viminacijuma: dekorativni malteri građevine termi

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    The hydraulicity of the Viminacium mortars is still somewhat unknown, but with laboratory analyses, performed on a small number of samples, and similar research performed worldwide, some conclusions can be drawn. These bring us closer to this topic, which again contribute to our becoming acquainted with the Viminacium building materials, their usage, behaviour in constructions and their mutual relationships. Throughout history, artificial products of soil, specifically bricks and ceramics, represent some of the most commonly used materials with pozzolanic features in the creation of hydraulic lime mortars. In accordance with their function, the Viminacium thermae represent a place with high levels of humidity in the air and water in a large number of rooms, thereby representing a suitable example for analysing the use of hydraulic mortars, which above all needed to be waterproof. This was achieved with the use of bricks, a material produced locally in Viminacium. Fragmentarily preserved remains of wall paintings from the Viminacium thermae are not only numerous and various, but they spatially also include almost all parts of the building. This paper includes the remains of decorative mortars discovered during archaeological research in 2004 and 2007 that had bricks in their structure, which was confirmed with a visual review of mortar cross-sections when brick was used in fragments. It was also suspected due to the reddish colour of some of the layers, most likely connected to the use of brick dust

    Fragmenti zidnog slikarstva sa termi iz Viminacijuma

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    Sistematska arheološka iskopavanja termi na Viminacijumu dopunjuju naša saznanja o životu antičkog grada. Novac nađen u pristoriji 1 i 2, datuje mlađu fazu termi iz druge polovine III veka, kada je objekat proširen dodavanjem novih bazena i pomoćnih prostorija. Ostaci zidnog slikarstva otkriveni u prostoriji 1 sugerišu način unutrašnjeg dekorisanja javnih zgrada. Konzervatorskim postupkom pojedini fragmenti su postavljeni na novi malterni nosač. Sačuvane ostatke fresaka nije bilo moguće potpuno rekonstruisati, već samo stabilizovati i od njih napraviti više prenosivih eksponata

    Body Function and Life Process of a Roman Building: Viminacium Baths

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    Viminacium baths, excavated from 1973 to 1974 and from 2004 to 2007, were in use from the second half of the 1st century AD until the end of the 4th century AD. Periods of the building life are confirmed by changes in masonry techniques and the existence of wall paintings with multiple layers, as well as by dating of pottery and numismatic finds. The aim of this paper is to analyze all these pieces of evidence, trying to find common causes for their occurrence
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