Analysis of the natural course and disability progression in relapsing-remitting multiple sclerosis patients : results of five years follow-up study in Serbia

Cilj: U cilju procene efekta terapije interferonom-beta na progresiju ireverzibilne onesposobljenosti obolelih od relapsno-remitentne forme multiple skleroze, sprovedena je prospektivna kohortna studija koja je poredila grupe lečenih i nelečenih bolesnika od multiple skleroze IFN-beta. Metode: Kohorta od 419 bolesnika sa relapsno-remitentnom formom MS (od toga je 236 bolesnika lečeno IFN-beta i 183 nelečenih) je praćena tokom 7 godina. Cox proporcionalni hazardni regresioni modeli prilagođeni broju relapsa u toku jedne godine pre prve posete su korišćeni za procenu razlika između dve grupe ispitanika za tri krajnje karakteristike ishoda bolesti: dostizanja sekundarne progresije (SP), i ireverzibilne onesposobljenosti procenjene EDSS skorovima 4 i 6. Vreme od početka bolesti je korišćeno kao varijabla vremena preživljavanja. Rezultati: Grupa bolesnika lečena IFN-beta je pokazala značajno visoko smanjenje rizika od razvoja sekundarne progresije (SP) (hazard ratio [HR], 0.34, 95% interval poverenja [CI] 0.19-0.61, p<0.001) u poređenju sa grupom nelečenih bolesnika. Postignuta je statistički značajna razlika u korist IFN-beta-lečene grupe bolesnika u vremenu proteklom od prve posete do dostizanja EDSS skora 4 (HR=0.45, 95%CI 0.28- 0.73, p=0.001) i EDSS skora 6 (HR=0.34, 95%CI 0.16-0.75, p=0.007). Zaključak: Ova opservaciona studija podržava ranije uverenje da IFN-beta može imati potencijalno koristan efekat na progresiju bolesti u RR formi multiple skleroze.Objective: To assess the impact of interferon (IFN)-beta treatment on the progression of unremitting disability in IFN-beta treated and untreated relapsing-remitting (RR) patients with multiple sclerosis (MS) using prospective cohort study. Methods: A cohort of 419 RRMS (236 IFN-beta–treated and 183 untreated) patients was followed for up to 7 years. Cox proportional hazards regression models adjusted for the number of relapses in the last year before first visit was used to assess the differences between the two groups for the three end points: secondary progression (SP), and sustained Expanded Disability Status Scale (EDSS) score 4 and 6. Time from disease onset was used as survival time variable. Results: The IFN-beta-treated group showed a highly significant reduction (hazard ratio [HR], 0.34, 95% confidence interval [CI] 0.19-0.61, p<0.001) in the risk of SP when compared with untreated patients. There were significant differences in favor of the IFN-beta-treated group for the end point EDSS score of 4 (HR=0.45, 95%CI 0.28-0.73, p=0.001) and EDSS score of 6 (HR=0.34, 95%CI 0.16-0.75, p=0.007). Conclusion: This observational study further supports the notion that IFN-beta could have potential beneficial effect on disease progression in RRMS

Poređenje kinetike bubrenja hidrogela delimično neutralisane poli(akrilne) kiseline u destilovanoj vodi i fiziološkom rastvoru

The isothermal kinetics Curves of the swelling of a poly(acrylic acid) hydrogel in distilled water and physiological Solution at temperatures ranging from 20 to 40 degrees C were determined. The possibility of applying both the Fick's kinetics model anti kinetics model of the first order chemical reaction to the swelling kinetics of the PAA hydrogel in distilled water and physiological Solution were examined. It was found that the possibilities of applying these models were limited. The new model of the kinetics of swelling in distilled water and physiological solution was established. The kinetic parameters (E-a, ln A) for the swelling in distilled water and physiological solution were determined. The decrease of the equilibrium degree of swelling and the saturation swelling rate of the swelling of the PAA hydrogel in physiological solution compared to swelling in distilled water could be explained by the decreased differences in the ionic osmotic pressures between the hydrogel and the swelling medium. The increase of the initial swelling rate in the physiological solution might be caused by an increased density of charges at the network and by an increased affinity of the network towards the water molecules. The increase of the activation energy of the swelling of the PAA hydrogel in the physiological solution is a consequence of its additional "ionic crosslinking".U radu su ispitivane izotermalne kinetičke krive bubrenja hidrogela delimično neutralisane poli(akrilne) kiseline u destilovanoj vodi i fiziološkom rastvoru u temperaturnom opsegu od 20 do 40 °C. Ispitivana je mogućnost primene Fikovog kinetičkog modela kao i kinetike i reda hemijskih reakcija na kinetiku bubrenja poliakrilnog hidrogela.Utvrđeno je da su mogućnosti za njihovu primenu vrlo ograničene. Iz tih razloga primenjen je novi model kinetike bubrenja. Određeni su kinetički parametri (Ea, lnA) za procese bubrenja u destilovanoj vodi i fiziološkom rastvoru. Smanjenje ravnotežnog stepena bubrenja i saturacione brzine bubrenja hidrogela delimično neutralisane poli(akrilne) kiseline u fiziološkom rastvoru u odnosu na destilovanu vodu može se objasniti smanjenjem razlike u jonskom osmotskom pritisku između hidrogela i medijuma za bubrenje. Povećanje inicijalne brzine bubrenja u fiziološkom rastvoru u odnosu na destilovanu vodu prouzrokovano je povećanjem gustine naelektrisanja na polimernoj mreži i povećanim afinitetom prema molekulima vode. Povećanje energije aktivacije hidrogela delimično neutralisane poli(akrilne) kiseline pri bubrenju u fiziološkom rastvoru se objašnjava dodatnim "jonskim umreženjem" hidrogela u fiziološkom rastvoru

Supplementary data for article : Kolarević, S.; Milovanović, D.; Kračun-Kolarević, M.; Kostić, J.; Sunjog, K.; Martinović, R.; Đorđević, J.; Novaković, I.; Sladić, D.; Vuković-Gačić, B. Evaluation of Genotoxic Potential of Avarol, Avarone, and Its Methoxy and Methylamino Derivatives in Prokaryotic and Eukaryotic Test Models. Drug and Chemical Toxicology 2019, 42 (2), 130–139. https://doi.org/10.1080/01480545.2017.1413108

Supplementary material for: [https://doi.org/10.1080/01480545.2017.1413108]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/322

Supplementary data for article : Kolarević, S.; Milovanović, D.; Kračun-Kolarević, M.; Kostić, J.; Sunjog, K.; Martinović, R.; Đorđević, J.; Novaković, I.; Sladić, D.; Vuković-Gačić, B. Evaluation of Genotoxic Potential of Avarol, Avarone, and Its Methoxy and Methylamino Derivatives in Prokaryotic and Eukaryotic Test Models. Drug and Chemical Toxicology 2019, 42 (2), 130–139. https://doi.org/10.1080/01480545.2017.1413108

Supplementary material for: [https://doi.org/10.1080/01480545.2017.1413108]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/322

Development of fluorinated indanone-based derivatives for the imaging of monoamine oxidase B via positron emission tomography

Ziel/Aim The monoamine oxidase B (MAO B) isoenzyme is known to be involved in the oxidative deamination of biogenic amines. While the use of MAO B inhibitors is already well-established for the treatment of Parkinson’s disease, recent reports suggest its involvement in certain types of brain tumors.1 We herein aim at the synthesis and preclinical evaluation of fluorinated indanone-based derivatives targeting MAO B in the brain via positron emission tomography (PET). Methodik/Methods A small series of fluorinated indanone derivatives was obtained via the O-alkylation or esterification starting with the commercially available 6-hydroxy-2,3-dihydro-1H-inden-1-one in one or two steps. Binding affinities towards the human MAO isoenzymes were estimated in vitro by radioligand displacement. HL126 was selected for radiofluorination via its corresponding boronic acid pinacol ester. In vitro autoradiography of [18F]HL126 was performed in mice brain slices. In vivo evaluation of [18F]HL126 in CD-1 mice was carried out and metabolism studies were performed in plasma and brain samples via radio-HPLC. Ergebnisse/Results The fluorinated indanone derivatives were synthesized in yields ranging from 65-89 %. The fluorophenyl ether derivative, HL126, was further selected for radiofluorination based on its high binding affinity towards MAO B (Ki = 6.9 ± 5.3 nM). [18F]HL126 was obtained by an alcohol-enhanced copper-mediated approach via the corresponding boronic acid pinacol ester precursor with radiochemical yields of about 11 ± 3 %, high radiochemical purities (≥99 %) and molar activities in the range of 20 GBq/mmol. In vitro autoradiography showed a specific blockade with selective MAO-A/B inhibitors. PET/MRI analyses revealed that [18F]HL126 readily enters the brain. Some radiometabolites do cross the blood-brain barrier. Schlussfolgerungen/Conclusions Although metabolism studies with [18F] HL126 revealed the presence of radiometabolites in the brain, the high binding affinity towards MAO B and the pronounced selectivity in in vitro autoradiography studies encourage further derivatization of indanone-based scaffolds for targeting MAO B

Halochromic cellulose textile obtained via dyeing with biocolorant isolated from Streptomyces sp. strain NP4

Halochromic (pH-responsive) material was obtained by dyeing functionalized viscose fabric with a crude extract from Streptomyces sp. strain NP4. The functionalization of the fabric before dyeing was performed to make cellulose susceptible to coloration with NP4 extract. Two combined pre-treatment steps were used, oxidation to obtain dialdehyde cellulose and chitosan deposition after oxidation. Chitosan was deposited onto untreated fabric as well, while only oxidized viscose was also investigated for dyeing. Functionalization by both protocols made viscose susceptible to dyeing with the notion that the deposition of chitosan onto oxidized viscose produced the darkest shade on the material. Dyed fabrics showed visual pH responsiveness in the range pH 4-10, with a color change from pink to red (pH 4-pH 7) and a major color change from red to blue (pH 7-pH 10) whereby fabric was tested and could withstand 10 color-changing cycles. Cytotoxicity assay confirmed the non-toxic nature of dyed material, which indicates its possible use as wound dressing's indicators

Abscisic Acid Effect on Improving Horse Chestnut Secondary Somatic Embryogenesis

The effect of abscisic acid on the development of primary androgenic embryo and secondary somatic embryogenesis was investigated with the aim of improving multiplication rates and secondary somatic embryo quality in horse chestnut microspore and anther culture. The early embryo stage (globular) had a better response than late stages (heart, torpedo, and cotyledonary) in both types of cultures. Also, microspore culture had a high potential for mass secondary embryo production. The number of secondary somatic embryos was three times higher on hormone-free medium than on medium enriched with 0.01 mg.L-1 abscisic acid. However, most of the embryos on hormone-free medium had abnormal morphology. For this reason, abscisic acid was added to the media to improve embryo quality. The morphology of abscisic acid treated embryos was better than abscisic acid non-treated embryos. The optimal abscisic acid concentration for secondary somatic embryo induction and production of high-quality embryos was 0.01 mg.L-1. Overall, the effect of abscisic acid on the induction of secondary somatic embryogenesis and plant regeneration of androgenic embryos of this species may be helpful for the further synthesis of secondary metabolites in vitro and their application in the pharmaceutical industry.Ministry of Education and Science of the Republic of Serbia [173015, III 43010

Impact of abscisic acid in overcoming the problem of albinism in horse chestnut androgenic embryos

Horse chestnut (Aesculus hyppocastanum L., Hyppocastanacea) is a relict species with a slow and complex reproductive cycle considered to have horticultural and medical importance. The cycle maybe circumvented via in vitro androgenesis. Androgenesis of horse chestnut was induced in microspores and anther culture on MS media. Some of the horse chestnut androgenic embryos were albinos. Addition of abscisic acid in media (in concentrations of 0.01, 0.1, 0.5, 1, 2, 5, 10, and 20 mg l(-1)) with horse chestnut androgenic embryos has circumvented the reproduction cycle barriers. The best results were achieved on medium with the lowest abscisic acid concentration (0.01 mg l(-1)) in microspore culture. The microspore culture proved to be a better model system for embryo production and albino embryo reduction than anther culture. Flow cytometry analysis after maturation treatments induced by ABA showed that 88 % of green embryos originating from microspore culture were haploid. However, 50 % of green embryos from anther culture were haploid. The remaining analyzed androgenic embryos, from both types of cultures were diploid.Ministry of Education and Science of Serbia [173015

Abscisic Acid Effect on Improving Horse Chestnut Secondary Somatic Embryogenesis

The effect of abscisic acid on the development of primary androgenic embryo and secondary somatic embryogenesis was investigated with the aim of improving multiplication rates and secondary somatic embryo quality in horse chestnut microspore and anther culture. The early embryo stage (globular) had a better response than late stages (heart, torpedo, and cotyledonary) in both types of cultures. Also, microspore culture had a high potential for mass secondary embryo production. The number of secondary somatic embryos was three times higher on hormone-free medium than on medium enriched with 0.01 mg.L-1 abscisic acid. However, most of the embryos on hormone-free medium had abnormal morphology. For this reason, abscisic acid was added to the media to improve embryo quality. The morphology of abscisic acid treated embryos was better than abscisic acid non-treated embryos. The optimal abscisic acid concentration for secondary somatic embryo induction and production of high-quality embryos was 0.01 mg.L-1. Overall, the effect of abscisic acid on the induction of secondary somatic embryogenesis and plant regeneration of androgenic embryos of this species may be helpful for the further synthesis of secondary metabolites in vitro and their application in the pharmaceutical industry.Ministry of Education and Science of the Republic of Serbia [173015, III 43010