The First Enantioselective Total Synthesis of (−)-trans-Dihydronarciclasine

A feasible and enantioselective total synthesis of (−)-trans-dihydronarciclasine [(−)-1], a highly biologically active alkaloid, was devised starting from vanillin (8). The key step of this new synthesis was an asymmetric, organocatalytic Michael addition, in which an optically active nitropentanone [(−)-13] was obtained from a butenone derivative (12). Excellent enantioselectivity (>99% ee) was achieved using the (8S,9S)-9-amino(9-deoxy)epiquinine (16) organocatalyst. The target molecule can be prepared in 13 steps from compound (−)-13. The total synthesis has provided a facile and first access to the ent-form of naturally occurring (+)-trans-dihydronarciclasine, a highly potent cytostatic alkaloid

Roma és nem roma munkanélküliek közegészségügyi helyzete az Ózdi kistérségben | Public health issues of Roma and non-Roma unemployed persons in the Ózd microregion

Bevezetés: Korábbi tanulmányukban a szerzők megállapították, hogy az Ózdi kistérség munkanélkülijeinek közegészségügyi-járványügyi biztonsága és szociális helyzete az országos átlaghoz képest rosszabb. Célkitűzés: Korábbi vizsgálataik folytatásaként célul tűzték ki annak meghatározását, hogy az Ózdi kistérség roma munkanélkülijeinek az országos átlagnál jelentősen nagyobb aránya hozzájárul-e a kistérségnek az ország más térségeinél rosszabb közegészségügyi-járványügyi biztonságához, a kistérség munkanélkülijei tanulásra alig vagy nem alkalmas lakókörnyezeti higiénés helyzetéhez. Módszer: 2012-ben és 2013-ban 400 fő 18–61 éves roma és nem roma férfi és nő munkanélkülit kérdőíves-önkitöltéses-kikérdezéses, valamint foglalkozás-orvostani módszerekkel vizsgáltak; az egyes csoportokba – a jelzett sorrendben – 96, 97, 114, 93 személy tartozott. Eredmények: Megállapították, hogy egyrészt valamennyi vizsgált paramétercsoport (közegészségügyi-járványügyi biztonság, in-door lakókörnyezeti higiéné, tanulási feltételek) a romák szignifikánsan hátrányosabb helyzetét jelezte a magyar munkanélküliekhez viszonyítva; másrészt roma személyekben a vizsgált paraméterek értéke az életminőségét hátrányosan befolyásoló tényezőktől függött (munkanélküliség, mélyszegénység, alacsonyabb szintű iskolázottság, rövidebb élet). A térségben a magyar munkanélküliek 1/10–1/5-ének életkörülménye hasonlított a roma munkanélküliek átlagos életkörülményéhez. Következtetések: 1. A romák Ózdi kistérségen belüli nagyobb aránya hozzájárul a kistérség rosszabb közegészségügyi-járványügyi biztonságához, munkanélkülijeinek az ország más térségeiben élő munkanélküliekénél rosszabb életkörülményéhez. 2. A romák megfelelő életkörülményt biztosító foglalkoztatásához szükséges képzettség elérését lehetővé tevő tanulási feltételek megteremtése elengedhetetlen. Orv. Hetil., 2014, 155(15), 582–589. | Introduction: In their previous studies authors of the present work showed that public health situation and socioeconomic position of unemployed Roma persons in the Ozd microregion were well below the average of the whole Hungarian population. Aim: To continue these previous studies, the authors wanted to determine whether the greater proportion of the unemployed Roma persons in the Ózd microregion compared to the country average could contribute to the worse public health situation and the poor hygienic situation of the living environment of unemployed persons hardly or not suitable for learning. Method: Data from 400 unemployed Roma (96 males, 97 females) and caucasian non-Roma subjects (114 males, 93 females) obtained in 2012 and 2013 using self-completed and interview questionnaires were analysed. In addition, occupational medical examination methods were applied and the results were analysed. Results: It was found that all studied parameters (public health and epidemiological safety, in-door living environmental hygiene, conditions for learning) indicated significantly disadvantaged situation of the Roma compared to the non-Roma unemployed persons. There was a clear relationship between these examined parameters and other factors adversely influencing the quality of life of Roma persons (unemployment, deep poverty, lower level of education, shorter life span). Finally, the results showed that the quality of life conditions of the lowest 1/10, 1/5 of the non-Roma unemployed persons were comparable to those found in the average of Roma unemployed persons. Conclusions: The authors conclude that i) the greater proportion of unemployed Roma persons in the Ozd microregion contributes to the worse public health, epidemiological safety and the worse living conditions of unemployed persons in this regions of the country; ii) It would be essential to provide Roma persons with conditions appropriate for learning, which could enable them to get qualification necessary for employment. Orv. Hetil., 2014, 155(15), 582–589

Novel Polyurethane Scaffolds Containing Sucrose Crosslinker for Dental Application

In this paper, the synthesis, characterization, and properties of crosslinked poly(ε-caprolactone)-based polyurethanes as potential tissue replacement materials are reported. The polyurethane prepolymers were prepared from poly(ε-caprolactone)diol (PCD), polyethylene glycol (PEG)/polylactic acid diol (PLAD), and 1,6-hexamethylene diisocyanate (HDI). In these segmented polyurethanes, the role of PEG/PLAD was to tune the hydrophobic/hydrophilic character of the resulting polymer while sucrose served as a crosslinking agent. PLAD was synthesized by the polycondensation reaction of D,L-lactic acid and investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nuclear magnetic resonance spectroscopy (NMR). The crosslinked polyurethane samples (SUPURs) obtained were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (AT-FT-IR), swelling, and mechanical (uniaxial tensile tests) experiments. The thermo and thermomechanical behavior were studied by differential scanning calorimetry (DSC) and dynamical mechanical analysis (DMA). The viability of dental pulp stem cells was investigated in the case of polyurethanes composed of fully biocompatible elements. In our studies, none of our polymers showed toxicity to stem cells (DPSCs)

Poly(ADP-ribose) polymerase-2 depletion reduces doxorubicin-induced damage through SIRT1 induction

AIMS: Doxorubicin (DOX) is widely used in cytostatic treatments, although it may cause cardiovascular dysfunction as a side effect. DOX treatment leads to enhanced free radical production that in turn causes DNA strand breakage culminating in poly(ADP-ribose) polymerase (PARP) activation and mitochondrial and cellular dysfunction. DNA nicks can activate numerous enzymes, such as PARP-2. Depletion of PARP-2 has been shown to result in a protective phenotype against free radical-mediated diseases, suggesting similar properties in the case of DOX-induced vascular damage. METHODS AND RESULTS: PARP-2(+/+) and PARP-2(-/-) mice and aortic smooth muscle (MOVAS) cells were treated with DOX (25 mg/kg or 3 μM, respectively). Aortas were harvested 2-day post-treatment while MOVAS cells were treated with DOX for 7 hours. Aortas from PARP-2(-/-) mice displayed partial protection against DOX toxicity, and the protection depended on the conservation of smooth muscle but not on the conservation of endothelial function. DOX treatment evoked free radical production, DNA breakage and PARP activation. Importantly, depletion of PARP-2 did not quench any of these phenomena, suggesting an alternative mechanism. Depletion of PARP-2 prevented DOX-induced mitochondrial dysfunction through SIRT1 activation. Genetic deletion of PARP-2 resulted in the induction of the SIRT1 promoter and consequently increased SIRT1 expression both in aortas and in MOVAS cells. SIRT1 activation enhanced mitochondrial biogenesis, which provided protection against DOX-induced mitochondrial damage. CONCLUSION: Our data identify PARP-2 as a mediator of DOX toxicity by regulating vascular SIRT1 activity and mitochondrial biogenesis. Moreover, to the best of our knowledge, this is the first report of SIRT1 as a protective factor in the vasculature upon oxidative stress