DNA adducts in human urinary bladder and other tissues.

Tobacco smoking is associated with an increased risk of cancer in a number of organs, including bladder and lung. Tobacco smoke contains at least 50 known chemical carcinogens that exert their biological effects through their covalent binding to cellular DNA. Examining human DNA for the presence of altered nucleotides is a means of monitoring exposure to genotoxic chemicals. DNA isolated from 73 human bladder biopsies has been analyzed by 32P-postlabeling for the presence of aromatic/hydrophobic adducts. Butanol extraction of DNA digests resulted in up to a 3-fold greater recovery of adducts than nuclease P1 digestion. Among 16 nonsmokers, adduct levels were in the range 3.2-20.8/10(8) nucleotides (mean 9.7). Eight ex-smokers had values in the range 2.6-12.3 (mean 7.1). Thirteen smokers had adduct levels between 1.3 and 26.7 adducts/10(8) nucleotides (mean 9.5, not different from nonsmokers). Six cigar smokers had higher levels of adducts (mean 12.1, range 7.3-15.0), but pipe smokers did not (five samples, mean 8.6, range 2.9-12.7). A further 8 samples from nonsmokers and 17 from smokers were examined in more detail. Although most of the DNA binding appears not to be smoking related, the levels of one adduct were found to be on average 2-fold higher in smokers (p < 0.005, one-tailed t test). Studies on tissues of the respiratory tract demonstrate a correlation between DNA adduct levels and exposure to tobacco smoke. Evidence to date on the influence of smoking on adducts in peripheral blood cells is equivocal; some studies demonstrate a significant effect, whereas others do not.(ABSTRACT TRUNCATED AT 250 WORDS

Adult liver transplantation in the congenital absence of inferior vena cava

Whereas congenital absence of inferior vena cava observed in paediatric population more often than not, as an isolated or syndromic variety, this is seldom encountered in adult liver transplant recipients. There appear few sporadic reports in the literature on experience of such anomaly in adults. Given the rarity of situation, surprising encounters of such anomalies may pose challenge to the unprepared transplant surgeon and unfavourable outcomes may even have resulted in under-reportage of this condition. In this brief report we document our recent experience with two such cases and this is supplemented with extensive reference to the literature on classification of such anomalies with the endeavour to document implications of such in the adult liver transplant setting. (C) 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub

Heterogeneous slow dynamics in a two dimensional doped classical antiferromagnet

We introduce a lattice model for a classical doped two dimensional antiferromagnet which has no quenched disorder, yet displays slow dynamics similar to those observed in supercooled liquids. We calculate two-time spatial and spin correlations via Monte Carlo simulations and find that for sufficiently low temperatures, there is anomalous diffusion and stretched-exponential relaxation of spin correlations. The relaxation times associated with spin correlations and diffusion both diverge at low temperatures in a sub-Arrhenius fashion if the fit is done over a large temperature-window or an Arrhenius fashion if only low temperatures are considered. We find evidence of spatially heterogeneous dynamics, in which vacancies created by changes in occupation facilitate spin flips on neighbouring sites. We find violations of the Stokes-Einstein relation and Debye-Stokes-Einstein relation and show that the probability distributions of local spatial correlations indicate fast and slow populations of sites, and local spin correlations indicate a wide distribution of relaxation times, similar to observ ations in other glassy systems with and without quenched disorder.Comment: 12 pages, 17 figures, corrected erroneous figure, and improved quality of manuscript, updated reference

Organization of atomic bond tensions in model glasses

In order to understand whether internal stresses in glasses are correlated or randomly distributed, we study the organization of atomic bond tensions (normal forces between pairs of atoms). Measurements of the invariants of the atomic bond tension tensor in simulated 2D and 3D binary Lennard-Jones glasses, reveal new and unexpected correlations and provide support for Alexander's conjecture about the non-random character of internal stresses in amorphous solids