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Buenos Aires, Argentina

Andres N.C.,CONICET | Fermento M.E.,CONICET | Gandini N.A.,CONICET | Romero A.L.,IACA Laboratorios | And 4 more authors.
Experimental and Molecular Pathology

The expression of heme oxygenase-1 (HO-1) has been shown to be up-regulated in colorectal cancer (CRC), but the role it plays in this cancer type has not yet been addressed. The aims of this study have been to analyze HO-1 expression in human invasive CRC, evaluate its correlation with clinical and histo-pathological parameters and to investigate the mechanisms through which the enzyme influences tumor progression. We confirmed that HO-1 was over-expressed in human invasive CRC and found that the expression of the enzyme was associated with a longer overall survival time. In addition, we observed in a chemically-induced CRC animal model that total and nuclear HO-1 expression increases with tumor progression. Our investigation of the mechanisms involved in HO-1 action in CRC demonstrates that the protein reduces cell viability through induction of cell cycle arrest and apoptosis and, importantly, that a functional p53 tumor suppressor protein is required for these effects. This reduction in cell viability is accompanied by modulation of the levels of p21, p27, and cyclin D1 and by modulation of Akt and PKC pathways. Altogether, our results demonstrate an antitumoral role of HO-1 and points to the importance of p53 status in this antitumor activity. © 2014 Elsevier Inc.. Source

Crespillo M.,Mixture Commission of the GHEP ISFG | Crespillo M.,INTCF National Institute of Toxicology and Forensic Science | Barrio P.A.,Mixture Commission of the GHEP ISFG | Barrio P.A.,INTCF National Institute of Toxicology and Forensic Science | And 33 more authors.
Forensic Science International: Genetics

One of the main objectives of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the area of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, three exercises have been organized (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03), with 32, 24 and 17 participant laboratories respectively. The exercise aims to give a general vision by addressing, through the proposal of mock cases, aspects related to the edition of mixture profiles and the statistical treatment. The main conclusions obtained from these exercises may be summarized as follows. Firstly, the data show an increased tendency of the laboratories toward validation of DNA mixture profiles analysis following international recommendations (ISO/IEC 17025:2005). Secondly, the majority of discrepancies are mainly encountered in stutters positions (53.4%, 96.0% and 74.9%, respectively for the three editions). On the other hand, the results submitted reveal the importance of performing duplicate analysis by using different kits in order to reduce errors as much as possible. Regarding the statistical aspect (GHEP-MIX02 and 03), all participants employed the likelihood ratio (LR) parameter to evaluate the statistical compatibility and the formulas employed were quite similar. When the hypotheses to evaluate the LR value were locked by the coordinators (GHEP-MIX02) the results revealed a minor number of discrepancies that were mainly due to clerical reasons. However, the GHEP-MIX03 exercise allowed the participants to freely come up with their own hypotheses to calculate the LR value. In this situation the laboratories reported several options to explain the mock cases proposed and therefore significant differences between the final LR values were obtained. Complete information concerning the background of the criminal case is a critical aspect in order to select the adequate hypotheses to calculate the LR value. Although this should be a task for the judicial court to decide, it is important for the expert to account for the different possibilities and scenarios, and also offer this expertise to the judge. In addition, continuing education in the analysis and interpretation of mixture DNA profiles may also be a priority for the vast majority of forensic laboratories. © 2014 Elsevier Ireland Ltd. Source

Streitenberger E.R.,IACA Laboratorios | Chavez C.M.,IACA Laboratorios | Rizzo M.S.,Hospital Interzonal Dr. Jose Penna | Suarez A.I.,IACA Laboratorios
Revista Argentina de Microbiologia

Anaerobiospirillum thomasii has been reported as a causative agent of diarrhea in humans; however no bacteremia associated with this pathogen has been described so far. We present here the first case of fatal A. thomasii bacteremia in an alcoholic patient. © 2015 Asociación Argentina de Microbiología. Published by Elsevier España, S.L.U. Source

Keller G.A.,University of Buenos Aires | Keller G.A.,Favaloro University | De Mena F.,IACA Laboratorios | Simoni M.V.,IACA Laboratorios | And 2 more authors.
Current Medical Research and Opinion

Objective: To evaluate the relative bioavailability of a new formulation containing 5mg mosapride and 10mg rabeprazole (T) and compare it with the branded formulations of both drugs co-administered in separate tablets (R) to meet the regulatory requirements of bioequivalence in Argentina. Methods: A randomized-sequence, open-label, two-period crossover study was conducted on 24 healthy Caucasian volunteers in a fasting state. A single oral dose of either T or R formulations was followed by a 7-day washout period. Blood samples for mosapride were collected before administration (baseline) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, and 24h after administration. Samples for rabeprazole were taken baseline and at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8 and 10h after dosing. Mosapride and rabeprazole concentrations were determined using a validated LC-MS/MS method. Adverse events were monitored based on clinical parameters and volunteer reports. Results: The geometric means (90% CI) Cmax for mosapride in T and R were 23.13 (20.0539.45) and 23.09 (21.6932.37) ng/mL, the AUC0-t were 70.80 (66.23102.37) and 70.81 (66.3593.26) ngh/mL and the AUC0-∞ were 74.05 (69.29106.11) and 74.98 (70.4397.77) ngh/mL. For rabeprazole T and R the Cmax were 197.42 (186.12239.91) and 195.50 (186.08250.07) ng/mL, the AUC0-t were 294.90 (275.13374.15) and 296.96 (280.11387.89) ngh/mL and the AUC0-∞ were 301.12 (280.78380.82) and 304.07 (286.60394.21), respectively. No differences were detected between the formulations. The T/R ratios (90% CI) for Cmax, AUC 0-t and AUC0-∞ were 100.17% (82.35121.84), 99.99% (87.58114.16) and 98.77% (87.02112.11) for mosapride, and 100.99% (85.14119.77), 99.31% (84.74116.38) and 99.03% (85.07115.28) for rabeprazole. No subject complained of adverse events. Conclusions: In this single-dose study, the mosapride/rabeprazole tablets (test formulation) met the criterion for bioequivalence with the reference formulations. Study limitations include single-dose, open-label design, and a small sample of healthy volunteers. © 2011 Informa UK Ltd. Source

Suldrup N.A.F.,IACA Laboratorios | Streitenberger E.R.,IACA Laboratorios
Acta Bioquimica Clinica Latinoamericana

In Argentina, newborn screening is mandatory by law for certain conditions, but not for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. G6PD deficiency is an X chromosome-linked disorder which causes, in most cases, neonatal jaundice, and even kernicterus and acute intravascular hemolysis proporcioin association with exposure to oxidizing substances, ingestion of certain foods, drugs or medications, some infections, or any other situation involving cellular stress. It is one of the most common enzymopathies in the world. The aim of this study was to determine the prevalence of G6PDH deficiency in Argentina. A total of 4.500 newborn male dried blood samples from different regions of the country were analyzed. The activity of the enzyme was quantitatively determined by an "in house" developed fluorometric method, measuring the rate of formation of NADPH. It was evaluated against a commercial method. A total of 13 (0.29%) children expressing total deficiency were found, while 33 (0.73%) demonstrated intermediate deficiency. This finding is important as such patients must receive a preventive and educational care. Screening for G6PDH deficiency is feasible and not only would it take early preventive measures against severe hemolysis in the neonatal period, but also other preventive measures later in life. Source

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