The influence of humic substances (HSs) upon the alkaline hydrolysis of N-methyl-N-nitroso-p-tolu... more The influence of humic substances (HSs) upon the alkaline hydrolysis of N-methyl-N-nitroso-p-toluene sulfonamide has been studied. Important inhibition of hydrolysis reaction has been reported. This inhibition has been explained in terms of association of reactants to the humic substances. Kinetic results have been modeled using the micellar pseudophase model. C
also reduced tumor growth in vivo and inhibited pS6 in the implanted tumors. In conclusion, by st... more also reduced tumor growth in vivo and inhibited pS6 in the implanted tumors. In conclusion, by studying the kinase profile of colorectal tumors, we identified relevant activated pathways, and a new multi-kinase compound with significant antitumor properties.
Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeuti... more Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options beyond chemotherapy. Therefore, identification of druggable vulnerabilities is an important aim. Protein kinases play a central role in cancer and particularly in TNBC. They are involved in many oncogenic functions including migration, proliferation, genetic stability or maintenance of stem-cell like properties. In this article we describe a novel multi-kinase inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine genes that showed antiproliferative effect and in vivo antitumoral activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest at the G2/M phase. Pathway analyses identified several deregulated functions including cell proliferation, migration, DNA dam...
Trypanosoma cruzi is a parasitic protist that causes Chagas disease, which is prevalent in Latin ... more Trypanosoma cruzi is a parasitic protist that causes Chagas disease, which is prevalent in Latin America. Because of the unavailability of an effective drug or vaccine, and because about 8 million people are infected with the parasite worldwide, the development of novel drugs demands urgent attention. T. cruzi infects a wide variety of mammalian nucleated cells, with a preference for myocardial cells. Non-dividing trypomastigotes in the bloodstream infect host cells where they are transformed into replication-capable amastigotes. The amastigotes revert to trypomastigotes (trypomastigogenesis) before being shed out of the host cells. Although trypomastigote transformation is an essential process for the parasite, the molecular mechanisms underlying this process have not yet been clarified, mainly because of the lack of an assay system to induce trypomastigogenesis in vitro. Cultivation of amastigotes in a transformation medium composed of 80% RPMI-1640 and 20% Grace's Insect Medi...
RESUMEN Las disoluciones poliméricas son ampliamente empleadas en reología y en la estabilización... more RESUMEN Las disoluciones poliméricas son ampliamente empleadas en reología y en la estabilización de sistemas comerciales. Estas disoluciones están fuertemente condicionadas por la temperatura del sistema y podrán encontrarse formando una única fase líquida homogénea o bien una mezcla de fases. A fin de determinar el valor de la temperatura crítica superior de disolución (UCST) se ha desarrollada un modelo basado en Redes Neuronales que es capaz de predecir con fiabilidad dicha temperatura, cometiendo un error medio en su cálculo del 4,47%. ABSTRACT The polymer solutions are widely used in rheology and in the stabilization of commercial systems. These solutions are strongly conditioned by the system temperature and they could form a single phase or a homogeneous liquid phase mixture. To determine the upper critical solution temperature (UCST) value it has been developed a model based on Neural Networks that is able to reliably predict this temperature, making an average error in its...
L as ciclodextrinas (CDs) son oligosacáridos cíclicos for-mados por unidades de glucosa (1). Las ... more L as ciclodextrinas (CDs) son oligosacáridos cíclicos for-mados por unidades de glucosa (1). Las formas más conocidas, -, -y -CD, están forma-das por seis, siete y ocho unidades de D-glucosa respectivamente. Sus moléculas son a menudo descritas como toroides, o "conos truncados de poca profundidad". Aunque más allá de los detalles de su estructura, la característica más importante de las CDs es su cavidad interna, pues permite formar complejos de inclu-sión con pequeñas moléculas hués-ped que tengan la forma, el tamaño y la polaridad adecuados (2). Gran variedad de compuestos que pue-Ciclodextrinas
This work sketches a reading on Orpheus' myth from three elements whose identity has remained... more This work sketches a reading on Orpheus' myth from three elements whose identity has remained unnoticed in the West, the Muses, the Pierides and the Sirens, as they represent a triple manifestation of the same mythic group.
Determinants of human papillomavirus (HPV)-16 serological conversion and persistence were assesse... more Determinants of human papillomavirus (HPV)-16 serological conversion and persistence were assessed in a population-based cohort of 10 049 women in Guanacaste, Costa Rica. Serologic responses to HPV-16 were measured in 7986 women by VLP-based enzyme-linked immunosorbent assay at both study enrollment (1993/94) and at 5-7 years of follow-up. Seropositive women were defined as >/=5 standard deviations above the mean optical density obtained for studied virgins at enrollment (n=573). Seroconnversion (n=409), persistence (n=675), and clearance (n=541) were defined based on enrollment and follow-up serology measurements. Age-specific distributions revealed that HPV-16 seroconversion was highest among 18- to 24-year-old women, steadily declining with age; HPV-16 seropersistence was lowest in women 65+ years. In age-adjusted multivariate logistic regression models, a 10-fold risk increase for HPV-16 seroconversion was associated with HPV-16 DNA detection at enrollment and follow-up; two-...
Human papillomavirus (HPV) seroprevalence and determinants of seropositivity were assessed in a 1... more Human papillomavirus (HPV) seroprevalence and determinants of seropositivity were assessed in a 10049-woman population-based cohort in Guanacaste, Costa Rica. Serologic responses based on VLP-based ELISA were obtained from the plasma collected at study enrollment in 1993/1994 for HPV-16 (n=9949), HPV-18 (n=9928), HPV-31 (n=9932), and HPV-45 (n=3019). Seropositivity was defined as five standard deviations above the mean optical density obtained for studied virgins (n=573). HPV-16, -18, -31, and -45 seroprevalence was 15, 15, 16, and 11%, respectively. Of women DNA-positive for HPV-16, -18, -31, or -45, seropositivity was 45, 34, 51, and 28%, respectively. Peak HPV seroprevalence occurred a decade after DNA prevalence; lifetime number of sexual partners was the key determinant of seropositivity independent of DNA status and age. DNA- and sero-positive women showed the highest risk for concurrent CIN3/cancer, followed by DNA-positive, sero-negative women.
The Costa Rica Vaccine Trial (CVT) was a randomized clinical trial conducted between 2004 and 201... more The Costa Rica Vaccine Trial (CVT) was a randomized clinical trial conducted between 2004 and 2010, which randomized 7466 women aged 18 to 25 to receive the bivalent HPV-16/18 vaccine or control Hepatitis-A vaccine. Participants were followed for 4 years with cross-over vaccination at the study end. In 2010 the long term follow-up (LTFU) study was initiated to evaluate the 10-year impact of HPV-16/18 vaccination, determinants of the immune response, and HPV natural history in a vaccinated population. Herein, the rationale, design and methods of the LTFU study are described, which actively follows CVT participants in the HPV-arm 6 additional years at biennial intervals (3 additional study visits for 10 years of total follow-up), or more often if clinically indicated. According to the initial commitment, women in the Hepatitis-A arm were offered HPV vaccination at cross-over; they were followed 2 additional years and exited from the study. 92% of eligible CVT women accepted participat...
The first systematic study of the CrðH 2 OÞ 0;1C n ðnZ 1K4Þ series of clusters is herein presente... more The first systematic study of the CrðH 2 OÞ 0;1C n ðnZ 1K4Þ series of clusters is herein presented at the level of the unrestricted DFT B3LYP level in conjunction with electron core potential basis sets. The present structures are relevant for laser-induced and laser-ablation syntheses of chromium compounds, and also for fundamental spectroscopy studies of metal-bearing species in the gas phase. Calculated properties include optimal geometries, total energies, bond lengths, bond angles, natural orbital analysis charges, hydration dissociation energies, and HOMO-LUMO gaps inter alia. Present results reveal a strict correlation between the clusters total energy and their spin state. Except for CrðH 2 OÞ 0C 4 , the most stable clusters in each CrðH 2 OÞ 0;1C n ðnZ 1-4Þ series are high-spin states. Comparisons with a few available theoretical results show good agreement. q Journal of Molecular Structure: THEOCHEM 756 (2005) 55-61 www.elsevier.com/locate/theochem 0166-1280/$ -see front matter q
CO 2 + ethanol mixtures have a huge scientific interest and enormous relevance for many industria... more CO 2 + ethanol mixtures have a huge scientific interest and enormous relevance for many industrial processes. Obtaining of their chemical and physical properties is a fundamental task. Relative permittivity ( r ) of these mixtures is a key property because allows a better knowledge of the structure and the interactions in other media. In this work predictive values of relative permittivity ( r ) of carbon dioxide + ethanol mixtures were obtained implementing artificial neural networks (ANN s ). They are used successfully in very different fields; therefore it is a very useful tool. In this case the obtained results enhance the ones from the usual multiple linear regression analysis. In both cases mass fraction, pressure and temperature experimental data from a direct capacitance method were used.
Nearly stoichiometric ternary LiVMnO spinels were prepared by a solgel method using propionic... more Nearly stoichiometric ternary LiVMnO spinels were prepared by a solgel method using propionic acid to form the resin framework, and subsequent calcination of the gel at 600° C. The resulting material was tested as cathode over the voltage range 5.22.0 V in lithium ...
Chagas disease is caused by an intracellular parasitic protist, Trypanosoma cruzi. As there are n... more Chagas disease is caused by an intracellular parasitic protist, Trypanosoma cruzi. As there are no highly effective drugs against this agent that also demonstrate low toxicity, there is an urgent need for development of new drugs to treat Chagas disease. We have previously demonstrated that the parasite inositol 1,4,5-trisphosphate receptor (TcIP3R) is crucial for invasion of the mammalian host cell by T. cruzi. Here, we report that TcIP3R is a short-lived protein and that its expression is significantly suppressed in trypomastigotes. Treatment of trypomastigotes, an infective stage of T. cruzi, with antisense oligonucleotides specific to TcIP3R deceased TcIP3R protein levels and impaired trypomastigote invasion of host cells. Due to the resulting instability and very low expression level of TcIP3R in trypomastigotes indicates that TcIP3R is a promising target for antisense therapy in Chagas disease.
The influence of humic substances (HSs) upon the alkaline hydrolysis of N-methyl-N-nitroso-p-tolu... more The influence of humic substances (HSs) upon the alkaline hydrolysis of N-methyl-N-nitroso-p-toluene sulfonamide has been studied. Important inhibition of hydrolysis reaction has been reported. This inhibition has been explained in terms of association of reactants to the humic substances. Kinetic results have been modeled using the micellar pseudophase model. C
also reduced tumor growth in vivo and inhibited pS6 in the implanted tumors. In conclusion, by st... more also reduced tumor growth in vivo and inhibited pS6 in the implanted tumors. In conclusion, by studying the kinase profile of colorectal tumors, we identified relevant activated pathways, and a new multi-kinase compound with significant antitumor properties.
Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeuti... more Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options beyond chemotherapy. Therefore, identification of druggable vulnerabilities is an important aim. Protein kinases play a central role in cancer and particularly in TNBC. They are involved in many oncogenic functions including migration, proliferation, genetic stability or maintenance of stem-cell like properties. In this article we describe a novel multi-kinase inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine genes that showed antiproliferative effect and in vivo antitumoral activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest at the G2/M phase. Pathway analyses identified several deregulated functions including cell proliferation, migration, DNA dam...
Trypanosoma cruzi is a parasitic protist that causes Chagas disease, which is prevalent in Latin ... more Trypanosoma cruzi is a parasitic protist that causes Chagas disease, which is prevalent in Latin America. Because of the unavailability of an effective drug or vaccine, and because about 8 million people are infected with the parasite worldwide, the development of novel drugs demands urgent attention. T. cruzi infects a wide variety of mammalian nucleated cells, with a preference for myocardial cells. Non-dividing trypomastigotes in the bloodstream infect host cells where they are transformed into replication-capable amastigotes. The amastigotes revert to trypomastigotes (trypomastigogenesis) before being shed out of the host cells. Although trypomastigote transformation is an essential process for the parasite, the molecular mechanisms underlying this process have not yet been clarified, mainly because of the lack of an assay system to induce trypomastigogenesis in vitro. Cultivation of amastigotes in a transformation medium composed of 80% RPMI-1640 and 20% Grace's Insect Medi...
RESUMEN Las disoluciones poliméricas son ampliamente empleadas en reología y en la estabilización... more RESUMEN Las disoluciones poliméricas son ampliamente empleadas en reología y en la estabilización de sistemas comerciales. Estas disoluciones están fuertemente condicionadas por la temperatura del sistema y podrán encontrarse formando una única fase líquida homogénea o bien una mezcla de fases. A fin de determinar el valor de la temperatura crítica superior de disolución (UCST) se ha desarrollada un modelo basado en Redes Neuronales que es capaz de predecir con fiabilidad dicha temperatura, cometiendo un error medio en su cálculo del 4,47%. ABSTRACT The polymer solutions are widely used in rheology and in the stabilization of commercial systems. These solutions are strongly conditioned by the system temperature and they could form a single phase or a homogeneous liquid phase mixture. To determine the upper critical solution temperature (UCST) value it has been developed a model based on Neural Networks that is able to reliably predict this temperature, making an average error in its...
L as ciclodextrinas (CDs) son oligosacáridos cíclicos for-mados por unidades de glucosa (1). Las ... more L as ciclodextrinas (CDs) son oligosacáridos cíclicos for-mados por unidades de glucosa (1). Las formas más conocidas, -, -y -CD, están forma-das por seis, siete y ocho unidades de D-glucosa respectivamente. Sus moléculas son a menudo descritas como toroides, o "conos truncados de poca profundidad". Aunque más allá de los detalles de su estructura, la característica más importante de las CDs es su cavidad interna, pues permite formar complejos de inclu-sión con pequeñas moléculas hués-ped que tengan la forma, el tamaño y la polaridad adecuados (2). Gran variedad de compuestos que pue-Ciclodextrinas
This work sketches a reading on Orpheus' myth from three elements whose identity has remained... more This work sketches a reading on Orpheus' myth from three elements whose identity has remained unnoticed in the West, the Muses, the Pierides and the Sirens, as they represent a triple manifestation of the same mythic group.
Determinants of human papillomavirus (HPV)-16 serological conversion and persistence were assesse... more Determinants of human papillomavirus (HPV)-16 serological conversion and persistence were assessed in a population-based cohort of 10 049 women in Guanacaste, Costa Rica. Serologic responses to HPV-16 were measured in 7986 women by VLP-based enzyme-linked immunosorbent assay at both study enrollment (1993/94) and at 5-7 years of follow-up. Seropositive women were defined as >/=5 standard deviations above the mean optical density obtained for studied virgins at enrollment (n=573). Seroconnversion (n=409), persistence (n=675), and clearance (n=541) were defined based on enrollment and follow-up serology measurements. Age-specific distributions revealed that HPV-16 seroconversion was highest among 18- to 24-year-old women, steadily declining with age; HPV-16 seropersistence was lowest in women 65+ years. In age-adjusted multivariate logistic regression models, a 10-fold risk increase for HPV-16 seroconversion was associated with HPV-16 DNA detection at enrollment and follow-up; two-...
Human papillomavirus (HPV) seroprevalence and determinants of seropositivity were assessed in a 1... more Human papillomavirus (HPV) seroprevalence and determinants of seropositivity were assessed in a 10049-woman population-based cohort in Guanacaste, Costa Rica. Serologic responses based on VLP-based ELISA were obtained from the plasma collected at study enrollment in 1993/1994 for HPV-16 (n=9949), HPV-18 (n=9928), HPV-31 (n=9932), and HPV-45 (n=3019). Seropositivity was defined as five standard deviations above the mean optical density obtained for studied virgins (n=573). HPV-16, -18, -31, and -45 seroprevalence was 15, 15, 16, and 11%, respectively. Of women DNA-positive for HPV-16, -18, -31, or -45, seropositivity was 45, 34, 51, and 28%, respectively. Peak HPV seroprevalence occurred a decade after DNA prevalence; lifetime number of sexual partners was the key determinant of seropositivity independent of DNA status and age. DNA- and sero-positive women showed the highest risk for concurrent CIN3/cancer, followed by DNA-positive, sero-negative women.
The Costa Rica Vaccine Trial (CVT) was a randomized clinical trial conducted between 2004 and 201... more The Costa Rica Vaccine Trial (CVT) was a randomized clinical trial conducted between 2004 and 2010, which randomized 7466 women aged 18 to 25 to receive the bivalent HPV-16/18 vaccine or control Hepatitis-A vaccine. Participants were followed for 4 years with cross-over vaccination at the study end. In 2010 the long term follow-up (LTFU) study was initiated to evaluate the 10-year impact of HPV-16/18 vaccination, determinants of the immune response, and HPV natural history in a vaccinated population. Herein, the rationale, design and methods of the LTFU study are described, which actively follows CVT participants in the HPV-arm 6 additional years at biennial intervals (3 additional study visits for 10 years of total follow-up), or more often if clinically indicated. According to the initial commitment, women in the Hepatitis-A arm were offered HPV vaccination at cross-over; they were followed 2 additional years and exited from the study. 92% of eligible CVT women accepted participat...
The first systematic study of the CrðH 2 OÞ 0;1C n ðnZ 1K4Þ series of clusters is herein presente... more The first systematic study of the CrðH 2 OÞ 0;1C n ðnZ 1K4Þ series of clusters is herein presented at the level of the unrestricted DFT B3LYP level in conjunction with electron core potential basis sets. The present structures are relevant for laser-induced and laser-ablation syntheses of chromium compounds, and also for fundamental spectroscopy studies of metal-bearing species in the gas phase. Calculated properties include optimal geometries, total energies, bond lengths, bond angles, natural orbital analysis charges, hydration dissociation energies, and HOMO-LUMO gaps inter alia. Present results reveal a strict correlation between the clusters total energy and their spin state. Except for CrðH 2 OÞ 0C 4 , the most stable clusters in each CrðH 2 OÞ 0;1C n ðnZ 1-4Þ series are high-spin states. Comparisons with a few available theoretical results show good agreement. q Journal of Molecular Structure: THEOCHEM 756 (2005) 55-61 www.elsevier.com/locate/theochem 0166-1280/$ -see front matter q
CO 2 + ethanol mixtures have a huge scientific interest and enormous relevance for many industria... more CO 2 + ethanol mixtures have a huge scientific interest and enormous relevance for many industrial processes. Obtaining of their chemical and physical properties is a fundamental task. Relative permittivity ( r ) of these mixtures is a key property because allows a better knowledge of the structure and the interactions in other media. In this work predictive values of relative permittivity ( r ) of carbon dioxide + ethanol mixtures were obtained implementing artificial neural networks (ANN s ). They are used successfully in very different fields; therefore it is a very useful tool. In this case the obtained results enhance the ones from the usual multiple linear regression analysis. In both cases mass fraction, pressure and temperature experimental data from a direct capacitance method were used.
Nearly stoichiometric ternary LiVMnO spinels were prepared by a solgel method using propionic... more Nearly stoichiometric ternary LiVMnO spinels were prepared by a solgel method using propionic acid to form the resin framework, and subsequent calcination of the gel at 600° C. The resulting material was tested as cathode over the voltage range 5.22.0 V in lithium ...
Chagas disease is caused by an intracellular parasitic protist, Trypanosoma cruzi. As there are n... more Chagas disease is caused by an intracellular parasitic protist, Trypanosoma cruzi. As there are no highly effective drugs against this agent that also demonstrate low toxicity, there is an urgent need for development of new drugs to treat Chagas disease. We have previously demonstrated that the parasite inositol 1,4,5-trisphosphate receptor (TcIP3R) is crucial for invasion of the mammalian host cell by T. cruzi. Here, we report that TcIP3R is a short-lived protein and that its expression is significantly suppressed in trypomastigotes. Treatment of trypomastigotes, an infective stage of T. cruzi, with antisense oligonucleotides specific to TcIP3R deceased TcIP3R protein levels and impaired trypomastigote invasion of host cells. Due to the resulting instability and very low expression level of TcIP3R in trypomastigotes indicates that TcIP3R is a promising target for antisense therapy in Chagas disease.
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