Efficacy of tafenoquine in the prophylaxis and treatment of malaria by Plasmodium vivax, systematic review and meta-analysis / Eficacia de la tafenoquina en la profilaxis y tratamiento de la malaria por Plasmodium vivax, revisión sistemática y metaanálisis

Introduction: Tafenoquine was approved in 2018 by the Food and Drug Administration in the United States and in 2019 by the Therapeutic Goods Administration in Australia. Its administration in a single dose and its mechanism of action in the acute and latent phases of the disease have been studied to change the treatment regimen for Plasmodium vivax malaria. Objective: To evaluate the available scientific evidence of the efficacy of tafenoquine in prophylaxis and treatment between 2009 and 2019. Materials and methods: We established the MeSH and DeCS descriptors and we used the syntax ((Malaria Vivax) AND (tafenoquine) AND (prophylaxis)) OR [(Malaria Vivax) AND (tafenoquine) AND (relapse)] in the following databases: Pubmed, The Cochrane Central Register of Controlled Clinical Trials (CENTRAL), ISIS Web of Science, Lilacs, and Scopus. The results obtained were subjected to critical analysis (CASPE matrix). The quantitative analysis was performed with risk differences in survival analysis (Kaplan Meier) in the final three articles. Results: Three studies underwent meta-analysis (Llanos-Cuentas, 2014; Llanos-Cuentas, 2019, and Lacerda, 2019) to evaluate the efficacy of the treatment with tafenoquine compared to primaquine. A global risk difference of 0.04 was obtained (95% CI: 0.00-0.08; p=0.07). Tafenoquine did not show inferiority in the efficacy of treatment compared to the primaquine scheme. Conclusion: Tafenoquine is a therapeutic alternative to primaquine that improves adherence, which could bring Colombia closer to the goals of the World Technical Strategy against Malaria 2016-2030.

Introducción. La tafenoquina fue aprobada en el 2018 por la Food and Drug Administration de Estados Unidos y, en el 2019, por la Therapeutic Goods Administration en Australia. Su administración en dosis única y su mecanismo de acción en las fases aguda y latente han sido objeto de estudio para cambiar el esquema de tratamiento de la malaria por Plasmodium vivax. Objetivo. Evaluar la evidencia científica disponible sobre la eficacia de la tafenoquina en la profilaxis y el tratamiento de la malaria por P. vivax, entre el 2009 y el 2019. Materiales y métodos. Se establecieron los descriptores MeSH y DeCS. Se utilizó la sintaxis ((Malaria Vivax) AND (tafenoquine) AND (prophylaxis)) OR [(Malaria Vivax) AND (tafenoquine) AND (relapse)] en las siguientes bases de datos: Pubmed, The Cochrane Central Register of Controlled Clinical Trials (CENTRAL), ISIS Web of Science, Lilacs y Scopus. Los resultados obtenidos se sometieron a análisis crítico (matriz CASPE). El análisis cuantitativo se realizó utilizando la diferencia de riesgos en análisis de supervivencia (Kaplan-Meier) en los tres artículos finales. Resultados. Se sometieron tres estudios a metaanálisis (Llanos-Cuentas, 2014; Llanos-Cuentas, 2019, y Lacerda, 2019) para evaluar la eficacia del tratamiento con tafenoquina en comparación con primaquina. Se obtuvo una diferencia de riesgo global de 0,04 (IC95% 0-0,08; p=0,07). La tafenoquina no mostró inferioridad en la eficacia del tratamiento frente al esquema de primaquina. Conclusión. La tafenoquina es una alternativa que mejora el cumplimiento del tratamiento, lo que podría acercar a Colombia a las metas de la Estrategia Técnica Mundial contra la Malaria, 2016-2030.

Structural Characterization of the Plasticizers' Role in Polymer Inclusion Membranes Used for Indium (III) Transport Containing IONQUEST® 801 as Carrier.

Polymer inclusion membranes containing cellulose triacetate as support, Ionquest® 801 ((2-ethylhexyl acid) -mono (2-ethylhexyl) phosphonic ester) as extractant, and 2NPOE (o-nitrophenyl octyl ether) or TBEP (tri (2-butoxyethyl phosphate)) as plasticizers were characterized using several instrumental techniques (Fourier Transform Infrared Spectroscopy (FT-IR), Reflection Infrared Mapping Microscopy (RIMM), Electrochemical Impedance Spectroscopy (EIS), Differential Scanning Calorimetry (DSC)) with the aim of determining physical and chemical parameters (structure, electric resistance, dielectric constant, thickness, components' distributions, glass transition temperature, stability) that allow a better comprehension of the role that the plasticizer plays in PIMs designed for In(III) transport. In comparison to TBEP, 2NPOE presents less dispersion and affinity in the PIMs, a plasticizer effect at higher content, higher membrane resistance and less permittivity, and a pronounced drop in the glass transition temperature. However, the increase in permittivity with In (III) sorption is more noticeable and, in general, PIMs with 2NPOE present higher permeability values. These facts indicate that In (III) transport is favored in membranes with chemical environment of high polarity and efficiently plasticized. A drawback is the decrease in stability because of the minor affinity among the components in 2NPOE-PIMs.

Prevalence of adult female acne in Colombia: A population-based study.

BACKGROUND: Acne is a common inflammatory skin disease with adolescents being the most affected by this condition; however, acne also occurs frequently in the adult population. Adult acne is defined as late-onset acne or acne that persists beyond age 25 years. In terms of epidemiologic data, reports of adult female acne prevalence range from 5.5% to 61.5% around the world. OBJECTIVE: The aim of this study was to estimate the prevalence and trace the trend of adult female acne in Colombia over the last 5 years. METHODS: Using nationwide data from the General System of Social Security and Health in Colombia through the Sistema Integrado de Información de la Protección Social database and International Classification of Diseases, 10th Revision, diagnostic codes, a cross-sectional study was conducted to estimate the prevalence of adult female acne in outpatients in Colombia from 2015 to 2019. RESULTS: For the 5-year study period, overall acne prevalence was 2.14 per 1000 population. The highest annual prevalence (2.94 per 1000 population) was in 2019 and the lowest prevalence (1.71 per 1000 population) was in 2015. Prevalence peaked in patients age 25 to 29 years, and decreased to <1 per 1000 population in those age <50 years. CONCLUSION: This nationwide study of adult female acne in Colombia suggests an increasing trend in prevalence over the last 5 years. We recommend further studies to determine risk factors involved in this condition.

ICT Services for Life Improvement for the Elderly.

Integrated care ICT Platform to support patients, care-givers and health/social professionals in the care of dementia and Parkinson's disease with training, empowerment, sensor-based data analysis and cooperation services based on user-friendly interfaces.

Pretreatment with laccase and a phenolic mediator degrades lignin and enhances saccharification of Eucalyptus feedstock.

BACKGROUND: Biofuel production from lignocellulosic material is hampered by biomass recalcitrance towards enzymatic hydrolysis due to the compact architecture of the plant cell wall and the presence of lignin. The purpose of this work is to study the ability of an industrially available laccase-mediator system to modify and remove lignin during pretreatment of wood (Eucalyptus globulus) feedstock, thus improving saccharification, and to analyze the chemical modifications produced in the whole material and especially in the recalcitrant lignin moiety. RESULTS: Up to 50% lignin removal from ground eucalypt wood was attained by pretreatment with recombinant Myceliophthora thermophila laccase and methyl syringate as mediator, followed by alkaline peroxide extraction in a multistage sequence. The lignin removal directly correlated with increases (approximately 40%) in glucose and xylose yields after enzymatic hydrolysis. The pretreatment using laccase alone (without mediator) removed up to 20% of lignin from eucalypt wood. Pyrolysis-gas chromatography/mass spectrometry of the pretreated wood revealed modifications of the lignin polymer, as shown by lignin markers with shortened side chains and increased syringyl-to-guaiacyl ratio. Additional information on the chemical modifications produced was obtained by two-dimensional nuclear magnetic resonance of the whole wood swollen in dimethylsulfoxide-d6. The spectra obtained revealed the removal of guaiacyl and syringyl lignin units, although with a preferential removal of the former, and the lower number of aliphatic side-chains per phenylpropane unit (involved in main ß-O-4' and ß-ß' inter-unit linkages), in agreement with the pyrolysis-gas chromatography/mass spectrometry results, without a substantial change in the wood polysaccharide signals. However, the most noticeable modification observed in the spectra was the formation of Cα-oxidized syringyl lignin units during the enzymatic treatment. Further insight into the modifications of lignin structure, affecting other inter-unit linkages and oxidized structures, was attained by nuclear magnetic resonance of the lignins isolated from the eucalypt feedstock after the enzymatic pretreatments. CONCLUSIONS: This work shows the potential of an oxidative enzymatic pretreatment to delignify and improve cellulase saccharification of a hardwood feedstock (eucalypt wood) when applied directly on the ground lignocellulosic material, and reveals the main chemical changes in the pretreated material, and its recalcitrant lignin moiety, behind the above results.

[Impact assessment of the rotavirus vaccine in Colombia using rapid evaluation methods]. / Evaluación del impacto de la vacuna contra rotavirus en Colombia usando métodos rápidos de evaluación.

OBJECTIVE: Estimate the effectiveness of the monovalent rotavirus vaccine in preventing the need to hospitalize children under 2 years old for acute diarrheal disease in five Colombian cities. METHODS: A population survey was conducted based on a probability sample of children over 2 months and under 24 months of age in five Colombian cities (Barranquilla, Bogotá, Cali, Cartagena, and Riohacha) over the period from August through October 2010. The vaccine had been introduced in the Expanded Program on Immunization in January 2009. Rotavirus vaccination coverage was estimated by age group; the cumulative incidence of hospitalization for severe diarrhea was determined; and the magnitude of correlation between vaccination with one or two doses of rotavirus vaccine and hospitalization for diarrhea was calculated using the age-adjusted probability ratio (PR) and other epidemiologically significant factors. Effectiveness of the vaccine was estimated using the expression 1-PR. RESULTS: Coverage with a single dose of the rotavirus vaccine was 87.3%. During the 12 months prior to the survey, 1 453 of the children under 24 months old in the study areas (43.2%) had presented with diarrhea, and of these, 174 (5.2%) had been hospitalized for this cause. The effectiveness of two doses of the vaccine in preventing hospitalization for severe diarrhea was 68% (CI 95% = 55%-77%). CONCLUSIONS: In Colombia, rotavirus vaccination protects against hospitalization for diarrhea due to any cause. The use of cross-sectional surveys appeared to be adequate for rapid evaluation of an immunization program's effectiveness with a new vaccine.

Evaluación del impacto de la vacuna contra rotavirus en Colombia usando métodos rápidos de evaluación / Impact assessment of the rotavirus vaccine in Colombia using rapid evaluation methods

OBJETIVO: Estimar la efectividad de la vacuna monovalente antirrotavírica para prevenir la hospitalización por enfermedad diarreica aguda en niños menores de 2 años en cinco ciudades de Colombia. MÉTODOS: Se realizó una encuesta poblacional sobre una muestra probabilística de niños mayores de 2 meses y menores de 24 meses de edad en cinco ciudades de Colombia (Barranquilla, Bogotá, Cali, Cartagena y Riohacha) en el período de agosto a octubre de 2010. La vacuna fue introducida en el Programa Ampliado de Inmunizaciones en enero de 2009. Se estimaron las coberturas de vacunación contra rotavirus por grupos de edad y la incidencia acumulada de hospitalización por diarrea severa, y se evaluó la magnitud de la asociación entre la vacunación con una o dos dosis de vacuna antirrotavírica y la hospitalización por diarrea, utilizando la razón de probabilidades (RP) ajustada por edad y otros factores de importancia epidemiológica. La efectividad de la vacunación se estimó usando la expresión 1 - RP. RESULTADOS: La cobertura de vacunación con una dosis de vacuna fue de 87,3%. En los 12 meses previos a la encuesta 43,2% (1 453 niños) de menores de 24 meses presentaron diarrea, y de ellos, 5,2% (174 niños) fueron hospitalizados por esta causa. La efectividad de dos dosis de vacuna antirrotavírica para prevenir la hospitalización por diarrea severa fue de 68% (intervalo de confianza de 95%: 55%-77%). CONCLUSIONES: La vacunación contra rotavirus en Colombia protege contra la hospitalización por diarrea por cualquier causa. El uso de encuestas transversales se mostró adecuado para evaluar rápidamente la efectividad de un programa de vacunación con una nueva vacuna.

OBJECTIVE: Estimate the effectiveness of the monovalent rotavirus vaccine in preventing the need to hospitalize children under 2 years old for acute diarrheal disease in five Colombian cities. METHODS:A population survey was conducted based on a probability sample of children over 2 months and under 24 months of age in five Colombian cities (Barranquilla, Bogotá, Cali, Cartagena, and Riohacha) over the period from August through October 2010. The vaccine had been introduced in the Expanded Program on Immunization in January 2009. Rotavirus vaccination coverage was estimated by age group; the cumulative incidence of hospitalization for severe diarrhea was determined; and the magnitude of correlation between vaccination with one or two doses of rotavirus vaccine and hospitalization for diarrhea was calculated using the age-adjusted probability ratio (PR) and other epidemiologically significant factors. Effectiveness of the vaccine was estimated using the expression 1-PR. RESULTS: Coverage with a single dose of the rotavirus vaccine was 87.3%. During the 12 months prior to the survey, 1 453 of the children under 24 months old in the study areas (43.2%) had presented with diarrhea, and of these, 174 (5.2%) had been hospitalized for this cause. The effectiveness of two doses of the vaccine in preventing hospitalization for severe diarrhea was 68% (CI 95% = 55%−77%). CONCLUSIONS: In Colombia, rotavirus vaccination protects against hospitalization for diarrhea due to any cause. The use of cross-sectional surveys appeared to be adequate for rapid evaluation of an immunization program's effectiveness with a new vaccine.

Demonstration of laccase-based removal of lignin from wood and non-wood plant feedstocks.

The ability of Trametes villosa laccase, in conjuction with 1-hydroxybenzotriazole (HBT) as mediator and alkaline extraction, to remove lignin was demonstrated during treatment of wood (Eucalyptus globulus) and non-wood (Pennisetum purpureum) feedstocks. At 50 Ug(-1) laccase and 2.5% HBT concentration, 48% and 32% of the Eucalyptus and Pennisetum lignin were removed, respectively. Two-dimensional nuclear magnetic resonance of the feedstocks, swollen in dimethylsulfoxide-d(6), revealed the removal of p-hydroxyphenyl, guaiacyl and syringyl lignin units and aliphatic (mainly ß-O-4'-linked) side-chains of lignin, and a moderate removal of p-coumaric acid (present in Pennisetum) without a substantial change in polysaccharide cross-signals. The enzymatic pretreatment (at 25 Ug(-1)) of Eucalyptus and Pennisetum feedstocks increased the glucose (by 61% and 12% in 72 h) and ethanol (by 4 and 2 g L(-1) in 17 h) yields from both lignocellulosic materials, respectively, as compared to those without enzyme treatment.

[Epidemiological and economic impact of tetanus vaccination in Colombian adults]. / Impacto epidemiológico y económico de la vacunación contra el tétanos en adultos de Colombia.

OBJECTIVE: Assess the potential epidemiological and economic impact of vaccinating the over-15 Colombian population against tetanus with a booster dose every 10 years. METHODS: A cost-effectiveness analysis of tetanus vaccination with a booster dose every 10 years was conducted in Colombia and compared with the current strategy (2, 4, 6, 18, and 60 months). Estimates of the burden of disease were based on three official data sources. A Markov model from the perspective of the third party payer was developed. The time horizon was the lifetime of a person. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In Colombia, 30 to 48 cases of tetanus resulting in 9.6 to 10.1 deaths are reported each year. Although booster vaccination for the entire population was cost-effective (the cost per disability-adjusted life year [DALY] avoided was US$ 11,314 in the entire population), gender-based differentiation of the results showed that it would not be cost-effective in women (cost per DALY avoided was US$ 4,903 in men and US$ 22,332 in women). CONCLUSIONS: This is the first study that evaluates the cost-effectiveness of a tetanus vaccine booster dose every 10 years in a developing country. Use of this measure would be cost-effective in Colombia, especially for men. As a result of the gender-based differences in the results, any decision about its use in women of childbearing age should take current vaccination into account.

Impacto epidemiológico y económico de la vacunación contra el tétanos en adultos de Colombia / Epidemiological and economic impact of tetanus vaccination in Colombian adults

OBJETIVO: Evaluar el potencial impacto epidemiológico y económico de la vacunación antitetánica en la población colombiana mayor de 15 años de edad, con dosis de refuerzo cada 10 años. MÉTODOS: Se realizó un análisis de costo-efectividad de la vacunación con refuerzo cada 10 años contra el tétanos en Colombia, comparándola con la actual estrategia (2, 4, 6, 18 y 60 meses). La carga de enfermedad se estimó con base en tres fuentes oficiales de datos. Se realizó un modelo de Markov desde la perspectiva del tercer pagador. El horizonte temporal fue el tiempo de vida de una persona. Se realizaron análisis de sensibilidad determinístico y probabilístico. RESULTADOS: En Colombia se notifican anualmente entre 30 y 48 casos de tétanos que ocasionan entre 9,6 y 10,1 muertes. Si bien la vacunación con refuerzo resultó costo-efectiva para toda la población (el costo por año de vida ajustado por discapacidad [AVAD] evitado fue de US$ 11 314 en toda la población), al discriminar los resultados por género no sería costoefectiva en las mujeres (el costo por AVAD evitado en hombres fue de US$ 4 903, y en mujeres de US$ 22 332). CONCLUSIONES: Este es el primer estudio que evalúa la costo- efectividad de una dosis de refuerzo cada 10 años de la vacuna contra el tétanos en un país en desarrollo. La aplicación de esta medida sería costo-efectiva en Colombia, especialmente para los hombres. Las diferencias en los resultados por género obliga a que cualquier decisión de implementación deba tener en cuenta la vacunación actual en mujeres en edad fértil.

OBJECTIVE: Assess the potential epidemiological and economic impact of vaccinating the over-15 Colombian population against tetanus with a booster dose every 10 years. METHODS: A cost-effectiveness analysis of tetanus vaccination with a booster dose every 10 years was conducted in Colombia and compared with the current strategy (2, 4, 6, 18, and 60 months). Estimates of the burden of disease were based on three official data sources. A Markov model from the perspective of the third party payer was developed. The time horizon was the lifetime of a person. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In Colombia, 30 to 48 cases of tetanus resulting in 9.6 to 10.1 deaths are reported each year. Although booster vaccination for the entire population was cost-effective (the cost per disability-adjusted life year [DALY] avoided was US$ 11,314 in the entire population), gender-based differentiation of the results showed that it would not be cost-effective in women (cost per DALY avoided was US$ 4,903 in men and US$ 22,332 in women). CONCLUSIONS: This is the first study that evaluates the cost-effectiveness of a tetanus vaccine booster dose every 10 years in a developing country. Use of this measure would be cost-effective in Colombia, especially for men. As a result of the gender-based differences in the results, any decision about its use in women of childbearing age should take current vaccination into account.

Towards industrially-feasible delignification and pitch removal by treating paper pulp with Myceliophthora thermophila laccase and a phenolic mediator.

The ability of two natural phenols to act as mediators of the recombinant Myceliophthora thermophila laccase (MtL) in eucalypt-pulp delignification was investigated. After alkaline peroxide extraction, the properties of the enzymatically-treated pulps improved with respect to the control. The pulp brightness increased (3.1 points) after the enzymatic treatment with MtL alone, but the highest improvements were obtained after the MtL treatment using syringaldehyde (4.7 points) and especially methyl syringate (8.3 points) as mediators. Likewise, a decrease in kappa number up to 2.7 points was obtained after the MtL-methyl syringate treatment, followed by decreases of 1.4 and 0.9 points after the treatments with MtL-syringaldehyde and MtL alone, respectively. On the other hand, removal of the main lipophilic extractives present in eucalypt pulp was observed after the above laccase-mediator treatments. Finally, the doses of both MtL and methyl syringate were reduced, and results compatible with industrial implementation were obtained.

[Flu vaccine effectiveness: a metaanalysis]. / Efectividad de la vacuna contra influenza: metanálisis de literatura.

INTRODUCTION: Seasonal influenza is a disease of great interest in public health due to its high rates of infection and big costs, especially in high-risk population. This situation has motivated studies related to development of control measures necessary to mitigate its impact. Immunization constitutes a key role in providing the necessary interventions; however, little information is available about its effectiveness as public health measure in tropical countries. OBJECTIVE: The vaccine effectiveness was evaluated by means of published results in the scientific literature. MATERIALS AND METHODS: Meta-analysis techniques were used to summarize the results of epidemiological analytical studies. A critical evaluation was undertaken for each study to identify the potential biases and methodological limitations. RESULTS: Two hundred and fifty-seven relevant studies were located, of which 28 were included in the analysis. The pooled estimator of the vaccine effectiveness for hospitalization was 0.74 [95% CI 0.68-0.81] in older adults (65 years and older) in cases-control studies. For cohort studies, the obtained estimator was 0.80 [95% CI 0.68-0.91]. CONCLUSION: Other conclusions were analyzed, and in general, a protective effect was demonstrated in the vaccine. About 1,200,000 were involved, 530,000 of them were vaccinated. Geographically, the analyzed studies came from developed countries in Europe, America and Asia.

Efectividad de la vacuna contra influenza: metanálisis de literatura / Flu vaccine effectiveness: a metaanalysis

Introducción. Las altas tasas de infección y los grandes costos, especialmente en población de alto riesgo, hacen de la influenza estacional una enfermedad de gran interés en salud pública. Esta situación ha motivado el desarrollo de investigaciones relacionadas con las medidas de control necesarias para mitigar su impacto. Desde esta perspectiva, la inmunización constituye una pieza clave en el entramado de las intervenciones requeridas. Sin embargo, el conocimiento existente frente a su efectividad como medida de salud pública en países tropicales, es relativamente poco. Objetivos. Evaluar la efectividad de la vacuna mediante los resultados reportados en la literatura publicada sobre el tema. Materiales y métodos. Mediante técnicas de metanálisis, se resumieron los resultados de estudios epidemiológicos analíticos observacionales. Se llevó a cabo una evaluación crítica de cada uno de los estudios para identificar los potenciales sesgos y limitaciones metodológicas. Resultados. Se encontraron 257 estudios, de los cuales se incluyeron 28 en el análisis final. El estimativo agregado de efectividad de la vacuna para hospitalización fue de 0,74 (IC95% 0,68-0,81) en adultos mayores en los estudios de casos y controles. Para los estudios de cohortes el estimativo obtenido fue de 0,80, (IC95% 0,68-0,91). También se analizaron otros desenlaces y, de manera general, se evidenció un efecto protector en la vacuna. Conclusiones. Los análisis sugieren la vacunación como medida masiva de control para influenza en adultos mayores de 65 años. Existe un importante vacío de conocimiento en la efectividad de la vacuna en niños menores de dos años y madres gestantes.

Introduction. Seasonal influenza is a disease of great interest in public health due to its high rates of infection and big costs, especially in high-risk population. This situation has motivated studies related to development of control measures necessary to mitigate its impact. Immunization constitutes a key role in providing the necessary interventions; however, little information is available about its effectiveness as public health measure in tropical countries. Objective. The vaccine effectiveness was evaluated by means of published results in the scientific literature. Materials and methods. Meta-analysis techniques were used to summarize the results of epidemiological analytical studies. A critical evaluation was undertaken for each study to identify the potential biases and methodological limitations. Results. Two hundred and fifty-seven relevant studies were located, of which 28 were included in the analysis. The pooled estimator of the vaccine effectiveness for hospitalization was 0.74 [95%CI 0.68-0.81] in older adults (65 years and older) in cases-control studies. For cohort studies, the obtained estimator was 0.80 [95%CI 0.68-0.91]. Conclusion. Other conclusions were analyzed, and in general, a protective effect was demonstrated in the vaccine. About 1,200,000 were involved, 530,000 of them were vaccinated. Geographically, the analyzed studies came from developed countries in Europe, America and Asia.

Evaluación de la citoxicidad de tres materiales de obturación radicular Terminal (mta,irm,super eba) en cultivos de fibroblastos, macrofagos y osteoblastos / In vitro evaluation of the cytoxicity of MTA, IRM and Super EBA filling materials

El propósito de este estudio fue comparar la citotoxidad del Mineral Trióxido Agregado (MTA) con otros materiales de obturación apical comúnmente utilizados como IRM y superEBA. Se utilizó el test MTT para evaluar la actividad de la enzima deshidrogenada mitocondrial en fibroblastos humanos, osteoblastos de ratones y macrófagos de la línea celular U937A luego de 4,24 y 100 horas de exposición con cada uno de los tres materiales. Como control positivo se usó el hipoclorito de sodio al 0.005 por ciento y los cultivos sin ningún material, como control negativo. Las diferencias en los valores encontrados en la viabilidad celular fueron analizadas mediante la prueba de ANOVA. La secuencia de toxicidad con los fibroblastos fue igual para IRM y superEBA y menor para MTA. Con respecto a los osteoblastos, SuperEBA tuvo mayor citotoxicidad que IRM y MTA...

The integral membrane protein p16.7 organizes in vivo phi29 DNA replication through interaction with both the terminal protein and ssDNA.

Remarkably little is known about the in vivo organization of membrane-associated prokaryotic DNA replication or the proteins involved. We have studied this fundamental process using the Bacillus subtilis phage phi29 as a model system. Previously, we demonstrated that the phi29-encoded dimeric integral membrane protein p16.7 binds to ssDNA and is involved in the organization of membrane-associated phi29 DNA replication. Here we demonstrate that p16.7 forms multimers, both in vitro and in vivo, and interacts with the phi29 terminal protein. In addition, we show that in vitro multimerization is enhanced in the presence of ssDNA and that the C-terminal region of p16.7 is required for multimerization but not for ssDNA binding or interaction with the terminal protein. Moreover, we provide evidence that the ability of p16.7 to form multimers is crucial for its ssDNA-binding mode. These and previous results indicate that p16.7 encompasses four distinct modules. An integrated model of the structural and functional domains of p16.7 in relation to the organization of in vivo phi29 DNA replication is presented.

The Bacillus subtilis phage phi 29 protein p16.7, involved in phi 29 DNA replication, is a membrane-localized single-stranded DNA-binding protein.

The functional role of the phi 29-encoded integral membrane protein p16.7 in phage DNA replication was studied using a soluble variant, p16.7A, lacking the N-terminal membrane-spanning domain. Because of the protein-primed mechanism of DNA replication, the bacteriophage phi 29 replication intermediates contain long stretches of single-stranded DNA (ssDNA). Protein p16.7A was found to be an ssDNA-binding protein. In addition, by direct and functional analysis we show that protein p16.7A binds to the stretches of ssDNA of the phi 29 DNA replication intermediates. Properties of protein p16.7A were compared with those of the phi 29-encoded single-stranded DNA-binding protein p5. The results obtained show that both proteins have different, non-overlapping functions. The likely role of p16.7 in attaching phi 29 DNA replication intermediates to the membrane of the infected cell is discussed. Homologues of gene 16.7 are present in phi 29-related phages, suggesting that the proposed role of p16.7 is conserved in this family of phages.