Bacterial reduction of N-oxides of tobacco- specific nitrosamines (TSNA)

1 Contrary to established metabolic pattern, a recent investigation of NNK metabolism produced in rat urine higher levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyri dyl)-1-butanol (NNAL) than their N-oxides, suggesting that reconversion of N-oxides could occur after urine formation. 2 To verify the possible role of bacteria in the reduction of NNK-N-oxide and NNAL-N-oxide to their respective parent compounds, NNK and NNAL, in smokers with urinary tract infection (UTI), the N-oxides were isolated from the urine of rats treated with 5-3HNNK and individually incubated at 37°C with ten bacterial species in sterile human urine under different pH regimens. After incubation with the bacteria, aliquots of culture media were analyzed by high pressure liquid chromatography (HPLC) with radiochemical detection. 3 Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Proteus mirabilis possessed varying capacity to regenerate NNK and NNAL from their N- oxides while others showed no detectable reductive capability within 24 h. 4 This result constitutes the first experimental evidence that in tobacco users with concomitant UTI, bacterial regeneration of the procarcinogenic NNK and NNAL from their N-oxides could occur in the bladder leading to increased carcinogen burden in these individuals

Sobre el problema geomorfológico del alineamiento de las cumbres en la region del lago Buenos Aires y la determinación de las líneas tectónicas en la parte sur de la Cordillera de Los Andes

En el presente trabajo se desarrolla un método de análisis geomorfológico-estadístico aplicado a la deducción de hechos geológicos generales. Es el método estadístico de los alineamientos, que se ha empleado para determinar las direcciones tectónicas de la región cordillerana del lago Buenos Aires, valiéndose del trazado de los alineamientos de las cumbres de la región considerada. De ese modo se ha inferido la existencia de cuatro direcciones tectónicas predominantes, caracterizadas por ángulos de 27°, 55°, 100° y 175°, medidos a partir de la dirección Norte y en ei sentido del movimiento de las agujas del reloj.The purpose of this work is to develope a method of a morphologic-statistical analysis applied to the deduction of general geological fats. This is the statistical method of the alinements, which has been applied to determine the tectonic directions of the Andes región in the vecinity of the Buenos Aires lalte, by establishing the alinements of the tops of the mountains in the above mentioned región. In this way it has possible to deduce the existance of four main tectonic directions, distinguished by angles of 27°, 55°, 100° and 175°, measured from the North and moving like of the hands of a dock

Curation of a CHO DG44 genome scale model and application to support cell culture development process

Genome scale models (GSM) have become a useful tool to connect different omics dataset into a single computational framework, thus giving a good overview of the flux distribution and metabolites interconnections in a specific environmental condition. A community genome-scale metabolic network reconstruction of Cricetulus griseus and cell line specific models have been recently developed 1. The main objectives with the use of the published CHO DG44 model were to enhance industrial bioprocess performance by suggesting genetic or metabolic targets, as well as strategies for medium optimization, and by bringing more fundamental knowledge about CHO cell metabolism. In a first step, some corrections were required in order to improve the biological relevancy of the predicted intracellular fluxes. The optimization method chosen was Parsimonious Flux Balance Analysis, based on the assumption that the cell is using a minimum amount of enzymes to reach a maximized objective value, under steady state. As the predictions were generating a lot of infeasible cycles, silencing of amino acid transporters that do not involve protons or sodium in the model allowed to reduce the incoming flow of amino acids and led to disappearance of infeasible cycles in the flux distribution solution. Four reactions involved in central carbon metabolism were manually added in the model, and some reactions were removed from the model to improve predictions such as the cytosolic enzyme fumarase, mainly localized in mitochondria, or L-asparaginase which is not reported to be present in CHO cells. As initial predictions for lactate production rate were overestimated compared to experimental measurements, the assumption of lipid accumulation during cell culture was added in the form of a constraint for a minimal level of triglyceride synthesis in the model (Figure 1). In a second step, the accuracy of the prediction from the curated model was tested with three independent data set obtained from a fed-batch experiment with a CHO DG44 cell line producing a monoclonal antibody in 2L stirred tank glass bioreactors. For modelling with GSM, pre-calculated input values are required in order to constraint the model with the environmental conditions, and thus to give a prediction that is representative of the experimental condition. Uptake rates of essential nutrients initially present in extracellular medium and consumed as the cells grow were used as the limit for a maximum uptake rate in the model. The objective function chosen was maximization of growth rate or maximization of specific productivity. As a result, correlation coefficients between experimental value and prediction indicate a good fit for growth rate and specific productivity (Qp) (Figure 2). Predicted amino acid consumption rates were comparable to experimental values, indicating the accuracy of the predicted stoichiometric requirements for cell growth and energy, except for 19% of the fluxes studied (Figure 3). As the extracellular flux values seem to correlate with experimental data, prediction of intracellular flux rates were analyzed at different timepoints of the culture, showing the activation of multiple metabolic pathways. Based on the results obtained, optimization of cell culture medium was performed to identify the limiting metabolites during the process that could lead to an increased growth rate and Qp. Please click Additional Files below to see the full abstract

Diagnosis and treatment of osteoporosis in spinal cord injury patients: A literature review

AbstractObjectiveTo present an up-to-date literature review of osteoporosis in spinal cord injury (SCI) patients, in view of the seriousness of this complication (with a high risk of fractures) and the complexity of its diagnosis, evaluation and treatment.MethodsA Medline search with the following keywords: immobilization osteoporosis, spinal cord injury, bone loss, dual energy X-ray absorptiometry (DEXA), bisphosphonate.ResultsOur analysis of the literature noted a bone metabolism imbalance in SCI patients, with accelerated early bone resorption (particularly during the first 6months post-injury). Although dual energy X-ray absorptiometry constitutes the “gold standard” diagnostic method, the decrease in bone mineral density only becomes significant 12months after the injury. Bisphosphonate therapy has proven efficacy. Despite the frequent use of various physical therapies, these methods have not been found to be effective.ConclusionAlthough our literature review did not identify any guidelines on the strategy for diagnosing and treating osteoporosis in SCI patients, several findings provide guidance on procedures for early diagnosis and preventive treatment

Añelo: repensar el territorio

En 2011 el BID puso en marcha la Plataforma Ciudades Emergentes y Sostenibles para ayudar a las ciudades intermedias de América Latina y el Caribe a identificar y priorizar proyectos de inversión para su desarrollo sostenible, impactando positivamente en la calidad de vida de los habitantes

Biomechanical analysis and modeling of lumbar belt: Preliminary study.

International audienceLow back pain is a major public health problem in European Countries. In France, about 50% of population is suffering of this pathology every year (Fassier 2011). Because of health care cost and sick leave (Fassier 2011; Leclerc et al. 2009), low back pain has both societal and economic adverse consequences. Many treatments are proposed. However no guideline is provided to physician. Treatment depends on patient, on low back pain type and evolution and also on physician knowledge and believes. Medical devices, as lumbar belt might be proposed to treat low back pain. Several clinical trials have shown their efficacy (Calmels et al. 2009). Nevertheless, both mechanical and physiological effects of lumbar belts remain unclear. In this study, the application of a lumbar belt on the trunk is simulated by a finite element model. It is often assumed that the pain comes from the toe of the intervertebral discs and is related only to the intradiscal pressure and the thoracolumbar posture. Beside, abdominal pressure is used by belt manufacturers as a marker of the lumbar belt efficiency, because a change in the abdominal pressure could bring a change in the thoracolumbar posture and consequently on the intradiscal pressure. That's why the goal of this study is to determine the mechanical effect of wearing lumbar belt: i) on abdominal pressure; ii) on thoracolumbar posture; iii) on intervertebral disc pressure