Beruflich Dokumente
Kultur Dokumente
Methanol poisoning is a fatal public health problem that affects population in both
developed and developing countries particularly as alcohol consumption increases in most
countries around the world. Several sources of poisoning are related to this issue (e.g.
adulterated beverages, inappropriate distillation processes, methylated spirits, accidental
exposure to this organic solvent, suicide attempt cases, among others). The inlet routes to
the systemic metabolism are usually ingestion, inhalation or absorption through the skin.
Several isolated cases of mass intoxications have taken place worldwide in recent years,
Nicaragua (788 cases, 2006); Colombia (31 cases, 1989 and 88 cases, 2004); Jordan (17
cases 2006), Estonia (154 cases, 2001) [1-6]. Nevertheless, the total of cases per year in
each country might be higher: Colombia (136 cases, 2007 and 250 cases, 2008); United
States (2283 possible cases, 2007) [7].
Methanol toxicity arises due to two main accepted mechanisms: i) central nervous system
depression and ii) biotransformation of methanol into formaldehyde and then to formic
acid. Therefore, current treatments approaches are related to alcohol dehydrogenase (ADH)
inhibition, since this enzyme is the one responsible for methanol metabolism to
formaldehyde (the toxic metabolite). In emergency settings and with the purpose of treating
patients for Methanol poisoning, inhibition is carried out using intravenous injection of
“pure” ethanol or 4-methylpirazole (fomepizole) because these compounds may compete
for the active sites on the ADH enzyme.
Several in-silico models for alcohols and glycols have been developed and the
physiologically based pharmacokinetic (PBPK) ones are the most common because these
enhance the fitting with experimental data keeping the physiological meaning of each
differential equation [7-8]. Nevertheless, in the state of art there are few models that include
non-reactive elimination pathways or dynamic control strategies in order to provide the
most accurate doses for the inhibition kinetics of ADH in a physiological media.
In this study a multi-compartment physiologically based pharmacokinetic model including
non-reactive elimination pathways, and a dynamic optimization technique is implemented
in order to minimize the formaldehyde production on the alcohol dehydrogenase ADH
enzyme using intra-venous ethanol as inhibitor. This technique is contrasted with a PID
control strategy designed to stabilize the vein formaldehyde concentration under critical
levels, the controller parameters are tuned up via nonlinear optimization techniques.
The proposed PBPK model includes separation between venous and arterial blood pools,
and the main organs for methanol, ethanol and its metabolites biodistribution have been
modeled in detail (i.e. Liver, lungs, kidneys, muscles and fat, stomach, gastrointestinal tract
and skin), and the reactive unit (liver) is modeled as series of CSTR reactors with a
reversible Michaelis-Menten kinetics. Additionally, the parameters for this model have
been adjusted and validated using experimental data from the literature.
[1] Pan American Health Organization, Methanol Poisoning in Leon, Nicaragua, Report,
September, (2006).
[2] Bennett I.L., Cary F.H., Mitchell G.L., et al., Acute methyl alcohol poisoning: A review
based on experiences in an outbreak of 323 cases. Medicine 32:431-463, (1953).
[3] Kane R.L., Talbert W., Harlan J., et al., A methanol poisoning outbreak in Kentucky. A
clinical epidemiologic study In Archives of Environmental Health, 17(1):119-29. (1968).
[4] Paasma R., Hovda K.E., Tikkerberi A., Jacobsen D., Methanol mass poisoning
in Estonia: outbreak in 154 patients. Clin Toxicol (Phila).45(2):152-7 (2007).
[5] Balaguer J., Intoxicación por Metanol. Toxicología Clínica. Bataller Editorial,
Published in Spain p. 60-64 (2004).
[6] Colombian National Health Institute, Methanol monitoring and poisoning control
(2010). (Original language: Protocolo de vigilancia y control de intoxicaciones por
metanol, Instituto nacional de salud de Colombia (2010)).
[7] BrentJ. Fomepizole for Ethylene Glycol and Methanol Poisoning. The new england
journal of medicine 360; 21 may 21, 2009
See more of this Session: Control In Medicine and Biology
See more of this Group/Topical: Computing and Systems Technology Division
(767a) Morphological and Surface
Dependant Nano-Particle Behavior
for Medical Imaging: Evaluation of
Magnetic Nanoparticles for MRI and
Gold Nanoparticles for CT-SCAN
The field of medical imaging has recently enhanced its medical potential applications based
on nanotechnology; this is due in part to an extensive interest from different disciplines.
Several researchers are currently focused on the development of molecular imagenology
using nanoparticles as contrast media. These techniques have been outlined as the “non-
invasive, quantitative and replicable imaging of targeted tissues or biological processes in
vivo and ex-vivo”. The future applications of molecular imaging are expected to include:
more accurate prognoses, personalized medicine, the ability to follow the effectiveness of
treatments, and the early detection of many diseases such as cancer [1].
Current development on gold nanostructures is related to plasmon phenomena
(e.g. Photothermal ablation) and its appeal arises from their potential use as both
therapeutic agents and contrast media for several medical imaging techniques (e.g.
photoacustic imaging and CT-SCAN). On the other hand, magnetic nanoparticles have
been widely studied for magnetic resonance imaging MRI due to the alterations they induce
in the spin–spin relaxation time when introduced into biological tissues.
The aim of this study is twofold. First, to provide experimental evidence as to how the
shape of gold nanoparticles can affect the X-rays attenuation behavior. Here, this is
achieved using gold nanoshells, nanorods, hollow gold nanoparticles and colloidal gold on
controlled experiments from which the evolution of X-rays attenuation is determined.
Second, to evaluate the effects of different surface modifications on superparamagnetic iron
oxide nanoparticles (SPION´s) with the purpose of gathering information on how these
modifications can alter the spin-spin relaxation time for MRI applications. The
nanoparticles studied in this case include: magnetite capped with polyvinylpyrrolidone
(PVP), magnetite capped with citrate, magnetite capped with an amino-silane, and core-
shell magnetite-SiO2. The introduction of different chemical groups on the surface of
magnetite is expected to modify the translational diffusion of water molecules to the
magnetic core, therefore affecting the spin-spin relaxation time.
Controlled synthesis of nanostructured materials with functional properties has been the
center of attention during the last decade because of their unique size and shape-dependent
properties (e.g. optical, electrical, magnetic, chemical, etc.). Therefore, several applications
on diverse disciplines such as medical diagnosis based on imaging and cancer treatment
research have recently been directed towards the use of nanomedicine.
Results have been successful in spite the fact that industrial scalability of these processes
nowadays is still in development, for instance the colloidal gold production with high
reproducibility and remarkable control of shape and size at concentrations in the range of
parts per million has been established; nonetheless, reproducible and facile synthesis
processes in order to obtain more concentrated colloidal dispersions of gold are yet to be
developed.
The present study evaluates three different techniques for production of highly concentrate
colloidal gold nanoparticles (hundreds of parts per million). The first synthesis is a green
chemistry approach based on the use of essential oils extracted from plants such
as pelargonium graveolens geranium and explores their use as both capping and
reductive agents. The second synthesis uses sodium citrate as the reductive agent,
polyvinylpyrrolidone (PVP) is used as capping agent, in addition, the process is carried out
at room temperature (293.15 K) and the effect of ultrasonic dispersion is also studied.
These two syntheses are contrasted with the well-known Turkevich method. It´s known that
this last traditional synthetic pathway may generate colloidal instabilities when certain
concentrations are required (> 40 ppm) due mainly to the electrical properties of the solid-
liquid interface and its relation with the zeta potential. Finally, for these three procedures
hydrogen potential (pH) and Temperature were followed rigorously in order to develop
kinetic models. Stability was monitored over time using UV-VIS-NIR spectroscopy.
The nanoparticles obtained from these techniques have been proven to be stable over
relatively long periods of time (months), making these products very useful for biomedical
applications and low cost of the reductive and capping agents used.
The PBPK models includes separation between venous and arterial blood pools, and the
main organs for nanoparticles biodistribution have been modeled in detail (i.e. Liver, lungs,
kidneys, spleen, hearth, brain), Additionally, the parameters for this model have been
adjusted and validated using different kinds of preclinical data in mice.
The enhanced permeability and retention (EPR) effect has been explored as an appealing
route for nanoparticle transport into tummoral tissues, due to the high rate of angiogenesis
in cancerous lymphomas among other neoplasms. The EPR effect allows nanoparticles to
penetrate a high number of blood vessels in comparison to non-cancerous tissues.
Nevertheless, classical models for diffusive and convective transport of nanoparticles
through biological tissues do not achieve the level of detail needed, because there are
several restrictions related to the behavior of the mean square displacement (MSD) in such
complex media (i.e. anomalous diffusion). In addition, today little is known on how
nanoparticles properties affect individual transportation kinetic parameters [1].
This study provides a model and its numerical solution for nanoparticle diffusion in an
emulated biological blood vessel with some simplifications, modeled by a three-
compartment model, where the nanoparticles mass transport within the tissue is assumed to
take place by an anomalous diffusion process, the first compartment is a reservoir with
high concentration of gold nanoparticles and with a pulsed inlet, the second compartment is
an emulated biological tissue that allows only a one-dimensional diffusion initially with a
null concentration of nanoparticles, through this compartment nanoparticles reach a well
mixed liquid cavity with no particle at the onset of the experiment.
The effect of the pulsed behavior in the first compartment is an interesting factor that is
studied in this model due to the fact that it is not straightforward to develop a prediction of
how a pulsed inlet condition could influence the behavior of the particles MSD within the
tissue. Fractional calculus strategies arise as the natural model for these kinds of transport
phenomena because the time fractional diffusion equation (TFDE) allows the inclusion of
memory effects into the model.
The simulation and experimental results are compared in order to analyze the distribution
and the efficiency of the separation of the magnetic core-shell nanoparticles. The results
show that the models developed in this study could be useful in assisting the design of
magnetic-field based separation Microsystems with potential applications on medical
diagnosis.
Topics:
Separations
(420i) Gold Nanoparticle-Based
Biosensor for Colorimetric
Detection of Helicobacter Pylori In
Water
Microfluidic devices has been the focus of attention in different areas, such as chemistry,
biology, bioengineering and health sciences in past few years due to the numerous
advantages in sample preparation, characterization and analysis. Despite of these
characteristics, the separation and mixing of particles or fluids are quite difficult to achieve
in such devices due to the diffusive regimen. As a possible solution to this problem, some
authors have proposed magnetic-field based separation and mixing. As a result, studies on
the behavior of diffusion as a function of the applied magnetic field on this type of systems
are of great interest.
In this work, we have studied the behavior of an aqueous suspension of magnetic
nanoparticles flowing through a microfludic system in the presence of an externally
imposed magnetic field. We have measured the concentration profile across the
microsystem and adjusted the diffusion coefficient to a non-regular diffusive regime.
The experimental work has involved the synthesis of magnetic nanoparticles and the
analysis of particles transport under the influence of different magnetic fields and flow
conditions. The nanoparticles used in this study are particles of magnetite, synthesized by
the coprecipitation method and stabilized with an electrolyte to screen electrostatic
interactions. Core-shell magnetic nanoparticles are also considered. In order to verify our
model we have develop numerical simulations using COMSOL Multiphysics to corroborate
the behavior of the microfluidic system and the concentration profile.
The simulation and experimental results are compared in order to analyze the non-regular
diffusive regime. The results obtained indicate an anomalous diffusion regime in the
presence of an external magnetic field in this type of systems.
(648d) Preparation and
Characterization of Funtionalized
Hematite-Magnetite Nano-Particles
for the Anticancer Drug Delivery of
Cisplatin
Conference: AIChE Annual Meeting
Year: 2010
Proceeding: 2010 AIChE Annual Meeting
Group: Nanoscale Science and Engineering Forum
Session:
Magnetic Nanoparticles in Biotechnology and Biomedicine II
Time:
Thursday, November 11, 2010 - 2:00pm-2:30pm
Authors:
Galvis, A. A., Universidad de los Andes
Reyes, J. R., Universidad de los Andes
Vargas, W. L., Universidad de los Andes
Controlled fabrication of nanostructured materials with functional properties has been the
focus of attention in recent years due to their unique size and shape-dependent properties
(optical, electrical, magnetic, catalytic, mechanical, chemical, etc.). Therefore, studies on
the controllable synthesis of nanomaterials are of great interest and are actively being
pursued.
In this study, we have attached the active anticancer drug cisplatin to a silica-modified
(hematite-magnetite) nanoparticle for improved drug delivery. Naked Fe2O3-Fe3O4
nanoparticles were covered with a thin shell of silica using the well-known method
developed by Stöber. The silica-modified (hematite-magnetite) nanoparticles were then
functionalized with a silane monolayer. Cisplatin was then added to the silanated surface to
yield a complex functionalized nanoparticle. The functionalized Fe2O3-Fe3O4 samples are
characterized by X-ray diffraction, Dynamic Light Scattering, Zeta potential, Scanning
Electron microscopy (SEM), Transmission electron microscopy (TEM), and Nuclear
Magnetic Resonance (NMR).
The platinum-tethered nanoparticles were also examined for in-vitro cytotoxicity (using a
hemolysis assay), drug uptake, and localization (by fluorecent tagging) in colorectal
adenocarcinoma cells. The results obtained show that nanoparticles developed in this study
could potentially be useful in the controlled delivery of cisplatin for cancer therapeutics and
may be considered a promising platform in targeted therapy of cancer.
(373c) Core-Shell Magnetic
Nanoparticles and Their Hemolytic
Activity
Conference: AIChE Annual Meeting
Year: 2010
Proceeding: 2010 AIChE Annual Meeting
Group: Nanoscale Science and Engineering Forum
Session:
Session: Nanoscale Science and Engineering
Time:
Tuesday, November 9, 2010 - 6:00pm-8:00pm
Authors:
Vargas, W. L., Universidad de los Andes
Galvis, A. A., Universidad de los Andes
Reyes, J. R., Universidad de los Andes
Bimetallic nanoparticles that exhibit a core-shell architecture have been the focus of
attention in recent years due to their unique size and shape-dependent properties (optical,
electrical, magnetic, catalytic, mechanical, chemical, etc.), when compared with their
monometallic counterparts. Introducing a magnetic element (core) in nanoparticles is
additionally attractive owing to their potential applications in different fields. Therefore,
studies on the controllable synthesis of nanomaterials with a core-shell structure are of
great interest and are actively being pursued.
In this study, a two-step seeding growth process has been used to produce silica-modified
hematite-magnetite nanoparticles as platforms for targeted drug delivery. Naked Fe2O3-
Fe3O4 nanoparticles obtained by a co-precipitation process were covered with a silica shell
of variable thickness using the well-known method developed by Stöber. The silica-
modified hematite-magnetite nanoparticles were then functionalized with a silane
monolayer. The functionalized Fe2O3-Fe3O4 samples are characterized by X-ray
diffraction, Dynamic Light Scattering, Zeta potential, Scanning Electron microscopy
(SEM), Transmission electron microscopy (TEM), and Nuclear Magnetic Resonance
(NMR).
This study also uses the measure of hemolysis to evaluate the toxicity of silica-modified
hematite-magnetite nanoparticles with and without surface modification and with varied
sizes and investigates the effects on the nanoparticle-cell interaction.
Topics:
Nanotechnology
Respetado/a:
Angel Galvis C.:
Reciba un cordial saludo del Comité Técnico de este XV Congreso Colombiano de Petróleo y Gas: “Innovación y desarrollo sostenible:
El futuro del país”.
Nos complace comunicarle que su trabajo: “Functional Advanced Material Development For Continuos Oil-Water Separation”
ha sido seleccionado para presentación oral durante el Congreso. El espacio para su presentación será notificada durante el mes
de octubre.
Recuerde que debe estar una hora antes del horario establecido, de lo contrario se entenderá que no habrá presentación y
el tiempo asignado debe ser cumplido estrictamente y confirmado con anterioridad. Le agradecemos hacernos llegar antes del
13 de Noviembre de 2013, una copia de la presentación correspondiente a su trabajo, adicionando una corta reseña biográfica
del autor para su presentación, al correo electrónico: congreso@acipet.com. Usted contará con todas las herramientas audiovisuales
necesarias para el desarrollo de su presentación, incluso un salón en el que podrá hacer prueba de su presentación previamente. S
i por algún motivo, usted no puede presentar su conferencia, le pedimos el favor de notificar lo antes posible al mismo correo.
Aprovechamos la oportunidad para agradecerle su interés en ser partícipe de este importante evento.
Cordialmente, Ing. Emiliano Mejía Duque Director Comité Técnico XV Congreso Colombiano de Petróleo y Gas.
NP
Nathalie Pinzón<congreso@acipet.com>
Responder a todos|
mar 05/11/2013, 12:41 p.m.
Angel Alberto Galvis Caballero
Bandeja de entrada
CORREGIMOS EL SALÓN ES EL 4
Reciba un cordial saludo del Comité Técnico de este XV Congreso Colombiano de Petróleo y
Gas: “Innovación y desarrollo sostenible: El futuro del país”.
Nos complace comunicarle que su trabajo: “Functional advanced material development for
continuos Oil-Water Separation” ha sido seleccionado para presentación oral durante el Congreso.
El espacio para su presentación ha sido programado para el Jueves 21 de Noviembre de
2013 de 09:10am a 09:40am, en el salón 4 del segundo nivel del Pabellón 11 al 16.
Cordialmente,
Nathalie Pinzón Pérez
Comité Técnico
Asociación Colombiana de Ingenieros de Petróleos – ACIPET
Cra. 11 A # 94 A – 56 Piso 4 – Bogotá, Colombia
Tel: 6 411 944 ext. 123