Magda Latorre - Academia.edu (original) (raw)

Papers by Magda Latorre

Research paper thumbnail of Enhanced reduction in cell viability

Enhanced reduction in cell viability

by hyperthermia induced by magnetic nanoparticles

Research paper thumbnail of Effects of Nanoparticle Surface Charge On Cellular Uptake and Elucidation of Molecular Mechanisms On Nanoparticle Internalization

Effects of Nanoparticle Surface Charge On Cellular Uptake and Elucidation of Molecular Mechanisms On Nanoparticle Internalization

ABSTRACT

Research paper thumbnail of Synthesis, stability, cellular uptake, and blood circulation time of carboxymethyl-inulin coated magnetic nanoparticles

Synthesis, stability, cellular uptake, and blood circulation time of carboxymethyl-inulin coated magnetic nanoparticles

Journal of Materials Chemistry B, 2013

Iron oxide nanoparticles were coated with the biocompatible, biodegradable, non-immunogenic polys... more Iron oxide nanoparticles were coated with the biocompatible, biodegradable, non-immunogenic polysaccharide inulin by introduction of carboxyl groups into the inulin structure and conjugation with amine groups on the surface of iron oxide nanoparticles grafted with 3-aminopropyltriethoxysilane. The resulting nanoparticles were characterized by FT-IR spectroscopy, transmission electron microscopy, dynamic light scattering, zeta potential, SQUID magnetometry, and with respect to their energy dissipation rate in applied alternating magnetic fields. The nanoparticles had a hydrodynamic diameter in the range of 70 ± 10 nm and were superparamagnetic, with energy dissipation rates in the range of 58-175 W/g for an applied field frequency of 233 kHz and an applied field amplitude in the range of 20-48 kA/m. The nanoparticles were stable in a range of pH, at temperatures between 23°C and 53°C, and in short term storage in water, PBS, and culture media. The particles were non-cytotoxic to the immortalized human cancer cell lines Hey A8 FDR, A2780, MDA 468, MCF-7 and Caco-2. The nanoparticles were readily taken up by Caco-2 cells in a time and concentration dependent fashion, and were found to have a pharmacokinetic time constant of 47 ± 3 min. The small size, non-cytotoxicity, and efficient energy dissipation of the particles could make them useful for biomedical applications such as magnetic fluid hyperthermia.

Research paper thumbnail of Enhanced reduction in cell viability by hyperthermia induced by magnetic nanoparticles

International Journal of Nanomedicine, 2011

Colloidal suspensions of iron oxide magnetic nanoparticles are known to dissipate energy when exp... more Colloidal suspensions of iron oxide magnetic nanoparticles are known to dissipate energy when exposed to an oscillating magnetic field. Such energy dissipation can be employed to locally raise temperature inside a tumor between 41°C and 45°C (hyperthermia) to promote cell death, a treatment known as magnetic fluid hyperthermia (MFH). This work seeks to quantify differences between MFH and hot-water hyperthermia (HWH) in terms of reduction in cell viability using two cancer cell culture models, Caco-2 (human epithelial colorectal adenocarcinoma) and MCF-7 (human breast cancer). Magnetite nanoparticles were synthesized via the co-precipitation method and functionalized with adsorbed carboxymethyl dextran. Cytotoxicity studies indicated that in the absence of an oscillating magnetic field, cell viability was not affected at concentrations of up to 0.6 mg iron oxide/mL. MFH resulted in a significant decrease in cell viability when exposed to a magnetic field for 120 minutes and allowed to rest for 48 hours, compared with similar field applications, but with shorter resting time. The results presented here suggest that MFH most likely induces apoptosis in both cell types. When compared with HWH, MFH produced a significant reduction in cell viability, and these effects appear to be cell-type related.

Research paper thumbnail of HST2 Mediates SIR2 -Independent Life-Span Extension by Calorie Restriction

HST2 Mediates SIR2 -Independent Life-Span Extension by Calorie Restriction

Science, 2005

Calorie restriction (CR) extends the life span of numerous species, from yeast to rodents. Yeast ... more Calorie restriction (CR) extends the life span of numerous species, from yeast to rodents. Yeast Sir2 is a nicotinamide adenine dinucleotide (NAD + -dependent histone deacetylase that has been proposed to mediate the effects of CR. However, this hypothesis has been challenged by the observation that CR can extend yeast life span in the absence of Sir2. Here, we show that Sir2-independent life-span extension is mediated by Hst2, a Sir2 homolog that promotes the stability of repetitive ribosomal DNA, the same mechanism by which Sir2 extends life span. These findings demonstrate that the maintenance of DNA stability is critical for yeast life-span extension by CR and suggest that, in higher organisms, multiple members of the Sir2 family may regulate life span in response to diet.

Research paper thumbnail of Yeast Life-Span Extension by Calorie Restriction Is Independent of NAD Fluctuation

Science, 2003

Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae ,... more Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae , this effect requires Sir2, a conserved NAD + -dependent deacetylase. We report that CR reduces nuclear NAD + levels in vivo. Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD + :NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR.

Research paper thumbnail of Effect of surface charge on the colloidal stability and in vitro uptake of carboxymethyl dextran-coated iron oxide nanoparticles

Journal of Nanoparticle Research, 2013

Nanoparticle physicochemical properties such as surface charge are considered to play an importan... more Nanoparticle physicochemical properties such as surface charge are considered to play an important role in cellular uptake and particle-cell interactions. In order to systematically evaluate the role of surface charge on the uptake of iron oxide nanoparticles, we prepared carboxymethylsubstituted dextrans with different degrees of substitution, ranging from 38 to 5 groups per chain, and reacted them using carbodiimide chemistry with amine-silane-coated iron oxide nanoparticles with narrow size distributions in the range of 33-45 nm. Surface charge of carboxymethylsubstituted dextran-coated nano-particles ranged from −50 to 5 mV as determined by zeta potential measurements, and was dependent on the number of carboxymethyl groups incorporated in the dextran chains. Nanoparticles were incubated with CaCo-2 human colon cancer cells. Nanoparticle-cell interactions were observed by confocal laser scanning microscopy and uptake was quantified by elemental analysis using inductively coupled plasma mass spectroscopy. Mechanisms of internalization were inferred using pharmacological inhibitors for fluid-phase, clathrin-mediated, and caveola-mediated endocytosis. Results showed increased uptake for nanoparticles with greater negative charge. Internalization patterns suggest that uptake of the most negatively charged particles occurs via non-specific interactions.

Research paper thumbnail of The effect of grafting method on the colloidal stability and in vitro cytotoxicity of carboxymethyl dextran coated magnetic nanoparticles

Journal of Materials Chemistry, 2010

Supporting information includes size distribution histogram from TEM imaging of iron oxide nanopa... more Supporting information includes size distribution histogram from TEM imaging of iron oxide nanoparticles (Fig. S1), equilibrium magnetization measurements for particles suspended in deionized water (Fig. S2), TGA curves for particles with adsorbed CMDx before and after suspension in PBS for 24 hours (Fig. S3), and FT-IR spectra for particles with adsorbed CMDx before and after suspension in PBS for 24 hours (Fig. S4). Fig. S1 Size distribution histogram of iron oxide (IO) magnetic nanoparticles synthesized by the coprecipitation method. A number mean diameter of 12.5 nm with a standard deviation of 2.78 nm were estimated from the normal distribution.

Research paper thumbnail of Preparation of epidermal growth factor (EGF) conjugated iron oxide nanoparticles and their internalization into colon cancer cells

Journal of Magnetism and Magnetic Materials, 2010

Epidermal growth factor (EGF) was conjugated with carboxymethyldextran (CMDx) coated iron oxide m... more Epidermal growth factor (EGF) was conjugated with carboxymethyldextran (CMDx) coated iron oxide magnetic nanoparticles using carbodiimide chemistry to obtain magnetic nanoparticles that target the epidermal growth factor receptor (EGFR). Epidermal growth factor modified magnetic nanoparticles were colloidally stable when suspended in biological buffers such as PBS and cell culture media. Both targeted and non-targeted nanoparticles were incubated with CaCo-2 cancer cells, known to overexpress EGFR. Nanoparticle localization within the cell was visualized by confocal laser scanning microscopy and light microscopy using Prussian blue stain. Results showed that targeted magnetic nanoparticles were rapidly accumulated in both flask-shaped small vesicles and large circular endocytic structures. Internalization patterns suggest that both clathrin-dependent and clathrin-independent receptors mediated endocytosis mechanisms are responsible for nanoparticle internalization.

Research paper thumbnail of Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1

Journal of Biological Chemistry, 2002

The Saccharomyces cerevisiae Sir2 protein is an NAD ؉dependent histone deacetylase that plays a c... more The Saccharomyces cerevisiae Sir2 protein is an NAD ؉dependent histone deacetylase that plays a critical role in transcriptional silencing, genome stability, and longevity. A human homologue of Sir2, SIRT1, regulates the activity of the p53 tumor suppressor and inhibits apoptosis. The Sir2 deacetylation reaction generates two products: O-acetyl-ADP-ribose and nicotinamide, a precursor of nicotinic acid and a form of niacin/vitamin B 3. We show here that nicotinamide strongly inhibits yeast silencing, increases rDNA recombination, and shortens replicative life span to that of a sir2 mutant. Nicotinamide abolishes silencing and leads to an eventual delocalization of Sir2 even in G 1-arrested cells, demonstrating that silent heterochromatin requires continual Sir2 activity. We show that physiological concentrations of nicotinamide noncompetitively inhibit both Sir2 and SIRT1 in vitro. The degree of inhibition by nicotinamide (IC 50 < 50 M) is equal to or better than the most effective known synthetic inhibitors of this class of proteins. We propose a model whereby nicotinamide inhibits deacetylation by binding to a conserved pocket adjacent to NAD ؉ , thereby blocking NAD ؉ hydrolysis. We discuss the possibility that nicotinamide is a physiologically relevant regulator of Sir2 enzymes.

Research paper thumbnail of Reconstructing the population history of Puerto Rico by means of mtDNA phylogeographic analysis

American Journal of Physical Anthropology, 2005

The haplogroup identities of 800 mtDNAs randomly and systematically selected to be representative... more The haplogroup identities of 800 mtDNAs randomly and systematically selected to be representative of the population of Puerto Rico were determined by restriction fragment length polymorphism (RFLP), revealing maternal ancestries in this highly mixed population of 61.3% Amerindian, 27.2% sub‐Saharan African, and 11.5% West Eurasian. West Eurasian frequencies were low in all 28 municipalities sampled, and displayed no geographic patterns. Thus, a statistically significant negative correlation was observed between the Amerindian and African frequencies of the municipalities. In addition, a statistically highly significant geographic pattern was observed for Amerindian and African mtDNAs. In a scenario in which Amerindian mtDNAs prevailed on either side of longitude 66°16′ West, Amerindian mtDNAs were more frequent west of longitude 66°16′ West than east of it, and the opposite was true for African mtDNAs. Haplogroup A had the highest frequency among Amerindian samples (52.4%), suggesti...

Research paper thumbnail of Scaffold Design for Bone Regeneration

Journal of Nanoscience and Nanotechnology, 2014

The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate ... more The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues.

Research paper thumbnail of Synthesis, Colloidal Stability, and Magnetic Properties of Nanoparticles for Magnetic Fluid Hyperthermia

Synthesis, Colloidal Stability, and Magnetic Properties of Nanoparticles for Magnetic Fluid Hyperthermia

ABSTRACT

Research paper thumbnail of Applications of magnetic nanoparticles in medicine: magnetic fluid hyperthermia

Puerto Rico health sciences journal, 2009

Nanoparticle systems are an intense subject of research for various biomedical applications. Coll... more Nanoparticle systems are an intense subject of research for various biomedical applications. Colloidal suspensions of magnetic nanoparticles are of special interest, particularly in bioimaging, and more recently, in Magnetic Fluid Hyperthermia (MFH). MFH promises to be a viable alternative in the treatment of localized cancerous tumors. The treatment consists of locally injecting magnetic nanoparticles in fluid suspension into the tumor site and exposing the site to an oscillating magnetic field, where nanoparticles dissipate energy in the form of heat, causing a localized rise in temperature and tumor cell death. Here we will review methods of magnetic nanoparticle synthesis, and the role of the nanoparticle surface coating in achieving colloidal stability, minimizing toxicity, and targeting. Finally, we review in vitro and in vivo MFH experiments, and clinical studies in the treatment of glioblastoma multiforme and prostate cancer.

Research paper thumbnail of Functionalization of Monodisperse Magnetite Nanoparticles with Fluorescent Amino-Silane-Carboxymethyl Dextran for Cancer Treatment

Functionalization of Monodisperse Magnetite Nanoparticles with Fluorescent Amino-Silane-Carboxymethyl Dextran for Cancer Treatment

The 2008 Annual …, 2008

Monodisperse magnetite nanoparticles coated with oleic acid were synthesized by the thermodecompo... more Monodisperse magnetite nanoparticles coated with oleic acid were synthesized by the thermodecomposition method. These nanoparticles were modified via ligand exchange with amine-silane molecules, which allowed the expression of amine (NH2) end groups onto the ...

Research paper thumbnail of 343261 In Vivo Assessment of Temporal and Spatial Behavior of Carboxyl Methyl Dextran Iron Oxide Nanoparticles in Breast Cancer Model

343261 In Vivo Assessment of Temporal and Spatial Behavior of Carboxyl Methyl Dextran Iron Oxide Nanoparticles in Breast Cancer Model

Hyperthermia consists of heating an organ or tissue to temperatures between 41 to 46˚C, which ind... more Hyperthermia consists of heating an organ or tissue to temperatures between 41 to 46˚C, which induces damage to cancer cells and triggers cell death and/or cell protective mechanisms. Magnetic fluid hyperthermia is being proposed to deliver heat at the desired area using magnetic nanoparticles. The main challenge in this area is to reach the necessary nanoparticle concentration in the tumor in order to be able to reach the necessary temperatures when administered through tail vein injection, to achieve this goal the temporal and spatial properties of the particles need to be assessed. For this purpose, iron oxide nanoparticles functionalized with carboxyl methyl dextran with various degrees of negative charge have been developed. Particles were designed to have different amounts of carboxyl groups per chain (30, 23 and 5 COOH). The objective of this work is to assess the in vivo temporal and spatial behavior of the particles described herein to assess the effect of particle charge o...

Research paper thumbnail of Enhanced reduction in cell viability

Enhanced reduction in cell viability

by hyperthermia induced by magnetic nanoparticles

Research paper thumbnail of Effects of Nanoparticle Surface Charge On Cellular Uptake and Elucidation of Molecular Mechanisms On Nanoparticle Internalization

Effects of Nanoparticle Surface Charge On Cellular Uptake and Elucidation of Molecular Mechanisms On Nanoparticle Internalization

ABSTRACT

Research paper thumbnail of Synthesis, stability, cellular uptake, and blood circulation time of carboxymethyl-inulin coated magnetic nanoparticles

Synthesis, stability, cellular uptake, and blood circulation time of carboxymethyl-inulin coated magnetic nanoparticles

Journal of Materials Chemistry B, 2013

Iron oxide nanoparticles were coated with the biocompatible, biodegradable, non-immunogenic polys... more Iron oxide nanoparticles were coated with the biocompatible, biodegradable, non-immunogenic polysaccharide inulin by introduction of carboxyl groups into the inulin structure and conjugation with amine groups on the surface of iron oxide nanoparticles grafted with 3-aminopropyltriethoxysilane. The resulting nanoparticles were characterized by FT-IR spectroscopy, transmission electron microscopy, dynamic light scattering, zeta potential, SQUID magnetometry, and with respect to their energy dissipation rate in applied alternating magnetic fields. The nanoparticles had a hydrodynamic diameter in the range of 70 ± 10 nm and were superparamagnetic, with energy dissipation rates in the range of 58-175 W/g for an applied field frequency of 233 kHz and an applied field amplitude in the range of 20-48 kA/m. The nanoparticles were stable in a range of pH, at temperatures between 23°C and 53°C, and in short term storage in water, PBS, and culture media. The particles were non-cytotoxic to the immortalized human cancer cell lines Hey A8 FDR, A2780, MDA 468, MCF-7 and Caco-2. The nanoparticles were readily taken up by Caco-2 cells in a time and concentration dependent fashion, and were found to have a pharmacokinetic time constant of 47 ± 3 min. The small size, non-cytotoxicity, and efficient energy dissipation of the particles could make them useful for biomedical applications such as magnetic fluid hyperthermia.

Research paper thumbnail of Enhanced reduction in cell viability by hyperthermia induced by magnetic nanoparticles

International Journal of Nanomedicine, 2011

Colloidal suspensions of iron oxide magnetic nanoparticles are known to dissipate energy when exp... more Colloidal suspensions of iron oxide magnetic nanoparticles are known to dissipate energy when exposed to an oscillating magnetic field. Such energy dissipation can be employed to locally raise temperature inside a tumor between 41°C and 45°C (hyperthermia) to promote cell death, a treatment known as magnetic fluid hyperthermia (MFH). This work seeks to quantify differences between MFH and hot-water hyperthermia (HWH) in terms of reduction in cell viability using two cancer cell culture models, Caco-2 (human epithelial colorectal adenocarcinoma) and MCF-7 (human breast cancer). Magnetite nanoparticles were synthesized via the co-precipitation method and functionalized with adsorbed carboxymethyl dextran. Cytotoxicity studies indicated that in the absence of an oscillating magnetic field, cell viability was not affected at concentrations of up to 0.6 mg iron oxide/mL. MFH resulted in a significant decrease in cell viability when exposed to a magnetic field for 120 minutes and allowed to rest for 48 hours, compared with similar field applications, but with shorter resting time. The results presented here suggest that MFH most likely induces apoptosis in both cell types. When compared with HWH, MFH produced a significant reduction in cell viability, and these effects appear to be cell-type related.

Research paper thumbnail of HST2 Mediates SIR2 -Independent Life-Span Extension by Calorie Restriction

HST2 Mediates SIR2 -Independent Life-Span Extension by Calorie Restriction

Science, 2005

Calorie restriction (CR) extends the life span of numerous species, from yeast to rodents. Yeast ... more Calorie restriction (CR) extends the life span of numerous species, from yeast to rodents. Yeast Sir2 is a nicotinamide adenine dinucleotide (NAD + -dependent histone deacetylase that has been proposed to mediate the effects of CR. However, this hypothesis has been challenged by the observation that CR can extend yeast life span in the absence of Sir2. Here, we show that Sir2-independent life-span extension is mediated by Hst2, a Sir2 homolog that promotes the stability of repetitive ribosomal DNA, the same mechanism by which Sir2 extends life span. These findings demonstrate that the maintenance of DNA stability is critical for yeast life-span extension by CR and suggest that, in higher organisms, multiple members of the Sir2 family may regulate life span in response to diet.

Research paper thumbnail of Yeast Life-Span Extension by Calorie Restriction Is Independent of NAD Fluctuation

Science, 2003

Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae ,... more Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae , this effect requires Sir2, a conserved NAD + -dependent deacetylase. We report that CR reduces nuclear NAD + levels in vivo. Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD + :NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR.

Research paper thumbnail of Effect of surface charge on the colloidal stability and in vitro uptake of carboxymethyl dextran-coated iron oxide nanoparticles

Journal of Nanoparticle Research, 2013

Nanoparticle physicochemical properties such as surface charge are considered to play an importan... more Nanoparticle physicochemical properties such as surface charge are considered to play an important role in cellular uptake and particle-cell interactions. In order to systematically evaluate the role of surface charge on the uptake of iron oxide nanoparticles, we prepared carboxymethylsubstituted dextrans with different degrees of substitution, ranging from 38 to 5 groups per chain, and reacted them using carbodiimide chemistry with amine-silane-coated iron oxide nanoparticles with narrow size distributions in the range of 33-45 nm. Surface charge of carboxymethylsubstituted dextran-coated nano-particles ranged from −50 to 5 mV as determined by zeta potential measurements, and was dependent on the number of carboxymethyl groups incorporated in the dextran chains. Nanoparticles were incubated with CaCo-2 human colon cancer cells. Nanoparticle-cell interactions were observed by confocal laser scanning microscopy and uptake was quantified by elemental analysis using inductively coupled plasma mass spectroscopy. Mechanisms of internalization were inferred using pharmacological inhibitors for fluid-phase, clathrin-mediated, and caveola-mediated endocytosis. Results showed increased uptake for nanoparticles with greater negative charge. Internalization patterns suggest that uptake of the most negatively charged particles occurs via non-specific interactions.

Research paper thumbnail of The effect of grafting method on the colloidal stability and in vitro cytotoxicity of carboxymethyl dextran coated magnetic nanoparticles

Journal of Materials Chemistry, 2010

Supporting information includes size distribution histogram from TEM imaging of iron oxide nanopa... more Supporting information includes size distribution histogram from TEM imaging of iron oxide nanoparticles (Fig. S1), equilibrium magnetization measurements for particles suspended in deionized water (Fig. S2), TGA curves for particles with adsorbed CMDx before and after suspension in PBS for 24 hours (Fig. S3), and FT-IR spectra for particles with adsorbed CMDx before and after suspension in PBS for 24 hours (Fig. S4). Fig. S1 Size distribution histogram of iron oxide (IO) magnetic nanoparticles synthesized by the coprecipitation method. A number mean diameter of 12.5 nm with a standard deviation of 2.78 nm were estimated from the normal distribution.

Research paper thumbnail of Preparation of epidermal growth factor (EGF) conjugated iron oxide nanoparticles and their internalization into colon cancer cells

Journal of Magnetism and Magnetic Materials, 2010

Epidermal growth factor (EGF) was conjugated with carboxymethyldextran (CMDx) coated iron oxide m... more Epidermal growth factor (EGF) was conjugated with carboxymethyldextran (CMDx) coated iron oxide magnetic nanoparticles using carbodiimide chemistry to obtain magnetic nanoparticles that target the epidermal growth factor receptor (EGFR). Epidermal growth factor modified magnetic nanoparticles were colloidally stable when suspended in biological buffers such as PBS and cell culture media. Both targeted and non-targeted nanoparticles were incubated with CaCo-2 cancer cells, known to overexpress EGFR. Nanoparticle localization within the cell was visualized by confocal laser scanning microscopy and light microscopy using Prussian blue stain. Results showed that targeted magnetic nanoparticles were rapidly accumulated in both flask-shaped small vesicles and large circular endocytic structures. Internalization patterns suggest that both clathrin-dependent and clathrin-independent receptors mediated endocytosis mechanisms are responsible for nanoparticle internalization.

Research paper thumbnail of Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1

Journal of Biological Chemistry, 2002

The Saccharomyces cerevisiae Sir2 protein is an NAD ؉dependent histone deacetylase that plays a c... more The Saccharomyces cerevisiae Sir2 protein is an NAD ؉dependent histone deacetylase that plays a critical role in transcriptional silencing, genome stability, and longevity. A human homologue of Sir2, SIRT1, regulates the activity of the p53 tumor suppressor and inhibits apoptosis. The Sir2 deacetylation reaction generates two products: O-acetyl-ADP-ribose and nicotinamide, a precursor of nicotinic acid and a form of niacin/vitamin B 3. We show here that nicotinamide strongly inhibits yeast silencing, increases rDNA recombination, and shortens replicative life span to that of a sir2 mutant. Nicotinamide abolishes silencing and leads to an eventual delocalization of Sir2 even in G 1-arrested cells, demonstrating that silent heterochromatin requires continual Sir2 activity. We show that physiological concentrations of nicotinamide noncompetitively inhibit both Sir2 and SIRT1 in vitro. The degree of inhibition by nicotinamide (IC 50 < 50 M) is equal to or better than the most effective known synthetic inhibitors of this class of proteins. We propose a model whereby nicotinamide inhibits deacetylation by binding to a conserved pocket adjacent to NAD ؉ , thereby blocking NAD ؉ hydrolysis. We discuss the possibility that nicotinamide is a physiologically relevant regulator of Sir2 enzymes.

Research paper thumbnail of Reconstructing the population history of Puerto Rico by means of mtDNA phylogeographic analysis

American Journal of Physical Anthropology, 2005

The haplogroup identities of 800 mtDNAs randomly and systematically selected to be representative... more The haplogroup identities of 800 mtDNAs randomly and systematically selected to be representative of the population of Puerto Rico were determined by restriction fragment length polymorphism (RFLP), revealing maternal ancestries in this highly mixed population of 61.3% Amerindian, 27.2% sub‐Saharan African, and 11.5% West Eurasian. West Eurasian frequencies were low in all 28 municipalities sampled, and displayed no geographic patterns. Thus, a statistically significant negative correlation was observed between the Amerindian and African frequencies of the municipalities. In addition, a statistically highly significant geographic pattern was observed for Amerindian and African mtDNAs. In a scenario in which Amerindian mtDNAs prevailed on either side of longitude 66°16′ West, Amerindian mtDNAs were more frequent west of longitude 66°16′ West than east of it, and the opposite was true for African mtDNAs. Haplogroup A had the highest frequency among Amerindian samples (52.4%), suggesti...

Research paper thumbnail of Scaffold Design for Bone Regeneration

Journal of Nanoscience and Nanotechnology, 2014

The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate ... more The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues.

Research paper thumbnail of Synthesis, Colloidal Stability, and Magnetic Properties of Nanoparticles for Magnetic Fluid Hyperthermia

Synthesis, Colloidal Stability, and Magnetic Properties of Nanoparticles for Magnetic Fluid Hyperthermia

ABSTRACT

Research paper thumbnail of Applications of magnetic nanoparticles in medicine: magnetic fluid hyperthermia

Puerto Rico health sciences journal, 2009

Nanoparticle systems are an intense subject of research for various biomedical applications. Coll... more Nanoparticle systems are an intense subject of research for various biomedical applications. Colloidal suspensions of magnetic nanoparticles are of special interest, particularly in bioimaging, and more recently, in Magnetic Fluid Hyperthermia (MFH). MFH promises to be a viable alternative in the treatment of localized cancerous tumors. The treatment consists of locally injecting magnetic nanoparticles in fluid suspension into the tumor site and exposing the site to an oscillating magnetic field, where nanoparticles dissipate energy in the form of heat, causing a localized rise in temperature and tumor cell death. Here we will review methods of magnetic nanoparticle synthesis, and the role of the nanoparticle surface coating in achieving colloidal stability, minimizing toxicity, and targeting. Finally, we review in vitro and in vivo MFH experiments, and clinical studies in the treatment of glioblastoma multiforme and prostate cancer.

Research paper thumbnail of Functionalization of Monodisperse Magnetite Nanoparticles with Fluorescent Amino-Silane-Carboxymethyl Dextran for Cancer Treatment

Functionalization of Monodisperse Magnetite Nanoparticles with Fluorescent Amino-Silane-Carboxymethyl Dextran for Cancer Treatment

The 2008 Annual …, 2008

Monodisperse magnetite nanoparticles coated with oleic acid were synthesized by the thermodecompo... more Monodisperse magnetite nanoparticles coated with oleic acid were synthesized by the thermodecomposition method. These nanoparticles were modified via ligand exchange with amine-silane molecules, which allowed the expression of amine (NH2) end groups onto the ...

Research paper thumbnail of 343261 In Vivo Assessment of Temporal and Spatial Behavior of Carboxyl Methyl Dextran Iron Oxide Nanoparticles in Breast Cancer Model

343261 In Vivo Assessment of Temporal and Spatial Behavior of Carboxyl Methyl Dextran Iron Oxide Nanoparticles in Breast Cancer Model

Hyperthermia consists of heating an organ or tissue to temperatures between 41 to 46˚C, which ind... more Hyperthermia consists of heating an organ or tissue to temperatures between 41 to 46˚C, which induces damage to cancer cells and triggers cell death and/or cell protective mechanisms. Magnetic fluid hyperthermia is being proposed to deliver heat at the desired area using magnetic nanoparticles. The main challenge in this area is to reach the necessary nanoparticle concentration in the tumor in order to be able to reach the necessary temperatures when administered through tail vein injection, to achieve this goal the temporal and spatial properties of the particles need to be assessed. For this purpose, iron oxide nanoparticles functionalized with carboxyl methyl dextran with various degrees of negative charge have been developed. Particles were designed to have different amounts of carboxyl groups per chain (30, 23 and 5 COOH). The objective of this work is to assess the in vivo temporal and spatial behavior of the particles described herein to assess the effect of particle charge o...