Elana Brief - Academia.edu (original) (raw)

Papers by Elana Brief

Physical Review A, Feb 27, 2006

Langmuir, May 1, 2009

The phase behavior and lipid mixing properties of an equimolar mixture of nonhydroxylated palmito... more The phase behavior and lipid mixing properties of an equimolar mixture of nonhydroxylated palmitoyl ceramide (Cer16), palmitic acid (PA), and cholesterol have been investigated using 2H NMR and vibrational spectroscopy. This mixture is formed by the three main classes of lipids found in the stratum corneum (SC), the top layer of the epidermis, and provides an optimized hydrophobic matching. Therefore, its behavior highlights the role played by hydrophobic matching on the phase behavior of SC lipids. We found that, below 45 degrees C, the mixture is essentially formed of coexisting crystalline domains with a small fraction of lipids (less than 20%) that forms a gel or fluid phase, likely ensuring cohesion between the solid domains. Upon heating, there is the formation of a liquid ordered phase mainly composed of PA and cholesterol, including a small fraction of Cer16. This finding is particularly highlighted by correlation vibrational microspectroscopy that indicates that domains enriched in cholesterol and PA include more disordered Cer16 than those found in the Cer16-rich domains. Solubilization of Cer16 in the fluid phase occurs progressively upon further heating, and this leads to the formation of a nonlamellar self-assembly where the motions are isotropic on the NMR time scale. It is found that the miscibility of Cer16 with cholesterol and PA is more limited than the one previously observed for ceramide III extracted from bovine brain, which is heterogeneous in chain composition and includes, in addition to Cer16, analogous ceramide with longer alkyl chains that are not hydrophobically matched with cholesterol and PA. Therefore, it is inferred that, in SC, the chain heterogeneity is a stronger criteria for lipid miscibility than chain hydrophobic matching.

NMR in Biomedicine, Dec 23, 2008

Magnetic resonance spectroscopy (MRS) has been coupled with a multi-echo imaging sequence to dete... more Magnetic resonance spectroscopy (MRS) has been coupled with a multi-echo imaging sequence to determine the relaxation corrected signal areas of the metabolites and the tissue water. Stimulated echo acquisition mode (STEAM) spectra (TE/TM/TR 30/13.7/5000 ms) acquired from gray and white matter voxels in 43 healthy volunteers were fit using LCModel. Corresponding water signals, measured using a multi-echo T(2) imaging sequence, were fit with a Non-Negative Least Squares algorithm. Using this approach the water area could be T(1) and T(2) corrected for all three water compartments: cerebrospinal fluid (CSF), intra- and extra-cellular water, and myelin water. The image-based water measurement is an improvement over spectroscopy methods because it can be more sensitive to water changes in diseased tissue. Metabolite areas were also corrected for relaxation losses. In occipital gray matter, the concentrations of Cho, Cr, and N-acetyl aspartate (NAA) were 1.27 (0.06), 8.9 (0.3), and 9.3 (0.3) mmol/L tissue, respectively and in parietal white matter they were 1.90 (0.05), 7.9 (0.2), and 9.8 (0.2) mmol/L tissue. The Cho and Cr concentrations were different in occipital gray compared to parietal white matter (p < 0.0001 and <0.005, respectively).

Alzheimers & Dementia, Jul 1, 2010

Minnesota journal of law, science & technology, 2012

Journal of Pharmaceutical Sciences, May 1, 2010

Triggered release of liposomal contents following tumor accumulation and mild local heating is pu... more Triggered release of liposomal contents following tumor accumulation and mild local heating is pursued as a means of improving the therapeutic index of chemotherapeutic drugs. Lysolipid-containing thermosensitive liposomes (LTSLs) are composed of dipalmitoylphosphatidylcholine (DPPC), the lysolipid monostearoylphosphatidylcholine (MSPC), and poly(ethylene glycol)-conjugated distearoylphosphatidylethanolamine (DSPE-PEG(2000)). We investigated the roles of DSPE-PEG(2000) and lysolipid in the functional performance of the LTSL-doxorubicin formulation. Varying PEG-lipid concentration (0-5 mol%) or bilayer orientation did not affect the release; however, lysolipid (0-10 mol%) had a concentration-dependent effect on drug release at 42 degrees C in vitro. Pharmacokinetics of various LTSL formulations were compared in mice with body temperature controlled at 37 degrees C. As expected, incorporation of the PEG-lipid increased doxorubicin plasma half-life; however, PEG-lipid orientation (bilayer vs. external leaflet) did not significantly improve circulation lifetime or drug retention in LTSL. Approximately 70% of lysolipid was lost within 1 h postinjection of LTSL, which could be due to interactions with the large membrane pool of the biological milieu. Considering that the present LTSL-doxorubicin formulation exhibits significant therapeutic activity when used in conjunction with mild heating, our current study provided critical insights into how the physicochemical properties of LTSL can be tailored to achieve better therapeutic activity.

Journal of Genetic Counseling, Oct 7, 2010

Minnesota journal of law, science & technology, 2012

An incidental finding is a finding “concerning an individual research participant that has potent... more An incidental finding is a finding “concerning an individual research participant that has potential health or reproductive importance and is discovered in the course of conducting the research but is beyond the aims of the study.”1 In a genetic family study, for example, a researcher may identify misattributed parentage of a study participant.2 Or, while surveying the genetic variation of a specific population for one disease (e.g., diabetes), a researcher may find an allelic variation in some individuals that puts them at risk for a different disease than the one under investigation (e.g., cardiovascular dis-

Journal of Academic Ethics, Jun 1, 2009

Journal of Genetic Counseling, 2011

A novel, pathogenic presenilin 1 (PS1) mutation has recently been identified in a large Aborigina... more A novel, pathogenic presenilin 1 (PS1) mutation has recently been identified in a large Aboriginal kindred living in dispersed communities throughout British Columbia, Canada. Disseminating genetic information and ensuring that appropriate genetic counseling services are provided to all concerned relatives have posed several unique challenges. These challenges include knowledge exchange and continuity of care in a geographically remote and culturally distinct community. To our knowledge, this is the first time a specific genetic counseling approach has been needed for early-onset familial Alzheimer disease (EOFAD) in a North American Aboriginal community.

Langmuir, Aug 1, 2009

The phase behavior and lipid mixing properties of an equimolar mixture of nonhydroxylated palmito... more The phase behavior and lipid mixing properties of an equimolar mixture of nonhydroxylated palmitoyl ceramide (Cer16), palmitic acid (PA), and cholesterol have been investigated using 2H NMR and vibrational spectroscopy. This mixture is formed by the three main classes of lipids found in the stratum corneum (SC), the top layer of the epidermis, and provides an optimized hydrophobic matching. Therefore, its behavior highlights the role played by hydrophobic matching on the phase behavior of SC lipids. We found that, below 45 degrees C, the mixture is essentially formed of coexisting crystalline domains with a small fraction of lipids (less than 20%) that forms a gel or fluid phase, likely ensuring cohesion between the solid domains. Upon heating, there is the formation of a liquid ordered phase mainly composed of PA and cholesterol, including a small fraction of Cer16. This finding is particularly highlighted by correlation vibrational microspectroscopy that indicates that domains enriched in cholesterol and PA include more disordered Cer16 than those found in the Cer16-rich domains. Solubilization of Cer16 in the fluid phase occurs progressively upon further heating, and this leads to the formation of a nonlamellar self-assembly where the motions are isotropic on the NMR time scale. It is found that the miscibility of Cer16 with cholesterol and PA is more limited than the one previously observed for ceramide III extracted from bovine brain, which is heterogeneous in chain composition and includes, in addition to Cer16, analogous ceramide with longer alkyl chains that are not hydrophobically matched with cholesterol and PA. Therefore, it is inferred that, in SC, the chain heterogeneity is a stronger criteria for lipid miscibility than chain hydrophobic matching.

Sociological Research Online, 2009

... by Cecilia Benoit, Leah Shumka, Kate Vallance, Helga Hallgrímsdóttir, Rachel Phillips, Karen ... more ... by Cecilia Benoit, Leah Shumka, Kate Vallance, Helga Hallgrímsdóttir, Rachel Phillips, Karen Kobayashi, Olena Hankivsky, Colleen Reid and Elana ... in health over time, as well as in comparative perspective (Benoit 2000; McDonough and Walters 2001; Denton, Walters and ...

Physical Review A, Feb 27, 2006

Langmuir, May 1, 2009

The phase behavior and lipid mixing properties of an equimolar mixture of nonhydroxylated palmito... more The phase behavior and lipid mixing properties of an equimolar mixture of nonhydroxylated palmitoyl ceramide (Cer16), palmitic acid (PA), and cholesterol have been investigated using 2H NMR and vibrational spectroscopy. This mixture is formed by the three main classes of lipids found in the stratum corneum (SC), the top layer of the epidermis, and provides an optimized hydrophobic matching. Therefore, its behavior highlights the role played by hydrophobic matching on the phase behavior of SC lipids. We found that, below 45 degrees C, the mixture is essentially formed of coexisting crystalline domains with a small fraction of lipids (less than 20%) that forms a gel or fluid phase, likely ensuring cohesion between the solid domains. Upon heating, there is the formation of a liquid ordered phase mainly composed of PA and cholesterol, including a small fraction of Cer16. This finding is particularly highlighted by correlation vibrational microspectroscopy that indicates that domains enriched in cholesterol and PA include more disordered Cer16 than those found in the Cer16-rich domains. Solubilization of Cer16 in the fluid phase occurs progressively upon further heating, and this leads to the formation of a nonlamellar self-assembly where the motions are isotropic on the NMR time scale. It is found that the miscibility of Cer16 with cholesterol and PA is more limited than the one previously observed for ceramide III extracted from bovine brain, which is heterogeneous in chain composition and includes, in addition to Cer16, analogous ceramide with longer alkyl chains that are not hydrophobically matched with cholesterol and PA. Therefore, it is inferred that, in SC, the chain heterogeneity is a stronger criteria for lipid miscibility than chain hydrophobic matching.

NMR in Biomedicine, Dec 23, 2008

Magnetic resonance spectroscopy (MRS) has been coupled with a multi-echo imaging sequence to dete... more Magnetic resonance spectroscopy (MRS) has been coupled with a multi-echo imaging sequence to determine the relaxation corrected signal areas of the metabolites and the tissue water. Stimulated echo acquisition mode (STEAM) spectra (TE/TM/TR 30/13.7/5000 ms) acquired from gray and white matter voxels in 43 healthy volunteers were fit using LCModel. Corresponding water signals, measured using a multi-echo T(2) imaging sequence, were fit with a Non-Negative Least Squares algorithm. Using this approach the water area could be T(1) and T(2) corrected for all three water compartments: cerebrospinal fluid (CSF), intra- and extra-cellular water, and myelin water. The image-based water measurement is an improvement over spectroscopy methods because it can be more sensitive to water changes in diseased tissue. Metabolite areas were also corrected for relaxation losses. In occipital gray matter, the concentrations of Cho, Cr, and N-acetyl aspartate (NAA) were 1.27 (0.06), 8.9 (0.3), and 9.3 (0.3) mmol/L tissue, respectively and in parietal white matter they were 1.90 (0.05), 7.9 (0.2), and 9.8 (0.2) mmol/L tissue. The Cho and Cr concentrations were different in occipital gray compared to parietal white matter (p < 0.0001 and <0.005, respectively).

Alzheimers & Dementia, Jul 1, 2010

Minnesota journal of law, science & technology, 2012

Journal of Pharmaceutical Sciences, May 1, 2010

Triggered release of liposomal contents following tumor accumulation and mild local heating is pu... more Triggered release of liposomal contents following tumor accumulation and mild local heating is pursued as a means of improving the therapeutic index of chemotherapeutic drugs. Lysolipid-containing thermosensitive liposomes (LTSLs) are composed of dipalmitoylphosphatidylcholine (DPPC), the lysolipid monostearoylphosphatidylcholine (MSPC), and poly(ethylene glycol)-conjugated distearoylphosphatidylethanolamine (DSPE-PEG(2000)). We investigated the roles of DSPE-PEG(2000) and lysolipid in the functional performance of the LTSL-doxorubicin formulation. Varying PEG-lipid concentration (0-5 mol%) or bilayer orientation did not affect the release; however, lysolipid (0-10 mol%) had a concentration-dependent effect on drug release at 42 degrees C in vitro. Pharmacokinetics of various LTSL formulations were compared in mice with body temperature controlled at 37 degrees C. As expected, incorporation of the PEG-lipid increased doxorubicin plasma half-life; however, PEG-lipid orientation (bilayer vs. external leaflet) did not significantly improve circulation lifetime or drug retention in LTSL. Approximately 70% of lysolipid was lost within 1 h postinjection of LTSL, which could be due to interactions with the large membrane pool of the biological milieu. Considering that the present LTSL-doxorubicin formulation exhibits significant therapeutic activity when used in conjunction with mild heating, our current study provided critical insights into how the physicochemical properties of LTSL can be tailored to achieve better therapeutic activity.

Journal of Genetic Counseling, Oct 7, 2010

Minnesota journal of law, science & technology, 2012

An incidental finding is a finding “concerning an individual research participant that has potent... more An incidental finding is a finding “concerning an individual research participant that has potential health or reproductive importance and is discovered in the course of conducting the research but is beyond the aims of the study.”1 In a genetic family study, for example, a researcher may identify misattributed parentage of a study participant.2 Or, while surveying the genetic variation of a specific population for one disease (e.g., diabetes), a researcher may find an allelic variation in some individuals that puts them at risk for a different disease than the one under investigation (e.g., cardiovascular dis-

Journal of Academic Ethics, Jun 1, 2009

Journal of Genetic Counseling, 2011

A novel, pathogenic presenilin 1 (PS1) mutation has recently been identified in a large Aborigina... more A novel, pathogenic presenilin 1 (PS1) mutation has recently been identified in a large Aboriginal kindred living in dispersed communities throughout British Columbia, Canada. Disseminating genetic information and ensuring that appropriate genetic counseling services are provided to all concerned relatives have posed several unique challenges. These challenges include knowledge exchange and continuity of care in a geographically remote and culturally distinct community. To our knowledge, this is the first time a specific genetic counseling approach has been needed for early-onset familial Alzheimer disease (EOFAD) in a North American Aboriginal community.

Langmuir, Aug 1, 2009

The phase behavior and lipid mixing properties of an equimolar mixture of nonhydroxylated palmito... more The phase behavior and lipid mixing properties of an equimolar mixture of nonhydroxylated palmitoyl ceramide (Cer16), palmitic acid (PA), and cholesterol have been investigated using 2H NMR and vibrational spectroscopy. This mixture is formed by the three main classes of lipids found in the stratum corneum (SC), the top layer of the epidermis, and provides an optimized hydrophobic matching. Therefore, its behavior highlights the role played by hydrophobic matching on the phase behavior of SC lipids. We found that, below 45 degrees C, the mixture is essentially formed of coexisting crystalline domains with a small fraction of lipids (less than 20%) that forms a gel or fluid phase, likely ensuring cohesion between the solid domains. Upon heating, there is the formation of a liquid ordered phase mainly composed of PA and cholesterol, including a small fraction of Cer16. This finding is particularly highlighted by correlation vibrational microspectroscopy that indicates that domains enriched in cholesterol and PA include more disordered Cer16 than those found in the Cer16-rich domains. Solubilization of Cer16 in the fluid phase occurs progressively upon further heating, and this leads to the formation of a nonlamellar self-assembly where the motions are isotropic on the NMR time scale. It is found that the miscibility of Cer16 with cholesterol and PA is more limited than the one previously observed for ceramide III extracted from bovine brain, which is heterogeneous in chain composition and includes, in addition to Cer16, analogous ceramide with longer alkyl chains that are not hydrophobically matched with cholesterol and PA. Therefore, it is inferred that, in SC, the chain heterogeneity is a stronger criteria for lipid miscibility than chain hydrophobic matching.

Sociological Research Online, 2009

... by Cecilia Benoit, Leah Shumka, Kate Vallance, Helga Hallgrímsdóttir, Rachel Phillips, Karen ... more ... by Cecilia Benoit, Leah Shumka, Kate Vallance, Helga Hallgrímsdóttir, Rachel Phillips, Karen Kobayashi, Olena Hankivsky, Colleen Reid and Elana ... in health over time, as well as in comparative perspective (Benoit 2000; McDonough and Walters 2001; Denton, Walters and ...