The purpose of these studies was to evaluate the effects of chronic caffeine ingestion on the myo... more The purpose of these studies was to evaluate the effects of chronic caffeine ingestion on the myocardium during fetal and neonatal growth and development. The isolated perfused working heart preparation was used to evaluate cardiac function. During gestation and lactation, one group of dams consumed a caffeine supplemented diet (10 mg/kg/day). Their offspring were sacrificed and the hearts analyzed 50 days after birth. We found that the intake of caffeine by the dams resulted in significant increases in the offspring's coronary flow, peak systolic pressure, and myocardial work. A second group of dams ingested a diet containing caffeine (10 mg/kg/day) during lactation only. Their pups continued to consume the caffeine diet until 50 days. Pup hearts exhibited significant reductions in cardiac output, stroke volume, pressure development, myocardial work, and external efficiency when compared to controls. Caffeine did not affect body or heart weight or adipose size or number in these experiments. Thus, continued caffeine consumption following birth may alter cardiac performance of the offspring.
The diagnostic and therapeutic approaches used for patients referred for bile duct injuries and o... more The diagnostic and therapeutic approaches used for patients referred for bile duct injuries and other major complications after laparoscopic cholecystectomy (LC) were reviewed and the results of a coordinated radiologic, endoscopic, and surgical approach were assessed.
Evidence has been presented suggesting that a reactive metabolite, 2-phenylpropenal (ATPAL), may ... more Evidence has been presented suggesting that a reactive metabolite, 2-phenylpropenal (ATPAL), may be responsible for the toxicities observed during therapy with the antiepileptic drug felbamate (FBM). Formation of ATPAL from its unstable immediate precursor, 3-carbamoyl-2-phenylpropionaldedhyde (CBMA) requires the loss of the hydrogen atom at position 2 in the propane chain, and it has been postulated that substitution of this atom with fluorine would prevent the formation of ATPAL. On the basis of this hypothesis, 2-fluoro-2-phenyl-1,3-propanediol dicarbamate (F-FBM) was synthesized and is presently undergoing drug development. To test this hypothesis, we compared the metabolism by human liver postmitochondrial suspensions (S9) in vitro of selected FBM and postulated F-FBM metabolites leading to formation of CBMA or 3-carbamoyl-2-fluoro-2-phenyl-propionaldehyde (F-CBMA). All S9 incubations included GSH as a trapping agent for any reactive metabolites formed. Our results indicated that, in phosphate buffer, pH 7.4, at 37 degrees C, the half-life for 4-hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one (CCMF) was 2.8 and 3.6 h in the presence or absence of GSH, respectively; compared to 4-hydroxy-5-fluoro-5-phenyl-tetrahydro-1,3-oxazin-2-one (F-CCMF) which lost only 2.5% or 4.9% over 24 h under the same conditions. When incubated with S9 in the presence of the cofactor, NAD+, 2-phenyl-1,3-propanediol monocarbamate (MCF) was oxidized to CCMF which was further oxidized to 3-carbamoyl-2-phenylpropionic acid (CPPA). 2-Fluoro-2-phenyl-1,3-propanediol monocarbamate (F-MCF) under similar conditions was stable, and no metabolites were observed. When CCMF was incubated with S9 in the presence of NAD+ cofactor, oxidation to CPPA and reduction to MCF were observed. In addition, a new atropic acid GSH adduct (ATPA-GSH) was identified by mass spectrometry. When F-CCMF was incubated under the same conditions as CCMF, both reduced and oxidized metabolites, F-MCF and 3-carbamoyl-2-fluoro-2-phenylpropionic acid (F-CPPA), respectively, were formed but at significantly lower rates, and no GSH conjugates were identified. Our results support the hypothesis that F-FBM and F-CCMF are not metabolized by S9 in vitro to the known reactive FBM metabolite, ATPAL.
Novel 5-[(alkylamino)methyl]thieno[2,3-b]furan-2-sulfonamides were prepared and evaluated in vitr... more Novel 5-[(alkylamino)methyl]thieno[2,3-b]furan-2-sulfonamides were prepared and evaluated in vitro for inhibition of human carbonic anhydrase II (CA II) and ex vivo for their ability to inhibit Ca II in the albino rabbit eye after topical administration. Compound 11a was found to lower intraocular pressure (IOP) in both the alpha-CT ocular hypertensive albino rabbit and the normal albino rabbit, but was ineffective at lowering IOP in a hypertensive, pigmented monkey model. Since 11a was highly bound to ocular pigment, a series of less basic analogs was prepared. Examples in this series were both less extensively bound to ocular pigment and more active at reducing IOP in pigmented rabbits after topical dosing. Key examples displayed moderate reactivity toward glutathione.
This article details new research showing that the majority of U.S. consumers have strong inclina... more This article details new research showing that the majority of U.S. consumers have strong inclinations to buy earth-sustainable food products. Contrary to prevailing beliefs in the industry, the market potential for these products is enormous—52 percent of consumers are willing to buy “green,” and nearly one-third (30 percent) can actually be considered as the core market for earth-sustainable food products. Yet these products currently represent only 2 percent of all food sales. This immense gap can be eliminated by turning our focus from supply (an endless stream of new product introductions) to demand (the needs of the consumer). Doing so requires a clear understanding of the consumer and the dispelling of several myths that pervade the marketplace today.Information in this article was taken from Phase 1 of The Hartman Report—Food and the Environment: A Consumer's Perspective, which examines the consumer segments in much more detail with regard to attitudinal, demographic, and psychographic profiles. The report was commissioned, in part, by The Kellogg Foundation, The Food Alliance, and Cascadian Farm. Phase II of the research more closely examines those segments that represent the key target markets for these products, including information on the effects of advertising, public relations, and labels in communicating environmentally sustainable product messages. Phase III will develop specific retail tactics that can be effective in delivering products and services to the most important segments. For information on obtaining a copy of the report, contact The Hartman Group at 206–451–9094.
... Jared M Ashcroft, Keith B Hartman, Yuri Mackeyev, Cristina Hofmann, Sean Pheasant, Lawrence B... more ... Jared M Ashcroft, Keith B Hartman, Yuri Mackeyev, Cristina Hofmann, Sean Pheasant, Lawrence B Alemany and Lon J Wilson Department of Chemistry, RE Smalley Institute for Nanoscale Science and Technology, and the Center for Biological and Environmental ...
In this article, we explore the world’s response to the increasing impact of carbon emissions on ... more In this article, we explore the world’s response to the increasing impact of carbon emissions on the sobering threat posed by global warming: the carbon offset market. Though the market is a relatively new one, numerous offset providers have quickly emerged under both regulated and voluntary regimes. Owing to the lack of technical literacy of some stakeholders who participate in the market, no common quality or certification structure has yet emerged for providers. To the contrary, the media warns that a relative “cowboy” atmosphere prevails in the current environment, and that there are “widespread instances of people and organizations buying worthless credits that do not yield any reductions in carbon emissions” (Harvey and Fidler, Financial Times, 2007). At this point in the evolution of the market, only a handful of offset provider-rating schemes exist; and, even these systems leave consumers with few answers when they seek to find a means by which to ensure that the said systems are having their intended impact. The purpose of this article is, first, to provide a grounded understanding of the nature of the offset market, a tendency toward carbon neutrality as a possible point of equilibrium, and the ethical tensions that surround it from the perspective of the consuming public. Second, we outline the standards environment for offset providers to illustrate most effectively the need for a single set of criteria among providers that is readily understandable by the common consumer stakeholder. We then explore the differences among the providers and articulate the specific criteria upon which providers may be evaluated by this particular stakeholder constituency, by bringing together best practices based on currently available analyses. Finally, we share the results of preliminary data collection in connection with 117 offset providers and highlight early findings. These findings allow us comparing providers effectively and efficiently on a common scale that services both providers, who thereby have greater guidance for self-assessment purposes, as well as consumer stakeholders, who then have the ability to make useful and more informed choices about carbon emission reduction in the future.
The purpose of these studies was to evaluate the effects of chronic caffeine ingestion on the myo... more The purpose of these studies was to evaluate the effects of chronic caffeine ingestion on the myocardium during fetal and neonatal growth and development. The isolated perfused working heart preparation was used to evaluate cardiac function. During gestation and lactation, one group of dams consumed a caffeine supplemented diet (10 mg/kg/day). Their offspring were sacrificed and the hearts analyzed 50 days after birth. We found that the intake of caffeine by the dams resulted in significant increases in the offspring's coronary flow, peak systolic pressure, and myocardial work. A second group of dams ingested a diet containing caffeine (10 mg/kg/day) during lactation only. Their pups continued to consume the caffeine diet until 50 days. Pup hearts exhibited significant reductions in cardiac output, stroke volume, pressure development, myocardial work, and external efficiency when compared to controls. Caffeine did not affect body or heart weight or adipose size or number in these experiments. Thus, continued caffeine consumption following birth may alter cardiac performance of the offspring.
The diagnostic and therapeutic approaches used for patients referred for bile duct injuries and o... more The diagnostic and therapeutic approaches used for patients referred for bile duct injuries and other major complications after laparoscopic cholecystectomy (LC) were reviewed and the results of a coordinated radiologic, endoscopic, and surgical approach were assessed.
Evidence has been presented suggesting that a reactive metabolite, 2-phenylpropenal (ATPAL), may ... more Evidence has been presented suggesting that a reactive metabolite, 2-phenylpropenal (ATPAL), may be responsible for the toxicities observed during therapy with the antiepileptic drug felbamate (FBM). Formation of ATPAL from its unstable immediate precursor, 3-carbamoyl-2-phenylpropionaldedhyde (CBMA) requires the loss of the hydrogen atom at position 2 in the propane chain, and it has been postulated that substitution of this atom with fluorine would prevent the formation of ATPAL. On the basis of this hypothesis, 2-fluoro-2-phenyl-1,3-propanediol dicarbamate (F-FBM) was synthesized and is presently undergoing drug development. To test this hypothesis, we compared the metabolism by human liver postmitochondrial suspensions (S9) in vitro of selected FBM and postulated F-FBM metabolites leading to formation of CBMA or 3-carbamoyl-2-fluoro-2-phenyl-propionaldehyde (F-CBMA). All S9 incubations included GSH as a trapping agent for any reactive metabolites formed. Our results indicated that, in phosphate buffer, pH 7.4, at 37 degrees C, the half-life for 4-hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one (CCMF) was 2.8 and 3.6 h in the presence or absence of GSH, respectively; compared to 4-hydroxy-5-fluoro-5-phenyl-tetrahydro-1,3-oxazin-2-one (F-CCMF) which lost only 2.5% or 4.9% over 24 h under the same conditions. When incubated with S9 in the presence of the cofactor, NAD+, 2-phenyl-1,3-propanediol monocarbamate (MCF) was oxidized to CCMF which was further oxidized to 3-carbamoyl-2-phenylpropionic acid (CPPA). 2-Fluoro-2-phenyl-1,3-propanediol monocarbamate (F-MCF) under similar conditions was stable, and no metabolites were observed. When CCMF was incubated with S9 in the presence of NAD+ cofactor, oxidation to CPPA and reduction to MCF were observed. In addition, a new atropic acid GSH adduct (ATPA-GSH) was identified by mass spectrometry. When F-CCMF was incubated under the same conditions as CCMF, both reduced and oxidized metabolites, F-MCF and 3-carbamoyl-2-fluoro-2-phenylpropionic acid (F-CPPA), respectively, were formed but at significantly lower rates, and no GSH conjugates were identified. Our results support the hypothesis that F-FBM and F-CCMF are not metabolized by S9 in vitro to the known reactive FBM metabolite, ATPAL.
Novel 5-[(alkylamino)methyl]thieno[2,3-b]furan-2-sulfonamides were prepared and evaluated in vitr... more Novel 5-[(alkylamino)methyl]thieno[2,3-b]furan-2-sulfonamides were prepared and evaluated in vitro for inhibition of human carbonic anhydrase II (CA II) and ex vivo for their ability to inhibit Ca II in the albino rabbit eye after topical administration. Compound 11a was found to lower intraocular pressure (IOP) in both the alpha-CT ocular hypertensive albino rabbit and the normal albino rabbit, but was ineffective at lowering IOP in a hypertensive, pigmented monkey model. Since 11a was highly bound to ocular pigment, a series of less basic analogs was prepared. Examples in this series were both less extensively bound to ocular pigment and more active at reducing IOP in pigmented rabbits after topical dosing. Key examples displayed moderate reactivity toward glutathione.
This article details new research showing that the majority of U.S. consumers have strong inclina... more This article details new research showing that the majority of U.S. consumers have strong inclinations to buy earth-sustainable food products. Contrary to prevailing beliefs in the industry, the market potential for these products is enormous—52 percent of consumers are willing to buy “green,” and nearly one-third (30 percent) can actually be considered as the core market for earth-sustainable food products. Yet these products currently represent only 2 percent of all food sales. This immense gap can be eliminated by turning our focus from supply (an endless stream of new product introductions) to demand (the needs of the consumer). Doing so requires a clear understanding of the consumer and the dispelling of several myths that pervade the marketplace today.Information in this article was taken from Phase 1 of The Hartman Report—Food and the Environment: A Consumer's Perspective, which examines the consumer segments in much more detail with regard to attitudinal, demographic, and psychographic profiles. The report was commissioned, in part, by The Kellogg Foundation, The Food Alliance, and Cascadian Farm. Phase II of the research more closely examines those segments that represent the key target markets for these products, including information on the effects of advertising, public relations, and labels in communicating environmentally sustainable product messages. Phase III will develop specific retail tactics that can be effective in delivering products and services to the most important segments. For information on obtaining a copy of the report, contact The Hartman Group at 206–451–9094.
... Jared M Ashcroft, Keith B Hartman, Yuri Mackeyev, Cristina Hofmann, Sean Pheasant, Lawrence B... more ... Jared M Ashcroft, Keith B Hartman, Yuri Mackeyev, Cristina Hofmann, Sean Pheasant, Lawrence B Alemany and Lon J Wilson Department of Chemistry, RE Smalley Institute for Nanoscale Science and Technology, and the Center for Biological and Environmental ...
In this article, we explore the world’s response to the increasing impact of carbon emissions on ... more In this article, we explore the world’s response to the increasing impact of carbon emissions on the sobering threat posed by global warming: the carbon offset market. Though the market is a relatively new one, numerous offset providers have quickly emerged under both regulated and voluntary regimes. Owing to the lack of technical literacy of some stakeholders who participate in the market, no common quality or certification structure has yet emerged for providers. To the contrary, the media warns that a relative “cowboy” atmosphere prevails in the current environment, and that there are “widespread instances of people and organizations buying worthless credits that do not yield any reductions in carbon emissions” (Harvey and Fidler, Financial Times, 2007). At this point in the evolution of the market, only a handful of offset provider-rating schemes exist; and, even these systems leave consumers with few answers when they seek to find a means by which to ensure that the said systems are having their intended impact. The purpose of this article is, first, to provide a grounded understanding of the nature of the offset market, a tendency toward carbon neutrality as a possible point of equilibrium, and the ethical tensions that surround it from the perspective of the consuming public. Second, we outline the standards environment for offset providers to illustrate most effectively the need for a single set of criteria among providers that is readily understandable by the common consumer stakeholder. We then explore the differences among the providers and articulate the specific criteria upon which providers may be evaluated by this particular stakeholder constituency, by bringing together best practices based on currently available analyses. Finally, we share the results of preliminary data collection in connection with 117 offset providers and highlight early findings. These findings allow us comparing providers effectively and efficiently on a common scale that services both providers, who thereby have greater guidance for self-assessment purposes, as well as consumer stakeholders, who then have the ability to make useful and more informed choices about carbon emission reduction in the future.
Uploads
Papers by Hartman Harvey