Biomedical subjects

A W Carr

Publications and source records attributed to A W Carr.

4 recordsLinked to original sources

PubMed2000

New diffusion-edited NMR experiments to expedite the dereplication of known compounds from natural product mixtures.

[reaction: see text] We present two new diffusion-edited NMR experiments, improved DECODES and HETDECODES, that sort the constituents in a mixture by their individual diffusion coefficients. These experiments should allow the partial NMR spectral assignment and cursory structure elucidation of compounds in a complex mixture as an aid in the dereplication of known or nuisance compounds.

Biological Factors↗

PubMed1993

Trifluoromethanesulfonamide anthelmintics. Protonophoric uncouplers of oxidative phosphorylation.

A series of trifluoromethanesulfonamides (TFMS) was synthesized and tested for uncoupling activity in rat liver mitochondria. With succinate as the mitochondrial substrate, and the respiratory control index (RCI) as an indicator of their uncoupling ability, we found that all of the TFMS tested were uncouplers of oxidative phosphorylation; the effective concentration (RCI I50) ranged from less than 1 microM to greater than 1000 microM. Correlation techniques were used to assess the strength of the relationship between the ability of a TFMS to uncouple oxidative phosphorylation and its ability to lower the electrical resistance of planar bimolecular lipid membranes. There was a highly significant (P < 0.001) positive linear relationship (r = 0.97) between the ability of a TFMS to uncouple oxidative phosphorylation and its ability to lower electrical resistance. These findings are consistent with the view that the TFMS are lipophilic protonophoric uncouplers of mitochondrial oxidative phosphorylation. Quantitative structure-activity relationship studies using experiment and semiempirical molecular orbital theory revealed that the hydrophobicity of a TFMS and its molecular dipole moment were the principal determinants of mitochondrial uncoupling activity within the pKa range examined.

Animals↗

PubMed1993

Uncoupling of rat liver mitochondrial oxidative phosphorylation by the fasciolicide triclabendazole and its sulfoxide and sulfone metabolites.

The uncoupling activity of a narrow-spectrum benzimidazole anthelmintic triclabendazole (TCZ, 6-chloro-5-[2,3-dichlorophenoxy]-2-methylthio-benzimidazole) and its 2 principal metabolites triclabendazole sulfoxide (TCZ sulfoxide, 6-chloro-5-[2,3-dichlorophenoxy]-2-methylsulfinyl-benzimidazole) and triclabendazole sulfone (TCZ sulfone, 6-chloro-5-[2,3-dichlorophenoxyl]-2methylsulfonyl- benzimidazole) has been determined using rat liver mitochondria. With glutamate or succinate as the mitchondrial substrate, and the respiratory control index (RCI) as an indicator of uncoupling activity, we found that TCZ and its 2 main metabolites were uncouplers of oxidative phosphorylation at micromolar concentrations. The rank order of in vitro activity was TCZ sulfone > TCZ sulfoxide > TCZ. Structure-activity relationship studies revealed that the electron-withdrawing power of the substituent in the 2-position was the principal determinant of mitochondrial uncoupling activity. Correlation techniques were used to assess the strength of the relationship between the ability of TCZ and its metabolites to uncouple oxidative phosphorylation and their ability to lower the electrical resistance of planar bimolecular lipid membranes. A log-log plot of RCI I50 vs. resistance effective concentration (REC I50) gave a linear fit with a correlation coefficient (r) of 0.98; an r of 0.98 indicates a high positive relationship between the ability of these fasciolicides to uncouple oxidative phosphorylation and their ability to lower electrical resistance. These findings are consistent with the view that TCZ and its sulfoxide and sulfone metabolites are lipophilic protonophoric uncouplers of rat liver mitochondrial oxidative phosphorylation.

2,4-Dinitrophenol↗

PubMed1987

Disguised countertransference in institutions.

The manifest reason for the hospitalization of psychiatric patients is that someone decides that they are in danger of suicide or homicide, or that they are unable sufficiently to care for or manage themselves. From another perspective, however, hospitalization can be understood as a consequence of limitations on the part of the family, the community, or the therapist in managing the affects generated in relation to these patients' behavior and communications. In other words, it is possible that patients may be hospitalized primarily because people in their lives (and often they themselves) cannot stand their own reactions to them and to their behavior. A less readily recognizable aspect of the institution, then, may be its use as a place to lock away unacknowledged, or at best uninterpreted problems of unbearable human responses to patients' psychopathology. In therapeutic relationships, where these issues are condensed, such responses are termed countertransference. The connections between individual relationships and institutional behavior are complex and inevitably contentious. In this paper, we suggest that a study of these connections may reveal disguised elements and illuminate some of the parameters of the complex phenomenon of countertransference.

Countertransference↗