Biomedical subjects

T C Stelly

Publications and source records attributed to T C Stelly.

4 recordsLinked to original sources

PubMed1995

Hemicorporectomy.

Intractable decubitus ulcers and femoropelvic osteomyelitis are rare sequelae of paraplegia. Therapy for these conditions ranges from the simple to the complex, including wound debridement and care, alimentary and urinary tract diversion, hip disarticulation, and myofasciocutaneous rotational flaps. Should the condition be recalcitrant to these modalities the only curative therapy is hemicorporectomy. A 28-year-old rendered paraplegic 3 years ago presented manifesting sepsis; marasmus; hip and knee flexion contractures; suppurative sacral and femoropelvic decubitus ulcers, exposed bone, and osteomyelitis; and fecal and urinary incontinence. Pre-operative nutritional supplementation, wound debridement and care, and psychological counselling were provided. Hemicorporectomy was performed, including colostomy, ureteroileal conduit, gastrostomy, and translumbar amputation. Several anatomical, physiological, and operative-technical perspectives are emphasized: a two-staged approach may be preferable--at the first setting an intra-peritoneal exploratory celiotomy with alimentary and urinary tract diversion; and at the second setting an extra-peritoneal hemicorporectomy; preservation of abdominal wall musculature and fasciae to facilitate wound closure; sequential and bilateral ligation of the arteriae et venae iliaca communis; translumbar amputation between the fourth and fifth lumbar vertebrae; extirpation of the fourth lumbar processus spinosus vertebrarum; closure of the dura mater and translation of musculi sacrospinalis into the vertebral canal; avoidance of hypervolemia and hyperthermia; avoidance of wound pressure; testosterone replacement therapy for eunuchism; and physical and occupational rehabilitation including adaptation to a customized bucket prosthesis.

Adult↗

PubMed1988

Hemipalmitoylcarnitinium, a strong competitive inhibitor of purified hepatic carnitine palmitoyltransferase.

We have synthesized (2S,6R:2R,6S)-6-carboxymethyl-2-hydroxy-2-pentadecyl-4,4-dimethylmorp holinium bromide (hemipalmitoylcarnitinium, HPC) which is a conformationally restricted analog inhibitor of carnitine palmitoyltransferase (CPT; EC 2.3.1.21). rac-HPC inhibits catalytic activity in purified rat liver CPT. In the forward reaction, HPC competes with both (R)-carnitine (Ki(app) = 5.1 +/- 0.7 microM) and palmitoyl-CoA (Ki(app) = 21.5 +/- 4.9 microM). In the reverse reaction, inhibition by HPC is competitive with palmitoyl-(R)-carnitine (Ki(app) = 1.6 +/- 0.6 microM), but inhibition is uncompetitive with CoA. The forward reaction is also competitively inhibited by its product, palmitoyl-(R)-carnitine, Ki(app)'s 14.2 +/- 2.1 microM relative to (R)-carnitine and 8.7 +/- 2.6 microM relative to palmitoyl-CoA. rac-HPC is the most potent synthetic reversible inhibitor of purified CPT. HPC fails to inhibit carnitine acetyltransferase (CAT; EC 2.3.1.7). Palmitoylcholine also inhibits CPT in the forward reaction, competing with (R)-carnitine (Ki(app) = 18.6 +/- 4.5 microM) and with palmitoyl CoA (Ki(app) = 10.4 +/- 2.5 microM). Choline is not an effective CPT inhibitor. We have shown [R.D. Gandour et al. (1986) Biochem. Biophys. Res. Commun. 138, 735-741] that hemiacetylcarnitinium inhibits CAT but not CPT. The combined data demonstrate further differences between the carnitine recognition sites in CPT and CAT.

Acyltransferases↗

PubMed1986

Active-site probes of carnitine acyltransferases. Inhibition of carnitine acetyltransferase by hemiacetylcarnitinium, a reaction intermediate analogue.

Hemiacetylcarnitinium (2S,6R:2R,65)-6-carboxymethyl-2-hydroxy-2,4,4- trimethylmorpholinium) chloride is a relatively potent competitive inhibitor (Ki = 0.89 mM) of pigeon breast carnitine acetyltransferase (CAT) and of the crude rat liver CAT (Ki = 4.72 mM) but is neither an inhibitor nor an effective substrate for purified rat liver carnitine palmitoyltransferase (CPT). It does not inhibit state 3 oxygen consumption in isolated hepatic mitochondria using palmitoyl-CoA or palmitoylcarnitine as substrates. This compound is a reaction intermediate analogue of the proposed tetrahedral intermediate for acetyl transfer between acetylcarnitine and CoASH. Because the hemiketal carbon is chiral, a suggestion is made that one of the enantiomers has the same relative configuration as the proposed tetrahedral intermediate.

Acetylcarnitine↗

PubMedDate not supplied

Inhibition of acetylcholinesterase by hemicholiniums, conformationally constrained choline analogues. Evaluation of aryl and alkyl substituents. Comparisons with choline and (3-hydroxyphenyl)trimethylammonium.

2-Substituted-2-hydroxy-4,4-dimethylmorpholiniums (hemicholiniums) inhibit acetylcholinesterase (EC 3.1.1.7)-catalyzed hydrolysis of acetylthiocholine (ATCh). The 4-substituted arenes [NH2, NHC(O)CH3, Cl, CN, and NO2] have values of inhibition constants (Ki) that range from 220 to 3690 microM, which correlate with Hammett sigma, rho approximately 0.8. The alkyl compounds, hydrogen, methyl, tert-butyl, and trifluoromethyl, have values of Ki of 550, 560, 1200, and 1200 microM, respectively. These values compare favorably with Ki = 960 microM for choline. The conformation of AChE-bound choline must be gauche to support our suggestion that hemicholiniums are conformationally constrained analogues of choline. (3-Hydroxyphenyl)trimethylammonium (5) inhibits most strongly, Ki = 0.21 microM, of the compounds examined in this study. The solvent isotope effect (H2OKi/D2OKi = 0.83 +/- 0.04) suggests that inhibition by 5 involves hydrogen bonding. The binding by AChE of the hemicholiniums of various sizes and the strong binding of 5 support an earlier proposal [Schowen, K. B., Smissman, E. E., and Stephen, W. F., Jr. (1975) J. Med. Chem. 18, 292-300] that the active site of AChE has ample space for rotation about the C-C bond in choline. Compound 5, which has one more carbon between the hydroxy and trimethylammonium than does choline, inhibits much more potently than either choline or the hemicholiniums. Compound 5 provides a correct spacer to span the trimethylammonium recognition site and the esteratic site of AChE. This aromatic spacer interacts favorably with the hydrophobic active site, and the phenolic hydroxyl probably hydrogen bonds to the histidine in the esteratic site. Choline in any conformation and the hemicholiniums are too short to make a strong hydrogen bond.

Animals↗