Abstract-Triglyceride-rich lipoprotein (TRL) remnants are formed in the circulation when apolipoprotein (apo) B-48 -containing chylomicrons of intestinal origin or apoB-100 -containing VLDL of hepatic origin are converted by lipoprotein lipase, and to a lesser extent by hepatic lipase, into smaller and more dense particles. Compared with their nascent precursors, TRL remnants are depleted of triglyceride, phospholipid, and C apolipoproteins and are enriched in cholesteryl esters and apoE. They can thus be identified, separated, and/or quantified in plasma according to their density, charge, size, specific lipid components, apolipoprotein composition, and/or apolipoprotein immunospecificity. Each of these approaches has contributed to our current understanding of the compositional characteristics of TRL remnants and their potential to promote atherosclerosis. An ongoing search is nevertheless under way for more accurate and clinically applicable remnant lipoprotein assays that will be able to better define coronary artery disease risk in patients with hypertriglyceridemia.

There is considerable clinical interest in the risks and benefits of offering oral water intake, in the form of water protocols, to patients with thin-liquid dysphagia. We describe the design and implementation of a water protocol for patients in a rehabilitation setting with videofluoroscopically confirmed thin-liquid aspiration. The GF Strong Water Protocol (GFSWP) is an interdisciplinary initiative, with roles and accountabilities specified for different members of the interprofessional health-care team. Rules of the water protocol specify mode of water access (independent, supervised), the implementation of any safe swallowing strategies recommended on the basis of the patient’s videofluoroscopy, and procedures for evaluating and addressing oral care needs. Trial implementation of the water protocol in 15 participants showed that they remained free of adverse events, including pneumonia, over the course of an initial 14-day trial and continuing until discharge from the facility (range = 13–108 days). Seven participants were randomly assigned to a 14-day control phase in which they received standard care (without water access). Fluid intake measures taken after the oral water intake phase were increased (mean = 1,845 cc; 95% confidence interval: 1,520–2,169 cc) compared to those in the control phase (mean = 1,474 cc; 95% CI: 1,113–1,836 cc), with oral water intake measures comprising, on average, 563 cc (range = 238–888 cc) of the total post water trial fluid intake values. Fluid intake increased at least 10% of the calculated fluid requirements in 11/15 participants who received oral water access. These participants reported favorable quality-of-life outcomes, measured using the Swal-QOL. These findings support the implementation of the GFSWP, including its exclusion criteria, rules, and plans of care, for rehabilitation patients who aspirate thin liquids.

We conducted an extensive mass isotopomer analysis of citric acid cycle and gluconeogenic metabolites isolated from livers of overnight fasted rats perfused with 4 mM glucose, 0.2 mM octanoate, 1 mM [U-13C3]lactate, and 0.2 mM [U-13C3]pyruvate, in the anterograde or retrograde mode. In both perfusion modes, two distinct isotopomer patterns were observed: (i) those of phosphoenolpyruvate, glucose, malate, and aspartate and (ii) those of citrate, alpha-ketoglutarate, glutamate, and glutamine. Key citric acid cycle parameters and, hence, rates of gluconeogenesis, calculated (Lee, W.-N.P. (1989) J. Biol. Chem. 264, 13002-13004 and Lee, W.-N.P. (1993) J. Biol. Chem. 268, 25522-25526) from our mass isotopomer data did not only vary, but lead to conclusions inconsistent with Lee's citric acid cycle model. Compared to lactate and pyruvate uptake, which sets an upper limit to glucose production, rates of gluconeogenesis calculated (i) with the phosphoenolpyruvate and citrate data were similar, but those calculated (ii) with the glutamate data amounted to only 60%, which is unlikely. All these conclusions are independent of the perfusion modes. We provide evidence that the following processes contribute to the observed labeling discrepancy: (i) the reversibility of the isocitrate dehydrogenase reaction and (ii) an active citrate cleavage pathway for the transfer of the oxaloacetate carbon skeleton from mitochondria to the cytosol. Also, a good fit of our labeling data was obtained with a model of citric acid cycle and gluconeogenesis which we developed to incorporate the above reactions (Fernandez, C.A., and Des Rosiers, C. (1995) J. Biol. Chem. 270, 10037-10042). The following conclusions can be drawn from the calculated reaction rates: (i) about half of the lactate conversion to glucose occurs via the citrate cleavage pathway, (ii) the flux through the reversal of the isocitrate dehydrogenase reaction is almost as fast as that through the citrate synthase reaction, and (iii) the flux through citrate synthase and alpha-ketoglutarate dehydrogenase is 1.6- and 3.2-fold that through pyruvate carboxylase, respectively.

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