Hydrogen/deuterium isotope effects on hydrophobic binding were examined by means of reversed-phase chromatographic separation of protiated and deuterated isotopologue pairs for a set of 10 nonpolar and low-polarity compounds with 10 stationary phases having alkyl and aryl groups bonded to the silica surface. It was found that protiated compounds bind to nonpolar moieties attached to silica more strongly than deuterated ones, demonstrating that the CH/CD bonds of the solutes are weakened or have less restricted motions when bound in the stationary phase compared with the aqueous solvent (mobile phase). The interactions responsible for binding have been further characterized by studies of the effects of changes in mobile phase composition, temperature dependence of binding, and QSRR (quantitative structure-chromatographic retention relationship) analysis, demonstrating the importance of enthalpic effects in binding and differentiation between the isotopologues. To explain our results showing the active role of the hydrophobic (stationary) phase we propose a plausible model that includes specific contributions from aromatic edge-to-face attractive interactions and attractive interactions of aliphatic groups with the pi clouds of aromatic groups present as the solute or in the stationary phase.

Interactions between alpha 1-acid glycoprotein (AGP) and 52 basic drugs were quantified by means of high-performance liquid chromatography (HPLC). The HPLC retention parameters were related quantitatively to the hydrophobicity and molecular modelling parameters, giving rise to the prediction of relative drug-AGP binding from the chemical structure of a drug. A structural model of one binding site on AGP, common for various classes of drugs, was defined which accounted for the observed and reported differences in binding to AGP. A combination of biochromatography and chemometrics has been presented as a promising new approach in biochemical/pharmacological studies.

The rapid rise in obesity-related diseases has increased interest in oral and dietary agents that disrupt fat metabolism, resulting in the excretion of dietary lipids in the feces. In this study, a rapid and convenient liquid chromatography method to comprehensively analyze fecal lipids in a single injection was developed. An evaporative light-scattering detector (ELSD) for routine analysis or atmosphere pressure chemical ionization tandem mass spectrometry [(+)APCI-MS/MS] for structural confirmation and peak purity was used. The method was applied to characterize lipid components of feces from hamsters fed high-fat diets with either 5% microcrystalline cellulose or 5% hydroxypropyl methylcellulose (HPMC) fibers, to test the effect of HPMC on lipid metabolism. HPMC is a nonfermentable, soluble cellulose fiber. The fecal lipid components identified using this method includes two secondary bile acids, deoxycholic acid, lithocholic acid, and neutral sterols including cholesterol, coprostanol, stigmastanol, and sitosterol. The profile of fecal lipid components was compared between two groups. It was found that the bile acid excretion was increased 2-fold in HPMC-fed hamsters. More interestingly, diacylglycerides and triacylglycerides were detected in feces from hamsters on HPMC-included high-fat diets. We believe that this is the first report of excretion of acylglycerides following neutral soluble fiber feeding.

OBJECTIVE -High-viscosity hydroxypropylmethylcellulose (HV-HPMC) is a modified cellulose fiber that produces a viscous gel in the gastrointestinal tract. Clinical trials demonstrate that consumption of HV-HPMC significantly lowers cholesterol, but limited information has been available on the influence of HV-HPMC on postprandial insulin and glucose responses. The objective of this investigation was to assess the influence of HV-HPMC on postprandial glucose and insulin responses in overweight and obese men and women.RESEARCH DESIGN AND METHODS -Participants were 31 overweight or obese men and women without diabetes who underwent three breakfast meal tests in random order, separated by Ն72 h. Test meals containing 75 g carbohydrate plus 4 or 8 g HV-HPMC or control meals containing 8 g cellulose were delivered in a double-blind fashion.RESULTS -Peak glucose was significantly lower (P Ͻ 0.001) after both HV-HPMCcontaining meals (7.4 mmol/l [4 g] and 7.4 mmol/l [8 g]) compared with the control meal (8.6 mmol/l). Peak insulin concentrations and the incremental areas for glucose and insulin from 0 to 120 min were also significantly reduced after both HV-HPMC doses versus control (all P Ͻ 0.01).CONCLUSIONS -These findings indicate that HV-HPMC consumption reduces postprandial glucose and insulin excursions, which may favorably alter risks for diabetes and cardiovascular disease. Diabetes Care 30:1039 -1043, 2007I nsulin resistance and compensatory hyperinsulinemia are believed to play important pathophysiological roles in the development of a number of conditions, including diabetes, coronary heart disease, and hypertension (1,2). Insulin resistance is a state in which a given circulating concentration of insulin produces subnormal clearance of glucose from the blood (2).In the presence of insulin resistance, the pancreas will increase insulin secretion to maintain normal glucose tolerance (2). However, the resulting excessive demand on the pancreatic ␤-cells may, over an extended period, lead to pancreatic exhaustion and the eventual development of glucose intolerance (1,2). Furthermore, insulin resistance may not be present to the same degree for all tissues and actions of insulin. Therefore, the hyperinsulinemia required to maintain normal glucose tolerance may produce undesirable physiological effects, including increased synthesis of VLDL, enhanced renal sodium reabsorption, and remodeling of vascular and cardiac tissues (1-3).Slowing the absorption of digestible dietary carbohydrates shows promise as a way to reduce hyperinsulinemia and its unwanted consequences on pancreatic function and the development of hemodynamic disturbances (1,4 -6). One class of medication, the ␣-glucosidase inhibitors, slows glucose absorption by reducing the rate of enzymatic digestion of starch, thereby delaying the release of glucose molecules for absorption. These agents reduce postprandial glucose and insulin levels (7). A Cochrane Review of five trials (2,360 participants) concluded that there is evidence that acarbose reduced the ...

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Objective: To determine the cholesterol-lowering efficacy of hydroxypropylmethylcellulose (HPMC) , and 12 and 15% at 15 g day À1 , respectively, over placebo. Adverse effects were minimal. Trial one: medium, high and ultra-high viscosity HPMC at 15 g day À1 for 1 week each; 1-week wash-out between treatments. Trial two: ultra-high viscosity HPMC at 5 or 15 g day À1 for 8 weeks. Conclusions: HPMC soluble fiber, especially high-viscosity grades, significantly lowers cholesterol at well-tolerated doses, showing promise as a treatment of hypercholesterolemia.

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