Water-like anomalies as a function of tetrahedrality.

Tetrahedral interactions describe the behavior of the most abundant and technologically important materials on Earth, such as water, silicon, carbon, germanium, and countless others. Despite their differences, these materials share unique common physical behaviors, such as liquid anomalies, open crystalline structures, and extremely poor glass-forming ability at ambient pressure. To reveal the physical origin of these anomalies and their link to the shape of the phase diagram, we systematically study the properties of the Stillinger-Weber potential as a function of the strength of the tetrahedral interaction [Formula: see text] We uncover a unique transition to a reentrant spinodal line at low values of [Formula: see text], accompanied with a change in the dynamical behavior, from non-Arrhenius to Arrhenius. We then show that a two-state model can provide a comprehensive understanding on how the thermodynamic and dynamic anomalies of this important class of materials depend on the strength of the tetrahedral interaction. Our work establishes a deep link between the shape of the phase diagram and the thermodynamic and dynamic properties through local structural ordering in liquids and hints at why water is so special among all substances.

A comparison between the combined effect of calcium carbonate with sucroferric oxyhydroxide and other phosphate binders: an in vitro and in vivo experimental study.

BACKGROUND: Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate. METHODS: For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2-8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance. RESULTS: In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic. CONCLUSIONS: These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.

Effects of combination of mitiglinide with various oral antidiabetic drugs in streptozotocin-nicotinamide-induced type 2 diabetic rats and Zucker fatty rats.

We examined the effects of combining the rapid insulin secretagogue, mitiglinide, with various oral hypoglycaemic drugs including biguanides, pioglitazone, α-glucosidase inhibitors, and sodium-glucose co-transporter 2 inhibitors in a rat model of type 2 diabetes. The oral glucose tolerance test (OGTT) using glucose, sucrose, or a liquid meal was used to compare the effects of mitiglinide with those of the four oral hypoglycaemic drugs and examine their combined effects on blood glucose levels and insulin secretion in the rat model. The combination of mitiglinide with other oral hypoglycaemic drugs suppressed the plasma glucose levels more than either agent did alone. Furthermore, the combination of these agents decreased insulin secretion more than mitiglinide did alone. These results indicate that mitiglinide is suitable for use in combination with other hypoglycaemic drugs because it inhibits postprandial hyperglycaemia by rapidly stimulating insulin secretion.

Altered D: -methionine kinetics in rats with renal impairment.

D: -Amino acids are now recognized to be widely present in mammals. In rats, exogenously administered D: -methionine is almost converted into the L: -enantiomer via 2-oxo-4-methylthiobutylic acid as an intermediate. D: -Amino acid oxidase is associated with conversion of D: -methionine into the 2-oxo acid. Since D: -amino acid oxidase is present at the highest activity in the kidney compared to other organ, kidney injury is suggested to cause accumulation of D: -methionine. The purpose of the present study is to assess the role of kidney in the elimination of D: -methionine and metabolic conversion into L: -methionine in rats using a stable isotope methodology. After a bolus i.v. administration of D: -[²H3)]methionine to 5/6-nephrectomized rats, plasma concentrations of D: -[²H3]methionine, L: -[²H3]methionine, and endogenous L: -methionine were determined by a stereoselective GC-MS method. Renal mass reduction slowed down the elimination of D: -[²H3]methionine. The clearance values of conversion of D: -[²H3]methionine into the L: -enantiomer in 5/6-nephrectomized rats were one-sixth of those in sham-operated rats. The elimination behavior of D: -[²H3]methionine observed in rats demonstrated that kidney was the principal organ responsible for chiral inversion of D: -methionine.

Rapid and specific detection of the thermostable direct hemolysin gene in Vibrio parahaemolyticus by loop-mediated isothermal amplification.

Several investigators have reported that thermostable direct hemolysin (TDH) and TDH-related hemolysin are important virulence factors of Vibrio parahaemolyticus, but it has been difficult to detect these factors rapidly in seafood and other environmental samples. A novel nucleic acid amplification method, termed the loop-mediated isothermal amplification (LAMP), which amplifies DNA with high specificity and rapidity under isothermal conditions, was applied. In this study, we designed tdh gene-specific LAMP primers for detection of TDH-producing V. parahaemolyticus. The specificity of this assay was evaluated with 32 strains of TDH-producing V. parahaemolyticus, one strain of TDH-producing Grimontia hollisae, 10 strains of TDH-nonproducing V. parahaemolyticus, and 94 strains of TDH-nonproducing bacteria, and the sensitivity was high enough to detect one cell per test. Moreover, to investigate the detection of TDH-producing V. parahaemolyticus in oysters, the LAMP assay was performed with enrichment culture in alkaline peptone water of oyster samples inoculated with TDH-producing V. parahaemolyticus and TDH-nonproducing V. parahaemolyticus and V. alginolyticus after enrichment in alkaline peptone water. These results suggest that the LAMP assay targeting tdh gene has high sensitivity and specificity and is useful to detect TDH-producing V. parahaemolyticus in oyster after enrichment.

Comparison of the Effects of Mitiglinide and Glibenclamide Administered in Combination with the Dipeptidyl Peptidase-IV Inhibitor Sitagliptin in Rats with Streptozotocin-Nicotinamide-Induced Type 2 Diabetes.

We compared the individual effects of mitiglinide and glibenclamide administered in combination with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin on plasma DPP-IV activity and blood glucose levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes (STZ-NA rats). We examined the inhibitory activity of mitiglinide and glibenclamide as well as their combination with sitagliptin on plasma DPP-IV activity in STZ-NA rats. The oral glucose tolerance test (OGTT) was used to compare effects of mitiglinide, glibenclamide, and their combination with sitagliptin on blood glucose levels in STZ-NA rats. Mitiglinide and glibenclamide did not inhibit rat DPP-IV and did not influence the inhibitory effect of sitagliptin on rat plasma DPP-IV activity. In STZ-NA rats, plasma glucose levels were stronger suppressed by a combination of mitiglinide and sitagliptin than by either drug used alone. However, no clear effect of the combination of glibenclamide and sitagliptin was observed. These results indicate that the combination of mitiglinide and sitagliptin has a lower risk of hypoglycemia in the rats with induced type 2 diabetes compared with the combination of glibenclamide and sitagliptin. The combination of mitiglinide and sitagliptin can be a promising combination for the treatment of diabetic patients.

A possible four-phase coexistence in a single-component system.

For different phases to coexist in equilibrium at constant temperature T and pressure P, the condition of equal chemical potential µ must be satisfied. This condition dictates that, for a single-component system, the maximum number of phases that can coexist is three. Historically this is known as the Gibbs phase rule, and is one of the oldest and venerable rules of thermodynamics. Here we make use of the fact that, by varying model parameters, the Gibbs phase rule can be generalized so that four phases can coexist even in single-component systems. To systematically search for the quadruple point, we use a monoatomic system interacting with a Stillinger-Weber potential with variable tetrahedrality. Our study indicates that the quadruple point provides flexibility in controlling multiple equilibrium phases and may be realized in systems with tunable interactions, which are nowadays feasible in several soft matter systems such as patchy colloids.

Determination of D- and L-enantiomers of methionine and [2H3]methionine in plasma by gas chromatography-mass spectrometry.

A method for the stereoselective determination of D- and L-enantiomers of both methionine and [(2)H3]methionine in rat plasma was developed using gas chromatography-mass spectrometry with selected-ion monitoring (GC-MS-SIM). DL-[(2)H7]Methionine was used as analytical internal standard to account for losses associated with the extraction, derivatization and chromatography. The amino acids were purified by cation-exchange chromatography using BondElut SCX cartridge and derivatized with HCl in methanol to form methyl ester followed by subsequent N-acylation with optically active (+)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride to form diastereomeric amide. Quantification was performed by SIM of the molecular-related ions of the diastereomers on the chemical ionization mode. Endogenous L-methionine concentrations in 50 microl of rat plasma were measured with relative intra- and inter-day precision of 4.0 and 6.3%, respectively. The intra- and inter-day reproducibility in the amounts of D- and L-[(2)H3]methionine determined were in good agreement with actual amount added.

Direct detection and evaluation of conversion of D-methionine into L-methionine in rats by stable isotope methodology.

The stereoselective kinetics of methionine enantiomers in rats was investigated to evaluate the fraction that converted from d-methionine to the L-enantiomer using a stable isotope methodology. After bolus i.v. administration of D- or L-[(2)H(3)]methionine, their plasma concentrations and that of endogenous L-methionine were determined by a stereoselective GC-MS method. L-[(2)H(3)]Methionine appeared rapidly after administration of D-[(2)H(3)]methionine, whereas D-[(2)H(3)]methionine was not detected after administration of L-[(2)H(3)]methionine. The fraction of conversion of D-[(2)H(3)]methionine into L-[(2)H(3)]methionine was estimated using the area under the plasma concentration vs. time curve of L-[(2)H(3)]methionine on D-[(2)H(3)]methionine administration and total clearance of L-[(2)H(3)]methionine on L-[(2)H(3)]methionine administration, and that fraction was >90%. This result demonstrates that almost all i.v. administered D-methionine is converted into the L-enantiomer in vivo.