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The seeded semibatch emulsion polymerization of n-butyl acrylate was investigated using potassium persulfate as initiator at 75 °C. The effect of initiator concentration and monomer feeding time (feed flow rate) on the kinetics, fraction of gel, molecular weight distributions, and level of branches were studied. It was found that the amount of gel formed was independent of initiator concentration and monomer feed flow rate if the process proceeded under starved conditions. On the other hand, the higher the initiator concentration and the feeding times, the higher the level of branches but the lower the molecular weights. A high level of branches was found, which was attributed to intramolecular transfer to polymer or backbiting.

A mathematical model for the computation of kinetics, branching frequency, sol molecular weight distribution, and gel fraction for the seeded semicontinuous emulsion polymerization of n-BA is presented. The model incorporates mechanistic features that have been found to play an important role in the polymerization of n-BA, such as the intramolecular transfer to polymer, so-called backbiting, and the low reactivity of the tertiary radicals resulting from such a reaction. Model parameters for which values are not available in the literature were obtained by fitting the model predictions to the kinetic data and structural properties of the polymer (fraction of gel, sol molecular weight distribution, and level of branches) gathered in seeded semicontinuous emulsion polymerizations of n-BA carried out at 75 °C with potassium persulfate as the initiator. The model fits all of these experimental data quite well.

The management of sodium intake is clinically important in many disease states including heart failure, kidney disease, and hypertension. Tenapanor is an inhibitor of the sodium-proton (Na(+)/H(+)) exchanger NHE3, which plays a prominent role in sodium handling in the gastrointestinal tract and kidney. When administered orally to rats, tenapanor acted exclusively in the gastrointestinal tract to inhibit sodium uptake. We showed that the systemic availability of tenapanor was negligible through plasma pharmacokinetic studies, as well as autoradiography and mass balance studies performed with (14)C-tenapanor. In humans, tenapanor reduced urinary sodium excretion by 20 to 50 mmol/day and led to an increase of similar magnitude in stool sodium. In salt-fed nephrectomized rats exhibiting hypervolemia, cardiac hypertrophy, and arterial stiffening, tenapanor reduced extracellular fluid volume, left ventricular hypertrophy, albuminuria, and blood pressure in a dose-dependent fashion. We observed these effects whether tenapanor was administered prophylactically or after disease was established. In addition, the combination of tenapanor and the blood pressure medication enalapril improved cardiac diastolic dysfunction and arterial pulse wave velocity relative to enalapril monotherapy in this animal model. Tenapanor prevented increases in glomerular area and urinary KIM-1, a marker of renal injury. The results suggest that therapeutic alteration of sodium transport in the gastrointestinal tract instead of the kidney--the target of current drugs--could lead to improved sodium management in renal disease.

The seeded semibatch emulsion polymerization of n-butyl acrylate, n-BA, with varying amounts of styrene as comonomer was investigated using potassium persulfate as initiator at 75 °C. The kinetics, the gel fraction, the molecular weight distribution, MWD, and the level of branches were determined. It was observed that the instantaneous conversion, the fraction of gel, the average molecular weights, and the level of branches were affected by the amount of styrene in the recipe. In particular, the fraction of gel decreased from 55% to almosnt nil and the level of branches decreased from 14 to 5 branches per 1000 carbons of the backbone when the amount of styrene increased from 0 to 10%. These results have technological implications because the amount of gel and the level of branches can be controlled; this is something that was not possible when initiator concentration or monomer feed rates were used as control variables. A mathematical model for predicting the kinetics, the fraction of gel, the level of branches and the MWD was used to analyze the effect of styrene on the seeded semibatch emulsion polymerization of n-BA. In addition, it is shown that the adhesive properties of these latexes can be modified by adding small amounts of styrene.

SummaryWe describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages. Ion transport phenotypes of monolayers from the proximal and distal colon and small intestine matched the known and unique physiology of these intestinal segments. The cultures secreted serotonin, GLP-1, and FGF19 and upregulated the epithelial sodium channel in response to known biologically active agents, suggesting intact secretory and absorptive functions. A screen of over 2,000 pharmacologically active compounds for inhibition of potassium ion transport in the mouse distal colon cultures led to the identification of a tool compound.