Page 9074. In section 4.3, the preliminary conclusion on the occurrence of the first-order phase transition is incorrect. By means of precise X-ray measurements, the discontinuous increases are found in the slopes of the lattice constants a and b vs T a plots, while the c and the b keep almost the same. As a result, the slope of the unit cell volume V vs T a plot also shows a discon-tinuous increase at T a) 157 °C, i.e. However, the volume itself changes continuously. This means V R2) V R2′. Hence, the above change should be the second-order phase transition. We denote the new phase R2′ form and the transition temperature T R2-R2′. As a matter of fact, we found that the volume thermal expansion coefficient of the R2′ phase is about 2.8 times larger than the one of the R2 phase at T) T R2-R2′ , sufficiently large to promote a fast lamellar thickening process. The main conclusions of the paper are in no way affected, accordingly. We apologize for the error and the inconvenience this might have caused to the readers.

Micrometer-sized (4-7 µm diameter) poly(methacrylic acid) (PMAA) hydrogel microspheres were synthesized by precipitation polymerization. Individual microspheres were held in a micropipet and visualized by interference contrast microscopy. They were characterized with regard to their mass, density, water content, electrophoretic mobility, and apparent pKa. Equilibrium changes in volume were measured as functions of the pH and NaCl concentration of the suspending solution. The maximum reduction in the microsphere equilibrium volume (Vrmax) at pH 3.0 was 0.28, where Vr was the ratio of the microsphere volume at the test pH to its volume at pH 6.6. A Donnan-based thermodynamic model, modified to include counterion binding because of the high fixed charge density in the microspheres (3.0 M), was applied to determine the difference in the ion concentration between the interior and exterior of the gel. The ion concentration differences (which were related to the osmotic pressure) predicted by the model were proportional to the microsphere equilibrium volume with changing pH and salt concentration. This supported the hypothesis that the equilibrium volume of the microspheres was set by a force balance between the osmotic pressure and the elasticity of the hydrogel matrix. Microspheres changed from their maximum equilibrium volume at pH 6.6 to their minimum equilibrium volume at pH 3.0 in 300 ms. This indicated that diffusion of the polymer matrix and not diffusion of ions into and out of the microsphere was the rate-limiting factor in determining a microsphere's swelling rate.

The distinct properties of tapentadol and tramadol generate different CNS functional activities, making each drug the prototype of different classes of opioid/nonopioid analgesics. Tramadol's analgesia derives from relatively weak µ-opioid receptor (MOR) agonism, plus norepinephrine and serotonin reuptake inhibition, provided collectively by the enantiomers of the parent drug and a metabolite that is a stronger MOR agonist, but has lower CNS penetration. Tapentadol's MOR agonist activity is several-fold greater than tramadol's, with prominent norepinephrine reuptake inhibition and minimal serotonin effect. Accordingly, tramadol is well-suited for pain conditions for which a strong opioid component is not needed-and it has the benefit of a low abuse potential; whereas tapentadol, a schedule-II controlled substance, is well-suited for pain conditions requiring a strong opioid component-and it has the benefit of greater gastrointestinal tolerability compared to classical strong opioids. Both drugs offer distinct and complementary clinical options.

Spherical micron-sized (4−7 μm diameter) poly(methacrylic acid-c o-nitrophenyl acrylate) microgels were synthesized by precipitation polymerization and selectively derivatized with carboxylic acid, glutamic acid, hydroxamic acid, sulfonic acid, and ethanol functional groups in five separate post-polymerization reactions. The pH and NaCl induced swelling response, drug loading, capacity (“capacity” = total number of functional ionic groups that bind protons), and density of the five different composition anionic microgels, each containing a different functional group as well as a baseline of carboxylic acid groups, were measured. Using the micropipet flow technique, it was found that the pH range of the swelling response for the five different microgel compositions shifted by an amount that was proportional to the solution pK a's of their functional groups. The degree of drug loading increased in proportion to the microgels' capacity. However, the drug loading did not decrease proportionately when the capacity was lowered.

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Spherical micron-sized (4-10 µm in diameter) poly(methacrylic acid-co-acrylic acid) microgels were synthesized by precipitation polymerization, and their chelation reactions with chloride salts of Mg 2+ , Ca 2+ , Sr 2+ , and Ba 2+ were investigated by isothermal titration calorimetry (ITC). Ion concentrations obtained by inductively coupled-plasma mass spectrometry (ICP-MS) were used to obtain binding constants and to verify the results obtained by ITC. Although the two methods agreed within 20%, the ITC measurements were experimentally easier to obtain and more accurate. Interference contrast microscopy and micropipet manipulation techniques were used to measure the volume change and corresponding dehydration of the microgels as a function of divalent ion type and concentration. The ITC results showed that the addition of MCl 2 electrolytes, where M represents a divalent metal, with the microgels was an entropy driven reaction in that ∆G ∼ -20 kJ/mol = T∆S. These data suggest that the free energy driving the ion exchange (M 2+ divalent ions for monovalent Na + ) is the result of the increase in the entropy of the system; this entropy increase is due to (1) water being "squeezed" from the microgels into the bulk solution and (2) the collapse of the entropy elastic network that accompanies the decrease in the volume of the microgels.

Residual oil fly ash (ROFA) is an industrial pollutant that contains metals, acids, and unknown materials complexed to a particulate core. The heterogeneous composition of ROFA hampers finding the mechanism(s) by which it and other particulate pollutants cause airway toxicity. To distinguish culpable factors contributing to the effects of ROFA, synthetic polymer microsphere (SPM) analogs were synthesized that resembled ROFA in particle size (2 and 6 microm in diameter) and zeta potential (-29 mV). BEAS-2B human bronchial epithelial cells and dorsal root ganglion neurons responded to both ROFA and charged SPMs with an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) and the release of the proinflammatory cytokine interleukin-6, whereas neutral SPMs bound with polyethylene glycol (0-mV zeta potential) were relatively ineffective. In dorsal root ganglion neurons, the SPM-induced increases in [Ca(2+)](i) were correlated with the presence of acid- and/or capsaicin-sensitive pathways. We hypothesized that the acidic microenvironment associated with negatively charged colloids like ROFA and SPMs activate irritant receptors in airway target cells. This causes subsequent cytokine release, which mediates the pathophysiology of neurogenic airway inflammation.

In a three-week oral gavage toxicity study in rats, a high incidence of respiratory symptoms and high mortality was noted in compound-dosed rats only. Because of audible respiration, an effect in the upper respiratory tract was suspected and the nasal cavity was included for examination. Histology revealed extensive necrosis and purulent inflammation within the nasal passages, indicative of direct irritation. Since posterior nasal regions were most affected, with food material present within the inflammatory exudates, reflux and retrograde aspiration of irritant material (possibly stomach contents with test formulation) into the nasal cavity were suspected. Lowering the dose volume and fasting the rats prior to gavage dosing substantially reduced the respiratory effects and mortality. The current article focuses on the histological changes in the nasal cavity indicative of gavage-related reflux and provides guidance on differentiation between technical gavage error and gavage-related reflux.Keywords: audible respiration; reflux; rat; gavage; dyspnea; nasal cavity; gastric emptying. INTRODUCTIONAfter oral administration of test articles to animals, compared with inhalation routes, compound-related nasal effects are less likely to occur. Therefore, histology of the nasal cavity is not required by regulatory guidelines for subchronic oral toxicity studies. When nasal changes are observed after oral dosing, they are generally attributed to systemic exposure to the test compound. In this case, the lesions often show a specific alteration and distribution pattern in correlation with the selective uptake and/or metabolism of the test compound in the nasal epithelium (Keller et al. 1997). Furthermore, indirect nasal toxicity may occur after oral administration as a consequence of compound-related immune suppression (Monticello et al. 1990) or inhibition of nasal mucous secretion, resulting in dryness of the nasal mucosa and subsequent increased susceptibility to nasal infections (Shimizu et al. 2003).Literature on nasal pathology in rats after oral gavage dosing unrelated to systemic exposure of nasal tissues to test articles is limited. The few articles available are restricted to short notes on ''unusual nasal changes after oral gavage dosing in rodents of uncertain etiology' ' (Lieder et al. 2009;Stadler et al. 2008;Williams et al. 1999), with the exception of De Jonghe et al. (2009), who focused on the nasal cavity in more detail. Sometimes, the posterior nose levels appeared to be most affected, and only treated rats were affected, showing a dose response of the nasal changes. Clinical signs included respiratory effects, such as dyspnea and audible respiration. In some instances, red/ brown perioral substance as well as chromorhinorrhea were observed (Lieder et al. 2009), indicative of nasal alteration. In all of these cases, reflux and accidental aspiration during the gavage administration had been suggested but had not been further investigated.In this article, the data from two rat gavage toxicity stud...