Effects of sugar ester and hydroxypropyl methylcellulose on the physicochemical stability of amorphous cefditoren pivoxil in aqueous suspension

The improvement in physicochemical stability of amorphous cefditoren pivoxil (CDTR-PI) in aqueous suspensions by addition of sugar ester (SE) and hydroxypropyl methylcellulose (HPMC) was explained by prolonging the induction period prior to crystallization and the reduction in crystal peak intensity. Furthermore, the stabilizing effect of these additives in a multiple additive system was greater than in a single additive system. To determine the mechanism, by which these additives stabilized the amorphous CDTR-PI, we evaluated the surface states of CDTR-PI in suspension by measuring Raman spectra and zeta potential. The change in Raman spectra demonstrated that SE and HPMC interacted with CDTR-PI at the same interaction sites on CDTR-PI. The zeta potential reflected the adsorption phenomena of the additives and indicated that both SE and HPMC adsorbed onto particles of CDTR-PI with no apparent competitive interaction and the response was complementary. It was considered, based on this study, that HPMC and SE would stabilize amorphous CDTR-PI by different mechanisms; HPMC would mainly inhibit crystal growth by small amount of adsorption and SE would inhibit both crystal growth and nucleation by large amount of adsorption. This was considered to result in the hybrid effect in the multiple additive system.     

Does the adjunctive peeling of juxtacanalicular tissue affect the outcome of two-site phaco-viscocanalostomy?

PURPOSE: To compare the surgical outcomes of combined corneal-incision cataract surgery and viscocanalostomy (phaco-VCS) with or without the adjunctive peeling of juxtacanalicular tissue (JCT) in 136 patients of open-angle glaucoma or ocular hypertension. METHODS: In a prospective clinical trial, 63 eyes underwent phaco-VCS (Peeling (-) group), and 73 eyes underwent phaco-VCS with the peeling of JCT (Peeling (+) group). The postoperative IOP, the probability of successful IOP reduction without medications, and postoperative complications were compared between the two groups. RESULTS: The mean preoperative IOP of 19.9 +/- 3.3 (+/-SD) mm Hg in the Peeling (-) group decreased significantly to 13.9 +/- 6.8 at 3 days, 14.6 +/- 3.1 at 12 months, and 15.5 +/- 2.3 mm Hg at 24 months. The IOP of 20.2 +/- 3.2 mm Hg in the Peeling (+) group decreased significantly to 11.4 +/- 5.1 at 3 days, 14.9 +/- 3.0 at 12 months, and 15.9 +/- 2.1 mm Hg at 24 months. There was no significant difference in IOP levels between the two groups (P >/= 0.1512) except for the IOP level at 3 postoperative days (P = 0.0265). The probabilities of achieving IOPs without medications under 21 mm Hg and 15 mm Hg at 24 months in the Peeling (-) groups were 61.0% and 10.4%, and those in the Peeling (+) group were 61.7% and 23.9% (P >/= 0.4389). The incidences of IOP spike more than 30 mm Hg (7.9%) and fibrin formation (15.8%) in the Peeling (-) group were higher than in the Peeling (+) group (0%; P = 0.0195, 5.5%; P = 0.1907). Slit-lamp microscopic hyphema, which included red blood cells in the anterior chamber was observed in about half, and bleb formation more than 1 month was less than 5% in both groups. CONCLUSION: Postoperative IOPs were significantly decreased in both groups. Although the peeling of JCT was not enhanced in long-term reduction of the IOP, it lowered IOP at postoperative 3 days and the incidence of IOP spike. The adjunctive procedure would be beneficial to glaucoma patients in phaco-VCS.     

Detection of lipid peroxidation in light-exposed mouse retina assessed by oxidative stress markers, total hydroxyoctadecadienoic acid and 8-iso-prostaglandin F2alpha

Exposure to excessive light induces retinal photoreceptor cell damage, which may involve lipid peroxidation. Morphological changes and the detection of internucleosomal DNA fragmentation confirmed the retinal damage caused by exposure of the retina of Balb/c mice to white fluorescent light (5000 lux, 2 h). The total amounts of hydroxyoctadecadienoic acid (tHODE) and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) in the retinas obtained from light-exposed mice were assessed after reduction and saponification. In this method, both the free and ester forms of hydroperoxides, hydroxides, and ketones of linoleic acid are measured as tHODE by gas chromatography-mass spectrometry (GC-MS) analysis. When compared with controls, a significant increase in the concentrations of tHODE and 8-iso-PGF2alpha was observed 24 h after light exposure. Furthermore, the stereoisomeric ratio (Z,E)-HODE/(E,E)-HODE decreased after light exposure, suggesting the involvement of free-radical-mediated peroxidation. By the immunohistochemical technique, it was confirmed that 8-iso-PGF2alpha increased in the inner plexiform layer (IPL), outer plexiform layer (OPL), rod outer segment, and choroidal layer, while 13-HODE increased in the OPL and rod inner segment after light exposure. These results demonstrate that tHODE and 8-iso-PGF2alpha assessed by the present method are appropriate biomarkers responding to retinal photooxidative stress in vivo.     

Chromium(III) oxide nanoparticles induced remarkable oxidative stress and apoptosis on culture cells

Chromium(III) oxide (Cr₂O₃) is used for industrial applications such as catalysts and pigments. In the classical form, namely the fine particle, Cr₂O₃ is insoluble and chemically stable. It is classified as a low‐toxicity chromium compound. Recently, industrial application of nanoparticles (a new form composed of small particles with a diameter of ≤100 nm, in at least one dimension) has been increasing. Cellular effects induced by Cr₂O₃ nanoparticles are not known. To shed light upon this, the release of soluble chromium from Cr₂O₃ nano‐ and fine‐particles in culture medium was compared. Fine Cr₂O₃ particles were insoluble in the culture medium; on the contrary, Cr₂O₃ nanoparticles released soluble hexavalent chromium into the culture medium. Cr₂O₃ nanoparticles showed severe cytotoxicity. The effect of Cr₂O₃ nanoparticles on cell viability was higher than that of fine particles. Cr₂O₃ nanoparticles showed cytotoxicity equal to that of hexavalent chromium (K₂Cr₂O₇). Human lung carcinoma A549 cells and human keratinocyte HaCaT cells showed an increase in intracellular reactive oxygen species (ROS) level and activation of antioxidant defense systems on exposure to Cr₂O₃ nanoparticles. Exposure of Cr₂O₃ nanoparticles led to caspase‐3 activation, showing that the decrease in cell viability by exposure to Cr₂O₃ nanoparticles was caused by apoptosis. Cellular responses were stronger in the Cr₂O₃ nanoparticles‐exposed cells than in fine Cr₂O₃‐ and CrCl₃‐exposed cells. Cellular uptake of Cr₂O₃ particles were observed in nano‐ and fine‐particles. The cellular influence of the extracellular soluble trivalent chromium was lower than that of Cr₂O₃ nanoparticles. Cr₂O₃ nanoparticles showed cytotoxicity by hexavalent chromium released at outside and inside of cells. The cellular influences of Cr₂O₃ nanoparticles matched those of hexavalent chromium. In conclusion, Cr₂O₃ nanoparticles have a high cytotoxic potential. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2013.     

Biomechanical analysis for stress fractures of the anterior middle third of the tibia in athletes: nonlinear analysis using a three-dimensional finite element method

We evaluated stresses in the anterior middle third of the tibia that have been reported to predict a poor prognosis for tibial stress fractures compared to other predominant sites (posteromedial regions of the distal third and proximal third). The effect of two different loads (bending-compression load and torsional load) on three sites was investigated using a three-dimensional finite element method. The model was constructed using the tibia, fibula, proximal tibiofibular joint, interosseous membrane, and tibiofibular ligament based on computed tomography scans obtained at 4-mm intervals of the lower leg of a 20-year-old woman who exhibited no abnormal findings on roentgenograms. First, a normal model was constructed using normal material properties, and then the model was modified to produce fracture models by varying the mechanical properties of each predominant site and expanding the area in three gradual phases on the assumption that the fracture advanced in three phases. Each model was tested against the same two loads, and stresses at the nodal points on the border of the fracture area and normal area were compared in each cross section to determine the effect of the load on fracture advancement. In response to torsional load, both the normal model and fracture models tended to show higher values for the posteromedial distal third than the anterior middle third. By examining the bending-compression load it could be seen that the mean peak value significantly decreased between the first and second phases in fracture models of the anterior middle third. This finding was inconsistent with our previous belief that the bending-compression load would have more serious consequences than the torsional load. In contrast, when the area of fracture was expanded into the third phase, maximum values were significantly higher than during the second phase. No similar finding was observed for the posteromedial distal third, suggesting that the anterior middle third may have the same stable biomechanical conditions as the posteromedial distal third at an earlier stage and thus have little influence on fractures. When the fracture is more advanced, however, the conditions change suddenly, and a bending-compression load may adversely affect the mechanical conditions in this area and thereby cause complete fracture.