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Non-camptothecin topoisomerase I inhibitor, Genz, shows potent activity against camptothecin-resistant cells through double-strand break induced cytotoxicity.

Since the range of access of each surgical approach around the elbow has limitations, it is difficult to treat all types of fractures using only one approach. In the case reported herein, anterior and medial fragments of the comminuted ulnar coronoid process fracture were treated by preparing two access routes through one skin incision and effectively performing the buttress plating of each fragment.The subject was a 27-year-old female who sustained a fracture of the coronoid process of the right ulna by falling during snowboarding. Computed tomography showed the concurrence of a type 2 subtype III and type 3 subtype I ulnar coronoid process fracture according to the O'Driscoll classification. The coronoid process was split into 3 parts: a fragment consisting of the anteromedial facet and upper half of the sublime tubercle (fragment 1), a central fragment including the tip (fragment 2), and a fragment extending from the radial side of the tip to the base of the coronoid process (fragment 3). A 12-cm-long skin incision was made on the anteromedial side of the elbow joint. The region of the anteromedial facet and sublime tubercle was reached by passage between the palmaris longus/flexor digitorum superficialis and humeral head of flexor carpi ulnaris using the over-the-top approach. Fragment 1 was fixed with a buttress plate. Using the anterior approach, the brachialis was then longitudinally split through by passage between the biceps and neurovascular bundle, fragments 2 and 3 were fixed together with a buttress plate.The “one incision-two windows” approach, which provides two approaches (the over-the-top window and the anterior window) by a single skin incision, was implemented for a multifragmentary ulnar coronoid process fracture. This approach is considered to offer access from the front to each of the anterior and medial fragments and permits appropriate buttress plate fixation.

To enhance bone regeneration, the use of bone morphogenetic protein (BMP)-2 is an attractive option. Unfortunately, the dose-dependent side effects prevent its widespread use. Therefore, a novel osteogenic agent using a different mechanism of action than BMP-2 is highly desirable. Previous reports demonstrated that prostaglandin E2 receptor 4 (EP4) agonists have potent osteogenic effects on non-human cells and are one of the potential alternatives for BMP-2. Here, we investigated the effects of an EP4 agonist (AKDS001) on human cells with a rat heterotopic xenograft model of human bone. Bone formation in the xenograft model was significantly enhanced by AKDS001 treatment. Histomorphometric analysis showed that the mode of bone formation by AKDS001 was minimodeling rather than remodeling. In cultured human mesenchymal stem cells, AKDS001 enhanced osteogenic differentiation and mineralization via the cAMP/PKA pathway. In cultured human preosteoclasts, AKDS001 suppressed bone resorption by inhibiting differentiation into mature osteoclasts. Thus, we conclude that AKDS001 can enhance bone formation in grafted autogenous bone by minimodeling while maintaining the volume of grafted bone. The combined use of an EP4 agonist and autogenous bone grafting may be a novel treatment option to enhance bone regeneration. However, we should be careful in interpreting the results because male xenografts were implanted in male rats in the present study. It remains to be seen whether females can benefit from the positive effects of AKDS001 MS by using female xenografts implanted in female rats in clinically relevant animal models.

As a preliminary study, the effects of target temperature on ejecta size were examined at an impact velocity of 3.5 km/s with the goal of improving the ISO11227. At first, the size of each ejecta collected from test chamber, was examined by the image analysis software using a photograph of each ejecta (direct method). The cumulative number distributions of ejecta size were discussed. The effects of target temperature on ejecta size were small within a predictable range. After that, we compared the ejecta size distribution of the direct method with the results of the international standard method using witness plate (indirect method). The number of ejecta impact craters evaluated by the international standard method was very small at the high temperature. The results of international standard method using witness plate were easily influenced by temperature of target at the high temperature. It is highly possible that the international standard method underestimate the ejecta from target at high temperature.

The molecular mobility and compatibility of plasticized polyhydroxyalkanoates (PHA) were investigated, focusing on changes due to copolymerization using either flexible poly (butylene succinate) (PBS) or rigid poly(lactic acid) (PLA) units. For the case of a poly(3-hydroxybutyrate) (PHB) unit in plasticized PHA, copolymerization of either PBS or PLA decreased 1H and 13C spin-lattice relaxation times in the laboratory frame (T1H and T1C) in the same manner, while PBS produced a lower 1H spin-lattice relaxation time in the rotating frame (T1ρH) than PLA. Both the signals of 1H MAS (magic-angle spinning) and 13C PST (pulse saturation transfer) MAS nuclear magnetic resonance (NMR) spectra were sharpened and increased by copolymerization with PBS. A variable temperature relaxation time analysis showed that the decrease of T1H values was dominated by the 1H spin diffusion via the interface between PHB and the added polyester because of the good compatibility. Meanwhile, the decrease of T1C values was dominated by increasingly rapid molecular motions of PHB because of the lowered crystallinity due to the plasticization. Slow molecular motions (kHz order) were enhanced more by the addition of PBS than PLA, although rapid molecular motions (MHz order) were enhanced by either polyester. Several NMR parameters were beneficial for analyzing the manufacturing process as the indexes of polymer compatibility and molecular motions.

The purpose of this investigation was to define the sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation. Data from twelve studies generated in the QT PRODACT project were used in this investigation. The study design was a 4 × 4 Latin square cross-over design and included the following drugs: MK-499, E-4031, terfenadine, haloperidol, cisapride, bepridil, propranolol, diphenhydramine, captopril, verapamil, amoxicillin, and ciprofloxacin. The estimated root squared error of the model, which estimated the slope of the QT-RR relationships for each animal, for all dogs during the pre-dosing period was 5.45%. Using the QT-RR model, the sensitivity and specificity in each cutoff value that judges QT prolongation were estimated based on the experiment errors and measurement errors in the 12 studies. When the cutoff value was 5%, the sensitivity in 10% prolongation was 0.978 and the specificity in 0% was 0.996. In conclusion, it was judged that a 5% cutoff value for changes in heart rate corrected QT interval using the canine telemetry assay is practical, and the sensitivity and specificity of the telemetry assay are very high when using the analytical method presented here. Based upon this information, the canine telemetry assay using the individual subject heart rate correction model is recommended as a sensitive test system for the in vivo assessment of risk for QT interval prolongation. Keywords:: dog, sensitivity, telemetry, QT, QTc