The pain-relieving effects of lactoferrin on oxaliplatin-induced neuropathic pain.

Oxaliplatin (OXL) therapy often causes side effects including chronic peripheral neuropathy. We investigated the pain-relieving effects of recombinant human lactoferrin (rhLf) as well as a long-acting IgG-Fc fused rhLf (rhLf-Fc) on OXL-induced neuropathic pain. We used the hLf in this study, because the homology between mouse Lf and hLf is higher than that of bovine Lf. In addition, rhLf-Fc is expected to enhance the analgesic effect due to the life extension effect in the body. We administered OXL (2 mg/kg, i.v.) to mice twice weekly for 4 weeks. Phosphate buffered saline (PBS), rhLf (100 mg/kg, i.p.) or rhLf-Fc (100 mg/kg, i.p.) was administered once a week from day 15 to 32. We also assessed the continuous infusion of same drugs (10 mg/kg/day) into the external jugular vein by using an osmotic pump. Both of rhLf and rhLf-Fc significantly reduced the hypersensitivity to mechanical stimulation when they were administered intraperitoneally. The continuous infusion of rhLf resulted in a more pronounced effect. Histopathological analysis of sciatic nerve showed that both rhLf and rhLf-Fc tended to reduce nerve fiber damage, but no significant difference was observed in nerve fiber cross-sectional area. Therefore, it was suggested that rhLf or rhLf-Fc injection could be an option for controlling neuropathic pain, which are side effects of OXL.

Association of Impact Velocity with Serious-injury and Fatality Risks to Cyclists in Commercial Truck-Cyclist Accidents.

This study aimed to clarify the relationship between truck-cyclist collision impact velocity and the serious-injury and fatality risks to cyclists, and to investigate the effects of road type and driving scenario on the frequency of cyclist fatalities due to collisions with vehicles. We used micro and macro truck-cyclist collision data from the Japanese Institute for Traffic Accident Research and Data Analysis (ITARDA) database. We classified vehicle type into five categories: heavy-duty trucks (gross vehicle weight [GVW] ≥11 × 103 kg [11 tons (t)], medium-duty trucks (5 × 103 kg [5 t] ≤ GVW < 11 × 103 kg [11 t]), light-duty trucks (GVW <5 × 103 kg [5 t]), box vans, and sedans. The fatality risk was ≤5% for light-duty trucks, box vans, and sedans at impact velocities ≤40 km/h and for medium-duty trucks at impact velocities ≤30 km/h. The fatality risk was 6% for heavy-duty trucks at impact velocities ≤10 km/h. Thus, the fatality risk appears strongly associated with vehicle class and impact velocity. The results revealed that a 10 km/h reduction in impact velocities could mitigate the severity of cyclist injuries at impact velocities ≥30 km/h for all five vehicle types. The frequency of cyclist fatalities at intersections with traffic signals involving heavy-duty trucks was significantly higher during daytime than that at nighttime. Fatalities involving vehicles making a left turn generally increased with vehicle weight. The frequency of cyclist fatalities involving vehicles making a left turn was the largest for heavy-duty trucks both during daytime (67.6%) and at nighttime (52.3%).

Association of Impact Velocity with Risks of Serious Injuries and Fatalities to Pedestrians in Commercial Truck-Pedestrian Accidents.

This study aimed to clarify the relationship between truck-pedestrian crash impact velocity and the risks of serious injury and fatality to pedestrians. We used micro and macro truck-pedestrian accident data from the Japanese Institute for Traffic Accident Research and Data Analysis (ITARDA) database. We classified vehicle type into five categories: heavy-duty trucks (gross vehicle weight [GVW] ≥11 × 103 kg [11 tons (t)], medium-duty trucks (5 × 103 kg [5 t] ≤ GVW < 11 × 103 kg [11 t]), light-duty trucks (GVW <5 × 103 kg [5 t]), box vans, and sedans. The fatality risk was ≤5% for light-duty trucks, box vans, and sedans at impact velocities ≤ 30 km/h and for medium-duty trucks at impact velocities ≤20 km/h. The fatality risk was ≤10% for heavy-duty trucks at impact velocities ≤10 km/h. Thus, fatality risk appears strongly associated with vehicle class. The results also revealed that a 10 km/h reduction in impact velocities could mitigate the severity of pedestrian injuries at impact velocities ≥30 km/h for all five analyzed vehicle types. Therefore, serious injuries and fatalities to pedestrians could be decreased by the development and deployment of collision mitigation systems (CMSs) to all vehicles, including to commercial trucks, because CMSs can detect pedestrians in even severe conditions, such as when the drive's view is obstructed, and can reduce the impact velocity. The present results indicate that CMS design specifications should differ between vehicle types because of the strong dependence of seriousinjury and fatality risks on vehicle type.

Protein-bound polysaccharide K suppresses tumor fibrosis in gastric cancer by inhibiting the TGF-ß signaling pathway.

Peritoneal carcinomatosis (PC) is the most frequent metastatic pattern of gastric cancer and its prognosis is extremely poor. PC is characterized by rich fibrosis and the development of obstructive disorders such as ileus, jaundice and hydronephrosis. Epithelial-mesenchymal transition (EMT) is one of the major causes of tissue fibrosis and transforming growth factor ß (TGF-ß) has a pivotal function in the progression of EMT. Protein-bound polysaccharide K (PSK) is a biological response modifier that can modulate the TGF-ß/Smad signaling pathway in vitro. In the present study, we established a fibrotic tumor model using human peritoneal mesothelial cells (HPMCs) and a human gastric cancer cell line to evaluate whether PSK attenuates tumor fibrosis. HPMCs exposed to PSK did not undergo the morphological change from a cobblestone-like pattern to a spindle-shape pattern normally induced by treatment with TGF-ß. Immunofluorescence further demonstrated that PSK suppressed TGF-ß-induced overexpression of α-SMA in the HPMCs. We further showed that HPMCs contributed to the proliferation of tumor fibrosis by using a mouse xenograft model. Additionally, PSK treatment of these mice significantly reduced the area of observable tumor fibrosis. These results suggest that seeded cancer cells transformed HPMCs into myofibroblast-like cells through their release of TGF-ß in the microenvironment, facilitating the development of fibrous tumors in organs covered with HPMCs. Therefore, our study indicates that PSK has potential utility as an anti-fibrotic agent in the treatment of gastric cancer patients with PC.

Development of a non-radiographic cephalometric system.

The purpose of the present study was to develop a three-dimensional (3D) non-radiographic cephalometric system based on Simon's three planes. In pursuit of cephalometry without irradiation of patients, readiness of data and simplicity of the system, a portable 3D computer-aided, contact-method cephalometric system, equipped with newly developed cephalometric software for chairside use, was developed. The feasibility of its clinical use was examined based on comparison of the measurements obtained with those from conventional radiographic cephalometry on a human dry skull, as well as on three living subjects. From a total of nine measurements, a statistically significant difference was seen in six measurements: FMPA, U1/FH, FMIA, ANB, IMPA, and A-Np for the dry skull; in four measurements: FPA, FMPA, U1/FH, and Pog-Np for subject A; in five measurements: FMPA, U1/FH, FMIA, AN/FH, and A-Np for subject B; and in seven measurements: FMA, FMPA, U1/FH, FMIA, ANB, IMPA, and AN/FH for subject C. A clinically significant difference was found only in one measurement, U1/FH for the dry skull, in four measurements FPA, FMPA, U1/FH, and Pog-Np for subject A, in one measurement AN/FH for subject B, and in three measurements U1/FH, FMIA, and AN/FH for subject C. While demonstrating workability as a chairside tool and whilst there is a need for further refinement in measurement accuracy, this newly developed cephalometric system shows potential applicability, not only in the clinic as an auxiliary to or as a substitute for existing radiographic cephalometry, but also outside the clinic as an epidemiological tool.