To evaluate the protective effects of Ginkgo biloba extract (GBe) which has antioxidant activity against peripheral neuropathy due to diabetes mellitus, slow axonal transport and morphology of sciatic nerve including endoneurial microvessels were examined in 12 rats with diabetes mellitus induced by streptozotocin (STZ, 60mg/kg, b.w., i.p.). Six of the diabetic rats were treated with 0.1% of GBe for 6 weeks from one week after the STZ injection. Serum glucose and lipid peroxide levels in GBe−treated diabetic rats were significantly lower than those in untreated diabetic rats (p<0.01, respectively), though the serum glucose level was higher than that in the control rats. L−[35S] methionine pulse radiolabeling with subsequent gel fluorography demonstrated that mean velocities (Vmean) of actin and β−tubulin, i.e. slow component b(SCb) transport in untreated diabetic rats were significantly lower than those in control rats (p<0.05, respectively); mean diameter of axons in the former rats was significantly smaller than that in the latter (p<0.01). Vmean of actin transport in GBe−treated diabetic rats was significantly faster than that in untreated diabetic rats (p<0.05). Vmean of slow axonal transport was significantly correlated with mean diameter of axons in the three groups of rats combined (p<0.01). On electron microscopy, severe altered endoneurial microvessels decreasing in luminal area together with endothelial cell degeneration or hypertrophy, pericyte debris and basement membrane thickening were observed in untreated diabetic rats; on the other hand these findings were less prominent in the diabetic rats treated with GBe. It is suggested that GBe treatment may protect disturbed slow axonal transport and pathological alterations of peripheral nerve with abnormal endoneurial microvasculature from diabetes mellitus by antioxidant activity.
Rattus norvegicus ; lower case pea ; Streptozocin ; Science of Morphology ; slow axonal transport

Background: In Japan, although clinicians have been extremely interested in conducting clinical research, the shortage of clinical researchers is a serious problem. Therefore, it is important to explore barriers to conducting clinical research.1) We mailed a cross-sectional survey to hospital managers asking about their interest in and barriers to conducting clinical research and training clinical researchers at their hospitals.2) Of 810 eligible hospital managers, 301 completed questionnaires (response rate: 37.2%).3) The managers of university hospitals and national medical centers were more interested in conducting clinical research than were managers of other hospitals.4) Furthermore, 60.6% of managers of university hospital and 18.8% of managers of other hospitals reported the need to employ physicians who specialized in clinical research. However, given public research grants, about 50% of hospital managers were willing to employ research residents.5) Our results suggest there are still barriers to conducting clinical research, such as a lack of time set aside for clinicians and specialists to teach clinical research. A substantial strategy is needed to address the shortage of clinical researchers in Japan.

  In Japan, few health care professionals have a basic understanding（core competency）of the design of clinical research and statistical analysis. We developed a blended distance–learning program comprising face–to–face lectures with e–learning for busy health care professionals who work in the clinical settings to achieve core competency in clinical research. The purpose of this study was to examine the educational effects of this program.
1）Four months after the end of the program, 64％ of the participants had started to conduct clinical research.
2）This program may increase the number of research colleagues that can discuss clinical research.
3）This program could enhance the confidence（self–efficacy）of health care professionals in clinical research.

Objective: The primary objective of this study was to evaluate the safety of niraparib 300 mg/day in Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. Methods: Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients with platinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens.The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30 days after initial niraparib administration) was justified by the incidences of a global pivotal phase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematological adverse event of niraparib. The overall safety analysis examined other treatment-emergent adverse events (TEAEs). Results: Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8–79.1) kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib 300 mg/day but this decreased in subsequent cycles (mean±standard deviation dose intensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration.Other common TEAEs included nausea, and decreased platelet or neutrophil counts. No progression-free or overall survival events occurred; only 1 of 4 response-evaluable patients had a post-baseline tumor assessment (stable disease). Conclusion The incidence of grade 3 or 4 thrombocytopenia-related events in Japanese ovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall, the safety profile was acceptable and consistent with the known safety profile and previous experience with niraparib.

Objective: To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs. Results: Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%. Conclusion Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified.