INTRODUCTION Clinical trials leading to drug approval (registra- tion trials) play a central role in the drug devel- opment process, and clinical trials in the general View and present status of personnel involved in clinical trials : a survey of particip

. Among the support staff, 36 (80% %) had more than 5 years of experience. The most common questionnaire answer selected for participation in the symposium was "willing to contact staff from other medical institutions or organizations" for support staff and "to obtain further knowledge concerning clinical trials" for medical staff. The overall view of the discussion ("Was the discussion satisfactory?") was favorable for 36 (53% %) respondents. This survey revealed that the group discussion in the present symposium appears to be valuable for participants, using overall satisfaction as a surrogate. Based on the information obtained in the present study, further development of the clinical trial infrastructure, including training opportunities and career development for support staff, is required. Due to the limitations of this study, further analysis is warranted to determine the optimal strategy for training support staff. J. Med. Invest. 58 : 81-85, February, 201

Goishi tea consumption inhibits airway hyperresponsiveness in BALB/c mice

<p>Abstract</p> <p>Background</p> <p>Airway hyperresponsiveness (AHR) is one of the important traits that characterize bronchial asthma. Goishi tea is a post-heating fermented tea that has been reported to have higher free radical scavenging activity. In this study, we evaluated the prophylactic effects of Goishi tea on AHR in BALB/c mice.</p> <p>Results</p> <p>The number of inflammatory cells in BAL fluid was considerably reduced in Goishi tea/<it>Der f </it>and Gallic acid/<it>Der f </it>groups as compared with Tap water/<it>Der f </it>group. Regarding inflammatory cells in BAL, a significant reduction of eosinophils and neutrophils was observed in Goishi tea-treated mice (p < 0.01), as well as in the Gallic acid/<it>Der f </it>group (p < 0.05), as compared with Tap water/<it>Der f </it>group. In asthmatic mice (Tap water/<it>Der f </it>group), the intensity of airway resistance increased simultaneously with the increase in acetylcholine concentration in a dose-dependant way. AHR was significantly inhibited in Goishi tea/<it>Der f </it>and Gallic acid/<it>Der f </it>(p < 0.01) groups as compared with the Tap water/<it>Der f </it>group. Regarding serum specific-IgG₁, significantly lower levels of this antibody were observed in Goishi tea/<it>Der f </it>and Gallic acid/<it>Der f </it>groups as compared with the Tap water/<it>Der f </it>group (p < 0.05). In addition, adiponectin level was significantly higher in the Goishi tea group as compared with the Tap water treated mice (p < 0.01).</p> <p>Conclusions</p> <p>The results suggest that Goishi tea consumption exerted an inhibitory effect on eosinophilic and neutrophilic infiltration in the lung, attenuated the increase in airway resistance and increased the production of adiponectin; thus reducing Der f induced allergic inflammatory process in mice.</p

View and present status of personnel involved in clinical trials : a survey of participants from the First Symposium of the Shikoku Collaborative Group for Promotion of Clinical Trials

Clinical trials leading to drug approval (registration trials) play a central role in the drug development process. Since the introduction of the Good Clinical Practice (GCP) standard in 1997, the Japanese infrastructure for registration trials has improved. The contribution of support staff, including clinical research coordinators (CRCs), to clinical trials is now widely recognized in Japan. Quality issues and career development for these support staff are being increasingly emphasized. The Shikoku Collaborative Group for Promotion of Clinical Trials was organized in 2008 to address these issues through communication with the personnel involved in clinical trials in regional areas of Japan. To understand the views and present status of personnel involved in clinical trials, we used questionnaires to survey the participants of the First Symposium of the Shikoku Collaborative Group for Promotion of Clinical Trials held in August 2009. Group discussions and special lectures occurred at the symposium. The questionnaire began with questions about basic patient characteristics, followed by practical questions. Of 110 participants, there were 68 respondents (62%), including clinical trial support staff (clinical research coordinators [n=36, 53%], administrative officers [n=9, 13%]), and medical staff [n=23, 34%]). Among the support staff, 36 (80%) had more than 5 years of experience. The most common questionnaire answer selected for participation in the symposium was “willing to contact staff from other medical institutions or organizations” for support staff and “to obtain further knowledge concerning clinical trials” for medical staff. The overall view of the discussion (“Was the discussion satisfactory?”) was favorable for 36 (53%) respondents. This survey revealed that the group discussion in the present symposium appears to be valuable for participants, using overall satisfaction as a surrogate. Based on the information obtained in the present study, further development of the clinical trial infrastructure, including training opportunities and career development for support staff, is required. Due to the limitations of this study, further analysis is warranted to determine the optimal strategy for training support staff

Atractylodes lancea (Thunb.) DC. [Asteraceae] rhizome-derived exosome-like nanoparticles suppress lipopolysaccharide-induced inflammation in murine microglial cells

BackgroundExosome-like nanoparticles (ELNs) mediate interspecies intercellular communications and modulate gene expression.Hypothesis/PurposeIn this study, we isolated and purified ELNs from the dried rhizome of Atractylodes lancea (Thunb.) DC. [Asteraceae] (ALR-ELNs), a traditional natural medicine, and investigated their potential as neuroinflammatory therapeutic agents.MethodsALR-ELN samples were isolated and purified using differential centrifugation, and their physical features and microRNA contents were analyzed through transmission electron microscopy and RNA sequencing, respectively. BV-2 microglial murine cells and primary mouse microglial cells were cultured in vitro, and their ability to uptake ALR-ELNs was explored using fluorescence microscopy. The capacity of ALR-ELNs to modulate the anti-inflammatory responses of these cells to lipopolysaccharide (LPS) exposure was assessed through mRNA and protein expression analyses.ResultsOverall, BV-2 cells were found to internalize ALR-ELNs, which comprised three microRNAs (ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p) that could have anti-inflammatory activity. Pretreatment of BV-2 cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide, interleukin-1β, interleukin-6, and tumor necrosis factor-α. Notably, the mRNA levels of Il1b, Il6, iNos, ccl2, and cxcl10 in BV-2 cells, which increased upon LPS exposure, were significantly reduced following ALR-ELN treatment. Moreover, the mRNA levels of heme oxygenase 1, Irf7, ccl12, and Irg1 also increased significantly following ALR-ELN treatment. In addition, pretreatment of primary mouse microglial cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide.ConclusionOur findings indicate that ALR-ELNs exhibit anti-inflammatory effects on murine microglial cells. Further validation may prove ALR-ELNs as a promising neuroinflammatory therapeutic agent

Difference between deep seawater and surface seawater in the preventive effect of atherosclerosis

Seawater has been used for thalassotherapy and atopic dermatitis for a long time in medical treatment. However, there are still many obscure points in the scientific evidence about the effective of medical treatment. Deep seawater at depths between about 500 m and 1000 m circulates around the world. 1) Deep seawater is known to have such characteristics as being clean and rich in mineral components compared to surface seawater, We reported previously that deep seawater was effective for hyperlipidemia and atherosclerosis prevention. 12) In this study, we prepared drinking water samples containing the same amounts of major mineral constituents Na, K, Ca, and Mg, with hardness of 1200, by filtering with a semipermeable membrane using surface and deep seawater collected in the sea area of Muroto, Kochi Prefecture, known for the up-flow of deep seawater, and examined the effects of the drinking water samples on the prevention of a typical lifestyle-related disorder, hyperlipidemia and atherosclerosis. MATERIALS AND METHODS Animals Male Japanese white rabbits weighing 1.8 to 2.0 kg (Shimizu, Kyoto, Japan) were used in this study. These animals were acclimatized on a 12 h light/dark cycle in a humidity-and temperature-controlled facility and allowed free access to food and water for 1 week before the experiment. Deep and Surface Seawater Deep seawater pumped up from a depth of 374 m off Muroto Cape (Kochi, Japan) was separated into desalinated water and concentrated by a semipermeable membrane. Various concentrations of water (with sodium eliminated etc.) were added to the desalinated water, and deep seawaters were prepared. (hardness of about 1200; Muroto Marinefood Corporation, Odanikokufun Corporation) The surface seawater of the Muroto Cape ocean space was taken and same process was performed to prepare the drinking water (hardness of about 1200; Kochi Prefectural Deep seawater Laboratory). The mineral-ingredient content of each drinking seawater is shown in Administration of Deep or Surface Seawater Cholesterol fed rabbits were divided into three groups and medicated with 150 ml/d of deep seawater, surface seawater and distilled water in a water-supply bottle ad libitum, and fed * To whom correspondence should be addressed. Murotomisaki-cho, Muroto, Kochi 781-7101, Japan: c Muroto Marinefood Corporation; 3507-5 Murotomisaki-cho, Muroto, Kochi 780-8123, Japan: and d Odanikokufun Corporation; 939-4 Takasu, Kochi, Kochi 780-8123, Japan. Received July 13, 2004; accepted September 9, 2004; published online September 10, 2004 Using surface and deep seawater collected in the sea area of Muroto Cape (Kochi, Japan), desalinated drinking samples of about 1200 hardness were prepared and examined for the effects on the prevention of atherosclerosis in dietary induced hyperlipidemia rabbits. The plasma LDL cholesterol level was lower in the deep seawater group than in the surface seawater group. GPx activity was significantly higher in the deep seawater group than in the control group, while there was no difference between the surface seawater and control groups. The level of LPO was also significantly lower in the deep seawater group than in the control group. The Sudan IV lipid stained area ratio on the inner surface of the aorta was significantly lower in the deep seawater groups than in the control group, while there was no difference between the surface seawater and control groups. The oil red O stained cross section of the aorta in the control and surface seawater administration group foam cells had accumulated to form thick layers, while in the deep seawater administration group, the degree of their accumulation was very low. These results suggested that the deep seawater was useful for the prevention of hyperlipidemia and arteriosclerosis compared to the surface seawater, and it was found that reduction of the LDL cholesterol level and enhancement of GPx activity were involved in its effects

Atractylodes lancea rhizome derived exosome-like nanoparticles prevent alpha-melanocyte stimulating hormone-induced melanogenesis in B16-F10 melanoma cells

Aberrant melanin overproduction can significantly impact an individual's appearance and cause mental and psychological distress. Current inhibitors of melanin production exert harmful side effects due to inadequate selectivity; thus a need to develop more selective melanin synthesis inhibitors is necessary. Extracellular vesicles are important agents of intercellular signalling in prokaryotes and eukaryotes. Recently, plant-derived nanoparticles, similar to mammalian exosomes, have attracted attention for their use in health research. In this study, to investigate the potential of plant-derived exosome-like nanoparticles (ELNs) as inhibitors of melanin production, we used hot water to extract ELNs from the rhizome of Atractylodes lancea (A-ELNs). The size of A-ENLs ranged from 34 to 401 nm and carried three microRNA: ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p. These A-ENLs were applied to B16-F10 melanoma cells treated with α-melanocyte-stimulating hormone (α-MSH). After A-ELNs were taken up by B16-F10 cells, their melanin levels were significantly reduced. Furthermore, A-ELNs significantly reduced tyrosinase activity in B16-F10 cells and mRNA expression of microphthalmia-associated transcription factor (Mitf), tyrosinase, tyrosinase-related protein 1, and DOPA chrome tautomerase. These results suggest that A-ELN suppresses melanogenic enzymes expression by downregulating Mitf, thereby inhibiting melanin synthesis. Hence, A-ELN can be developed into a novel topical drug after additional studies and optimization

Risk Factors for Anticancer Drug-Induced Hyponatremia: An Analysis Using the Japanese Adverse Drug Report (JADER) Database

Background and Objectives: Hyponatremia is among the most prevalent electrolyte abnormalities observed in patients with cancer during chemotherapy. Therefore, managing hyponatremia is crucial since it causes a severe electrolyte imbalance that can lead to significant mortality, and this study aimed to investigate the relationship between hyponatremia, anticancer drugs, and cancer types. Materials and Methods: Reported odds ratios were calculated and evaluated based on adverse event reports submitted to the Japanese Adverse Drug Event Report (JADER) database. Results: Overall, 2943 patients had hyponatremia. Notably, cisplatin, pemetrexed, and etoposide had marked hyponatremia signals. In addition, significant hyponatremia signals were detected for oesophageal, lung, and renal cancers. Conclusions: Hyponatremia has been reported in women and patients with lung cancer receiving cisplatin, with a growing trend in the number of elderly patients receiving cisplatin. Furthermore, since the onset of hyponatremia during cisplatin administration is frequently reported within 10 days, patient information should be thoroughly examined before and monitored throughout the administration, which can contribute to the early detection and prevention of hyponatremia

Non-Surgical Breast-Conserving Treatment (KORTUC-BCT) Using a New Radiosensitization Method (KORTUC II) for Patients with Stage I or II Breast Cancer

The purpose of the present study was to establish a non-surgical breast-conserving treatment (BCT) using KORTUC II radiosensitization treatment. A new radiosensitizing agent containing 0.5% hydrogen peroxide and 0.83% sodium hyaluronate (a CD44 ligand) has been developed for intra-tumoral injection into various tumors. This new method, named KORTUC II, was approved by our local ethics committee for the treatment of breast cancer and metastatic lymph nodes. A total of 72 early-stage breast cancer patients (stage 0, 1 patient; stage I, 23; stage II, 48) were enrolled in the KORTUC II trial after providing fully informed consent. The mean age of the patients was 59.7 years. A maximum of 6 mL (usually 3 mL for tumors of less than approximately 3 cm in diameter) of the agent was injected into breast tumor tissue twice a week under ultrasonographic guidance. For radiotherapy, hypofraction radiotherapy was administered using a tangential fields approach including an ipsilateral axillary region and field-in-field method; the energy level was 4 MV, and the total radiation dose was 44 Gy administered as 2.75 Gy/fraction. An electron boost of 3 Gy was added three times. Treatment was well tolerated with minimal adverse effects in all 72 patients. No patients showed any significant complications other than mild dermatitis. A total of 24 patients under 75 years old with stage II breast cancer underwent induction chemotherapy (EC and/or taxane) prior to KORTUC II treatment, and 58 patients with estrogen receptor-positive tumors also received hormonal therapy following KORTUC II. The mean duration of follow-up as of the end of September 2014 was 51.1 months, at which time 68 patients were alive without any distant metastases. Only one patient had local recurrence and died of cardiac failure at 6.5 years. Another one patient had bone metastases. For two of the 72 patients, follow-up ended after several months following KORTUC II treatment. In conclusion, non-surgical BCT can be performed using KORTUC II, which has three major characteristics: imaging guidance; enzyme-targeting; and targeting of breast cancer stem cells via the CD44 receptor