Sakurai, Japan
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Hara K.,Hosokawa Micron Corporation | Tsujimoto H.,Hosokawa Micron Corporation | Huang C.C.,Hosokawa Micron Powder Systems | Kawashima Y.,Aichi Gakuin University | And 4 more authors.
Journal of Toxicologic Pathology | Year: 2012

Polylactide-glycolide (PLGA) nanoparticles have been developed as pulmonary drug delivery carriers. To investigate their behavior, small- (d50 = 74 nm) and large-sized (d50 = 250 nm) FITC-conjugated PLGA nanoparticles were intratracheally administered to rats and were traced for 5, 30 and 60 minutes and 24 hours after administration (HAT). Immunohistochemically, a, FITCpositive reaction was observed in type-I alveolar epithelial cells (type-I AEC), endothelial cells and alveolar macrophages in the lungs from 5 minutes after treatment (MAT) to 24 HAT in both nanoparticle groups. In the kidneys, a positive reaction was observed in proximal tubular epithelial cells at 30 MAT; the reaction peaked at 60 MAT and was reduced at 24 HAT, while no positive reaction was seen in other sites. Ultrascructurally, the number of membrane-bound vesicles, which were approximately 70 nm in size and hard to distinguish from pinocytic vesicles, apparently increased in type-I AEC and endothelial cells at 5 MAT in the small-sized group, in comparison with the control group receiving physiological saline. The number of vesicles in the large-sized group was almost same as that in the control group. On the other hand, in both nanoparticle groups, lysosomes filled with nanoparticles appeared in alveolar macrophages from 30 MAT to 24 HAT. These results indicate that PLGA nanoparticles might be quickly transferred from the alveolar space to the blood vessel via type-I alveolar epithelial cells and excreted into urine, and that there is a threshold for particle size, less than approximately 70 nm in diameter, with regard to absorption through the alveolar wall. © 2012 The Japanese Society of Toxicologic Pathology.


Fujimoto N.,Okayama Rosai Hospital | Kato K.,Okayama University | Usami I.,Asahi Rosai Hospital | Sakai F.,International University of Japan | And 4 more authors.
Respiration | Year: 2014

Background: The clinical features of asbestos-related diffuse pleural thickening (DPT) remain unclear.Objectives: To clarify the association between radiological findings of DPT and respiratory function.Methods: Medical data from patients with asbestos-related DPT were collected, including their history of occupational or neighborhood asbestos exposure, initial symptoms, modified Medical Research Council dyspnea grade, smoking history, radiological findings, and respiratory function test results.Results: There were 106 DPT patients between 2005 and 2010 [i.e. 103 men (97.2%) and 3 women (2.8%)]. The median age at diagnosis was 69 years (range 46-88). Patient occupations related to asbestos exposure included: asbestos product manufacturing (n = 17); the shipbuilding industry (n = 14); the construction industry (n = 13); heat insulation work (n = 12); plumbing, asbestos spraying, and electrical work (n = 7 each), and transportation and demolition work (n = 4 each). The median duration of asbestos exposure was 25 years (range 2-54), and the median latency period before the onset of DPT was 46 years (range 25-66). Involvement of the costophrenic angle (CPA) was also negatively correlated with the percent vital capacity (%VC; r = -0.448, p < 0.01). Pleural thickness and the craniocaudal and horizontal extension of pleural thickening, as determined by chest computed tomography (CT), were also negatively correlated with %VC (r = -0.226, p < 0.05; r = -0.409, p < 0.01, and r = -0.408, p < 0.01, respectively).Conclusions: DPT develops after a long latency period following occupational asbestos exposure and causes marked respiratory dysfunction. The extension of DPT should be evaluated by chest CT, and chest X-ray would be important for the evaluation of the involvement of the CPA. © 2014 S. Karger AG, Basel.


PubMed | Hirao Hospital, Nara Prefecture General Medical Center, Saiseikai Chuwa Hospital, Nara Medical University and 2 more.
Type: | Journal: Neurourology and urodynamics | Year: 2016

We aimed to compare the efficacy and safety of mirabegron, a 3-adrenoceptor agonist, and imidafenacin, an anticholinergic agent, in overactive bladder patients.We conducted a multicenter, prospective randomized cross-over study at 5 hospitals in Japan from December 2012 to June 2015. We enrolled female patients with overactive bladder aged 50 years, who had never received treatment for the condition. The patients were assigned to Group A or B. Group A patients were administered mirabegron (50mg per day) for 8 weeks, followed by a 2-week washout period, and then imidafenacin (0.2mg per day) for 8 weeks. This order of drug administration was reversed in Group B.A total of 33 and 18 patients in Group A and 37 and 26 patients in Group B continued to receive treatment at weeks 8 and 18, respectively. Mirabegron administration significantly improved overactive bladder symptom score (OABSS), the urinary frequency per 24hr, voided volume per micturition, and number of nocturia episodes per night at week 8. Moreover, imidafenacin administration improved all these variables, except for the number of nocturia episodes per night at week 8. No significant difference was observed in the drug effects between mirabegron and imidafenacin. Although imidafenacin administration significantly increased the scores for dry mouth, blurred vision, and constipation, mirabegron administration did not.Mirabegron and imidafenacin have the same efficacy. Imidafenacin administration is associated with a higher rate of dry mouth, blurred vision, and constipation as compared to mirabegron administration. Neurourol. Urodynam. 2016 Wiley Periodicals, Inc.


PubMed | Tokyo Women's Medical University, Olympus Corporation and Saiseikai Chuwa Hospital
Type: Journal Article | Journal: Cell medicine | Year: 2017

The present study investigated whether transplantation of autologous adipose-derived stem cells (ASCs) administered into the systemic circulation of a mouse with chronic liver injury provides therapeutic efficacy in the absence of any undesirable side effects. The ASCs used were isolated from mice with the same genetic background as the recipient mice and expanded in vitro. For the induction of chronic liver injury, mice were repetitively administered twice a week with CCl


Iwata T.,Nara Prefectural Mimuro Hospital | Nakahashi K.,Saiseikai Chuwa Hospital | Inoue S.,Nara Medical University | Furuya H.,Nara Medical University
Saudi Journal of Anaesthesia | Year: 2013

Background: Ropivacaine, a long-acting local anesthetic agent, has been used for postoperative analgesia in brachial plexus block (BPB) at high doses. However, use of lower doses would reduce the occurrence of adverse effects. Methods: We applied BPB with low-dose ropivacaine (10 mL of 0.375% ropivacaine) after induction of general anesthesia for surgery of the upper extremities in 62 patients at our hospital. Ropivacaine was administered via a fluoroscopy-guided supraclavicular method. Analgesic effects during surgery, visual analog scale pain scores, skin sensation, muscle strength, and postoperative patient satisfaction indices were evaluated. Results: Fifty-six patients (90.3%) did not require supplemental analgesics during surgery. The remaining six patients were administered fentanyl due to the insufficient analgesic effects of the nerve block. Some adverse effects, including numbness and delayed motor and sensory recovery of the upper extremities, were observed. The mean postoperative patient-evaluated visual satisfaction scale was 94.1. Conclusions: Our results suggest that low-dose ropivacaine is clinically acceptable for BPB under general anesthesia.


Suzuki Y.,Juntendo University | Suzuki Y.,Nisshin Pharma Inc | Asano M.,Mukogawa Women's University | Sato K.,Kyoto Prefectural University | And 4 more authors.
Biomedical Research | Year: 2011

Wheat gluten hydrolysate (WGH) has been reported to mitigate chronic hepatitis in some patients. We aimed to reproduce and examine this phenomenon in a rat experimental model. Male Sprague-Dawley rats were injected with carbon tetrachloride twice a week for 25 weeks, and 3 weeks later WGH was added to the feed (none, 4%, and 8%) for the remaining 22 weeks. Transition of serum transaminases showed a temporary decrease in aspartate aminotransferase (AST) and a delay in the peaking of alanine aminotransferase (ALT) in the WGH groups. Macroscopically, at the end of the 25 weeks, the progress of cirrhosis was milder in the WGH groups, as indicated by less ascites fluid and the fewer tubercle formations. Histological and immunohistochemical analyses of the liver revealed fewer collagen fibers and less α-smooth muscle actin (SMA) in the 8% WGH group. The ethanol-soluble extract of liver tissue showed plasmin inhibiting activity in the 8% WGH group. The observed modification of the transition of serum transaminases during chronic CCl 4 challenge supports the possibility that WGH mitigates chronic hepatitis, and the liver manifestations after 25 weeks of CCl 4 treatment indicate that WGH ingestion alters the progress of cirrhosis.


Shimamoto T.,Wakayama Medical University | Tani M.,Wakayama Medical University | Kawai M.,Wakayama Medical University | Hirono S.,Wakayama Medical University | And 7 more authors.
Pancreas | Year: 2010

Objectives: Some intraductal papillary mucinous neoplasms (IPMNs) have no proliferation to malignant IPMNs, and benign IPMNs can observe the natural course without a surgical intervention. Therefore, an accurate assessment is required to determine the appropriate decision on managing malignant IPMNs. Methods: Quantitative real-time reverse transcription-polymerase chain reaction was performed for pancreatic juice by a LightCycler instrument focused on carcinoembryonic antigen, MUC1, and human telomerase reverse transcriptase. Results: MUC1/glyceraldehyde-3-phosphate dehydrogenase messenger RNA (mRNA) ratio in intraductal papillary mucinous carcinoma (IPMC; median, 4710.7) was significantly higher in intraductal papillary mucinous adenoma (IPMA; median, 727; P = 0.0229). Furthermore, the MUC1/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in carcinoma in situ and minimum invasive IPMC (median, 26,490) was significantly higher than that in IPMA (P = 0.0152). The cutoff level of MUC1 ratio was determined as 1600 for the division of IPMC from IPMA by the receiver-operating characteristic curve. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MUC1 mRNA were 88.9%, 71.4%, 80.0%, 83.3%, and 81.3%, respectively. Conclusions: Quantitative reverse transcription-polymerase chain reaction using MUC1 is useful for the detection of malignant IPMN in pure pancreatic juice. Copyright © 2010 by Lippincott Williams & Wilkins.


PubMed | Saiseikai Chuwa Hospital, Nagoya City University and Nara Medical University
Type: Journal Article | Journal: Oncotarget | Year: 2016

Despite progress in clinical cancer medicine in multiple fields, the prognosis of pancreatic cancer has remained dismal. Recently, chemopreventive strategies using phytochemicals have gained considerable attention as an alternative in the management of cancer. The present study aimed to evaluate the chemopreventive effects of resveratrol (RV) and apocynin (AC) in N-Nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamster. RV- and AC-treated hamsters showed significant reduction in the incidence of pancreatic cancer with a decrease in Ki-67 labeling index in dysplastic lesions. RV and AC suppressed cell proliferation of human and hamster pancreatic cancer cells by inhibiting the G1 phase of the cell cycle with cyclin D1 downregulation and inactivation of AKT-GSK3 and ERK1/2 signaling. Further, decreased levels of GSK3(Ser9) and ERK1/2 phosphorylation and cyclin D1 expression in the nuclear fraction were observed in cells treated with RV or AC. Nuclear expression of phosphorylated GSK3(Ser9) was also decreased in dysplastic lesions and adenocarcinomas of hamsters treated with RV or AC in vivo. These results suggest that RV and AC reduce phosphorylated GSK3(Ser9) and ERK1/2 in the nucleus, resulting in inhibition of the AKT-GSK3 and ERK1/2 signaling pathways and cell cycle arrest in vitro and in vivo. Taken together, the present study indicates that RV and AC have potential as chemopreventive agents for pancreatic cancer.


Aoyama Y.-I.,Shiraniwa Hospital | Ohta S.,Shiraniwa Hospital | Sakaki S.,Shiraniwa Hospital | Fujita T.,Saiseikai Chuwa Hospital
Neurological Surgery | Year: 2015

A 59-year-old woman was admitted with to our hospital with a sudden severe headache that had lasted for 5 days. Neck stiffness was present, but no other neurological deficits were present. Subarachnoid hemorrhage and intra-tumor hemorrhage were not noted on a head computed tomography (HCT). The patient's cerebrospinal fluid was xanthochromic. Magnetic resonance imaging (MRI) demonstrated a gadolinium-enhanced tumor with hemorrhagic changes around the foramen magnum. After conservative therapy, MRI showed a decrease in tumor size and a dural tail sign. This tumor was diagnosed as a hemorrhagic meningioma, and was resected with a posterior suboccipital approach. Histology confirmed that this tumor was a benign transitional meningioma with hemorrhagic change. This is a rare case involving benign meningioma onset by hemorrhagic change. Postoperative tumor recurrence was not present.


PubMed | Saiseikai Chuwa Hospital and Nara Medical University
Type: Journal Article | Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy | Year: 2016

An 82-year-old man with percutaneous nephrostomy presented to our Hospital with dysuria for one day. The patients percutaneous nephrostomy tube was exchanged, with about 20mL of creamy purulent urine being collected. Direct smear of the urine specimen showed polymorphonuclear leukocytes and small Gram-negative bacilli, some of which had undergone phagocytosis. This organism was identified as Kerstersia gyiorum using 16S ribosomal RNA gene analysis. He was successfully recovered with exchange of his percutaneous nephrostomy tube and fluoroquinolone internal use treatment. This is the first case report of urinary tract infection due to K.gyiorum.

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