BACKGROUND: Propofol is an intravenous anesthetic which has antioxidant effects due to its similarity in molecular structure to α-tocopherol. It has been reported that α-tocopherol increases osteoclast fusion and bone resorption. Here, we investigated the effects of propofol on signaling pathways of osteoclastogenic gene expression, as well as osteoclastogenesis and bone resorption using bone marrow-derived macrophages (BMMs). METHODS: BMMs were cultured with macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus receptor activator of nuclear factor kappa B ligand (RANKL) in the presence of propofol (0–50 µM) for 4 days. Mature osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) and the numbers of TRAP-positive multinucleated osteoclasts were counted. To examine the resorption activities of osteoclasts, a bone resorption assay was performed. To identify the mechanism of action of propofol on the formation of multinucleated osteoclasts, we focused on dendritic cell-specific transmembrane protein (DC-STAMP), a protein essential for pre-osteoclastic cell fusion. RESULTS: Propofol increased the formation of TRAP-positive multinucleated osteoclasts. In addition, the bone resorption assay revealed that propofol increased the bone resorption area on dentin discs. The mRNA expression of DC-STAMP was upregulated most strongly in the presence of both RANKL and propofol. However, SB203580, a p38 inhibitor, significantly suppressed the propofol/RANKL-induced increase in mRNA expression of DC-STAMP. CONCLUSION: We have demonstrated that propofol enhances osteoclast differentiation and maturation, and subsequently increases bone resorption. Additionally, we identified the regulatory pathway underlying osteoclast cell-cell fusion, which was enhanced by propofol through p38-mediated DC-STAMP expression.
Acid Phosphatase ; Antioxidants ; Bone Resorption ; Cell Fusion ; Dentin ; Gene Expression ; Macrophage Colony-Stimulating Factor ; Macrophages ; Molecular Structure ; Osteoclasts ; p38 Mitogen-Activated Protein Kinases ; Propofol ; RANK Ligand ; RNA, Messenger

OBJECTIVETo evaluate the clinical efficacy of electrical stimulation (ES) of auricular acupressure on reducing the ocular symptoms and signs before and after treatment for dry eye.

METHODSThe inclusion criteria were the tear film break-up time (TFBUT) below 5 s and a Schirmer test-I below 5 mm in dry eyes with ocular symptoms for at least 6 months. Subjects were randomized into a treatment group (50 cases) with continuous low frequency ES under auricular acupressure at acupoints and a no ES under auricular acupressure (no-ES, control group, 50 cases) on the same acupoints. Auricular acupressure were stimulated with ES at 4 master points of both ears, which were performed twice a week for 4 weeks at each point for 30 s. The ocular symptoms, the TFBUT, and Schirmer test-I were evaluated before and after this procedure.

RESULTSThere were significantly better scores in TFBUT (P=0.032), the Schirmer test-I (P=0.044) and ocular symptoms (P=0.029) at 3 months post-treatment in the treatment group than in the control group. The total effective rate in the treatment group was accomplished in 41 (82%) of the 50 cases of dry eye.

CONCLUSIONSAuricular acupressure with ES at auricular acupoint improves ocular symptoms and signs of dry eye for a period of at least 3 months.

BACKGROUND: The shortage of human hearts for allotransplantation makes xenotransplantation a possible option for controllable organ providers. To detect acute xenograft rejection, invasive biopsy seems inevitable; however, this occasionally results in poor incision wound healing or infection. To date, no method of noninvasive imaging for early detection of xenograft rejection has been established. We hypothesized that ultrasound speckle tracking would better detect xenograft failure than routine left ventricular ejection fractions (EF). METHODS: From August 2013 to July 2015, a total of six cardiac heterotopic xenotransplants (α 1, 3-galactosyltransferase gene-knockout porcine heart) into cynomolgus monkeys were monitored with echocardiography every 3 to 7 days. M-mode and two-dimensional (2D)-EF measurements and myocardial strain analyses were performed. Cardiac xenograft pathology was reviewed from the immediate postoperative biopsy, as well as the necropsy. RESULTS: Myocardial speckle tracking analysis was feasible in all six cases. The longest survival was 43 days. Only one pathology-proven immunologic rejection occurred. Cardiac xenograft failure appeared as two types: a dilated pattern with decreased EF or a myocardial-thickening pattern with preserved EF. Both antibody-mediated rejection (n=1) and sepsis-induced myocardial dysfunction (n=2) revealed decreased radial or circumferential strains, but normal-range EF. Xenograft functional decline was significant with respect to radial or circumferential strain (P=0.028), but not to conventional M-mode or 2D-EFs (P=0.600, P=0.340, respectively). CONCLUSIONS: Radial and circumferential strains were significantly decreased in both types of xenograft failure, regardless of EF. Further studies are warranted to correlate the strain analysis and immunopathological details.
Biopsy ; Echocardiography ; Heart ; Heart Transplantation ; Heterografts ; Humans ; Macaca fascicularis ; Methods ; Pathology ; Stroke Volume ; Transplantation, Heterologous* ; Transplants* ; Ultrasonography ; Wound Healing

PURPOSE: Although Roux-en-Y (R-Y) reconstruction after distal gastrectomy has several advantages, such as prevention of bile reflux into the remnant stomach, it is rarely used because of the technical difficulty. This prospective randomized clinical trial aimed to show the efficacy of a novel method of R-Y reconstruction involving the use of 2 circular staplers by comparing this novel method to Billroth-I (B-I) reconstruction. MATERIALS AND METHODS: A total of 118 patients were randomly allocated into the R-Y (59 patients) and B-I reconstruction (59 patients) groups. R-Y anastomosis was performed using two circular staplers and no hand sewing. The primary end-point of this clinical trial was the reflux of bile into the remnant stomach evaluated using endoscopic and histological findings at 6 months after surgery. RESULTS: No significant differences in clinicopathological findings were observed between the 2 groups. Although anastomosis time was significantly longer for the patients of the R-Y group (P<0.001), no difference was detected between the 2 groups in terms of the total surgery duration (P=0.112). Endoscopic findings showed a significant reduction of bile reflux in the remnant stomach in the R-Y group (P<0.001), and the histological findings showed that reflux gastritis was more significant in the B-I group than in the R-Y group (P=0.026). CONCLUSIONS: The results of this randomized controlled clinical trial showed that compared with B-I reconstruction, R-Y reconstruction using circular staplers is a safe and feasible procedure. This clinical trial study was registered at www.ClinicalTrials.gov (registration No. NCT01142271).
Bile ; Bile Reflux ; Gastrectomy* ; Gastric Stump ; Gastritis ; Hand ; Humans ; Methods ; Prospective Studies ; Stomach Neoplasms*

Solitary fibrous tumor of the pleura (SFTP) is a rare primary intrathoracic tumor that arises from mesenchymal tissue underlying the mesothelial layer of the pleura. It usually has an indolent clinical course. The hypoglycemia that accompanies SFTP was first described by Doege and Potter independently in 1930, hence the eponym Doege-Potter syndrome (DPS). The incidence of DPS is reported to be ~4%. In this report, we present a typical case of DPS that was cured through complete surgical resection.
Eponyms ; Hypoglycemia* ; Incidence ; Pleura* ; Solitary Fibrous Tumor, Pleural ; Solitary Fibrous Tumors

Melatonin affects diverse physiological functions through its receptor and plays an important role in the central nervous system. In the present study, we compared immunoreactivity patterns of arylalkylamine N-acetyltransferase (AANAT), an enzyme essential for melatonin synthesis, and melatonin receptor type 1B (MT2) in the spinal cord of young adult (2~3 years) and aged (10~12 years) beagle dogs using immunohistochemistry and Western blotting. AANAT-specific immunoreactivity was observed in the nuclei of spinal neurons, and was significantly increased in aged dog spinal neurons compared to young adult spinal neurons. MT2-specific immunoreactivity was found in the cytoplasm of spinal neurons, and was predominantly increased in the margin of the neuron cytoplasm in aged spinal cord compared to that in the young adult dogs. These increased levels of AANAT and MT2 immunoreactivity in aged spinal cord might be a feature of normal aging and associated with a feedback mechanism that compensates for decreased production of melatonin during aging.
Age Factors ; Aging/physiology ; Animals ; Arylalkylamine N-Acetyltransferase/*analysis/immunology/physiology ; Blotting, Western ; Dogs ; Fluorescent Antibody Technique ; Male ; Receptor, Melatonin, MT2/*analysis/immunology/physiology ; Spinal Cord/*chemistry/immunology/physiology

Alpha-synuclein (alpha-syn) is a presynaptic protein that is richly expressed in the central and peripheral nervous systems of mammals, and it is related to the pathogenesis of Parkinson's disease and other neurodegenerative disorders. In the present study, we compared the distribution of the immunoreactivity of alpha-syn and its related gliosis in the spinal cord of young adult (2-3 years) and aged (10-12 years) beagle dogs. We discovered that alpha-syn immunoreactivity was present in many neurons in the thoracic level of the aged spinal cord, however, its protein level was not distinct inform that of the adult spinal cord. In addition, ionized calcium-binding adapter molecule-1 (a marker for microglia) immunoreactivity, and not glial fibrillary acidic protein (a marker for astrocytes) immunoreactivity, was somewhat increased in the aged group compared to the adult group. These results indicate that alpha-syn immunoreactivity was not dramatically changed in the dog spinal cord during aging.
Adult ; Aged ; Aging ; alpha-Synuclein ; Animals ; Dogs ; Glial Fibrillary Acidic Protein ; Gliosis ; Humans ; Mammals ; Neurodegenerative Diseases ; Neurons ; Parkinson Disease ; Peripheral Nervous System ; Spinal Cord ; Young Adult

Neurogenesis in the adult brain occurs continuously throughout life. The main olfactory bulb (MOB) is the first central relay of the olfactory system. We examined proliferation of newly generated cells in each layer of the gerbil MOB after 5 min of transient cerebral ischemia using doublecortin (DCX), a marker of neuronal progenitors. Many DCX immunoreactive neuroblasts were found in the all layers of the MOBs of control and ischemia groups. Ten to 15 days after ischemia/reperfusion, no difference in numbers of DCX immunoreactive neuroblasts was found in the MOB. Thirty days after ischemia/reperfusion, significant increase of DCX immunoreactive cells was observed in all layers of ischemic MOB. This result indicates that neuroblasts increase in the MOB from 30 days after transient cerebral ischemia in gerbils.
Adult ; Brain ; Gerbillinae ; Humans ; Ischemia ; Ischemic Attack, Transient ; Neurogenesis ; Neurons ; Olfactory Bulb

BACKGROUND/AIMS: Intestinal involvement with bleeding and perforation is one of the main causes of morbidity and mortality in patients with Behcet's disease (BD); however, the clinical course of intestinal BD has not been defined. The aim of this study was to determine the clinical course of intestinal BD based on the characteristics of ulcers visualized during colonoscopy. METHODS: We retrospectively reviewed the medical records and colonoscopic findings of 41 patients with intestinal BD. All patients were classified into subgroups according to ulcer depth, size, and number, and we analyzed the clinical manifestations, subset type of BD, medications, surgical procedures, and relapse rate among the subgroups. RESULTS: The median age at the time of diagnosis was 38 years (range, 18-74 years); 25 patients were females (M:F=1:1.56). Abdominal pain (n=40), diarrhea (n=27), and RLQ tenderness (n=21) were common symptoms. The number of complete, incomplete, and suspected types was 3, 17, and 21, respectively. In an analysis according to ulcer depth, the rate of steroid use and intestinal surgeries was more frequent in the deep ulcer group compared with the aphthous and shallow ulcer groups (50.0% vs. 0% vs. 17.6%; P=0.012; 42.9% vs. 0% vs. 23.5%: P=0.013) The rate of steroid use and relapse tended to be higher as the size of the ulcer increased; however, there was no difference in the rates of steroid use, surgeries, and relapse based on the number of intestinal ulcers. CONCLUSIONS: The prognosis was worse in patients with intestinal BD who have deeper and larger ulcers. Therefore, we suggest that such patients need to be treated aggressively.
Abdominal Pain ; Colonoscopy ; Diarrhea ; Female ; Hemorrhage ; Humans ; Medical Records ; Prognosis ; Recurrence ; Retrospective Studies ; Ulcer

BACKGROUND/AIMS: Intestinal involvement with bleeding and perforation is one of the main causes of morbidity and mortality in patients with Behcet's disease (BD); however, the clinical course of intestinal BD has not been defined. The aim of this study was to determine the clinical course of intestinal BD based on the characteristics of ulcers visualized during colonoscopy. METHODS: We retrospectively reviewed the medical records and colonoscopic findings of 41 patients with intestinal BD. All patients were classified into subgroups according to ulcer depth, size, and number, and we analyzed the clinical manifestations, subset type of BD, medications, surgical procedures, and relapse rate among the subgroups. RESULTS: The median age at the time of diagnosis was 38 years (range, 18-74 years); 25 patients were females (M:F=1:1.56). Abdominal pain (n=40), diarrhea (n=27), and RLQ tenderness (n=21) were common symptoms. The number of complete, incomplete, and suspected types was 3, 17, and 21, respectively. In an analysis according to ulcer depth, the rate of steroid use and intestinal surgeries was more frequent in the deep ulcer group compared with the aphthous and shallow ulcer groups (50.0% vs. 0% vs. 17.6%; P=0.012; 42.9% vs. 0% vs. 23.5%: P=0.013) The rate of steroid use and relapse tended to be higher as the size of the ulcer increased; however, there was no difference in the rates of steroid use, surgeries, and relapse based on the number of intestinal ulcers. CONCLUSIONS: The prognosis was worse in patients with intestinal BD who have deeper and larger ulcers. Therefore, we suggest that such patients need to be treated aggressively.
Abdominal Pain ; Colonoscopy ; Diarrhea ; Female ; Hemorrhage ; Humans ; Medical Records ; Prognosis ; Recurrence ; Retrospective Studies ; Ulcer