Alpha-lipoic acid (ALA) is a naturally occurring antioxidant and has been previously used to treat diabetes and cardiovascular disease. However, the autophagy effects of ALA against oxidative stress-induced dopaminergic neuronal cell injury remain unclear. The aim of this study was to investigate the role of ALA in autophagy and apoptosis against oxidative stress in the SH-SY5Y human dopaminergic neuronal cell line. We examined SH-SY5Y phenotypes using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (cell viability/proliferation), 4′,6-diamidino-2-phenylindole dihydrochloride nuclear staining, Live/Dead cell assay, cellular reactive oxygen species (ROS) assay, immunoblotting, and immunocytochemistry. Our data showed ALA attenuated hydrogen peroxide (H2O2)-induced ROS generation and cell death. ALA effectively suppressed Bax up-regulation and Bcl-2 and BclxL down-regulation. Furthermore, ALA increased the expression of the antioxidant enzyme, heme oxygenase-1. Moreover, the expression of Beclin-1 and LC-3 autophagy biomarkers was decreased by ALA in our cell model. Combined, these data suggest ALA protects human dopaminergic neuronal cells against H2O2-induced cell injury by inhibiting autophagy and apoptosis.

Alpha-lipoic acid (ALA) is a naturally occurring antioxidant and has been previously used to treat diabetes and cardiovascular disease. However, the autophagy effects of ALA against oxidative stress-induced dopaminergic neuronal cell injury remain unclear. The aim of this study was to investigate the role of ALA in autophagy and apoptosis against oxidative stress in the SH-SY5Y human dopaminergic neuronal cell line. We examined SH-SY5Y phenotypes using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (cell viability/proliferation), 4′,6-diamidino-2-phenylindole dihydrochloride nuclear staining, Live/Dead cell assay, cellular reactive oxygen species (ROS) assay, immunoblotting, and immunocytochemistry. Our data showed ALA attenuated hydrogen peroxide (H2O2)-induced ROS generation and cell death. ALA effectively suppressed Bax up-regulation and Bcl-2 and BclxL down-regulation. Furthermore, ALA increased the expression of the antioxidant enzyme, heme oxygenase-1. Moreover, the expression of Beclin-1 and LC-3 autophagy biomarkers was decreased by ALA in our cell model. Combined, these data suggest ALA protects human dopaminergic neuronal cells against H2O2-induced cell injury by inhibiting autophagy and apoptosis.

PURPOSE: Periodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults. METHODS: A total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices. RESULTS: The RA group had significantly higher values than the control group for all investigated periodontal indices (P < 0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r = 0.125, P = 0.049), RA disease duration (r = 0.253, P < 0.001), erythrocyte sedimentation rate (ESR) (r = 0.162, P = 0.010), and anti-CCP antibody titer (r = 0.205, P = 0.004). Probing pocket depth (PPD) was correlated with ESR (r = 0.139, P = 0.027) and anti-Pg antibody titer (r = 0.203, P = 0.001). Bleeding on probing (BOP) was correlated with DAS28 (r = 0.137, P = 0.030), RA disease duration (r = 0.202, P = 0.001), ESR (r = 0.136, P = 0.030), anti-Pg antibody titer (r = 0.177, P = 0.005), and anti-CCP antibody titer (r = 0.188, P = 0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r = 0.201, P = 0.002; the latter r = 0.175, P = 0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r = 0.148, P = 0.020). CONCLUSIONS: The GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.
Adult ; Arthritis ; Arthritis, Rheumatoid ; Autoantibodies ; Blood Sedimentation ; Cross-Sectional Studies ; Hemorrhage ; Humans ; Periodontal Index ; Periodontitis ; Porphyromonas gingivalis ; Prevalence ; Prospective Studies ; Tooth

Sarcoidosis is a multisystem inflammatory disease of unknown etiology characterized by noncaseating epithelioid granuloma formation. Although the relationship between sarcoidosis and malignancy has been noted in recent decades, there are few case reports describing the concurrent diagnosis of sarcoidosis and malignancy. Herein, we describe a case of biopsy-proven splenic sarcoidosis mimicking metastasis at the time of ovarian adenocarcinoma. Imaging studies including positron-emission tomography-computed tomography were not useful for differentiating sarcoidosis from malignancy. Thus, our case highlights the importance of histopathological examination to rule out nonmalignant conditions before the diagnosis of metastatic disease is made.
Adenocarcinoma ; Diagnosis* ; Granuloma ; Neoplasm Metastasis ; Ovarian Neoplasms* ; Positron-Emission Tomography ; Sarcoidosis*

BACKGROUND/AIMS: Antispasmodic agents have been used in the management of irritable bowel syndrome. However, systematic reviews have come to different conclusions about the efficacy in irritable bowel syndrome. Fenoverine acts as a synchronizer of smooth muscle in modulating the intracellular influx of calcium. We compared fenoverine with trimebutine for the treatment of patients with IBS. METHODS: A multicenter, randomized, double-blind, non-inferiority clinical study was conducted to compared fenoverine with trimebutine. Subjects were randomized to receive either fenoverine (100 mg three times a day) or trimebutine (150 mg three times a day) for 8 weeks. A total of 197 patients were analyzed by the intention-to-treat approach. The primary endpoint was the proportion of patients who had 30% reduction in abdominal pain or discomfort measured by bowel symptom scale (BSS) score at week 8 compared to the baseline. The secondary endpoints were changes of abdominal bloating, diarrhea, constipation, overall and total scores of BSS, and overall satisfaction. RESULTS: At week 8, fenoverine was shown to be non-inferior to trimebutine (treatment difference, 1.76%; 90% CI, -10.30-13.82; p=0.81); 69.23% (54 of 78 patients) of patients taking fenoverine and 67.47% (56 of 83 patients) of patients taking trimebutine showed 30% reduction in abdominal pain or discomfort compared to the baseline. There results of the secondary endpoints were also comparable between the fenoverine group and the trimebutine group. CONCLUSIONS: Fenoverine is non-inferior to trimebutine for treating IBS in terms of both efficacy and tolerability.
Abdominal Pain/etiology ; Adult ; Constipation/etiology ; Diarrhea/etiology ; Double-Blind Method ; Drug Administration Schedule ; Female ; Humans ; Irritable Bowel Syndrome/complications/*drug therapy ; Male ; Middle Aged ; Parasympatholytics/*therapeutic use ; Phenothiazines/*therapeutic use ; Severity of Illness Index ; Treatment Outcome ; Trimebutine/*therapeutic use

PURPOSE: The purpose of this study was to investigate the effects of the immunosuppressants FK506 and cyclosporin A (CsA) on the osteogenic differentiation of rat mesenchymal stem cells (MSCs). METHODS: The effect of FK506 and CsA on rat MSCs was assessed in vitro. The MTT assay was used to determine the deleterious effect of immunosuppressants on stem cell proliferation at 1, 3, and 7 days. Alkaline phosphatase (ALP) activity was analyzed on days 3, 7, and 14. Alizarin red S staining was done on day 21 to check mineralization nodule formation. Real-time polymerase chain reaction (RT-PCR) was also performed to detect the expressions of bone tissue-specific genes on days 1 and 7. RESULTS: Cell proliferation was promoted more in the FK506 groups than the control or CsA groups on days 3 and 7. The FK506 groups showed increased ALP activity compared to the other groups during the experimental period. The ALP activity of the CsA groups did not differ from the control group in any of the assessments. Mineralization nodule formation was most prominent in the FK506 groups at 21 days. RT-PCR results of the FK506 groups showed that several bone-related genes-osteopontin, osteonectin, and type I collagen (Col-I)-were expressed more than the control in the beginning, but the intensity of expression decreased over time. Runx2 and Dlx5 gene expression were up-regulated on day 7. The effects of 50 nM CsA on osteonectin and Col-I were similar to those of the FK506 groups, but in the 500 nM CsA group, most of the genes were less expressed compared to the control. CONCLUSIONS: These results suggest that FK506 enhances the osteoblastic differentiation of rat MSCs. Therefore, FK506 might have a beneficial effect on bone regeneration when immunosuppressants are needed in xenogenic or allogenic stem cell transplantation to treat bone defects.
Alkaline Phosphatase ; Animals ; Anthraquinones ; Bone Regeneration ; Cell Differentiation ; Cell Proliferation ; Collagen Type I ; Cyclosporine ; Durapatite ; Gene Expression ; Immunosuppressive Agents ; Mesenchymal Stromal Cells ; Osteoblasts ; Osteonectin ; Rats ; Real-Time Polymerase Chain Reaction ; Stem Cell Transplantation ; Stem Cells ; Tacrolimus

PURPOSE: Few reports have documented psychopathological abnormalities in patients with primary spontaneous pneumothorax (PSP). We analyzed the results of a multiphasic personal inventory test to investigate the psychopathologic impact of PSP in young Korean males. MATERIALS AND METHODS: The authors reviewed the results of a Korean military multiphasic personal inventory (KMPI) administered to military conscripts in South Korea. A total of 234 young males participated in this study. The normal volunteer group (n=175) comprised individuals who did not have any lung disease. The PSP group (n=59) included individuals with PSP. None of the examinees had any psychological problems. The KMPI results of both groups were compared. RESULTS: There were more abnormal responses in the PSP group (17.0%) than the normal volunteer group (9.1%, p=0.002). The anxiety scale and depression scale scores of the neurosis category were greater for the PSP group than the normal group (p=0.039 and 0.014, respectively). The personality disorder and paranoia scale scores of the psychopathy category were greater for the PSP group than the normal group (p=0.007 and 0.018, respectively). CONCLUSION: Young males with PSP may have greater tendencies to suffer from anxiety, depression, personality disorders, and paranoia compared to normal individuals. Clinicians should be advised to evaluate the psychopathological aspects of patients with PSP.
Anxiety ; Depression ; Healthy Volunteers ; Humans ; Korea ; Lung Diseases ; Male* ; Military Personnel ; Paranoid Disorders ; Personality Disorders ; Pneumothorax* ; Psychopathology

BACKGROUND: Wake-up tests may be necessary during surgery for kypho-scoliosis to ensure that spinal function remains intact. It is difficult to predict the time when patients can respond to a verbal command. We evaluated the effectiveness of the bispectral index (BIS) and its relation to patients' levels of consciousness in wake-up tests during desflurane and sevoflurane anesthesia. METHODS: Eighteen patients each were enrolled in the desflurane and sevoflurane groups for spinal correction surgery. We measured BIS values, blood pressure, heart rate, and consciousness state and time, at the points when patients responded during the wake-up test. RESULTS: The BIS values when patients made fists upon a verbal command (T3) were 86.7 +/- 7.5 for desflurane and 90.3 +/- 5.4 for sevoflurane. Patients in the desflurane group had significantly shorter wake up delays than those in the sevoflurane group (6.9 +/- 1.8 min vs. 11.8 +/- 3.6 min). However, there was no difference between the groups in the time between the response to a verbal command and the time when a patient moved their toes in response to verbal commands. No recall of the wake-up tests occurred in either group. CONCLUSIONS: The values obtained using the BIS index could to some extent predict the time of a patient's and would be informative during desflurane and sevoflurane anesthesia. Moreover, desflurane permitted faster responses to verbal commands than sevoflurane, and allowed the wake-up test to be performed sooner.
Anesthesia ; Blood Pressure ; Consciousness ; Dietary Sucrose ; Heart Rate ; Humans ; Isoflurane ; Methyl Ethers ; Toes

PURPOSE: The aim of this study is to determine whether certain biomaterials have the potential to support cell attachment. After seeding bone marrow stromal cells onto the biomaterials, we investigated their responses to each material in vitro. METHODS: Rat bone marrow derived stromal cells were used. The biomaterials were deproteinized bovine bone mineral (DBBM), DBBM coated with fibronectin (FN), synthetic hydroxyapatite (HA), HA coated with FN, HA coated with beta-tricalcium phosphate (TCP), and pure beta-TCP. With confocal laser scanning microscopy, actin filaments and vinculin were observed after 6, 12, and 24 hours of cell seeding. The morphological features of cells on each biomaterial were observed using scanning electron microscopy at day 1 and 7. RESULTS: The cells on HA/FN and HA spread widely and showed better defined actin cytoskeletons than those on the other biomaterials. At the initial phase, FN seemed to have a favorable effect on cell adhesion. In DBBM, very few cells adhered to the surface. CONCLUSIONS: Within the limitations of this study, we can conclude that in contrast with DBBM not supporting cell attachment, HA provided a more favorable environment with respect to cell attachment.
Actin Cytoskeleton ; Animals ; Biocompatible Materials ; Bone Marrow ; Bone Substitutes ; Calcium Phosphates ; Cell Adhesion ; Durapatite ; Fibronectins ; Mesenchymal Stromal Cells ; Microscopy, Confocal ; Microscopy, Electron, Scanning ; Rats ; Seeds ; Stem Cells ; Stromal Cells ; Transplants ; Vinculin

PURPOSE: The aim of this study was to compare osteoblast behavior on zirconia and titanium under conditions cultured with bone morphogenetic protein-2. METHODS: MC3T3-E1 cells were cultured on sandblasted zirconia and sandblasted/etched titanium discs. At 24 hours after seeding MC3T3-E1, the demineralized bone matrix (DBM) gel alone and the DBM gel with bone morphogenetic protein-2 (BMP-2) were added to the culture medium. The surface topography was examined by confocal laser scanning microscopy. Cellular proliferation was measured at 1, 4, and 7 days after gel loading. Alkaline phosphatase activity was measured at 7 days after gel loading. The mRNA expression of ALPase, bone sialoprotein, type I collagen, runt-related transcription factor 2 (Runx-2), osteocalcin, and osterix were evaluated by real-time polymerase chain reaction at 4 days and 7 days. RESULTS: At 1, 4, and 7 days after loading the DBM gel alone and the DBM gel with BMP-2, cellular proliferation on the zirconia and titanium discs was similar and that of the groups cultured with the DBM gel alone and the DBM gel with BMP-2 was not significantly different, except for titanium with BMP-2 gel. ALPase activity was higher in the cells cultured with BMP-2 than in the other groups, but there was no difference between the zirconia and titanium. In ALPase, bone sialoprotein, osteocalcin, Runx-2 and osterix gene expression, that of cells on zirconia or titanium with BMP-2 gel was much more highly increased than titanium without gel at day 7. The gene expression level of cells cultured on zirconia with BMP-2 was higher than that on titanium with BMP-2 at day 7. CONCLUSIONS: The data in this study demonstrate that the osteoblastic cell attachment and proliferation of zirconia were comparable to those of titanium. With the stimulation of BMP-2, zirconia has a more pronounced effect on the proliferation and differentiation of the osteoblastic cells compared with titanium.
Alkaline Phosphatase ; Bone Matrix ; Cell Differentiation ; Cell Proliferation ; Collagen Type I ; Gene Expression ; Integrin-Binding Sialoprotein ; Microscopy, Confocal ; Osteoblasts ; Osteocalcin ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Seeds ; Titanium ; Transcription Factors ; Zirconium